Gholamreza Houshmand1, Bahareh Naghizadeh2, Behnam Ghorbanzadeh3, Zahra Ghafouri4, Mehdi Goudarzi5,6, Mohammad Taghi Mansouri2,6. 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
OBJECTIVES: 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.
OBJECTIVES: 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.
Entities:
Keywords:
Carrageenan; Celecoxib; Cytokines; Oxidative stress; PPAR-γ; Pioglitazone; Rat
Authors: Shailesh P Dudhgaonkar; Surendra K Tandan; Abdul Shakoor Bhat; Sachin H Jadhav; Dinesh Kumar Journal: Life Sci Date: 2005-08-16 Impact factor: 5.037