RT Journal Article
SR Electronic
T1 Metabolism of allylbenzene 2',3'-oxide and estragole 2',3'-oxide in the isolated perfused rat liver.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 588
OP 596
VO 272
IS 2
A1 G Luo
A1 T M Guenthner
YR 1995
UL http://jpet.aspetjournals.org/content/272/2/588.abstract
AB The metabolism of allylbenzene 2',3'-oxide, estragole 2',3'-oxide, allylbenzene and estragole was studied in the isolated perfused rat liver. Formation of dihydrodiol and glutathione conjugate metabolites was detected for both epoxides and the presence of dihydrodiol metabolites after perfusion of allylbenzene or estragole indicated the formation of allylic epoxide intermediates in the intact liver. A comparison of elimination kinetics for parent compounds and epoxides indicated that epoxides were relatively rapidly detoxified and probably do not accumulate on formation in vivo. Acute toxicity of epoxides, measured as the release of alanine aminotransferase activity into the perfusate, or genetic toxicity, determined as covalent binding of radiolabeled epoxide to DNA, were not observed. It was concluded that both epoxide hydrolases and glutathione S-transferases can effectively detoxify the allylic epoxides derived from either allylbenzene or estragole and effectively prevent cellular or genetic toxicity of these reactive intermediates. Epoxide hydrolases appear to play the major role in the detoxication of these epoxides in vivo.