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乙二醇单甲醚蒸气对大鼠的剂量依赖性毒性。

Dose-dependent toxicity of ethylene glycol monomethyl ether vapour in the rat.

作者信息

Heinonen T, Vainio H

出版信息

Eur J Drug Metab Pharmacokinet. 1981;6(4):275-80. doi: 10.1007/BF03189526.

Abstract

Wistar male rats were exposed by inhalation to 50, 100 or 400 ppm of ethylene glycol monomethyl ether (EGME) for 1 to 2 weeks. The overall hepatic drug oxidation reactions, O-deethylation of 7-ethoxycoumarin and 7-ethoxyresorufin and cytochrome P-450 content were only slightly affected by the EGME exposures. NADPH cytochrome c reductase activity showed a tendency toward a dose-dependent decrease in liver, the activity being 73% and 64% of that in the controls after one and two weeks of exposure, at 400 ppm respectively. UDP glucuronosyl transferase activity exhibited a dose-dependent enhancement in liver microsomes after exposure for two weeks to EGME. The enhancement was 1.3- 1.7- and 3.0 fold with exposure to 50, 100 and 400 ppm of EGME respectively. After exposure for one week the UDPglucuronosyltransferase activity in kidney microsomes was similarly enhanced. A dose-related increase in measurable UDPglucuronosyltransferase activity was also obtained in Triton X-100 treated hepatic microsomes. GSH levels of the liver and kidneys in EGME treated animals showed a tendency towards a dose-dependent increase. The activities of low-Km and high-Km aldehyde dehydrogenases in liver were decreased 6 - 14% of that in the controls with exposure to 400 ppm of EGME when glycolaldehyde was used as a substrate. Serum alanine aminotransferase activity was not influenced by inhalation exposures to EGME.

摘要

将雄性Wistar大鼠通过吸入方式暴露于50、100或400 ppm的乙二醇单甲醚(EGME)中1至2周。EGME暴露对肝脏整体药物氧化反应、7-乙氧基香豆素和7-乙氧基试卤灵的O-脱乙基反应以及细胞色素P-450含量仅有轻微影响。NADPH细胞色素c还原酶活性在肝脏中呈现出剂量依赖性降低的趋势,在400 ppm暴露1周和2周后,其活性分别为对照组的73%和64%。暴露于EGME两周后,肝脏微粒体中的UDP-葡萄糖醛酸基转移酶活性呈现出剂量依赖性增强。暴露于50、100和400 ppm的EGME时,增强倍数分别为1.3倍、1.7倍和3.0倍。暴露1周后,肾微粒体中的UDP-葡萄糖醛酸基转移酶活性也有类似增强。在经Triton X-100处理的肝脏微粒体中也观察到可测量的UDP-葡萄糖醛酸基转移酶活性呈剂量相关增加。EGME处理动物的肝脏和肾脏中谷胱甘肽水平呈现出剂量依赖性增加的趋势。当以乙醇醛为底物时,暴露于400 ppm的EGME会使肝脏中低Km和高Km醛脱氢酶的活性降低至对照组的6%-14%。吸入EGME对血清丙氨酸氨基转移酶活性没有影响。

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