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螯合剂对大鼠体内无机汞排泄影响的进一步研究。

Further study of effects of chelating agents on excretion of inorganic mercury in rats.

作者信息

Shimada H, Fukudome S, Kiyozumi M, Funakoshi T, Adachi T, Yasutake A, Kojima S

机构信息

Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.

出版信息

Toxicology. 1993 Jan 29;77(1-2):157-69. doi: 10.1016/0300-483x(93)90146-j.

Abstract

The effects of three chelating agents, N-benzyl-D-glucamine dithiocarbamate (BGD), 2,3-dimercaptopropanol (BAL) and D-penicillamine (D-PEN), on the excretion of mercury in rats exposed to mercuric chloride (HgCl2), the chemical forms of mercury compounds excreted in the bile and urine and the intestinal reabsorption of mercury compounds in the bile were studied. Rats were injected intraperitoneally with 203HgCl2 (300 micrograms Hg and 74 kBq of 203Hg/kg) and 24 h later, they were injected intraperitoneally with a chelating agent (a quarter of an LD50). The injection of the chelating agents significantly enhanced the biliary and urinary excretions of mercury. The enhancing effect of BGD on the excretions of mercury was almost the same as that of BAL and much larger than that of D-PEN. The major chemical form of mercury in the bile and urine of rats injected with BGD after HgCl2 treatment was Hg-BGD compounds. The chemical form of mercury in the bile and urine of rats injected with BAL after HgCl2 treatment was mainly Hg-GSH compound. The mercury after HgCl2 and D-PEN treatment was excreted mainly via the urine in the form of Hg-D-PEN compound. The intestinal reabsorption of mercury from the bile of rats injected with BGD or D-PEN was only 0.18% or 0.38% of the dose, respectively. The intestinal reabsorption of mercury from the bile of rats injected with BAL was 27.38% of the dose. It was suggested that the Hg-GSH compound excreted in the bile after HgCl2 and BAL treatment is partly degraded to Hg-cysteine (Cys) by the intestinal membranous enzymes and that the ligand of Hg-Cys is replaced by BAL in the bile, resulting in the effective reabsorption of Hg-BAL compound from the intestine.

摘要

研究了三种螯合剂,即N-苄基-D-葡糖胺二硫代甲酸盐(BGD)、2,3-二巯基丙醇(BAL)和D-青霉胺(D-PEN),对暴露于氯化汞(HgCl₂)的大鼠体内汞排泄、胆汁和尿液中排泄的汞化合物的化学形式以及胆汁中汞化合物的肠道重吸收的影响。大鼠腹腔注射²⁰³HgCl₂(300微克汞和74千贝克勒尔的²⁰³Hg/千克),24小时后,腹腔注射一种螯合剂(LD₅₀的四分之一)。螯合剂的注射显著增强了汞的胆汁和尿液排泄。BGD对汞排泄的增强作用与BAL几乎相同,且远大于D-PEN。HgCl₂处理后注射BGD的大鼠胆汁和尿液中汞的主要化学形式是Hg-BGD化合物。HgCl₂处理后注射BAL的大鼠胆汁和尿液中汞的化学形式主要是Hg-GSH化合物。HgCl₂和D-PEN处理后的汞主要以Hg-D-PEN化合物的形式经尿液排泄。注射BGD或D-PEN的大鼠胆汁中汞的肠道重吸收分别仅为剂量的0.18%或0.38%。注射BAL的大鼠胆汁中汞的肠道重吸收为剂量的27.38%。有人提出,HgCl₂和BAL处理后胆汁中排泄的Hg-GSH化合物部分被肠膜酶降解为Hg-半胱氨酸(Cys),且胆汁中Hg-Cys的配体被BAL取代,导致Hg-BAL化合物从肠道有效重吸收。

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