Mizutani T, Suzuki K, Murakami M, Yoshida K, Nakanishi K
Department of Food Science and Nutrition, Kyoto Prefectural University, Japan.
Res Commun Mol Pathol Pharmacol. 1996 Oct;94(1):89-101.
Administration of thioformamide (TFA) (> 2 mmol/kg, sc) in combination with DL-buthionine sulfoximine (BSO) (4 mmol/kg, i.p.), an inhibitor of glutathione (GSH) synthesis, caused kidney injury in male mice. The injury was characterized by tubular necrosis, increases in relative kidney weight and serum urea nitrogen concentration, and a decrease in renal GSH concentration. In contrast to results in male mice, no overt nephrotoxic effects were observed in female mice given TFA in combination with BSO. These features of nephrotoxicity were very similar to those reported for thiabendazole and other nephrotoxic thiazoles in mice depleted of GSH by treatment with BSO; this resemblance supports the suggestion that TFA as a ring cleavage metabolite, or a further metabolite thereof, is responsible for the toxicity of the nephrotoxic thiazoles (Mizutani, T., Yoshida, K., and Kawazoe, S. (1993) Chem. Res. Toxicol. 6, 174-179).
硫代甲酰胺（TFA）（>2 mmol/kg，皮下注射）与谷胱甘肽（GSH）合成抑制剂DL-丁硫氨酸亚砜胺（BSO）（4 mmol/kg，腹腔注射）联合给药，可导致雄性小鼠肾损伤。损伤的特征为肾小管坏死、相对肾重量增加、血清尿素氮浓度升高以及肾GSH浓度降低。与雄性小鼠的结果相反，联合给予TFA和BSO的雌性小鼠未观察到明显的肾毒性作用。这些肾毒性特征与用BSO处理使GSH耗竭的小鼠中关于噻苯达唑和其他肾毒性噻唑报道的特征非常相似；这种相似性支持了以下观点，即TFA作为一种开环代谢物或其进一步的代谢物，是肾毒性噻唑毒性的原因（水谷哲、吉田健、川添胜（1993年）《化学研究毒理学》6，174 - 179）。
