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异硫氰酸烯丙酯:大鼠和小鼠体内的比较分布

Allyl isothiocyanate: comparative disposition in rats and mice.

作者信息

Ioannou Y M, Burka L T, Matthews H B

出版信息

Toxicol Appl Pharmacol. 1984 Sep 15;75(2):173-81. doi: 10.1016/0041-008x(84)90199-6.

Abstract

Allyl isothiocyanate (AITC), the major component of volatile oil of mustard, was recently reported to induce transitional-cell papillomas in the urinary bladder of male Fischer 344 rats, but not in the bladders of female rats or B6C3F1 mice. The present investigation of comparative disposition in both sexes of each species was designed to detect sex or species differences in disposition which might explain susceptibility to AITC toxicity. AITC was readily cleared from all rat and mouse tissues so that within 24 hr after administration less than 5% of the total dose was retained in tissues. The highest concentration of AITC-derived radioactivity was observed in male rat bladder. Clearance of AITC-derived radioactivity by each species was primarily in urine (70 to 80%) and in exhaled air (13 to 15%) with lesser amounts in feces (3 to 5%). Rats excreted one major and four minor metabolites in urine. The major metabolite from rat urine was identified by NMR spectroscopy to be the mercapturic acid N-acetyl-S-(N-allylthiocarbamoyl)-L-cysteine. Mice excreted in urine the same major metabolite identified in rat urine as well as three other major and two minor metabolites. Sex-related variations were observed in the relative amounts of these metabolites. Both species excreted a single metabolite in feces. Metabolism of AITC by male and female rats was similar, but female rats excreted over twice the urine volume of male rats. Results of the present study indicate that excretion of a more concentrated solution of AITC metabolite(s) in urine may account for the toxic effects of AITC on the bladder of male rats.

摘要

异硫氰酸烯丙酯(AITC)是芥子挥发油的主要成分,最近有报道称,它可在雄性Fischer 344大鼠的膀胱中诱发移行细胞乳头状瘤,但在雌性大鼠或B6C3F1小鼠的膀胱中则不会诱发。本研究对每个物种的雌雄两性进行了比较处置研究,旨在检测处置过程中的性别或物种差异,这些差异可能解释对AITC毒性的易感性。AITC很容易从所有大鼠和小鼠组织中清除,因此给药后24小时内,组织中保留的总剂量不到5%。在雄性大鼠膀胱中观察到AITC衍生放射性的最高浓度。每个物种对AITC衍生放射性的清除主要通过尿液(70%至80%)和呼出空气(13%至15%),粪便中的清除量较少(3%至5%)。大鼠尿液中排泄出一种主要代谢物和四种次要代谢物。通过核磁共振光谱法鉴定,大鼠尿液中的主要代谢物为硫醚氨酸N-乙酰-S-(N-烯丙基硫代氨基甲酰基)-L-半胱氨酸。小鼠尿液中排泄出与大鼠尿液中相同的主要代谢物以及其他三种主要代谢物和两种次要代谢物。观察到这些代谢物的相对含量存在与性别相关的差异。两个物种在粪便中都排泄出一种单一的代谢物。雄性和雌性大鼠对AITC的代谢相似,但雌性大鼠排泄的尿量是雄性大鼠的两倍多。本研究结果表明,尿液中排泄出更浓缩的AITC代谢物溶液可能是AITC对雄性大鼠膀胱产生毒性作用的原因。

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