Abstract
Binge alcohol drinking is fast becoming a global health concern, with the liver among the first organ involved and the one afflicted with the greatest degree of injury. Oxidative stress, alterations in hepatic metabolism, immunity and inflammation have all been reported to contribute to the development of alcoholic liver disease (ALD). Hydrogen gas (H2) serves a key role in the modulation of hepatic redox, immune and inflammatory homeostasis. However, the effects of treatment using intraperitoneal injection of H2 on ALD remain unexplored. Therefore, the aim of the present study was to investigate the effects and underlying mechanism of intraperitoneal injection of H2 on acute alcohol-induced liver injury in a mouse model. H2 was administered by daily intraperitoneal injections (1.0 ml/100 g) for 4 days. On day 4, the mice received H2 after fasting for 5.5 h. After 30 min, the mice were administered with 33% (v/v) ethanol at a cumulative dose of 4.5 g/kg body weight by four equally divided gavages at 20-min intervals. Blood and liver tissues were collected at 16 h after the first ethanol gavage. Subsequently, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride and total cholesterol (TC) levels were analyzed using an Automatic Clinical Analyzer. Hepatic JNK activity and GAPDH levels were examined by western blotting. It was observed that acute ethanol gavage induced liver injury, as indicated by significantly increased serum ALT and AST levels, which were effectively decreased by H2 at 16 h after the first ethanol gavage. In addition, H2 treatment reduced serum TC levels in the Alcohol+H2 group when compared with those in Alcohol group. Mechanistically, H2 attenuated hepatic JNK phosphorylation induced by acute ethanol gavage. Therefore, the results of the present study demonstrated that treatment with exogenous H2 by intraperitoneal injection may alleviate acute alcohol-induced liver injury by inhibiting hepatic JNK activation, which may represent a novel therapeutic strategy for ALD.