Memantine ameliorates oxaliplatin-induced neurotoxicity via mitochondrial protection

Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced neurotoxicity has been well documented. Memantine is a drug for the management of Alzheimer's Disease (AD) due to its promising neuroprotective properties. We hypothesize that Memantine possesses a beneficial role against chemotherapy-induced neuronal damages. In this study, we established an oxaliplatin-induced neurotoxicity assay model in human SHSY-5Y neuronal cells and investigated the protective effect of Memantine. We showed that Memantine treatment ameliorated oxaliplatin-elevated intracellular production of reactive oxygen species (ROS), lipid product malondialdehyde (MDA), and NOX-2 expression. Memantine alleviated impairment of the mitochondrial membrane potential and ATP production by oxaliplatin. As a result, Memantine showed a protective role against oxaliplatin-induced cytotoxicity. Moreover, the terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) apoptosis assay revealed that Memantine protected oxaliplatin-induced apoptosis through mitigating the ratio of Bax/Bcl-2 and Caspase-3 cleavage. We concluded Memantine ameliorated the neurotoxicity of oxaliplatin in a mitochondrial-dependent pathway.