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Keywords:

  • Mercury;
  • Mercuric Ion;
  • Superoxide;
  • Dismutation;
  • Hydrogen Peroxide;
  • Oxidative;
  • Kidney;
  • Renal;
  • Mitochondria;
  • Nephrotoxicity

Abstract

Mercuric ion, a well-known nephrotoxin, promotes oxidative tissue damage to kidney cells. One principal toxic action of Hg(II) is the disruption of mitochondrial functions, although the exact significance of this effect with regard to Hg(II) toxicity is poorly understood. In studies of the effects of Hg(II) on superoxide (Omath image) and hydrogen peroxide (H2O2) production by rat kidney mitochondria, Hg(II) (1–6 μM), in the presence of antimycin A, caused a concentration-dependent increase (up to fivefold) in mitochondrial H2O2 production but an apparent decrease in mitochondrial Omath image production. Hg(II) also inhibited Omath image-dependent cytochrome c reduction (IC50 ≈2–3 μM) when Omath image was produced from xanthine oxidase. In contrast, Hg(I) did not react with Omath image in either system, suggesting little involvement of Hg(I) in the apparent dismutation of Omath image by Hg(II). Hg(II) also inhibited the reactions of KO2 (i.e., Omath image) with hemin or horseradish peroxidase dissolved in dimethyl sulfoxide (DMSO). Finally, a combination of Hg(II) and KO2 in DMSO resulted in a stable UV absorbance spectrum [currently assigned Hg(II)-peroxide] distinct from either Hg(II) or KO2. These results suggest that Hg(II), despite possessing little redox activity, enhances the rate of Omath image dismutation, leading to increased production of H2O2 by renal mitochondria. This property of Hg(II) may contribute to the oxidative tissue-damaging properties of mercury compounds.