Protective effects of chelating agents against renal toxicity of gold sodium thiomalate in rats

Abstract

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.

Principles and Recent Developments in Chelation Treatment of Metal Intoxication

“…Experimental animal studies have demonstrated that DMSA and DMPS are efficient antidotes against acute gold intoxication and efficiently reduce the toxicity of ip-administered sodium bis(thiosulfato)gold(I) 194 or the nephrotoxicity of injected sodium thiomalate . In these and other studies, − MSA, DMPS, and DPA significantly enhanced the excretion of gold after injection of gold compounds to rats or mice.…”

“…195 In these and other studies, [196][197][198][199] MSA, DMPS, and DPA significantly enhanced the excretion of gold after injection of gold compounds to rats or mice.…”

Chelators as Antidotes of Metal Toxicity: Therapeutic and Experimental Aspects

“…It has also been successfully used for elemental, inorganic and organic mercury, arsenic, antimony, and copper chelation in humans [136,138,[149][150][151][152]. In animal experiments, meso-DMSA was an efficient chelator for gold [153][154][155][156] and nickel [104,105]. Controversial results were obtained for cadmium [73,75,157,158], thallium [136,159], and platinum, either for tissue platinum reduction, or for platinum nephrotoxicity [160][161][162][163].…”