PROTECTIVE EFFECT OF A 21-AMINOSTEROID AGAINST HEMORRHAGE-INDUCED ISCHEMIA-REPERFUSION INJURY IN THE RAT STOMACH - ROLE OF LIPID-PEROXIDATION

We investigated the role that lipid peroxidation plays in a hemorrhage -induced ischemia-reperfusion model of gastric injury. Rats were pretr eated with an inhibitor of this process, a 21-aminosteroid (U-74389G, 10 mg/kg), or an appropriate control solution intravenously 15 min pri or to 20 min of ischemia, followed by 20 min of reperfusion. Results i ndicated that U-74389G pretreatment significantly attenuated gastric d amage compared with corresponding control animals (19.8 vs. 176.8 mm(2 ), p < .001). Enaldehyde revels (picomoles/mg protein), a biochemical index of lipid peroxidation, paralleled these injury findings (12 vs. 960, p < .001). Histologically, U-74389G pretreatment almost completel y prevented gastric injury compared to control stomachs. Additional st udies revealed that lipid peroxidation preceded the formation of gastr ic damage, and injury occurred predominantly during reperfusion, becau se animals subjected to ischemia alone without reperfusion failed to d evelop appreciable injury or enhanced enaldehyde formation. Further, i f U-74389G was given intravenously after ischemia, but prior to reperf usion, gastric injury and enaldehyde formation were similarly attenuat ed. Our findings are consistent with the hypothesis that lipid peroxid ation likely plays an important role in hemorrhage-induced ischemia-re perfusion injury to the stomach.