Species differences in the renal toxicity of the antiarthritic drug, gold sodium thiomalate.
Two gold compounds, gold sodium thiomalate (AuTM) and auranofin, are presently in clinical use in therapy of rheumatoid arthritis. In these studies, AuTM administered to Sprague-Dawley rats and three strains of mice, Swiss-Webster, C3H/HeJ, and DBA/2J, were studied with regard to its effect on liver and renal monooxygenases, metallothionein contents, and serum levels of alanine aminotransferase and urea nitrogen. These effects of AuTM were compared to those of cadmium, since the latter metal has exhibited tissue and species differences in the induction of metallothionein. Benzo(a)pyrene hydroxylase and benzphetamine N-demethylase activities were not altered by AuTM in livers of rats and the three strains of mice. Benzo(a)pyrene hydroxylase activity was significantly decreased in rat kidney, whereas this enzyme activity was not affected in the kidneys of mice. In rats, AuTM caused a sevenfold induction in liver metallothionein, while in mice, liver metallothionein was induced twofold in Swiss-Webster mice and about fivefold in the inbred strains. AuTM caused minimal changes in renal metallothionein contents in the three strains of mice studied. Serum alanine amino-transferase, an indicator of hepatotoxicity, was not altered by AuTM in rats and mice studied. Blood urea nitrogen, an indicator of kidney dysfunction, was increased threefold in rats, but not in AuTM-treated mice. These data demonstrate that AuTM, a nephrotoxic agent in rats and humans, showed no nephrotoxic effects in the mouse strains studied here.
Cheriathundam
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Department of Pharmacology, Uniformed Services University, School of Medicine, Bethesda, MD 20814-4799, USA.
Alvares
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AP
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006052:Gold Sodium Thiomalate / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D013045:Species Specificity
D018501:Antirheumatic Agents; D002104:Cadmium; D006052:Gold Sodium Thiomalate; D003577:Cytochrome P-450 Enzyme System; D008668:Metallothionein; D001579:Benzopyrene Hydroxylase; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D000410:Alanine Transaminase