Karaca Onur, Şimşek Hasan, Akaras Nurhan, Gür Cihan, İleritürk Mustafa, Kandemir Özge, Küçükler Sefa, Karaca Şeyda Öte, Kandemir Fatih Mehmet
Department of Anesthesiology and Reanimation, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Department of Physiology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Mol Neurobiol. 2025 Apr 7. doi: 10.1007/s12035-025-04892-8.
Tramadol (TRM) is a synthetic opioid analgesic that acts on the central nervous system and is used to treat moderate or severe pain. However, the incidence of its abuse is increasing. Rosmarinic acid (RA) is a natural flavonoid known for its antioxidant, anti-inflammatory, and neuroprotective properties. In this study, we determined the ameliorative effects of RA against TRM-induced neurotoxicity. Thirty five rats were divided into 5 groups; control, RA, TRM, TRM + RA25 and TRM + RA50. TRM 50 mg/kg was administered intraperitoneally, and RA 25 and 50 mg/kg doses were administered by oral gavage for 14 days. Water Maze Test (WMT) was performed to assess cognitive function. Oxidative stress, inflammation, endoplasmic reticulum (ER) stress, apoptosis damage pathways, glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF) activities were determined in brain and hippocampus tissues. The structural and functional integrity of the tissues were also analyzed. RA decreased TRM-induced increased oxidative stress, inflammation, ER stress, and apoptotic damage levels. In addition, it improved neuronal survival and activity by bringing BDNF and GFAP activities closer to normal in brain tissue. RA restored the structural properties of brain and hippocampus tissues disrupted by tramadol. These findings were also demonstrated using WMT, which improved the arrival time to the quadrant in which the platform was located and the time spent in the quadrant. RA reduces TRM-induced neurotoxicity by reducing inflammation, oxidative stress, ER stress, and apoptotic damage and increases neuronal survival and activity.
曲马多（TRM）是一种作用于中枢神经系统的合成阿片类镇痛药，用于治疗中度或重度疼痛。然而，其滥用发生率正在上升。迷迭香酸（RA）是一种天然类黄酮，以其抗氧化、抗炎和神经保护特性而闻名。在本研究中，我们确定了RA对TRM诱导的神经毒性的改善作用。将35只大鼠分为5组：对照组、RA组、TRM组、TRM + RA25组和TRM + RA50组。腹腔注射TRM 50 mg/kg，口服给予RA 25和50 mg/kg剂量，持续14天。进行水迷宫试验（WMT）以评估认知功能。测定脑和海马组织中的氧化应激、炎症、内质网（ER）应激、凋亡损伤途径、胶质纤维酸性蛋白（GFAP）和脑源性神经营养因子（BDNF）活性。还分析了组织的结构和功能完整性。RA降低了TRM诱导的氧化应激、炎症、ER应激和凋亡损伤水平的升高。此外，它通过使脑组织中的BDNF和GFAP活性接近正常水平，改善了神经元的存活和活性。RA恢复了被曲马多破坏的脑和海马组织的结构特性。这些发现也通过WMT得到了证实，WMT改善了到达平台所在象限的时间和在该象限花费的时间。RA通过减轻炎症、氧化应激、ER应激和凋亡损伤来降低TRM诱导的神经毒性，并增加神经元的存活和活性。
