Yeni Yesim, Cicek Betul, Hacimuftuoglu Ahmet, Ozkaraca Mustafa, Lacin Burak Batuhan
Faculty of Medicine, Department of Medical Pharmacology, Malatya Turgut Ozal University, Malatya, Turkey.
Faculty of Medicine, Department of Pharmacology, Malatya Turgut Ozal University, Battalgazi-Malatya, 44210, Turkey.
J Neuroimmune Pharmacol. 2025 May 13;20(1):53. doi: 10.1007/s11481-025-10213-6.
During or after chemotherapy, cognitive impairments characterized by forgetfulness, difficulty concentrating, and depressive and anxiety-like symptoms are observed. There is limited research examining the effects of rosuvastatin (RVS), an HMG-CoA reductase inhibitor, in the context of neuroinflammation-related cognitive disruption. Here, we aimed to investigate the neuroprotective potential of RVS against doxorubicin (DOX)-induced cognitive impairments. Experimental groups were planned as control (normal saline, intraperitoneal), DOX (total cumulative dose 10 mg/kg, intraperitoneal), RVS (10 mg/kg, oral, 20 days), and RVS + DOX. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, genetic, histopathological, and immunohistochemical examinations. Results from Morris water maze (MWM), passive avoidance, locomotion activity, and elevated plus maze (EPM) tests showed that DOX administration caused behavioral disorders. Moreover, DOX increased the levels of inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α), while decreasing the levels of interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase, catalase (SOD), endothelial nitric oxide (eNOS), and catalase (CAT). Co-treatment with RSV significantly attenuated DOX-induced behavioral changes and oxidative stress markers. In addition, similar to the immunohistochemical results, we determined that it increased the expression levels of extracellular signal-related kinases 1/2 (ERK1/2), cyclic adenosine monophosphate response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) and restored the histopathological structure of the brain. Therefore, these results indicated that RSV has a neuroprotective effect against DOX-induced cognitive impairment by reducing neurobehavioral impairments, exerting antioxidant and anti-inflammatory effects, and modulating brain growth factors.
在化疗期间或之后，会观察到以健忘、注意力难以集中以及抑郁和焦虑样症状为特征的认知障碍。关于HMG-CoA还原酶抑制剂瑞舒伐他汀（RVS）在神经炎症相关认知破坏背景下的作用，研究有限。在此，我们旨在研究RVS对阿霉素（DOX）诱导的认知障碍的神经保护潜力。实验组计划分为对照组（腹腔注射生理盐水）、DOX组（总累积剂量10mg/kg，腹腔注射）、RVS组（10mg/kg，口服，20天）以及RVS+DOX组。通过一系列行为评估以及生化、基因、组织病理学和免疫组织化学检查来监测疗效。莫里斯水迷宫（MWM）、被动回避、运动活动和高架十字迷宫（EPM）测试结果表明，给予DOX会导致行为障碍。此外，DOX会增加诱导型一氧化氮合酶（iNOS）、丙二醛（MDA）和肿瘤坏死因子-α（TNF-α）的水平，同时降低白细胞介素-10（IL-10）、谷胱甘肽（GSH）超氧化物歧化酶、过氧化氢酶（SOD）、内皮型一氧化氮（eNOS）和过氧化氢酶（CAT）的水平。与RSV联合治疗可显著减轻DOX诱导的行为变化和氧化应激标志物。此外，与免疫组织化学结果相似，我们确定它增加了细胞外信号调节激酶1/2（ERK1/2）、环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）的表达水平，并恢复了大脑的组织病理学结构。因此，这些结果表明，RSV通过减少神经行为障碍、发挥抗氧化和抗炎作用以及调节脑生长因子，对DOX诱导的认知障碍具有神经保护作用。
