The role of cyclooxygenase-mediated eicosanoids in alcohol-associated liver disease.

Authors

Weilun Ai, Viswanathan Saraswathi

Published in

Prostaglandins, leukotrienes, and essential fatty acids. Volume 210. Pages 102764. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Alcohol-associated liver disease (ALD) is a main health issue worldwide, which is reported as the second leading cause for liver transplantation. Chronic or heavy alcohol use exerts adverse effects on the liver, leading to dysregulated lipid metabolism, inflammatory response, generation of oxidative stress, and fibrosis. Emerging evidence has shown that chronic or heavy alcohol consumption alters the production of cyclooxygenase (COX)-mediated eicosanoids, including thromboxane A2 (TXA2), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), prostaglandin D2 (PGD2), and prostaglandin F2α (PGF2α), in the liver. These eicosanoids play diverse roles in altering steatosis, inflammation, oxidative stress, vascular dysfunction, fibrogenesis, and impaired liver regeneration in different liver diseases. In this review, we evaluate the roles of COX-mediated eicosanoids in mediating the pathogenesis of ALD. Of note, emerging evidence suggests that COX-mediated eicosanoids exert distinct effects in ALD: TXA2 largely drives inflammation and fibrosis, PGI2 and PGD2 show predominantly protective or reparative roles, and PGE2 displays effects that vary depending on receptor subtype and experimental model. Additionally, key knowledge gaps regarding those eicosanoids were identified, including poor understanding of receptor‑specific downstream signaling pathways, limited use of hepatic cell‑specific genetic models, and insufficient study of inter‑organ crosstalk in ALD progression. We also provide future directions aimed at answering these questions and eventually provide insight into the development of effective interventions for ALD by targeting COX‑mediated eicosanoid-related pathways.

PMID:
42551113
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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