Stimulation by chlordane of hepatic drug metabolism in the squirrel monkey.

Abstract

Abstract An experiment was performed to determine whether treatment with chlordane, a commonly used insecticide, would affect several hepatic drug metabolic pathways in the squirrel monkey. Intraperitoneal injection of γ-chlordane (10 mg. per kilogram) once daily for 7 days resulted in a two- to sixfold increase in the activity of hepatic microsomal enzymes which metabolize benzpyrene, zoxazolamine, hexobarbital, and p-nitrobenzoic acid, and in the appearance of significant metabolic activity for the metabolism of aminopyrine. This latter enzyme system was extremely low or undetectable in control (untreated) monkeys. Also significantly enhanced by γ-chlordane pretreatment was the ability of hepatic microsomes to oxidize NADPH and bind carbon monoxide, capacities which have been postulated by several authors to be involved in microsomal hydroxylations. Livers of γ-chlordane-pretreated monkeys exhibited a significant increase over control livers in weight and in the total amount of nitrogen in the subfraction containing the drug metabolizing enzymes. Thus, the effects of γ-chlordane on several hepatic microsomal systems of the squirrel monkey are qualitatively similar to those previously observed in other phylogenetically lower species, namely mice, rabbits, and rats.