Detoxication of the 2',3'-epoxide metabolites of allylbenzene and estragole. Conjugation with glutathione.
The enzymatic detoxication in vitro of the 2',3'-epoxide derivatives of allylbenzene and estragole was examined, and the relative rates of enzymatic glutathione conjugation and epoxide hydrolysis were compared with those for styrene 1',2'-oxide. HPLC was used to determine the amounts of dihydrodiol and glutathione conjugate metabolites formed by cell extracts from several sources. Although some differences among species were observed, in general, the rates of epoxide inactivation by both pathways are similar. We conclude that one explanation for the apparent lack of genotoxicity of these allylic epoxides in vivo may be their rapid metabolic inactivation by both glutathione S-transferases and epoxide hydrolases, which occur to approximately equal degrees in vitro.
Department of Pharmacology, University of Illinois College of Medicine at Chicago 60612.
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D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000378:metabolism*; D001555:Benzene Derivatives / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004851:Epoxide Hydrolases / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism*; D005421:Flavoring Agents / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D001555:Benzene Derivatives; D004852:Epoxy Compounds; D005421:Flavoring Agents; C091757:allylbenzene 2',3'-epoxide; C030062:estragole-2',3'-oxide; C007633:estragole; C013690:styrene oxide; D004851:Epoxide Hydrolases; D005978:Glutathione