Treatment with cromolyn sodium at early reperfusion but not before ischemia attenuates intestinal ischemia/reperfusion induced lung injury in mice

Abstract

Mast cell degranulation plays a key role in small intestinal ischemia/reperfusion (IIR)-induced lung injury. Studies showed that administration of mast cell stabilizers both before ischemia and at reperfusion can dramatically attenuate IIR injury. However, the relative effectiveness of mast cell inhibition before ischemia or during reperfusion on IIR-induced lung injury has yet to be determined. Cromolyn Sodium (mast cell stabilizer, 25mg/kg i.v.) was administrated either for 15 min before inducing small intestinal ischemia in mice by occluding the superior mesenteric artery for 30 min, or for 15 min upon reperfusion. Small IIR resulted in significant intestinal injury manifested as increased Chiu's scores with concomitant lung injury evidenced as elevations in lung injury scores, lung wet/dry weight ratio and increases in lung tissue tryptase and mast cell protease 7 protein expressions in lung in 3 hours after reperfusion, accompanied with decreased survival rates at 3 day after reperfusion (all P<0.05, vs. Sham control). All these changes were significantly alleviated in mice treated with Cromolyn Sodium on reperfusion (P<0.05, vs. IIR untreated) but not in mice pre-treated with Cromolyn Sodium. The results indicate mast cell inhibition at early reperfusion is an effective therapeutic approach in attenuating intestinal IR mediated remote organ injury.