Neurotoxicity caused by cisplatin is a major obstacle during chemotherapy. Oxidative stress and inflammation are considered the primary mechanism behind neuronal damage which affects the continuing chemotherapy regimen. Agomelatine was recently described as a neuroprotective compound against toxic insults in the nervous systems. It is an analog of the well-known antioxidant and anti-inflammatory compound melatonin and currently used for depression and sleep disturbances. In the current study, we investigated the possible neuroprotective role of agomelatine against cisplatin-induced oxidative, inflammatory, and behavioral alterations in male rats. Our results show that agomelatine prevented cisplatin-induced neurotoxicity in the HT-22 mouse hippocampal neuronal cell line. Additionally, agomelatine treatment inhibited cisplatin-induced behavioral deficits and neuronal integrity in vivo. For the evaluation of the effect of agomelatine on oxidative stress and inflammation, GSH, MDA, TNF, and IL-6 levels were analyzed in HT-22 cells and hippocampal tissues. Agomelatine significantly attenuated oxidative stress and inflammation due to the cisplatin insult in vitro and in vivo. Also, agomelatine treatment ameliorated the neuronal pathology in the hippocampus, which is strongly related to cognition and memory. Taken together, our results indicate that in males, the neuroprotective effect of agomelatine is mediated through its antioxidant and anti-inflammatory actions abrogating functional deficits.

顺铂引起的神经毒性是化疗过程中的主要障碍。氧化应激和炎症被认为是影响持续化疗方案的神经元损伤背后的主要机制。阿戈美拉汀最近被描述为一种神经保护化合物，可抵抗神经系统中的毒性损伤。它是众所周知的抗氧化剂和抗炎化合物褪黑激素的类似物，目前用于治疗抑郁症和睡眠障碍。在当前的研究中，我们调查了阿戈美拉汀对顺铂诱导的雄性大鼠氧化、炎症和行为改变的可能神经保护作用。我们的结果表明，阿戈美拉汀可防止顺铂诱导的 HT-22 小鼠海马神经元细胞系神经毒性。此外，体内。为了评估阿戈美拉汀对氧化应激和炎症的影响，分析了 HT-22 细胞和海马组织中的 GSH、MDA、TNF 和 IL-6 水平。阿戈美拉汀在体外和体内显着减轻顺铂损伤引起的氧化应激和炎症。此外，阿戈美拉汀治疗改善了与认知和记忆密切相关的海马神经元病理学。总之，我们的结果表明，在男性中，阿戈美拉汀的神经保护作用是通过其抗氧化和抗炎作用消除功能缺陷来介导的。