EXPERIMENTAL STUDIES ON GLUCURONIDATION : I. THE INFLUENCE OF 4-ALLYL-2-METHOXY PHENOL (EUGENOL)

Abstract

The present animal experiment was designed to clarify or otherwise elucidate themetabolic response, especially that of glucuronidation, in animals administered withmassive doses of glucosidurogenic drugs.In his review of literature, DUTTON (1966) mentioned that a specific stimulation ofUDP-glucuronyltransferase (GT) had not been achieved by treatment with an acceptorsubstrate, and that no drug tolerance had been correlated with an increased GT activityfor the drug or its metabolites. HARTIALA et al. (1966) reported on the competitiveinhibition of GT by eugenol in vitro.The present paper deals with this inhibition by eugenol. The influence of eugenolon the glucuronidation in rats by oral administration was also observed.The following results were obtained.l) A 50% inhibition was shown by 1.1 X 10 M of eugenol upon substrate (2.0X10 M of p-nitrophenol)-enzyme (5, ODD X g, 10 min. supernatant of rat liver homogenate)system (Fig. 1).2) The nature of inhibition was competitive. The Ki value was 0.5xI0-4 M. Inaddutuon, the Km value was 1.7 X 10 M in this experiment (Fig. 2).3) When a large amount (200 mg, about a half of LD..) was administered orallyto adult male rats, a large amourit of the ether type of glucuronide (0-G) was excretedinto the urine (Table l), and a significant increase was observed in GT activity of theliver (Table 2).From these results, it was concluded that eucenol was one of the most electivebglucosidurogenic drugs, and that liver GT might be induced in the rat by oral administra-tion of eugenol.