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.
