Effect of Dithiothreitol on Mercuric Chloride - and Uranyl Nitrate-Induced Acute Renal Failure in the Rat.

摘要

Effect of dithiothreitol on mercuric chloride and uranyl nitrate induced acute renal failure in the rat. The current study was undertaken to examine the effects of dithiothreitol (DTT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat, Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone, and HgCl2 plus DTT. UN injected alone produced azotemia, decreased creatinine clearance, and rising fractional sodium excretion over the 48 hr of study. These effects of UN on renal function were not observed when DTT was administered 30 min after UN injection. Qualitatively similar results were obtained with HgCl2 induced acute renal failure, Groups of rats were killed at 6 hr after UN alone. Treatment with DTT did not alter the renal accumulation of 203 Hg, suggesting that this agent does not act by limiting renal exposure to the heavy metals. Thus, DTT ameliorates the course of heavy metal-induced ARF, and this effect is associated with prevention of heavy metal-induced alterations in sodium excretion and reninangiotensin system activity.