Comparative effects of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats.
The effects of various chelating agents, such as (2S)-1-(3-mercaptopropionyl)-L-proline (captopril), N-(2-mercaptopropionyl)-glycine (tiopronin), L-cysteine (L-Cys), D-cysteine (D-Cys), N-acetyl-L-cysteine (L-NAC), N-benzyl-D-glucamine dithiocarbamate (BGD), and ethylenediaminetetraacetate (EDTA), on the distribution, excretion, and renal toxicity of gold sodium thiomalate (AuTM) in rats were investigated. Rats were intraperitoneally injected with the chelating agents (1.2 mmol/kg each) immediately after intravenous injection of AuTM (0.026 mmol/kg). Treatment with captopril or tiopronin significantly prevented increases in the urinary excretion of protein, aspartate aminotransferase (AST), and glucose and the blood urea nitrogen (BUN) level after AuTM injection. L-NAC and D-Cys significantly prevented increases in the urinary excretion of protein, AST, and glucose after AuTM injection, but did not reduce to control levels. Treatment with BGD, EDTA, or L-Cys did not prevent AuTM-induced increases in the urinary excretion of protein, AST, and glucose and BUN level. Tiopronin significantly increased the urinary excretion of gold. Captopril slightly promoted both the urinary and fecal excretion of gold, resulting in the significant increase in the total excretion of the metal. Tiopronin and captopril significantly decreased the gold concentration in the kidney and liver. L-Cys, D-Cys, L-NAC, BGD, and EDTA had no significant effect on the excretion or distribution of gold at 7 days after AuTM injection. These results indicate that tiopronin and captopril can ameliorate the renal toxicity induced by AuTM. In addition, the comparative effects of 2,3-dimercaptopropane sulfonate (DMPS), N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), captopril, and tiopronin at various dose levels (1.2, 0.4 or 0.2 mmol/kg) on the distribution and renal toxicity of gold were studied. DMPS was effective in removing gold from the kidney and in protecting against the renal toxicity after AuTM injection at the even lower dose level (0.2 mmol/kg). Bucillamine and tiopronin protected against the renal toxicity of gold at dose levels of 0.4 and 1.2 mmol/kg and captopril ameliorated the gold toxicity only at higher dose level (1.2 mmol/kg).
NTT Kyushu General Hospital, Kumamoto, Japan.
Y
Y
Takahashi
T
T
Funakoshi
H
H
Shimada
S
S
Kojima
D000818:Animals; D001219:Aspartate Aminotransferases / Q000652:urine; D001806:Blood Urea Nitrogen; D002614:Chelating Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006029:Glycosuria / Q000139:chemically induced; D006052:Gold Sodium Thiomalate / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D002614:Chelating Agents; D006052:Gold Sodium Thiomalate; D001219:Aspartate Aminotransferases