Celecoxib inhibits acute edema and inflammatory biomarkers through peroxisome proliferator-activated receptor-γ in rats

Objective(s): Celecoxib (CLX), a selective cyclooxygenase-II (COX-2) inhibitor, has been used for management of several inflammatory disorders. The present study aimed to explore the role of peroxisome proliferator-activated receptor-gamma (PPAR gamma) in CLX induced anti-inflammatory response in rats. Materials and Methods: Carrageenan-induced paw edema was used as an acute inflammation model. Rats were treated with various intra-peritoneal (IP) doses of CLX (0.3-30 mg/kg) and pioglitazone (PGL; PPAR gamma agonist, 1-20 mg/kg) alone or in combination. Amounts of PPAR gamma, COX-2, and prostaglandin E2 (PGE2) in paw tissue, and extents of TNF-alpha and IL-10 in serum were measured. Moreover, levels of oxidative stress parameters as malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) activity in the cortex, hippocampus, and paw tissues were also determined. Results: CLX and PGL dose-dependent administration (IP), alone or in combination reduced carrageenan-induced paw edema. Further, both agents, alone or in combination, reduced either the amounts of COX-2, PGE2, and MDA in the inflamed paw, and the levels of TNF-alpha in serum which were elevated by carrageenan. Both drugs also increased both levels of PPAR gamma, GSH, GPx activity in paws, and serum levels of IL-10 that were decreased by carrageenan. Intraplantar injection of GW-9662 (IPL), a selective PPAR gamma antagonist, inhibited all biochemical modifications caused by both single and combined drug treatments. Conclusion: CLX produced its anti-inflammatory effects probably through PPAR gamma receptor activation. Besides, increased anti-inflammatory effects of CLX with PGL suggest that their combination might be applied for the clinical management of inflammation especially in patients suffering from diabetes.