School of Health Sciences, Purdue University, West Lafayette, Indiana 47907-2051, USA.
Drug Chem Toxicol. 2011 Oct;34(4):440-4. doi: 10.3109/01480545.2011.562899. Epub 2011 Jul 12.
Styrene is known to be hepatotoxic and pneumotoxic in rodents, and these adverse effects are related to its metabolism. Mice deficient in the enzymes responsible for both the activation and detoxification of styrene are useful in examining this relationship more closely. In the current study, mice deficient in glutathione S-transferase P1P2(-/-) (GST(-/-)) were compared with wild-type mice. Similar changes in serum sorbitol dehydrogenase, as an indicator of hepatotoxicity, and bronchioalveolar levels of protein, cells, and lactate dehydrogenase, as indicators of pneumotoxicity, were observed after styrene administration. Glutathione depletion followed a similar pattern. The administration of the toxic metabolite, styrene oxide, which is a direct substrate for glutathione metabolism, and 4-vinylphenol, which is a minor metabolite but is more potent than either styrene oxide, yielded results similar to those of styrene. The results indicate that either other isoforms of glutathione S-transferase are more important than the P1P2 form in styrene detoxification or that this pathway contributes in only a minor way to styrene detoxification, compared to other pathways.
苯乙烯在啮齿动物中已知具有肝毒性和肺毒性，这些不良反应与其代谢有关。缺乏负责苯乙烯激活和解毒的酶的小鼠在更仔细地检查这种关系方面非常有用。在当前的研究中，比较了缺乏谷胱甘肽 S-转移酶 P1P2(-/-)(GST(-/-))的小鼠与野生型小鼠。苯乙烯给药后，血清山梨醇脱氢酶（作为肝毒性的指标）和支气管肺泡蛋白、细胞和乳酸脱氢酶水平（作为肺毒性的指标）均发生类似变化。谷胱甘肽耗竭也呈现出类似的模式。苯乙烯氧化物（谷胱甘肽代谢的直接底物）和 4-乙烯基苯酚（一种次要代谢物，但比苯乙烯氧化物更有效）的毒性代谢物的给药，产生的结果与苯乙烯相似。结果表明，在苯乙烯解毒中，其他谷胱甘肽 S-转移酶同工酶比 P1P2 形式更为重要，或者与其他途径相比，该途径对苯乙烯解毒的贡献较小。
