EFFECTS OF THE NATURALLY-OCCURRING ALKENYLBENZENES EUGENOL AND TRANS-ANETHOLE ON DRUG-METABOLIZING-ENZYMES IN THE RAT-LIVER

In order to study the effects of trans-anethole and eugenol on drug-metabolizing enzyme activities in vivo, male Wistar rats were treated by gavage with trans-anethole (125 or 250 mg/kg body weight) or eugenol (250, 500 or 1000 mg/kg body weight) daily for 10 days. In fiver microsomes and cytosol various phase-I and phase-II biotransformation enzyme activities were determined. No effect on total cytochrome P450 content in liver microsomes from rats treated with eugenol or trans-anethole was observed. Administration of 1000 mg eugenol/kg body weight, but not the lower doses, significantly increased cytochrome P-450-dependent 7-ethoxy-resorufin O-deethylation (EROD) and 7-pentoxy-resorufin O-depentylation (PROD); administration of trans-anethole (125 or 250 mg/kg body weight) did not alter EROD and PROD activities. In rat fiver cytosol, UDP-glucuronyl transferase (GT) activity towards the substrate 4-chlorophenol was significantly increased in all treated rats, and activity towards 4-hydroxybiphenyl as substrate was significantly increased in rats treated with 250 mg trans-anethole/kg or with 500 or 1000 mg eugenol/kg. DT-diaphorase (DTD) activity was only significantly enhanced in the fiver cytosol of rats treated with trans-anethole at 250 mg/kg body weight. Enhancement of cytosolic glutathione S-transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene was found for all eugenol- and trans-anethole-treated rats. In addition, significantly increased levels of GST subunit 2 were measured by HPLC in the fiver cytosol of rats treated with eugenol (500 or 1000 mg/kg body weight) or trans-anethole (250 mg/kg body weight). It is concluded that both eugenol and trans-anethole preferentially induce phase II biotransformation enzymes in rat liver in vivo.