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[14C]2,3,7,8-四氯二苯并对二噁英(TCDD)在小鼠体内的代谢命运研究。

Studies on the metabolic fate of [14C]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the mouse.

作者信息

Koshakji R P, Harbison R D, Bush M T

出版信息

Toxicol Appl Pharmacol. 1984 Mar 30;73(1):69-77. doi: 10.1016/0041-008x(84)90054-1.

Abstract

Studies on the Metabolic Fate of [14C]2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in the Mouse. KOSHAKJI, R. P., HARBISON, R. D., and BUSH, M. T. (1984). Toxicol. Appl. Pharmacol. 73, 69-77. After a single po dose (135 micrograms/kg; 62 microCi/kg) of 14C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in male ICR/Ha Swiss mice, 67 to 76% of the administered dose was eliminated via the feces and 1 to 2% in the urine during the first 24 hr following treatment. It seems likely that most of this material was simply not absorbed. Much of the remaining chemical was then excreted slowly in the urine (2%) and feces (7%) during the next 10 days, partly as the unchanged compound and partly as metabolites. One of the metabolites (Fraction II) appears to be a single polar, acidic metabolite characterized in urine (0.4 +/- 0.1%) and feces (2.2 +/- 0.2%), and is also likely excreted as a glucuronide conjugate. The rest of the radioactivity was in the form of unchanged TCDD in the animal body (17 +/- 2%). Steady rates of decline in the concentrations of the 14C as well as of the unchanged TCDD were reached in the feces and urine after the fifth day following the administration of the chemical. Based on this steady rate, the half-life of the radioactivity in the body was approximately 20 days. Urine, feces, and whole body were analyzed by solvent extraction, 14C counting, thin-layer chromatography, and countercurrent distribution.

摘要

[14C]2,3,7,8-四氯二苯并-对-二恶英(TCDD)在小鼠体内的代谢命运研究。科沙克吉,R.P.,哈比森,R.D.,以及布什,M.T.(1984年)。《毒理学与应用药理学》73卷,69 - 77页。给雄性ICR/Ha瑞士小鼠单次经口给予剂量为135微克/千克(62微居里/千克)的14C标记的2,3,7,8-四氯二苯并-对-二恶英(TCDD)后,在给药后的头24小时内,67%至76%的给药剂量通过粪便排出,1%至2%通过尿液排出。看起来大部分这种物质根本没有被吸收。在接下来的10天里,剩余的大部分化学物质随后缓慢地通过尿液(2%)和粪便(7%)排出,部分以未变化的化合物形式,部分以代谢物形式。其中一种代谢物(组分II)似乎是一种单一的极性酸性代谢物。在尿液(0.4±0.1%)和粪便(2.2±0.2%)中被鉴定出来,并且也可能以葡糖醛酸缀合物的形式排出。其余的放射性以未变化的TCDD形式存在于动物体内(17±2%)。在给予该化学物质后的第五天之后,粪便和尿液中14C以及未变化的TCDD的浓度达到稳定的下降速率。基于这个稳定速率,体内放射性的半衰期约为20天。通过溶剂萃取、14C计数、薄层色谱法和逆流分配法对尿液、粪便和整个身体进行了分析。

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