The effect of FR167653 on pulmonary ischemia-reperfusion injury in rats

Background: A novel synthesized organic compound, FR167653, has been charac terized as a potent suppressant of interleukin-1 and tumor necrosis factor- alpha. We designed this experimental study to evaluate the effect of FR1676 53 on ischemia-reperfusion injury of the rat lung. Methods: Following general anesthesia, the left bronchus, pulmonary artery and vein were clamped for 1 hour. FR167653 was administered continuously be ginning 30 minutes before the onset of ischemia and extending for 2 hours a fter reperfusion. Thirty-eight Wistar rats were divided into 4 groups accor ding to the dose of FR167653 at the rate of 0.1, 0.05 and 0.025 mg/kg/hr in each group. After the optimal dose was obtained from the result of 1-week survival rate, the group with the optimal dose was compared with a control group by using such parameters as arterial oxygen saturation (SaO(2)), arte rial oxygen tension (PaO2), cytokines, the expression of p38 MAP kinase and histologic study. esults: Survival rate of the group received FR at the rate of 0.1 mg/kg/hr (FR0.1 group) was best among the 4 groups. SaO(2) levels and PaO2 levels af ter 2-hour of reperfusion were significantly (p < 0.05, respectively) highe r in the FR0.1 group than in the control group, After 2-hour reperfusion, I L-1 beta was lower in the FRO,1 group than in the control group, and the ex pression of p38 MAP kinase was reduced in the FR0.1 group compared with the control group. In histologic study after 2-hour of reperfusion, alveolar d amage with edema and interstitial thickening localized along the alveolar d uct were observed in the control group, whereas these findings were remarka bly less evident in the FR0.1 group. Conclusions: We conclude that FR167653 ameliorates ischemia-reperfusion inj ury of the lung and may inhibit the production of proinflammatory cytokines by means of the inhibition of p38 MAP kinase.