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Abstract: Strain difference in the accumulation of cadmium (Cd) by liver slices was examined in inbred Cd-resistant Wistar-Imamichi (WI) and Cd-sensitive Fischer 344 (F344) rats. The accumulation of Cd by liver slices of WI rats was significantly lower than that of F344 rats, suggesting strain-related differences in the transport of Cd into the liver cells of these two rat strains. In addition, a similar strain difference was observed in the accumulation of zinc (Zn) by liver slices from WI and F344 rats. Cd accumulation by F344 liver slices decreased when Zn was added to the medium in combination with Cd. Furthermore, in F344 liver slices, Zn accumulation was significantly decreased when Cd was added to the medium. These results suggest that the accumulation of Cd by the liver is probably mediated, at least in part, by Zn transport systems. However, we found no strain difference in hepatic ZnT3 or ZIP3 transcript levels between WI and F344 rats. Further work is in progress to identify the transporter that causes the strain differences in hepatic Cd accumulation seen with WI and F344 rats. [Copyright &y& Elsevier]

We previously reported that Wistar–Imamichi (WI) rats have a strong resistance to cadmium (Cd)-induced lethality compared to other strains such as Fischer 344 (Fischer) rats. The present study was designed to establish biochemical and histological differences in Cd toxicity in WI and Fischer rats, and to clarify the mechanistic basis of these strain differences. A single Cd (4.5 mg/kg, s.c.) treatment caused a significant increase in serum alanine aminotransferase activity, indicative of hepatotoxicity, in Fischer rats, but did not in WI rats. This difference in hepatotoxic response to Cd was supported by pathological analysis. After treatment with Cd at doses of 3.0, 3.5 and 4.5 mg/kg, the hepatic and renal accumulation of Cd was significantly lower in the WI rats than in the Fischer rats, indicating a kinetic mechanism for the observed strain differences in Cd toxicity. Thus, the remarkable resistance to Cd-induced hepatotoxicity in WI rats is associated, at least in part, with a lower tissue accumulation of the metal. Hepatic and renal zinc (Zn) contents after administration were similarly lower in WI than in Fischer rats. When Zn was administered in combination with Cd to Fischer rats, it decreased Cd contents in the liver and kidney, and exhibited a significant protective effect against the toxicity of Cd. We propose the possibility that Zn transporter plays an important role in the strain difference of Cd toxicity in WI and Fischer rats. [Copyright &y& Elsevier]