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首页> 外文期刊>産業衛生学雑誌 >Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea Pigs
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Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea Pigs

机译:豚鼠三氯乙烯和三氯乙醇代谢的性差异

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Objectives: Trichloroethylene (TRI) has the potential to cause generalized dermatitis complicated with hepatitis. The guinea pig maximization test (GPMT) also suggests that both TRI and its metabolite trichloroethanol (TCE) exhibit immunogenicity and possible sex differences in guinea pigs. However, TRI and TCE metabolisms in guinea pigs have not been elucidated in detail. The first issue to clarify may be the sex differences in relation to the immunogenicity. Methods: We collected urine from Hartley male and female guinea pigs 24 hours after intracutaneous injection of TRI, TCE or trichloroacetic acid (TCA) during a GPMT and measured the urinary metabolites by gas chroma-tography-mass spectrometry. Results: After TRI treatment, the amount of TCA was significantly greater in females than males, while there was no sex difference in the total amount (TCA+TCE). TCA was only detected in urine after TCA treatment. Interestingly, not only TCE but also TCA was detected in urine of both sexes after TCE treatment, and the amount of TCA was also greater in females than males. An additional experiment showed that TCE treatment did not result in the detection of urinary TCA in cytochrome P450 (CYP)2E1-null mice but did in wild-type mice, suggesting the involvement of CYP2E1 in the metabolism from TCE to TCA. The constitutive expression of CYP2E1 in the liver of guinea pigs was greater in females than males. Conclusions: The sex difference in urinary TCA excretion after TRI and TCE treatments may be due to variation of the constitutive expression of CYP2E1.
机译:目的:三氯乙烯(三)有可能导致广泛性皮炎与肝炎合并。豚鼠最大化试验(GPMT)还表明TRI及其代谢产物三氯乙醇(TCE)在豚鼠中表现出免疫原性和可能的​​性别差异。然而,没有详细阐明豚鼠中的TRI和TCE代谢。澄清的第一个问题可能是与免疫原性有关的性别差异。方法:在GPMT期间,在皮层,TCE或三氯乙酸(TCA)后24小时收集来自Hartley男性和女性豚鼠的尿液,并通过气相色谱 - 质谱法测量尿代谢物。结果:在TRI治疗后,女性的TCA量明显大于男性,而总量没有性别差异(TCA + TCE)。 TCA仅在TCA治疗后在尿液中检测到。有趣的是,TCE治疗后,不仅在两性的尿液中检测到TCA,而且患有TCA的数量也比男性更大。另外的实验表明,TCE治疗没有导致细胞色素P450(CYP)2E1-零小鼠中尿TCA的检测,但在野生型小鼠中表明CYP2E1参与来自TCE到TCA的新陈代谢。在豚鼠肝脏中CYP2E1的组成型表达在女性比男性更大。结论:TRI和TCE治疗后尿TCA排泄的性别差异可能是由于CYP2E1的组成型表达的变化。

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