Amelioration of mercuric chloride-induced acute renal failure by dithiothreitol.
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.
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D004229:Dithiothreitol / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury / Q000378:metabolism; D008630:Mercury Poisoning / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014018:Tissue Distribution
D008627:Mercuric Chloride; D008628:Mercury; D004229:Dithiothreitol