Mercury-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria.
Mercuric ion (Hg(II)) causes oxidative tissue damage in kidney cortical cells. We studied the in vitro effects of Hg(II) on hydrogen peroxide (H2O2) production by rat kidney mitochondria, a principal intracellular target of Hg(II). In mitochondria supplemented with a respiratory chain substrate (succinate or malate/glutamate) and an electron transport inhibitor (antimycin A (AA) or rotenone), Hg(II) (30 nmol/mg protein) increased H2O2 formation approximately 4-fold at the ubiquinone-cytochrome b region (AA-inhibited) and 2-fold at the NADH dehydrogenase region (rotenone-inhibited). Concomitantly, Hg(II) increased iron-dependent lipid peroxidation 3.5-fold at the NADH dehydrogenase region, but only by 25% at the ubiquinone-cytochrome b region. The mitochondrial concentration of reduced glutathione (GSH) decreased both with incubation time and Hg(II) concentration. Hg(II), at a concentration of 12 nmol/mg protein, caused almost complete depletion of measurable GSH in substrate-supplemented mitochondria after a 30-min incubation. In electron transport-inhibited mitochondria, Hg(II) caused greater depletion of GSH in rotenone-inhibited than in AA-inhibited mitochondria, consistent with the effects of Hg(II) on lipid peroxidation. These results suggest that Hg(II) at low concentrations depletes mitochondrial GSH and enhances H2O2 formation in kidney mitochondria under conditions of impaired respiratory chain electron transport. The increased H2O2 formation by Hg(II) may lead to oxidative tissue damage, such as lipid peroxidation, observed in mercury-induced nephrotoxicity.
Lund
B O
BO
Department of Environmental Health, University of Washington, Seattle 98195.
Miller
D M
DM
Woods
J S
JS
D000818:Animals; D004579:Electron Transport; D005978:Glutathione / Q000032:analysis; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains
D008627:Mercuric Chloride; D006861:Hydrogen Peroxide; D005978:Glutathione