Amino acids mixture ameliorates alcohol-induced liver and behavioral impairments by modulating Nrf2 and ethanol metabolism

This study evaluated the protective effects of Amino Liver Mixture (ALM), a formulation of branched-chain amino acids, L-arginine, L-methionine, and L-alanine, against ethanol-induced hepatic and behavioral impairments. In vitro, ALM reduced reactive oxygen species and malondialdehyde, restored alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity, activated the Nrf2/Keap1/HO-1 pathway, and suppressed TNF-α, IL-6, and IL-1β expression. In vivo, ALM pretreatment in mice decreased serum ethanol, acetaldehyde, AST, ALT, and lactate dehydrogenase (LDH), while enhancing ADH and ALDH activity and downregulating CYP2E1. ALM also alleviated oxidative stress, restored antioxidant gene expression, and reduced hepatic inflammatory cytokines. Behavioral tests showed dose-dependent improvements in ethanol-induced motor coordination and anxiety-like behaviors. These findings demonstrate that ALM provides hepatoprotective and neurobehavioral benefits by modulating ethanol metabolism, oxidative stress, and inflammation, supporting its potential as a functional food for alcohol-related disorders. • Amino Liver Mixture (ALM) protected against ethanol-induced liver and behavioral impairments. • ALM enhanced ADH/ALDH activity while suppressing CYP2E1, promoting ethanol metabolism. • ALM activated the Nrf2/Keap11/HO-1 pathway and restored antioxidant enzyme expression. • ALM reduced oxidative stress, improving motor coordination and anxiety-like behaviors. • ALM shows potential as a functional food ingredient for alcohol-related health disorders.