Enhancement of microsomal monooxygenase, epoxide hydrase and UDPglucuronyltransferase by aldrin, dieldrin and isosafrole administrations in rat liver.
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 aldrin, the eposidized derivative of aldrin, was a more potent inducer than the parent compound itself. NADPH CYTOCHROME C REDUCTASE ACTIVITY WAS EHANCED 2.5-FOLD, P-NITROANISOLE O-demethylase 7-fold, benzpyrene 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 reducatase activkty was increased 2-fold, cytochrome P-450 content 1.2-fold, benzpyrene hydrozylase 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 days with isosafrole. This increase was, however, only to be seen in in vitro digitonin-activated microsomes due to the latency of UDPglucuronyltransferase.
D000452:Aldrin / Q000494:pharmacology*; D000818:Animals; D004026:Dieldrin / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006602:Hexosyltransferases / Q000378:metabolism*; D006836:Hydro-Lyases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D012451:Safrole / Q000494:pharmacology*; D013268:Stimulation, Chemical
D004149:Dioxoles; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D006602:Hexosyltransferases; D014453:Glucuronosyltransferase; D004851:Epoxide Hydrolases; D006836:Hydro-Lyases; D004026:Dieldrin; D000452:Aldrin; D012451:Safrole