O-15 MARESIN1 REVERSES CHRONIC LIVER FIBROSIS AND IMPROVES REGENERATION

Abstract

Introduction and Objectives

Hepatic fibrosis (HF) is characterized by the progressive accumulation of extracellular matrix (ECM), which destroys the physiological architecture of the liver. Pathologically, chronic liver diseases lead to damaged hepatocytes and infiltration of immune cells that activate collagen-producing hepatic stellate cells (HSCs), leading to excessive ECM production, and causing uncontrolled scarring. Maresin1 is a derivative of -3 docosahexaenoic acid (DHA), which has been shown to have pro-resolving and anti-inflammatory effects in various organs like those observed for DHA. This study aimed Mar1+DHA supplementation would prevent the development of fibrosis and promote regeneration in an animal model of chronic liver damage.

Materials and Methods

FH was induced in Sprague-Dawley rats by injections of diethylnitrosamine (DEN, 50 mg/kg) and treated with MaR1 (4ng/g) and/or DHA (375 mg/kg) for five weeks. Transaminases, liver histology, and proteins were analyzed by western blot.

Results

the DHA+ MaR1 group showed a greater positive response (significant) than MaR1 in terms of normalization of AST and ALT levels, and architecture of the liver. Reducing inflammation and necrosis. Furthermore, both MaR1 and DHA reduced the levels of TGF-, its receptor TGFRII, and TIMP1, increasing MMP1. Results that coincide with the quantification of type I collagen fibers in tissue. On the other hand, they would promote liver regeneration by increasing Cyclin D1.

Conclusions

Both MaR1 and MaR1/DHA improve regeneration and DEN-induced liver fibrosis parameters, promoting regeneration and acting as an antifibrotic agent. Results that open the possibility that MaR1/DHA are potential therapeutic agents in fibrosis and other liver pathologies.