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

Document Type : Original Article

Authors

1 Department of Pharmacology, School of Medicine, Mazandaran University of Medical Sciences (MAZUMS), Sari, Iran

2 Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA

3 Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran

4 Department of Biochemistry Biophysics and Genetics, School of Medicine, Mazandaran University of Medical Sciences (MAZUMS), Sari, Iran

5 Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

6 Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

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 (PPARγ) 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; PPARγ agonist, 1–20 mg/kg) alone or in combination. Amounts of PPARγ, COX-2, and prostaglandin E2 (PGE2) in paw tissue, and extents of TNF-α 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-α in serum which were elevated by carrageenan. Both drugs also increased both levels of PPARγ, GSH, GPx activity in paws, and serum levels of IL-10 that were decreased by carrageenan. Intraplantar injection of GW-9662 (IPL), a selective PPARγ antagonist, inhibited all biochemical modifications caused by both single and combined drug treatments.
Conclusion: CLX produced its anti-inflammatory effects probably through PPARγ 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.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 23, Issue 12
December 2020
Pages 1544-1550

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