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 < 0.001) and monocyte H2O2 production (P < 0.05). A dose response relationship was observed for both leukocytes, as the 100-mu-M drug concentration was significantly (P < 0.05) more effective than the 10-mu-M 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.