COMPARISON OF STYRENE OXIDE ENANTIOMERS FOR HEPATOTOXIC AND PNEUMOTOXIC EFFECTS IN MICROSOMAL EPOXIDE HYDROLASE-DEFICIENT MICE

Styrene is hepatotoxic and pneumotoxic in mice. Styrene oxide, the active metabolite, is detoxified via hydrolysis by microsomal epoxide hydrolase (mEH). Racemic styrene oxide was previously found to be more lethal and produced increased toxicity in mEH(-/-) mice compared to wild-type mice. The hepatotoxicity and pneumotoxicity of the R-and S-styrene oxide (SO) enantiomers were compared in wild-type and mEH-deficient mice (mEH(-/-)). Twenty-four hours following administration of 150 mg/kg ip, neither enantiomer produced hepatotoxicity, but S-SO was more pneumotoxic. However, in mEH(-/-) mice R-SO produced greater decreases in hepatic glutathione levels 3 h after administration. The basis for the unusual greater toxicity of S-SO, rather than the generally more toxic R-SO, in mEH(-/-) mice may be related to differences in detoxification by EH.