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Bhagat N, Nalawala Z, Patel J, Das D, Baldha R, Sarolia J, Rathod S. Self-Assembled systems for Nose-to-Brain delivery of Temozolamide (TMZ) in brain tumor therapy. Int J Pharm 2025; 675:125540. [PMID: 40174811 DOI: 10.1016/j.ijpharm.2025.125540] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 03/20/2025] [Accepted: 03/27/2025] [Indexed: 04/04/2025]
Abstract
Glioblastoma multiforme (GBM) is an aggressive and highly invasive primary brain tumor with poor prognosis and resistance to conventional therapies. The therapeutic efficacy of existing treatments is significantly hampered by the presence of the blood-brain barrier (BBB), tumor heterogeneity, and intrinsic drug resistance mechanisms. Temozolomide (TMZ), the standard chemotherapeutic agent for GBM, suffers from low bioavailability, rapid systemic clearance, and enzymatic degradation, limiting its clinical success. This review highlights the potential of self-assembled nanocarrier-based drug delivery systems for enhancing the therapeutic index of TMZ through intranasal administration, which provides a direct and non-invasive route to the brain, circumventing the BBB and improving central nervous system (CNS) drug bioavailability. Self-assembled systems are highly customizable, allowing for precise control over particle size, surface charge, and release profiles, which can be tailored to improve the penetration and retention of TMZ in the brain. We comprehensively discuss recent advancements in polymeric nanoparticles, liposomes, micelles, niosomes, and solid lipid nanoparticles, emphasizing their physicochemical properties, pharmacokinetics, and mechanisms of targeted drug release. Additionally, we explore molecular and oxidative stress-related pathways contributing to GBM progression and TMZ resistance. Emerging research suggests that nanocarrier-based intranasal delivery of TMZ enhances drug stability, prolongs brain retention time, and minimizes systemic toxicity, offering a promising avenue for improving GBM treatment outcomes.
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Affiliation(s)
- Nishank Bhagat
- Parul Institute of Pharmacy & Research, Parul University, Wagodia 391760
| | - Zainab Nalawala
- Parul Institute of Pharmacy & Research, Parul University, Wagodia 391760
| | - Jemini Patel
- Parul Institute of Pharmacy & Research, Parul University, Wagodia 391760
| | - Diponkar Das
- Parul Institute of Pharmacy & Research, Parul University, Wagodia 391760
| | - Raj Baldha
- Parul Institute of Pharmacy & Research, Parul University, Wagodia 391760.
| | | | - Sachin Rathod
- Parul Institute of Pharmacy & Research, Parul University, Wagodia 391760; Maliba Pharmacy College, Maliba Campus, 394350.
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Meinke MC, Hasse S, Schleusener J, Hahn V, Gerling T, Hadian Rasnani K, Bernhardt T, Ficht PK, Staffeld A, Bekeschus S, Lademann J, Emmert S, Lohan SB, Boeckmann L. Radical formation in skin and preclinical characterization of a novel medical plasma device for dermatology after single application. Free Radic Biol Med 2025; 226:199-215. [PMID: 39549883 DOI: 10.1016/j.freeradbiomed.2024.11.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 11/06/2024] [Accepted: 11/13/2024] [Indexed: 11/18/2024]
Abstract
Cold atmospheric plasma (CAP) enables painless tissue treatment by producing reactive species including excited molecules and charged particles and is of great interest for medical applications. Medical CAP sources work in contact with air at ambient pressure, resulting in the generation of substantial amounts of reactive oxygen and nitrogen radicals. These radicals have a significant influence on cellular biochemistry, are crucial components of the immune system, and play a central role in wound therapy. CAP has a variety of applications, with a particular emphasis on tissue treatment in dermatology. It eradicates microorganisms by preventing biofilm formation so that wounds can be effectively disinfected and treated antiseptically. Using both in vitro and ex vivo methods, a comprehensive preclinical assessment of a novel battery-operated cold plasma handheld device with a reusable, and autoclavable glass cylinder was performed. The objectives were to evaluate the potential impact of single CAP application on radical formation with and without wound dressing, by directly measuring radicals in skin, to investigate the influence of CAP application on antimicrobial activity and cytotoxicity in vitro, and to assess skin tolerance ex vivo. The direct effect of CAP on the formation of radicals in the skin after plasma application at different levels with and without wound dressing was demonstrated quantitatively for the first time using electron paramagnetic resonance spectroscopy. Free radicals were measured in the skin as a function of the duration of CAP treatment. Furthermore, it was found that an alginate or wound plaster dressing does not significantly inhibit radical formation in skin compared to application without a dressing. In vitro and ex vivo data showed no cytotoxic potential with simultaneous efficacy against bacteria strains and no risk of temperature rise, pH change, skin barrier or DNA damage. These results show a high potential for wound healing applications in vivo.
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Affiliation(s)
- Martina C Meinke
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charitéplatz 1, 10117, Berlin, Germany.
| | - Sybille Hasse
- Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany
| | - Johannes Schleusener
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charitéplatz 1, 10117, Berlin, Germany
| | - Veronika Hahn
- Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany
| | - Torsten Gerling
- Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany; Diabetes Competence Centre Karlsburg (KDK), Leibniz Institute for Plasma Science and Technology (INP), Greifswalder Str. 11, 17495, Karlsburg, Germany
| | - Katayoon Hadian Rasnani
- Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany
| | - Thoralf Bernhardt
- Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, Strempelstraße 13, 18057, Rostock, Germany
| | - Philipp-Kjell Ficht
- Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, Strempelstraße 13, 18057, Rostock, Germany
| | - Anna Staffeld
- Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, Strempelstraße 13, 18057, Rostock, Germany
| | - Sander Bekeschus
- Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany; Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, Strempelstraße 13, 18057, Rostock, Germany
| | - Jürgen Lademann
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charitéplatz 1, 10117, Berlin, Germany
| | - Steffen Emmert
- Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, Strempelstraße 13, 18057, Rostock, Germany
| | - Silke B Lohan
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charitéplatz 1, 10117, Berlin, Germany
| | - Lars Boeckmann
- Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, Strempelstraße 13, 18057, Rostock, Germany
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Balestra C, Leveque C, Mrakic-Sposta S, Coulon M, Tumbarello R, Vezzoli A, Bosco G, Imtiyaz Z, Thom SR. Inert Gas Mild Pressure Action on Healthy Humans: The "IPA" Study. Int J Mol Sci 2024; 25:12067. [PMID: 39596136 PMCID: PMC11593890 DOI: 10.3390/ijms252212067] [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: 10/08/2024] [Revised: 11/05/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
The goal of this study was to evaluate inflammatory and oxidative stress responses in human subjects (9 females and 15 males) (age [29.6 ± 11.5 years old (mean ± SD)], height [172.0 ± 10.05 cm], and weight [67.8 ± 12.4 kg]) exposed to 1.45 ATA of helium (He) or nitrogen (N2) without concurrent hyperoxia. We hypothesized that elevated gas pressures would elicit an inflammatory response concurrent with oxidative stress. Consistent with ex vivo studies, both gasses elicited neutrophil activation, small elevations in microparticles (MPs) and increases in intra-MP interleukin (IL)-1β and inflammatory nitric oxide synthase, and an increase in urinary IL-6 concurrent with a marked reduction in plasma gelsolin. Mixed responses indictive of oxidative stress, with some biomarker elevations but little change in others and a decrease in some, were observed. Overall, these results demonstrate that exposure to typical diving gasses at a mildly elevated partial pressure will initiate inflammatory responses, which may play a significant role in decompression sickness (DCS). The complex pattern of oxidative stress responses may be indicative of competing systemic reactions and sampling different body fluids.
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Affiliation(s)
- Costantino Balestra
- Environmental, Occupational, Aging (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1160 Brussels, Belgium; (C.L.); (M.C.); (R.T.)
- Anatomical Research and Clinical Studies, Vrije Universiteit Brussels (VUB), 1090 Brussels, Belgium
- DAN Europe Research Division (Roseto-Brussels), 1160 Brussels, Belgium
- Physical Activity Teaching Unit, Motor Sciences Department, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium
| | - Clément Leveque
- Environmental, Occupational, Aging (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1160 Brussels, Belgium; (C.L.); (M.C.); (R.T.)
| | - Simona Mrakic-Sposta
- Institute of Clinical Physiology-National Research Council (CNR-IFC), 20142 Milano, Italy; (S.M.-S.); (A.V.)
| | - Mathias Coulon
- Environmental, Occupational, Aging (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1160 Brussels, Belgium; (C.L.); (M.C.); (R.T.)
| | - Romain Tumbarello
- Environmental, Occupational, Aging (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1160 Brussels, Belgium; (C.L.); (M.C.); (R.T.)
| | - Alessandra Vezzoli
- Institute of Clinical Physiology-National Research Council (CNR-IFC), 20142 Milano, Italy; (S.M.-S.); (A.V.)
- Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy;
| | - Gerardo Bosco
- Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy;
| | - Zuha Imtiyaz
- Department of Emergency Medicine, School of Medicine, University of Maryland, Baltimore, MD 21250, USA; (Z.I.); (S.R.T.)
| | - Stephen R. Thom
- Department of Emergency Medicine, School of Medicine, University of Maryland, Baltimore, MD 21250, USA; (Z.I.); (S.R.T.)
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Dhahi RM. Biofabrication of Nanosilver From Punica granatum Peel Extract and Their Anticoagulant Applications. INTERNATIONAL JOURNAL OF FOOD SCIENCE 2024; 2024:6623228. [PMID: 39363887 PMCID: PMC11449558 DOI: 10.1155/2024/6623228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 09/05/2024] [Indexed: 10/05/2024]
Abstract
For utilizing biodegradable waste as a natural source for nanofabrication, this study was designed to highlight a simple, sustainable, safe, environmentally friendly, and energy consumption reduction waste management approach using hot aqueous extract of Punica granatum (pomegranate) peel waste (PPE) to biosynthesize silver nanoparticles (PPE-AgNPs). The fabrication of biosynthesized nanosilver was confirmed by UV-visible spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and atomic force microscope (AFM). The initial pale brown color change upon adding silver nitrate to PPE confirmed bioreduction. For PPE, the absorption spectrum for UV-vis spectroscopy in the visible light region was 230-290 nm, while for PPE-AgNPs, the graph shows that surface plasmon resonance (SPR) spectrum for nanosilver at 360-460 nm. The XRD analysis proved that the PPE-AgNPs were crystalline in nature. The SEM micrograph revealed that silver nanoparticles were sphere-shaped, homogenous accumulations with particle size in the range of 21.63-30.97 ± 0.4 nm. The EDX data analysis also proved the presence of a sharp peak of silver element with 8.83% weight at 3 keV. The 3D AFM images of Ag nanoparticles illustrated that the diameter is around 7.20-14.80 nm with a median of 7.16 ± 1.3 nm and the root mean square (RMS) value corresponds to 1.40 ± 0.4 nm. The PPE-AgNPs efficiently exhibited a potent antioxidant and dose-dependent DPPH inhibition action. Visual and microscopic observations of fresh human blood when treated with 25, 50, 75, and 100 μg/mL of PPE-AgNPs were proven to be biocompatible with no morphological changes and no coagulation. This study predicts that PPE can be utilized to synthesize biocompatible nanosilver.
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Shrivastav D, Dabla PK, Sharma J, Viswas A, Mir R. Insights on antioxidant therapeutic strategies in type 2 diabetes mellitus: A narrative review of randomized control trials. World J Diabetes 2023; 14:919-929. [PMID: 37383600 PMCID: PMC10294058 DOI: 10.4239/wjd.v14.i6.919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/11/2023] [Accepted: 05/11/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a metabolic disease of impaired glucose utilization. Imbalance in generation and elimination of free radicals generate oxidative stress which modulates glucose metabolism and insulin regulation, resulting in the occurrence and progression of diabetes and associated complications. Antioxidant supplements in T2DM can be seen as a potential preventive and effective therapeutic strategy. AIM To compare randomized controlled trials (RCTs) in which antioxidants have been shown to have a therapeutic effect in T2DM patients. METHODS We systematically searched the electronic database PubMed by keywords. RCTs evaluating the effect of antioxidant therapy on glycaemic control as well as oxidant and antioxidant status as primary outcomes were included. The outcomes considered were: A reduction in blood glucose; changes in oxidative stress and antioxidant markers. Full-length papers of the shortlisted articles were assessed for the eligibility criteria and 17 RCTs were included. RESULTS The administration of fixed-dose antioxidants significantly reduces fasting blood sugar and glycated hemoglobin and is associated with decreased malondialdehyde, advanced oxidation protein products, and increased total antioxidant capacity. CONCLUSION Antioxidant supplements can be a beneficial approach for the treatment of T2DM.
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Affiliation(s)
| | - Pradeep Kumar Dabla
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
| | - Jitender Sharma
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
| | - Aroop Viswas
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India
| | - Rashid Mir
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
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Shrivastav D, Dabla PK, Sharma J, Viswas A, Mir R. Insights on antioxidant therapeutic strategies in type 2 diabetes mellitus: A narrative review of randomized control trials. World J Diabetes 2023; 14:919-929. [DOI: 10.4239/wjd.v14.i6.919 shrivastav d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2023] Open
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Marković Z, Komolkin AV, Egorov AV, Milenković D, Jeremić S. Alizarin as a potential protector of proteins against damage caused by hydroperoxyl radical. Chem Biol Interact 2023; 373:110395. [PMID: 36758887 DOI: 10.1016/j.cbi.2023.110395] [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: 09/01/2022] [Revised: 01/30/2023] [Accepted: 02/06/2023] [Indexed: 02/10/2023]
Abstract
Alizarin is a natural anthraquinone molecule with moderate antioxidative capacity. Some earlier investigations indicated that it can inhibit osteosarcoma and breast carcinoma cell proliferation by inhibiting of phosphorylation process of ERK protein (extracellular signal-regulated kinases). Several mechanisms of deactivation of one of the most reactive oxygen species, hydroperoxyl radical, by alizarin are estimated: hydrogen atom abstraction (HAA), radical adduct formation (RAF), and single electron transfer (SET). The plausibility of those mechanisms is estimated using density functional theory. The obtained results indicated HAA as the only thermodynamically plausible mechanism. For that purpose, two possible mechanistic pathways for hydrogen atom abstraction are studied in detail: hydrogen atom transfer (HAT) and proton-coupled electron transfer (PCET). Water and benzene are used as models of solvents with opposite polarity. To examine the difference between HAT and PCET is used kinetical approach based on the Transition state theory (TST) and determined rate constants (k). Important data used for a distinction between HAT and PCET mechanisms are obtained by applying the Quantum Theory of Atoms in Molecules (QTAIM), and by the analysis of single occupied molecular orbitals (SOMOs) in transition states for two examined mechanisms. The molecular docking analysis and molecular dynamic are used to predict the most probable positions of binding of alizarin to the sequence of ApoB-100 protein, a protein component of plasma low-density lipoproteins (LDL). It is found that alizarin links the nitrated polypeptide forming the π-π interactions with the amino acids Phenylalanine and Nitrotyrosine. The ability of alizarin to scavenge hydroperoxyl radical when it is in a sandwich structure between the polypeptide and radical species, as the operative reaction mechanism, is not significantly changed concerning its antioxidant capacity in the absence of polypeptide. Therefore, alizarin can protect the polypeptide from harmful hydroperoxyl radical attack, positioning itself between the polypeptide chain and the reactive oxygen species.
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Affiliation(s)
- Zoran Marković
- Institute for Information Technologies, Department of Science, University of Kragujevac, Jovana Cvijića bb, 34000, Kragujevac, Serbia; Department of Natural Science and Mathematics, State University of Novi Pazar, Serbia.
| | - Andrei V Komolkin
- Faculty of Physics, Department of Nuclear-Physics Research Methods, St. Petersburg State University, Saint Petersburg, Russia
| | - Andrei V Egorov
- Faculty of Physics, Department of Nuclear-Physics Research Methods, St. Petersburg State University, Saint Petersburg, Russia
| | - Dejan Milenković
- Institute for Information Technologies, Department of Science, University of Kragujevac, Jovana Cvijića bb, 34000, Kragujevac, Serbia
| | - Svetlana Jeremić
- Department of Natural Science and Mathematics, State University of Novi Pazar, Serbia.
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Mao Z, Gray ALH, Thyagarajan B, Bostick RM. Antioxidant enzyme and DNA base repair genetic risk scores' associations with systemic oxidative stress biomarker in pooled cross-sectional studies. FRONTIERS IN AGING 2023; 4:1000166. [PMID: 37152862 PMCID: PMC10161255 DOI: 10.3389/fragi.2023.1000166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 03/28/2023] [Indexed: 05/09/2023]
Abstract
Background: Oxidative stress is hypothesized to contribute to the pathogenesis of several chronic diseases. Numerous dietary and lifestyle factors are associated with oxidative stress; however, little is known about associations of genetic factors, individually or jointly with dietary and lifestyle factors, with oxidative stress in humans. Methods: We genotyped 22 haplotype-tagging single nucleotide polymorphisms (SNPs) in 3 antioxidant enzyme (AE) genes and 79 SNPs in 14 DNA base excision repair (BER) genes to develop oxidative stress-specific AE and BER genetic risk scores (GRS) in two pooled cross-sectional studies (n = 245) of 30-74-year-old, White, cancer- and inflammatory bowel disease-free adults. Of the genotypes, based on their associations with a systemic oxidative stress biomarker, plasma F2-isoprostanes (FiP) concentrations, we selected 4 GSTP1 SNPs for an AE GRS, and 12 SNPs of 5 genes (XRCC1, TDG, PNKP, MUTYH, and FEN1) for a BER GRS. We also calculated a previously-reported, validated, questionnaire-based, oxidative stress biomarker-weighted oxidative balance score (OBS) comprising 17 anti- and pro-oxidant dietary and lifestyle exposures, with higher scores representing a higher predominance of antioxidant exposures. We used general linear regression to assess adjusted mean FiP concentrations across GRS and OBS tertiles, separately and jointly. Results: The adjusted mean FiP concentrations among those in the highest relative to the lowest oxidative stress-specific AE and BER GRS tertiles were, proportionately, 11.8% (p = 0.12) and 21.2% (p = 0.002) higher, respectively. In the joint AE/BER GRS analysis, the highest estimated mean FiP concentration was among those with jointly high AE/BER GRS. Mean FiP concentrations across OBS tertiles were similar across AE and BER GRS strata. Conclusion: Our pilot study findings suggest that DNA BER, and possibly AE, genotypes collectively may be associated with systemic oxidative stress in humans, and support further research in larger, general populations.
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Affiliation(s)
- Ziling Mao
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Abigail L. H. Gray
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Bharat Thyagarajan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
| | - Roberd M. Bostick
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States
- Winship Cancer Institute, Emory University, Atlanta, GA, United States
- *Correspondence: Roberd M. Bostick,
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Tiwary E, Hu M, Prasain JK. Sperm-Guiding Unconventional Prostaglandins in C. elegans: Synthesis and Signaling. Metabolites 2021; 11:metabo11120853. [PMID: 34940611 PMCID: PMC8705762 DOI: 10.3390/metabo11120853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/02/2021] [Accepted: 12/04/2021] [Indexed: 02/02/2023] Open
Abstract
Prostaglandins comprise a family of lipid signaling molecules derived from polyunsaturated fatty acids and are involved in a wide array of biological processes, including fertilization. Prostaglandin-endoperoxide synthase (a.k.a. cyclooxygenase or Cox) initiates prostaglandin synthesis from 20-carbon polyunsaturated fatty acids, such as arachidonic acid. Oocytes of Caenorhabditis elegans (C. elegans) have been shown to secrete sperm-guidance cues prostaglandins, independent of Cox enzymes. Both prostaglandin synthesis and signal transduction in C. elegans are environmentally modulated pathways that regulate sperm guidance to the fertilization site. Environmental factors such as food triggers insulin and TGF-β secretion and their levels regulate tissue-specific prostaglandin synthesis in C. elegans. This novel PG pathway is abundant in mouse and human ovarian follicular fluid, where their functions, mechanism of synthesis and pathways remain to be established. Given the importance of prostaglandins in reproductive processes, a better understanding of how diets and other environmental factors influence their synthesis and function may lead to new strategies towards improving fertility in mammals.
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Affiliation(s)
- Ekta Tiwary
- Department of Medicines, University of Alabama at Birmingham, Birmingham, AL 35205, USA;
| | - Muhan Hu
- Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL 35205, USA;
| | - Jeevan K. Prasain
- Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Correspondence: ; Tel.: +1-(205)-996-2612
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Associations of dietary, lifestyle, other participant characteristics, and oxidative balance scores with plasma F 2-isoprostanes concentrations in a pooled cross-sectional study. Eur J Nutr 2021; 61:1541-1560. [PMID: 34860269 DOI: 10.1007/s00394-021-02754-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 11/20/2021] [Indexed: 12/23/2022]
Abstract
PURPOSE Plasma F2-isoprostanes (FiP) concentration, a reliably measured, valid, systemic oxidative stress biomarker, has been associated with multiple health-related outcomes; however, associations of most individual dietary and lifestyle exposures with FiP are unclear, and there is no reported oxidative balance score (OBS) comprising multiple dietary and/or lifestyle components weighted by their associations with FiP. METHODS To investigate cross-sectional associations of dietary and lifestyle characteristics with plasma FiP concentrations, we used multivariable general linear models to compare adjusted mean FiP concentrations across categories of dietary nutrient and whole-food intakes and lifestyle characteristics in two pooled cross-sectional studies (n = 386). We also developed equal-weight and weighted OBS (nutrient- and foods-based dietary OBS, lifestyle OBS, and total OBS), and compared adjusted mean FiP concentrations across OBS tertiles. RESULTS Among men and women combined, adjusted mean FiP concentrations were statistically significantly, proportionately 28.1% higher among those who were obese relative to those who were normal weight; among those in the highest relative to the lowest total nutrient intake tertiles, FiP concentrations were statistically significantly lower by 9.8% for carotenes, 13.6% for lutein/zeaxanthin, 10.9% for vitamin C, 12.2% for vitamin E, 11.5% for glucosinolates, and 5% for calcium. Of the various OBS, the weighted OBS that combined total nutrient intakes and lifestyle exposures was most strongly associated with FiP concentrations: among those in the highest relative to the lowest total OBS, mean FiP concentrations were statistically significantly 29.7% lower (P < 0.001). CONCLUSION Multiple dietary and lifestyle characteristics, individually, and especially collectively, may contribute to systemic oxidative stress.
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Nakamura T, Tachibana Y, Murata T. 8-iso-prostaglandin E 2 induces nasal obstruction via thromboxane receptor in murine model of allergic rhinitis. FASEB J 2021; 35:e21941. [PMID: 34559928 DOI: 10.1096/fj.202100827r] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/23/2021] [Accepted: 09/07/2021] [Indexed: 01/22/2023]
Abstract
Thromboxane receptor (TP) mediates nasal obstruction, a typical symptom of allergic rhinitis. Since it has been reported that several types of eicosanoids, such as non-enzymatic oxidation product of arachidonic acid isoprostane, act as a TP ligand, there is a possibility that some other eicosanoids contribute to the TP-mediated nasal obstruction. The aim of this study is to investigate the mechanisms of TP-mediated nasal obstruction. Intranasal challenges of ovalbumin (OVA) induced nasal obstruction in mice. Pharmacological blockade of TP receptor but not thromboxane A2 synthase inhibited OVA-induced nasal obstruction. Simultaneous analysis of eicosanoids in nasal lavage fluid and the responses in trans-endothelial resistance suggested that 8-iso-prostaglandin E2 (PGE2 ) can be a candidate for TP ligand. Intranasal challenge of 8-iso-PGE2 induced vascular hyperpermeability and nasal obstruction in TP receptor-dependent manner. Wholemount immunostaining of nasal septum mucosa revealed that 8-iso-PGE2 increased plasma leakage accompanied by distention of venous sinusoids. This study shows that 8-iso-PGE2 is a contributor in TP-mediated nasal obstruction in mice.
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Affiliation(s)
- Tatsuro Nakamura
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Yuri Tachibana
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Takahisa Murata
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
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Flieger J, Flieger W, Baj J, Maciejewski R. Antioxidants: Classification, Natural Sources, Activity/Capacity Measurements, and Usefulness for the Synthesis of Nanoparticles. MATERIALS (BASEL, SWITZERLAND) 2021; 14:4135. [PMID: 34361329 PMCID: PMC8347950 DOI: 10.3390/ma14154135] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/15/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023]
Abstract
Natural extracts are the source of many antioxidant substances. They have proven useful not only as supplements preventing diseases caused by oxidative stress and food additives preventing oxidation but also as system components for the production of metallic nanoparticles by the so-called green synthesis. This is important given the drastically increased demand for nanomaterials in biomedical fields. The source of ecological technology for producing nanoparticles can be plants or microorganisms (yeast, algae, cyanobacteria, fungi, and bacteria). This review presents recently published research on the green synthesis of nanoparticles. The conditions of biosynthesis and possible mechanisms of nanoparticle formation with the participation of bacteria are presented. The potential of natural extracts for biogenic synthesis depends on the content of reducing substances. The assessment of the antioxidant activity of extracts as multicomponent mixtures is still a challenge for analytical chemistry. There is still no universal test for measuring total antioxidant capacity (TAC). There are many in vitro chemical tests that quantify the antioxidant scavenging activity of free radicals and their ability to chelate metals and that reduce free radical damage. This paper presents the classification of antioxidants and non-enzymatic methods of testing antioxidant capacity in vitro, with particular emphasis on methods based on nanoparticles. Examples of recent studies on the antioxidant activity of natural extracts obtained from different species such as plants, fungi, bacteria, algae, lichens, actinomycetes were collected, giving evaluation methods, reference antioxidants, and details on the preparation of extracts.
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Affiliation(s)
- Jolanta Flieger
- Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4A, 20-093 Lublin, Poland
| | - Wojciech Flieger
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (W.F.); (J.B.); (R.M.)
| | - Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (W.F.); (J.B.); (R.M.)
| | - Ryszard Maciejewski
- Chair and Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (W.F.); (J.B.); (R.M.)
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Pyrazoles and Pyrazolines as Anti-Inflammatory Agents. Molecules 2021; 26:molecules26113439. [PMID: 34198914 PMCID: PMC8201324 DOI: 10.3390/molecules26113439] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/01/2021] [Accepted: 06/03/2021] [Indexed: 12/14/2022] Open
Abstract
The five-membered heterocyclic group of pyrazoles/pyrazolines plays important role in drug discovery. Pyrazoles and pyrazolines present a wide range of biological activities. The synthesis of the pyrazolines and pyrazole derivatives was accomplished via the condensation of the appropriate substituted aldehydes and acetophenones, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid. The compounds are obtained in good yields 68-99% and their structure was confirmed using IR, 1H-NMR, 13C-NMR and elemental analysis. The novel derivatives were studied in vitro for their antioxidant, anti-lipid peroxidation (AAPH) activities and inhibitory activity of lipoxygenase. Both classes strongly inhibit lipid peroxidation. Compound 2g was the most potent lipoxygenase inhibitor (IC50 = 80 µM). The inhibition of the carrageenin-induced paw edema (CPE) and nociception was also determined, with compounds 2d and 2e being the most potent. Compound 2e inhibited nociception higher than 2d. Pyrazoline 2d was found to be active in a preliminary test, for the investigation of anti-adjuvant-induced disease (AID) activity. Pyrazoline derivatives were found to be more potent than pyrazoles. Docking studies of the most potent LOX inhibitor 2g highlight hydrophobic interactions with VAL126, PHE143, VAL520 and LYS526 and a halogen bond between the chlorine atom and ARG182.
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Savage K, Kingshott D, Gubko A, Thee AW, Burjawi T, Croft K, Sarris J, Stough C. The Relationship between Oxidative Stress and Anxiety in a Healthy Older Population. Exp Aging Res 2021; 47:322-346. [PMID: 33616006 DOI: 10.1080/0361073x.2021.1883966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Background/study context: F2-Isoprostanes are putative markers of oxidative stress, one of the processes associated with biological senescence. Evidence exists for elevated F2-Isoprostanes in chronic conditions including psychiatric disorders. Few studies have examined the relationship between oxidative stress and mood in older healthy samples, to establish the influence on mental health. Given current aging demographics in many nations, management of brain and mental health is crucial for longevity, chronic disease management, and quality of life.Method: We investigated the relationship between F2-Isoprostanes, a marker for oxidative stress, and anxiety and mood in 262 healthy adults aged 60-75 years, using baseline data from the Australian Research Council Longevity Intervention (ARCLI; ANZCTR12611000487910), a 12-month nutraceutical intervention study.Results: Higher F2 levels significantly predicted increased Depression-dejection and Anger-hostility subscale scores from the Profile of Mood States (POMS). Fatigue-inertia subscale was predicted by increased Body Mass Index. Spielberger State-Trait Inventory (STAI) scores were significantly higher in females.Conclusion: While the primary outcome data did not find a definitive relationship between F2 and total mood or general anxiety levels, the sub-scale data adds weight toward growing literature that biological processes such as oxidative stress are in part related to mood. This is a modifiable risk factor contributing to physical and mental wellbeing that are crucial to healthy aging.
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Affiliation(s)
- Karen Savage
- Centre for Human Psychopharmacology, Swinburne University of Technology, Advanced Technologies Centre, Hawthorn, Australia.,Professorial Unit, the Melbourne Clinic, Department of Psychiatry, Melbourne University, Richmond, Australia
| | - Davy Kingshott
- Centre for Human Psychopharmacology, Swinburne University of Technology, Advanced Technologies Centre, Hawthorn, Australia
| | - Andrew Gubko
- Centre for Human Psychopharmacology, Swinburne University of Technology, Advanced Technologies Centre, Hawthorn, Australia
| | - Alicia Wt Thee
- Centre for Human Psychopharmacology, Swinburne University of Technology, Advanced Technologies Centre, Hawthorn, Australia
| | - Tamer Burjawi
- Centre for Human Psychopharmacology, Swinburne University of Technology, Advanced Technologies Centre, Hawthorn, Australia
| | - Kevin Croft
- School of Biomedical Science, The University of Western Australia, Crawley, Australia
| | - Jerome Sarris
- Professorial Unit, the Melbourne Clinic, Department of Psychiatry, Melbourne University, Richmond, Australia.,NICM Health Research Institute, Western Sydney University, Westmead, Australia
| | - Con Stough
- Centre for Human Psychopharmacology, Swinburne University of Technology, Advanced Technologies Centre, Hawthorn, Australia
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Free Radicals as a Double-Edged Sword: The Cancer Preventive and Therapeutic Roles of Curcumin. Molecules 2020; 25:molecules25225390. [PMID: 33217990 PMCID: PMC7698794 DOI: 10.3390/molecules25225390] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/13/2020] [Accepted: 11/15/2020] [Indexed: 01/07/2023] Open
Abstract
Free radicals, generally composed of reactive oxygen species (ROS) and reactive nitrogen species (RNS), are generated in the body by various endogenous and exogenous systems. The overproduction of free radicals is known to cause several chronic diseases including cancer. However, increased production of free radicals by chemotherapeutic drugs is also associated with apoptosis in cancer cells, indicating the dual nature of free radicals. Among various natural compounds, curcumin manifests as an antioxidant in normal cells that helps in the prevention of carcinogenesis. It also acts as a prooxidant in cancer cells and is associated with inducing apoptosis. Curcumin quenches free radicals, induces antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and upregulates antioxidative protein markers-Nrf2 and HO-1 that lead to the suppression of cellular oxidative stress. In cancer cells, curcumin aggressively increases ROS that results in DNA damage and subsequently cancer cell death. It also sensitizes drug-resistant cancer cells and increases the anticancer effects of chemotherapeutic drugs. Thus, curcumin shows beneficial effects in prevention, treatment and chemosensitization of cancer cells. In this review, we will discuss the dual role of free radicals as well as the chemopreventive and chemotherapeutic effects of curcumin and its analogues against cancer.
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16
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González NT, Otali E, Machanda Z, Muller MN, Wrangham R, Thompson ME. Urinary markers of oxidative stress respond to infection and late-life in wild chimpanzees. PLoS One 2020; 15:e0238066. [PMID: 32916689 PMCID: PMC7486137 DOI: 10.1371/journal.pone.0238066] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 08/08/2020] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress (OS) plays a marked role in aging and results from a variety of stressors, making it a powerful measure of health and a way to examine costs associated with life history investments within and across species. However, few urinary OS markers have been examined under field conditions, particularly in primates, and their utility to non-invasively monitor the costs of acute stressors versus the long-term damage associated with aging is poorly understood. In this study, we examined variation in 5 urinary markers of oxidative damage and protection under 5 validation paradigms for 37 wild, chimpanzees living in the Kibale National Park, Uganda. We used 924 urine samples to examine responses to acute immune challenge (respiratory illness or severe wounding), as well as mixed-longitudinal and intra-individual variation with age. DNA damage (8-OHdG) correlated positively with all other markers of damage (F-isoprostanes, MDA-TBARS, and neopterin) but did not correlate with protection (total antioxidant capacity). Within individuals, all markers of damage responded to at least one if not both types of acute infection. While OS is expected to increase with age, this was not generally true in chimpanzees. However, significant changes in oxidative damage were detected within past-prime individuals and those close to death. Our results indicate that OS can be measured using field-collected urine and integrates short- and long-term aspects of health. They further suggest that more data are needed from long-lived, wild animals to illuminate if common age-related increases in inflammation and OS damage are typical or recently aberrant in humans.
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Affiliation(s)
- Nicole Thompson González
- University of New Mexico, Department of Anthropology, Albuquerque, NM, United States of America
- University of New Mexico, Academic Science Education and Research Training Program, Health Sciences Center, Albuquerque, NM, United States of America
- * E-mail:
| | - Emily Otali
- Kibale Chimpanzee Project, Fort Portal, Uganda
| | - Zarin Machanda
- Kibale Chimpanzee Project, Fort Portal, Uganda
- Tufts University, Department of Anthropology, Medford, MA, United States of America
| | - Martin N. Muller
- University of New Mexico, Department of Anthropology, Albuquerque, NM, United States of America
- Kibale Chimpanzee Project, Fort Portal, Uganda
| | - Richard Wrangham
- Kibale Chimpanzee Project, Fort Portal, Uganda
- Harvard University, Department of Human Evolutionary Biology, Cambridge, MA, United States of America
| | - Melissa Emery Thompson
- University of New Mexico, Department of Anthropology, Albuquerque, NM, United States of America
- Kibale Chimpanzee Project, Fort Portal, Uganda
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Alkadi H. A Review on Free Radicals and Antioxidants. Infect Disord Drug Targets 2020; 20:16-26. [PMID: 29952268 DOI: 10.2174/1871526518666180628124323] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 06/21/2018] [Accepted: 06/22/2018] [Indexed: 05/16/2023]
Abstract
Free radicals are generated in our body by several systems. A balance among free radicals and antioxidants is an important matter for appropriate physiological function. If free radicals become greater than the ability of the body to control them, a case known as oxidative stress appears, as a result of that, a number of human diseases spread in the body. Antioxidants can contribute to facingthis oxidative stress. The present review provides a brief overview of free radicals, oxidative stress, some natural antioxidants and the relationship between them.
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Affiliation(s)
- Hourieh Alkadi
- Department of Pharmaceutical Chemistry & Drug Control, Faculty of Pharmacy, Arab International University, Daraa, Syrian Arab Republic
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18
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Papachristoforou E, Lambadiari V, Maratou E, Makrilakis K. Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) with Oxidative Stress and Diabetic Complications. J Diabetes Res 2020; 2020:7489795. [PMID: 33123598 PMCID: PMC7585656 DOI: 10.1155/2020/7489795] [Citation(s) in RCA: 226] [Impact Index Per Article: 45.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 09/16/2020] [Accepted: 09/23/2020] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress (OS) is defined as a disturbance in the prooxidant-antioxidant balance of the cell, in favor of the former, which results in the antioxidant capacity of the cell to be overpowered. Excess reactive oxygen species (ROS) production is very harmful to cell constituents, especially proteins, lipids, and DNA, thus causing damage to the cell. Oxidative stress has been associated with a variety of pathologic conditions, including diabetes mellitus (DM), cancer, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and accelerated aging. Regarding DM specifically, previous experimental and clinical studies have pointed to the fact that oxidative stress probably plays a major role in the pathogenesis and development of diabetic complications. It is postulated that hyperglycemia induces free radicals and impairs endogenous antioxidant defense systems through several different mechanisms. In particular, hyperglycemia promotes the creation of advanced glycation end-products (AGEs), the activation of protein kinase C (PKC), and the hyperactivity of hexosamine and sorbitol pathways, leading to the development of insulin resistance, impaired insulin secretion, and endothelial dysfunction, by inducing excessive ROS production and OS. Furthermore, glucose variability has been associated with OS as well, and recent evidence suggests that also hypoglycemia may be playing an important role in favoring diabetic vascular complications through OS, inflammation, prothrombotic events, and endothelial dysfunction. The association of these diabetic parameters (i.e., hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress will be reviewed here.
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Affiliation(s)
- Eleftheria Papachristoforou
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, Athens, Greece
| | - Vaia Lambadiari
- Second Department of Internal Medicine, Research Unit and Diabetes Centre, National and Kapodistrian University of Athens Medical School, Attikon Hospital, Athens, Greece
| | - Eirini Maratou
- Second Department of Internal Medicine, Research Unit and Diabetes Centre, National and Kapodistrian University of Athens Medical School, Attikon Hospital, Athens, Greece
| | - Konstantinos Makrilakis
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, Athens, Greece
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19
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Köktürk M, Alak G, Atamanalp M. The effects of n-butanol on oxidative stress and apoptosis in zebra fish (Danio rerio) larvae. Comp Biochem Physiol C Toxicol Pharmacol 2020; 227:108636. [PMID: 31669665 DOI: 10.1016/j.cbpc.2019.108636] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 09/23/2019] [Accepted: 09/26/2019] [Indexed: 02/06/2023]
Abstract
In recent years, n-butanol has growing use in many areas, including the food industry. In this study, acute toxic effects of n-butanol to zebrafish (Danio rerio) larvae by applying different concentrations (10, 50, 250, 500, 750, 1000 and 1250 mg/L) to embryos were evaluated. For this purpose the data of oxidative stress, antioxidant - acetyl cholinesterase enzyme activities, malondialdehyde level and apoptosis were taken into consideration. At the end of the 96 h, antioxidant (Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)) and acetylcholinesterase (AChE) enzyme activities were decreased, however lipid peroxidation level, apoptotic cells, and reactive oxygen species increased (p < .05). As a result, it has been observed that high concentrations of n-butanol with its amphiphilic structure causes quite intense toxic effects in zebrafish embryos.
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Affiliation(s)
- Mine Köktürk
- Department of Organic Farming, School of Applied Science, Igdır University, TR-76000 Igdır, Turkey
| | - Gonca Alak
- Department of Aquaculture, Faculty of Fisheries, Ataturk University, TR-25030 Erzurum, Turkey
| | - Muhammed Atamanalp
- Department of Aquaculture, Faculty of Fisheries, Ataturk University, TR-25030 Erzurum, Turkey.
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20
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Hagen DM, Ekena JL, Geesaman BM, Viviano KR. Antioxidant supplementation during illness in dogs: effect on oxidative stress and outcome, an exploratory study. J Small Anim Pract 2019; 60:543-550. [PMID: 31292973 DOI: 10.1111/jsap.13050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 03/08/2019] [Accepted: 05/09/2019] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To assess whether combination antioxidant supplementation for 30 days in systemically ill dogs alters antioxidant status, degree of lipid peroxidation, clinical score and survival. MATERIALS AND METHODS Forty client-owned systemically-ill hospitalised dogs were eligible for inclusion. Dogs were randomised to no supplementation (NS; n=19) or supplementation with N-acetylcysteine/S-adenosylmethionine/silybin and vitamin E (AS; n=20) for 30 days. Clinical score and oxidative biomarkers including glutathione, cysteine, vitamin E, selenium and urine isoprostanes/creatinine (F2 -IsoPs/Cr) were determined on days 0 and 30. Glutathione, cysteine, vitamin E and urine F2 -IsoPs/Cr were quantified by high-performance liquid chromatography, and selenium concentrations determined using atomic absorption spectroscopy. RESULTS Thirty-two dogs completed the study (NS, n=16; AS, n=16). Vitamin E concentrations were significantly greater in the supplemented compared to the non-supplemented group. No other markers of oxidative stress significantly changed with supplementation. There was no difference in Day 30 clinical scores or survival between the two groups. CLINICAL SIGNIFICANCE In this population of systemically-ill hospitalised dogs, combination antioxidant supplementation did not alter redox state or clinical outcome.
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Affiliation(s)
- D M Hagen
- VCA Bay Area Veterinary Specialists & Emergency Hospital, San Leandro, California, 94578, USA
| | - J L Ekena
- Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA
| | - B M Geesaman
- Carolina Veterinary Specialist, Winston-Salem, North Carolina, 27103, USA
| | - K R Viviano
- Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA
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21
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Terrington DL, Hayton C, Peel A, Fowler SJ, Fraser W, Wilson AM. The role of measuring exhaled breath biomarkers in sarcoidosis: a systematic review. J Breath Res 2019; 13:036015. [DOI: 10.1088/1752-7163/ab1284] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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El-Khodary MSM, Hasan SE, Hassan WA, El-Lamie MM, Eissa IAM, Khalil WF, Aly SM. How to Return the Death Programs of Cancer Cells to Work again and Cure Cancer within a Short Time? Cell 2019. [DOI: 10.4236/cellbio.2019.82002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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23
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Smith TJ, Johnson JL, Habtewold A, Burmeister MA. Cardiovascular Risk Reduction: A Pharmacotherapeutic Update for Antiplatelet Medications. Crit Care Nurs Clin North Am 2018; 31:15-30. [PMID: 30736932 DOI: 10.1016/j.cnc.2018.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
This update presents evidence for new antiplatelet therapies including modified P2Y12 inhibitors and a new class of thromboxane antagonists. Discussed are emerging data on established antihyperlipidemic medications that support an additional antiplatelet effect. Current information about the effectiveness of several bleeding reversal agents is discussed, and the concept of personalized antiplatelet therapy, wherein selection of an antiplatelet therapy is based on genetic factors or laboratory testing that predict response to therapy and risk of adverse effects. Finally, future drug targets are introduced and drug interactions that can be leveraged to design more effective and safe antiplatelet therapies are described.
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Affiliation(s)
- Troy J Smith
- Department of Pharmacy Practice and Administration, William Carey University School of Pharmacy, 19640 MS-67, Biloxi, MS 39532, USA.
| | - Jessica L Johnson
- Department of Pharmacy Practice and Administration, William Carey University School of Pharmacy, 19640 MS-67, Biloxi, MS 39532, USA
| | - Abiy Habtewold
- Department of Pharmaceutical Sciences, William Carey University School of Pharmacy, 19640 MS-67, Biloxi, MS 39532, USA
| | - Melissa A Burmeister
- Department of Pharmaceutical Sciences, William Carey University School of Pharmacy, 19640 MS-67, Biloxi, MS 39532, USA
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24
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Pais RT, Sousa ACA, Pastorinho MR. A circular toxicity approach to isoprostanes: From markers of oxidative stress, to epidemiological warning systems and agents of aquatic toxicity. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2018; 243:654-660. [PMID: 30223241 DOI: 10.1016/j.envpol.2018.09.033] [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: 03/11/2018] [Revised: 09/03/2018] [Accepted: 09/05/2018] [Indexed: 06/08/2023]
Abstract
Isoprostanes (IsoPs) are a class of oxidation products naturally formed in vivo that are indicative of endogenous oxidative stress. In individuals with chronic and oxidative stress related diseases, IsoPs are increased to pathological levels. Since they are excreted through urine into sewage systems, IsoPs can be detected in wastewater treatment plants' (WWTPs) effluents and thus can be used to evaluate the health status of a given population. The underlying principle is that higher isoprostanes WWTPs' levels correspond to populations undergoing higher levels of oxidative stress, and thus disease. However, IsoPs are not eliminated by WWTPs and will end up being released into the aquatic environment, where they will be available for uptake by aquatic species. Being bioactive molecules, it has been suggested that IsoPs in the environment may elicit oxidative stress in aquatic organisms. In this context, we have critically reviewed the available data on IsoPs as products and effectors of toxicity, and propose the new concept of "circular toxicity". In general, IsoPs excreted by humans as a consequence of oxidative stress are released into the aquatic environment where they may interact with aquatic organisms and induce the production of more IsoPs. These stress markers, in turn, will also be excreted, increasing the already high levels of stressors in the aquatic environment and thus create an escalating cycle of oxidative stress.
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Affiliation(s)
- Ricardo Teles Pais
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal
| | - Ana C A Sousa
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal; CNRS LabEx DRIIHM, CNRS - INEE - ECCOREV (Unité FR3098), OHMi Estarreja-OHM Bassin Minier de Provence, Europôle méditerranéen de L'Arbois, Bât du CEREGE - BP 80, 13545, Aix en Provence Cedex 4, France; CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal; NuESA - Health and Environment Study Unit, Faculty of Health Sciences, University of Beira Interior, 6200-506, Covilhã, Portugal.
| | - M Ramiro Pastorinho
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal; NuESA - Health and Environment Study Unit, Faculty of Health Sciences, University of Beira Interior, 6200-506, Covilhã, Portugal; Faculty of Health Sciences, University of Beira Interior, 6200-506, Covilhã, Portugal
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25
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Meng S, Chanda P, Thandavarayan RA, Cooke JP. Transflammation: How Innate Immune Activation and Free Radicals Drive Nuclear Reprogramming. Antioxid Redox Signal 2018; 29:205-218. [PMID: 29634341 PMCID: PMC6003401 DOI: 10.1089/ars.2017.7364] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
SIGNIFICANCE Yamanaka and colleagues galvanized the field of stem cell biology and regenerative medicine by their generation of induced pluripotent stem cells. Evidence is emerging that activation of innate immune signaling is critical for efficient reprogramming to pluripotency and for the nuclear reprogramming occurring in transdifferentiation. Recent Advances: We have shown that innate immune signaling triggers a global change in the expression of epigenetic modifiers to enhance DNA accessibility. In this state of epigenetic plasticity, overexpression of lineage determination factors, and/or environmental cues and paracrine factors, can induce pluripotency, or can direct transdifferentiation to another somatic cell lineage. Accumulating evidence reveals that innate immune activation triggers the generation of reactive oxygen species and reactive nitrogen species, and that these free radicals are required for nuclear reprogramming to pluripotency or for transdifferentiation. CRITICAL ISSUES We have discovered a limb of innate immune signaling that regulates DNA accessibility, in part, by the action of free radicals to induce post-translational modification of epigenetic modifiers. FUTURE DIRECTIONS It is of scientific interest and clinical relevance to understand the mechanisms by which free radicals influence epigenetic plasticity, and how these mechanisms may be therapeutically modulated. Antioxid. Redox Signal. 00, 000-000.
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Affiliation(s)
- Shu Meng
- Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute , Houston, Texas
| | - Palas Chanda
- Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute , Houston, Texas
| | - Rajarajan A Thandavarayan
- Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute , Houston, Texas
| | - John P Cooke
- Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute , Houston, Texas
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26
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Jeremić S, Amić A, Stanojević-Pirković M, Marković Z. Selected anthraquinones as potential free radical scavengers and P-glycoprotein inhibitors. Org Biomol Chem 2018; 16:1890-1902. [DOI: 10.1039/c8ob00060c] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In this article, we estimated the scavenger capacity of six selected anthraquinones toward free radicals and their efficacy as inhibitors of P-glycoproteins.
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Affiliation(s)
- S. Jeremić
- Department of Chemical-Technological Sciences
- State University of Novi Pazar
- 36300 Novi Pazar
- Serbia
| | - A. Amić
- Department of Chemistry
- Josip Juraj Strossmayer University of Osijek
- 31000 Osijek
- Croatia
| | | | - Z. Marković
- Department of Chemical-Technological Sciences
- State University of Novi Pazar
- 36300 Novi Pazar
- Serbia
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El-Khodary MSM. Quranic Verse No. 8 of Surat Al-Jumu’ah Leads us to Describe Cancer and Determine Its True Cause (Part-III). Cell 2018. [DOI: 10.4236/cellbio.2018.73004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Evaluating the Risk of Tumors Diseases Based on Measurement of Urinary and Serumal Antioxidants Using the New Agar Diffusion Methods. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:6578453. [PMID: 28458777 PMCID: PMC5387840 DOI: 10.1155/2017/6578453] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 02/22/2017] [Indexed: 01/14/2023]
Abstract
Objectives. To discuss the characteristics of the amount of urinary total antioxidants in tumor diseases and the possibility of utilizing the changing regulation of urinary antioxidants to diagnose tumor diseases. Method. Urine and serum specimens from 130 healthy people were used to investigate the variation of antioxidant capacity against age. Urine and serum specimens from 44 unselected patients with tumors and 44 healthy people with same age background were used to explore the significance of urinary antioxidant capacity in clinic to diagnose tumor diseases. Potassium permanganate agar method and iodine starch method were used to determine the amount of total antioxidants. Results. In healthy people, more antioxidants in urine were measured in older people, while the results were opposite in serum. More antioxidants were found in urine of tumor patients than in healthy people with same age-range. Conclusions. According to the results of 130 measurements, the amount of antioxidants in urine varies by age. By using agar methods to measure antioxidants, the effect of age is required to be considered. Antioxidants levels from tumor patients were significantly higher than healthy individuals in urine. The combination of urine and serum to determine total antioxidants can better diagnose tumor diseases based on iodine starch method, with area under the receiver operating characteristics curve at 0.787.
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Shaver A, Nichols A, Thompson E, Mallick A, Payne K, Jones C, Manne NDPK, Sundaram S, Shapiro JI, Sodhi K. Role of Serum Biomarkers in Early Detection of Diabetic Cardiomyopathy in the West Virginian Population. Int J Med Sci 2016; 13:161-8. [PMID: 26941576 PMCID: PMC4773280 DOI: 10.7150/ijms.14141] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2015] [Accepted: 01/04/2016] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVES Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM. METHODS The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group. RESULTS Echocardiography images indicated severe diastolic dysfunction in patients with DD+DM and DD compared to DM or control patients. In the DM and DM+DD groups, TNFα, isoprostane, and leptin were elevated compared to control (p<0.05), as were clinical markers HDL, glucose and hemoglobin A1C. Fibrotic markers IGFBP7 and TGF-β followed the same trend. The Control group showed higher beneficial levels of adiponectin and bilirubin, which were reduced in the DM and DM+DD groups (p<0.05). CONCLUSION The results from our study support the clinical application of biomarkers in diagnosing early stage DCM, which will enable attenuation of disease progression prior to the onset of irreversible complications.
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Affiliation(s)
- Adam Shaver
- 1. Department of Medicine Joan C. Edwards School of Medicine, Marshall University
| | - Alexandra Nichols
- 1. Department of Medicine Joan C. Edwards School of Medicine, Marshall University
| | | | - Amrita Mallick
- 1. Department of Medicine Joan C. Edwards School of Medicine, Marshall University
| | - Kristen Payne
- 1. Department of Medicine Joan C. Edwards School of Medicine, Marshall University
| | - Chris Jones
- 2. Department of Cardiology, Marshall University
| | | | - Shanmuga Sundaram
- 1. Department of Medicine Joan C. Edwards School of Medicine, Marshall University
| | - Joseph I Shapiro
- 1. Department of Medicine Joan C. Edwards School of Medicine, Marshall University
| | - Komal Sodhi
- 4. Department of Surgery and Pharmacology, Marshall University, USA
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The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 2015; 97:55-74. [PMID: 25942353 DOI: 10.1016/j.ejmech.2015.04.040] [Citation(s) in RCA: 1548] [Impact Index Per Article: 154.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Revised: 04/13/2015] [Accepted: 04/18/2015] [Indexed: 02/07/2023]
Abstract
This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress. Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite. Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases. The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded.
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Adomaityte J, Mullin GE, Dobs AS. Anti-aging diet and supplements: fact or fiction? Nutr Clin Pract 2014; 29:844-6. [PMID: 25257683 DOI: 10.1177/0884533614546889] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Affiliation(s)
| | | | - Adrian S Dobs
- Johns Hopkins School of Medicine, Baltimore, Maryland
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Kong SYJ, Bostick RM, Flanders WD, McClellan WM, Thyagarajan B, Gross MD, Judd S, Goodman M. Oxidative balance score, colorectal adenoma, and markers of oxidative stress and inflammation. Cancer Epidemiol Biomarkers Prev 2014; 23:545-54. [PMID: 24443405 DOI: 10.1158/1055-9965.epi-13-0619] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND An oxidative balance score (OBS) that combines pro- and antioxidant exposures was previously reported to be associated with incident sporadic colorectal adenoma. We extend the previous analyses by assessing associations of the OBS and colorectal adenoma with circulating biomarkers of oxidative stress [F2-isoprostanes (FIP) and fluorescent oxidation products (FOP)], and inflammation [C-reactive protein (CRP)]. METHODS Using pooled data from two previously conducted colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 365), the OBS was constructed and divided into three approximately equal intervals, with the lowest interval used as the reference. Biomarker levels were dichotomized as "high" versus "low" based on the median values among controls. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS For the OBS-adenoma association, the ORs (95% CIs) for the middle and highest (relative to the lowest) score intervals were 0.81 (0.46-1.43) and 0.39 (0.17-0.89), respectively. The corresponding OBS category-specific ORs (95% CIs) were 0.50 (0.25-1.01) and 0.25 (0.10-0.65) for FIP, 2.01 (1.13-3.75) and 3.48 (1.51-8.02) for FOP, and 0.57 (0.31-1.04) and 0.21 (0.09-0.49) for CRP. The ORs (95% CIs) reflecting associations of adenoma with high levels of FIP, FOP, and CRP were 1.89 (1.08-3.30), 1.82 (1.11-2.99), and 1.45 (0.88-2.40), respectively. CONCLUSIONS As hypothesized, the OBS was inversely associated with colorectal adenoma and circulating FIP and CRP levels. The reason for the unexpected direct OBS-FOP association is unknown. IMPACT These data support the use of combined measures of pro- and antioxidant exposures in studies of colorectal neoplasia.
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Affiliation(s)
- So Yeon J Kong
- Authors' Affiliations: Department of Epidemiology, Rollins School of Public Health; Winship Cancer Institute, Emory University, Atlanta, Georgia; Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, Minnesota; and Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama
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Oxidative stress in Alzheimer's disease: why did antioxidant therapy fail? OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:427318. [PMID: 24669288 PMCID: PMC3941783 DOI: 10.1155/2014/427318] [Citation(s) in RCA: 202] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/13/2013] [Accepted: 12/06/2013] [Indexed: 01/04/2023]
Abstract
Alzheimer's disease (AD) is the most common form of dementia in the elderly, with increasing prevalence and no disease-modifying treatment available yet. A remarkable amount of data supports the hypothesis that oxidative stress is an early and important pathogenic operator in AD. However, all clinical studies conducted to date did not prove a clear beneficial effect of antioxidant treatment in AD patients. In the current work, we review the current knowledge about oxidative stress in AD pathogeny and we suggest future paths that are worth to be explored in animal models and clinical studies, in order to get a better approach of oxidative imbalance in this inexorable neurodegenerative disease.
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Solomon R, Sandhu H, Phumeetham S, Gowda KMN, Heidemann SM. Detection of inflammation and oxidative lung injury in exhaled breath condensate of rats with acute lung injury due to Staphylococcal enterotoxin B. J Breath Res 2013; 7:026003. [DOI: 10.1088/1752-7155/7/2/026003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidant stress: an overview. ACTA ACUST UNITED AC 2013; Chapter 17:Unit 17.5. [PMID: 23045114 DOI: 10.1002/0471140856.tx1705s24] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The isoprostanes are a unique series of prostaglandin-like compounds formed in vivo via a non-enzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid. This unit summarizes selected aspects regarding current knowledge of these compounds and their value as markers of oxidative injury. Novel aspects related to the biochemistry of isoprostane formation are discussed and methods by which these compounds can be analyzed and quantified are summarized. A considerable portion of this unit examines the utility of F(2)-isoprostanes as markers of oxidant injury in vitro and in vivo. Numerous studies carried out over the past decade have shown that these compounds are extremely accurate measures of lipid peroxidation in animals and humans and have illuminated the role of oxidant injury in a number of human diseases.
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Affiliation(s)
- Erik S Musiek
- Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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Albers E, Donahue BS, Milne G, Saville BR, Wang W, Bichell D, McLaughlin B. Perioperative plasma F(2)-Isoprostane levels correlate with markers of impaired ventilation in infants with single-ventricle physiology undergoing stage 2 surgical palliation on the cardiopulmonary bypass. Pediatr Cardiol 2012; 33:562-8. [PMID: 22327227 PMCID: PMC3641818 DOI: 10.1007/s00246-012-0166-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Accepted: 10/04/2011] [Indexed: 10/14/2022]
Abstract
Cardiopulmonary bypass (CPB) produces inflammation and oxidative stress, which contribute to postoperative complications after cardiac surgery. F(2)-Isoprostanes (F(2)-IsoPs) are products of lipid oxidative injury and represent the most accurate markers of oxidative stress. In adults undergoing cardiac surgery, CPB is associated with elevated IsoPs. The relationship between F(2)-IsoPs and perioperative end-organ function in infants with single-ventricle physiology, however, has not been well studied. This study prospectively enrolled 20 infants (ages 3-12 months) with univentricular physiology undergoing elective stage 2 palliation (bidirectional cavopulmonary anastomosis). Blood samples were collected before the surgical incision (T0), 30 min after initiation of CPB (T1), immediately after separation from CPB (T2), and 24 h postoperatively (T3). Plasma F(2)-IsoP levels were measured at each time point and correlated with indices of pulmonary function and other relevant clinical variables. Plasma F(2)-IsoPs increased significantly during surgery, with highest levels seen immediately after separation from CPB (p < 0.001). After separation from CPB, increased F(2)-IsoP was associated with lower arterial pH (ρ = -0.564; p = 0.012), higher partial pressure of carbon dioxide (PaCO(2); ρ = 0.633; p = 0.004), and decreased lung compliance (ρ = -0.783; p ≤ 0.001). After CPB, F(2)-IsoPs did not correlate with duration of CPB, arterial lactate, or immediate postoperative outcomes. In infants with single-ventricle physiology, CPB produces oxidative stress, as quantified by elevated F(2)-IsoP levels. Increased F(2)-IsoP levels correlated with impaired ventilation in the postoperative period. The extent to which F(2)-IsoPs and other bioactive products of lipid oxidative injury might predict or contribute to organ-specific stress warrants further investigation.
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Affiliation(s)
- Erin Albers
- Division of Pediatric Cardiology, Vanderbilt University Medical Center, 2200 Children's Way, Suite 5230, Nashville, TN 37232-6602, USA.
| | - Brian S. Donahue
- Vanderbilt University Medical Center, Division of Anesthesiology, Nashville, TN 37232-6602
| | - Ginger Milne
- Vanderbilt University Medical Center, Division of Clinical Pharmacology, Nashville, TN 37232-6602
| | - Benjamin R. Saville
- Vanderbilt University Medical Center, Division of Biostatistics, Nashville, TN 37232-6602
| | - Wenli Wang
- Vanderbilt University Medical Center, Division of Biostatistics, Nashville, TN 37232-6602
| | - David Bichell
- Vanderbilt University Medical Center, Division of Cardiothoracic Surgery, Nashville, TN 37232-6602
| | - BethAnn McLaughlin
- Vanderbilt University Medical Center, Division of Pharmacology, Nashville, TN 37232-6602,Vanderbilt University Medical Center, Division of Neurology, Nashville, TN 37232-6602,The Vanderbilt Kennedy Center, Nashville, TN 37232-6602
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Bastani NE, Gundersen TE, Blomhoff R. Dried blood spot (DBS) sample collection for determination of the oxidative stress biomarker 8-epi-PGF(2α) in humans using liquid chromatography/tandem mass spectrometry. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2012; 26:645-652. [PMID: 22328218 DOI: 10.1002/rcm.6149] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
RATIONALE F2-isoprostanes are a series of prostaglandin F2-like compounds that are formed by free-radical-catalyzed peroxidation of arachidonic acid (ARA). Several F2-isoprostanes, but in particular 8-epi-PGF(2α), are widely used as oxidative stress biomarkers. In this study we have developed an analytical tool for finger-tip blood sampling and analysis of 8-epi-PGF(2α) from dried blood spots (DBS). METHODS We have applied solid-phase extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the extraction, separation and detection of 8-epi-PGF(2α) in DBS and have studied the stability of this marker using the DBS collection platform. RESULTS The mass limit of detection (mLOD) for 8-epi-PGF(2α) extracted from DBS samples was 1.5 pg while the concentration limit of detection (cLOD) and concentration limit of quantitation (cLOQ) were 6 pg/mL and 18 pg/mL, respectively. All values based on triplicate analysis. Sufficient stability of 8-epi-PGF(2α) in DBS was achieved by preconditioning DBS paper with vitamin E and BHT. CONCLUSIONS The developed method is sensitive, specific, robust, efficient, and can accurately measure endogenous concentrations of 8-epi-PGF(2α) in DBS. Thus, it offers an analytical approach to measure 8-epi-PGF(2α) by a novel sample collection technique that is less invasive and costly than conventional techniques.
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Affiliation(s)
- Nasser E Bastani
- Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1046 Blindern, N-0316, Oslo, Norway.
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Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 2011; 254:86-99. [PMID: 21296097 DOI: 10.1016/j.taap.2009.11.028] [Citation(s) in RCA: 305] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2008] [Revised: 11/29/2009] [Accepted: 11/29/2009] [Indexed: 12/13/2022]
Abstract
Reactive oxygen species (ROS) are induced through a variety of endogenous and exogenous sources. Overwhelming of antioxidant and DNA repair mechanisms in the cell by ROS may result in oxidative stress and oxidative damage to the cell. This resulting oxidative stress can damage critical cellular macromolecules and/or modulate gene expression pathways. Cancer induction by chemical and physical agents involves a multi-step process. This process includes multiple molecular and cellular events to transform a normal cell to a malignant neoplastic cell. Oxidative damage resulting from ROS generation can participate in all stages of the cancer process. An association of ROS generation and human cancer induction has been shown. It appears that oxidative stress may both cause as well as modify the cancer process. Recently association between polymorphisms in oxidative DNA repair genes and antioxidant genes (single nucleotide polymorphisms) and human cancer susceptibility has been shown.
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Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010; 4:118-26. [PMID: 22228951 PMCID: PMC3249911 DOI: 10.4103/0973-7847.70902] [Citation(s) in RCA: 2549] [Impact Index Per Article: 169.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2010] [Revised: 03/08/2010] [Indexed: 02/06/2023] Open
Abstract
In recent years, there has been a great deal of attention toward the field of free radical chemistry. Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Hence application of external source of antioxidants can assist in coping this oxidative stress. Synthetic antioxidants such as butylated hydroxytoluene and butylated hydroxyanisole have recently been reported to be dangerous for human health. Thus, the search for effective, nontoxic natural compounds with antioxidative activity has been intensified in recent years. The present review provides a brief overview on oxidative stress mediated cellular damages and role of dietary antioxidants as functional foods in the management of human diseases.
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Affiliation(s)
- V. Lobo
- Department of Botany, Birla College, Kalyan – 421 304, Maharastra, India
| | - A. Patil
- Department of Botany, Birla College, Kalyan – 421 304, Maharastra, India
| | - A. Phatak
- Department of Botany, Birla College, Kalyan – 421 304, Maharastra, India
| | - N. Chandra
- Department of Botany, Birla College, Kalyan – 421 304, Maharastra, India
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Is Lipid Peroxidation of Polyunsaturated Acids the Only Source of Free Radicals That Induce Aging and Age-Related Diseases? Rejuvenation Res 2010; 13:91-103. [DOI: 10.1089/rej.2009.0934] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Narasimha AJ, Watanabe J, Ishikawa TO, Priceman SJ, Wu L, Herschman HR, Reddy ST. Absence of myeloid COX-2 attenuates acute inflammation but does not influence development of atherosclerosis in apolipoprotein E null mice. Arterioscler Thromb Vasc Biol 2009; 30:260-8. [PMID: 19926832 DOI: 10.1161/atvbaha.109.198762] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
OBJECTIVE The role of myeloid cell cyclooxygenase-2 (COX-2) in the progression of atherosclerosis has not been clearly defined. METHODS AND RESULTS We investigated the role of COX-2 expressed in the myeloid lineage in the development of atherosclerosis using a myeloid-specific COX-2(-/-) (COX-2(-M/-M)) mouse on a hyperlipidemic apolipoprotein (apo) E(-/-) background (COX-2(-M/-M)/apoE(-/-)). Myeloid COX-2 depletion resulted in significant attenuation of acute inflammation corresponding with decreased PGE(2) levels in an air pouch model. COX-2 depletion in myeloid cells did not influence development of atherosclerosis in COX-2(-M/-M)/apoE(-/-) when compared to apoE(-/-) littermates fed either chow or western diets. The unanticipated lack of contribution of myeloid COX-2 to the development atherosclerosis is not attributable to altered maintenance, differentiation, or mobilization of myeloid and lymphoid populations. Moreover, myeloid COX-2 depletion resulted in unaltered serum prostanoid levels and cellular composition of atherosclerotic lesions of COX-2(-M/-M)/apoE(-/-) mice. CONCLUSIONS Our results suggest that COX-2 expression in myeloid cells, including macrophages, does not influence the development of atherosclerosis in mice.
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Affiliation(s)
- Ajay J Narasimha
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Calif 90095, USA
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Ono K, Koizumi T, Tsushima K, Yoshikawa S, Yokoyama T, Nakagawa R, Obata T. Increased isoprostane levels in oleic acid-induced lung injury. Biochem Biophys Res Commun 2009; 388:297-300. [PMID: 19664592 DOI: 10.1016/j.bbrc.2009.07.157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2009] [Accepted: 07/31/2009] [Indexed: 05/28/2023]
Abstract
The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2alpha). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.
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Affiliation(s)
- Koichi Ono
- Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto, Japan
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Noschka E, Moore JN, Peroni JF, Lewis SJ, Morrow JD, Robertson TP. Thromboxane and isoprostanes as inflammatory and vasoactive mediators in black walnut heartwood extract induced equine laminitis. Vet Immunol Immunopathol 2009; 129:200-10. [DOI: 10.1016/j.vetimm.2008.11.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Lubrano V, Boni G, L'Abbate A, Turchi G. Antioxidant Activity of Plicatin B on Cultured Human Microvascular Endothelial Cells Exposed to H2O2. Drug Chem Toxicol 2008; 30:311-25. [DOI: 10.1080/01480540701522148] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Yin H. New techniques to detect oxidative stress markers: mass spectrometry-based methods to detect isoprostanes as the gold standard for oxidative stress in vivo. Biofactors 2008; 34:109-24. [PMID: 19706977 DOI: 10.1002/biof.5520340203] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Free radical-induced lipid oxidation under oxidative stress has been implicated in a number of human diseases. Isoprostanes (IsoPs), isomers of prostaglandins, are one of the major classes of oxidation products derived from this oxidation process. Measurement of the levels of IsoPs by Mass Spectrometry-based methods has become the "gold standard" biomarker of oxidative stress in vivo. Significant advances have been made in understanding this important pathway of lipid peroxidation since the discovery of IsoP formation in vivo 18 years ago. Studies from our laboratory and others are discussed that have provided insights into the mechanism of formation. Furthermore, new independent studies have demonstrated that IsoPs are the most reliable available marker of lipid peroxidation in vivo, and recent work examining IsoP formation has provided valuable information about the pathogenesis of numerous human diseases. Thus, the complexity of the IsoP pathway has expanded, providing novel insights into mechanisms of lipid peroxidation in vivo and allowing investigators to explore the role of oxidative stress in human disease.
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Affiliation(s)
- Huiyong Yin
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
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Tomey KM, Sowers MR, Li X, McConnell DS, Crawford S, Gold EB, Lasley B, Randolph JF. Dietary fat subgroups, zinc, and vegetable components are related to urine F2a-isoprostane concentration, a measure of oxidative stress, in midlife women. J Nutr 2007; 137:2412-9. [PMID: 17951478 PMCID: PMC2730459 DOI: 10.1093/jn/137.11.2412] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Smoking, diet, and physical activity may impact chronic diseases in part by promoting or attenuating oxidative stress. We evaluated associations between lifestyle factors and urine F(2a)-isoprostanes, a marker of oxidative stress in 1610 participants of the Study of Women's Health Across the Nation (SWAN). Dietary intake and physical activity were assessed at baseline and the 5th year 05 (Y05). These data were related to Y05 urinary F(2a)-isoprostane concentration with regression analyses. Median urine F(2a)-isoprostane concentration was 433 ng/L overall, 917 ng/L in smokers [inter-quartile range (IQR): 467, 1832 ng/L], and 403 ng/L in nonsmokers (IQR: 228, 709 ng/L; P < 0.0001 for difference). Higher trans fat intake was associated with higher urine F(2a)-isoprostane concentration; partial Spearman correlations (rho(x|y)) between Y05 urine F(2a)-isoprostane concentration and trans fatty acids was 0.19 (P = 0.03) in smokers and 0.13 (P < 0.0001) in nonsmokers. Increased log trans fat intake from baseline to Y05 was associated with higher concentration of log urine F(2a)-isoprostanes in nonsmokers (beta = 0.131, SE = 0.04, P = 0.0003). In nonsmokers, the partial correlation (rho(x|y)) between lutein and urine F(2a)-isoprostane concentration was -0.13 (P < 0.0001). Increased intake of log lutein from baseline to Y05 was also associated with lower log urine F(2a)-isoprostane concentration (beta = -0.096, SE = 0.03, P = 0.0005) in nonsmokers. Increased zinc intake from baseline to Y05 was associated with lower log urine F(2a)-isoprostane concentration in smokers and nonsmokers (beta = -0.346, SE = 0.14, P = 0.01), and -0.117, 0.04 (P = 0.001), respectively]. In conclusion, diet (fat subtypes, zinc, and vegetable components) and smoking were associated with urine F(2a)-isoprostanes, a marker of oxidative stress.
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Affiliation(s)
- Kristin M Tomey
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48104, USA
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Abstract
Diabetes mellitus affects about 8% of the adult population. The estimated number of patients with diabetes, presently about 170 million people, is expected to increase by 50-70% within the next 25 years. Diabetes is an important component of the complex of 'common' cardiovascular risk factors, and is responsible for acceleration and worsening of atherothrombosis. Major cardiovascular events cause about 80% of the total mortality in diabetic patients. Diabetes also induces peculiar microangiopathic changes leading to diabetic nephropathy conducive to end-stage renal failure, and to diabetic retinopathy that may progress to vision loss and blindness. In terms of major cardiovascular events, coronary heart disease and ischaemic stroke are the main causes of morbidity and mortality in diabetic patients. Peripheral arterial disease frequently occurs, and is more likely to be conducive to critical limb ischaemia and amputation than in the absence of diabetes. Although there are a number of differences in the pathogenesis and clinical features of diabetic macroangiopathy and microangiopathy, these two entities often coexist and induce mutually worsening effects. Endothelial injury, dysfunction and damage are common starting points for both conditions. Causes of endothelial injury can be distinguished into those 'common' to nondiabetic atherothrombosis, such as hypertension, dyslipidaemia, smoking, hypercoagulability and platelet activation; and those more specific and in some cases 'unique' to diabetes and directly related to the metabolic derangement of the disease, such as (i) desulfation of glycosaminoglycans (GAGs) of the vascular matrix; (ii) formation of advanced glycation end-products (AGE) and their endothelial receptors (RAGE); (iii) oxidative and reductive stress; (iv) decline in nitric oxide production; (v) activation of the renin-angiotensin aldosterone system (RAAS); and (vi) endothelial inflammation caused by glucose, insulin, insulin precursors and AGE/RAGE. Prevention of major cardiovascular events with the antithrombotic agent aspirin (acetylsalicylic acid) is widely recommended, but reportedly underutilised in patients with diabetes. However, some data suggest that aspirin may be less effective than expected in preventing cardiovascular events and especially mortality in patients with diabetes, as well as in slowing progression of retinopathy. In contrast, a recent study found picotamide, a direct thromboxane inhibitor, to be superior to aspirin in diabetic patients. Clopidogrel was either equivalent or less active in diabetic versus nondiabetic patients, depending upon different clinical settings.Recent studies have shown that some GAG compounds are able to reduce micro- and macroalbuminuria in diabetic nephropathy, and hard exudates in diabetic retinopathy, but it is as yet unknown whether these agents also influence the natural history of microvascular complications of diabetes. Lifestyle changes and physical exercise are also essential in preventing cardiovascular events in diabetic patients. Available data on the control of the metabolic state and the main risk factors show that careful adjustment of blood sugar and glycated haemoglobin is more effective in counteracting microvascular damage than in preventing major cardiovascular events. The latter objective requires a more comprehensive approach to the whole constellation of risk factors both specific for diabetes and common to atherothrombosis. This approach includes lifestyle modifications, such as dietary changes and smoking cessation and the use of HMG-CoA reductase inhibitors (statins), which are able to correct the lipid status and to prevent major cardiovascular events independently of the baseline lipidaemic or cardiovascular status. Tight control of hypertension is essential to reduce not only major cardiovascular events but also microvascular complications. Among antihypertensive measures, blockade of the RAAS by means of ACE inhibitors or angiotensin II receptor antagonists recently emerged as a potentially polyvalent approach, not only for treating hypertension and reducing cardiovascular events, but also to prevent or reduce albuminuria, counteract diabetic nephropathy and lower the occurrence of new type 2 diabetes in individuals at risk.
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Noninvasive Assessment of the Role of Cyclooxygenases in Cardiovascular Health: A Detailed HPLC/MS/MS Method. Methods Enzymol 2007; 433:51-72. [DOI: 10.1016/s0076-6879(07)33003-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Milne GL, Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers 2006; 10 Suppl 1:S10-23. [PMID: 16298907 DOI: 10.1080/13547500500216546] [Citation(s) in RCA: 242] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The isoprostanes are a unique series of prostaglandin-like compounds formed in vivo via a non-enzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid. This article summarizes selected aspects regarding current knowledge of these compounds and their value as markers of oxidative injury. Novel aspects related to the biochemistry of isoprostane formation are discussed and methods by which these compounds can be analysed and quantified are summarized. A considerable portion of this article examines the utility of F(2)-isoprostanes as markers of oxidant injury in vivo. Numerous studies carried out over the past decade have shown that these compounds are extremely accurate measures of lipid peroxidation and have illuminated the role of oxidant injury in a number of human diseases including atherosclerosis, Alzheimer's disease and pulmonary disorders.
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Affiliation(s)
- Ginger L Milne
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA
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Cesari M, Kritchevsky SB, Leeuwenburgh C, Pahor M. Oxidative damage and platelet activation as new predictors of mobility disability and mortality in elders. Antioxid Redox Signal 2006; 8:609-19. [PMID: 16677104 DOI: 10.1089/ars.2006.8.609] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Mobility disability is an early phase of the disablement process in older adults, and represents a major risk factor for physical disability and mortality. Pathophysiological mechanisms responsible for the onset of mobility limitation are still largely unknown. Oxidative damage, responsible for the disruption of the equilibrium of biological systems by damaging major constituent molecules, might play an important role in the pathway leading to major health-related events. It has been suggested the existence of a vicious cycle involving oxidative damage, platelet activation, and inflammation as promoter of pathophysiological changes occurring with aging. This hypothesis is based on the following observations: (a) oxidative damage is associated with diseases and clinical conditions potentially leading to disability and mortality; (b) oxidative damage is associated with platelet activation, and a vicious cycle involving oxidative damage, platelet activation, and inflammation has been demonstrated in several metabolic disorders potentially leading to mobility disability; (c) the age-related physical decline may be associated to the oxidative damage due to the excess of free radicals; (d) antioxidant defense and behavioral factors (e.g., physical activity, dietary restriction, smoking cessation) play an important role in the reduction of oxidative damage levels and are associated with improved physical performance and muscle strength.
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Affiliation(s)
- Matteo Cesari
- Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida, Gainesville, Florida 36208, USA.
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