Interactions of human blood plasma with hydrogen peroxide and hypochlorous acid.
Activated neutrophils produce both hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Previous work has shown that HOCl depletes antioxidants, modifies proteins, and forms fatty acid chlorohydrins but does not cause significant lipid peroxidation in human plasma. Because activated phagocytes have been claimed to stimulate lipid peroxidation in plasma, we examined the effects of H2O2 and HOCl alone and in combination on plasma constituents. Hydrogen peroxide at concentrations below 0.5 mmol/L had little effect, but 1 to 2 mmol/L H2O2 caused loss of ascorbic acid and protein thiol groups, an effect potentiated by preincubation of the plasma with sodium azide to inhibit catalase. H2O2 caused no detectable lipid peroxidation or loss of alpha-tocopherol in plasma, but some depletion of ubiquinol occurred. The combination of HOCl and H2O2 caused more lipid peroxidation than either agent alone. Peroxidation was not inhibited by the metal chelators ethylenediaminetetraacetic acid and deferoxamine or by the singlet O2/hydroxyl radical scavenger histidine. We hypothesize that the phagocyte-derived H2O2 and HOCl could interact in the microenvironment of the activated leukocyte to induce lipid peroxidation of plasma lipoproteins or cell membranes (or both).
van der Vliet
A
A
Department of Pulmonary-Critical Care Medicine, University of California-Davis Medical Center, Sacramento 95817.
Hu
M L
ML
O'Neill
C A
CA
Cross
C E
CE
Halliwell
B
B
D000975:Antioxidants / Q000032:analysis; D004357:Drug Synergism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D050356:Lipid Metabolism; D010084:Oxidation-Reduction; D010949:Plasma / Q000187:drug effects*
D000975:Antioxidants; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide