Human red cells scavenge extracellular hydrogen peroxide and inhibit formation of hypochlorous acid and hydroxyl radical.

Abstract

The ability of intact human red cells to scavenge extracellularly generated H202 and Oj, and to prevent formation of hydroxyl radicals and hypochlorous acid has been examined. Red cells inhibited oxidation of ferrocytochrome c by H202. Cells treated with aminotriazole no longer inhibited, indicating that protection was almost entirely due to intracellular catalase. Contribution by the GSH system was slight, and apparent only with low H202 concentrations when catalase was inhibited by aminotriazole. The cells were about a quarter as efficient at inhibiting cytochrome c oxidation as an equivalent concentration of purified catalase. No inhibition of 0--dependent reduction of ferricytochrome c or nitroblue tetrazolium was observed, although extracted red cell superoxide dismutase inhibited nitroblue tetrazolium reduction at one fortieth the concentration of that in the cells. Red cells efficiently inhibited deoxyribose oxidation by hydroxyl radicals generated from

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

“…Speculation that pegloticase therapy may increase H 2 O 2 to toxic levels (25) implies a greater rate of production than elimination. Before clinical testing we considered this possibility unlikely for these reasons: (i) because of PEGylation, infused pegloticase would be restricted to plasma (20); (ii) H 2 O 2 freely crosses cell membranes; and (iii) erythrocytes are known to have a prodigious capacity to decompose H 2 O 2 generated within the vascular compartment (26,27). We estimate that erythrocytes can eliminate H 2 O 2 2-3 orders of magnitude faster than it can be produced by pegloticase therapy (Table 1).…”

“…† The rate at which intact human erythrocytes scavenge extracellularly generated H 2 O 2 is based on a previous study (27), and assumes a hematocrit of 40. Effect of urate plus pegloticase on Prx2 in reconstituted blood.…”

Cerebral Oxidative Stress and Mitochondrial Dysfunction in Oxonate-Induced Hyperuricemic Mice

“…In erythrocytes, catalase is supposed to be a more predominant H 2 O 2 -removing enzyme than GPx [22][23][24] and to have an important role in the disposal of exogenous H 2 O 2 , particularly in brain, heart and skeletal muscle. 2,3) Therefore, it is likely that catalase inhibition and the resulting elevation of extracellular H 2 O 2 level by increased blood uric acid cause oxidative stress in the tissues of those patients with hyperuricemia or gout. It was reported that there was an influence regarding catalase deficiency to mental retardation in WAGR syndrome and to H 2 O 2 -caused oxidative stress.…”

“…2) Intact erythrocytes are capable of protecting other cells or tissues against several injuries by extracellular H 2 O 2 . 3,4) Since H 2 O 2 readily diffuses through membranes, erythrocyte catalase is regarded as a primary enzyme for the removal of extracellular H 2 O 2 . 4,5) Therefore erythrocyte catalase may pro-reduction of erythrocyte catalase activity and the resulting increase in H 2 O 2 levels would cause cerebral disorders in patients with hyperuricemia or gout.…”

Impact of erythrocytes on mouse embryonal development in vitro

“…Predominantly, because of amphlpathic nature of H 2 0 2 , this reactive species occurring extracellularly is readily transferred across membranellipid bilayers and degraded intracellular by various cells, such as erythrocytes [12]. To elUCIdate the pathogenesis of 2-cell block, effects of SOD, catalase and erythrocytes on fertilized oocytes and embryos were studied in vitro.…”