Inhibition of hypochlorous acid-induced oxidative reactions by nitrite: is nitrite an antioxidant?
Acute and chronic inflammation result in increased nitrogen monoxide (z.rad;NO) formation and the accumulation of nitrite (NO(2)(-)). Neutrophils stimulated by various inflammatory mediators release myeloperoxidase to produce the cytotoxic agent hypochlorous acid (HOCl). At physiologically attainable concentrations, we found that NO(2)(-) significantly inhibits HOCl-mediated DNA strand breakage and ascorbate depletion. HOCl-mediated inactivation of pure alpha(1)-antiproteinase or of the elastase inhibitory capacity of human plasma was inhibited by the addition of NO(2)(-). NO(2)(-) was more effective than ascorbate, GSH, and urate at inhibiting HOCl-mediated toxicity to human HepG2 cells in culture. These data suggest that NO(2)(-) may act in an antioxidant manner by removing HOCl at sites of inflammation where both HOCl and z.rad;NO are overproduced.
Whiteman
Matthew
M
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore. bchwml@nus.edu.sg
Rose
Peter
P
Halliwell
Barry
B
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000097:blood / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009566:Nitrates / Q000494:pharmacology; D009573:Nitrites / Q000494:pharmacology*; D016877:Oxidants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000097:blood; D014407:Tumor Cells, Cultured; D014527:Uric Acid / Q000097:blood / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; D016877:Oxidants; D013438:Sulfhydryl Compounds; D000515:alpha 1-Antitrypsin; D014527:Uric Acid; D006997:Hypochlorous Acid; D005978:Glutathione; D001205:Ascorbic Acid