Effect of chlorpyrifos on hepatic gamma-glutamyl transferase, serum cholinesterase and xenobiotic metabolizing enzyme activities in rats.

Abstract

Chlorpyrifos (O,Odiethyl-O-[3-5-6-trichloro-2-pyridyl] phosphorothioate) (CAS Registry No. 2921-88-2) is the active ingredient in Dursban and Lorsban insecticides. These insecticides were introduced in 1963 as an active ingredient in organophosphate pesticide formulations for agriculture and household application (AbouDonia 1995). Chlorpyrifos is metabolized in the liver by microsomal xenobioticmetabolizing enzymes. These enzymes catalyze the oxidative desulfuration of chlorpyrifos to chlorpyrifos oxon. Chlorpyrifos oxon elicits its toxic effects by phosphorylating acetylcholinesterase, ultimately resulting in failure to hydrolyze acetylcholine neurotransmitter. This cascade of reactions results in accumulation of acetylcholine at both muscarinic and cholinergic receptors (Abou-Donia 1995). Both chlorpyrifos and chlorpyrifos oxon are rapidly hydrolyzed to 3,5,6 trichloro2-pyridinol by hepatic mixed function oxidases (Sultatos and Murphy 1983). The induction or inhibition of these microsomal xenobiotic enzymes may increase or decrease the toxicity of organophosphorus insecticides depending on the structure of the compound. The hepatotoxicity and hepatocarcinogenic activity of test substances were assessed by the status of gamma-glutamyl transferase (GGT) enzyme (Shukla et al. 1989). Gamma-glutamyl transferase catalyzes the transfer of the gamma-glutamyl group from a gamma-glutamyl peptide to an amino acid or another peptide. This enzyme is widely used as a biomarker in preneoplastic lesions of the liver during chemical carcinogenesis (Peraino et al. 1983).