Clinical analysis department, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Basic Science Department, College of Medicine, Hawler Medical University, Erbil, Iraq.
Cell Mol Biol (Noisy-le-grand). 2023 Sep 30;69(9):100-105. doi: 10.14715/cmb/2023.69.9.14.
Non-steroidal anti-inflammatory drugs decrease pain and fever while corticosteroids regulate inflammation and immune response, both are prescribed to reduce inflammation and control pain. The present study aimed to study the effects of their monotherapy and co-administration on the brain tissue structure of experimental rats. P-glycoprotein (PGP), a transporter membrane protein, plays an important role in various physiological and physio-pathological conditions, drug-drug and drug-food interactions, and multi-drug resistance. Male rats were divided into four groups and received normal saline, dexamethasone, diclofenac sodium and their dual therapy respectively, then after one-month rats were sacrificed and brain tissues proceeded for hematoxylin and eosin staining to study their histopathology and immunohistochemically staining of NSE, S100-B and GFAP biomarkers were performed. Additionally, in silico molecular docking studies were conducted to elucidate interactions between PGP and used compounds. Resultsshowed that dexamethasone or diclofenac sodium treatments showed abnormalities like edema, neuronal vacuoles, astrocytes hyperplasia and microglial cells with positive reaction to NSE, S100 and GFAP antibodies while the dual therapy displayed less edema and other signs of damage with negative and weak positive staining of NSE, S100 and GFAP antibodies respectively. The molecular docking showed that there were different affinities toward the involved PGP active site. These interaction results were great with Dexamethasone -9.6 kcal/mol forming hydrophobic interactions with the highest affinity when compared with Diclofenac sodium which gave -8.4 kcal/mol. In conclusion, the side effects of the two types of anti-inflammatory drugs may be minimized through their interactions. However, Molecular Dynamic Simulations studies are required to explain the exact dynamic behaviors and protein-ligand stability.
非甾体抗炎药可减轻疼痛和发热，而皮质类固醇则可调节炎症和免疫反应，两者均可用于减轻炎症和控制疼痛。本研究旨在研究其单药治疗和联合用药对实验大鼠脑组织结构的影响。P 糖蛋白（PGP）是一种跨膜转运蛋白，在多种生理和病理生理条件下、药物-药物和药物-食物相互作用以及多药耐药中发挥重要作用。雄性大鼠分为四组，分别给予生理盐水、地塞米松、双氯芬酸钠及其联合治疗，一个月后处死大鼠，取脑组织进行苏木精-伊红染色，研究其组织病理学，并进行 NSE、S100-B 和 GFAP 生物标志物的免疫组织化学染色。此外，还进行了计算机分子对接研究，以阐明 PGP 与所用化合物之间的相互作用。结果表明，地塞米松或双氯芬酸钠治疗后出现水肿、神经元空泡、星形胶质细胞增生和小胶质细胞呈 NSE、S100 和 GFAP 抗体阳性反应等异常，而联合治疗后水肿等损伤迹象较少，NSE、S100 和 GFAP 抗体的染色呈阴性和弱阳性。分子对接表明，两种抗炎药对 PGP 活性部位的亲和力不同。与双氯芬酸钠相比，地塞米松与 PGP 活性部位的亲和力最高，形成 -9.6 kcal/mol 的疏水相互作用，这些相互作用结果非常好。总之，两种类型的抗炎药的副作用可能通过它们的相互作用最小化。然而，需要进行分子动力学模拟研究来解释确切的动态行为和蛋白质-配体稳定性。
