Taylor A, King L J, Marks V
Department of Biochemistry, University of Surrey, Guildford, U.K.
Toxicology. 1987 Dec 14;47(3):339-50. doi: 10.1016/0300-483x(87)90063-1.
Sodium aurothiomalate was given to male Wistar rats (initial body weights: 150 g) by subcutaneous (s.c.) injection at doses of up to 7.5 mg/kg (corresponding to 4.27 mg gold/kg), twice a week, for 4-5 weeks. The concentrations of Ca, Mg, Fe, Cu and Zn were measured in serum, urine, faeces and in the liver, kidney, spleen, heart, lung, testis, bone and muscle. Kidney cytosol was separated by gel chromatography and the fractions analysed for protein, copper, zinc, iron and gold concentrations. The concentration of copper was increased 5-fold in kidney while smaller increases of zinc in kidney, copper in muscle, iron in muscle and testis and calcium in spleen were found. There was a significant reduction in the concentration of copper in serum. Kidney cytosol from gold-treated but not from control animals contained a low molecular weight protein which was associated with copper, zinc and gold. The rats developed proteinuria and microscopic changes to renal tubular cell structure were also observed. It is suggested that the gold-induced accumulation of copper may follow from an increased rate of synthesis of metallothionein and could be responsible for the renal dysfunction which develops in a proportion of rheumatoid arthritis patients who are treated with gold.
将硫代苹果酸金钠皮下注射给雄性Wistar大鼠(初始体重:150克),剂量高达7.5毫克/千克(相当于4.27毫克金/千克),每周两次,持续4至5周。测定血清、尿液、粪便以及肝脏、肾脏、脾脏、心脏、肺、睾丸、骨骼和肌肉中的钙、镁、铁、铜和锌浓度。通过凝胶色谱法分离肾脏胞质溶胶,并分析各部分的蛋白质、铜、锌、铁和金浓度。肾脏中的铜浓度增加了5倍,而肾脏中的锌、肌肉中的铜、肌肉和睾丸中的铁以及脾脏中的钙有较小幅度的增加。血清中的铜浓度显著降低。来自经金处理的动物而非对照动物的肾脏胞质溶胶含有一种与铜、锌和金相关的低分子量蛋白质。大鼠出现蛋白尿,还观察到肾小管细胞结构的微观变化。有人认为,金诱导的铜积累可能源于金属硫蛋白合成速率的增加,并且可能是导致一部分接受金治疗的类风湿性关节炎患者出现肾功能障碍的原因。