Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats

The fact that oxaliplatin (OXL), a platinum-based chemotherapeutic drug, causes severe neuropathy greatly limits its clinical use. This study investigated the effects of lycopene, a potent antioxidant, on OXL-induced central and peripheral neuropathy. In this study, 30 min after oral administration of LY at a dose of 2 mg/kg b.w./day and 4 mg/kg b.w./day on 1 st, 2nd, 4th and 5th days, rats were given 4 mg/kg b.w./day of OXL intraperitoneally. It was detected that LY decreased OXL-induced lipid peroxidation and increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and the levels of glutathione (GSH) in brain tissue. LY showed anti-inflammatory effects by decreasing levels of mitogen-activated protein kinase-14 (MAPK14), nuclear factor kappa-B (NF-kappa B) and tumor necrosis factor-alpha (TNF-alpha) in brain and sciatic tissue. It was determined that OXL-induced endoplasmic reticulum stress (ERS) decreased because LY administration reduced the expressions of activating transcription factor-6 (ATF6), glucose-regulated protein-78 (GRP78), RNA-activated protein kinase (PKR)-like ER kinase and inositol-requiring enzyme-1 (IRE1). LY administration also reduced the damage of OXL-induced brain and sciatic tissue by increasing NCAM levels and decreasing GFAP levels. It was determined that caspase-3 immunopositivity markedly decreased by OXL and LY in combination. It was also observed that LY provided neuronal protection by increasing brain-derived neurotrophic factor (BDNF) levels, which decreased with OXL administration in sciatic tissue. The results demonstrate that LY can be beneficial in ameliorating OXL-induced central and peripheral nerve injuries by showing antioxidant, anti-inflammatory and anti-apoptotic properties in the brain and sciatic tissue.