Mechanistic Insights into FOLFOX-Induced Neurotoxicity and Determination of Its Concentrations via a Novel, Simultaneous HPLC Quantification Method in Brain Tissue

This study identified a novel mechanisms underlying FOLFOX neurotoxicity involving activation of the pro-apoptotic BAX/cCaspase-3 pathway and suppression of the Nrf2/KEAP-1/SOD2/HO-1 antioxidant defense mechanism. These disorders induced a neuronal injury, evidenced by altered GFAP and NCAM expression. The findings highlight the synergistic role of FOLFOX components in driving oxidative stress, apoptosis, and inflammation, collectively contributing to neurotoxicity.