EFFECT OF THE HISTAMINE H-2-RECEPTOR ANTAGONIST (+ L]METHYL]THIO]ETHYL]-2''-(METHYLSULFONYL)GUANIDINE ON ACUTE GASTRIC-MUCOSAL INJURY IN RATS AND ITS FREE-RADICAL SCAVENGING ACTIVITIES/

The protective effect of T-593 ylamino)methyl-2-furyl]methyl]thio]ethy l]-2<double prime>-(methylsulfonyl)guanidine, CAS 140695-21-2), a new histamine H-2-receptor antagonist, was investigated in rats with acute gastric mucosal injury. An ischemic injury followed by reperfusion wa s produced by applying a small vascular clamp to the celiac artery for 30 min and then removing it for 60 min. T-593 significantly reduced t he area of the lesion in the stomach in a dose-dependent manner, and d oses of 0.3 and 3.0 mg/kg inhibited the increase of lipid peroxides in the gastric mucosa after ischemia-reperfusion. A spin-trapping method using 5,5-dimethyl-1-pyrroline-N-oxide showed that T-593 scavenged hy droxyl radicals generated by the hydrogen peroxide-ferrous iron sulfat e system. T-593 also significantly inhibited the increase of lipid per oxides induced by free-radical initiators in gastric mucosal homogenat es. Thus, the protective effect of T-593 against acute gastric mucosal injury induced by ischemia and followed by reperfusion may result, in part, from its antioxidant properties.