Zinc protects renal function during cadmium intoxication in the rat

Abstract

This study investigates the effect in the rat of chronic CdCl₂intoxication (500 μg Cd²⁺/kg, daily ip injection for 5 days) on renal function and the changes in tight junction proteins claudin-2, claudin-3, and claudin-5 present in rat kidney. We also studied the effect of coadministration of ZnCl₂(500 μg Zn²⁺/kg) during chronic CdCl₂intoxication. Our results indicate that 1) most of the filtered Cd²⁺is reabsorbed within the kidney; 2) chronic Cd²⁺intoxication can induce a change in renal handling of ions without altering glomerular filtration rate; 3) a delayed nephropathy, showing Fanconi-like features, appears more than 5 days after the end of CdCl₂exposure; 4) epithelial integrity is altered by chronic Cd²⁺intoxication affecting the expression and localization of claudin tight junction proteins; and 5) cotreatment with Zn²⁺protects against the renal toxic effects of Cd²⁺, preventing altered claudin expression and inhibiting apoptosis. In conclusion, these results show that Cd²⁺toxicity and cellular toxic mechanisms are complex, probably affecting both membrane transporters and tight junction proteins. Finally, Zn²⁺supplementation may provide a basis for future treatments.