Effect of single binge alcohol consumption on alcohol-naïve and -exposed drinking mouse models

Binge alcohol exposure is underestimated compared to chronic intake, particularly in young or alcohol-naïve individuals. This study investigates the effects of single binge drinking, on both alcohol-naïve and alcohol-dependent drinking subjects. C57BL/6J mice received a binge ethanol dose (6 g/kg body weight; 40 % ethanol(v/v)), and subsequent haematological, hepatic, transcriptomic, and metabolomic changes were analyzed. In naïve mice, binge alcohol elevated serum AST levels, indicating acute liver injury. In ethanol-dependent mice (20 g/kg/day; 6 % ethanol(v/v)), single binge episode altered haematological parameters and affected liver-to-body weight ratios. Both naïve and previously exposed animals showed downregulation of hepatic ADH1, Cat, and antioxidant enzyme SOD expression. Liver ROS was triggered across alcohol-drinking groups, more pronounced in binge-treated mice. Additionally, ethanol exposure induced lipid accumulation and ROS generation in liver tissue, upregulated lipogenic and downregulated fatty acid oxidation genes-effects exacerbated in previously exposed animals. Metabolomic analysis revealed alterations in amino acid and energy metabolism pathways following binge exposure. These findings can confirm the hazard of binge drinking on both previously exposed "alcohol-consumers" and "naïve-drinkers". Moreover, it highlights severe physiological disruptions caused by a single binge episode and the necessity for deeper experimental and clinical exploration of binge drinking, given its prevalence for long-term health consequences.