Combination of Cysteine and Glutathione Prevents Ethanol-Induced Hangover and Liver Damage by Modulation of Nrf2 Signaling in HepG2 Cells and Mice

Excessive alcohol consumption increases oxidative stress, leading to alcoholic liver disease. In this study, the protective effects of a mixture of cysteine and glutathione against ethanol-induced hangover and liver damage were evaluated in mice and HepG2 cells. Ethanol (2 mL/kg) was orally administered to the mice 30 min before receiving the test compounds (200 mg/kg), and the behavioral and oxidative stress-related biochemical parameters altered by ethanol were analyzed. Acute ethanol administration increased anxiety behavior and decreased balance coordination in mice (p < 0.001); however, a mixture of cysteine and glutathione (MIX) in a 3:1 ratio improved alcohol-induced behavior more effectively than the individual compounds (p < 0.001). The MIX group showed higher ethanol-metabolizing enzyme activity than the control group (p < 0.001) and significantly suppressed the elevation of serum alcohol (p < 0.01) and acetaldehyde (p < 0.001) levels after 1 h of ethanol administration. In HepG2 cells, 2.5 mM MIX accelerated ethanol metabolism and reduced cytochrome P450 2E1 mRNA expression (p < 0.001). MIX also increased the expression of antioxidant enzymes through the upregulation of nuclear erythroid 2-related factor 2 (Nrf2) signaling and consequently suppressed the overproduction of reactive oxygen species and malondialdehyde (p < 0.001). Collectively, MIX alleviates the hangover symptoms and attenuates the alcohol-induced oxidative stress by regulating the Nrf2 pathway.