NORMALIZATION OF NAD REDOX BALANCE AS A STRATEGY FOR PREVENTING ALCOHOL-INDUCED HEPATOTOXICITY: PRECLINICAL EVALUATION

Background. Chronic ethanol intake disrupts hepatic NAD redox homeostasis, representing a critical mechanism in the pathogenesis of alcohol-induced liver injury. Restoration of the NAD pool is increasingly recognized as a promising preventive strategy of alcoholic liver disease. The objective of this study was to evaluate the preventive efficacy of NAD biosynthesis precursors (nicotinamide, nicotinamide riboside, and nicotinamide mononucleotide) against the development of liver damage in a model of chronic alcohol intoxication. Material and Methods. Mature male Wistar rats were administered 30% ethanol (10 g/kg/day) for 14 days, with concurrent treatment using NAD biosynthetic precursors at 2.05 mmol/kg/day. The evaluation included serum biochemical parameters, hepatic histology, activities of ethanol-metabolizing and antioxidant enzymes, NAD/NADH ratios, and markers of oxidative stress. Results. NAD biosynthetic precursors markedly attenuated elevated serum markers, histopathological alterations, and oxidative stress, while restoring the NAD/NADH balance and normalizing the activities of ethanol- and acetaldehyde-metabolizing enzymes. Conclusion. Prophylactic administration of nicotinamide riboside and nicotinamide mononucleotide mitigates alcohol-induced liver injury by restoring NAD redox balance, promoting acetaldehyde detoxification, and attenuating oxidative stress.