Nephrotoxicity mechanism of perfluorinated compounds PFOA and PFOS in rats

抄録

Perfluorinated compounds, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are persistent organic pollutants that can cause severe toxicity in mammals. However, the underlying molecular mechanisms are not clearly understood. The aim of our study is to investigate mode of actions for PFOA- or PFOS-induced nephrotoxicity in male rats. PFOA (20 mg/kg b.w.) or PFOS (20 mg/kg b.w.) were administered by oral gavage for consecutive 20 days. Additionally, we compared the apoptotic cell death in normal rat kidney epithelial (NRK52E) cells. Data showed that PFOA and PFOS significantly increased the blood urea nitrogen (BUN) and creatinine levels in serum of rats. PFOA and PFOS significantly increased malondialdehyde (MDA) levels, decreased GSH peroxidase (GSH-Px) activity in kidney tissues. PFOA and PFOS exposure significantly elevated urinary protein biomarkers including pyruvate kinase M2 (PKM2), kidney injury molecules-1 (Kim-1), and selenium-binding protein 1 (SBP1) in urine of rats. Histological analysis revealed epithelial degeneration and necrotic cell death were exhibited in the proximal tubules of the kidney. For further investigation of the potential mechanism of PFOA- or PFOS-induced renal cell apoptosis, the expression of Bcl-2/Bax ratios were reduced in NRK52E cells. PFOA- or PFOS-mediated ROS production was increased in a dose-dependent manner in NRK-52E cells. These data indicated that PFOS-induced nephrotoxicity was closely related with the renal tubular cells apoptosis via the JNK signaling pathway.