Lactobacillus helveticus HY7804 Alleviates Ethanol-Induced Liver Injury and Modulates Oxidative Stress and Inflammatory Responses in a Chronic-Binge Ethanol-Fed Mouse Model

Alcohol-associated liver disease (ALD) contributes substantially to the global burden of chronic liver disease, yet few effective pharmacological treatments are currently available. The hepatoprotective potential of Lactobacillus helveticus HY7804 was evaluated in ethanol-exposed HepG2 cells and in a modified chronic-binge ethanol-fed mouse model adapted from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) paradigm. Ethanol-induced cytotoxicity in HepG2 cells was attenuated by HY7804, as demonstrated by the recovery of cell viability and the reduction in lactate dehydrogenase release. HY7804 also decreased ethanol-induced inflammatory cytokine production, including IL-6, TNF-α, IL-1β, and IL-8, and modulated apoptosis-related gene expression. In chronic-binge ethanol-fed mice, HY7804 reduced serum AST from 183.4 ± 34.1 to 129.4 ± 16.4 U/L (p < 0.01) and ALT from 67.5 ± 4.5 to 52.1 ± 4.7 U/L (p < 0.05). Hepatic lipid accumulation was also significantly reduced by HY7804 treatment compared with the EtOH group, as indicated by the decreased Oil Red O-positive area (p < 0.01). Hepatic MDA levels decreased from 46.01 ± 3.38 to 30.58 ± 6.38 nmol/mg tissue (p < 0.01). In addition, HY7804 modulated hepatic inflammatory cytokine profiles, antioxidant-related responses, and the Bax/Bcl-2 expression ratio. These findings suggest that HY7804 mitigates ethanol-induced hepatic injury, with associated changes in inflammatory responses, antioxidant-related markers, lipid peroxidation, and apoptosis-related gene expression.