Effects of tempol, a membrane-permeable radical scavenger, on local and remote organ injuries caused by intestinal ischemia/reperfusion in rats.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Teke
Zafer
Z
Department of General Surgery, Pamukkale University, School of Medicine, Denizli, Turkey. zteke_md@yahoo.com
Kabay
Burhan
B
Ozden
Akin
A
Yenisey
Cigdem
C
Bir
Ferda
F
Demirkan
Nese Calli
NC
Bicakci
Tuncay
T
Erdem
Ergun
E
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000517:prevention & control; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017538:Mesenteric Artery, Superior; D008641:Mesenteric Vascular Occlusion / Q000150:complications / Q000188:drug therapy; D009504:Neutrophils / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013113:Spin Labels
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D013113:Spin Labels; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione; C001803:tempol