Cadmium: zinc binding to metallothionein (MT) and renal cell injury

The purpose of the present study is to investigate the role of Cd-Mt binding in the pathogenesis of Cd-induced renal cell injury. Experimental nephrotoxicity occurs over a range of Cd concentrations but the critical Cd concentration is unknown. The injected Cd daily (0.6 mg/Kg as CdCl/sub 2/, sc) for up to 8 wks in male rats. Animals were killed at 2 wk intervals; kidneys, livers, and 24-hr urine samples were obtained for Cd, Zn, and Cu analyses. Partitioning of Cd bound and not bound to Mt was determined in liver and kidney. Cd and Mt levels (..mu..mol/g) rose in both tissues through week 8 (Liver: Cd=3.01, Mt = 0.47; Kidney: Cd = 1.83, Mt = 0.22). Zn and Cu levels rose until wk 4-6 and then stabilized (Liver: Zn = 1.37, Cu = 0.19; Kidney = Zn = 0.49, Cu = 0.44). Excretion of Zn and Cu initially dropped but rose rapidly, as did Cd, by wk 8. The percent and total amount of Mt dedicated to binding Cd increased to nearly 80%. NMR nuclear magnetic resonance) studies by others have identified 3 of the 7 metal binding sites on a Mt molecule as preferential Zn sites. Initially, Zn occupiesmore » nearly all binding sites. With Cd exposure, a greater percentage of sites contain Cd. As Cd-binding exceeds 57%, Zn retention on Mt and other cellular ligands is reduced and Cd, Zn, and Cu increase in the urine. This study suggests that Cd and Zn binding to Mt are related and implicate impairment of Zn metabolism in the pathogenesis of Cd-induced renal cell injury.« less