Protective effects of chelating agents against renal toxicity of gold sodium thiomalate in rats.
The protective effects of various chelating agents such as D-penicillamine (D-PEN), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane sulphonate (DMPS), and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), on the renal damage induced by gold sodium thiomalate (AuTM) in rats were studied. Rats were injected i.v. with AuTM at doses of 0.026, 0.066, 0.132, and 0.198 mmol/kg. Urinary excretion of protein, aspartate aminotransferase (AST), and glucose in rats injected with AuTM significantly increased compared to the control levels within 1 day after the injection and thereafter decreased nearly to the control levels at 3 or 7 days. Gold was excreted rapidly during the first day after AuTM injection and excreted gradually thereafter. The concentrations of gold in the kidney and liver at 1 or 7 days after AuTM administration were approximately dose dependent. Treatment with D-PEN, DMSA, DMPS, and bucillamine (1.2 mmol/kg) significantly prevented increases in the urinary excretion of protein, AST, and glucose and the BUN level after AuTM (0.026 mmol/kg) injection. The injection of the chelating agents after AuTM administration showed that D-PEN, DMSA, and DMPS enhanced mainly the urinary excretion of gold and that bucillamine enhanced mainly the fecal excretion of the metal. These chelating agents significantly decreased the gold concentrations in the kidney and liver. The findings suggest that the chelating agents tested can ameliorate the renal damage induced by AuTM.
Kojima
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Takahashi
Y
Y
Kiyozumi
M
M
Tagawa
Y
Y
D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D003545:Cysteine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006029:Glycosuria / Q000139:chemically induced / Q000517:prevention & control; D006052:Gold Sodium Thiomalate / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D010396:Penicillamine / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D004113:Succimer / Q000627:therapeutic use; D014494:Unithiol / Q000627:therapeutic use
D002614:Chelating Agents; D006052:Gold Sodium Thiomalate; D014494:Unithiol; D004113:Succimer; D010396:Penicillamine; D003545:Cysteine; C026535:bucillamine