Nonylphenol induces apoptosis via mitochondria- and Fas-l-mediated pathways in the liver of adult male rat

Abstract

Nonylphenol (NP) is an environmental contaminant known to possess estrogenic properties. Humans are constantly exposed to NP by contaminated water and food products. In the present study we sought to investigate whether treatment with low doses of NP induces apoptosis in the liver of adult rats. Rats were administered with NP by oral gavage at the doses of 15,150 and 1500μg/kg body weight per day for 45days. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assayed. Apoptosis-related proteins namely cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l, and expression of bcl-2 mRNA and bax mRNA were examined in the liver. Levels of AST and ALT were increased in the treated rats. Western blot analysis revealed elevation in the levels of cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l in the liver of NP-treated rats. Decreased expression of bcl-2 mRNA (anti-apoptotic) and increased expression of bax mRNA (apoptotic) were observed in the liver of treated rats. Increased localization of caspase-3 in the hepatocytes and DNA damage were observed in the liver of treated rat. It is concluded that NP induces apoptosis in liver involving both mitochondria-dependent and Fas–Fas-l pathways and thereby, leading to hepatic damage in rats.