A novel selectin blocker alleviates oxidative stress of lung reperfusion injury

Background. The importance of reactive oxygen species released through inte raction of leukocyte/ endothelial cell in ischemia-reperfusion injury of th e lung is not yet fully understood. A novel selectin blocker, OJ-R9188, whi ch inhibits the interaction, may alleviate oxidative stress and pulmonary d ysfunction after warm ischemia-reperfusion. Materials and methods. Rat lungs were reperfused at 37 degreesC for 60 min with an ex vivo model and were divided into three groups (n = 10). In the f resh group, lungs were reperfused immediately after harvest. In the OJ-R (- ) and OJ-R (+) groups, lungs were reperfused after warm ischemia at 37 degr eesC for 90 min. In the OJ-R (+) group, rats received 100 mug per body of O JR9188 intravenously 10 min before the harvest. The electron spin resonance method was used to assess the direct scavenging activity of OJ-R9188. Results. Both shunt fractions and wet/dry weight ratios of the lung tissue after reperfusion in the OJ-R (+) group were significantly lower than those in the OJ-R (-) group. Oxidative DNA damage in the alveolar wall of the OJ -R (+) group, assessed by immunohistochemical quantitation of 8-hydroxy-2 ' -deoxyguanosine, was significantly lower than that of the OJ-R (-) group. Immunostaining of 3-nitro-L-tyrosine, which represents nitric oxide-mediate d oxidative damage, was also more intense in the OJ-R (-) group than in the OJ-R (+) group. Direct scavenging activity of OJ-R9188 was not ob-served, and the number of leukocytes infiltrated to the lung tissue as seen by myel operoxidase activity was not different between the OJ-R (-) and OJ-R (+) gr oups. Conclusions. A novel selectin blocker, OJ-R9188, improves pulmonary functio n after warm ischemia-reperfusion and alleviates reperfusion-induced oxidat ive alveolar damage. (C) 2001 Academic Press.