Reactivity of Hg(II) with superoxide: Evidence for the catalytic dismutation of superoxide by HG(II)

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 (O2-) and hydrogen peroxide (H2O2) production by rat kidney mitochondria, Hg(II) (1-6 microM), in the presence of antimycin A, caused a concentration-dependent increase (up to fivefold) in mitochondrial H2O2 production but an apparent decrease in mitochondrial O2- production. Hg(II) also inhibited O(2-)-dependent cytochrome c reduction (IC50 approximately 2-3 microM) when O2- was produced from xanthine oxidase. In contrast, Hg(I) did not react with O2- in either system, suggesting little involvement of Hg(I) in the apparent dismutation of O2- by Hg(II). Hg(II) also inhibited the reactions of KO2 (i.e., O2-) 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 O2- 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.

Dynamics of nonphotochemical superoxide production in the Great Barrier Reef lagoon

“…However HgCl 2 addition appeared to decrease MCLA CL to an even greater extent than SOD addition. This may be due to the fact that Hg II also reacts with O 2 2 (Miller et al 1991), and, given the relatively high molecular weight of SOD, HgCl 2 may be able to access compartments where O 2 2 is produced that are also accessible to MCLA but not to SOD (e.g., the periplasm of gram-negative bacteria or, depending on the cell permeability of MCLA, potentially even within the cytoplasm). In any case, the extent of truly extracellular O 2 2 production (i.e., production occurring outside the cell's outer membrane) will still be accurately determined by the microplate assay, since any reaction of MCLA with perisplasmic or cytoplasmic O 2 2 will not be inhibited by exogenous SOD.…”

The Hepatoprotective Effect of Gallic Acid on Mercuric Chloride-Induced Liver Damage in Rats

“…In fact, HgCl 2 enhances the formation of reactive oxygen species (ROS, including hydrogen peroxides, lipid peroxides, and highly reactive hydroxyl radicals) (5), which may cause cell membrane damage and cell destruction (6). HgCl 2 depletes protective antioxidants (eg, glutathione) and inhibits the activities of free radical scavenging systems, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (7)(8)(9).…”

Delayed DMSO Administration Protects the Kidney from Mercuric Chloride-Induced Injury

“…For example, HgCl 2 increases the production of many endogenous oxidants such as hydrogen peroxide (14), depletes protective antioxidants such as glutathione (GSH), and reduces free radical scavenging systems such as SOD and GSH peroxidase (GPx) (15). Indeed, HgCl 2 -induced injury can be ameliorated by SOD or the antioxidants NAc and melatonin in some (3,7,8) but not all (2) studies.…”