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Turesky RJ, Jones C, Guo J, Cammerrer K, Maertens LA, Antonarakis ES, Lu Z, Spector LG. Biomonitoring PhIP, a Potential Prostatic Carcinogen, in the Hair of Healthy Men of African and European Ancestry. TOXICS 2025; 13:42. [PMID: 39853040 PMCID: PMC11769170 DOI: 10.3390/toxics13010042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 12/20/2024] [Accepted: 01/04/2025] [Indexed: 01/26/2025]
Abstract
Heterocyclic aromatic amines (HAAs), formed during the cooking of meat, are potential human carcinogens, underscoring the need for long-lived biomarkers to assess exposure and cancer risk. Frequent consumption of well-done meats containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a prevalent HAA that is a prostatic carcinogen in rodents and DNA-damaging agent in human prostate cells, has been linked to aggressive prostate cancer (PC) pathology. African American (AA) men face nearly twice the risk for developing and dying from PC compared to White men. We previously demonstrated that scalp hair is a reliable biospecimen for measuring PhIP intake using liquid chromatography-mass spectrometry. This study aimed to determine whether PhIP dietary intake is higher in AA men, potentially contributing to this health disparity. Healthy AA men were found to have a significantly higher mean hair PhIP level (2.12-fold) than White men on free-choice diets. However, this difference was not statistically significant after adjusting for melanin content. Further research is needed to understand how hair pigmentation, follicular density, and other morphological features of hair influence PhIP accumulation. These insights can improve the accuracy of using hair PhIP levels as a biomarker for exposure and its potential associations with cancer risk.
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Affiliation(s)
- Robert J. Turesky
- Masonic Cancer Center, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; (J.G.); (K.C.)
| | - Clarence Jones
- Hue-Man Partnership, 2400 Park Ave., Minneapolis, MN 55404, USA;
| | - Jingshu Guo
- Masonic Cancer Center, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; (J.G.); (K.C.)
- Clinical Research and Toxicology, Chromatography and Mass Spectrometry Division, Thermo Fisher Scientific, 355 River Oaks Parkway, San Jose, CA 95134, USA
| | - Kari Cammerrer
- Masonic Cancer Center, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; (J.G.); (K.C.)
| | - Laura A. Maertens
- Masonic Cancer Center, Division of Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA;
| | | | - Zhanni Lu
- Masonic Cancer Center, Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN 55455, USA;
| | - Logan G. Spector
- Masonic Cancer Center, Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN 55455, USA;
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2
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Yang Y, Xu S, He H, Zhu X, Liu Y, Ai X, Chen Y. Mechanism of sturgeon intestinal inflammation induced by Yersinia ruckeri and the effect of florfenicol intervention. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 273:116138. [PMID: 38394759 DOI: 10.1016/j.ecoenv.2024.116138] [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: 12/19/2023] [Revised: 01/29/2024] [Accepted: 02/19/2024] [Indexed: 02/25/2024]
Abstract
The mechanism by which Y. ruckeri infection induces enteritis in Chinese sturgeon remains unclear, and the efficacy of drug prevention and control measures is not only poor but also plagued with numerous issues. We conducted transcriptomic and 16 S rRNA sequencing analyses to examine the differences in the intestinal tract of hybrid sturgeon before and after Y. ruckeri infection and florfenicol intervention. Our findings revealed that Y. ruckeri induced the expression of multiple inflammatory factors, including il1β, il6, and various chemokines, as well as casp3, casp8, and multiple tumor necrosis factor family members, resulting in pathological injury to the body. Additionally, at the phylum level, the relative abundance of Firmicutes and Bacteroidota increased, while the abundance of Plesiomonas and Cetobacterium decreased at the genus level, altering the composition of the intestinal flora. Following florfenicol intervention, the expression of multiple apoptosis and inflammation-related genes was down-regulated, promoting tissue repair. However, the flora became further dysregulated, increasing the risk of infection. In conclusion, our analysis of the transcriptome and intestinal microbial composition demonstrated that Y. ruckeri induces intestinal pathological damage by triggering apoptosis and altering the composition of the intestinal microbiota. Florfenicol intervention can repair pathological damage, but it also exacerbates flora imbalance, leading to a higher risk of infection. These findings help elucidate the molecular mechanism of Y. ruckeri-induced enteritis in sturgeon and evaluate the therapeutic effect of drugs on intestinal inflammation in sturgeon.
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Affiliation(s)
- Yibin Yang
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; Key Laboratory of Sturgeon Genetics and Breeding, Ministry of Agriculture and Rural Affairs, Hangzhou Qiandao Lake Sturgeon Technology Co., Ltd., Hangzhou 311799, China
| | - Shijian Xu
- Key Laboratory of Sturgeon Genetics and Breeding, Ministry of Agriculture and Rural Affairs, Hangzhou Qiandao Lake Sturgeon Technology Co., Ltd., Hangzhou 311799, China.
| | - Hao He
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China
| | - Xia Zhu
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China
| | - Yongtao Liu
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China
| | - Xiaohui Ai
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China.
| | - Yuhua Chen
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
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3
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Dai Z, Wu Y, Xiong Y, Wu J, Wang M, Sun X, Ding X, Yang L, Sun X, Ge G. CYP1A inhibitors: Recent progress, current challenges, and future perspectives. Med Res Rev 2024; 44:169-234. [PMID: 37337403 DOI: 10.1002/med.21982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 03/28/2023] [Accepted: 05/23/2023] [Indexed: 06/21/2023]
Abstract
Mammalian cytochrome P450 1A (CYP1A) are key phase I xenobiotic-metabolizing enzymes that play a distinctive role in metabolic activation or metabolic clearance of a variety of procarcinogens, drugs, and endogenous substances. Human CYP1A subfamily contains two members (hCYP1A1 and hCYP1A2), which are known to catalyze the oxidative activation of some environmental procarcinogens into carcinogenic species. Increasing evidence has demonstrated that CYP1A inhibitor therapies are promising strategies for cancer chemoprevention or overcoming CYP1A-associated drug toxicity and resistance. Herein, we reviewed recent advances in the discovery and characterization of hCYP1A inhibitors, from the discovery approaches to structural features and biomedical applications of hCYP1A inhibitors. The inhibition potentials, inhibition modes, and inhibition constants of all reported hCYP1A inhibitors are comprehensively summarized. Meanwhile, the structural features and structure-activity relationships of different classes of hCYP1A1 and hCYP1A2 inhibitors are analyzed and discussed in depth. Furthermore, the major challenges and future directions for this field are presented and highlighted. Collectively, the information and knowledge presented here will strongly facilitate the researchers to discover and develop more efficacious CYP1A inhibitors for specific purposes, such as chemo-preventive agents or as tool molecules in hCYP1A-related fundamental studies.
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Affiliation(s)
- Ziru Dai
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yue Wu
- Shanghai Frontiers Science Center for TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuan Xiong
- Shanghai Frontiers Science Center for TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jingjing Wu
- Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China
| | - Min Wang
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiao Sun
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xinxin Ding
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, America
| | - Ling Yang
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Xiaobo Sun
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Guangbo Ge
- Shanghai Frontiers Science Center for TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Manning TJ, Livingston T, Persaud C, Patel A, Adair M, Taylor T, Bland P. Ethanol Inhalation as a Method to Denature the Spike Protein of SARS-CoV-2. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1457:45-77. [PMID: 39283420 DOI: 10.1007/978-3-031-61939-7_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2024]
Abstract
The SARS-CoV-2 virus caused the 2019 COVID pandemic by infecting almost eight hundred million people worldwide. Because it was a new viral infection, there were no vaccines or small molecule medications that could prevent or treat the disease. This chapter provides some details for an obscure treatment for COVID-19, that has decades of anti-viral activity data both in vitro and in vivo in the literature. The medicinal molecules are compared to other small molecules that were identified as possible medications for COVID-19. We developed a computational method that ranks small molecules and their ability to penetrate mucus in the lungs of a COVID-19 patient. Our focus is ethanol as a COVID-19 treatment. The results discussed here are based on Lipinski Rules and QSAR computational methods as well as in vitro and in vivo data. These parameters indicate that ethanol should be a strong candidate for future evaluations.
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Affiliation(s)
- Thomas J Manning
- Chemistry Department, Valdosta State University, Valdosta, GA, 31698, USA.
| | | | - Capri Persaud
- Chemistry Department, Valdosta State University, Valdosta, GA, 31698, USA
| | - Akshil Patel
- Chemistry Department, Valdosta State University, Valdosta, GA, 31698, USA
| | - Madelyn Adair
- Chemistry Department, Valdosta State University, Valdosta, GA, 31698, USA
| | - Taylor Taylor
- Chemistry Department, Valdosta State University, Valdosta, GA, 31698, USA
| | - Paige Bland
- Chemistry Department, Valdosta State University, Valdosta, GA, 31698, USA
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5
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Kejík Z, Koubková N, Krčová L, Sýkora D, Abramenko N, Veselá K, Kaplánek R, Hajduch J, Houdová Megová M, Bušek P, Šedo A, Lacina L, Smetana K, Martásek P, Jakubek M. Combination of quinoxaline with pentamethinium system: Mitochondrial staining and targeting. Bioorg Chem 2023; 141:106816. [PMID: 37716274 DOI: 10.1016/j.bioorg.2023.106816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 08/15/2023] [Accepted: 08/26/2023] [Indexed: 09/18/2023]
Abstract
Pentamethinium indolium salts are promising fluorescence probes and anticancer agents with high mitochondrial selectivity. We synthesized two indolium pentamethinium salts: a cyclic form with quinoxaline directly incorporated in the pentamethinium chain (cPMS) and an open form with quinoxaline substitution in the γ-position (oPMS). To better understand their properties, we studied their interaction with mitochondrial phospholipids (cardiolipin and phosphatidylcholine) by spectroscopic methods (UV-Vis, fluorescence, and NMR spectroscopy). Both compounds displayed significant affinity for cardiolipin and phosphatidylcholine, which was associated with a strong change in their UV-Vis spectra. Nevertheless, we surprisingly observed that fluorescence properties of cPMS changed in complex with both cardiolipin and phosphatidylcholine, whereas those of oPMS only changed in complex with cardiolipin. Both salts, especially cPMS, display high usability in mitochondrial imaging and are cytotoxic for cancer cells. The above clearly indicates that conjugates of pentamethinium and quinoxaline group, especially cPMS, represent promising structural motifs for designing mitochondrial-specific agents.
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Affiliation(s)
- Zdeněk Kejík
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
| | - Nela Koubková
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
| | - Lucie Krčová
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
| | - David Sýkora
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
| | - Nikita Abramenko
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - Kateřina Veselá
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - Robert Kaplánek
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
| | - Jan Hajduch
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic
| | - Magdalena Houdová Megová
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague 2, CZ-120 00 Prague, Czech Republic
| | - Petr Bušek
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague 2, CZ-120 00 Prague, Czech Republic
| | - Aleksi Šedo
- Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague 2, CZ-120 00 Prague, Czech Republic
| | - Lukáš Lacina
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Dermatovenerology, First Faculty of Medicine, Charles University and General University Hospital, CZ-128 08 Prague, Czech Republic; Institute of Anatomy, First Faculty of Medicine, Charles University, Prague 2, CZ-120 00 Prague, Czech Republic
| | - Karel Smetana
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Institute of Anatomy, First Faculty of Medicine, Charles University, Prague 2, CZ-120 00 Prague, Czech Republic
| | - Pavel Martásek
- Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic
| | - Milan Jakubek
- BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Prumyslová 595, 252 50 Vestec, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 6, 166 28 Prague, Czech Republic.
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6
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Zhang J, Qiu Z, Zhang Y, Wang G, Hao H. Intracellular spatiotemporal metabolism in connection to target engagement. Adv Drug Deliv Rev 2023; 200:115024. [PMID: 37516411 DOI: 10.1016/j.addr.2023.115024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 07/05/2023] [Accepted: 07/26/2023] [Indexed: 07/31/2023]
Abstract
The metabolism in eukaryotic cells is a highly ordered system involving various cellular compartments, which fluctuates based on physiological rhythms. Organelles, as the smallest independent sub-cell unit, are important contributors to cell metabolism and drug metabolism, collectively designated intracellular metabolism. However, disruption of intracellular spatiotemporal metabolism can lead to disease development and progression, as well as drug treatment interference. In this review, we systematically discuss spatiotemporal metabolism in cells and cell subpopulations. In particular, we focused on metabolism compartmentalization and physiological rhythms, including the variation and regulation of metabolic enzymes, metabolic pathways, and metabolites. Additionally, the intricate relationship among intracellular spatiotemporal metabolism, metabolism-related diseases, and drug therapy/toxicity has been discussed. Finally, approaches and strategies for intracellular spatiotemporal metabolism analysis and potential target identification are introduced, along with examples of potential new drug design based on this.
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Affiliation(s)
- Jingwei Zhang
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China
| | - Zhixia Qiu
- Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yongjie Zhang
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Guangji Wang
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China; Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, Nanjing, China.
| | - Haiping Hao
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
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7
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Moslemi M, Jannat B, Mahmoudzadeh M, Ghasemlou M, Abedi A. Detoxification activity of bioactive food compounds against ethanol-induced injuries and hangover symptoms: A review. Food Sci Nutr 2023; 11:5028-5040. [PMID: 37701198 PMCID: PMC10494618 DOI: 10.1002/fsn3.3520] [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: 08/13/2022] [Revised: 04/08/2023] [Accepted: 06/08/2023] [Indexed: 09/14/2023] Open
Abstract
Alcohol drinking is a popular activity among adolescents in many countries, largely due to its pleasant, relaxing effects. As a major concern, ethanol consumption put the drinkers at risk of nutrients' deficiency due to the disordered eating, anorexia, and malabsorption of nutrients. Moreover, alcohol drinking may lead to the development of hangover symptoms including diarrhea, thirsty, fatigue, and oxidative stress. A broad range of functional food components with antioxidant and/or anti-inflammatory properties including pectin, aloe vera polysaccharides, chito-oligosaccharides, and other herbal components have been explored due to their detoxification effects against ethanol. The underlying anti-hangover mechanisms include reducing the intestinal absorption of ethanol or its metabolites, increasing the activity of ethanol metabolizing enzymes, development of fatty acid β-oxidation in mitochondria, inhibition of inflammatory response, blocking the target receptors of ethanol in the body, and possession of antioxidant activity under the oxidative stress developed by ethanol consumption. Therefore, the development of bioactive food-based therapeutic formula can assist clinicians and also drinkers in the alleviation of alcohol side effects.
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Affiliation(s)
- Masoumeh Moslemi
- Halal Research Center of IRIMinistry of Health and Medical EducationTehranIran
| | - Behrooz Jannat
- Halal Research Center of IRIMinistry of Health and Medical EducationTehranIran
| | - Maryam Mahmoudzadeh
- Nutrition Research Center and Department of Food Science and Technology, Faculty of Nutrition and Food ScienceTabriz University of Medical SciencesTabrizIran
| | - Mehran Ghasemlou
- School of ScienceSTEM College, RMIT UniversityMelbourneVictoriaAustralia
| | - Abdol‐Samad Abedi
- Department of Research Deputy, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food TechnologyShahid Beheshti University of Medical SciencesTehranIran
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8
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Stipp MC, Kulik JD, Corso CR, Galindo CM, Adami ER, Evangelista AG, Luciano FB, Winnischofer SMB, Cadena SMSC, Sassaki GL, Acco A. Influence of red wine polysaccharides on cytochrome P450 enzymes and inflammatory parameters in tumor models. Int J Biol Macromol 2023; 240:124385. [PMID: 37060983 DOI: 10.1016/j.ijbiomac.2023.124385] [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: 02/01/2023] [Revised: 04/04/2023] [Accepted: 04/05/2023] [Indexed: 04/17/2023]
Abstract
The soluble fraction of polysaccharides from cabernet franc red wine (SFP) previously showed antitumoral effects by modulating the immune system. The present study tested the hypothesis that the SFP can regulate CYPs in vitro in HepG2 cells and in vivo in Walker-256 tumor-bearing rats. The SFP was used in the following protocols: (i) solid tumor, (ii) liquid tumor, and (iii) chemopreventive solid tumor. The SFP reduced solid tumor growth in both solid tumor protocols but did not inhibit liquid tumor development. The SFP reduced total CYP levels in the solid and liquid tumor protocols and reduced the gene expression of Cyp1a1 and Cyp2e1 in rats and CYP1A2 in HepG2 cells. An increase of N-acetylglucosaminidase activity was observed in all SFP-treated rats, and TNF-α levels increased in the solid tumor protocol in the vehicle, SFP, and vincristine (positive control) groups. The chemopreventive solid tumor protocol did not modify CYP levels in the liver or intestine or N-acetylglucosaminidase and myeloperoxidase activity in the liver. The in vitro digestion and nuclear magnetic resonance analyses suggested that SFP was minimally modified in the gastrointestinal system. In conclusion, SFP inhibited CYPs both in vivo and in vitro, likely as a result of its immunoinflammatory actions.
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Affiliation(s)
| | - Juliana Danna Kulik
- Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil
| | - Claudia Rita Corso
- Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil
| | | | | | | | | | | | | | - Guilherme Lanzi Sassaki
- Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil
| | - Alexandra Acco
- Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
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9
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Han SC, Huang RP, Zhang QY, Yan CY, Li XY, Li YF, He RR, Li WX. Antialcohol and Hepatoprotective Effects of Tamarind Shell Extract on Ethanol-Induced Damage to HepG2 Cells and Animal Models. Foods 2023; 12:1078. [PMID: 36900595 PMCID: PMC10000874 DOI: 10.3390/foods12051078] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 02/28/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Alcohol liver disease (ALD) is one of the leading outcomes of acute and chronic liver injury. Accumulative evidence has confirmed that oxidative stress is involved in the development of ALD. In this study, we used chick embryos to establish ALD model to study the hepatoprotective effects of tamarind shell exttract (TSE). Chick embryos received 25% ethanol (75 μL) and TSE (250, 500, 750 μg/egg/75 μL) from embryonic development day (EDD) 5.5. Both ethanol and TSE were administrated every two days until EDD15. Ethanol-exposed zebrafish and HepG2 cell model were also employed. The results suggested that TSE effectively reversed the pathological changes, liver dysfunction and ethanol-metabolic enzyme disorder in ethanol-treated chick embryo liver, zebrafish and HepG2 cells. TSE suppressed the excessive reactive oxygen species (ROS) in zebrafish and HepG2 cells, as well as rebuilt the irrupted mitochondrial membrane potential. Meanwhile, the declined antioxidative activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), together with the content of total glutathione (T-GSH) were recovered by TSE. Moreover, TSE upregulated nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxyense-1 (HO-1) expression in protein and mRNA level. All the phenomena suggested that TSE attenuated ALD through activating NRF2 to repress the oxidative stress induced by ethanol.
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Affiliation(s)
- Shao-Cong Han
- College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
| | - Rong-Ping Huang
- College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
| | - Qiong-Yi Zhang
- Guangdong Engineering Research Centre of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China
| | - Chang-Yu Yan
- Guangdong Engineering Research Centre of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China
| | - Xi-You Li
- College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
| | - Yi-Fang Li
- Guangdong Engineering Research Centre of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China
| | - Rong-Rong He
- Guangdong Engineering Research Centre of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China
| | - Wei-Xi Li
- College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
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10
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Starek-Świechowicz B, Budziszewska B, Starek A. Alcohol and breast cancer. Pharmacol Rep 2023; 75:69-84. [PMID: 36310188 PMCID: PMC9889462 DOI: 10.1007/s43440-022-00426-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 10/05/2022] [Accepted: 10/06/2022] [Indexed: 02/04/2023]
Abstract
Breast cancer is one of the main causes of death in women worldwide. In women, breast cancer includes over half of all tumours caused by alcohol. This paper discusses both ethanol metabolism and the mechanisms of mammary tumourigenesis caused by alcohol. Numerous signalling pathways in neoplastic transformation following alcohol consumption in women have been presented. In addition, primary and secondary prevention, phytochemicals, synthetic chemicals, specific inhibitors of enzymes and selective receptor modulators have been described.
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Affiliation(s)
- Beata Starek-Świechowicz
- Department of Biochemical Toxicology, Chair of Toxicology, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland
| | - Bogusława Budziszewska
- Department of Biochemical Toxicology, Chair of Toxicology, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland
| | - Andrzej Starek
- Department of Biochemical Toxicology, Chair of Toxicology, Medical College, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland
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11
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Chung J, Akter S, Han S, Shin Y, Choi TG, Kang I, Kim SS. Diagnosis by Volatile Organic Compounds in Exhaled Breath in Exhaled Breath from Patients with Gastric and Colorectal Cancers. Int J Mol Sci 2022; 24:129. [PMID: 36613569 PMCID: PMC9820758 DOI: 10.3390/ijms24010129] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 12/15/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
One in three cancer deaths worldwide are caused by gastric and colorectal cancer malignancies. Although the incidence and fatality rates differ significantly from country to country, the rates of these cancers in East Asian nations such as South Korea and Japan have been increasing each year. Above all, the biggest danger of this disease is how challenging it is to recognize in its early stages. Moreover, most patients with these cancers do not present with any disease symptoms before receiving a definitive diagnosis. Currently, volatile organic compounds (VOCs) are being used for the early prediction of several other diseases, and research has been carried out on these applications. Exhaled VOCs from patients possess remarkable potential as novel biomarkers, and their analysis could be transformative in the prevention and early diagnosis of colon and stomach cancers. VOCs have been spotlighted in recent studies due to their ease of use. Diagnosis on the basis of patient VOC analysis takes less time than methods using gas chromatography, and results in the literature demonstrate that it is possible to determine whether a patient has certain diseases by using organic compounds in their breath as indicators. This study describes how VOCs can be used to precisely detect cancers; as more data are accumulated, the accuracy of this method will increase, and it can be applied in more fields.
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Affiliation(s)
- Jinwook Chung
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Salima Akter
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Sunhee Han
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Yoonhwa Shin
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Tae Gyu Choi
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Insug Kang
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Sung Soo Kim
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
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12
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Creatine supplementation protects against diet-induced non-alcoholic fatty liver but exacerbates alcoholic fatty liver. Life Sci 2022; 310:121064. [PMID: 36220368 DOI: 10.1016/j.lfs.2022.121064] [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: 08/09/2022] [Revised: 09/26/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022]
Abstract
AIMS This work investigated the effects of creatine supplementation on different pathways related to the pathogenesis of non-alcoholic fatty liver disease and alcoholic liver disease. MAIN METHODS To induce alcoholic liver disease, male Swiss mice were divided into three groups: control, ethanol and ethanol supplemented with creatine. To induce non-alcoholic fatty liver disease, mice were divided into three groups: control, high-fat diet and high-fat diet supplemented with creatine. Each group consisted of eight animals. In both cases, creatine monohydrate was added to the diets (1 %; weight/vol). KEY FINDINGS Creatine supplementation prevented high-fat diet-induced non-alcoholic fatty liver disease progression, demonstrated by attenuated liver fat accumulation and liver damage. On the other hand, when combined with ethanol, creatine supplementation up-regulated key genes related to ethanol metabolism, oxidative stress, inflammation and lipid synthesis, and exacerbated ethanol-induced liver steatosis and damage, demonstrated by increased liver fat accumulation and histopathological score, as well as elevated oxidative damage markers and inflammatory mediators. SIGNIFICANCE Our results clearly demonstrated creatine supplementation exerts different outcomes in relation to non-alcoholic fatty liver disease and alcoholic liver disease, namely it protects against high-fat diet-induced non-alcoholic fatty liver disease but exacerbates ethanol-induced alcoholic liver disease. The exacerbating effects of the creatine and ethanol combination appear to be related to oxidative stress and inflammation-mediated up-regulation of ethanol metabolism.
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13
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Wang Y, Charkoftaki G, Davidson E, Orlicky DJ, Tanguay RL, Thompson DC, Vasiliou V, Chen Y. Oxidative stress, glutathione, and CYP2E1 in 1,4-dioxane liver cytotoxicity and genotoxicity: insights from animal models. CURRENT OPINION IN ENVIRONMENTAL SCIENCE & HEALTH 2022; 29:100389. [PMID: 37483863 PMCID: PMC10361651 DOI: 10.1016/j.coesh.2022.100389] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
1,4-Dioxane (DX) is an emerging drinking water contaminant worldwide, which poses a threat to public health due to its demonstrated liver carcinogenicity and potential for human exposure. The lack of drinking water standards for DX is attributed to undetermined mechanisms of DX carcinogenicity. This mini-review provides a brief discussion of a series of mechanistic studies, wherein unique mouse models were exposed to DX in drinking water to elucidate redox changes associated with DX cytotoxicity and genotoxicity. The overall conclusions from these studies support a direct genotoxic effect by high dose DX and imply that oxidative stress involving CYP2E1 activation may play a causal role in DX liver genotoxicity and potentially carcinogenicity. The mechanistic data derived from these studies can serve as important references to refine the assessment of carcinogenic pathways that may be triggered at environmentally relevant low doses of DX in future animal and human studies.
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Affiliation(s)
- Yewei Wang
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - Georgia Charkoftaki
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - Emily Davidson
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
- Department of Cellular & Molecular Physiology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA
| | - David J. Orlicky
- Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Center, University of Colorado, Aurora, CO 80045, USA
| | - Robyn L. Tanguay
- Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
| | - David C. Thompson
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - Vasilis Vasiliou
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - Ying Chen
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
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14
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Jiang YH, Wang L, Chen WD, Duan YT, Sun MJ, Huang JJ, Peng DY, Yu NJ, Wang YY, Zhang Y. Poria cocos polysaccharide prevents alcohol-induced hepatic injury and inflammation by repressing oxidative stress and gut leakiness. Front Nutr 2022; 9:963598. [PMID: 36061887 PMCID: PMC9428680 DOI: 10.3389/fnut.2022.963598] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/25/2022] [Indexed: 12/24/2022] Open
Abstract
Alcoholic liver disease (ALD) is a major worldwide chronic liver disease accompanied by hepatic inflammation, gut leakiness, and abnormal oxidative stress. Our previous study demonstrated substantial hepatoprotective activity of the active Poria cocos polysaccharide (PCP-1C). The present study explored whether PCP-1C protects against ALD among hepatic inflammation, gut leakiness, and abnormal oxidative stress. The results showed that PCP-1C significantly improved alcohol-induced liver injury by decreasing serum biochemical parameters, alleviating hepatic steatosis, and reducing lipid accumulation caused by ALD. Moreover, PCP-1C treatment reduced hepatic inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and also improved hepatocyte apoptosis by inhibiting the cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/mitogen-activated protein kinases (MAPKs) signaling pathway. Regarding intestinal protection, PCP-1C could repair the intestinal barrier and reduce lipopolysaccharide (LPS) leakage. Generally, PCP-1C exerts a positive therapeutic effect on ALD, which may play a pivotal of decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and improving intestinal barrier injury.
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Affiliation(s)
- Yue-hang Jiang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Lei Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, China
- Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, China
| | - Wei-dong Chen
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, China
- Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, China
- Institute of Conservation and Development of Traditional Chinese Medicine Resources, Hefei, China
| | - Yu-ting Duan
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Ming-jie Sun
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Jia-jing Huang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
| | - Dai-yin Peng
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, China
- Institute of Conservation and Development of Traditional Chinese Medicine Resources, Hefei, China
| | - Nian-jun Yu
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, China
- Institute of Conservation and Development of Traditional Chinese Medicine Resources, Hefei, China
| | - Yan-yan Wang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, China
- *Correspondence: Yan-yan Wang,
| | - Yue Zhang
- School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China
- MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, China
- Yue Zhang,
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15
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Ohira H, Oikawa D, Kurokawa Y, Aoki Y, Omura A, Kiyomoto K, Nakagawa W, Mamoto R, Fujioka Y, Nakayama T. Suppression of colonic oxidative stress caused by chronic ethanol administration and attenuation of ethanol-induced colitis and gut leakiness by oral administration of sesaminol in mice. Food Funct 2022; 13:9285-9298. [PMID: 35968694 DOI: 10.1039/d1fo04120g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Chronic consumption of excess ethanol is one of the major risk factors for colorectal cancer (CRC), and the pathogenesis of ethanol-related CRC (ER-CRC) involves ethanol-induced oxidative-stress and inflammation in the colon and rectum, as well as gut leakiness. In this study, we hypothesised that oral administration of sesaminol, a sesame lignan, lowers the risk of ER-CRC because we found that it is a strong antioxidant with very low prooxidant activity. This hypothesis was examined using a mouse model, in which 2.0% v/v ethanol was administered ad libitum for 2 weeks with or without oral gavage with sesaminol (2.5 mg per day). Oral sesaminol administration suppressed the ethanol-induced colonic lesions and the ethanol-induced elevation of the colonic levels of oxidative stress markers (8-hydroxy-2'-deoxyguanosine, malondialdehyde, and 4-hydroxyalkenals). It consistently suppressed the chronic ethanol-induced expressions of cytochrome P450-2E1 and inducible nitric oxide synthase and upregulated heme oxygenase-1 expression, probably via the nuclear factor erythroid-derived 2-like 2 pathway in the mouse colon. Oral sesaminol administration also suppressed the chronic ethanol-induced elevation of colonic inflammation marker levels, such as those of tumour necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, probably via the nuclear factor-kappa B pathway. Moreover, it prevented the chronic ethanol-induced gut leakiness by restoring tight junction proteins, giving rise to lower plasma endotoxin levels compared with those of ethanol-administered mice. All of these results suggest that dietary supplementation of sesaminol may lower the risk of ER-CRC by suppressing each of the above-mentioned steps in ER-CRC pathogenesis.
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Affiliation(s)
- Hideo Ohira
- Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University, Kobe 651-2180, Japan
| | - Daiki Oikawa
- Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579, Japan
| | - Yoichi Kurokawa
- Faculty of Bioscience, Fukui Prefectural University, Fukui 910-1195, Japan
| | - Yuichi Aoki
- Tohoku University Tohoku Medical Megabank Organization, Seiryo 2-1, Sendai, Miyagi 980-8573, Japan
| | - Ayano Omura
- Kiyomoto Co., Ltd., 6-1633 Totoro-cho, Nobeoka, Miyazaki 889-0595, Japan
| | - Kunio Kiyomoto
- Kiyomoto Co., Ltd., 6-1633 Totoro-cho, Nobeoka, Miyazaki 889-0595, Japan
| | - Wao Nakagawa
- Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University, Kobe 651-2180, Japan
| | - Rie Mamoto
- Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University, Kobe 651-2180, Japan
| | - Yoshio Fujioka
- Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University, Kobe 651-2180, Japan
| | - Toru Nakayama
- Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579, Japan
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16
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Sun X, Zhong X, Ma W, Feng W, Huang Q, Ma M, Lv M, Hu R, Han Z, Li J, Zhou X. Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis. Exp Ther Med 2022; 24:456. [PMID: 35747157 PMCID: PMC9204551 DOI: 10.3892/etm.2022.11383] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 04/14/2022] [Indexed: 11/09/2022] Open
Abstract
Liver cancer is a highly lethal malignancy. Despite considerable efforts made in recent years, the prognosis of patients with liver cancer remains poor. Curcuma zedoaria (known as Ezhu in Chinese) is widely prescribed in traditional Chinese medicine. Germacrone (GM) is a sesquiterpene constituent derived from the essential oil of Ezhu, and exerts anti-carcinogenic effects by inducing apoptosis in various cancer cells. The present study investigated the potential mechanism of GM in HepG2 cells. Cell Counting Kit-8, colony-formation and lactate dehydrogenase-release assays, as well as cell death assays using flow cytometry, were performed to evaluate HepG2 cell proliferation following GM treatment. HepG2 cells were transfected with caspase-3 small interfering RNA and then treated with GM. Caspase-3 expression levels were determined by reverse transcription-quantitative PCR and western blotting. The present study showed that GM inhibited the growth of HepG2 cells and induced the proteolytic cleavage of caspase 3, with concomitant cleavage of gasdermin E (GSDME), by markedly increasing the production of reactive oxygen species (ROS). This led to caspase 3-dependent cleavage of GSDME, thereby promoting pyroptosis in HepG2 cells. However, these changes were rescued by ROS scavengers, such as N-acetylcysteine. Furthermore, GM inhibited tumor growth by promoting the cleavage of caspase 3 and GSDME in HepG2 cell xenograft models. These results indicated that GM induced GSDME-dependent pyroptosis through caspase 3 activation, at least in part, by damaging the mitochondria and enhancing ROS production, thereby supporting the possible development of GM as a candidate for the prevention and treatment of liver cancer.
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Affiliation(s)
- Xinfeng Sun
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Xin Zhong
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Wenfeng Ma
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Wenxing Feng
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Qi Huang
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Mengqing Ma
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Minling Lv
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Rui Hu
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Zhiyi Han
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Jing Li
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
| | - Xiaozhou Zhou
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.,Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China
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17
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Yang Y, Zhu X, Huang Y, Zhang H, Liu Y, Xu N, Fu G, Ai X. RNA-Seq and 16S rRNA Analysis Revealed the Effect of Deltamethrin on Channel Catfish in the Early Stage of Acute Exposure. Front Immunol 2022; 13:916100. [PMID: 35747138 PMCID: PMC9211022 DOI: 10.3389/fimmu.2022.916100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/09/2022] [Indexed: 12/02/2022] Open
Abstract
Deltamethrin (Del) is a widely used pyrethroid insecticide and a dangerous material that has brought serious problems to the healthy breeding of aquatic animals. However, the toxicological mechanisms of Del on channel catfish remain unclear. In the present study, we exposed channel catfish to 0, 0.5, and 5 μg/L Del for 6 h, and analyzed the changes in histopathology, trunk kidney transcriptome, and intestinal microbiota composition. The pathological analyses showed that a high concentration of Del damaged the intestine and trunk kidney of channel catfish in the early stage. The transcriptome analysis detected 32 and 1837 differentially expressed genes (DEGs) in channel catfish trunk kidneys after exposure to 0.5 and 5 μg/L Del, respectively. Moreover, the KEGG pathway and GO enrichment analyses showed that the apoptosis signaling pathway was significantly enriched, and apoptosis-related DEGs, including cathepsin L, p53, Bax, and caspase-3, were also detected. These results suggested that apoptosis occurs in the trunk kidney of channel catfish in the early stage of acute exposure to Del. We also detected some DEGs and signaling pathways related to immunity and drug metabolism, indicating that early exposure to Del can lead to immunotoxicity and metabolic disorder of channel catfish, which increases the risk of pathogenic infections and energy metabolism disorders. Additionally, 16S rRNA gene sequencing showed that the composition of the intestinal microbiome significantly changed in channel catfish treated with Del. At the phylum level, the abundance of Firmicutes, Fusobacteria, and Actinobacteria significantly decreased in the early stage of Del exposure. At the genus level, the abundance of Romboutsia, Lactobacillus, and Cetobacterium decreased after Del exposure. Overall, early exposure to Del can lead to tissue damage, metabolic disorder, immunotoxicity, and apoptosis in channel catfish, and affect the composition of its intestinal microbiota. Herein, we clarified the toxic effects of Del on channel catfish in the early stage of exposure and explored why fish under Del stress are more vulnerable to microbial infections and slow growth.
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Affiliation(s)
- Yibin Yang
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China
| | - Xia Zhu
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China
| | - Ying Huang
- Fishery Resource and Environment Research Center, Chinese Academy of Fishery Sciences, Beijing, China
| | - Hongyu Zhang
- Fishery Resource and Environment Research Center, Chinese Academy of Fishery Sciences, Beijing, China
| | - Yongtao Liu
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China
| | - Ning Xu
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China
| | - Guihong Fu
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, China
| | - Xiaohui Ai
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China
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18
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Elazab MFA, Elbaiomy AEA, Ahmed MS, Alsharif KF, Dahran N, Elmahallawy EK, Mokhbatly AA. Ameliorative Effects of Bovine Lactoferrin on Benzene-Induced Hematotoxicity in Albino Rats. Front Vet Sci 2022; 9:907580. [PMID: 35812844 PMCID: PMC9257330 DOI: 10.3389/fvets.2022.907580] [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: 03/29/2022] [Accepted: 05/16/2022] [Indexed: 11/13/2022] Open
Abstract
Benzene (Bz) is one of the major products of the petrochemical industry globally, which induces aplastic anemia and leukemia in humans and animals. This study aimed to investigate the modulatory effects of bovine lactoferrin (bLf) on Bz-induced hematotoxicity in albino rats. Eighty male rats were randomly divided into eight groups: corn oil group [2 mL/kg body weight (BW)], bLf groups (100, 200, and 300 mg/kg BW), Bz group (Bz 2 mL/kg BW; corn oil 2 mL/kg BW), and Bz + bLf groups (Bz 2 mL/kg BW; corn oil 2 mL/kg BW; bLf 100, 200, and 300 mg/kg BW). Hematobiochemical results exhibited marked pancytopenia, a significant decrease in total protein, albumin, α2- and γ-globulin, ferritin, serum iron, and total iron-binding capacity (TIBC), and an increase in serum bioactivities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and erythropoietin hormone levels in Bz-treated rats. Histopathological examination revealed a marked reduction in all hematopoietic cell lines in the bone marrow (BM), necrosis in the white pulp of the spleen and cytosolic hydrops, and apoptosis of hepatocytes in the Bz-treated group. Rats treated with bLf (300 mg/kg BW) revealed marked increases in total protein, albumin, α2- and γ-globulin, ferritin, serum iron, and TIBC levels and decreases both in ALP and LDH bioactivities and erythropoietin hormone levels compared with the Bz-treated group. Histopathological results were concomitant with hematobiochemical parameters in rats treated with bLf (300 mg/kg BW), almost showing restoration of the normal cellularity of BM, the architecture of red and white pulps of the spleen, and even the normal hypertrophy of hepatocytes compared with the control groups. To conclude, bLf (300 mg/kg BW) can be recommended to treat Bz-induced hematotoxicity.
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Affiliation(s)
- Mohamed F. Abou Elazab
- Clinical Pathology Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt
| | - Asmaa E. A. Elbaiomy
- Clinical Pathology Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt
| | - Mohamed S. Ahmed
- Pathology Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Khalaf F. Alsharif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - Naief Dahran
- Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Ehab Kotb Elmahallawy
- Department of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt
| | - Abdallah A. Mokhbatly
- Clinical Pathology Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt
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19
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Khalatbari A, Aghazadeh Z, Ji C. Adverse Effects of Anti-Covid-19 Drug Candidates and Alcohol on Cellular Stress Responses of Hepatocytes. Hepatol Commun 2022; 6:1262-1277. [PMID: 34910385 PMCID: PMC9134820 DOI: 10.1002/hep4.1887] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 11/16/2021] [Accepted: 12/12/2021] [Indexed: 12/15/2022] Open
Abstract
During the pandemic, dexamethasone (DEX), remdesivir (RDV), hydroxychloroquine (HCQ), thapsigargin (TG), camostat mesylate (CaM), and pralatrexate were repurposed drugs for coronavirus disease 2019 (COVID-19). However, the side effects on the liver associated with the anti-COVID therapies are unknown. Cellular stresses by these drugs at 0-30 μM were studied using HepG2, Huh7, and/or primary human hepatocytes. DEX or RDV induced endoplasmic reticulum stress with increased X-box binding protein 1 and autophagic response with increased accumulation of microtubule-associated protein 1A/1B-light chain 3 (LC3-II). DEX and RDV had additive effects on the stress responses in the liver cells, which further increased expression of activating transcription factor 4 and C/EBP homology protein 1 (CHOP), and cell death. Alcohol pretreatment (50 mM) and DEX induced greater cellular stress responses than DEX and RDV. Pralatrexate induced Golgi fragmentation, cell cycle arrest at G0/G1 phase, activations of poly (ADP-ribose) polymerase-1 (PARP) and caspases, and cell death. Pralatrexate and alcohol had synergistic effects on the cell death mediators of Bim, caspase3, and PARP. The protease inhibitor CaM and TG induced autophagic response and mitochondrial stress with altered mitochondrial membrane potential, B-cell lymphoma 2, and cytochrome C. TG and HCQ induced autophagic response markers of Unc-51 like autophagy activating kinase, LC3-II, Beclin1, and Atg5, and severe ER stress marker CHOP. Conclusion: These results suggest that the anti-COVID-19 drugs, especially with drug-drug or alcohol-drug combinations, cause cellular stress responses and injuries in the liver cells.
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Affiliation(s)
- Atousa Khalatbari
- Department of MedicineKeck School of Medicine of USCUniversity of Southern CaliforniaLos AngelesCAUSA
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20
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Lai X, Wang X, Wen S, Sun L, Chen R, Zhang Z, Li Q, Cao J, Lai Z, Li Z, Sun S, Liu X. Six Types of Tea Reduce Acute Alcoholism in Mice by Enhancing Ethanol Metabolism, Suppressing Oxidative Stress and Inflammation. Front Nutr 2022; 9:848918. [PMID: 35677547 PMCID: PMC9169692 DOI: 10.3389/fnut.2022.848918] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 05/02/2022] [Indexed: 12/12/2022] Open
Abstract
Acute alcoholic intoxication (AAI) is a pathological process of multiple system damage caused by a large amount of alcohol, especially in the liver. Although tea extracts alleviate AAI and alcohol-induced liver damage, the mechanisms underlying the protective actions of different types of Chinese tea are unclear. In this study, the AAI mice model was used to explore the functions and mechanisms of six types of tea extract (WEATs) in alleviating AAI. The losing righting reflexes of mice were evaluated to assess the effects of the WEATs on AAI. The levels of the ethanol metabolism enzymes (ADH, ALDH2, CYP2E1), the oxidative stress-related indicators (NRF-2, HO-1, SOD, GSH, CAT, and TG) and the inflammatory factors (TNF-α, iNOS, IL-6, and IL-10) were determined. Black tea and dark tea significantly shortened the sleep time (duration of the loss of righting reflex) and had a good sobering effect. Green tea and oolong tea had the dual effect of prolonging tolerance time (time of losing righting reflex) and shortening sleep time. While white tea had the most significant effect on prolonging tolerance time but with no obvious sobering effect. Black tea, dark tea, and oolong tea significantly up-regulated ADH and ALDH2, and down-regulated CYP2E1. Green tea and white tea significantly increased the levels of Nrf2, GSH, and CAT. Black tea, dark tea and oolong tea markedly increased the levels of HO-1, IL-10, and inhibited TG. Therefore, it is possible that black tea, dark tea and oolong tea reduced AAI by increasing ethanol metabolism, suppressing oxidative stress and inflammation. While green tea was mainly by regulating oxidative stress. White tea may prolong the tolerance time by increasing ethanol metabolism and reducing oxidative stress. Different types of tea have specific chemical compositions and can alleviate AAI. In conclusion, despite variations in the composition and mechanism of action, tea is a potent natural product to alleviate a hangover and protect the liver.
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Affiliation(s)
- Xingfei Lai
- College of Tea Science, Yunnan Agricultural University, Kunming, China
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Xinrong Wang
- College of Tea Science, Yunnan Agricultural University, Kunming, China
| | - Shuai Wen
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Lingli Sun
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Ruohong Chen
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Zhenbiao Zhang
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Qiuhua Li
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Junxi Cao
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Zhaoxiang Lai
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Zhigang Li
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Shili Sun
- Guangdong Provincial Key Laboratory of Tea Plant Resources Innovation and Utilization, Tea Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
- *Correspondence: Shili Sun,
| | - Xiaohui Liu
- College of Tea Science, Yunnan Agricultural University, Kunming, China
- Xiaohui Liu,
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21
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Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization. Int J Mol Sci 2022; 23:ijms23073564. [PMID: 35408925 PMCID: PMC8998613 DOI: 10.3390/ijms23073564] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/14/2022] [Accepted: 03/21/2022] [Indexed: 12/15/2022] Open
Abstract
In cattle, phenobarbital (PB) upregulates target drug-metabolizing enzyme (DME) mRNA levels. However, few data about PB's post-transcriptional effects are actually available. This work provides the first, and an almost complete, characterization of PB-dependent changes in DME catalytic activities in bovine liver using common probe substrates and confirmatory immunoblotting investigations. As expected, PB increased the total cytochrome P450 (CYP) content and the extent of metyrapone binding; moreover, an augmentation of protein amounts and related enzyme activities was observed for known PB targets such as CYP2B, 2C, and 3A, but also CYP2E1. However, contradictory results were obtained for CYP1A, while a decreased catalytic activity was observed for flavin-containing monooxygenases 1 and 3. The barbiturate had no effect on the chosen hydrolytic and conjugative DMEs. For the first time, we also measured the 26S proteasome activity, and the increase observed in PB-treated cattle would suggest this post-translational event might contribute to cattle DME regulation. Overall, this study increased the knowledge of cattle hepatic drug metabolism, and further confirmed the presence of species differences in DME expression and activity between cattle, humans, and rodents. This reinforced the need for an extensive characterization and understanding of comparative molecular mechanisms involved in expression, regulation, and function of DMEs.
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22
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Chen Y, Wang Y, Charkoftaki G, Orlicky DJ, Davidson E, Wan F, Ginsberg G, Thompson DC, Vasiliou V. Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 806:150703. [PMID: 34600989 PMCID: PMC8633123 DOI: 10.1016/j.scitotenv.2021.150703] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/27/2021] [Accepted: 09/27/2021] [Indexed: 05/19/2023]
Abstract
1,4-Dioxane (DX) is a synthetic chemical used as a stabilizer for industrial solvents. Recent occurrence data show widespread and significant contamination of drinking water with DX in the US. DX is classified by the International Agency for Research on Cancer as a group 2B carcinogen with the primary target organ being the liver in animal studies. Despite the exposure and cancer risk, US EPA has not established a drinking water Maximum Contaminant Level (MCL) for DX and a wide range of drinking water targets have been established across the US and by Health Canada. The DX carcinogenic mechanism remains unknown; this information gap contributes to the varied approaches to its regulation. Our recent mice study indicated alterations in oxidative stress response accompanying DNA damage as an early change by high dose DX (5000 ppm) in drinking water. Herein, we report a follow-up study, in which we used glutathione (GSH)-deficient glutamate-cysteine ligase modifier subunit (Gclm)-null mice to investigate the role of redox homeostasis in DX-induced liver cytotoxicity and genotoxicity. Gclm-null and wild-type mice were exposed to DX for one week (1000 mg/kg/day by oral gavage) or three months (5000 ppm in drinking water). Subchronic exposure of high dose DX caused mild liver cytotoxicity. DX induced assorted molecular changes in the liver including: (i) a compensatory nuclear factor erythroid 2-related factor 2 (NRF2) anti-oxidative response at the early stage (one week), (ii) progressive CYP2E1 induction, (iii) development of oxidative stress, as evidenced by persistent NRF2 induction, oxidation of GSH pool, and accumulation of the lipid peroxidation by-product 4-hydroxynonenal, and (iv) elevations in oxidative DNA damage and DNA repair response. These DX-elicited changes were exaggerated in GSH-deficient mice. Collectively, the current study provides additional evidence linking redox dysregulation to DX liver genotoxicity, implying oxidative stress as a candidate mechanism of DX liver carcinogenicity.
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Affiliation(s)
- Ying Chen
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.
| | - Yewei Wang
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - Georgia Charkoftaki
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - David J Orlicky
- Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Center, University of Colorado, Aurora, CO 80045, USA
| | - Emily Davidson
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; Department of Cellular & Molecular Physiology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA
| | - Fengjie Wan
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - Gary Ginsberg
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA
| | - David C Thompson
- Department of Clinical Pharmacy, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado, Aurora, CO 80045, USA
| | - Vasilis Vasiliou
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.
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23
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D’Alessandro C, Benedetti A, Di Paolo A, Giannese D, Cupisti A. Interactions between Food and Drugs, and Nutritional Status in Renal Patients: A Narrative Review. Nutrients 2022; 14:nu14010212. [PMID: 35011087 PMCID: PMC8747252 DOI: 10.3390/nu14010212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 12/14/2021] [Accepted: 12/16/2021] [Indexed: 12/17/2022] Open
Abstract
Drugs and food interact mutually: drugs may affect the nutritional status of the body, acting on senses, appetite, resting energy expenditure, and food intake; conversely, food or one of its components may affect bioavailability and half-life, circulating plasma concentrations of drugs resulting in an increased risk of toxicity and its adverse effects, or therapeutic failure. Therefore, the knowledge of these possible interactions is fundamental for the implementation of a nutritional treatment in the presence of a pharmacological therapy. This is the case of chronic kidney disease (CKD), for which the medication burden could be a problem, and nutritional therapy plays an important role in the patient’s treatment. The aim of this paper was to review the interactions that take place between drugs and foods that can potentially be used in renal patients, and the changes in nutritional status induced by drugs. A proper definition of the amount of food/nutrient intake, an adequate definition of the timing of meal consumption, and a proper adjustment of the drug dosing schedule may avoid these interactions, safeguarding the quality of life of the patients and guaranteeing the effectiveness of drug therapy. Hence, a close collaboration between the nephrologist, the renal dietitian, and the patient is crucial. Dietitians should consider that food may interact with drugs and that drugs may affect nutritional status, in order to provide the patient with proper dietary suggestions, and to allow the maximum effectiveness and safety of drug therapy, while preserving/correcting the nutritional status.
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24
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Wang M, Wang LS, Fang JN, Du GC, Zhang TT, Li RG. Transcriptomic Profiling of Bursaphelenchus xylophilus Reveals Differentially Expressed Genes in Response to Ethanol. Mol Biochem Parasitol 2022; 248:111460. [DOI: 10.1016/j.molbiopara.2022.111460] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 01/18/2023]
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25
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Stafford AM, Yamamoto BK, Phillips TJ. Combined and sequential effects of alcohol and methamphetamine in animal models. Neurosci Biobehav Rev 2021; 131:248-269. [PMID: 34543650 PMCID: PMC8642292 DOI: 10.1016/j.neubiorev.2021.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 09/11/2021] [Accepted: 09/12/2021] [Indexed: 11/16/2022]
Abstract
Comorbid drug use, often alcohol with other drugs, poses significant health and societal concerns. Methamphetamine is among the illicit drugs most often co-used with alcohol. The current review examines the animal literature for impacts of comorbid alcohol and methamphetamine exposure. We found evidence for additive or synergistic effects of combined or sequential exposure on behavior and physiology. Dopaminergic, serotonergic, and glutamatergic systems are all impacted by combined exposure to alcohol and methamphetamine and cyclooxygenase-2 activity plays an important role in their combined neurotoxic effects. Adverse consequences of comorbid exposure include altered brain development with prenatal exposure, impaired learning and memory, motor deficits, gastrotoxicity, hepatotoxicity, and augmented intake under some conditions. Given high susceptibility to drug experimentation in adolescence, studies of co-exposure during the adolescent period and of how adolescent exposure to one drug impacts later use or sensitivity to the other drug should be a priority. Further, to gain traction on prevention and treatment, additional research to identify motivational and neurobiological drivers and consequences of comorbid use is needed.
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Affiliation(s)
- Alexandra M Stafford
- Department of Behavioral Neuroscience, Portland Alcohol Abuse Research Center and Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR, USA.
| | - Bryan K Yamamoto
- Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Tamara J Phillips
- Department of Behavioral Neuroscience, Portland Alcohol Abuse Research Center and Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR, USA; Veterans Affairs Portland Health Care System, Portland, OR, USA
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26
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Li X, Wu Q, Zhou B, Liu Y, Lv J, Chang Q, Zhao Y. Umbrella Review on Associations Between Single Nucleotide Polymorphisms and Lung Cancer Risk. Front Mol Biosci 2021; 8:687105. [PMID: 34540891 PMCID: PMC8446528 DOI: 10.3389/fmolb.2021.687105] [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: 03/29/2021] [Accepted: 08/18/2021] [Indexed: 12/03/2022] Open
Abstract
The aim is to comprehensively and accurately assess potential relationships between single nucleotide polymorphisms (SNP) and lung cancer (LC) risk by summarizing the evidence in systematic reviews and meta-analyses. This umbrella review was registered with the PROSPERO international prospective register of systematic reviews under registration number CRD42020204685. The PubMed, Web of Science, and Embase databases were searched to identify eligible systematic reviews and meta-analyses from inception to August 14, 2020. The evaluation of cumulative evidence was conducted for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). This umbrella review finally included 120 articles of a total of 190 SNP. The median number of studies and sample size included in the meta-analyses were five (range, 3–52) and 4 389 (range, 354–256 490), respectively. A total of 85 SNP (in 218 genetic models) were nominally statistically associated with LC risk. Based on the Venice criteria and FPRP, 13 SNP (in 22 genetic models), 47 SNP (in 99 genetic models), and 55 SNP (in 94 genetic models) had strong, moderate, and weak cumulative evidence of associations with LC risk, respectively. In conclusion, this umbrella review indicated that only 13 SNP (of 11 genes and one miRNA) were strongly correlated to LC risk. These findings can serve as a general and helpful reference for further genetic studies.
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Affiliation(s)
- Xiaoying Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qijun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Baosen Zhou
- Department of Clinical Epidemiology, First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yashu Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jiale Lv
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qing Chang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yuhong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
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27
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Le TK, Kim J, Anh Nguyen N, Huong Ha Nguyen T, Sun EG, Yee SM, Kang HS, Yeom SJ, Beum Park C, Yun CH. Solar-Powered Whole-Cell P450 Catalytic Platform for C-Hydroxylation Reactions. CHEMSUSCHEM 2021; 14:3054-3058. [PMID: 34085413 DOI: 10.1002/cssc.202100944] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/02/2021] [Indexed: 06/12/2023]
Abstract
Photobiocatalysis is a green platform for driving redox enzymatic reactions using solar energy, not needing high-cost cofactors and redox partners. Here, a visible light-driven whole-cell platform for human cytochrome P450 (CYP) photobiocatalysis was developed using natural flavins as a photosensitizer. Photoexcited flavins mediate NADPH/reductase-free, light-driven biocatalysis by human CYP2E1 both in vitro and in the whole-cell systems. In vitro tests demonstrated that the photobiocatalytic activity of CYP2E1 is dependent on the substrate type, the presence of catalase, and the acid type used as a sacificial electron donor. A protective effect of catalase was found against the inactivation of CYP2E1 heme by H2 O2 and the direct transfer of photo-induced electrons to the heme iron not by peroxide shunt. Furthermore, the P450 photobiocatalysis in whole cells containing human CYPs 1A1, 1A2, 1B1, and 3A4 demonstrated the general applicability of the solar-powered, flavin-mediated P450 photobiocatalytic system.
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Affiliation(s)
- Thien-Kim Le
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Jinhyun Kim
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 335 Science Road, Daejeon, 34141, Republic of Korea
| | - Ngoc Anh Nguyen
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Thi Huong Ha Nguyen
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Eun-Gene Sun
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Su-Min Yee
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Hyung-Sik Kang
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Soo-Jin Yeom
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Chan Beum Park
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 335 Science Road, Daejeon, 34141, Republic of Korea
| | - Chul-Ho Yun
- School of Biological Sciences and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea
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28
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Yang H, Li SQ, Wang SL, Song Y, Cheng WG, Wang Y, Zhang BB, Wang DM, Wang YL. Comparison of the Effects of Intraperitoneal Injection with Carbon Tetrachloride on Acute Liver Toxicity in Male and Female Kunming Mice. Med Sci Monit 2021; 27:e931427. [PMID: 34366426 PMCID: PMC8362337 DOI: 10.12659/msm.931427] [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] [Indexed: 11/09/2022] Open
Abstract
Background Acute chemical liver injury needs to be further explored. The present study aimed to compare the effects of intraperitoneal injection with carbon tetrachloride on acute liver toxicity after 24 h in male and female Kunming mice. Material/Methods In this study, female and male mice were simultaneously divided into 3 different groups. Each group was treated differently, and after 24 h, blood samples were collected to check for changes in the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were used to assess liver toxicity. Liver samples were used for hematoxylin-eosin staining, and periodic acid Schiff reagent staining was performed to detect the pathological changes of each group. The expression level of biomarker molecules in liver cells was also systematically analyzed. Results Our results showed that, compared with male mice, female mice showed more serious damage: reduced glycogen and higher degree of necrosis, and the levels of heatshock protein 27 (HSP27), heat-shock protein 70 (HSP70), proliferating cell nuclear antigen (PCNA) and B cell lymphoma/lewkmia-2 (Bcl-2) were significantly lower than in the male group (P<0.05 or P<0.01), while the results of Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase 3 (Caspase3), and cytochrome P450 2E1 (CYP2E1) were the opposite (P<0.05 or P<0.01). Conclusions The findings from this study showed that, compared with male mice, at 24 h after CCl4 toxicity, female mice showed more severe changes of hepatocyte necrosis and PAS-positivity, with significantly reduced expression of HSP27, HSP70, PCNA, and Bcl-2, and significantly increased expression of Bax, caspase-3, and CYP2E1.
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Affiliation(s)
- Huan Yang
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, Henan, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - San-Qiang Li
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, Henan, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - Shan-Long Wang
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, Henan, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - Ying Song
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, Henan, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - Wei-Gang Cheng
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - Yong Wang
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, Henan, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - Bing-Bing Zhang
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, Henan, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - Dong-Mei Wang
- The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, Henan, China (mainland).,Henan Center for Engineering and Technology Research on Prevention and Treatment of liver Diseases, Luoyang, Henan, China (mainland)
| | - Yun-Long Wang
- Henan Bioengineering Research Center, Zhengzhou, Henan, China (mainland)
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29
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Rodriguez FD, Coveñas R. Biochemical Mechanisms Associating Alcohol Use Disorders with Cancers. Cancers (Basel) 2021; 13:cancers13143548. [PMID: 34298760 PMCID: PMC8306032 DOI: 10.3390/cancers13143548] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/01/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Of all yearly deaths attributable to alcohol consumption globally, approximately 12% are due to cancers, representing approximately 0.4 million deceased individuals. Ethanol metabolism disturbs cell biochemistry by targeting the structure and function of essential biomolecules (proteins, nucleic acids, and lipids) and by provoking alterations in cell programming that lead to cancer development and cancer malignancy. A better understanding of the metabolic and cell signaling realm affected by ethanol is paramount to designing effective treatments and preventive actions tailored to specific neoplasias. Abstract The World Health Organization identifies alcohol as a cause of several neoplasias of the oropharynx cavity, esophagus, gastrointestinal tract, larynx, liver, or female breast. We review ethanol’s nonoxidative and oxidative metabolism and one-carbon metabolism that encompasses both redox and transfer reactions that influence crucial cell proliferation machinery. Ethanol favors the uncontrolled production and action of free radicals, which interfere with the maintenance of essential cellular functions. We focus on the generation of protein, DNA, and lipid adducts that interfere with the cellular processes related to growth and differentiation. Ethanol’s effects on stem cells, which are responsible for building and repairing tissues, are reviewed. Cancer stem cells (CSCs) of different origins suffer disturbances related to the expression of cell surface markers, enzymes, and transcription factors after ethanol exposure with the consequent dysregulation of mechanisms related to cancer metastasis or resistance to treatments. Our analysis aims to underline and discuss potential targets that show more sensitivity to ethanol’s action and identify specific metabolic routes and metabolic realms that may be corrected to recover metabolic homeostasis after pharmacological intervention. Specifically, research should pay attention to re-establishing metabolic fluxes by fine-tuning the functioning of specific pathways related to one-carbon metabolism and antioxidant processes.
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Affiliation(s)
- Francisco D. Rodriguez
- Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Salamanca, 37007 Salamanca, Spain
- Group GIR USAL: BMD (Bases Moleculares del Desarrollo), 37007 Salamanca, Spain;
- Correspondence: ; Tel.: +34-677-510-030
| | - Rafael Coveñas
- Group GIR USAL: BMD (Bases Moleculares del Desarrollo), 37007 Salamanca, Spain;
- Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, 37007 Salamanca, Spain
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30
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Michalak A, Lach T, Cichoż-Lach H. Oxidative Stress-A Key Player in the Course of Alcohol-Related Liver Disease. J Clin Med 2021; 10:jcm10143011. [PMID: 34300175 PMCID: PMC8303854 DOI: 10.3390/jcm10143011] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/04/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
Oxidative stress is known to be an inseparable factor involved in the presentation of liver disorders. Free radicals interfere with DNA, proteins, and lipids, which are crucial in liver metabolism, changing their expression and biological functions. Additionally, oxidative stress modifies the function of micro-RNAs, impairing the metabolism of hepatocytes. Free radicals have also been proven to influence the function of certain transcriptional factors and to alter the cell cycle. The pathological appearance of alcohol-related liver disease (ALD) constitutes an ideal example of harmful effects due to the redox state. Finally, ethanol-induced toxicity and overproduction of free radicals provoke irreversible changes within liver parenchyma. Understanding the underlying mechanisms associated with the redox state in the course of ALD creates new possibilities of treatment for patients. The future of hepatology may become directly dependent on the effective action against reactive oxygen species. This review summarizes current data on the redox state in the natural history of ALD, highlighting the newest reports on this topic.
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Affiliation(s)
- Agata Michalak
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland;
| | - Tomasz Lach
- Department of Orthopedics and Traumatology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland;
| | - Halina Cichoż-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland;
- Correspondence: ; Tel.: +48-601377656; Fax: +48-814796135
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Engelward BP. Implications of an epidemiological study showing an association between in utero NDMA exposure and childhood cancer. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2021; 62:288-292. [PMID: 33963777 PMCID: PMC8361697 DOI: 10.1002/em.22434] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 04/30/2021] [Accepted: 05/04/2021] [Indexed: 05/10/2023]
Abstract
Exposure to N-nitrosodimethylamine (NDMA) has recently been linked to a childhood cancer cluster in Wilmington, MA, which is home to the Olin Chemical Superfund Site. When it was discovered in the 1990's that 22 children in a town of under 22,000 people got cancer, the community took action and pressed for an investigation into the possibility that chemicals from the Olin Chemical site had contaminated their water. This led to the eventual discovery that NDMA was present in the town water supply. NDMA has long been known for its potent carcinogenicity in animal models, and so the community pointed to NDMA as a possible cause. This led to an investigation by the Massachusetts Department of Public Health, which, in 2021, released its findings showing an association between NDMA exposure in utero and childhood cancer. The mission of the NIEHS Superfund Research Program is to protect human health from hazardous substances. In 2017, in response to community concerns, a team at MIT created the MIT Superfund Research Program Center with a focus on research related to NDMA. Just 1 week prior to the release of the Department of Public Health study, the MIT Superfund Research Program Center published a manuscript in Cell Reports that identifies the Alkyladenine DNA glycosylase (AAG) as a possible genetic susceptibility factor. This commentary provides an author's perspective on the context and implications of this and related research.
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Affiliation(s)
- Bevin P. Engelward
- MIT Superfund Research Program, Department of Biological Engineering, Center for Environmental Health SciencesMassachusetts Institute of TechnologyCambridgeMassachusettsUSA
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32
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Sterken MG, van Wijk MH, Quamme EC, Riksen JAG, Carnell L, Mathies LD, Davies AG, Kammenga JE, Bettinger JC. Transcriptional analysis of the response of C. elegans to ethanol exposure. Sci Rep 2021; 11:10993. [PMID: 34040055 PMCID: PMC8155136 DOI: 10.1038/s41598-021-90282-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 05/07/2021] [Indexed: 11/30/2022] Open
Abstract
Ethanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source.
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Affiliation(s)
- Mark G Sterken
- Laboratory of Nematology, Wageningen University and Research, 6708 PB, Wageningen, The Netherlands
| | - Marijke H van Wijk
- Laboratory of Nematology, Wageningen University and Research, 6708 PB, Wageningen, The Netherlands
| | - Elizabeth C Quamme
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Box 980613, Richmond, VA, 23298, USA
| | - Joost A G Riksen
- Laboratory of Nematology, Wageningen University and Research, 6708 PB, Wageningen, The Netherlands
| | - Lucinda Carnell
- Department of Biological Sciences, Central Washington University, Ellensburg, WA, 98926, USA
| | - Laura D Mathies
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Box 980613, Richmond, VA, 23298, USA
- Virginia Commonwealth University Alcohol Research Center, Richmond, VA, USA
| | - Andrew G Davies
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Box 980613, Richmond, VA, 23298, USA
- Virginia Commonwealth University Alcohol Research Center, Richmond, VA, USA
| | - Jan E Kammenga
- Laboratory of Nematology, Wageningen University and Research, 6708 PB, Wageningen, The Netherlands
| | - Jill C Bettinger
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Box 980613, Richmond, VA, 23298, USA.
- Virginia Commonwealth University Alcohol Research Center, Richmond, VA, USA.
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Li H, Shi W, Li C, Zhang X, Gong J, Shi J, Koffas MA, Xu Z. Impact of ethylene glycol on DHEA dihydroxylation in Colletotrichum lini: Increasing the expression of cytochrome P450 and 6-phosphogluconate dehydrogenase and enhancing the generation of NADPH. Biochem Eng J 2021. [DOI: 10.1016/j.bej.2020.107860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update. Arch Toxicol 2021; 95:395-472. [PMID: 33459808 DOI: 10.1007/s00204-020-02971-4] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 12/29/2020] [Indexed: 12/17/2022]
Abstract
This is an overview of the metabolic activation of drugs, natural products, physiological compounds, and general chemicals by the catalytic activity of cytochrome P450 enzymes belonging to Families 1-4. The data were collected from > 5152 references. The total number of data entries of reactions catalyzed by P450s Families 1-4 was 7696 of which 1121 (~ 15%) were defined as bioactivation reactions of different degrees. The data were divided into groups of General Chemicals, Drugs, Natural Products, and Physiological Compounds, presented in tabular form. The metabolism and bioactivation of selected examples of each group are discussed. In most of the cases, the metabolites are directly toxic chemicals reacting with cell macromolecules, but in some cases the metabolites formed are not direct toxicants but participate as substrates in succeeding metabolic reactions (e.g., conjugation reactions), the products of which are final toxicants. We identified a high level of activation for three groups of compounds (General Chemicals, Drugs, and Natural Products) yielding activated metabolites and the generally low participation of Physiological Compounds in bioactivation reactions. In the group of General Chemicals, P450 enzymes 1A1, 1A2, and 1B1 dominate in the formation of activated metabolites. Drugs are mostly activated by the enzyme P450 3A4, and Natural Products by P450s 1A2, 2E1, and 3A4. Physiological Compounds showed no clearly dominant enzyme, but the highest numbers of activations are attributed to P450 1A, 1B1, and 3A enzymes. The results thus show, perhaps not surprisingly, that Physiological Compounds are infrequent substrates in bioactivation reactions catalyzed by P450 enzyme Families 1-4, with the exception of estrogens and arachidonic acid. The results thus provide information on the enzymes that activate specific groups of chemicals to toxic metabolites.
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Rendic S, Guengerich FP. Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters. Curr Drug Metab 2021; 21:1127-1135. [PMID: 33292107 DOI: 10.2174/1389200221999201208211537] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 09/24/2020] [Accepted: 10/08/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND In clinical practice, chloroquine and hydroxychloroquine are often co-administered with other drugs in the treatment of malaria, chronic inflammatory diseases, and COVID-19. Therefore, their metabolic properties and the effects on the activity of cytochrome P450 (P450, CYP) enzymes and drug transporters should be considered when developing the most efficient treatments for patients. METHODS Scientific literature on the interactions of chloroquine and hydroxychloroquine with human P450 enzymes and drug transporters, was searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/) and the ADME database (https://life-science.kyushu.fujitsu.com/admedb/). RESULTS Chloroquine and hydroxychloroquine are metabolized by P450 1A2, 2C8, 2C19, 2D6, and 3A4/5 in vitro and by P450s 2C8 and 3A4/5 in vivo by N-deethylation. Chloroquine effectively inhibited P450 2D6 in vitro; however, in vivo inhibition was not apparent except in individuals with limited P450 2D6 activity. Chloroquine is both an inhibitor and inducer of the transporter MRP1 and is also a substrate of the Mate and MRP1 transport systems. Hydroxychloroquine also inhibited P450 2D6 and the transporter OATP1A2. CONCLUSIONS Chloroquine caused a statistically significant decrease in P450 2D6 activity in vitro and in vivo, also inhibiting its own metabolism by the enzyme. The inhibition indicates a potential for clinical drug-drug interactions when taken with other drugs that are predominant substrates of the P450 2D6. When chloroquine and hydroxychloroquine are used clinically with other drugs, substrates of P450 2D6 enzyme, attention should be given to substrate-specific metabolism by P450 2D6 alleles present in individuals taking the drugs.
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Affiliation(s)
| | - Frederick Peter Guengerich
- Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, United States
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Buyco DG, Martin J, Jeon S, Hooks R, Lin C, Carr R. Experimental models of metabolic and alcoholic fatty liver disease. World J Gastroenterol 2021; 27:1-18. [PMID: 33505147 PMCID: PMC7789066 DOI: 10.3748/wjg.v27.i1.1] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 11/01/2020] [Accepted: 12/06/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome (MetS). Because alcohol consumption in NAFLD patients is common, there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease (ALD). Indeed, MetS also significantly contributes to liver injury in ALD patients. This “syndrome of metabolic and alcoholic steatohepatitis” (SMASH) is thus expected to be a more prevalent presentation in liver patients, as the obesity epidemic continues. Several pre-clinical experimental models that couple alcohol consumption with NAFLD-inducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH. These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation, oxidative stress, and the induction of innate immune response. There are significant limitations in the applicability of these models to human disease, such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption. Thus, there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.
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Affiliation(s)
- Delfin Gerard Buyco
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Jasmin Martin
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Sookyoung Jeon
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Royce Hooks
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Chelsea Lin
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Rotonya Carr
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
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Abstract
Significance: In humans, imbalances in the reduction-oxidation (redox) status of cells are associated with many pathological states. In addition, many therapeutics and prophylactics used as interventions for diverse pathologies either directly modulate oxidant levels or otherwise influence endogenous cellular redox systems. Recent Advances: The cellular machineries that maintain redox homeostasis or that function within antioxidant defense systems rely heavily on the regulated reactivities of sulfur atoms either within or derived from the amino acids cysteine and methionine. Recent advances have substantially advanced our understanding of the complex and essential chemistry of biological sulfur-containing molecules. Critical Issues: The redox machineries that maintain cellular homeostasis under diverse stresses can consume large amounts of energy to generate reducing power and/or large amounts of sulfur-containing nutrients to replenish or sustain intracellular stores. By understanding the metabolic pathways underlying these responses, one can better predict how to protect cells from specific stresses. Future Directions: Here, we summarize the current state of knowledge about the impacts of different stresses on cellular metabolism of sulfur-containing molecules. This analysis suggests that there remains more to be learned about how cells use sulfur chemistry to respond to stresses, which could in turn lead to advances in therapeutic interventions for some exposures or conditions.
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Affiliation(s)
- Colin G Miller
- Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, USA
| | - Edward E Schmidt
- Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, USA
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38
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Biochemical and Histopathological Alterations in Different Tissues of Rats Due to Repeated Oral Dose Toxicity of Cymoxanil. Animals (Basel) 2020; 10:ani10122205. [PMID: 33255611 PMCID: PMC7760546 DOI: 10.3390/ani10122205] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/13/2020] [Accepted: 11/19/2020] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Cymoxanil is a broad-spectrum fungicide used to protect many fruits, vegetables, and field crops against several fungal diseases. Investigating the potential hazards and toxicological effects of this fungicide is very important as cymoxanil can be a major human health concern. The present study investigated the effect of repeated oral doses of cymoxanil on different tissues of treated rats by measuring different biochemical parameters and investigating the histopathological changes. Interestingly, our study reported a dose-dependent effect of cymoxanil that was combined with marked alteration on biochemical enzymes. Moreover, the alteration was combined with marked histopathological changes in various tissues of treated rats, mainly liver, brain, and kidney tissues. Our study collectively reveals that cymoxanil can be a source of major concern for human health with respect to long-term and low dose exposure. Abstract Evaluating potential adverse health impacts caused by pesticides is an important parameter in human toxicity. This study focuses on the importance of subchronic toxicity assessment of cymoxanil fungicide in rats with special reference to target biochemical enzymes and histopathological changes in different tissues. In this regard, a 21-day toxicity study with repeated cymoxanil oral doses was conducted. It has been shown that low doses (0.5 mg/kg) were less effective than medium (1 mg/kg) and high (2 mg/kg) doses. Moreover, high dose dose-treated rats showed piecemeal necrosis in the liver, interstitial nephritis and tubular degeneration in the kidneys, interstitial pneumonia and type II pneumocyte hyperplasia in the lungs, gliosis, spongiosis, and malacia in the brain, and testicular edema and degeneration in the testes. Cymoxanil significantly increased AST, ALT, and ALP in serum and liver, indicating tissue necrosis and possible leakage of these enzymes into the bloodstream. Creatinine levels increased, indicating renal damage. Similarly, significant inhibition was recorded in brain acetylcholinesterase, indicating that both synaptic transmission and nerve conduction were affected. Importantly, these histopathological and biochemical alterations were dose-dependent. Taken together, our study reported interesting biochemical and histopathological alterations in different rat tissues following repeated toxicity with oral doses of cymoxanil. Our study suggests future studies on different pesticides at different concentrations that would help urge governments to create more restrictive regulations concerning these compounds’ levels.
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Kito K, Ishihara J, Kotemori A, Zha L, Liu R, Sawada N, Iwasaki M, Sobue T, Tsugane S. Dietary Acrylamide Intake and the Risk of Pancreatic Cancer: The Japan Public Health Center-Based Prospective Study. Nutrients 2020; 12:E3584. [PMID: 33266487 PMCID: PMC7700165 DOI: 10.3390/nu12113584] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 11/10/2020] [Accepted: 11/20/2020] [Indexed: 12/15/2022] Open
Abstract
Acrylamide is a probable carcinogen in humans. Few studies have assessed dietary acrylamide intake and the risk of pancreatic cancer; however, these studies are based on Western populations. Our purpose was to investigate the association of dietary acrylamide intake with the risk of pancreatic cancer utilizing data from the Japan Public Health Center-based Prospective Study. We evaluated the data of 89,729 participants aged 45-74 years, who replied to a questionnaire on past medical history and lifestyle habits from 1995-1998. Dietary acrylamide intake was estimated utilizing a validated food frequency questionnaire. We calculated the hazard ratios and 95% confidence intervals by using Cox proportional-hazards regression models. The average follow-up was 15.2 years, and 576 cases of pancreatic cancer were diagnosed. In the multivariate-adjusted model, an association between dietary acrylamide intake and pancreatic cancer risk was not demonstrated (hazard ratio for the highest vs. lowest quartile = 0.83, 95% confidence interval: 0.65-1.05, p for trend = 0.07). Furthermore, in the analyses stratified by sex, smoking status, coffee consumption, green tea consumption, alcohol consumption, and body mass index, no significant association was detected. Dietary acrylamide intake was not associated with the pancreatic cancer risk in Japanese individuals.
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Affiliation(s)
- Kumiko Kito
- Graduate School of Environmental Health, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan;
| | - Junko Ishihara
- Department of Food and Life Science, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan;
| | - Ayaka Kotemori
- Department of Food and Life Science, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan;
| | - Ling Zha
- Department of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; (L.Z.); (R.L.); (T.S.)
| | - Rong Liu
- Department of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; (L.Z.); (R.L.); (T.S.)
| | - Norie Sawada
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (N.S.); (M.I.); (S.T.)
| | - Motoki Iwasaki
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (N.S.); (M.I.); (S.T.)
| | - Tomotaka Sobue
- Department of Environmental Medicine and Population Sciences, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; (L.Z.); (R.L.); (T.S.)
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (N.S.); (M.I.); (S.T.)
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Angireddy R, Chowdhury AR, Zielonka J, Ruthel G, Kalyanaraman B, Avadhani NG. Alcohol-induced CYP2E1, mitochondrial dynamics and retrograde signaling in human hepatic 3D organoids. Free Radic Biol Med 2020; 159:1-14. [PMID: 32738395 DOI: 10.1016/j.freeradbiomed.2020.06.030] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 06/19/2020] [Accepted: 06/21/2020] [Indexed: 12/20/2022]
Abstract
Alcohol toxicity is a significant health problem with ~3 million estimated deaths per year globally. Alcohol is metabolized to the toxic metabolite, acetaldehyde by alcohol dehydrogenase or CYP2E1 in the hepatic tissue, and also induces reactive oxygen species (ROS), which together play a pivotal role in cell and tissue damage. Our previous studies with COS-7 cells transduced with unique human CYP2E1 variants that mostly localize to either microsomes or mitochondria revealed that mitochondrially-localized CYP2E1 drives alcohol toxicity through the generation of higher levels of ROS, which has a consequent effect on cytochrome c oxidase (CcO) and mitochondrial oxidative function. Alcohol treatment of human hepatocyte cell line, HepaRG, in monolayer cultures increased ROS, affected CcO activity/stability, and induced mitophagy. Alcohol treatment of 3D organoids of HepaRG cells induced higher levels of CYP2E1 mRNA and activated mitochondrial stress-induced retrograde signaling, and also induced markers of hepatic steatosis. Knock down of CYP2E1 mRNA using specific shRNA, FK506, a Calcineurin inhibitor, and Mdivi-1, a DRP1 inhibitor, ameliorated alcohol-induced mitochondrial retrograde signaling, and hepatic steatosis. These results for the first time present a mechanistic link between CYP2E1 function and alcohol mediated mitochondrial dysfunction, retrograde signaling, and activation of hepatic steatosis in a 3D organoid system that closely recapitulates the in vivo liver response.
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Affiliation(s)
- Rajesh Angireddy
- Department of Biomedical Sciences, School of Veterinary Medicine, 3800 Spruce Street, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Anindya Roy Chowdhury
- Department of Biomedical Sciences, School of Veterinary Medicine, 3800 Spruce Street, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Jacek Zielonka
- Department of Biophysics and, Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Gordon Ruthel
- Department of Pathobiology, Veterinary Center for Imaging, Hill Pavilion, School of Veterinary Medicine, University of Pennsylvania, PA, 19104, USA
| | - Balaraman Kalyanaraman
- Department of Biophysics and, Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Narayan G Avadhani
- Department of Biomedical Sciences, School of Veterinary Medicine, 3800 Spruce Street, University of Pennsylvania, Philadelphia, PA, 19104, USA.
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He B, Ni Y, Jin Y, Fu Z. Pesticides-induced energy metabolic disorders. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 729:139033. [PMID: 32388131 DOI: 10.1016/j.scitotenv.2020.139033] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/17/2020] [Accepted: 04/25/2020] [Indexed: 06/11/2023]
Abstract
Metabolic disorders have become a heavy burden on society. Recently, through excessive use, pesticides have been found to be present in environmental matrixes and sometimes even accumulate in humans or other mammals through the food chain, which then causes health concerns. Evidence has indicated that pesticides have the potential to induce energy metabolic disorders by disturbing the physical process of energy absorption in the intestine and energy storage in the liver, adipose tissue and skeletal muscle in humans or other mammals. In addition, the homeostasis of energy regulation by the pancreas and immune cells is also affected by pesticides. These pesticide-induced disruptions ultimately cause abnormal levels of blood glucose and lipids, which in turn induce the development of related metabolic diseases, including overweight, underweight, insulin resistance and even diabetes. In this review, the results of previous studies focused on the induction of metabolic disorders by pesticides are summarized. We hope that this work will facilitate the discovery of a potential strategy for the treatment of diseases caused by pesticides.
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Affiliation(s)
- Bingnan He
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yinhua Ni
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yuanxiang Jin
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Zhengwei Fu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
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D'Arcy MS. A review of the chemopreventative and chemotherapeutic properties of the phytochemicals berberine, resveratrol and curcumin, and their influence on cell death via the pathways of apoptosis and autophagy. Cell Biol Int 2020; 44:1781-1791. [PMID: 32449796 DOI: 10.1002/cbin.11402] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 05/15/2020] [Accepted: 05/23/2020] [Indexed: 12/22/2022]
Abstract
Phytochemicals are a diverse group of compounds found in a variety of fruits, vegetables and herbs, and have been reported to possess a number of health benefits. Marketed as supplements by health food retailers, this group of naturally occurring compounds have been investigated for a number of years to determine if they possess any chemopreventative and/or chemotherapeutic benefits. In this comprehensive review, the phytochemicals resveratrol, berberine and curcumin will be discussed, with particular focus being given to their proposed anticancer applications. The purpose of this review is to help clarify whether there is any truth in the claims that are regularly made regarding the efficacy of these compounds. To this end, a number of significant studies that involved the use of these phytochemicals will be identified, discussed and evaluated, to determine if they show promise in the ongoing fight to reduce the incidence rates and severity of various cancers. Specifically, it is the aim of this review to present and discuss key studies performed over the last two decades using these compounds and to evaluate, compare and contrast their effectiveness as chemopreventatives and chemotherapeutics. This should provide the reader with an overarching picture of how these structurally similar phytochemicals might be used in both clinical and nonclinical settings, as a part of the ongoing effort by clinicians, to help to slow down the increasing rate of cancers observed over the last few decades.
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Affiliation(s)
- Mark Sean D'Arcy
- Biology Division, Hertfordshire International College, College Lane Campus, Hatfield, UK
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Sharma J, Krupenko SA. Folate pathways mediating the effects of ethanol in tumorigenesis. Chem Biol Interact 2020; 324:109091. [PMID: 32283069 DOI: 10.1016/j.cbi.2020.109091] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 04/02/2020] [Indexed: 02/08/2023]
Abstract
Folate and alcohol are dietary factors affecting the risk of cancer development in humans. The interaction between folate status and alcohol consumption in carcinogenesis involves multiple mechanisms. Alcoholism is typically associated with folate deficiency due to reduced dietary folate intake. Heavy alcohol consumption also decreases folate absorption, enhances urinary folate excretion and inhibits enzymes pivotal for one-carbon metabolism. While folate metabolism is involved in several key biochemical pathways, aberrant DNA methylation, due to the deficiency of methyl donors, is considered as a common downstream target of the folate-mediated effects of ethanol. The negative effects of low intakes of nutrients that provide dietary methyl groups, with high intakes of alcohol are additive in general. For example, low methionine, low-folate diets coupled with alcohol consumption could increase the risk for colorectal cancer in men. To counteract the negative effects of alcohol consumption, increased intake of nutrients, such as folate, providing dietary methyl groups is generally recommended. Here mechanisms involving dietary folate and folate metabolism in cancer disease, as well as links between these mechanisms and alcohol effects, are discussed. These mechanisms include direct effects on folate pathways and indirect mediation by oxidative stress, hypoxia, and microRNAs.
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Affiliation(s)
- Jaspreet Sharma
- Nutrition Research Institute and Department of Nutrition, University of North Carolina, Chapel Hill, USA
| | - Sergey A Krupenko
- Nutrition Research Institute and Department of Nutrition, University of North Carolina, Chapel Hill, USA; Department of Nutrition, University of North Carolina, Chapel Hill, USA.
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44
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Igelman SJ, Na C, Simpson EL. Alcohol-induced facial flushing in a patient with atopic dermatitis treated with dupilumab. JAAD Case Rep 2020; 6:139-140. [PMID: 32021896 PMCID: PMC6994276 DOI: 10.1016/j.jdcr.2019.12.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Sean J. Igelman
- Saint Louis University School of Medicine, St. Louis, Missouri
- Correspondence to: Sean J. Igelman, BS, Saint Louis University School of Medicine, 1402 S Grand Blvd, St Louis, MO 63104.
| | - Chanho Na
- Chosun University School of Medicine, Department of Dermatology, Gwangju, South Korea
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Song BJ, Abdelmegeed MA, Cho YE, Akbar M, Rhim JS, Song MK, Hardwick JP. Contributing Roles of CYP2E1 and Other Cytochrome P450 Isoforms in Alcohol-Related Tissue Injury and Carcinogenesis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1164:73-87. [PMID: 31576541 DOI: 10.1007/978-3-030-22254-3_6] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The purpose of this review is to briefly summarize the roles of alcohol (ethanol) and related compounds in promoting cancer and inflammatory injury in many tissues. Long-term chronic heavy alcohol exposure is known to increase the chances of inflammation, oxidative DNA damage, and cancer development in many organs. The rates of alcohol-mediated organ damage and cancer risks are significantly elevated in the presence of co-morbidity factors such as poor nutrition, unhealthy diets, smoking, infection with bacteria or viruses, and exposure to pro-carcinogens. Chronic ingestion of alcohol and its metabolite acetaldehyde may initiate and/or promote the development of cancer in the liver, oral cavity, esophagus, stomach, gastrointestinal tract, pancreas, prostate, and female breast. In this chapter, we summarize the important roles of ethanol/acetaldehyde in promoting inflammatory injury and carcinogenesis in several tissues. We also review the updated roles of the ethanol-inducible cytochrome P450-2E1 (CYP2E1) and other cytochrome P450 isozymes in the metabolism of various potentially toxic substrates, and consequent toxicities, including carcinogenesis in different tissues. We also briefly describe the potential implications of endogenous ethanol produced by gut bacteria, as frequently observed in the experimental models and patients of nonalcoholic fatty liver disease, in promoting DNA mutation and cancer development in the liver and other tissues, including the gastrointestinal tract.
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Affiliation(s)
- Byoung-Joon Song
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
| | - Mohamed A Abdelmegeed
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - Young-Eun Cho
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.,Department of Food Science and Nutrition, Andong National University, Andong, Republic of Korea
| | - Mohammed Akbar
- Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - Johng S Rhim
- Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Min-Kyung Song
- Investigational Drug Branch, National Cancer Institute, NIH, Bethesda, MD, USA
| | - James P Hardwick
- Biochemistry and Molecular Pathology in the Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA
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