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 <0.5 mg/dl at all times. Furthermore, a mixture of HgCl₂ and equimolar amounts of dimethylthiouria 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⁺.