INTESTINAL ISCHEMIA AND REPERFUSION INJURY IN TRANSGENIC MICE OVEREXPRESSING COPPER-ZINC SUPEROXIDE-DISMUTASE

Superoxide dismutase (SOD) scavenges oxygen radicals that are implicat ed in the pathogenesis of intestinal ischemia-reperfusion injury. The effect of intestinal ischemia and reperfusion was investigated in tran sgenic mice overexpressing human Cu-Zn SOD. Ischemia was induced by oc cluding the superior mesenteric artery. Myeloperoxidase activity was d etermined as an index of neutrophil infiltration, and malondialdehyde levels were measured as an indicator of lipid peroxidation. Forty-five minutes of intestinal ischemia followed by 4 h of reperfusion caused an increase in intestinal levels of malondialdehyde in both nontransge nic and transgenic mice, but the concentration of malondialdehyde was significantly greater in nontransgenic mice. Intestinal ischemia-reper fusion also caused an increase in intestinal and pulmonary myeloperoxi dase activity in nontransgenic and transgenic mice, but the transgenic mice had significantly lower levels of myeloperoxidase activity than nontransgenic mice. Transgenic mice had higher levels of intestinal SO D activity than nontransgenic mice. There were no significant differen ces in the catalase or glutathione peroxidase activities. In conclusio n, our study demonstrates that the overexpression of SOD protects tiss ues from neutrophil infiltration and lipid peroxidation during intesti nal ischemia-reperfusion.