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首页> 外文期刊>Journal of applied toxicology >Identification of the 1-cyano-3,4-epithiobutane-derived urinary mercapturic acid N-acetyl-S-(4-cyano-2-thio-1-butyl)-cysteine in male Fischer 344 rats.
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Identification of the 1-cyano-3,4-epithiobutane-derived urinary mercapturic acid N-acetyl-S-(4-cyano-2-thio-1-butyl)-cysteine in male Fischer 344 rats.

机译：在雄性Fischer 344大鼠中鉴定出1-cyano-3,4-epithiobutane衍生的尿巯基酸N-乙酰基-S-（4-cyano-2-thio-1-丁基）-半胱氨酸。

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摘要

1-Cyano-3,4-epithiobutane (CEB), a naturally occurring nitrile derived from cruciferous plants, causes nephrotoxicity in male Fischer 344 rats. Nephrotoxicity induced by CEB is dependent on glutathione (GSH) conjugation and bioactivation. Conjugation with GSH and subsequent metabolism leads to the formation of specific urinary metabolites. The objectives of the present study were to identify CEB-derived urinary metabolites and quantify urinary non-protein thiols and thioethers in male Fischer 344 rats. Animals received 125 mg kg(-1) of CEB alone or following pretreatment with one of three selective inhibitors of GSH metabolism: acivicin, probenecid or aminooxyacetic acid. Total non-protein urinary thiol and urinary thioether concentrations were elevated in all treated groups at 12 and 24 h; however, elevations in non-protein thiols were not significantly greater in rats administered CEB alone as compared to negative controls. A single predominant urinary metabolite was identified as the CEB-derived mercapturic acid N-acetyl-S-(4-cyano-thio-1-butyl)-cysteine. Evidence for other CEB-derived metabolites was also demonstrated. These findings represent the identification of a unique compound and provide further evidence for the importance of GSH conjugation as a significant pathway in CEB metabolism. Copyright 2000 John Wiley & Sons, Ltd.
机译：1-Cyano-3,4-epithiobutane（CEB），一种来自十字花科植物的天然腈，在Fischer 344雄性大鼠中引起肾毒性。 CEB诱导的肾毒性取决于谷胱甘肽（GSH）的结合和生物激活。与GSH结合以及随后的代谢会导致特定的尿代谢产物的形成。本研究的目的是鉴定雄性Fischer 344大鼠中CEB衍生的尿液代谢产物并定量尿液中非蛋白质硫醇和硫醚。动物可以单独接受125 mg kg（-1）的CEB，也可以用以下三种GSH选择性抑制剂之一进行预处理：阿西维奇，丙磺舒或氨氧基乙酸。在第12和24小时，所有治疗组的总非蛋白质尿硫醇和尿硫醚浓度升高;然而，与阴性对照组相比，单独施用CEB的大鼠中非蛋白质硫醇的升高并不明显更大。单一的主要尿代谢物被鉴定为CEB衍生的巯基乙酸N-乙酰基-S-（4-氰基-硫代-1-丁基）-半胱氨酸。还证明了其他CEB衍生代谢产物的证据。这些发现代表了独特化合物的鉴定，并为GSH偶联作为CEB代谢的重要途径的重要性提供了进一步的证据。版权所有2000 John Wiley＆Sons，Ltd.

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