Dexpanthenol Attenuates High Fructose Corn Syrup-Induced Brain Injury by Modulating Oxidative Stress, Neuroinflammation, Apoptotic Signaling and Amyloidogenic Gene Expression.

High fructose corn syrup (HFCS) consumption may lead to oxidative stress-related neurodegeneration. Dexpanthenol (DEX), with antioxidant and cytoprotective properties, may exert neuroprotective effects; however, its efficacy against HFCS-induced neurotoxicity remains unclear. This study examined DEX's effects against HFCS-induced neurotoxicity across multiple pathways. Rats were randomly assigned to four experimental groups (n = 8, for each group): Control, HFCS (20%, for 8 weeks), HFCS + DEX (500 mg/kg), and DEX. Brain tissues were analyzed by histopathology, immunohistochemistry (tumor necrosis factor-α; TNF-α and caspase-3), biochemical assays, and RT-qPCR of genes related to mitochondrial biogenesis, antioxidant defense, apoptosis, inflammation, neurotrophic signaling (brain-derived neurotrophic factor; BDNF), and amyloidogenic gene expression (amyloid precursor protein; APP, beta-site APP cleaving enzyme 1; BACE1, presenilin-1,2; PSEN1,2). HFCS significantly increased total oxidant status (TOS) (p < 0.01) along with pronounced histopathological damage including gliosis, neuronal degeneration, and Purkinje cell loss. It also increased TNF-α and caspase-3 immunoreactivity (p < 0.001), upregulated APP, BACE1, PSEN1 and PSEN2 gene expression, and reduced BDNF expression. DEX significantly reduced TOS and oxidative stress index (OSI) (p < 0.001), decreased TNF-α and caspase-3 immunoreactivity (p < 0.001), increased BDNF expression (p < 0.01), and significantly downregulated BACE1 and PSEN1 gene expression (p < 0.05). These findings suggest that DEX may attenuate HFCS-associated brain injury by modulating oxidative stress, inflammatory responses and apoptotic signaling, and amyloidogenic gene-expression changes.