School of Health Sciences, Purdue University, West Lafayette, Indiana 47907-2051, USA.
J Toxicol Environ Health A. 2011;74(6):347-50. doi: 10.1080/15287394.2011.539130.
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.
苯乙烯在小鼠中具有肝毒性和肺毒性。其活性代谢物氧化苯乙烯通过微粒体环氧化物水解酶（mEH）水解解毒。先前发现，外消旋氧化苯乙烯比野生型小鼠中的 mEH-/- 小鼠更具致命性和更高的毒性。在野生型和 mEH 缺乏型（mEH-/-）小鼠中比较了 R-和 S-氧化苯乙烯（SO）对映体的肝毒性和肺毒性。ip 给予 150mg/kg 后 24 小时，两种对映体均未产生肝毒性，但 S-SO 更具肺毒性。然而，在 mEH-/- 小鼠中，R-SO 在给药 3 小时后引起肝内谷胱甘肽水平的更大降低。在 mEH-/- 小鼠中，S-SO 的异常更高毒性，而不是通常更具毒性的 R-SO，其原因可能与 EH 的解毒差异有关。
