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) wasexamined after iv administration of various dosages to mice.The lowest dosage of Cd-MT that produced renal injury was 0.2mg Cd/kg. This dosage of Cd-MT resulted in 10 µ Cd/g inthe kidneys 24 hr after administration. A time-course experimentutilizing a higher (0.3 mg Cd/kg) nephrotoxic dose of Cd-MTdemonstrated that the renal Cd concentration at 4 and 12 hrwas much higher than the critical concentration, but thereafterdecreased to about 10 Mg Cd/g wet tissue by 24 hr. Thus, Cdin excess of 10 Mg/g appears to damage the kidney and then distributesto other tissues and/or is excreted into urine. When a totalof 0.3, 0.4, and 0.8 mg of Cd/kg as Cd-MT was administered individed dosages over 4 days, as much as 30 Mg Cd/g was detectedin the kidney but no renal injury was observed. Thus, the criticalconcentration for producing renal injury after acute administrationof Cd-MT is estimated to be approximately 10 Mg Cd/g wet weight.However, with repeated exposure to Cd-MT, this acute criticalconcentration can be exceeded without producing renal injury,as tolerance to the nephrotoxic effects of Cd-MT develops.