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Mhatre-Winters I, Eid A, Blum N, Han Y, Sammoura FM, Wu LJ, Richardson JR. Effects of Pesticide Exposure on Neuroinflammation and Microglial Gene Expression: Relevance to Mechanisms of Alzheimer's Disease Risk. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.14.638293. [PMID: 40027678 PMCID: PMC11870447 DOI: 10.1101/2025.02.14.638293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
Background Alzheimer's disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models. Objective Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice. Methods Effects of DDT on inflammation and disease-associated microglia were determined in primary mouse microglia and C57BL/6J mice. Results PMG exposed to DDT (0.5-5.0 µM) elicited a ∼2-3-fold increase in Il-1b mRNA levels, with similar concentration-dependent upregulation in Il-6, Nos2, and Tnfa . These effects were blocked by the sodium channel antagonist tetrodotoxin, demonstrating the role of DDT-microglial sodium channel interactions in mediating this response. Additionally, NOS2 protein levels increased by ∼1.5-2-fold, while TNFa was elevated by 2-4-fold. C57BL/6J male and female mice exposed to DDT (30 mg/kg) demonstrated significantly increased mRNA levels of Nos2 , Il-1b , and Il-6 in the frontal cortex (1.5-2.3-fold), and Nos2 , Il-1b, and Tnfa (1.5-1.8-fold) in the hippocampus. Furthermore, microglial homeostatic genes, Cx3cr1 , P2ry12, and Tmem119 , were downregulated, while stage 1 disease-associated microglia genes were upregulated both in vitro and in vivo . Notably, Apoe and Trem2 were only upregulated in the frontal cortex and hippocampus of females. Conclusion These data indicate that DDT increases neuroinflammation, which may result from direct actions of DDT on microglia, providing a novel pathway by which DDT may contribute to AD risk.
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Alehashem M, Alcaraz AJ, Hogan N, Weber L, Siciliano SD, Hecker M. Linking pesticide exposure to neurodegenerative diseases: An in vitro investigation with human neuroblastoma cells. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 933:173041. [PMID: 38723972 DOI: 10.1016/j.scitotenv.2024.173041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 05/05/2024] [Accepted: 05/05/2024] [Indexed: 05/18/2024]
Abstract
Although many organochlorine pesticides (OCPs) have been banned or restricted because of their persistence and linkage to neurodegenerative diseases, there is evidence of continued human exposure. In contrast, registered herbicides are reported to have a moderate to low level of toxicity; however, there is little information regarding their toxicity to humans or their combined effects with OCPs. This study aimed to characterize the mechanism of toxicity of banned OCP insecticides (aldrin, dieldrin, heptachlor, and lindane) and registered herbicides (trifluralin, triallate, and clopyralid) detected at a legacy contaminated pesticide manufacturing and packing site using SH-SY5Y cells. Cell viability, LDH release, production of reactive oxygen species (ROS), and caspase 3/7 activity were evaluated following 24 h of exposure to the biocides. In addition, RNASeq was conducted at sublethal concentrations to investigate potential mechanisms involved in cellular toxicity. Our findings suggested that aldrin and heptachlor were the most toxic, while dieldrin, lindane, trifluralin, and triallate exhibited moderate toxicity, and clopyralid was not toxic to SH-SY5Y cells. While aldrin and heptachlor induced their toxicity through damage to the cell membrane, the toxicity of dieldrin was partially attributed to necrosis and apoptosis. Moreover, toxic effects of lindane, trifluralin, and triallate, at least partially, were associated with ROS generation. Gene expression profiles suggested that decreased cell viability induced by most of the tested biocides was related to inhibited cell proliferation. The dysregulation of genes encoding for proteins with anti-apoptotic properties also supported the absence of caspase activation. Identified enriched terms showed that OCP toxicity in SH-SY5Y cells was mediated through pathways associated with the pathogenesis of neurodegenerative diseases. In conclusion, this study provides a basis for elucidating the molecular mechanisms of pesticide-induced neurotoxicity. Moreover, it introduced SH-SY5Y cells as a relevant in vitro model for investigating the neurotoxicity of pesticides in humans.
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Affiliation(s)
- M Alehashem
- Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
| | - A J Alcaraz
- Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
| | - N Hogan
- Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada; Department of Animal Science, University of Saskatchewan, Saskatoon, SK, Canada
| | - L Weber
- Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
| | - S D Siciliano
- Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada; Department of Soil Science, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
| | - M Hecker
- Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada; School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK S7N 5C8, Canada.
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Suresh S, Singh S A, Rushendran R, Vellapandian C, Prajapati B. Alzheimer's disease: the role of extrinsic factors in its development, an investigation of the environmental enigma. Front Neurol 2023; 14:1303111. [PMID: 38125832 PMCID: PMC10730937 DOI: 10.3389/fneur.2023.1303111] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023] Open
Abstract
In the realm of Alzheimer's disease, the most prevalent form of dementia, the impact of environmental factors has ignited intense curiosity due to its substantial burden on global health. Recent investigations have unveiled these environmental factors as key contributors, shedding new light on their profound influence. Notably, emerging evidence highlights the detrimental role of various environmental contaminants in the incidence and progression of Alzheimer's disease. These contaminants encompass a broad spectrum, including air pollutants laden with ozone, neurotoxic metals like lead, aluminum, manganese, and cadmium, pesticides with their insidious effects, and the ubiquitous presence of plastics and microplastics. By meticulously delving into the intricate web connecting environmental pollutants and this devastating neurological disorder, this comprehensive chapter takes a deep dive into their involvement as significant risk factors for Alzheimer's disease. Furthermore, it explores the underlying molecular mechanisms through which these contaminants exert their influence, aiming to unravel the complex interactions that drive the pathogenesis of the disease. Additionally, this chapter proposes potential strategies to mitigate the detrimental effects of these environmental contaminants on brain health, with the ultimate goal of restoring and preserving typical cognitive function. Through this comprehensive exploration, we aim to enhance our understanding of the multifaceted relationship between neurotoxins and Alzheimer's disease, providing a solid foundation for developing innovative in-vivo models and advancing our knowledge of the intricate pathological processes underlying this debilitating condition.
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Affiliation(s)
- Swathi Suresh
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Ankul Singh S
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Rapuru Rushendran
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Chitra Vellapandian
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Bhupendra Prajapati
- Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India
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Torres-Sánchez ED, Ortiz GG, Reyes-Uribe E, Torres-Jasso JH, Salazar-Flores J. Effect of pesticides on phosphorylation of tau protein, and its influence on Alzheimer's disease. World J Clin Cases 2023; 11:5628-5642. [PMID: 37727721 PMCID: PMC10506003 DOI: 10.12998/wjcc.v11.i24.5628] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 07/17/2023] [Accepted: 08/08/2023] [Indexed: 08/24/2023] Open
Abstract
Alzheimer's disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.
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Affiliation(s)
- Erandis D Torres-Sánchez
- Department of Medical and Life Sciences, University Center of la Cienega, University of Guadalajara, Ocotlan 47820, Jalisco, Mexico
| | - Genaro G Ortiz
- Department of Philosophical and Methodological Disciplines and Service of Molecular Biology in Medicine Hospital Civil, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Emmanuel Reyes-Uribe
- Department of Medical and Life Sciences, University Center of la Cienega, University of Guadalajara, Ocotlan 47820, Jalisco, Mexico
| | - Juan H Torres-Jasso
- Department of Biological Sciences, CUCOSTA, University of Guadalajara, Puerto Vallarta 48280, Jalisco, Mexico
| | - Joel Salazar-Flores
- Department of Medical and Life Sciences, University Center of la Cienega, University of Guadalajara, Ocotlan 47820, Jalisco, Mexico
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Rao RV, Subramaniam KG, Gregory J, Bredesen AL, Coward C, Okada S, Kelly L, Bredesen DE. Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer's Disease and MCI: A Review. Int J Mol Sci 2023; 24:ijms24021659. [PMID: 36675177 PMCID: PMC9865291 DOI: 10.3390/ijms24021659] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/03/2023] [Accepted: 01/09/2023] [Indexed: 01/18/2023] Open
Abstract
Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease typically characterized by memory loss, personality changes, and a decline in overall cognitive function. Usually manifesting in individuals over the age of 60, this is the most prevalent type of dementia and remains the fifth leading cause of death among Americans aged 65 and older. While the development of effective treatment and prevention for AD is a major healthcare goal, unfortunately, therapeutic approaches to date have yet to find a treatment plan that produces long-term cognitive improvement. Drugs that may be able to slow down the progression rate of AD are being introduced to the market; however, there has been no previous solution for preventing or reversing the disease-associated cognitive decline. Recent studies have identified several factors that contribute to the progression and severity of the disease: diet, lifestyle, stress, sleep, nutrient deficiencies, mental health, socialization, and toxins. Thus, increasing evidence supports dietary and other lifestyle changes as potentially effective ways to prevent, slow, or reverse AD progression. Studies also have demonstrated that a personalized, multi-therapeutic approach is needed to improve metabolic abnormalities and AD-associated cognitive decline. These studies suggest the effects of abnormalities, such as insulin resistance, chronic inflammation, hypovitaminosis D, hormonal deficiencies, and hyperhomocysteinemia, in the AD process. Therefore a personalized, multi-therapeutic program based on an individual's genetics and biochemistry may be preferable over a single-drug/mono-therapeutic approach. This article reviews these multi-therapeutic strategies that identify and attenuate all the risk factors specific to each affected individual. This article systematically reviews studies that have incorporated multiple strategies that target numerous factors simultaneously to reverse or treat cognitive decline. We included high-quality clinical trials and observational studies that focused on the cognitive effects of programs comprising lifestyle, physical, and mental activity, as well as nutritional aspects. Articles from PubMed Central, Scopus, and Google Scholar databases were collected, and abstracts were reviewed for relevance to the subject matter. Epidemiological, pathological, toxicological, genetic, and biochemical studies have all concluded that AD represents a complex network insufficiency. The research studies explored in this manuscript confirm the need for a multifactorial approach to target the various risk factors of AD. A single-drug approach may delay the progression of memory loss but, to date, has not prevented or reversed it. Diet, physical activity, sleep, stress, and environment all contribute to the progression of the disease, and, therefore, a multi-factorial optimization of network support and function offers a rational therapeutic strategy. Thus, a multi-therapeutic program that simultaneously targets multiple factors underlying the AD network may be more effective than a mono-therapeutic approach.
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Affiliation(s)
- Rammohan V. Rao
- Apollo Health, Burlingame, CA 94011, USA
- Correspondence: (R.V.R.); (D.E.B.)
| | | | | | | | | | - Sho Okada
- Apollo Health, Burlingame, CA 94011, USA
| | | | - Dale E. Bredesen
- Apollo Health, Burlingame, CA 94011, USA
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90024, USA
- Correspondence: (R.V.R.); (D.E.B.)
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Arab A, Mostafalou S. Neurotoxicity of pesticides in the context of CNS chronic diseases. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2022; 32:2718-2755. [PMID: 34663153 DOI: 10.1080/09603123.2021.1987396] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 09/26/2021] [Indexed: 06/13/2023]
Abstract
Following the introduction and application of pesticides in human life, they have always been along with health concerns both in acute poisoning and chronic toxicities. Neurotoxicity of pesticides in chronic exposures has been known as one of the most important human health problems, as most of these chemicals act through interacting with some elements of nervous system. Pesticide-induced neurotoxicity can be defined in different categories of neurological disorders including neurodegenerative (Alzheimer, Parkinson, amyotrophic lateral sclerosis, multiple sclerosis), neurodevelopmental (attention deficit hyperactivity disorder, autism spectrum disorders, developmental delay, and intellectual disability), neurobehavioral and neuropsychiatric (depression/suicide attempt, anxiety/insomnia, and cognitive impairment) disorders some of which are among the most debilitating human health problems. In this review, neurotoxicity of pesticides in the mentioned categories and sub-categories of neurological diseases have been systematically presented in relation to different route of exposures including general, occupational, environmental, prenatal, postnatal, and paternal.
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Affiliation(s)
- Ali Arab
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sara Mostafalou
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
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7
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Neurodegeneration in a Regulatory Context: The Need for Speed. CURRENT OPINION IN TOXICOLOGY 2022. [DOI: 10.1016/j.cotox.2022.100383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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Costantini E, Masciarelli E, Casorri L, Di Luigi M, Reale M. Medicinal herbs and multiple sclerosis: Overview on the hard balance between new therapeutic strategy and occupational health risk. Front Cell Neurosci 2022; 16:985943. [PMID: 36439198 PMCID: PMC9688751 DOI: 10.3389/fncel.2022.985943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 10/20/2022] [Indexed: 11/11/2022] Open
Abstract
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss of the central nervous system (CNS). Despite its spread throughout the world, the mechanisms that determine its onset are still to be defined. Immunological, genetic, viral, and environmental factors and exposure to chemicals may trigger MS. Many studies have highlighted the anti-inflammatory and anti-oxidant effects of medicinal herbs, which make them a natural and complementary treatment for neurodegenerative diseases. A severe reduction of several MS symptoms occurs with herbal therapy. Thus, the request for medicinal plants with potential beneficial effects, for MS patients, is constantly increasing. Consequently, a production increase needs. Unfortunately, many medicinal herbs were untested and their action mechanism, possible adverse effects, contraindications, or interactions with other drugs, are poorly or not investigated. Keeping in mind the pathological mechanisms of MS and the oxidative damages and mitochondrial dysfunctions induced by pesticides, it is important to understand if pesticides used to increase agricultural productivity and their residues in medicinal plants, may increase the risk of developing MS in both workers and consumers. Studies providing some indication about the relationship between environmental exposure to pesticides and MS disease incidence are few, fragmentary, and discordant. The aim of this article is to provide a glance at the therapeutic potential of medicinal plants and at the risk for MS onset of pesticides used by medicinal plant growers and present in medicinal herbs.
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Affiliation(s)
- Erica Costantini
- Department of Medicine and Science of Aging, G. d’Annunzio University of Chieti–Pescara, Chieti, Italy
| | - Eva Masciarelli
- Department of Technological Innovations and Safety of Plants, Products and Anthropic Settlements, National Institute for Insurance Against Accidents at Work, Rome, Italy
| | - Laura Casorri
- Department of Technological Innovations and Safety of Plants, Products and Anthropic Settlements, National Institute for Insurance Against Accidents at Work, Rome, Italy
| | - Marco Di Luigi
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL Research Center, National Institute for Insurance Against Accidents at Work, Rome, Italy
| | - Marcella Reale
- Department of Innovative Technologies in Medicine and Dentistry, G. d’Annunzio University of Chieti–Pescara, Chieti, Italy
- *Correspondence: Marcella Reale,
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9
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Eid A, Mhatre-Winters I, Sammoura FM, Edler MK, von Stein R, Hossain MM, Han Y, Lisci M, Carney K, Konsolaki M, Hart RP, Bennett JW, Richardson JR. Effects of DDT on Amyloid Precursor Protein Levels and Amyloid Beta Pathology: Mechanistic Links to Alzheimer's Disease Risk. ENVIRONMENTAL HEALTH PERSPECTIVES 2022; 130:87005. [PMID: 35946953 PMCID: PMC9364816 DOI: 10.1289/ehp10576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
BACKGROUND The interaction of aging-related, genetic, and environmental factors is thought to contribute to the etiology of late-onset, sporadic Alzheimer's disease (AD). We previously reported that serum levels of p,p'-dichlorodiphenyldichloroethylene (DDE), a long-lasting metabolite of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT), were significantly elevated in patients with AD and associated with the risk of AD diagnosis. However, the mechanism by which DDT may contribute to AD pathogenesis is unknown. OBJECTIVES This study sought to assess effects of DDT exposure on the amyloid pathway in multiple in vitro and in vivo models. METHODS Cultured cells (SH-SY5Y and primary neurons), transgenic flies overexpressing amyloid beta (Aβ), and C57BL/6J and 3xTG-AD mice were treated with DDT to assess impacts on the amyloid pathway. Real time quantitative polymerase chain reaction, multiplex assay, western immunoblotting and immunohistochemical methods were used to assess the effects of DDT on amyloid precursor protein (APP) and other contributors to amyloid processing and deposition. RESULTS Exposure to DDT revealed significantly higher APP mRNA and protein levels in immortalized and primary neurons, as well as in wild-type and AD-models. This was accompanied by higher levels of secreted Aβ in SH-SY5Y cells, an effect abolished by the sodium channel antagonist tetrodotoxin. Transgenic flies and 3xTG-AD mice had more Aβ pathology following DDT exposure. Furthermore, loss of the synaptic markers synaptophysin and PSD95 were observed in the cortex of the brains of 3xTG-AD mice. DISCUSSION Sporadic Alzheimer's disease risk involves contributions from genetic and environmental factors. Here, we used multiple model systems, including primary neurons, transgenic flies, and mice to demonstrate the effects of DDT on APP and its pathological product Aβ. These data, combined with our previous epidemiological findings, provide a mechanistic framework by which DDT exposure may contribute to increased risk of AD by impacting the amyloid pathway. https://doi.org/10.1289/EHP10576.
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Affiliation(s)
- Aseel Eid
- Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
| | - Isha Mhatre-Winters
- Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
- School of Biomedical Sciences, Kent State University, Kent, Ohio, USA
| | - Ferass M. Sammoura
- Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
| | - Melissa K. Edler
- School of Biomedical Sciences, Kent State University, Kent, Ohio, USA
- Department of Anthropology, Kent State University, Kent, Ohio, USA
- Brain Health Research Institute, Kent State University, Kent, Ohio, USA
| | - Richard von Stein
- Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA
| | - Muhammad M. Hossain
- Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
- Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA
| | - Yoonhee Han
- Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
| | - Miriam Lisci
- Department of Genetics, Rutgers University, Piscataway, New Jersey, USA
| | - Kristina Carney
- Department of Genetics, Rutgers University, Piscataway, New Jersey, USA
| | - Mary Konsolaki
- Department of Genetics, Rutgers University, Piscataway, New Jersey, USA
- Federated Department of Biological Sciences, New Jersey Institute of Technology, Newark, New Jersey, USA
| | - Ronald P. Hart
- Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA
| | - Joan W. Bennett
- Department of Plant Sciences, Rutgers University, New Brunswick, New Jersey, USA
| | - Jason R. Richardson
- Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
- Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA
- Center for Neurodegenerative Disease and Aging, Northeast Ohio Medical University, Rootstown, Ohio, USA
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Fghihi-Zarandi A, Dabaghzadeh F, Vaziri A, Karami-Mohajeri S, Ghorbaninejad B, Zamani A, Rahimi-Sadegh K. Occupational risk assessment of organophosphates with an emphasis on psychological and oxidative stress factors. Toxicol Ind Health 2022; 38:342-350. [PMID: 35513771 DOI: 10.1177/07482337221096315] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Organophosphate pesticides (OPPs) are widely used all over the world in domestic and industrial settings, but these chemicals affect the nervous system, induce suicidal thoughts, depression and anxiety, and impair sleep quality. The purpose of this study was to investigate the relationship between the main toxicity mechanisms of OPPs, oxidative stress and cholinesterase inhibition, and psychological parameters in chronic exposure to OPPs. This cross-sectional study was conducted on 56 male OPPs factory workers as the worker group and 47 unexposed individuals within the same age range as the control group. Psychological factors were assessed using validated questionnaires. The activity of plasma cholinesterase and oxidative stress biomarkers, total antioxidant capacity of plasma, lipid peroxidation (LPO), and protein carbonylation were determined in blood samples by spectrophotometer. Sleep quality score in the factory workers was lower, and depression and suicidal ideation scores were higher than those in the control group. These factory workers showed 35% lower levels of plasma cholinesterase activity than did the controls. Compared to the control group, a significant impairment in oxidative stress biomarkers was also observed in the workers. Meanwhile, there was a significant relationship between the duration of employment and the level of LPO as well as a significant correlation between the quality of sleep and plasma cholinesterase in the workers. In conclusion, long-term exposure to OPPs could cause oxidative damages and neurobehavioral effects. The close monitoring of workplace exposure to organophosphates pesticides and also their respective solvents along with the reduction of working hours are of the necessities to avoid the adverse impacts of exposure to these pesticides.
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Affiliation(s)
- Ali Fghihi-Zarandi
- Department of Occupational Health Engineering, School of Public Health, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Fatemeh Dabaghzadeh
- Pharmaceutics Research Center, Institute of Neuropharmacology, 48463Kerman University of Medical Sciences, Kerman, Iran.,Departments of Toxicology and Pharmacology, School of Pharmacy, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Ali Vaziri
- Department of Chemical and Petroleum Engineering, 68106Science and Research Branch of Islamic Azad, Tehran, Iran
| | - Somayyeh Karami-Mohajeri
- Departments of Toxicology and Pharmacology, School of Pharmacy, 48463Kerman University of Medical Sciences, Kerman, Iran.,Department of Chemical and Petroleum Engineering, 68106Science and Research Branch of Islamic Azad, Tehran, Iran
| | - Behnam Ghorbaninejad
- Departments of Toxicology and Pharmacology, School of Pharmacy, 48463Kerman University of Medical Sciences, Kerman, Iran
| | - Ahmadreza Zamani
- Vice_chancellery of Health, 48463Kerman University of Medical Sciences, Kerman, Iran
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Salcedo-Bellido I, Amaya E, Pérez-Díaz C, Soler A, Vela-Soria F, Requena P, Barrios-Rodríguez R, Echeverría R, Pérez-Carrascosa FM, Quesada-Jiménez R, Martín-Olmedo P, Arrebola JP. Differential Bioaccumulation Patterns of α, β-Hexachlorobenzene and Dicofol in Adipose Tissue from the GraMo Cohort (Southern Spain). INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:3344. [PMID: 35329028 PMCID: PMC8954870 DOI: 10.3390/ijerph19063344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/04/2022] [Accepted: 03/08/2022] [Indexed: 02/01/2023]
Abstract
To identify bioaccumulation patterns of α-, β- hexachlorocyclohexane (HCH) and dicofol in relation to sociodemographic, dietary, and lifestyle factors, adipose tissue samples of 387 subjects from GraMo cohort in Southern Spain were analyzed. Potential predictors of these organochlorine pesticides (OCP) levels were collected by face-to-face interviews and assessed by multivariable linear and logistic regression. OCPs were detected in 84.2% (β-HCH), 21.7% (α-HCH), and 19.6% (dicofol) of the population. β-HCH levels were positively related to age, body mass index (BMI), mother's occupation in agriculture during pregnancy, living in Poniente and Alpujarras, white fish, milk and water consumption, and negatively related to being male, living near to an agricultural area, working ≥10 years in agriculture, and beer consumption. Detectable α-HCH levels were positively related to age, BMI, milk consumption, mother's occupation in agriculture during pregnancy, and negatively with residence in Poniente and Alpujarras, Granada city, and Granada Metropolitan Area. Residence near to an agricultural area, smoking habit, white fish and water consumption, and living in Poniente and Alpujarras, Granada city and Granada Metropolitan Area were negatively associated with detectable dicofol levels. Our study revealed different bioaccumulation patterns of α, β-HCH and dicofol, probably due to their dissimilar period of use, and emphasize the need for assessing the exposure to frequently overlooked pollutants.
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Affiliation(s)
- Inmaculada Salcedo-Bellido
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
| | - Esperanza Amaya
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
| | - Celia Pérez-Díaz
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
| | - Anabel Soler
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
| | - Fernando Vela-Soria
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
- Biomedical Research Center (CIBM), University of Granada, 18016 Granada, Spain
| | - Pilar Requena
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
| | - Rocío Barrios-Rodríguez
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
| | - Ruth Echeverría
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
| | - Francisco M. Pérez-Carrascosa
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
- Servicio de Oncología Radioterápica, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain
| | - Raquel Quesada-Jiménez
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
| | - Piedad Martín-Olmedo
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
- Andalusian School of Public Health (EASP), 18011 Granada, Spain
| | - Juan Pedro Arrebola
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, 18071 Granada, Spain; (I.S.-B.); (C.P.-D.); (A.S.); (P.R.); (R.B.-R.); (R.E.); (F.M.P.-C.)
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Instituto de Investigación Biosanitaria (ibs. GRANADA), 18014 Granada, Spain; (E.A.); (F.V.-S.); (R.Q.-J.); (P.M.-O.)
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de Andrade JC, Galvan D, Effting L, Tessaro L, Aquino A, Conte-Junior CA. Multiclass Pesticide Residues in Fruits and Vegetables from Brazil: A Systematic Review of Sample Preparation Until Post-Harvest. Crit Rev Anal Chem 2021; 53:1174-1196. [PMID: 34908509 DOI: 10.1080/10408347.2021.2013157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
Brazil annually produces around 43 million tons of fruits and vegetables. Therefore, large amounts of pesticides are needed to grow these foods. The use of unauthorized or indiscriminate pesticides can lead to the adherence of residues of these compounds to the product in a concentration above the maximum residue limit (MRL). Pesticide residues (PRs) monitoring is a continuous challenge due to several factors influencing the detection of these compounds in the food matrix. Currently, several adaptations to conventional techniques have been developed to minimize these problems. This systematic review presents the main information obtained from 52 research articles, taken from five databases, on changes and advances in Brazil in sample preparation methods for determining PRs in fruits and vegetables in the last nine years. We cover the preexisting ones and some others that might be suitable alternatives approaches. In addition, we present a brief discussion on the monitoring of PRs in different Brazilian regions, and we found that residues belonging to the organophosphate and pyrethroid classes were detected more frequently. Approximately 67% of the residues detected are of irregular use in 28 types of fruits and vegetables commonly consumed and exported by Brazil.
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Affiliation(s)
- Jelmir Craveiro de Andrade
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Nanotechnology Network, Carlos Chagas Filho Research Support Foundation of the State of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Diego Galvan
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Nanotechnology Network, Carlos Chagas Filho Research Support Foundation of the State of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Luciane Effting
- Chemistry Department, State University of Londrina (UEL), Londrina, Brazil
| | - Letícia Tessaro
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Nanotechnology Network, Carlos Chagas Filho Research Support Foundation of the State of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Adriano Aquino
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Nanotechnology Network, Carlos Chagas Filho Research Support Foundation of the State of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Carlos Adam Conte-Junior
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, Brazil
- Nanotechnology Network, Carlos Chagas Filho Research Support Foundation of the State of Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
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Xu S, Yang X, Qian Y, Luo Q, Song Y, Xiao Q. Analysis of serum levels of organochlorine pesticides and related factors in Parkinson's disease. Neurotoxicology 2021; 88:216-223. [PMID: 34864106 DOI: 10.1016/j.neuro.2021.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/31/2021] [Accepted: 12/01/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND There is evidence that environmental factors contribute to the onset and progression of Parkinson's disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of developing PD. However, few studies have investigated the association between specific pesticides and PD, especially in China, which was one of the first countries to adopt the use of pesticides. METHODS In this study, serum levels of 19 pesticides were measured in 90 patients with PD and 90 healthy spouse controls. We also analyzed the interaction between specific pesticides and PD. In addition, the association between pesticides and clinical features of PD was also investigated. Finally, we investigated the underlying mechanism of the association between pesticides and PD. RESULTS Serum levels of organochlorine pesticides, which included α-hexachlorocyclohexane (HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p'-dichlorodiphenyltrichloroethane and o,p'-dichloro-diphenyl-trichloroethane were higher in PD patients than controls. Moreover, α-HCH and propanil levels were associated with PD. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. In SH-SY5Y cells, α-HCH and propanil increased level of reactive oxygen species and decreased mitochondrial membrane potential. Furthermore, propanil, but not α-HCH, induced the aggregation of α-synuclein. CONCLUSIONS This study revealed that elevated serum levels of α-HCH and propanil were associated with PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. Moreover, propanil, but not α-HCH, induced the aggregation of α-synuclein. Further research is needed to fully elucidate the effects of pesticides on PD.
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Affiliation(s)
- Shaoqing Xu
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
| | - Xiaodong Yang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
| | - Yiwei Qian
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
| | - Qian Luo
- Core Facility of School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Yanyan Song
- Department of Biostatistics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
| | - Qin Xiao
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
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Xue H, He S, Kang C, Liu H, Peng F, Tang X. Photochemical degradation of β-hexachlorocyclohexane in snow and ice. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:68244-68250. [PMID: 34268694 DOI: 10.1007/s11356-021-15341-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 07/03/2021] [Indexed: 06/13/2023]
Abstract
Hexachlorocyclohexane (HCH), a typical organochloride pesticide, is one of the persistent organic pollutants. Despite the ban on technical grade HCH, it has been continuously observed at a steady level in the environment. The photochemical degradation of β-HCH in snow and ice under ultraviolet (UV) irradiation was investigated in this study. The effects of pH as well as common chemical components in snow on the degradation kinetics were investigated. In addition, the photodegradation products were determined and the reaction mechanism was hypothesized. The results showed that under UV irradiation, β-HCH can be photolyzed in snow and ice, with the photochemical degradation process conforming to the first-order kinetic equation. Changing the pH and adding Fe2+ had minimal effect on the photochemical degradation kinetics, while the presence of acetone, NO2-, NO3- and Fe3+ significantly inhibited the process. The addition of hydrogen peroxide slightly inhibited the photochemical degradation of β-HCH. Finally, the reaction rate, products and degradation mechanism of β-HCH in snow were compared with those in the ice phase. The photochemical degradation rate of β-HCH in snow was approximately 24 times faster than that in the ice phase. The photolysis product of β-HCH in snow was α-HCH, produced by the isomerization of β-HCH. However, in ice, in addition to α-HCH, pentachlorocyclohexene was produced by dechlorination. The results of this study are helpful in understanding the transformation of organochlorine pesticides in snow and ice, as well as in providing a theoretical basis for snow and ice pollution prevention and control.
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Affiliation(s)
- Honghai Xue
- Key Laboratory of Songliao Aquatic Environment, Ministry of Education, Jilin Jianzhu University, Changchun, 130118, P.R. China
- Key Laboratory of Groundwater Resources and Environment, Ministry of Education, Jilin University, Changchun, 130012, P.R. China
| | - Shuiyuan He
- Key Laboratory of Groundwater Resources and Environment, Ministry of Education, Jilin University, Changchun, 130012, P.R. China
| | - Chunli Kang
- Key Laboratory of Groundwater Resources and Environment, Ministry of Education, Jilin University, Changchun, 130012, P.R. China.
| | - Hanfei Liu
- China Construction Industrial & Energy Engineering Group Co., Ltd., Nanjing, 210023, P.R. China
| | - Fei Peng
- Hydrological Bureau (Information Center), Songliao Water Resources Commission, Changchun, 130021, P.R. China
| | - Xiaojian Tang
- Key Laboratory of Songliao Aquatic Environment, Ministry of Education, Jilin Jianzhu University, Changchun, 130118, P.R. China
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Kumar M, Bansal N. A Revisit to Etiopathogenesis and Therapeutic Strategies in Alzheimer's Disease. Curr Drug Targets 2021; 23:486-512. [PMID: 34792002 DOI: 10.2174/1389450122666211118125233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 09/05/2021] [Accepted: 09/13/2021] [Indexed: 11/22/2022]
Abstract
Dementia is a cluster of brain abnormalities that trigger progressive memory deficits and other cognitive abilities such as skills, language, or executive function. Alzheimer's disease (AD) is the foremost type of age-associated dementia that involves progressive neurodegeneration accompanied by profound cognitive deficits in advanced stages that severely hamper social or occupational abilities with or without the involvement of any other psychiatric condition. The last two decades witnessed a sharp increase (~123%) in mortality due to AD type dementia, typically owing to a very low disclosure rate (~45%) and hence, the prophylactic, as well as the therapeutic cure of AD, has been a huge challenge. Although understanding of AD pathogenesis has witnessed a remarkable growth (e.g., tauopathy, oxidative stress, lipid transport, glucose uptake, apoptosis, synaptic dysfunction, inflammation, and immune system), still a dearth of an effective therapeutic agent in the management of AD prompts the quest for newer pharmacological targets in the purview of its growing epidemiological status. Most of the current therapeutic strategies focus on modulation of a single target, e.g., inhibition of acetylcholinesterase, glutamate excitotoxicity (memantine), or nootropics (piracetam), even though AD is a multifaceted neurological disorder. There is an impedance urgency to find not only symptomatic but effective disease-modifying therapies. The present review focuses on the risk / protective factors and pathogenic mechanisms involved in AD. In addition to the existing symptomatic therapeutic approach, a diverse array of possible targets linked to pathogenic cascades have been re-investigated to envisage the pharmacotherapeutic strategies in AD.
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Affiliation(s)
- Manish Kumar
- Chitkara College of Pharmacy, Chitkara University, Punjab. India
| | - Nitin Bansal
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University (CBLU), Bhiwani, Haryana 127021. India
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Sarrouilhe D, Defamie N, Mesnil M. Is the Exposome Involved in Brain Disorders through the Serotoninergic System? Biomedicines 2021; 9:1351. [PMID: 34680468 PMCID: PMC8533279 DOI: 10.3390/biomedicines9101351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/17/2021] [Accepted: 09/23/2021] [Indexed: 11/24/2022] Open
Abstract
Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine acting as a neurotransmitter in the central nervous system (CNS), local mediator in the gut, and vasoactive agent in the blood. It has been linked to a variety of CNS functions and is implicated in many CNS and psychiatric disorders. The high comorbidity between some neuropathies can be partially understood by the fact that these diseases share a common etiology involving the serotoninergic system. In addition to its well-known functions, serotonin has been shown to be a mitogenic factor for a wide range of normal and tumor cells, including glioma cells, in vitro. The developing CNS of fetus and newborn is particularly susceptible to the deleterious effects of neurotoxic substances in our environment, and perinatal exposure could result in the later development of diseases, a hypothesis known as the developmental origin of health and disease. Some of these substances affect the serotoninergic system and could therefore be the source of a silent pandemic of neurodevelopmental toxicity. This review presents the available data that are contributing to the appreciation of the effects of the exposome on the serotoninergic system and their potential link with brain pathologies (neurodevelopmental, neurodegenerative, neurobehavioral disorders, and glioblastoma).
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Affiliation(s)
- Denis Sarrouilhe
- Laboratoire de Physiologie Humaine, Faculté de Médecine et Pharmacie, 6 Rue de la Milétrie, Bât D1, TSA 51115, CEDEX 09, 86073 Poitiers, France
| | - Norah Defamie
- Laboratoire STIM, ERL7003 CNRS-Université de Poitiers, 1 Rue G. Bonnet–TSA 51106, CEDEX 09, 86073 Poitiers, France; (N.D.); (M.M.)
| | - Marc Mesnil
- Laboratoire STIM, ERL7003 CNRS-Université de Poitiers, 1 Rue G. Bonnet–TSA 51106, CEDEX 09, 86073 Poitiers, France; (N.D.); (M.M.)
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Wu D, Hu Y, Song M, Li G. Dichlorodiphenyltrichloroethane Impairs Amyloid Beta Clearance by Decreasing Liver X Receptor α Expression. Front Aging Neurosci 2021; 13:634948. [PMID: 34045954 PMCID: PMC8144330 DOI: 10.3389/fnagi.2021.634948] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/22/2021] [Indexed: 11/30/2022] Open
Abstract
Abnormal amyloid beta (Aβ) clearance is a distinctive pathological mechanism for Alzheimer’s disease (AD). ATP-binding cassette transporter A1 (ABCA1), which mediates the lipidation of apolipoprotein E, plays a critical role in Aβ clearance. As an environmental factor for AD, dichlorodiphenyltrichloroethane (DDT) can decrease ATP-binding cassette transporter A1 (ABCA1) expression and disrupt Aβ clearance. Liver X receptor α (LXRα) is an autoregulatory transcription factor for ABCA1 and a target of some environmental pollutants, such as organophosphate pesticides. In this study, we aimed to investigate whether DDT could affect Aβ clearance by targeting LXRα. The DDT-pretreated H4 human neuroglioma cells and immortalized astrocytes were incubated with exogenous Aβ to evaluate Aβ consumption. Meanwhile, cytotoxicity and LXRα expression were determined in the DDT-treated cells. Subsequently, the antagonism of DDT on LXRα agonist T0901317 was determined in vitro. The interaction between DDT and LXRα was predicted by molecular docking and molecular dynamics simulation technology. We observed that DDT could inhibit Aβ clearance and decrease the levels of LXRα mRNA and LXRα protein. Moreover, DDT is supposed to strongly bind to LXRα and exert antagonistic effects on LXRα. In conclusion, this study firstly presented that DDT could inhibit LXRα expression, which would contribute to Aβ clearance decline in vitro. It provides an experimental basis to search for potential therapeutic targets of AD.
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Affiliation(s)
- Dongmei Wu
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Hu
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Song
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Gongbo Li
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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18
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Li Y, Fang R, Liu Z, Jiang L, Zhang J, Li H, Liu C, Li F. The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis. CHEMOSPHERE 2021; 263:128238. [PMID: 33297185 DOI: 10.1016/j.chemosphere.2020.128238] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 08/16/2020] [Accepted: 08/31/2020] [Indexed: 06/12/2023]
Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g., pesticide) and AD has attracted considerable attention. However, no systematic analysis has been performed and make it difficult to provide deeper insights of AD correlated with pesticide exposure. Hence, this study utilized a bibliometric and visual approach that included map collaborations, co-citations, and keywords, to identifying the knowledge structure, hot topics and the research trends based on 372 publications from the Web of Science Core Collection and PubMed databases. The results showed that 116 institutions from 52 countries published articles in this field. The United States and Israel played a leading role with numerous publications in related journals, as well as prolific institutions and authors, respectively. Three hot topics in pesticide-induced AD were recognized based on co-occurrence keywords detection, including acetylcholinesterase (AChE) inhibitor, oxidative stress, and AChE. Moreover, analysis of keywords burst suggests that some potential molecular mechanisms and therapy targets of pesticide-induced AD, especially for mitochondrial dysfunction and monoamine oxidase-B (MAO-B) that catalyzes the oxidative deamination and causes oxidative stress, are emerging trends. In addition, the study of various pesticides and the assessment method of pesticide exposure will step forward as well. To the best of our knowledge, this study is the first to specifically visualize the relationship between AD and pesticide exposure and to predict potential future research directions.
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Affiliation(s)
- Yanan Li
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China
| | - Ruying Fang
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China
| | - Zehua Liu
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China
| | - Luping Jiang
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China
| | - Jingdong Zhang
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China
| | - Honghu Li
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China
| | - Chaoyang Liu
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China; Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430073, China.
| | - Fei Li
- Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China; Key Laboratory of Virtual Geographic Environment (Ministry of Education), Nanjing Normal University, Nanjing, 210023, China.
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19
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Nafees S, Akram MF, Khan MA. Drug Therapy of Alzheimer’s Disease: Cholinesterase Inhibitors, NMDA Antagonists. AUTISM SPECTRUM DISORDER AND ALZHEIMER'S DISEASE 2021:95-110. [DOI: 10.1007/978-981-16-4558-7_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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20
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Mir RH, Sawhney G, Pottoo FH, Mohi-Ud-Din R, Madishetti S, Jachak SM, Ahmed Z, Masoodi MH. Role of environmental pollutants in Alzheimer's disease: a review. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:44724-44742. [PMID: 32715424 DOI: 10.1007/s11356-020-09964-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 06/30/2020] [Indexed: 06/11/2023]
Abstract
Neurodegenerative disorders are commonly erratic influenced by various factors including lifestyle, environmental, and genetic factors. In recent observations, it has been hypothesized that exposure to various environmental factors enhances the risk of Alzheimer's disease (AD). The exact etiology of Alzheimer's disease is still unclear; however, the contribution of environmental factors in the pathology of AD is widely acknowledged. Based on the available literature, the review aims to culminate in the prospective correlation between the various environmental factors and AD. The prolonged exposure to the various well-known environmental factors including heavy metals, air pollutants (particulate matter), pesticides, nanoparticles containing metals, industrial chemicals results in accelerating the progression of AD. Common mechanisms have been documented in the field of environmental contaminants for enhancing amyloid-β (Aβ) peptide along with tau phosphorylation, resulting in the initiation of senile plaques and neurofibrillary tangles, which results in the death of neurons. This review offers a compilation of available data to support the long-suspected correlation between environmental risk factors and AD pathology. Graphical abstract .
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Affiliation(s)
- Reyaz Hassan Mir
- Pharmaceutical Chemistry Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar, Kashmir, 190006, India.
| | - Gifty Sawhney
- Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, Jammu, 180001, India
| | - Faheem Hyder Pottoo
- Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O.BOX 1982, Dammam, 31441, Saudi Arabia
| | - Roohi Mohi-Ud-Din
- Pharmacognosy Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar, Kashmir, 190006, India
| | - Sreedhar Madishetti
- Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, Jammu, 180001, India
| | - Sanjay M Jachak
- Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Mohali, Punjab, 160062, India
| | - Zabeer Ahmed
- Inflammation Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, Jammu, 180001, India
| | - Mubashir Hussain Masoodi
- Pharmaceutical Chemistry Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar, Kashmir, 190006, India.
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21
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Sun X, Zhan F, Yu RQ, Chen L, Wu Y. Bio-accumulation of organic contaminants in Indo-Pacific humpback dolphins: Preliminary unique features of the brain and testes. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2020; 267:115511. [PMID: 32892017 DOI: 10.1016/j.envpol.2020.115511] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 08/23/2020] [Accepted: 08/24/2020] [Indexed: 06/11/2023]
Abstract
There is little information about the residue levels and congener composition of organic contaminants (OCs) in cetaceans. In the present study, we investigated the polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in the blubber, blood, brain and testes of Indo-Pacific humpback dolphins (Sousa chinensis) stranded in the Pearl River Estuary (PRE), China. The lowest blubber/tissue partition coefficients were found for sum hexachlorocyclohexanes (ΣHCHs) and ΣPAHs, while the highest were in ΣPCBs and sum dichlorodiphenyltrichloroethanes (ΣDDTs), likely attributing to the octanol-water partition features. The low levels of OCs in brain and testes theoretically resulted from the blood-brain barrier, blood-testes barrier, contaminant molecule dimensions and unique lipid compositions in the brain and testes. Compared with other contaminants, the higher mean brain/blood and testes/blood partition coefficients found for mirex, heptachlor, dieldrin and endrin would increase the risks associated with exposure-related toxicity and the bioavailability of contaminants within these tissues. Observations also suggest that as lipid mobilizes from blubber, contaminants may redistribute, leading to elevated tissue (such as brain) concentrations. Therefore, dolphins with less blubber may be more susceptible to health risks. The Indo-Pacific humpback dolphins living in PRE are at great risk due to variety of OCs in indirect contact with non-target organisms, affecting the health of animals (toxic effects and accumulation). Our findings contribute to the knowledge of the potential effects of OCs exposure on developmental neurotoxicity and reproductive damage in marine mammals.
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Affiliation(s)
- Xian Sun
- Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai Key Laboratory of Marine Bioresources and Environment, Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510275, China
| | - Fengping Zhan
- Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai Key Laboratory of Marine Bioresources and Environment, Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510275, China
| | - Ri-Qing Yu
- Department of Biology, University of Texas at Tyler, Tyler, TX, 75799, USA
| | - Laiguo Chen
- Urban Environment and Ecology Research Center, South China Institute of Environmental Sciences (SCIES), Ministry of Environmental Protection, Guangzhou, 510655, China
| | - Yuping Wu
- Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai Key Laboratory of Marine Bioresources and Environment, Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
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22
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Pesticides, cognitive functions and dementia: A review. Toxicol Lett 2020; 326:31-51. [PMID: 32145396 DOI: 10.1016/j.toxlet.2020.03.005] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 03/02/2020] [Accepted: 03/03/2020] [Indexed: 12/13/2022]
Abstract
Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person's quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the association between pesticide exposure, cognition and dementia. Additionally, we present potential mechanisms through which pesticides may act neurotoxically and lead to neurodegeneration. Study designs rarely presented homogeneity and the estimation of the exposure to pesticides has been most frequently performed without measuring the synergic effects and the possible interactions between the toxicants within mixtures, and also overlooking low exposures to environmental toxicants. It is possible that a Real-Life Risk Simulation approach would represent a robust alternative for future studies, so that the safe exposure limits and the net risk that pesticides confer to impaired cognitive function can be examined. Previous studies that evaluated the effect of low dose chronic exposure to mixtures of pesticides and other chemicals intending to simulate real life exposure scenarios showed that hormetic neurobehavioral effects can appear after mixture exposure at doses considered safe for individual compounds and these effects can be exacerbated by a coexistence with specific conditions such as vitamin deficiency. However, there is an overall indication, derived from both epidemiologic and laboratory evidence, supporting an association between exposure to neurotoxic pesticides and cognitive dysfunction, dementia and Alzheimer's disease.
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23
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Prenatal β-Hexachlorocyclohexane (β-HCH) Exposure and 7-Year Child IQ in the CHAMACOS Birth Cohort. Neurotox Res 2020; 37:553-563. [PMID: 31955369 DOI: 10.1007/s12640-020-00160-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 12/02/2019] [Accepted: 01/04/2020] [Indexed: 12/17/2022]
Abstract
Fetal and infant exposures to β-hexachlorocyclohexane (β-HCH) occur through placental and breastmilk transfers. No studies have examined the relationship between β-HCH and child intelligence quotient (IQ). This study examined associations between in utero β-HCH exposure and cognitive development in 7-year-old children. Data from women and children (n = 256) participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study were evaluated. We assessed exposure to β-HCH by measuring maternal serum concentration during pregnancy. We administered the Wechsler Intelligence Scale for Children (WISC), Fourth Edition, to children at age 7. Analyses were adjusted for maternal age, country of birth, work status, parity, and other pesticide exposures, language used for child cognitive assessment, and duration of breastfeeding. Higher serum β-HCH concentrations were associated with higher cognitive scores across all unadjusted models for the full-scale and sub-scale cognitive tests. In the adjusted models, a 10-fold increase in serum β-HCH concentration was associated with a 4.5-point increase in Working Memory IQ score (95% CI, 0.6 to 8.3; p = 0.02). We observed no significant interaction by length of breastfeeding or sex on associations. Our findings suggest that prenatal exposure to β-HCH is not adversely related to IQ at age 7 in a cohort of Mexican American children with fairly high exposure in utero as measured by maternal serum levels. Future research must replicate these findings in other study cohorts of women and children.
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24
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Longoni B, Fasciani I, Kolachalam S, Pietrantoni I, Marampon F, Petragnano F, Aloisi G, Coppolino MF, Rossi M, Scarselli M, Maggio R. Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease. Curr Pharm Des 2020; 25:4510-4522. [DOI: 10.2174/1381612825666191113103537] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 11/13/2019] [Indexed: 01/06/2023]
Abstract
:Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.
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Affiliation(s)
- Biancamaria Longoni
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Irene Fasciani
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | - Shivakumar Kolachalam
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Ilaria Pietrantoni
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | | | - Francesco Petragnano
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | - Gabriella Aloisi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | - Maria F. Coppolino
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | - Mario Rossi
- Institute of Molecular Cell and Systems Biology, University of Glasgow, United Kingdom
| | - Marco Scarselli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy
| | - Roberto Maggio
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
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25
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Manivannan B, Yegambaram M, Supowit S, Beach TG, Halden RU. Assessment of Persistent, Bioaccumulative and Toxic Organic Environmental Pollutants in Liver and Adipose Tissue of Alzheimer’s Disease Patients and Age-matched Controls. Curr Alzheimer Res 2019; 16:1039-1049. [DOI: 10.2174/1567205016666191010114744] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 09/19/2019] [Accepted: 10/03/2019] [Indexed: 02/07/2023]
Abstract
Background:
Lifetime exposure to environmental (neuro) toxicants may contribute to the
pathogenesis of Alzheimer’s Disease (AD). Since many contaminants do not cross the blood-brain
barrier, brain tissue alone cannot serve to assess the spectrum of environmental exposures.
Methods:
We used liquid and gas chromatography tandem mass spectrometry to monitor, in postmortem
liver and adipose tissues of AD patients and age-matched controls, the occurrence and
concentrations of 11 environmental contaminants.
Results:
Seven toxicants were detected at 100% frequency: p,p'-DDE, dieldrin, triclosan,
methylparaben, bisphenol A, fipronil and tetrabromobisphenol A (TBBPA). Intra-individual, tissuedependent
differences were detected for triclosan, methylparaben, fipronil and TBBPA. High
concentrations of p,p’-DDE and dieldrin were observed in adipose tissue when compared to liver values
for both AD cases and controls.
Conclusion:
This study provides vital data on organ-specific human body burdens to select analytes and
demonstrate the feasibility of analyzing small sample quantities for toxicants suspected to constitute AD
risk factors.
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Affiliation(s)
- Bhagyashree Manivannan
- Biodesign Center for Environmental Health Engineering, Arizona State University, Tempe, AZ, United States
| | - Manivannan Yegambaram
- Biodesign Center for Environmental Health Engineering, Arizona State University, Tempe, AZ, United States
| | - Samuel Supowit
- Biodesign Center for Environmental Health Engineering, Arizona State University, Tempe, AZ, United States
| | - Thomas G. Beach
- Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ-85287, United States
| | - Rolf U. Halden
- Biodesign Center for Environmental Health Engineering, Arizona State University, Tempe, AZ, United States
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26
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Wacławek S, Silvestri D, Hrabák P, Padil VVT, Torres-Mendieta R, Wacławek M, Černík M, Dionysiou DD. Chemical oxidation and reduction of hexachlorocyclohexanes: A review. WATER RESEARCH 2019; 162:302-319. [PMID: 31288141 DOI: 10.1016/j.watres.2019.06.072] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 06/25/2019] [Accepted: 06/27/2019] [Indexed: 06/09/2023]
Abstract
Lindane (γ-hexachlorocyclohexane) and its isomers (HCH) are some of the most common and most easily detected organochlorine pesticides in the environment. The widespread distribution of lindane is due to its use as an insecticide, accompanied by its persistence and bioaccumulation, whereas HCH were disposed of as waste in unmanaged landfills. Unfortunately, certain HCH (especially the most reactive ones: γ- and α-HCH) are harmful to the central nervous system and to reproductive and endocrine systems, therefore development of suitable remediation methods is needed to remove them from contaminated soil and water. This paper provides a short history of the use of lindane and a description of the properties of HCH, as well as their determination methods. The main focus of the paper, however, is a review of oxidative and reductive treatment methods. Although these methods of HCH remediation are popular, there are no review papers summarising their principles, history, advantages and disadvantages. Furthermore, recent advances in the chemical treatment of HCH are discussed and risks concerning these processes are given.
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Affiliation(s)
- Stanisław Wacławek
- Centre for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec 1, Czech Republic.
| | - Daniele Silvestri
- Centre for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec 1, Czech Republic
| | - Pavel Hrabák
- Centre for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec 1, Czech Republic
| | - Vinod V T Padil
- Centre for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec 1, Czech Republic
| | - Rafael Torres-Mendieta
- Centre for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec 1, Czech Republic
| | - Maria Wacławek
- Faculty of Natural Sciences and Technology, University of Opole, ul. kard. B. Kominka 6, 45-032, Opole, Poland
| | - Miroslav Černík
- Centre for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec 1, Czech Republic.
| | - Dionysios D Dionysiou
- Environmental Engineering and Science Program, Department of Chemical and Environmental Engineering, University of Cincinnati, 705 Engineering Research Center, Cincinnati, OH, 45221-0012, USA
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27
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Eid A, Mhatre I, Richardson JR. Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine. Pharmacol Ther 2019; 199:173-187. [PMID: 30877021 DOI: 10.1016/j.pharmthera.2019.03.005] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 03/01/2019] [Indexed: 12/19/2022]
Abstract
Alzheimer's disease (AD) is the leading cause of dementia in the United States and afflicts >5.7 million Americans in 2018. Therapeutic options remain extremely limited to those that are symptom targeting, while no drugs have been approved for the modification or reversal of the disease itself. Risk factors for AD including aging, the female sex, as well as carrying an APOE4 genotype. These risk factors have been extensively examined in the literature, while less attention has been paid to modifiable risk factors, including lifestyle, and environmental risk factors such as exposures to air pollution and pesticides. This review highlights the most recent data on risk factors in AD and identifies gene by environment interactions that have been investigated. It also provides a suggested framework for a personalized therapeutic approach to AD, by combining genetic, environmental and lifestyle risk factors. Understanding modifiable risk factors and their interaction with non-modifiable factors (age, susceptibility alleles, and sex) is paramount for designing personalized therapeutic interventions.
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Affiliation(s)
- Aseel Eid
- Department of Environmental Health, Robert Stempel School of Public Health and Social Work, Florida International University, Miami, FL, United States of America
| | - Isha Mhatre
- Department of Environmental Health, Robert Stempel School of Public Health and Social Work, Florida International University, Miami, FL, United States of America; Department of Neurosciences, School of Biomedical Sciences, Kent State University, Kent, OH
| | - Jason R Richardson
- Department of Environmental Health, Robert Stempel School of Public Health and Social Work, Florida International University, Miami, FL, United States of America.
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28
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Kori RK, Singh MK, Jain AK, Yadav RS. Neurochemical and Behavioral Dysfunctions in Pesticide Exposed Farm Workers: A Clinical Outcome. Indian J Clin Biochem 2018; 33:372-381. [PMID: 30319182 DOI: 10.1007/s12291-018-0791-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 09/11/2018] [Indexed: 02/04/2023]
Abstract
The problem of pesticides is not new and its exposure to human due to indiscriminate use is largely associated with the health related problems including neurotoxicological alterations. High levels of pesticide residues and their metabolites in the dietary constituents, food materials, maternal blood, cord blood, placenta breast milk have been reported and linked to alterations in birth weight, crown heel length, head circumference, mid-arm circumference and ponderal index of the neonates. Epidemiological studies have suggested that exposure of pesticide to human could be a significant risk factor for neurological disorders, including Parkinson's disease, Alzheimer's disease and multiple sclerosis. Cholinergic and non-cholinergic dysfunctions in pesticide exposed population, especially in children have also been frequently reported in recent years. Developmental neurotoxicity is another concern in the area where pregnant are more prone towards its exposure and which results in the abnormalities in the fetus. In view of the increasing risk of human health through pesticide exposure, the present review has been focused on the studies pertaining to pesticide induced neurochemical alterations and associated behavioral abnormalities in farm workers which could establish a possible link between the its exposure and associated health hazards.
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Affiliation(s)
- Rajesh Kumar Kori
- 1Department of Criminology and Forensic Science, School of Applied Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, MP 470 003 India
| | - Manish Kumar Singh
- Department of Biochemistry, Government Medical College, Badaun, UP 243601 India
| | - Abhishek Kumar Jain
- 3University Health Centre, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, MP 470 003 India
| | - Rajesh Singh Yadav
- 1Department of Criminology and Forensic Science, School of Applied Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, MP 470 003 India
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29
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Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer's Disease. BIOMED RESEARCH INTERNATIONAL 2018; 2018:1483791. [PMID: 30112360 PMCID: PMC6077677 DOI: 10.1155/2018/1483791] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 06/19/2018] [Indexed: 12/16/2022]
Abstract
Alzheimer's disease (AD) and multiple sclerosis are major neurodegenerative diseases, which are characterized by the accumulation of abnormal pathogenic proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy, and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we reviewed the utility of plant polyphenols in regulating proliferation and differentiation of stem cells for inducing brain self-repair in AD and multiple sclerosis. Firstly, we discussed the genetic, physiological, and environmental factors involved in the pathophysiology of both the disorders. Next, we reviewed various stem cell therapies available and how they have proved useful in animal models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize the potential of stem cells, either complementing their therapeutic effects or stimulating endogenous and exogenous neurogenesis, against these diseases. We suggest that polyphenols could be a potential candidate for stem cell therapy against neurodegenerative disorders.
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30
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Sharma N, Garg D, Deb R, Samtani R. Toxicological profile of organochlorines aldrin and dieldrin: an Indian perspective. REVIEWS ON ENVIRONMENTAL HEALTH 2017; 32:361-372. [PMID: 28915126 DOI: 10.1515/reveh-2017-0013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Accepted: 07/30/2017] [Indexed: 06/07/2023]
Abstract
Several epidemiological studies have suggested various environmental factors as a possible cause for increased incidence of various abnormalities. Of the various environmental contaminants, the most prevalent and the most discussed are the endocrine disrupting chemicals. Contact of such disruptors with humans has become inevitable today. They are cosmopolitan and present from agriculture to industrial sectors, even in day-to-day consumer products. Aldrin and dieldrin belong to one such class of substances which are known to have a toxic effect on various physiological systems of the human body. Despite an imposed ban on their manufacture and commercial use, these pesticides could still be detected in probable areas of consumption like agriculture. The present review discusses the known possible toxic effects of aldrin and dieldrin and their current existence in the ecosystem across India.
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31
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Abstract
PURPOSE OF REVIEW The rising prevalence of obesity and diabetes cannot be fully explained by known risk factors, such as unhealthy diet, a sedentary lifestyle, and family history. This review summarizes the available studies linking persistent organic pollutants (POPs) to obesity and diabetes and discusses plausible underlying mechanisms. RECENT FINDINGS Increasing evidence suggest that POPs may act as obesogens and diabetogens to promote the development of obesity and diabetes and induce metabolic dysfunction. POPs are synthesized chemicals and are used widely in our daily life. These chemicals are resistant to degradation in chemical or biological processes, which enable them to exist in the environment persistently and to be bio-accumulated in animal and human tissue through the food chain. Increasingly, epidemiologic studies suggest a positive association between POPs and risk of developing diabetes. Understanding the relationship of POPs with obesity and diabetes may shed light on preventive strategies for obesity and diabetes.
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Affiliation(s)
- Chunxue Yang
- Partner, State Key Laboratory of Environmental and Biological Analysis, and Department of Chemistry, Hong Kong Baptist University, 224, Waterloo Road, Kowloon Tong, Hong Kong, China
| | - Alice Pik Shan Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China
- Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China
| | - Zongwei Cai
- Partner, State Key Laboratory of Environmental and Biological Analysis, and Department of Chemistry, Hong Kong Baptist University, 224, Waterloo Road, Kowloon Tong, Hong Kong, China.
- HKBU Institute for Research and Continuing Education, Shenzhen, China.
| | - Arthur C K Chung
- Partner, State Key Laboratory of Environmental and Biological Analysis, and Department of Chemistry, Hong Kong Baptist University, 224, Waterloo Road, Kowloon Tong, Hong Kong, China.
- HKBU Institute for Research and Continuing Education, Shenzhen, China.
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32
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Slade L, Cowie A, Martyniuk CJ, Kienesberger PC, Pulinilkunnil T. Dieldrin Augments mTOR Signaling and Regulates Genes Associated with Cardiovascular Disease in the Adult Zebrafish Heart ( Danio rerio). J Pharmacol Exp Ther 2017; 361:375-385. [PMID: 28385952 DOI: 10.1124/jpet.116.239806] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 04/05/2017] [Indexed: 03/08/2025] Open
Abstract
Dieldrin is a legacy organochlorine pesticide that is persistent in the environment, despite being discontinued from use in North America since the 1970s. Some epidemiologic studies suggest that exposure to dieldrin is associated with increased risks of neurodegenerative disease and breast cancer by inducing inflammatory responses in tissues as well as oxidative stress. However, the direct effects of organochlorine pesticides on the heart have not been adequately addressed to date given that these chemicals are detectable in human serum and are environmentally persistent; thus, individuals may show latent adverse effects in the cardiovascular system due to long-term, low-dose exposure over time. Our objective was to determine whether low-level exposure to dieldrin at an environmentally relevant dose results in aberrant molecular signaling in the vertebrate heart. Using transcriptomic profiling and immunoblotting, we determined the global gene and targeted protein expression response to dieldrin treatment and show that dieldrin affects gene networks in the heart that are associated with processes related to cardiovascular disease, specifically cardiac arrest and ventricular fibrillation. We report that genes regulating inflammatory responses, a significant risk factor for cardiovascular disease, are upregulated by dieldrin whereas transcripts related to lysosomal function are significantly downregulated. To verify these findings, proteins in these pathways were examined with immunoblotting, and our results demonstrate that dieldrin constitutively activates Akt/mTOR signaling and downregulates lysosomal genes, participating in autophagy. Our data demonstrate that dieldrin induces genes associated with cardiovascular dysfunction and compromised lysosomal physiology, thereby identifying a novel mechanism for pesticide-induced cardiotoxicity.
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Affiliation(s)
- Logan Slade
- Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick (DMNB), Saint John, New Brunswick, Canada (L.S., A.C., P.C.K., T.P.); and Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, University of Florida, College of Veterinary Medicine, Gainesville, Florida (C.J.M.)
| | - Andrew Cowie
- Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick (DMNB), Saint John, New Brunswick, Canada (L.S., A.C., P.C.K., T.P.); and Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, University of Florida, College of Veterinary Medicine, Gainesville, Florida (C.J.M.)
| | - Chris J Martyniuk
- Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick (DMNB), Saint John, New Brunswick, Canada (L.S., A.C., P.C.K., T.P.); and Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, University of Florida, College of Veterinary Medicine, Gainesville, Florida (C.J.M.)
| | - Petra C Kienesberger
- Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick (DMNB), Saint John, New Brunswick, Canada (L.S., A.C., P.C.K., T.P.); and Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, University of Florida, College of Veterinary Medicine, Gainesville, Florida (C.J.M.)
| | - Thomas Pulinilkunnil
- Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick (DMNB), Saint John, New Brunswick, Canada (L.S., A.C., P.C.K., T.P.); and Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, University of Florida, College of Veterinary Medicine, Gainesville, Florida (C.J.M.)
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33
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de Silva MWA. Bio-media Citizenship and Chronic Kidney Disease of Unknown Etiology in Sri Lanka. Med Anthropol 2017; 37:221-235. [PMID: 28394638 DOI: 10.1080/01459740.2017.1311886] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
In this article, I examine the crucial role of the biomedical industry, epidemiological and biomedical research, and the media in forming attitudes to and the understanding of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka. Local conceptions of CKDu have been shaped by the circulation in the media of epidemiological research findings pertaining to the disease, biomedical interventions in the management of the disease in hospitals and clinics, community programs involving mass blood surveys and the testing of well water, and local food and health education programs carried out through village health committees. This process of circulation I identify as bio-media citizenship.
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Affiliation(s)
- M W Amarasiri de Silva
- a Department of Behavioral and Community Health Sciences , Graduate School of Public Health, University of Pittsburgh , Pittsburgh , Pennsylvania , USA
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34
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Singh S, Nelapati K. Effect of food processing on degradation of hexachlorocyclohexane and its isomers in milk. Vet World 2017; 10:270-275. [PMID: 28435187 PMCID: PMC5387652 DOI: 10.14202/vetworld.2017.270-275] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 01/24/2017] [Indexed: 11/16/2022] Open
Abstract
AIM To study the effect of different food processing techniques on the degradation of organochlorine compounds (α, β, ɣ and δ hexachlorocyclohexane isomers (HCH)) residues in both natural and fortified samples of milk. MATERIALS AND METHODS Raw milk samples are collected from the local areas of Hyderabad, India. Naturally and fortified milk samples (HCH) were subjected to various food processing techniques, pasteurization (63ºC for ½ h), sterilization (121ºC for 15 min) and boiling for 5 min and analyzed by gas chromatography with electron capture detector using quick, easy, cheap, effective, rugged and safe method for multiresidue analysis of pesticides in milk with slight modification. RESULTS The final mean residual concentration of pesticide in milk after heat processing and percentage of degradation were calculated with respective treatments. CONCLUSION Heat treatments are highly effective on reduction of mean residual concentration of HCH in milk. In which Sterilization and boiling proved to be more effective in degradation of HCH isomers.
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Affiliation(s)
- Sujatha Singh
- Department of Veterinary Public Health and Epidemiology, College of Veterinary Science, P. V. Narsimha Rao Telangana Veterinary University, Rajendranagar, Hyderabad - 500 030, Telangana, India
| | - Krishnaiah Nelapati
- Department of Veterinary Public Health and Epidemiology, College of Veterinary Science, P. V. Narsimha Rao Telangana Veterinary University, Rajendranagar, Hyderabad - 500 030, Telangana, India
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Koureas M, Karagkouni F, Rakitskii V, Hadjichristodoulou C, Tsatsakis A, Tsakalof A. Serum levels of organochlorine pesticides in the general population of Thessaly, Greece, determined by HS-SPME GC-MS method. ENVIRONMENTAL RESEARCH 2016; 148:318-321. [PMID: 27107243 DOI: 10.1016/j.envres.2016.04.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Revised: 04/09/2016] [Accepted: 04/12/2016] [Indexed: 06/05/2023]
Abstract
In this study, exposure levels of organochlorine pesticides (OCs) were determined in general population residing in Larissa, central Greece. Serum samples from 103 volunteers were analyzed by optimized headspace solid-phase microextraction gas chromatography-mass spectrometry, to detect and quantify OC levels. The most frequently detected analytes were p,p'-DDE (frequency 99%, median:1.25ng/ml) and Hexachlorobenzene (HCB) (frequency 69%, median: 0.13ng/ml). Statistical analysis revealed a significant relationship of p,p'-DDE and HCB levels with age.
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Affiliation(s)
- Michalis Koureas
- Department of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 22 Papakyriazi Street, Larissa 41222, Greece
| | - Foteini Karagkouni
- Department of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 22 Papakyriazi Street, Larissa 41222, Greece
| | - Valerii Rakitskii
- Federal Scientific Center of Hygiene named after F.F. Erisman, Mitischy, Russia
| | - Christos Hadjichristodoulou
- Department of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 22 Papakyriazi Street, Larissa 41222, Greece
| | - Aristidis Tsatsakis
- Laboratory of Toxicology, University of Crete, Medical School, Crete 71409, Greece
| | - Andreas Tsakalof
- Department of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 22 Papakyriazi Street, Larissa 41222, Greece.
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Li G, Kim C, Kim J, Yoon H, Zhou H, Kim J. Common Pesticide, Dichlorodiphenyltrichloroethane (DDT), Increases Amyloid-β Levels by Impairing the Function of ABCA1 and IDE: Implication for Alzheimer's Disease. J Alzheimers Dis 2016; 46:109-22. [PMID: 25720399 DOI: 10.3233/jad-150024] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
While early-onset familial Alzheimer's disease (AD) is caused by a genetic mutation, the vast majority of late-onset AD is likely caused by the combination of genetic and environmental factors. Unlike genetic studies, potential environmental factors affecting AD pathogenesis have not yet been thoroughly investigated. Among environmental factors, pesticides seem to be one of critical environmental contributors to late-onset AD. Recent studies reported that the serum and brains of AD patients have dramatically higher levels of a metabolite of dichlorodiphenyltrichloroethane (DDT). While these epidemiological studies provided initial clues to the environmental risks potentially contributing to disease pathogenesis, a functional approach is required to determine whether they actually have a causal role in disease development. In our study, we addressed this critical knowledge gap by investigating possible mechanisms by which DDT affects amyloid-β (Aβ) levels. We treated H4-AβPPswe or H4 cells with DDT to analyze its effect on Aβ metabolism using Aβ production, clearance, and degradation assays. We found that DDT significantly increased the levels of amyloid-β protein precursor (AβPP) and β-site AβPP-cleaving enzyme1 (BACE1), affecting Aβ synthesis pathway in H4-AβPPswe cells. Additionally, DDT impaired the clearance and extracellular degradation of Aβ peptides. Most importantly, we identified for the first time that ATP-binding cassette transporter A1 (ABCA1) and insulin-degrading enzyme (IDE) are the downstream target genes adversely affected by DDT. Our findings provide insight into the molecular mechanisms by which DDT exposure may increase the risk of AD, and it further supports that ABCA1 and IDE may be potential therapeutic targets.
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Affiliation(s)
- Gongbo Li
- Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.,Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
| | - Chaeyoung Kim
- Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
| | - Jaekwang Kim
- Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
| | - Hyejin Yoon
- Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA.,Neurobiology of Disease Graduate Program, Mayo Graduate School, Jacksonville, FL, USA
| | - Huadong Zhou
- Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Jungsu Kim
- Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA.,Neurobiology of Disease Graduate Program, Mayo Graduate School, Jacksonville, FL, USA
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Lee DH, Lind PM, Jacobs DR, Salihovic S, van Bavel B, Lind L. Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: A prospective study that accounts for weight change. ENVIRONMENT INTERNATIONAL 2016; 89-90:179-84. [PMID: 26878283 DOI: 10.1016/j.envint.2016.02.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 01/05/2016] [Accepted: 02/01/2016] [Indexed: 05/03/2023]
Abstract
BACKGROUND Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case-control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change. METHODS Plasma concentrations of 3 OC pesticides (p,p'-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases. RESULTS The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides <25th percentile, adjusted hazard ratios (HRs) in those with 25th-<75th and ≥75th percentiles were 3.5 (95% confidence interval: 1.5-8.5) and 3.2 (1.1-7.6), respectively (Ptrend=0.04). Among 506 subjects who maintained or gained body weight, adjusted HRs were 6.9 and 11.6 (1.4-92.6) among the elderly in the 25th-<75th and ≥75th percentiles compared to <25th percentile (Ptrend<0.01). CONCLUSIONS This prospective study demonstrates that background exposure to OC pesticides are linked to the risk of developing cognitive impairment in elderly. The role of the chronic exposure to low dose OC pesticides in the development of dementia should be further evaluated in other populations.
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Affiliation(s)
- Duk-Hee Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea
| | - P Monica Lind
- Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden
| | - David R Jacobs
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
| | - Samira Salihovic
- MTM Research Center, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Bert van Bavel
- MTM Research Center, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Lars Lind
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
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Saeedi Saravi SS, Dehpour AR. Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: A review. Life Sci 2016; 145:255-264. [PMID: 26549647 DOI: 10.1016/j.lfs.2015.11.006] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 11/01/2015] [Accepted: 11/04/2015] [Indexed: 12/27/2022]
Abstract
Organochlorine pesticides (OCPs) are persistent and bioaccumulative environmental contaminants with potential neurotoxic effects. The growing body of evidence has demonstrated that prenatal exposure to organochlorines (OCs) is associated with impairment of neuropsychological development. The hypothesis is consistent with recent studies emphasizing the correlation of environmental as well as genetic factors to the pathophysiology of neurodevelopmental and neurobehavioral defects. It has been suggested that maternal exposure to OCPs results in impaired motor and cognitive development in newborns and infants. Moreover, in utero exposure to these compounds contributes to the etiology of autism. Although impaired neurodevelopment occurs through prenatal exposure to OCs, breastfeeding causes postnatal toxicity in the infants. Parkinson's disease (PD) is another neurological disorder, which has been associated with exposure to OCs, leading to α-synuclein accumulation and depletion of dopaminergic neurons. The study aimed to review the potential association between pre- and post-natal exposure to OCs and impaired neurodevelopmental processes during pregnancy and neuropsychological diseases such as PD, behavioral alterations, seizures and autism.
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Affiliation(s)
- Seyed Soheil Saeedi Saravi
- Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology-Pharmacology, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
| | - Ahmad Reza Dehpour
- Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Kim SA, Lee YM, Lee HW, Jacobs DR, Lee DH. Can Inconsistent Association between Hypertension and Cognition in Elders be Explained by Levels of Organochlorine Pesticides? PLoS One 2015; 10:e0144205. [PMID: 26630154 PMCID: PMC4668046 DOI: 10.1371/journal.pone.0144205] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 11/13/2015] [Indexed: 12/20/2022] Open
Abstract
The relation between hypertension and cognition in elders remains unclear, and studies on the effect of antihypertensive drugs on cognition have demonstrated conflicting results. This study was performed to evaluate if the association between hypertension and cognition in elders differed depending on serum concentrations of organochlorine (OC) pesticides, common neurotoxic chemicals. Participants were 644 elders aged 60–85 years who participated in the National Health and Nutrition Examination Survey 1999–2002 and were able to complete a cognitive test. We selected 6 OC pesticides that were commonly detected in the elderly. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a relevant tool for evaluating hypertension-related cognitive function, and low cognition was defined by the DSST score < 25th percentile. When OC pesticides were not considered in the analyses, elders with hypertension had about 1.7 times higher risk of low cognition than those without hypertension. However, in analyses stratified by serum concentrations of OC pesticides, the associations between hypertension and low cognition were stronger the higher the serum concentrations of p,p’-DDT, p,p’-DDE, β-hexachlorocyclohexane, and trans-nonachlor increased. Among elders in the 3rd tertile of these pesticides, adjusted odds ratios were from 2.5 to 3.5. In contrast, hypertension was not clearly associated with the risk of low cognition in elders in the 1st tertile of these pesticides. Similar patterns were observed for the continuous DSST score dependent variable. The difference in the association between hypertension and DSST scores according to the levels of OC pesticides suggest a key role of OC pesticides in the development of hypertension-related cognitive impairment and may help to identify hypertensive elders who are at a high risk of cognitive impairment.
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Affiliation(s)
- Se-A Kim
- Department of Biomedical Science, Kyungpook National University, Daegu, Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea
| | - Yu-Mi Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Ho-Won Lee
- Department of Neurology, School of Medicine, Kyungpook National University, Daegu, Korea
- Brain Science & Engineering Institute, Kyungpook National University, Daegu, Korea
| | - David R. Jacobs
- Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
| | - Duk-Hee Lee
- Department of Biomedical Science, Kyungpook National University, Daegu, Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
- * E-mail:
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Gasull M, Pallarès N, Salcedo N, Pumarega J, Alonso J, Porta M. Self-rated health and chronic conditions are associated with blood concentrations of persistent organic pollutants in the general population of Catalonia, Spain. ENVIRONMENTAL RESEARCH 2015; 143:211-220. [PMID: 26505651 DOI: 10.1016/j.envres.2015.10.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 09/09/2015] [Accepted: 10/05/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Self-rated health (SRH) is a powerful predictor of mortality, morbidity, and need for health services. SRH generally increases with educational level, and decreases with age, number of chronic conditions, and body mass index (BMI). Because human concentrations of most persistent organic pollutants (POPs) also vary by age, education, and BMI, and because of the physiological and clinical effects of POPs, we hypothesized that body concentrations of POPs are inversely associated with SRH. OBJECTIVES To analyze the relation between serum concentrations of POPs and SRH in the general population of Catalonia, Spain, taking into account sociodemographic factors and BMI, as well as chronic health conditions and mental disorders, measured by the General Health Questionnaire-12 (GHQ-12). METHODS POP serum concentrations were measured by gas chromatography with electron-capture detection in 919 participants of the Catalan Health Interview Survey. RESULTS Individuals with higher concentrations of POPs had significantly poorer SRH; e.g., the median concentration of HCB in subjects with poor SRH was twice as high as in subjects with excellent SRH (366 ng/g vs. 169 ng/g, respectively; p-value<0.001). In crude models and in models adjusted for sex and BMI, the POPs-SRH association was often dose-dependent, and the likelihood of poor or regular SRH was 2 to 4-times higher in subjects with POP concentrations in the top quartile. In models adjusted for age or for chronic conditions virtually all ORs were near unity. No associations were found between POP levels and GHQ-12. CONCLUSIONS Individuals with higher concentrations of POPs had significantly poorer SRH, an association likely due to age and chronic conditions, but not to sex, education, social class, BMI, or mental disorders.
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Affiliation(s)
- Magda Gasull
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; School of Medicine, Universitat Autònoma de Barcelona, Spain
| | - Natàlia Pallarès
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; School of Medicine, Universitat Autònoma de Barcelona, Spain
| | - Natalia Salcedo
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; School of Medicine, Universitat Autònoma de Barcelona, Spain
| | - José Pumarega
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
| | - Jordi Alonso
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Universitat Pompeu Fabra, Catalonia, Spain
| | - Miquel Porta
- Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; School of Medicine, Universitat Autònoma de Barcelona, Spain.
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Kim SA, Lee YM, Lee HW, Jacobs DR, Lee DH. Greater cognitive decline with aging among elders with high serum concentrations of organochlorine pesticides. PLoS One 2015; 10:e0130623. [PMID: 26107947 PMCID: PMC4480979 DOI: 10.1371/journal.pone.0130623] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 05/21/2015] [Indexed: 11/18/2022] Open
Abstract
Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. “Lower cognitive function” was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in prospective studies.
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Affiliation(s)
- Se-A Kim
- Department of Biomedical Science, Kyungpook National University, Daegu, Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea
| | - Yu-Mi Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Ho-Won Lee
- Department of Neurology, School of Medicine, Kyungpook National University, Daegu, Korea
- Brain Science & Engineering Institute, Kyungpook National University, Daegu, Korea
| | - David R Jacobs
- Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Duk-Hee Lee
- Department of Biomedical Science, Kyungpook National University, Daegu, Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
- * E-mail:
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Ulutaş OK, Çok I, Darendeliler F, Aydin B, Çoban A, Henkelmann B, Schramm KW. Blood levels of polychlorinated biphenlys and organochlorinated pesticides in women from Istanbul, Turkey. ENVIRONMENTAL MONITORING AND ASSESSMENT 2015; 187:132. [PMID: 25701473 DOI: 10.1007/s10661-015-4358-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 02/09/2015] [Indexed: 06/04/2023]
Abstract
The human body is not a chemically uncontaminated system. Every simple action that humans undertake, such as drinking water, eating, nursing, and even breathing air, puts the system under environmental xenobiotic exposure stress. Environmental chemicals have been shown to produce unwanted effects on health and remove the right to healthy living, starting from the first encounter in utero to geriatrics, throughout the lifespan. Organochlorine pesticides (OCPs) and polychlorinated biphenyl (PCB) levels, important members of the persistent organic pollutants (POPs), have been detected before in human breast milk and also in the adipose tissue of women from different regions of Turkey; however, there was no information about the blood levels of these chemicals. This study generated the first information that evaluates OCP and PCB contamination levels in the blood of the women living in Turkey. The current study measured the blood concentrations of OCPs and PCBs in 58 healthy women (age 20-41 years; mean age 28 years) who were living in Istanbul, Turkey, in the years 2010-2012. Samples were analyzed for 29 OCPs and 18 PCB congeners using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). PCB 153 was the predominant congener (643.2 pg/g lipid), followed by PCB 138 and PCB 180. 4,4'-DDE (24872.8 pg/g lipid) was the most common organochlorinated pesticide contaminant in studied blood samples. Results for analyzed chlorinated compounds were as follows: ∑PCB 2682 ± 3300 pg/g lipid; ∑DDT 25,938 ± 28,644 pg/g lipid; and ∑HCH 2930 ± 2222 pg/g lipid, respectively. The mean concentration of ∑WHOPCB-TEQ was 0.037 pg/g on a lipid basis. This information will be important base data during the assessment of the general health concerns of women, as well as for studies about how endocrine disruptors affect humans for forthcoming studies.
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Affiliation(s)
- Onur Kenan Ulutaş
- Department of Toxicology, Gazi University, Faculty of Pharmacy, 06330, Hipodrom, Ankara, Turkey,
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Kim KS, Lee YM, Lee HW, Jacobs DR, Lee DH. Associations between organochlorine pesticides and cognition in U.S. elders: National Health and Nutrition Examination Survey 1999-2002. ENVIRONMENT INTERNATIONAL 2015; 75:87-92. [PMID: 25461417 DOI: 10.1016/j.envint.2014.11.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 11/03/2014] [Accepted: 11/11/2014] [Indexed: 05/06/2023]
Abstract
There is limited evidence about whether background exposure to organochlorine pesticides is related to impairment of cognitive function in general populations. This study was performed to investigate cross-sectional associations between serum concentrations of organochlorine pesticides and cognitive function, a predictor of dementia, among U.S. elders without overt dementia. Study subjects were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. We selected 6 organochlorine pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE), trans-nonachlor, oxychlordane, heptachlor epoxide, and β-hexachlorocyclohexane) which were commonly detected in current general population. Cognitive function was assessed with the Digit-Symbol Substitution Test. All 6 compounds showed statistically significant or marginally significant inverse associations with cognitive score after adjusting for covariates including education levels. The strongest association was observed with p,p'-DDT. With the outcome of low cognitive score defined as <25th percentile, elders in the highest quartile of p,p'-DDT, p,p'-DDE, and β-hexachlorocyclohexane had 2 to 3 times higher risks than those in the lowest quartile. In particular, when their concentrations were further divided with the cutoff points of 90th and 95th percentiles, p,p'-DDT in the highest 5th percentile showed 6.5 (95% confidence interval: 2.6-16.3) times higher risk of low cognitive score. On the other hand, non-persistent pesticides like organophosphates or pyrethroid showed little association with this cognitive score. The potential role of background exposure to organochlorine pesticides in the development of dementia should be explored in future prospective studies and in-vitro/in-vivo experimental studies.
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Affiliation(s)
- Ki-Su Kim
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Yu-Mi Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Ho-Won Lee
- Dept. of Neurology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
| | - David R Jacobs
- Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN, USA
| | - Duk-Hee Lee
- Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
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Yegambaram M, Manivannan B, Beach TG, Halden RU. Role of environmental contaminants in the etiology of Alzheimer's disease: a review. Curr Alzheimer Res 2015; 12:116-46. [PMID: 25654508 PMCID: PMC4428475 DOI: 10.2174/1567205012666150204121719] [Citation(s) in RCA: 177] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 12/10/2014] [Accepted: 01/14/2015] [Indexed: 12/11/2022]
Abstract
Alzheimer's dis ease (AD) is a leading cause of mortality in the developed world with 70% risk attributable to genetics. The remaining 30% of AD risk is hypothesized to include environmental factors and human lifestyle patterns. Environmental factors possibly include inorganic and organic hazards, exposure to toxic metals (aluminium, copper), pesticides (organochlorine and organophosphate insecticides), industrial chemicals (flame retardants) and air pollutants (particulate matter). Long term exposures to these environmental contaminants together with bioaccumulation over an individual's life-time are speculated to induce neuroinflammation and neuropathology paving the way for developing AD. Epidemiologic associations between environmental contaminant exposures and AD are still limited. However, many in vitro and animal studies have identified toxic effects of environmental contaminants at the cellular level, revealing alterations of pathways and metabolisms associated with AD that warrant further investigations. This review provides an overview of in vitro, animal and epidemiological studies on the etiology of AD, highlighting available data supportive of the long hypothesized link between toxic environmental exposures and development of AD pathology.
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Affiliation(s)
| | | | | | - Rolf U Halden
- Center for Environmental Security, The Biodesign Institute, Arizona State University, PO Box 875904 Tempe, AZ 85287, USA.
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The disease intersection of susceptibility and exposure: Chemical exposures and neurodegenerative disease risk. Alzheimers Dement 2014; 10:S213-25. [DOI: 10.1016/j.jalz.2014.04.014] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Singh NK, Banerjee BD, Bala K, Basu M, Chhillar N. Polymorphism in Cytochrome P450 2D6, Glutathione S-Transferases Pi 1 Genes, and Organochlorine Pesticides in Alzheimer Disease: A Case-Control Study in North Indian Population. J Geriatr Psychiatry Neurol 2014; 27:119-27. [PMID: 24584466 DOI: 10.1177/0891988714522698] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Accepted: 11/06/2013] [Indexed: 11/16/2022]
Abstract
OBJECTIVES It has been assumed that the association between Alzheimer disease (AD) and pesticides may be stronger among genetically susceptible individuals. The aim of the study was to examine the genetic polymorphism in cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to organochlorine pesticides (OCPs) and metals in AD. METHODS This study included 100 patients with AD and 100 age-matched controls. The genetic polymorphisms were analyzed by restriction fragment length polymorphism. The OCPs and serum metal levels were determined using gas chromatography and an autoanalyzer, respectively. RESULTS We found a statistically significant association between AD and high levels of β-hexachlorocyclohexane (β-HCH; odds ratio [OR] = 2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086, 95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C (P = .011) allelic variants were associated with increase in AD risk. CONCLUSION This study demonstrates that the GSTP1*B and *C allelic variants may be considered a candidate gene for AD. It can be suggested that although CYP2D6*4 polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may interact with β-HCH, dieldrin, and copper to influence the risk of AD.
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Affiliation(s)
- Neeraj Kumar Singh
- Department of Neurochemistry, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India
| | - B D Banerjee
- Department of Biochemistry, Environmental Biochemistry Laboratory, University College of Medical Science & G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi, India
| | - Kiran Bala
- Department of Neurology, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India
| | - Mitra Basu
- Health Centre, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India
| | - Neelam Chhillar
- Department of Neurochemistry, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India
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Richardson JR, Roy A, Shalat SL, von Stein RT, Hossain MM, Buckley B, Gearing M, Levey AI, German DC. Elevated serum pesticide levels and risk for Alzheimer disease. JAMA Neurol 2014; 71:284-90. [PMID: 24473795 DOI: 10.1001/jamaneurol.2013.6030] [Citation(s) in RCA: 142] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
IMPORTANCE The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). OBJECTIVE To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. DESIGN, SETTING, AND PARTICIPANTS A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. MAIN OUTCOMES AND MEASURES Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. RESULTS Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were -1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. CONCLUSIONS AND RELEVANCE Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD.
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Affiliation(s)
- Jason R Richardson
- Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey2Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey
| | - Ananya Roy
- Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey
| | - Stuart L Shalat
- Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey2Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey
| | - Richard T von Stein
- Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey
| | - Muhammad M Hossain
- Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey2Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey
| | - Brian Buckley
- Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey
| | - Marla Gearing
- Department of Pathology, Emory University School of Medicine, Atlanta, Georgia
| | - Allan I Levey
- Department of Neurology and Alzheimer's Disease, Emory University School of Medicine, Atlanta, Georgia
| | - Dwight C German
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
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Carpenter SK, Mateus-Pinilla NE, Singh K, Lehner A, Satterthwaite-Phillips D, Bluett RD, Rivera NA, Novakofski JE. River otters as biomonitors for organochlorine pesticides, PCBs, and PBDEs in Illinois. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2014; 100:99-104. [PMID: 24119654 DOI: 10.1016/j.ecoenv.2013.07.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Revised: 07/29/2013] [Accepted: 07/30/2013] [Indexed: 06/02/2023]
Abstract
The North American river otter (Lontra canadensis) is a biomonitor for organohalogenated compounds (OHCs) associated with a wide range of deleterious health effects in wildlife and humans. We determined concentrations of twenty OHCs in livers of 23 river otters salvaged by the Illinois Department of Natural Resources from 2009 to 2011, determined sex-dependent distribution of OHCs, and compared our results to the reported concentrations of four OHCs in Illinois river otters from 1984 to 1989. Since these contaminants have been banned for over 30 years, we predicted smaller mean concentrations than those previously reported in Illinois otters. We detected eleven of twenty OHCs; PCBs (polychlorinated biphenyls), dieldrin, and 4,4'-DDE (dichlorodiphenyldichloroethylene) were present in the greatest mean concentrations. We report the largest mean concentration of dieldrin to date in the liver of North American river otters (mean: 174, range: 14.4-534 parts per billion wet wt [ppb]). Mean PCB concentrations were significantly higher in males (mean: 851; range: 30-3450 ppb) than females (mean: 282; range: 40-850 ppb; p=0.04). Mean concentrations of dieldrin were greater than those detected in otters from 1984 to 1989 (mean: 90; range: 30-130 ppb; p<0.05). Our results suggest OHC exposure remains a concern. Future research in Illinois should focus on evaluating OHCs exposures, particularly dieldrin, at the watershed level.
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Affiliation(s)
- Samantha K Carpenter
- Illinois Natural History Survey, University of Illinois Urbana-Champaign, 1816 South Oak St., Champaign IL 61820, United States.
| | - Nohra E Mateus-Pinilla
- Illinois Natural History Survey, University of Illinois Urbana-Champaign, 1816 South Oak St., Champaign IL 61820, United States.
| | - Kuldeep Singh
- College of Veterinary Medicine, University of Illinois Urbana-Champaign, 2001 South Lincoln Ave., Urbana, IL 61802, United States.
| | - Andreas Lehner
- Diagnostic Center for Population and Animal Health, Michigan State University, 4125 Beaumont Rd., Lansing, MI 48910, United States.
| | - Damian Satterthwaite-Phillips
- Illinois Natural History Survey, University of Illinois Urbana-Champaign, 1816 South Oak St., Champaign IL 61820, United States.
| | - Robert D Bluett
- Illinois Department of Natural Resources, One Natural Resources Way, Springfield, IL 62702-1271, United States.
| | - Nelda A Rivera
- Illinois Natural History Survey, University of Illinois Urbana-Champaign, 1816 South Oak St., Champaign IL 61820, United States.
| | - Jan E Novakofski
- Department of Animal Sciences, University of Illinois Urbana-Champaign, 205 Meat Science Lab 1503S Maryland Dr M/C 010, Urbana, IL 61801, United States.
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A short review on the implications of base excision repair pathway for neurons: relevance to neurodegenerative diseases. Mitochondrion 2013; 16:38-49. [PMID: 24220222 DOI: 10.1016/j.mito.2013.10.007] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 10/31/2013] [Accepted: 10/31/2013] [Indexed: 12/13/2022]
Abstract
Oxidative DNA damage results from the attack by reactive oxygen and nitrogen species (ROS/RNS) on human genome. This includes base modifications such as oxidized bases, abasic (AP) sites, and single-strand breaks (SSBs), all of which are repaired by the base excision repair (BER) pathway, one among the six known repair pathways. BER-pathway in mammalian cells involves several evolutionarily conserved proteins and is also linked to genome replication and transcription. The BER-pathway enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease (APE1), form complexes with downstream repair enzymes via protein-protein and DNA-protein interactions. An emerging concept for BER proteins is their involvement in non-canonical functions associated to RNA metabolism, which is opening new interesting perspectives. Various mechanisms that are underlined in maintaining neuronal cell genome integrity are identified, but are inconclusive in providing protection against oxidative damage in neurodegenerative disorders, main emphasis is given towards the role played by the proteins of BER-pathway that is discussed. In addition, mechanisms of action of BER-pathway in nuclear vs. mitochondria as well as the non-canonical functions are discussed in connection to human neurodegenerative diseases.
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