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

[Display omitted] •OXL induced oxidative stress while LY reduced it, in brain tissue.•OXL exposure triggered apoptosis whereas LY reduced it, in both the brain and sciatic nerve tissue.•OXL caused inflammation, but LY reduced it, in both the brain and sciatic nerve tissue.•OXL exposure caused ER stress while LY suppressed it, in both the brain and sciatic nerve tissue.•OXL suppressed BDNF expression whereas LY triggered it in the brain tissue. 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-κB) and tumor necrosis factor-α (TNF-α) 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.