Effect of N-benzyl-D-glucamine dithiocarbamate on renal toxicity induced by cadmium-metallothionein in rats.
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.
Kojima
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Ono
H
H
Furukawa
A
A
Kiyozumi
M
M
D000596:Amino Acids / Q000652:urine; D000818:Animals; D001219:Aspartate Aminotransferases / Q000652:urine; D001646:Bile / Q000378:metabolism; D002104:Cadmium / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D002614:Chelating Agents / Q000627:therapeutic use*; D006029:Glycosuria / Q000517:prevention & control; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013859:Thiocarbamates / Q000627:therapeutic use*; D014018:Tissue Distribution
D000596:Amino Acids; D002614:Chelating Agents; D013859:Thiocarbamates; C004203:cadmium-binding protein; D002104:Cadmium; D013012:Sorbitol; D008668:Metallothionein; D001219:Aspartate Aminotransferases; C048763:N-benzylglucamine dithiocarbamate