Ebselen decreases ozone-induced pulmonary inflammation in rats

We studied the effects of ebselen on rat lung inflammatory responses agains t ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) si gnificantly decreased pulmonary inflammation as indicated by the albumin co ncentration and the number of neutrophils in the bronchoalveolar lavage flu id 18 h after the ozone exposure. Although treatment with ebselen did not a lter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-ind uced pulmonary inflammation. Treatment with ebselen also enhanced the pulmo nary expression of both copper, zinc, and manganous superoxide dismutases a t the same time point. These enzymes may also contribute to a decrease in t he formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain a cute lung injuries by modulating the oxidant-related inflammatory process.