Experiments were conducted to determine if administration of the sulfhydryl
reducing agent and
metal chelator dithiothreitol (31 mg/kg body wt) alters the development of renal dysfunction in the first 3 hr after injection of
mercuric chloride (3 mg/kg).
Mercuric chloride alone resulted in elevation of urine flow rate and fractional excretion of solutes within 30 min of injection. In animals injected with
dithiothreitol 60 min after
mercuric chloride, urine flow rate and fractional excretion of solutes were reduced within 30 min to values intermediate between control and
mercuric chloride-treated rats. Neither the injection of
mercuric chloride alone nor when followed by
dithiothreitol resulted in changes in mean arterial blood pressure or glomerular filtration rate. In addition,
dithiothreitol did not reduce urine flow rate or fractional excretion of solutes when these parameters were elevated during extracellular fluid volume expansion. Measurement of
mercury in organs of those rats injected with
mercuric chloride alone or prior to
dithiothreitol revealed no alteration in organ distribution. The renal cortex contained the highest concentrations of
mercury, and these concentrations were comparable in both groups of rats. These studies demonstrate that
dithiothreitol can ameliorate the renal toxicity of
mercury and suggest that this effect is mediated through an intrarenal site of action.