Haddadi Rasool, Cheraghi-Poor Mohammad
Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran.
Medicinal plant and natural products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Mar;397(3):1633-1646. doi: 10.1007/s00210-023-02715-y. Epub 2023 Sep 12.
The aim of this study was the investigation of analgesic and anti-inflammatory activity of naproxen and pioglitazone following intra-plantar injection of carrageenan and assessment of the PPAR-γ receptor involvement in these effects. Rats were intra-plantarly injected with carrageenan (1%, 100 μl) to induce thermal hyperalgesia and paw inflammation. Different groups of rats were pre-treated intraperitoneally with naproxen (1 and 10 mg/kg) or pioglitazone (3 and 10 mg/kg) or GW9662 (a selective PPAR-γ antagonist, 100 μl/paw). The volume of the paw was evaluated using a plethysmometer, and the hot plate test was employed to assess the pain threshold in the animals. Finally, TNF-α, IL-1ß, IL-6, and myeloperoxidase (MPO) activity status were evaluated in the hind paw tissue. Naproxen and pioglitazone demonstrated analgesic and anti-inflammatory activity. Concurrent injection of an ineffective dose of naproxen (1 mg/kg) with an ineffective dose of pioglitazone (3 mg/kg) caused augmented analgesic and anti-inflammatory activity, significantly (p≤0.001 and p≤0.01, respectively). Additionally, intra-plantar injection of GW-9662 before naproxen or pioglitazone significantly suppressed their analgesic (p≤0.001) and anti-inflammatory activity (p≤0.01). Also, naproxen and pioglitazone (10 mg/kg) significantly (p≤0.001) reduced carrageenan-induced MPO activity and TNF-α, IL-6, and IL-1ß releasing. Furthermore, PPAR-γ blockade significantly prevented suppressive effects of naproxen and pioglitazone on the MPO activity and inflammatory cytokines. Pioglitazone significantly increased analgesic and anti-inflammatory effects of naproxen. This study proposes that concurrent treatment with naproxen and pioglitazone may be a substitute for overcome pain and inflammation clinically, in the future, particularly in patients with cardiovascular disorders and diabetes.
本研究旨在探讨萘普生和吡格列酮在足底注射角叉菜胶后的镇痛和抗炎活性，并评估PPAR-γ受体在这些作用中的参与情况。给大鼠足底注射角叉菜胶（1%，100μl）以诱导热痛觉过敏和爪部炎症。不同组的大鼠腹腔内预先给予萘普生（1和10mg/kg）或吡格列酮（3和10mg/kg）或GW9662（一种选择性PPAR-γ拮抗剂，100μl/爪）。使用体积描记器评估爪部体积，并采用热板试验评估动物的痛阈。最后，评估后爪组织中TNF-α、IL-1β、IL-6和髓过氧化物酶（MPO）的活性状态。萘普生和吡格列酮表现出镇痛和抗炎活性。无效剂量的萘普生（1mg/kg）与无效剂量的吡格列酮（3mg/kg）同时注射可显著增强镇痛和抗炎活性（分别为p≤0.001和p≤0.01）。此外，在萘普生或吡格列酮之前足底注射GW-9662可显著抑制它们的镇痛（p≤0.001）和抗炎活性（p≤0.01）。而且，萘普生和吡格列酮（10mg/kg）可显著（p≤0.001）降低角叉菜胶诱导的MPO活性以及TNF-α、IL-6和IL-1β的释放。此外，PPAR-γ阻断可显著阻止萘普生和吡格列酮对MPO活性和炎性细胞因子的抑制作用。吡格列酮可显著增强萘普生的镇痛和抗炎作用。本研究表明，未来萘普生和吡格列酮联合治疗可能在临床上替代用于克服疼痛和炎症，特别是在患有心血管疾病和糖尿病的患者中。
