Perfluorooctane sulphonate induces oxidative hepatic damage via mitochondria-dependent and NF-κB/TNF-α-mediated pathway. (January 2018)

• Record Type: Journal Article
• Authors: Han, Rui; Hu, Mingxian; Zhong, Qiang; Wan, Chong; Liu, Limin; Li, Fang; Zhang, Fang; Ding, Wenjun
• Is Part Of: Chemosphere. Volume 191(2018)
• Page Start: 1056
• Page End: 1064
• Publication Date: 2018-01
• Subjects: PFOS -- Oxidative stress -- Hepatotoxicity -- NF-κB/TNF-α; ALT alanine aminotransferase -- AST aspartate transaminase -- APAP acetaminophen -- BSA bovine serum albumin -- CAT catalase -- Cyt c cytochrome c -- DCFDA 2, 7-dichlorofluorescein diacetate -- DMSO dimethyl sulfoxide -- FITC fluorescein isothiocyanate -- GSH glutathione -- GSSG glutathione disulphide -- iNOS inducible nitric oxide synthase -- MDA malondialdehyde -- NF-κB transcription factor nuclear factor-κB -- NO nitric oxide -- PFOS perfluorooctane sulphonate -- PARP poly(ADPribose) polymerase -- PCNA proliferating cell nuclear antigen -- RNS reactive nitrogen species -- ROS reactive oxygen species -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis -- SOD superoxide dismutase -- TBA thiobarbituric acid -- TBST tris-buffered saline-Tween -- TNF-α tumor necrosis factor-α -- TNFR1 TNF-α receptor 1 -- TRADD TNF receptor 1-associated death domain protein; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2017.08.070
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Perfluorooctane sulphonate (PFOS) has been reported to accumulate in liver and cause damage. The molecular mechanism of the PFOS-induced hepatotoxicity has not been completely elucidated. The aim of the present study was to investigate whether PFOS-induced oxidative stress plays an important role in liver damage, and if so, what pathway it undergoes for the mechanism of its toxicological action. Male Sprague-Dawley (SD) rats were orally administrated with PFOS at single dose of 1 or 10 mg/kg body weight for 28 consecutive days. Increased serum levels of liver enzymes and abnormal ultra structural changes were observed in the PFOS-exposed rats. Particularly, PFOS exposure significantly increased intracellular reactive oxygen species (ROS) and nitric oxide (NO) production, but weakened intracellular antioxidant defence by inhibiting catalase and superoxide dismutase activities. Signal transduction studies showed that PFOS exposure significantly elevated inducible nitric oxide synthase (iNOS), Bax, cytochrome c, cleaved caspase-9 and cleaved caspase-3, indicating the mitochondria-dependent apoptotic pathway was activated. On the other hand, significant alterations of the PFOS-induced protein expression of NF-κB and IκBα in association with an enhanced level of TNF-α were observed. Taken together, these results indicate that mitochondria play an important role in PFOS-induced hepatotoxicity. Graphical abstract: Image 1 Highlights: PFOS exposure is capable to cause liver dysfunction. PFOS exposure induces oxidative stress and apoptosis in liver. PFOS exposure induces hepatic apoptosis via mitochondria-dependent pathway. PFOS induced oxidative hepatic damage via NF-κB/TNF-α pathway.