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人肾皮质和髓质中药物代谢酶的概况

Profile of drug-metabolizing enzymes in the cortex and medulla of the human kidney.

作者信息

Pacifici G M, Viani A, Franchi M, Gervasi P G, Longo V, Di Simplicio P, Temellini A, Romiti P, Santerini S, Vannucci L

机构信息

Department of General Pathology, Medical School, University of Pisa, Italy.

出版信息

Pharmacology. 1989;39(5):299-308. doi: 10.1159/000138613.

DOI:10.1159/000138613
PMID:2616633
Abstract

The cortex and medulla were isolated from kidneys whose donors (5 men and 1 woman, aged between 44 and 68 years) were undergoing nephrectomy to remove a tumor. Kidneys with normal architecture for at least two thirds of the organ were included in the study. Tissue specimens used in our experiments were free from pathological changes. The activities of the following enzymes of phase I NADPH cytochrome c reductase, aminopyrine N-demethylase, ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase, microsomal and cytosolic epoxide hydrolases, glutathione reductase and glutathione peroxidase, and those of the following enzymes of phase II glutathione transferase, glucuronyl transferase, sulphotransferase, acetyltransferase, thiomethyltransferase, thiopurinemethyltransferase, thioltransferase and glyoxalase were measured. The activity in renal cortex was significantly higher than in medulla for NADPH cytochrome c reductase, cytosolic epoxide hydrolase, glutathione reductase and glutathione peroxidase (phase I enzymes), and glutathione transferase, acetyltransferase, thiomethyltransferase, thiopurinemethyltransferase, thioltransferase and glyoxalase (phase II enzymes). The other enzymes had similar activity in cortex and medulla. The distribution pattern of drug-metabolizing enzymes in the human kidney cannot be considered as a single pattern because of the observed enzyme-dependent differences between cortex and medulla.

摘要

皮质和髓质取自供体(5名男性和1名女性,年龄在44至68岁之间)正在接受肾切除术以切除肿瘤的肾脏。研究纳入了至少三分之二器官结构正常的肾脏。我们实验中使用的组织标本无病理变化。测定了以下I相酶(NADPH细胞色素c还原酶、氨基比林N-脱甲基酶、乙氧香豆素O-脱乙基酶、乙氧试卤灵O-脱乙基酶、微粒体和胞质环氧化物水解酶、谷胱甘肽还原酶和谷胱甘肽过氧化物酶)以及以下II相酶(谷胱甘肽转移酶、葡糖醛酸转移酶、磺基转移酶、乙酰转移酶、硫甲基转移酶、硫嘌呤甲基转移酶、硫醇转移酶和乙二醛酶)的活性。对于NADPH细胞色素c还原酶、胞质环氧化物水解酶、谷胱甘肽还原酶和谷胱甘肽过氧化物酶(I相酶),以及谷胱甘肽转移酶、乙酰转移酶、硫甲基转移酶、硫嘌呤甲基转移酶、硫醇转移酶和乙二醛酶(II相酶),肾皮质中的活性显著高于髓质。其他酶在皮质和髓质中的活性相似。由于观察到皮质和髓质之间存在酶依赖性差异,人类肾脏中药物代谢酶的分布模式不能被视为单一模式。

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