METABOLISM OF ALLYLBENZENE 2',3'-OXIDE AND ESTRAGOLE 2','-OXIDE IN THE ISOLATED-PERFUSED RAT-LIVER

The metabolism of allylbenzene 2',3'-oxide, estragole 2',3'-oxide, all ylbenzene and estragole was studied in the isolated perfused rat liver . Formation of dihydrodiol and glutathione conjugate metabolites was d etected for both epoxides and the presence of dihydrodiol metabolites after perfusion of allylbenzene or estragole indicated the formation o f allylic epoxide intermediates in the intact liver. A comparison of e limination kinetics for parent compounds and epoxides indicated that e poxides were relatively rapidly detoxified and probably do not accumul ate on formation in vivo. Acute toxicity of epoxides, measured as the release of alanine aminotransferase activity into the perfusate, or ge netic toxicity, determined as covalent binding of radiolabeled epoxide to DNA, were not observed. It was concluded that both epoxide hydrola ses and glutathione S-transferases can effectively detoxify the allyli c epoxides derived from either allylbenzene or estragole and effective ly prevent cellular or genetic toxicity of these reactive intermediate s. Epoxide hydrolases appear to play the major role in the detoxicatio n of these epoxides in vivo.