Delayed nephrotoxic effects of cadmium and their reversibility by chelation.

A single injection of CdCl2 (15 mumol/kg) together with 300 mumol/kg mercaptoethanol into adult male rats induced renal dysfunction only after a delay of at least 12 h; in contrast, the peak value of cadmium in renal cortex (34 +/- 3 micrograms/g) was reached within 2 h. The chelator methoxybenzylglucaminedithioate (MBGDT) rapidly reduced the renal Cd level by 2/3, primarily by extracting the metal from the sedimentable rather than the cytosolic fraction. MBGDT prevented the subsequent onset of malfunction, but only when given at an early stage after Cd administration (2 h). It follows that the renal damage seen after the initiation period is independent of the Cd concentration at that time. The changes occurring during initiation remain unexplained.