Inhibition of stimulated human leukocyte hydrogen peroxide generation by a novel antioxidant, OPC-14117.
Oxygen free radicals generated by leukocytes may contribute to tissue injury after central nervous system (CNS) focal ischemia or trauma. Inhibiting oxygen free radicals has improved outcome in experimental models of these conditions and antioxidant therapy appears promising. We evaluated the ability of a novel antioxidant, OPC-14117, to reduce hydrogen peroxide (H2O2) production by stimulated human polymorphonuclear (PMN) leukocytes and monocytes. Stimulated PMN and monocytes were incubated with several concentrations of OPC-14117 for 20 min and H2O2 production, nmol/1 x 10(6) cells/30 min, was measured. OPC-14117 significantly reduced PMN H2O2 production (P less than 0.001) and monocyte H2O2 production (P less than 0.05). A dose response relationship was observed for both leukocytes, as the 100 microM drug concentration was significantly (P less than 0.05) more effective than the 10 microM concentration. These results demonstrate that OPC-14117 inhibits H2O2 generation by stimulated human leukocytes and support further studies of its effects in disorders such as CNS focal ischemia and trauma, conditions where antioxidant therapy may be beneficial.
Fisher
M
M
Department of Neurology and Medicine, University of Massachusetts Medical School, Worcester 01605.
Arpano
M M
MM
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007189:Indans / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D016897:Respiratory Burst / Q000187:drug effects*
D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D007189:Indans; D010879:Piperazines; C074852:OPC 14117; D006861:Hydrogen Peroxide