Superoxide dismutase: a cellular protective enzyme in bowel ischemia.
Recent data suggest that the free-radical anion superoxide (O-2), an unstable, cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel injury. This study evaluates the role of superoxide dismutase (SOD), an enzyme specific for enzymatic conversion of O-2 in protecting the bowel from an ischemic insult. At laparotomy, the superior mesenteric artery was occluded for 1 min in 90-g weanling rats (n = 144). Animals were divided into four groups: I, untreated controls (n = 41); II, received aminophylline (AMN) 40 mg/kg ip, a substrate for (O-2) generation (n = 21); III, received superoxide dismutase (SOD) 2.5 mg/kg iv (n = 20); IV, received both AMN and SOD (n = 22). Rats were evaluated for bowel infarction, perforation, and mortality over a 7-day observation period. In 40 additional rats (10 per group) bowel ultrastructure was evaluated by scanning electron microscopy (EM) during occlusive ischemia and at various time intervals following reperfusion. Mortality was 63.4% in controls (26/41) with necrosis noted in 19 and perforation in 7. AMN resulted in a 90% mortality (19/21) (chi 2, P less than 0.05 vs control), with necrosis in 15 and perforation in 4. SOD reduced mortality to 25% (5/20) with necrosis in 4 and perforation in 1 (chi 2, P less than 0.02 vs controls) and, when added to AMN, 45.5% (10/22) (chi 2, P less than 0.01 vs AMN alone). On EM, tissue damage was minimal during occlusive ischemia, worsened by duration of reperfusion, enhanced by AMN, and reduced by SOD. These data suggest that following hypoxia, the injured bowel may be unable to appropriately handle reoxygenation. Tissue damage was related to duration of reperfusion and was worse following AMN, a xanthine derivative that might generate (O-2), a cytotoxic free radical. SOD detoxifies O2-, increases survival, and protects the bowel during reperfusion.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000382:microbiology; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000201:enzymology* / Q000401:mortality; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000502:physiology*
D000628:Aminophylline; D013482:Superoxide Dismutase