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三氯乙烯的吸收、消除与代谢:大鼠与小鼠之间的定量比较

Absorption, elimination and metabolism of trichloroethylene: a quantitative comparison between rats and mice.

作者信息

Dekant W, Schulz A, Metzler M, Henschler D

出版信息

Xenobiotica. 1986 Feb;16(2):143-52. doi: 10.3109/00498258609043517.

Abstract

The absorption, elimination and metabolism of 14C-trichloroethylene (Tri) was studied in adult female Wistar rats and NMRI mice after administration of 200, 20 and 2 mg/kg Tri. Dose-dependent biotransformation of Tri to metabolites was observed in both species. Induction of hepatic mono-oxygenases by phenobarbital or polychlorinated biphenyls resulted in a higher rate of biotransformation after a single oral dose of 200 mg/kg 14C-Tri to rats. An increase in radioactivity covalently bound to liver and kidney macromolecules of induced rats as compared to control rats parallels the toxic effects of Tri on these organs after induction of cytochrome P-450. The urinary metabolites were analysed by h.p.l.c. In both species, 1,1,1-trichlorocompounds (trichloroacetic acid, trichloroethanol and its glucuronide, comprising 88.9-93.5% of the radioactivity excreted in the urine) constituted the main metabolites; in addition, N-(hydroxyacetyl)-aminoethanol (4.1-7.2%), dichloroacetic acid (0.1-2.0%) and oxalic acid (0.7-1.8%) were identified. The pattern of metabolites in the 72 h urine remained constant for each species in the dose range studied and no change was induced by pretreatment. The percentage of radioactivity exhaled as 14CO2 increased with dose in mice, which may indicate dose-dependent formation of dichloroacetic acid and saturation of deactivating mechanisms for reactive intermediates in mice.

摘要

在成年雌性Wistar大鼠和NMRI小鼠中,给予200、20和2mg/kg三氯乙烯(Tri)后,研究了14C-三氯乙烯的吸收、消除和代谢情况。在这两个物种中均观察到Tri向代谢产物的剂量依赖性生物转化。苯巴比妥或多氯联苯诱导肝单加氧酶后,给大鼠单次口服200mg/kg 14C-Tri后生物转化速率更高。与对照大鼠相比,诱导大鼠肝脏和肾脏大分子共价结合的放射性增加,这与细胞色素P-450诱导后Tri对这些器官的毒性作用平行。通过高效液相色谱法分析尿代谢产物。在这两个物种中,1,1,1-三氯化合物(三氯乙酸、三氯乙醇及其葡糖醛酸苷,占尿中排泄放射性的88.9-93.5%)是主要代谢产物;此外,还鉴定出N-(羟乙酰基)-氨基乙醇(4.1-7.2%)、二氯乙酸(0.1-2.0%)和草酸(0.7-1.8%)。在所研究的剂量范围内,每个物种72小时尿液中的代谢产物模式保持不变,预处理未引起变化。在小鼠中,以14CO2呼出的放射性百分比随剂量增加,这可能表明小鼠中二氯乙酸的剂量依赖性形成以及反应性中间体失活机制的饱和。

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