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亚硫酸盐氧化酶缺乏症中药物代谢酶的改变。

Alteration of drug metabolizing enzymes in sulphite oxidase deficiency.

机构信息

Department of Biology, University of Pamukkale, 20070 Kinikli-Denizli, Turkey.

出版信息

J Clin Biochem Nutr. 2012 Jul;51(1):50-4. doi: 10.3164/jcbn.11-79. Epub 2012 Mar 30.

Abstract

The aim of this study was to investigate the possible effects of sulphite oxidase (SOX, E.C. 1.8.3.1) deficiency on xenobiotic metabolism. For this purpose, SOX deficiency was produced in rats by the administration of a low molybdenum diet with concurrent addition of 200 ppm tungsten to their drinking water. First, hepatic SOX activity in deficient groups was measured to confirm SOX deficiency. Then, aminopyrine N-demethylase, aniline 4-hydroxylase, aromatase, caffeine N-demethylase, cytochrome b5 reductase, erythromycin N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase, N-nitrosodimethylamine N-demethylase and penthoxyresorufin O-deethylase activities were determined to follow changes in the activity of drug metabolizing enzymes in SOX-deficient rats. Our results clearly demonstrated that SOX deficiency significantly elevated A4H, caffeine N-demethylase, erythromycin N-demethylase and N-nitrosodimethylamine N-demethylase activities while decreasing ethoxyresorufin O-deethylase and aromatase activities. These alterations in drug metabolizing enzymes can contribute to the varying susceptibility and response of sulphite-sensitive individuals to different drugs and/or therapeutics used for treatments.

摘要

本研究旨在探讨亚硫酸盐氧化酶(SOX,EC 1.8.3.1)缺乏对异生物质代谢的可能影响。为此,通过给予低钼饮食并同时在饮水中添加 200ppm 钨来在大鼠中产生 SOX 缺乏。首先,测量缺乏组的肝 SOX 活性以确认 SOX 缺乏。然后,测定氨基比林 N-去甲基酶、苯胺 4-羟化酶、芳香酶、咖啡因 N-去甲基酶、细胞色素 b5 还原酶、红霉素 N-去甲基酶、乙氧基 RESO 去乙基酶、谷胱甘肽 S-转移酶、N-亚硝二甲胺 N-去甲基酶和戊氧基 RESO 去乙基酶活性,以跟踪 SOX 缺乏大鼠中药物代谢酶活性的变化。我们的结果清楚地表明,SOX 缺乏显著增加了 A4H、咖啡因 N-去甲基酶、红霉素 N-去甲基酶和 N-亚硝二甲胺 N-去甲基酶的活性,同时降低了乙氧基 RESO 去乙基酶和芳香酶的活性。这些药物代谢酶的改变可能导致亚硫酸盐敏感个体对不同药物和/或用于治疗的治疗方法的不同敏感性和反应性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18ea/3391863/54ed2f56fe02/jcbn11-79f01.jpg

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