Effects of lecithinized superoxide dismutase and a neutrophil elastase inhibitor (ONO-5046) on hyperoxic lung injury in rat

Reactive oxygen and neutrophil metabolites have been implicated in the deve lopment of hyperoxic lung injury. We determined the protective effects of e ither a superoxide dismutase or neutrophil elastase inhibitor and the combi nation of both agents on the development of hyperoxic lung injury in rats. Two drugs (lecithinized superoxide dismutase and ONO-5046) were used in the present study. Lecithinized superoxide dismutase, a lecithin derivative bo und to recombinant CuZn superoxide dismutase, has a higher affinity for cel ls such as polymorphonuclear leukocytes and endothelial cells than recombin ant human superoxide dismutase. N-[2-[4-2,2-dimethylpropionyloxy) phenylsul fonylamino] benzoyl]} aminoacetic acid (ONO-5046), a specific neutrophil el astase inhibitor, which was developed as a low-molecular weight inhibitor, showed protective effects against various lung injuries. Rats were exposed to over 90% oxygen for 72 h, and bronchoalveolar lavage was performed to ev aluate the permeability and neutrophil accumulation in the lungs. Rats were treated with lecithinized superoxide dismutase (30,000 U/day, intravenousl y n = 7) or ONO-5046 (10 mg/kg, intramuscularly twice a day, n = 7) or a co mbination of both drugs (n = 7). Albumin concentration and neutrophil count s in bronchoalveolar lavage fluid were compared between animals with and wi thout drug treatment. Either lecithinized superoxide dismutase or ONO-5046 treatment significantly decreased albumin concentration and neutrophil coun ts in bronchoalveolar lavage fluid compared to those in the animals of the hyperoxia-alone group (n = 9). However, albumin leakage and neutrophil accu mulation in the rat lung treated with combined agents were identical to tha t of either the lecithinized superoxide dismutase or ONO-5046 treatment. Th ese findings suggest that lecithinized superoxide dismutase and ONO-5046 ar e useful drugs to protect against hyperoxic lung injury in rats. However, t here were no additive effects by the combination in preventing hyperoxic lu ng injury. (C) 2000 Elsevier Science B.V. All rights reserved.