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5-硝基咪唑类药物罗硝唑的药物残留形成。VI. 罗硝唑还原代谢产物和衍生物的致突变活性缺乏。

Drug residue formation from ronidazole, a 5-nitroimidazole. VI. Lack of mutagenic activity of reduced metabolites and derivatives of ronidazole.

作者信息

Wislocki P G, Bagan E S, Cook M M, Bradley M O, Wolf F J, Lu A Y

出版信息

Chem Biol Interact. 1984 Apr;49(1-2):27-38. doi: 10.1016/0009-2797(84)90050-4.

DOI:10.1016/0009-2797(84)90050-4
PMID:6722938
Abstract

The potential toxicity of ronidazole residues present in the tissues of food-producing animals was assessed using the Ames mutagenicity test. Since ronidazole is activated by reduction, reduced derivatives of ronidazole and metabolites formed by enzymatic reduction of ronidazole were tested for mutagenicity. When tested at levels several orders of magnitude higher than that at which ronidazole was mutagenic, 5-amino-4-S-cysteinyl-1,2- dimethylimidazole , a product of the dithionite reduction of ronidazole in the presence of cysteine, the 5-N-acetylamino derivative of ronidazole and 5-amino-1,2- dimethylimidazole all lacked mutagenic activity in Ames strain TA100. The metabolites of ronidazole formed by the incubation of ronidazole with microsomes under anaerobic conditions were also not mutagenic. These data demonstrate that although ronidazole is a potent mutagen, residues from it which may be present in the tissues of food-producing animals lack any mutagenic activity.

摘要

使用艾姆斯诱变试验评估了产食用动物组织中存在的罗硝唑残留的潜在毒性。由于罗硝唑通过还原作用被激活,因此对罗硝唑的还原衍生物以及通过罗硝唑的酶促还原形成的代谢物进行了诱变性测试。当以比罗硝唑具有诱变性的水平高几个数量级的水平进行测试时,在半胱氨酸存在下罗硝唑经连二亚硫酸盐还原的产物5-氨基-4-S-半胱氨酰-1,2-二甲基咪唑、罗硝唑的5-N-乙酰氨基衍生物和5-氨基-1,2-二甲基咪唑在艾姆斯TA100菌株中均缺乏诱变活性。在厌氧条件下将罗硝唑与微粒体孵育形成的罗硝唑代谢物也没有诱变性。这些数据表明,尽管罗硝唑是一种强效诱变剂,但可能存在于产食用动物组织中的罗硝唑残留缺乏任何诱变活性。

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