Induction of CYP1A1, 2B, 2E1 and 3A in rat liver by organochlorine pesticide dicofol

Abstract

The present study has determined the ability of dicofol, an organochlorine pesticide, to induce cytochrome P450 using rats treated with 1, 10, and 25 mg/kg dicofol intraperitoneally for 4 days. Treatments with 10 and 25 mg/kg dicofol produced dose-related increases of cytochrome P450 and cytochrome b(5) contents and NADPH-cytochrome c reductase, 7-ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase, aniline hydroxylase, and erythromycin N-demethylase activities in liver microsomes. The treatments also increased glutathione S-transferase and superoxide dismutase activities in liver cytosol. Dicofol at 1 mg/kg produced a general trend towards increases of the aforementioned enzyme levels. The results of immunoblot analyses showed that 10 and 25 mg/kg dicofol increased protein levels of CYP1A1, CYP2B, CYP2E1, and 3A in liver. RT-PCR data indicated that dicofol induced mRNA expression of liver CYP1A1, CYP2B, and CYP3A. Pretreatments of rats with 10 and 25 mg/kg dicofol decreased phenobarbital-induced sleeping time by 34% and 39%, respectively. Dicofol pretreatment at 25 mg/kg increased CCl(4)-induced serum alanine aminotransferase activity by 4.3-fold and aspartate aminotransferase activity by 4.1-fold. The present study demonstrates that dicofol has the ability to induce CYP1A1. CYP2B, CYP2E1, and CYP3A in the liver and increase phenobarbital metabolism and CCl(4) toxicity in rats. (C) 2009 Elsevier Ireland Ltd. All rights reserved.