Zinc-induced protection against cadmium-metallothionein nephrotoxicity depends on glutathione status

The mechanism by which zinc (Zn) protects against the acute nephrotoxicity of cadmium-metallothionein (CdMT) is unknown. Since Zn offers protection even in metallothionein-null (MT-null) mice, we investigated the role of glutathione (GSH) in Zn-induced protection. Pretreatment of mice with a high dose of Zn, which elevated renal cortex, GSH levels protected against CdMT nephrotoxicity. Elevation of renal GSH was not essential for Zn-induced protection since a lower dose of Zn, which did not affect renal cortex GSH level, was also protective. Normal GSH levels, however, were required for the Zn-induced protection as inhibition of GSH synthesis by buthionine sulfoximine (BSO) in Zn-pretreated mice completely abolished the beneficial effect of Zn. Pretreatment with Zn reduced the accumulation of Cd in the renal cortex and this appears to be the mechanism by which Zn may exert its protective action. These results suggest that although Zn protects against CdMT nephrotoxicity apparently by decreasing Cd accumulation in the renal cortex, maintenance of normal GSH status is essential for Zn to he effective.