Effect of peroxisome proliferator- activated receptor-gamma [PPAR-Y] ligands on gastric mucosal injury induced by ischemia/reperfusion in rats

ABSTRACT

Peroxisome proliferator-activated receptor-gamma [PPAR-y] has recently been implicated as regulator of cellular proliferation and inflammatory responses. The aim of the present study was to investigate the effects of two PPAR-y agonists [rosiglitazone and pioglitazone] on ischemia-reperfusion [I/R]- induced gastric mucosal injury in rats, one and 24 h after reperfusion. Methods: Gastric ischemia was induced for 30 min by applying a small vascular clamp to the celiac artery and reperfusion was produced by removal of the clamp in male albino rats. The drugs and vehicle were given orally, 2 h before the vascular clamping. The results showed that I/R elevated the mucosal levels of lipid peroxide [LPX], lactate dehydrogenase [LDH] and tumor necrosis factor-alpha [TNF-alpha] and myeloperoxidase [MPO] activity in the gastric mucosa. On the other hand, I/R decreased the mucosal levels of reduced glutathione [GSH] and superoxide dismutase [SOD]. These biochemical changes were accompanied by an increase in the formation of gastric lesions, which was reduced by either rosiglitazone or pioglitazone. Both drugs tended to normalize the estimated biochemical changes one and 24h after reperfusion. The results indicate that both rosiglitazone and pioglitazone possess a gastroprotective effect against mucosal injury induced by I/R in rats, which could be attributed to their antioxidant effects and their anti-inflammatory properties