title: Perfluorooctanoic acid induces peroxisomal fatty acid oxidation and cytokine expression in the liver of male Japanese medaka (Oryzias latipes).
abstract: Widespread contamination of perfluorooctanoic acid (PFOA) in the marine environment draws a great concern over its ecotoxicological impact on marine mammals and wildlife. In the present study, male Japanese medaka (Oryzias latipes) was adapted to seawater to mimic the marine environment and was then exposed to the nominal concentrations of 10, 50, 100 mg L(-1) PFOA for 7d. There were no impact on survival, relative liver and gonad size, and condition factor (measure of growth) at any concentration tested. Peroxisomal acyl-CoA oxidase (ACO) activity was elevated at the highest dose with a marginal significance (P=0.06). The increase of ACO activity was paralleled by the significant upregulation of PPAR-α expression at the same dose. PFOA induced a significant inhibition of catalase (CAT) activity at high doses with no changes of superoxide dismutase (SOD) or glutathione peroxidase (GPx) activities in the liver. These results strongly suggest that PFOA may induce peroxisomal fatty acid oxidation and impose the oxidative stress through the alteration of cellular oxidative homeostasis in the liver. PFOA increased the mRNA levels of proinflammatory cytokines such as IL-6, TNF-α and IL-1β, suggesting that it may be involved in inflammation and tissue injury. This study may contribute to understanding the mechanism of PFOA-induced hepatic toxicity in Japanese medaka and assessing the potential risk of PFOA in marine fish and wildlife. In addition, the present results obtained at the high concentrations may provide important biological endpoints relevant to situations such as environmental spills.
authors.affiliation: Department of Pharmacology, School of Medicine, Catholic University of Daegu, Republic of Korea. yangjh@cu.ac.kr
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Yang
mesh_terms: D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005466:Fluorocarbons / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009990:Oryzias / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D002210:Caprylates; D016207:Cytokines; D005227:Fatty Acids; D005466:Fluorocarbons; D047492:Peroxisome Proliferator-Activated Receptors; D014874:Water Pollutants, Chemical; C023036:perfluorooctanoic acid; D042962:Acyl-CoA Oxidase