Skate cartilage-derived chondroitin attenuates ethanol-induced liver injury by modulating oxidative stress and lipid metabolism

Abstract

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

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

This work was supported by the National Research Foundation of Korea grant funded by the Korean government (Grant no.: RS-2022-NR070862).

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

LST conducted the main investigation, including experimental design and analysis, and wrote original-draft of manuscript. NSS, HBP, LS, and SP were responsible for investigation and analysis. KHK and HWK also contributed to classification, identification, and data interpretation. JWP and ML provided supervision. DYR conceptualized and supervised the study and contributed to manuscript review and editing. All authors reviewed and approved the final manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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