γ-Glutamylcysteine alleviates ethanol-induced hepatotoxicity via suppressing oxidative stress, apoptosis, and inflammation

Alcohol abuse is a major cause of alcoholic liver disease (ALD) and can result in fibrosis and cirrhosis. gamma-glutamylcysteine (gamma-GC) is a precursor of glutathione (GSH) with antioxidant and anti-inflammatory properties. Our research aimed to explore the protective impact of gamma-GC on ALD and its potential mechanisms of efficiency in vitro and in vivo. L02 cells were pretreated with gamma-GC (20, 40, and 80 mu M) for 2 h and exposed to ethanol for 24 h. Cell viability, apoptosis, oxidative stress, and inflammatory levels were measured. The expression of protein cleaved caspase-3 and cleaved PARP and flow cytometry results indicated that gamma-GC decreases apoptosis on L02 cells after ethanol treatment. Moreover, gamma-GC also attenuated oxidative stress and mitochondrial damage in hepatocytes caused by ethanol via increasing cellular GSH, SOD activity, and mitochondrial membrane potential. In vivo experiments, gamma-GC effectively reduced the AST, ALT, and TG levels in mice. The inflammation of ALD was alleviated by gamma-GC both in vivo and in vitro. Additionally, histopathological examination demonstrated that gamma-GC treatment lessened lipid droplet formation and inflammatory damage. In conclusion, these results showed that gamma-GC has anti-inflammatory and anti-apoptotic effects on ALD because it could help hepatocytes maintain sufficient GSH levels to combat the excess reactive oxygen species (ROS) generated during ethanol metabolism.