title: Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated rat liver and brain mitochondria.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran Zanjan Applied Pharmacology Research Center, Zanjan University of Medical sciences, Zanjan, Iran.
authors.forename: V
authors.initials: V
authors.lastname: Mashayekhi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: K Haj Mohammad Ebrahim
authors.initials: KH
authors.lastname: Tehrani
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Hashemzaei
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.
authors.forename: K
authors.initials: K
authors.lastname: Tabrizian
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran jafar.shahraki@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Shahraki
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran Zanjan Applied Pharmacology Research Center, Zanjan University of Medical sciences, Zanjan, Iran jamal_hossini@yahoo.com.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Hosseini
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain; D002210:Caprylates / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008933:Mitochondrial Swelling / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013501:Surface-Active Agents / Q000633:toxicity*
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D000255:Adenosine Triphosphate; D045304:Cytochromes c; C023036:perfluorooctanoic acid; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005978:Glutathione
keywords: Perfluorooctanoic acid (PFOA); cytochrome c; mitochondrial toxicity; oxidative stress