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[关于一氧化碳暴露易感性。一氧化碳暴露对小鼠肝脏药物代谢酶的影响]

[On susceptibility for carbon monoxide exposure. The effect of carbon monoxide exposure on hepatic drug metabolizing enzymes of mice].

作者信息

Umeda M, Ishikawa K, Kinouchi N

出版信息

Sangyo Igaku. 1982 Nov;24(6):663-71. doi: 10.1539/joh1959.24.663.

Abstract

Male mice were exposed to three levels of carbon monoxide, i.e. 500, 1,000 and 3,000 ppm for 60, 10 and 7 minutes per day respectively. Durations of the exposure were 1 and 5 days and 3, 6 and 9 weeks. As the effect of carbon monoxide exposure, induction of the drug metabolizing enzyme was observed, which was ascertained by the decrease of sleeping time by pentobarbital and by the increase of activities of liver microsomal p-nitroanisole demethylase and of aniline hydroxylase. These results should be due to an adaptive response to carbon monoxide exposure, but the mechanisms of the enzyme induction were not fully explained in this study. In 5 days' exposure to carbon monoxide, there was a dose-response relationship between the degree of carbon monoxide exposure and the extent of enzyme induction. But in the prolonged exposure to higher concentrations of carbon monoxide (1,000 and 3,000 ppm), the increase of drug metabolism became less pronounced and by 9 weeks' exposure to 1,000 ppm carbon monoxide, little induction of the drug metabolizing enzyme was observed. These results suggest that the induction of the drug metabolizing enzyme by carbon monoxide exposure has a certain limit.

摘要

雄性小鼠分别暴露于三种一氧化碳水平,即500、1000和3000 ppm,每天分别暴露60、10和7分钟。暴露持续时间为1天和5天以及3、6和9周。作为一氧化碳暴露的影响,观察到药物代谢酶的诱导,这通过戊巴比妥睡眠时间的减少以及肝微粒体对硝基苯甲醚脱甲基酶和苯胺羟化酶活性的增加来确定。这些结果应该归因于对一氧化碳暴露的适应性反应,但本研究中酶诱导的机制并未得到充分解释。在暴露于一氧化碳5天的情况下,一氧化碳暴露程度与酶诱导程度之间存在剂量反应关系。但在长时间暴露于较高浓度的一氧化碳(1000和3000 ppm)时,药物代谢的增加变得不那么明显,并且在暴露于1000 ppm一氧化碳9周时,几乎未观察到药物代谢酶的诱导。这些结果表明,一氧化碳暴露对药物代谢酶的诱导有一定限度。

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