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

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.