Free radical scavengers in mercuric chloride-induced acute renal failure in the rat.
Oxygen free radicals have recently been found to mediate cell injury after ischemia in the kidney. We sought to determine whether oxygen free radicals mediate damage in mercuric chloride (HgCl2)-induced acute renal failure, a toxic model of acute renal failure. Neither superoxide dismutase nor allopurinol, which scavenges or inhibits production of superoxide radical, respectively, provided protection against renal dysfunction after HgCl2. Similarly, the hydroxyl radical scavengers tryptophan, N-acetyl-tryptophan, and ascorbic acid were unable to protect against HgCl2. However, dimethylthiourea and dimethyl sulfoxide, both hydroxyl radical scavengers, were beneficial. Dimethylthiourea completely prevented the rise in plasma creatinine concentration after HgCL2. In control rats plasma creatinine concentration rose from 0.4 mg/dl to 3.2 +/- 0.8, 5.1 +/- 1.0, and 6.1 +/- 1.6 mg/dl at 24, 48, and 72 hours after HgCl2. Dimethylthiourea-treated rats had plasma creatinine concentration less than 0.5 mg/dl at all times. Furthermore, a mixture of HgCl2 and equimolar amounts of dimethylthiourea was less toxic than HgCl2 alone. Dimethyl sulfoxide attenuated the HgCl2-induced rise in creatinine concentration: 1.3 +/- 0.2, 3.2 +/- 0.3, and 3.1 +/- 0.2 mg/dl at 24, 48, and 72 hours after HgCl2. Measurement of kidney malondialdehyde content after HgCl2 provided no evidence for oxygen free radical-mediated lipid peroxidation. We conclude that there is no convincing role for oxygen free radicals in the pathogenesis of HgCl2-induced acute renal failure. The ability of dimethylthiourea and dimethyl sulfoxide to protect against HgCl2-induced renal dysfunction may be related to their ability to form complexes with Hg2+.
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004347:Drug Interactions; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology
D008054:Lipid Peroxides; D008627:Mercuric Chloride; D000493:Allopurinol; D014364:Tryptophan; C038983:1,3-dimethylthiourea; D003404:Creatinine; D013482:Superoxide Dismutase; D013890:Thiourea; D001205:Ascorbic Acid; D004121:Dimethyl Sulfoxide