EFFECTS OF ZINC, SELENIUM, AND CALCIUM ON THE NEPHROTOXICITY OF CADMIUM IN PRIMARY CULTURES OF RAT RENAL PROXIMAL EPITHELIAL-CELLS

The influence of essential metals, like zinc, selenium, and calcium, on the nephrotoxicity of cadmium was studied in primary cultures of rat proximal tubular cells. Damage to kidney cells was assessed by measuring the release of lactate dehydrogenase (LDH), gamma-glutamyltranspeptidase (GTP), and beta-N-acetylglucosaminidase (NAG) from cells into the medium and the cellular concentration of protein. Incubation with 200 muM cadmium in the presence of equivalent molar or lower concentrations of zinc and selenium showed greater release of LDH and NAG than cadmium alone, indicating an enhanced effect. However, metallothionein (MT) induced by pretreatment with a nontoxic concentration of zinc decreased significantly the release of enzyme from cells and elevated cellular protein levels in response to MT levels. MT provided partial protection against the nephrotoxicity of cadmium. Decreased calcium levels in the incubation medium also resulted in markedly increased release of LDH and NAG from cells exposed to cadmium and reduced cellular protein levels. These findings suggest that variations in zinc and calcium intake may affect the development of cadmium-induced renal dysfunction.