(2015) Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated rat liver and brain mitochondria. Human & Experimental Toxicology. pp. 985-96. ISSN 1477-0903 (Electronic) 0960-3271 (Linking)
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Abstract
BACKGROUND: Perfluorooctanoic acid (PFOA) is one of the most widely used perfluoroalkanes as surfactants, lubricants and processing aids in the production of polymers, which has also been detected in the environment, wildlife and human body. Animal studies indicated that PFOA caused a wide array of toxic effects including liver and brain dysfunction, carcinogenicity and reproductive and developmental toxicity. Based on the established role of mitochondria-mediated pathways in the observed toxic effects of many drugs and chemicals, in this study, the potential toxic effects of PFOA on mitochondria isolated from rat liver and brain have been investigated. METHOD: Mitochondria were isolated by differential centrifugation method and incubated with different concentrations of PFOA (0.5-1.5 mM). The effects of PFOA were assessed on a series of mitochondrial parameters including reactive oxygen species (ROS) formation, activities of mitochondrial complexes I/II/III, reduced glutathione (GSH) content, adenosine triphosphate (ATP) level, membrane potential, lipid peroxidation (LPO), mitochondrial swelling and cytochrome c release. RESULTS: The data on liver mitochondria indicated that PFOA-induced ROS elevation in both mitochondrial complexes I and III, mitochondrial membrane potential collapse, swelling, cytochrome c release and decreased ATP level which induces apoptosis or necrosis. On brain mitochondria, PFOA showed fairly similar effects on the above-mentioned parameters. However, different results were obtained when the effect of PFOA was assessed on LPO and complex II activity. CONCLUSIONS: Due to the fact that PFOA had toxic effects on the mitochondria isolated, it could be suggested that mitochondrial toxicity could be a plausible mechanism for the toxic effects of this fluorochemical on liver and brain function.
Item Type: | Article |
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Keywords: | Adenosine Triphosphate/metabolism Animals Brain Caprylates/*toxicity Cytochromes c/metabolism Electron Transport Complex I/metabolism Electron Transport Complex II/metabolism Electron Transport Complex III/metabolism Environmental Pollutants/*toxicity Fluorocarbons/*toxicity Glutathione/metabolism Lipid Peroxidation/drug effects Liver Male Membrane Potential, Mitochondrial/drug effects Mitochondria/*drug effects/metabolism/physiology Mitochondrial Swelling/drug effects Rats, Sprague-Dawley Reactive Oxygen Species/metabolism Surface-Active Agents/*toxicity Perfluorooctanoic acid (PFOA) cytochrome c mitochondrial toxicity oxidative stress |
Divisions: | |
Page Range: | pp. 985-96 |
Journal or Publication Title: | Human & Experimental Toxicology |
Volume: | 34 |
Number: | 10 |
Identification Number: | 10.1177/0960327114565492 |
ISSN: | 1477-0903 (Electronic) 0960-3271 (Linking) |
Depositing User: | مهندس مهدی شریفی |
URI: | http://eprints.zbmu.ac.ir/id/eprint/2937 |
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