Molecular Mechanisms of Perfluorooctanoate-Induced Hepatocyte Apoptosis in Mice Using Proteomic Techniques

The stability of perfluorooctanoate (PFOA) coupled with its wide use cause serious concerns regarding its potential risk to human health. The molecular mechanisms of PFOA-induced hepatotoxicity relevant to human health was investigated using both in vivo (mouse model) and in vitro (human hepatocyte cells, HL-7702) techniques. Both male and female Balb/c mice were administered PFOA at 0.05, 0.5, or 2.5 mg/kg-d for 28-d, with serum PFOA concentrations after exposure being found at environmentally relevant levels. Liver samples were examined for histology and proteomic change using iTRAQ and Western Blotting, showing dose-dependent hepatocyte apoptosis and peroxisome proliferation. At high doses, genotoxicity resulting from ROS hypergeneration was due to suppression of Complex I subunits in the electron transport chain and activation of PPARα in both genders. However, at 0.05 mg/kg-d, Complex I suppression occurred only in females, making them more sensitive to PFOA-induced apoptosis. In vitro assays using H...