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The current study was undertaken to examine the effects of dithiothreitol (DDT), 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 plus DTT, HgCl2 alone, or HgCl2 plus DTT; and determinations of plasma renin activity (PRA) and renin activities of the superficial and deep juxtaglomerular apparatus (JGA) were performed. PRA's and JGA renins were increased in animals receiving either UN or HgCl2 alone, but not in the rats receiving both DTT and UN or HgCl2. The effect of DTT on distribution of 203Hg was also examined. Treatment with DTT did not alter the renal accumulation of 203Hg, 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 renin-angiotensin system activity.
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
September 1983,
Toxicology and applied pharmacology,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
February 1983,
Nihon Hinyokika Gakkai zasshi. The japanese journal of urology,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
January 1980,
Virchows Archiv. B, Cell pathology including molecular pathology,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
April 1991,
Nihon Jinzo Gakkai shi,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
December 1974,
Kidney international,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
May 1973,
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.),
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
January 1986,
Nephron,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
January 1980,
New York state journal of medicine,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
January 1979,
Acta physiologica Academiae Scientiarum Hungaricae,
J G Kleinman, and
J S McNeil, and
J H Schwartz, and
R J Hamburger, and
W Flamenbaum
April 1985,
The Journal of laboratory and clinical medicine,
