Modulatory effect of simvastatin on redox status, caspase-3 expression, p-protein kinase B (p-Akt), and brain-derived neurotrophic factor (BDNF) in an ethanol-induced neurodegeneration model.

Neurodegenerative diseases are a common cause of morbidity and mortality worldwide, with oxidative stress, inflammation, and protein aggregation representing the main underlying mechanisms that ultimately lead to cell death. Ethanol has shown strong neurodegenerative consequences in experimental animal brains. Statins are a class of lipid-lowering drugs with many pleotropic effects. Therefore, the aim of the present study was to explore the modulatory effect of simvastatin (10 mg·kg·day) before and after the development of neurodegeneration (for 55 and 25 days, respectively) on redox state, caspase-3 expression, p-protein kinase B (p-Akt), and brain-derived neurotrophic factor (BDNF) in ethanol-induced (15% ethanol solution for 55 days) neurodegeneration. Seventy female Albino Swiss mice were included and randomly divided into five groups: C, control group; E, ethanol group; ES, group treated with simvastatin from the first day of ethanol intake; E + S, group treated with simvastatin after neurodegeneration development; and S, simvastatin group. Administration of simvastatin from the first day improved the biochemical changes, suppressed apoptosis, and induced autophagy and neurogenesis; however, its administration after the development of neurodegeneration resulted in partial improvement. The histopathological findings confirmed the biochemical changes. In conclusion, simvastatin has a neuroprotective effect against the development of ethanol-induced neurodegeneration and its progression.