Nephrotoxicity of Intravenously Injected Cadmium-Metallothionein: Critical Concentration and Tolerance
Nephrotoxicity of Intravenously Injected Cadmium-Metallothionein: Critical Concentration and Tolerance. MAITANI, T., CUPPAGE, F. E. AND KLAASSEN, C. D. (1988). Fundam. Appl Toxicol. 10, 98-108. The nephrotoxicity of Cd-metallothionein (Cd-MT) was examined after iv administration of various dosages t...
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Veröffentlicht in: | Toxicological sciences 1988-01, Vol.10 (1), p.98-108 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Nephrotoxicity of Intravenously Injected Cadmium-Metallothionein: Critical Concentration and Tolerance. MAITANI, T., CUPPAGE, F. E. AND KLAASSEN, C. D. (1988). Fundam. Appl Toxicol. 10, 98-108. The nephrotoxicity of Cd-metallothionein (Cd-MT) was examined after iv administration of various dosages to mice. The lowest dosage of Cd-MT that produced renal injury was 0.2 mg Cd/kg. This dosage of Cd-MT resulted in 10 μ Cd/g in the kidneys 24 hr after administration. A time-course experiment utilizing a higher (0.3 mg Cd/kg) nephrotoxic dose of Cd-MT demonstrated that the renal Cd concentration at 4 and 12 hr was much higher than the critical concentration, but thereafter decreased to about 10 Mg Cd/g wet tissue by 24 hr. Thus, Cd in excess of 10 Mg/g appears to damage the kidney and then distributes to other tissues and/or is excreted into urine. When a total of 0.3, 0.4, and 0.8 mg of Cd/kg as Cd-MT was administered in divided dosages over 4 days, as much as 30 Mg Cd/g was detected in the kidney but no renal injury was observed. Thus, the critical concentration for producing renal injury after acute administration of Cd-MT is estimated to be approximately 10 Mg Cd/g wet weight. However, with repeated exposure to Cd-MT, this acute critical concentration can be exceeded without producing renal injury, as tolerance to the nephrotoxic effects of Cd-MT develops. |
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ISSN: | 1096-6080 1096-0929 |
DOI: | 10.1093/toxsci/10.1.98 |