Houshmand Gholamreza, Naghizadeh Bahareh, Ghorbanzadeh Behnam, Ghafouri Zahra, Goudarzi Mehdi, Mansouri Mohammad Taghi
Department of Pharmacology, School of Medicine, Mazandaran University of Medical Sciences (MAZUMS), Sari, Iran.
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Iran J Basic Med Sci. 2020 Dec;23(12):1544-1550. doi: 10.22038/ijbms.2020.43995.10315.
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.
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.
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.
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.
塞来昔布（CLX）是一种选择性环氧化酶 - II（COX - 2）抑制剂，已被用于治疗多种炎症性疾病。本研究旨在探讨过氧化物酶体增殖物激活受体 - γ（PPARγ）在CLX诱导的大鼠抗炎反应中的作用。
角叉菜胶诱导的爪肿胀用作急性炎症模型。大鼠单独或联合接受不同腹腔内（IP）剂量的CLX（0.3 - 30 mg/kg）和吡格列酮（PGL；PPARγ激动剂，1 - 20 mg/kg）治疗。测量爪组织中PPARγ、COX - 2和前列腺素E2（PGE2）的含量，以及血清中TNF - α和IL - 10的水平。此外，还测定了皮质、海马和爪组织中氧化应激参数如丙二醛（MDA）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPx）活性的水平。
CLX和PGL单独或联合腹腔内剂量依赖性给药均可减轻角叉菜胶诱导的爪肿胀。此外，两种药物单独或联合使用均可降低炎症爪中COX - 2、PGE2和MDA的含量，以及角叉菜胶升高的血清中TNF - α的水平。两种药物还均可提高爪中PPARγ、GSH、GPx活性的水平以及角叉菜胶降低的血清中IL - 10的水平。足底注射选择性PPARγ拮抗剂GW - 9662（IPL）可抑制单药和联合用药治疗引起的所有生化改变。
CLX可能通过激活PPARγ受体产生抗炎作用。此外，CLX与PGL联合使用时抗炎作用增强，提示它们的联合应用可能适用于炎症的临床治疗，尤其是糖尿病患者。
