The effects of sodium chromate and carbon tetrachloride on the urinary excretion and tissue distribution of cadmium in cadmium-pretreated rats

Abstract

Rats were administered nontoxic doses of Cd 2+ by the oral or intraperitoneal routes. They were subsequently treated with either Na 2CrO 4 (10 or 20 mg/kg, sc) or CCl 4 (0.5 or 1 ml/kg, intragastric). Evidence of renal damage was obtained from the determination in urine of total protein and amino acids and from the analysis of the urinary proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liver damage was evaluated by determining the serum activities of sorbitol dehydrogenase and glutamate pyruvate transaminase. The effects of CCl 4 on the urinary excretion and the tissue distribution of Cd 2+ vary depending on whether liver damage is associated or not with extensive renal lesions. When renal function was not or only moderately altered, induction of liver damage by CCl 4 resulted in a transfer of Cd 2+ from the liver to the kidney. This transfer was evidenced by a decrease of total Cd 2+ as well as metallothionein-bound Cd 2+ in the liver and an increase of the same parameters in the kidney. The urinary excretion of Cd 2+ was only slightly increased. When liver damage induced by CCl 4 was associated with extensive kidney lesions, the accumulation of Cd 2+ released from the liver in the kidney was considerably reduced and large amounts of Cd 2+ were excreted in urine. Administration of Na 2CrO 4 to Cd 2+-pretreated rats gave rise to a sharp and reversible increase in the urinary excretion of Cd 2+. This increase was proportional to the amount of Cd 2+ stored in kidney and to the dose of Na 2CrO 4 administered. The Cd 2+ excreted in urine originated mainly from the kidney in which total Cd 2+ and metallothionein-bound Cd 2+ were reduced in proportion to the dose of Na 2CrO 4 administered. These results suggest that two mechanisms may lead to an increased urinary excretion of Cd 2+; a direct release of Cd 2+ into urine from damaged kidney (i.e., Na 2CrO 4) or a decreased tubular reabsorption of plasma circulating Cd 2+ evidenced when large amounts of Cd 2+ are released into blood from damaged liver (i.e., CCl 4). These results tend to support the hypothesis that kidney damage due to chronic Cd 2+ poisoning may lead to an increased loss of the Cd 2+ stored in the kidney.