Chitosan Oligosaccharides Prevent Alcohol-Induced Liver Disease by Attenuating Inflammation and Oxidative Stress.

Alcoholic liver disease (ALD) is a liver disorder resulting from excessive alcohol intake, and currently, there are no therapeutics approved by the FDA for its treatment. This study investigates the protective effects and underlying pharmacological mechanisms of two chitosan oligosaccharides, COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da), in mitigating alcohol-induced liver disease (ALD). In animal models, we evaluated the changes in ALD following treatment with COST and COSM. Histopathological analysis revealed that both COST and COSM interventions mitigated hepatic steatosis and inflammatory infiltration. Additionally, these compounds reduced various markers of liver injury, enhanced antioxidant enzyme levels, and significantly improved liver function. Western blot analysis demonstrated that COSM markedly decreased the expression of the hepatic metabolic enzyme CYP2E1, activated the Keap-1/Nrf-2/HO-1 pathway, and restrained the NF-κB and MAPK pathways. In an in vitro model of alcohol-induced hepatocyte L02 injury, both COST and COSM exhibited protective effects on hepatocytes, corroborating the findings from the animal studies. Collectively, in vivo and in vitro experiments confirmed that COST and COSM can reduce oxidative damage, enhance antioxidant capacity, and ameliorate steatosis and inflammatory damage in the liver, thereby significantly attenuating alcohol-induced injury. Notably, COSM exhibited slightly superior efficacy compared to COST.