Mizutani T, Yoshida K, Ito K
Department of Food Science and Nutrition, Kyoto Prefectural University, Japan.
Res Commun Chem Pathol Pharmacol. 1992 Jan;75(1):29-38.
In mice depleted of glutathione (GSH) by treatment with DL-buthionine sulfoximine (BSO), thiabendazole [2-(4'-thiazolyl)benzimidazole, TBZ] produces renal damage characterized by increases in relative kidney weight and serum urea nitrogen (SUN) concentration. Several thiazole and benzimidazole compounds related to TBZ were examined for the ability to cause nephrotoxicity in mice pretreated with BSO. 4-Methyl- and 4-phenylthiazoles were highly effective compounds. In the absence of BSO, 4-methylthiazole resulted in no nephrotoxicity; inhibitors of hepatic and renal cytochrome P-450 enzymes such as methoxsalen and piperonyl butoxide prevented the nephrotoxicity of 4-methylthiazole given in combination with BSO. In addition, there was a sex difference in the nephrotoxicity of 4-methylthiazole in combination with BSO; the nephrotoxicity was observed only in males. These features of nephrotoxicity of 4-methylthiazole are well in accord with those of TBZ previously reported. This suggests that TBZ and 4-methylthiazole share a common mechanism of nephrotoxicity.
在用DL-丁硫氨酸亚砜亚胺（BSO）处理使谷胱甘肽（GSH）耗竭的小鼠中，噻苯达唑[2-(4'-噻唑基)苯并咪唑，TBZ]会导致肾脏损伤，其特征为相对肾重和血清尿素氮（SUN）浓度增加。研究了几种与TBZ相关的噻唑和苯并咪唑化合物在经BSO预处理的小鼠中引起肾毒性的能力。4-甲基噻唑和4-苯基噻唑是高效化合物。在没有BSO的情况下，4-甲基噻唑不会导致肾毒性；肝和肾细胞色素P-450酶的抑制剂如甲氧沙林和胡椒基丁醚可预防与BSO联合使用时4-甲基噻唑的肾毒性。此外，4-甲基噻唑与BSO联合使用时的肾毒性存在性别差异；仅在雄性小鼠中观察到肾毒性。4-甲基噻唑的这些肾毒性特征与先前报道的TBZ的特征非常一致。这表明TBZ和4-甲基噻唑具有共同的肾毒性机制。
