Agomelatine protects hippocampal neurons against doxorubicin induced toxicity

Doxorubicin (DOX) is a powerful chemotherapy drug used in numerous cancer treatments, known to causes neurotoxicity and impair cognitive function in cancer patients. The main mechanism thought to be responsible for the neuronal damage related to chemotherapy is oxidative stress. Agomelatine (AGM) has recently been identified as a neuroprotective agent against toxicity and the effect of AGM on DOX-induced neurotoxicity was investigated in this study. In order to evaluate the effect of AGM on oxidative stress and apoptosis, malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and Caspase-3 expression were analyzed in the HT-22 cell line. AGM considerably reduced oxidative damage due to DOX in vitro. MDA and Caspase-3 were considerably higher in the DOX group. These values were dramatically decreased by AGM. AGM greatly increased the CAT and SOD levels when compared to the DOX group. These results suggest that DOX therapy alters antioxidant status in hippocampus, a critical cognition-related region. So if we are aware of the functional effects of DOX, it is possible to avoid some of the disabling side effects of chemotherapy in cancer patients and may prevent these effects with antioxidant agents such as AGM