Objective: To evaluate the hepatoprotective effects of skate-derived bioactives—collagen peptides (CPs) and chondroitin—against ethanol (EtOH)-induced liver injury and to elucidate their underlying mechanisms. Methods: The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models. Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers (NRF2 and GCLC). EtOH metabolism was examined by measuring alchohol-metabolizing enzymes (alcohol dehydrogenase and aldehyde dehydrogenase) and cytochrome P450 enzymes. Furthermore, lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers (SREBP-1 and FAS). Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase, and performing histological analysis. Results: In hepatocytes and zebrafish, both CPs and chondroitin reduced oxidative stress, downregulated cytochrome P450 enzymes and lipogenic markers, and enhanced antioxidant defenses, with chondroitin showing the strongest hepatoprotection. In EtOH-fed mice, chondroitin significantly improved liver enzyme profiles, reduced hepatic lipid accumulation and inflammation, and restored antioxidant and metabolic homeostasis. Conclusions: Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress, EtOH metabolism, and lipid regulation. These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage. KEYWORDS: Alcohol-associated liver disease; Chondroitin; Collagen peptides; Liver injury; Oxidative stress; Lipid metabolism
Thakuri et al. (Wed,) studied this question.