Dexamethasone prevents acute cadmium-induced hepatic injury but exacerbates kidney dysfunction in rabbits

Cadmium is a potent hepatotoxicant for which neither effective preventive m ethods nor the mechanism of toxicity has been established. We investigated the preventive effect of dexamethasone against cadmium toxicity on cadmium- induced liver injury in rabbits. Pretreatment with dexamethasone at 1 mg/kg increased the rate of survival in rabbits administered 2.5 mg/kg iv cadmiu m. Cadmium induced acute severe liver injury characterized by hepatocellula r necrosis, infiltration by inflammatory cells, and increases of plasma GOT , GPT, LDH, and LDH5. Dexamethasone mitigated the acute hepatotoxic effect of cadmium, but exacerbated cadmium-induced kidney dysfunction, with destru ction of renal tubular cells and increases in excretion of protein, glucose , and amino acids into urine. The cadmium concentration in liver and kidney of rabbits administered cadmium was not changed by dexamethasone pretreatm ent. Although metallothionein mRNA expression. induced by cadmium was not a ffected by dexamethasone in liver or kidney, cadmium-induced metallothionei n protein production was augmented at the early phase in liver and decrease d at the later phase in kidney. Neutrophilia observed after cadmium adminis tration was enhanced initially by dexamethasone pretreatment. These results indicate that dexamethasone pretreatment potently prevented cadmium-induce d liver injury, but exacerbated renal tubular dysfunction. (C) 2001 Academi c Press.