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饥饿和丙酮对大鼠生物转化酶系统及外源性物质(细胞色素P450 2E1底物)毒性的影响

[Effect of starvation and acetone on the enzyme systems of biotransformation and toxicity of xenobiotics--CYP2E1 substrates in rats].

作者信息

Kachula S O, Pentiuk O O

出版信息

Ukr Biokhim Zh (1999). 2004 Jan-Feb;76(1):114-22.

Abstract

In experiments on 205 rats it was fixed, that starvation during 2-3 days, as well as introduction of acetone (250 and 1000 mg/kg) considerably increases CYP2E1-dependent aniline and p-nitrophenol hydroxylase activity in the liver, kidneys, lungs and CYP3A dependent erythromycin N-demethylase activity, at the same time, suppress in a liver activity enzymes, dependent CYP2D, CYP1A2 and CYP2C as well as of activity UDP-glucuronosyl-transferase, sulfotransferase and glutathione-S-transferase. The starvation causes accumulation of KoA and increases activity of N-acetyltransferase in the liver. Starvation induces the change of enzymes activity and correlates with the intensifying of the processes of lipolysis, glycogenolysis, gluconeogenesis and, especially, ketogenesis which are appreciably initiated by introduction of acetone. The starvation and introduction of acetone increases metabolism of acetanilide and brombenzene, and, increasing the formation of toxic metabolites, raise its hepato-, nephro- and pulmotoxicity. The starvation attenuates elimination of indometacin from blood plasma, but intensifies conjugation of sulfadimidine with acetic acid.

摘要

在对205只大鼠进行的实验中发现,2 - 3天的饥饿以及丙酮(250和1000毫克/千克)的注入,会显著增加肝脏、肾脏、肺中CYP2E1依赖的苯胺和对硝基苯酚羟化酶活性以及CYP3A依赖的红霉素N - 脱甲基酶活性,同时抑制肝脏中依赖CYP2D、CYP1A2和CYP2C的酶活性以及UDP - 葡萄糖醛酸基转移酶、磺基转移酶和谷胱甘肽 - S - 转移酶的活性。饥饿会导致肝脏中乙酰辅酶A的积累并增加N - 乙酰转移酶的活性。饥饿会诱导酶活性的变化,并与脂肪分解、糖原分解、糖异生,尤其是酮体生成过程的增强相关,而丙酮的注入会明显引发这些过程。饥饿和丙酮的注入会增加乙酰苯胺和溴苯的代谢,并且由于增加了有毒代谢物的形成,会提高其肝毒性、肾毒性和肺毒性。饥饿会减弱血浆中吲哚美辛的消除,但会增强磺胺嘧啶与乙酸的结合。

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