Kojima S, Ono H, Furukawa A, Kiyozumi M
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Arch Toxicol. 1990;64(2):91-6. doi: 10.1007/BF01974392.
The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity induced by acute exposure to cadmium-metallothionein (Cd-MT) in rats was studied. Rats were injected intraperitoneally with BGD (400 mumol/kg) 6, 12, or 24 h after intraperitoneal injection of Cd-MT (1.78 mumol Cd as Cd-MT/kg) and thereafter they received three injections of BGD (400 mumol/kg) daily for 3 days. Urinary protein concentration and aspartate aminotransferase (AST) activity significantly increased 1 day after Cd-MT treatment and decreased to control levels at 9 days after the treatment. Urinary excretion of glucose and amino acids rose gradually reaching maximum levels 5 days after Cd-MT treatment and returned to the control levels at 9 days. BGD injection significantly reduced the increases in the urinary excretion of protein, AST, glucose and amino acid, which were produced by Cd-MT treatment. Significant increases in urine volume were observed after Cd-MT treatment. BGD injection inhibited the increase in urine volume caused by Cd-MT treatment. A long time interval (12 and 24 h) between the administrations of Cd-MT and BGD resulted in a decreased protective effect of BGD against Cd-MT-induced renal damage. Following Cd-MT injection, the major route of excretion of cadmium (Cd) was via the urine and the kidney was the major site of accumulation of Cd. BGD injection remarkably increased the urinary excretion of Cd, resulting in a significant reduction in the kidney Cd concentration. The results of this study indicate that BGD injection is effective in decreasing the Cd concentration in the kidney, resulting in the protective effect on Cd-MT-induced renal damage.
研究了N-苄基-D-葡糖胺二硫代甲酸盐(BGD)对大鼠急性暴露于镉-金属硫蛋白(Cd-MT)所致肾毒性的影响。大鼠腹腔注射Cd-MT(1.78 μmol镉,以Cd-MT计,每千克体重)后6、12或24小时,腹腔注射BGD(400 μmol/kg),此后每天注射3次BGD(400 μmol/kg),共3天。Cd-MT处理后1天,尿蛋白浓度和天冬氨酸转氨酶(AST)活性显著升高,处理后9天降至对照水平。Cd-MT处理后,尿中葡萄糖和氨基酸排泄量逐渐上升,在处理后5天达到最高水平,9天恢复到对照水平。注射BGD显著降低了Cd-MT处理所致尿蛋白、AST、葡萄糖和氨基酸排泄量的增加。Cd-MT处理后尿量显著增加。注射BGD抑制了Cd-MT处理所致的尿量增加。Cd-MT和BGD给药之间的长时间间隔(12和24小时)导致BGD对Cd-MT诱导的肾损伤的保护作用降低。注射Cd-MT后,镉(Cd)的主要排泄途径是通过尿液,肾脏是Cd积累的主要部位。注射BGD显著增加了尿Cd排泄量,导致肾脏Cd浓度显著降低。本研究结果表明,注射BGD可有效降低肾脏中Cd浓度,对Cd-MT诱导的肾损伤具有保护作用。