Comparison of Renal Toxicity after Long-Term Oral Administration of Cadmium Chloride and Cadmium-Metallothionein in Rats

Abstract

Comparison of Renal Toxicity after Long-Term Oral Administration of Cadmium Chloride and Cadmium-Metallothionein in Rats. Groten, J. P., Koeman, J. H., van Nesselrooij, J. H. J., Luten, J. B., Fentener van Vlissingen, J. M., Stenhuis, W. S., and van Bladeren, P. J. (1994). Fundam. Appl. Toxicol. 23, 544-552. There is a clear lack of information on the toxicological risk of dietary intake of cadmium-metallothionein (CdMt). The present study aimed at establishing dose-dependent cadmium (Cd) disposition and to investigate differences in renal toxicity after long-term dietary exposure to CdMt or cadmium chloride (CdCl 2) in rats. Male Wistar rats were fed diets containing 0.3, 3, 30, or 90 mg Cd/kg either as CdMt or as CdCl 2 for 10 months. In rats fed 30 and 90 mg/kg Cd as CdCl 2 the Cd concentrations in intestine, liver, and kidneys were all higher than in rats fed the same doses in the form of CdMt. The kidney/liver Cd concentration ratio was higher with CdMt than with CdCl 2. At the lower Cd concentrations (0.3 and 3 mg/kg), no differences in Cd accumulation between CdMt and CdCl 2 groups were observed and the kidney/liver Cd ratio was also similar. When based on the amount of CdMt per milligram Cd in the tissue, rats fed CdMt and those fed CdCl 2 had a similar relative CdMt concentration in liver and kidney. First signs of renal injury, indicated by an increase of urinary lactate dehydrogenase (LDH) activity, were seen 4 months after exposure to 90 mg/kg Cd as CdCl 2. After 8 and 10 months the renal effect of 90 mg/kg Cd as CdCl 2 became more pronounced and urinary enzyme activities of LDH, N -acetyl-β- d-glucosaminidase and alkaline phosphatase were all elevated. The only clinical effect of CdMt at the dose level of 90 mg/kg was a slight increase in urinary γ-glutamyl transpeptidase activity at 8 and 10 months. Histopathological changes (e.g., glomerulonephrosis and basophilic tubules) were observed after 10 months of exposure in rats fed 30 and 90 mg/kg Cd as CdCl 2. Rats fed 90 mg/kg as CdMt also showed slight histomorphological changes, but the effect was less pronounced than that of CdCl 2 and was mainly restricted to the tubules. In conclusion, no difference was observed in renal disposition between CdMt and CdCl 2 after long-term exposure to low (≤3 mg/kg) dietary doses. Nephrotoxicity was mainly related to the total renal Cd concentration and, in contrast to Cd administered intravenously, not to a difference in sensitivity between CdMt and CdCl 2. Therefore, the health risk of dietary intake of Cd at low doses does not seem to differ between CdMt and CdCl 2.