Abstract
The natural products safrole and isosafrole together with the pesticide sinergist piperonyl butoxide have been shown to elicit pronounced alterations in the characteristics of the rat hepatic microsomal menobiotic metabolising complex. Furthermore, these three methylenedioxyphenyl compounds were found to form stable cytochrome P450-metabolite adducts. The dietary administration of either safrole, isosafrole, or piperonyl butoxide to rats was found to result in the induction of aryl hydrocarbon hydrocylase activity both in the liver and in a number of extrahepatic tissues. Induction studies with isosafrole is an atypical index of extrahepatic xenobiotic metabolism. In addiction, ethanol and some industrial chemicals were examined as potential inducers of hepatic drug metabolising enzymes. Finally, the diurnal variation of hepatic microsomal binding and metabolism of drugs and steroids has been investigated in the hamster.