NADH and NRH as potential dietary supplements or pharmacological agents for early liver injury caused by acute alcohol exposure

Alcoholism leads to many diseases, and it is also the social and economic burden of the society. Alcohol intake is the main cause of acute liver injury and chronic liver disease. Here, the ameliorative effect of NADH and dihydronicotinamide riboside (NRH) against alcohol-induced liver damage was studied and its possible mechanism was further clarified. In vitro studies showed that NADH and NRH are effective NAD+ concentration-enhancing agents. Compared with NMN, NADH and NRH can provide greater NAD+ increase at the same concentrations. Intraperitoneal injection of NADH and NRH in C57BL/6J mice also significantly increased the NAD+ content in liver, blood, brain, fat and kidney. Importantly, NADH and NRH significantly increased the liver NAD+/NADH ratio, but did not induce apoptosis markers in cells. The intragastric administration of 500 mg/kg NRH, 500 mg/kg NADH 15 min prior to acute alcohol ingestion (8 ml/kg, 40% w/v, in tap water) could dramatically enhance alcohol metabolism as revealed by the reduced concentrations of ethanol and acetaldehyde in blood as well as the decreased duration of the loss of righting reflex (LORR). Both Pretreatment and posttreatment with NADH or NRH could significantly reduce the increase of serum aspartate transaminase (AST) and alanine transaminase (ALT) after alcohol administration, indicating that they have a certain therapeutic effect on alcoholic hepatotoxicity besides preventing the adverse effects caused by alcohol. NADH and NRH could also alleviate lipid peroxidation as indicated by the repressed malondialdehyde (MDA) level and the elevated activities of superoxide dismutase (SOD) in liver tissues. Additionally, NADH or NRH can mitigate the abnormal lipid metabolism in acute alcoholic liver damage. These benefits obviously suggested that NADH or NRH could be a potential nutraceutical or pharmacological agent for promoting alcohol metabolism and preventing or treating early liver injury caused by acute alcohol exposure.