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 liver microsomes and cytosol various phase-I and phase-II biotransformation enzyme activities were determined. No effect on total cytochrome P-450 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-pentoxyresorufin O-depentylation (PROD); administration of trans-anethole (125 or 250 mg/kg body weight) did not alter EROD and PROD activities. In rat liver 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 liver 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 liver cytosol of rats treated with eugenol (500 or 1000 mg/kg body eight) or trans-anethole (250 mg/kg body weight). It is concluded that both eugenol and trans-anethole preferentially induced phase II biotransformation enzymes in rat liver in vivo.
Rompelberg
C J
CJ
TNO Toxicology and Nutrition Institute, Department of Biological Toxicology, Zeist, The Netherlands.
Verhagen
H
H
van Bladeren
P J
PJ
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects*; D005054:Eugenol / Q000494:pharmacology*; D005421:Flavoring Agents / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D005421:Flavoring Agents; D005054:Eugenol; D005982:Glutathione Transferase; C006578:anethole