Llobet J M, Domingo J L, Corbella J
Laboratory of Toxicology and Biochemistry, Faculty of Medicine, University of Barcelona, Spain.
Res Commun Chem Pathol Pharmacol. 1988 May;60(2):225-33.
Effects of repeated ip administration of glutathione, N-acetyl-L-cysteine (NAC), 2,3-dimercaptosuccinic acid (DMSA), ethylendiamine-tetraacetic acid (EDTA), and diethylentriamepentaacetic acid (DTPA) on the distribution and excretion of cobalt were assessed in Sprague-Dawley rats. Groups of ten animals received intraperitoneally 0.06 mmol CoCl2/kg/day, three days/week for four weeks. 24 hr after the last injection, daily chelation therapy was initiated. Rats received one of the chelators or saline for 5 days. The animals were housed in metabolic cages and urine and feces were collected daily for 5 days after which time the rats were killed and the concentration of cobalt was determined in various tissues. Glutathione, NAC and DTPA significantly increased the excretion of cobalt into urine whereas EDTA, NAC and DMSA were the most effective chelators increasing the fecal elimination of cobalt. The concentration of cobalt in the various tissues was only decreased by NAC (liver and spleen) and glutathione (spleen). The observed increase in the cobalt excretion with certain chelators would suggest that increasing the duration of chelation therapy may decrease the concentrations of cobalt in tissues and hence, reduce the toxicity of the metal.
在斯普拉格-道利大鼠中评估了腹腔内重复注射谷胱甘肽、N-乙酰-L-半胱氨酸（NAC）、2,3-二巯基琥珀酸（DMSA）、乙二胺四乙酸（EDTA）和二乙三胺五乙酸（DTPA）对钴分布和排泄的影响。每组十只动物腹腔注射0.06 mmol CoCl₂/kg/天，每周三天，共四周。最后一次注射后24小时，开始每日螯合疗法。大鼠接受其中一种螯合剂或生理盐水注射5天。动物饲养在代谢笼中，每天收集尿液和粪便，持续5天，之后处死大鼠并测定各种组织中的钴浓度。谷胱甘肽、NAC和DTPA显著增加了钴向尿液中的排泄，而EDTA、NAC和DMSA是增加钴粪便排泄的最有效螯合剂。只有NAC（肝脏和脾脏）和谷胱甘肽（脾脏）降低了各种组织中的钴浓度。观察到某些螯合剂使钴排泄增加，这表明延长螯合疗法的持续时间可能会降低组织中钴的浓度，从而降低金属的毒性。
