Several studies have shown that peroxisome proliferator-activated receptor- (PPAR) agonists protect against ischemia/re-perfusion (I/R) damage in different organs. This study was carried out to assess the possible role of PPAR on intestinal I/R-mediated tissue injury. This was achieved by evaluating the effects of the PPAR agonist rosiglitazone and the PPAR antagonist bisphenol A diglycidyl ether (BADGE) on experimentally-induced intestinal I/R. The possible underlying mechanisms,

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... changes in the release of NO and/or inflammatory cytokines (such as tumor necrosis factor-alpha, TNF), infiltration of neutrophils, and apoptotic cell death were investigated. Rats were divided into sham-operated and I/R groups. The I/R group was further divided into sub-groups, and these rats were treated 30 min before induction of ischemia with rosiglitazone, BADGE, or a combination of BADGE + rosiglitazone; control rats received vehicle in place of the drugs. Intestinal I/R was then induced in each rat by occlusion of the superior mesenteric artery (SMA) for 45 min via non-traumatic clamp, followed by re-perfusion for 120 min before the rats were euthanized and intestinal tissues recovered for analyses. Rats in the control I/R group showed a significant increase in intestinal malondialdehyde (MDA), NO, and TNF contents, as well as increases in myeloperoxidase (MPO) enzyme activity, diffuse histological damage, and strong levels of Fas staining. Pre-treatment of rats with rosiglitazone resulted in a significant reduction in the intestinal MDA, NO, and TNF contents and MPO enzyme activity associated with I/R; these rats also evidenced only mild histological damage and Fas staining. The protective effects of rosiglitazone were completely abolished by BADGE administration. Therefore, based on the results of this study, we conclude that the PPAR system plays an important role in intestinal I/R injury. We also note that free radicals (including NO), neutrophil infiltration, as well as select cytokines, are important mediators in I/R injuries.