Enhancement of microsomal monooxygenase, epoxide hydrase and udpglucuronyltransferase by aldrin, dieldrin and isosafrole administrations in rat liver

Abstract

The effects of intraperitoneal administration of aldrin (10 mg/kg), dieldrin (10 mg/kg) and isosafrole (50 mg/kg) were investigated on the activities of drug biotransformation enzymes in rat liver. All the compounds studied were found to enhance the activities of microsomal monooxygenase (e.g. p-nitroanisole O-demethylase, aryl hydrocarbon hydroxylase), epoxide hydrase (styrene oxide as substrate) and UDPglucuronyltransferase ( p-nitrophenol as aglycone). Dieldrin, the epoxidized derivative of aldrin, was a more potent inducer than the parent compound itself. NADPH cytochrome c reductase activity was enhanced 2.5-fold, p-nitroanisole O-demethylase 7-fold, benzopyrene hydroxylase 2-fold, and epoxide hydrase 5-fold after treating rats with dieldrin for 6 days. The increase in activity of the microsomal UDPglucuronyltransferase could be only detected after an in vitro digitonin treatment of microsomal membranes, the enhancement being about 1.5-fold after administering dieldrin for 6 days. The administration of isosafrole to rats increased especially p-nitroanisole O-demethylase activity in liver microsomes (10-fold in 3 days). NADPH cytochrome c reductase activity was increased 2-fold, cytochrome P-450 content 1.2-fold, benzpyrene hydroxylase activity 2.5-fold and epoxide hydrase activity 1.2-fold after treatment of rats for 3 days. UDPglucuronyltransferase activity increased 2.2-fold by treating rats for 6 dyas with isosafrole. This increase was, however, only to be seen in in vitro digitonin-activated microsomes due to the latency of UDPglucoronyltransferase.