使用肾皮质切片模型研究1,2 - 二氯丙烷肾毒性的体外机制。

In-vitro mechanisms of 1,2-dichloropropane nephrotoxicity using the renal cortical slice model.

Trevisan A, Meneghetti P, Maso S, Troso O

Istituto di Medicina del Lavoro, Laboratorio di Tossicologia Industriale, Università di Padova, Italy.

Hum Exp Toxicol. 1993 Mar;12(2):117-21. doi: 10.1177/096032719301200204.

Abstract

Renal cortical slices isolated from the kidneys of male Wistar rats were used as an experimental model for studying the nephrotoxicity induced by 1,2-dichloropropane. 2. The solvent causes a depletion of renal reduced glutathione content and slight, but significant, lipid peroxidation. The block of the oxidative pathway with carbon monoxide prevents glutathione content depletion, and shows that this conjugation is the major step in 1,2-dichloropropane metabolism. 3. Loss of organic anion accumulation and release into the incubation medium of tubular enzymes, mainly from the soluble fraction, are the toxic effects of the solvent. The brush border is only slightly affected. 4. The mechanism of nephrotoxicity appears to occur via mercapturic acid metabolism. Acivicin and aminooxyacetic acid, inhibitors of gamma-glutamyltransferase and beta-lyase activity, respectively, partially but significantly prevent the loss of organic anion accumulation induced by 1,2-dichloropropane. Furthermore, alpha-ketobutyrate, an activator of beta-lyase, enhances the effects of 1,2-dichloropropane on the target, but is itself toxic for organic anion accumulation.

摘要

从雄性Wistar大鼠肾脏分离得到的肾皮质切片被用作研究1,2 - 二氯丙烷诱导的肾毒性的实验模型。2. 该溶剂导致肾脏还原型谷胱甘肽含量减少以及轻微但显著的脂质过氧化。用一氧化碳阻断氧化途径可防止谷胱甘肽含量减少，表明这种结合是1,2 - 二氯丙烷代谢的主要步骤。3. 有机阴离子积累的丧失以及主要来自可溶性部分的管状酶释放到孵育培养基中是该溶剂的毒性作用。刷状缘仅受到轻微影响。4. 肾毒性机制似乎通过硫醚氨酸代谢发生。阿西维辛和氨基氧乙酸分别是γ - 谷氨酰转移酶和β - 裂解酶活性的抑制剂，它们部分但显著地防止了1,2 - 二氯丙烷诱导的有机阴离子积累的丧失。此外，β - 裂解酶的激活剂α - 酮丁酸增强了1,2 - 二氯丙烷对靶点的作用，但它本身对有机阴离子积累有毒性。