Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, protects against gastric ischemia-reperfusion damage in rats: role of oxygen free radicals generation.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a nuclear hormone receptor super family that has recently been implicated in atherosclerosis, inflammation, cancer, infertility, and demyelination. Oxidative stress, neutrophil infiltration, proinflammatory cytokines, and the exhibition of luminal acid play a role in the pathogenesis of gastric injury induced by ischemia-reperfusion. Rosiglitazone, a specific PPAR-gamma ligand, has been shown to have antiinflammatory activity, but its effects on experimental ischemia-reperfusion gastric injury remain unknown. We have investigated the effects of the rosiglitazone on gastric injury caused by ischemia following reperfusion in rats. Tumour necrosis factor-alpha (TNF-alpha) levels and changes in enzymatic activities of myeloperoxidase, as a marker of neutrophils infiltration, xanthine oxidase, superoxide dismutase, and glutathione peroxidase, were determined. Histological analysis of the lesions was also carried out. Pretreatment with 1 or 4 mg/kg of rosiglitazone ameliorated the gastric damage induced by clamping the celiac artery for 30 min followed by 60 min of reperfusion. It significantly (P<0.05) reduced the index of neutrophil infiltration and the levels of the cytokine. Rosiglitazone did not revert the reduced glutathione peroxidase activity but enhanced significantly (P<0.01) the decreased xanthine oxidase and superoxide dismutase activities in gastric mucosa of ischemic rats. In conclusion, rosiglitazone reduces the damage in ischemia-reperfusion gastric injury and alleviates the inflammatory response and the oxidative events.
Villegas
Isabel
I
Department of Pharmacology, Faculty of Pharmacy, University of Sevilla, Professor García González Street, 41012 Seville, Spain.
Martín
Antonio Ramón
AR
Toma
Walber
W
de la Lastra
Catalina Alarcón
CA
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists*; D009195:Peroxidase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D000077154:Rosiglitazone; D013270:Stomach / Q000098:blood supply / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014969:Xanthine Oxidase / Q000378:metabolism
D008565:Membrane Proteins; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D009195:Peroxidase; D005979:Glutathione Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase