Lauro Filomena, Ilari Sara, Giancotti Luigino Antonio, Ventura Cinzia Anna, Morabito Chiara, Gliozzi Micaela, Malafoglia Valentina, Palma Ernesto, Paolino Donatella, Mollace Vincenzo, Muscoli Carolina
IRCCS San Raffaele, Roccelletta di Borgia, 88021, Catanzaro, Italy.
Department of Drug Science & Health Products, University of Messina, Viale Annunziata, 98168, Messina, Italy.
Pharmacol Res. 2016 Sep;111:767-773. doi: 10.1016/j.phrs.2016.07.043. Epub 2016 Jul 29.
Considerable evidence demonstrated that the central role of reactive oxygen species and reactive nitrogen species (ROS and RNS) in the development of thermal hyperalgesia is associated to acute and chronic inflammation. Idebenone (IDE), a synthetic analogue of the endogenous cellular antioxidant coenzyme Q10 (CoQ10), is an active drug in the central nervous system which shows a protection in a variety of neurological disorders. Since it is lipophilic, poorly water soluble and highly bound to plasma proteins, different technological approaches have been explored to increase its solubility and new pharmaceutical properties. Therefore, it has been complexed with HP-β-cyclodextrins (HP) and its efficacy has been assessed in an animal model of carrageenan-induced thermal hyperalgesia. All male rats used for this study received a subplantar injection of carrageenan into the right hindpaw in the presence or absence of IDE alone and IDE/HP complex. We observed that IDE poorly reduced painful carrageenan effects whereas IDE/HP complex was able to prevent carrageenan-induced hyperalgesia and edema in a dose-dependent manner, reducing spinal MDA levels and protein nitration. Hence, our results demonstrated that when complexed with HP, idebenone exerts a potent analgesic and anti-inflammatory efficacy.
大量证据表明，活性氧和活性氮物质（ROS和RNS）在热痛觉过敏发展中的核心作用与急性和慢性炎症相关。艾地苯醌（IDE）是内源性细胞抗氧化剂辅酶Q10（CoQ10）的合成类似物，是一种在中枢神经系统中具有活性的药物，在多种神经疾病中显示出保护作用。由于它具有亲脂性、水溶性差且与血浆蛋白高度结合，人们探索了不同的技术方法来提高其溶解度和新的药物特性。因此，它已与羟丙基-β-环糊精（HP）形成复合物，并在角叉菜胶诱导的热痛觉过敏动物模型中评估了其疗效。本研究中使用的所有雄性大鼠在右后爪足底皮下注射角叉菜胶，同时单独给予或给予IDE/HP复合物。我们观察到，艾地苯醌对角叉菜胶引起的疼痛效果降低作用不佳，而IDE/HP复合物能够以剂量依赖的方式预防角叉菜胶诱导的痛觉过敏和水肿，降低脊髓丙二醛水平和蛋白质硝化。因此，我们的结果表明，与HP复合后，艾地苯醌具有强大的镇痛和抗炎功效。
