Alpha-Lipoic Acid in Early-Stage Alcohol-Related Brain Damage in Rats: A Comparative Pilot Study

Alcohol misuse can lead to alcohol-related brain damage (ARBD), a condition linked to long-term cognitive impairment and considerable disease burden. The pharmacological characteristics of alpha-lipoic acid (ALA) make it a promising candidate for the treatment of ARBD. In this study, adult male Wistar rats were divided into eight experimental groups. Four groups received a 20% (v/v) ethanol-tap water solution ad libitum for 15 weeks to induce early-stage ARBD, while the remaining received only tap water. After 14 weeks, all groups were administered daily injections for one week with either ALA, rivastigmine, or memantine. Behavioral testing included the step-through passive avoidance and rotarod performance tests. Whole-brain biochemical analyses assessed acetylcholinesterase activity, brain-derived neurotrophic factor, and oxidative stress biomarkers. Brain weight, relative brain weight, and brain histopathological changes were also evaluated. Results showed that, similar to memantine and rivastigmine, ALA improved STL at both 24 h and 8 days and reduced ethanol-induced Purkinje cell damage. It also decreased lipid peroxidation levels by 44%, unlike the reference drugs, and superoxide dismutase activity by 33%, similar to them. No other significant changes were detected. Albeit several limitations, this is the first study comparing ALA with rivastigmine and memantine in this experimental context.