Intestinal ischemia and reperfusion injury in transgenic mice overexpressing copper-zinc superoxide dismutase.
Superoxide dismutase (SOD) scavenges oxygen radicals that are implicated in the pathogenesis of intestinal ischemia-reperfusion injury. The effect of intestinal ischemia and reperfusion was investigated in transgenic mice overexpressing human Cu-Zn SOD. Ischemia was induced by occluding the superior mesenteric artery. Myeloperoxidase activity was determined 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 nontransgenic and transgenic mice, but the concentration of malondialdehyde was significantly greater in nontransgenic mice. Intestinal ischemia-reperfusion also caused an increase in intestinal and pulmonary myeloperoxidase 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 SOD activity than nontransgenic mice. There were no significant differences in the catalase or glutathione peroxidase activities. In conclusion, our study demonstrates that the overexpression of SOD protects tissues from neutrophil infiltration and lipid peroxidation during intestinal ischemia-reperfusion.
Deshmukh
D R
DR
Department of Surgery, University of Medicine and Dentistry of New Jersey, New Brunswick 08903-0019, USA.
Mirochnitchenko
O
O
Ghole
V S
VS
Agnese
D
D
Shah
P C
PC
Reddell
M
M
Brolin
R E
RE
Inouye
M
M
D000818:Animals; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000201:enzymology / Q000401:mortality / Q000503:physiopathology*; D017538:Mesenteric Artery, Superior; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase