Effects of Tempol, a Membrane-Permeable Radical Scavenger, on Local and Remote Organ Injuries Caused by Intestinal Ischemia/Reperfusion in Rats

Abstract

Tempol is a stable piperidine nitroxide of low molecular weight that permeates biological membranes and scavenges superoxide anions in vitro. In a variety of animal models, deleterious effects of reperfusion injury on both local and remote organs have been demonstrated. In this study, we aimed to investigate the effects of a membrane-permeable radical scavenger, Tempol, on local and remote organ injuries caused by intestinal ischemia/reperfusion (I/R) in rats. Male Wistar-albino rats were randomized into three groups: (I) Sham-operated control group, laparotomy without I/R injury (n = 12); (II) Intestinal I/R group, 60 min of ischemia by superior mesenteric artery occlusion followed by 2-h of reperfusion (n = 12); and (III) I/R + Tempol-treated group, identical to I/R group except for Tempol administration, 30 mg/kg bolus injection 5 min before reperfusion, followed by an infusion of 30 mg/kg/h intravenously (n = 12). Histopathologically, intestinal mucosal lesions were assessed by Chiu's classification, and pulmonary parenchymal damage was appraised by pulmonary neutrophil infiltration and acute lung injury scaling. Biochemically, myeloperoxidase activity, malondialdehyde, glutathione, and nitrite/nitrate (NO(x)) levels were determined in both intestinal mucosa and lung parenchyma. Evans blue dye concentration and organ wet/dry weight ratios were used as a marker of organ edema. Animal survival was observed up to 1 week. Intestinal mucosal lesions and pulmonary parenchymal damage were significantly attenuated with Tempol treatment, histopathologically (P < 0.05). Tempol administration significantly reduced myeloperoxidase activity and malondialdehyde levels, and also significantly increased glutathione and NO(x) levels of both intestinal and lung tissues, biochemically (P < 0.05). Evans blue dye extravasation and wet/dry weight ratios of organs were significantly reduced with Tempol injection (P < 0.05). The survival rates of rats in Tempol-treated group were significantly higher than that of I/R-treated group (P < 0.05). The present study suggests that Tempol administration significantly reduces both local and remote organ injuries caused by intestinal I/R before and throughout the reperfusion period. Further clinical studies are needed to clarify whether Tempol may be a useful therapeutic agent to use in particular operations where the reperfusion injury occurs.