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用N-亚硝基(2-羟丙基)(2-氧代丙基)胺处理的仓鼠和大鼠中的主要尿液代谢物。

Major urinary metabolites in hamsters and rats treated with N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine.

作者信息

Kokkinakis D M, Hollenberg P F, Scarpelli D G

出版信息

Cancer Res. 1985 Aug;45(8):3586-92.

PMID:4016739
Abstract

Rats and hamsters were administered a single dose of N-[1-14C]nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), and their urinary metabolites were examined at various time intervals. In both species, urinary excretion of radiolabeled metabolites reached a plateau at 6 h following injection. At this time, 35 and 28% of the total dose was found in the urine of rats and hamsters, respectively. Separation by liquid chromatography and subsequent characterization by nuclear magnetic resonance, gas chromatography-mass spectroscopy, and infrared showed that the major metabolites in rat urine were HPOP, N-nitrosobis(2-hydroxypropyl)amine (BHP), and their glucuronic acid conjugates. The conjugates accounted for 30 and 9%, while free HPOP and BHP accounted for 42 and 16% of the total metabolites, respectively. Hamster urine, on the other hand, contained free HPOP, BHP, their glucuronic acid conjugates, and a sulfate ester of HPOP not found in rat urine. Six h following administration of HPOP, hamster urine contained BHP, BHP glucuronide, HPOP, HPOP glucuronide, and HPOP sulfate ester at levels of 35, 9, 16, 9, and 14%, respectively. These data suggest that hamsters reduce HPOP to BHP more efficiently than rats, while rats are more effective in forming their glucuronic acid conjugates. Hamsters differ significantly from rats in their capacity to form and excrete the sulfate ester of HPOP.

摘要

给大鼠和仓鼠单次给予剂量为N-[1-¹⁴C]亚硝基(2-羟丙基)(2-氧代丙基)胺(HPOP),并在不同时间间隔检查它们的尿液代谢产物。在这两个物种中,注射后6小时放射性标记代谢产物的尿排泄量达到平台期。此时,在大鼠和仓鼠尿液中分别发现总剂量的35%和28%。通过液相色谱分离,随后通过核磁共振、气相色谱-质谱和红外进行表征,结果表明大鼠尿液中的主要代谢产物是HPOP、N-亚硝基双(2-羟丙基)胺(BHP)及其葡萄糖醛酸结合物。结合物分别占总代谢产物的30%和9%,而游离的HPOP和BHP分别占总代谢产物的42%和16%。另一方面,仓鼠尿液中含有游离的HPOP、BHP、它们的葡萄糖醛酸结合物以及大鼠尿液中未发现的HPOP硫酸酯。给予HPOP 6小时后,仓鼠尿液中BHP、BHP葡萄糖醛酸苷、HPOP、HPOP葡萄糖醛酸苷和HPOP硫酸酯的含量分别为35%、9%、16%、9%和14%。这些数据表明,仓鼠将HPOP还原为BHP的效率比大鼠更高,而大鼠在形成其葡萄糖醛酸结合物方面更有效。仓鼠在形成和排泄HPOP硫酸酯的能力上与大鼠有显著差异。

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