Hepatoprotective potential of cardionogen-1, a Wnt/β-catenin signaling inhibitor against alcohol-induced chronic liver injury in C57BL/6J mice.

Hepatoprotective effects of resolvin D1 in mice exposed to ethanol and galactosamine

Background: Alcohol-associated liver disease (ALD) is a major global health condition characterized by inflammation, hepatocellular injury, fibrosis, and impaired liver regeneration. To capture key features of severe ALD, we employed a murine model combining ethanol (EtOH) exposure with galactosamine (GalN), a hepatotoxic agent that sensitizes the liver to endotoxin-induced injury. Using this model, we evaluated the therapeutic efficacy of resolvin D1 (RvD1), a lipid mediator with potent anti-inflammatory and tissue-protective actions. Methods: C57BL/6J male mice were fed 5% EtOH-containing liquid diet for 10 days and administered GalN (500 mg/kg, i.p.) on days 9, 10, and 11, followed by a single EtOH binge (5 g/kg) on day 11. A separate cohort also received RvD1 (500 ng/mouse, days 7–12) as a therapy. Markers of endotoxemia, liver injury, inflammation, fibrosis, and regeneration were evaluated at 9 and 48 hours after the binge. Results: The EtOH+GalN model reproduced hallmark features of advanced ALD, including acute liver injury, sustained inflammation, induction of pro-fibrotic gene markers, reduced hepatic synthetic function, and markedly impaired regenerative capacity. RvD1 treatment significantly mitigated EtOH+GalN-induced pathology, lowering plasma endotoxin and ALT levels, reducing hepatic necrosis, and limiting neutrophil infiltration. RvD1 also decreased hepatic IL-6 levels at 9 hours and reduced IFN-γ at 48 hours. In addition, RvD1 attenuated the expression of pro-fibrotic genes and improved the diminished regenerative response in EtOH+GalN-treated mice, increasing hepatocyte proliferation at 48 hours and partially restoring plasma albumin concentrations. Conclusion: This study established an EtOH+GalN exposure mouse model of severe ALD and demonstrated that RvD1 exerts significant hepatoprotective effects. The findings support RvD1 as a promising therapeutic candidate for advanced ALD and provide the rationale for further mechanistic studies and translational evaluation.

Differential Role Of Prkcε In The Pathogenesis Of Chronic Alcohol-Induced Liver Injury

Chronic alcohol consumption is a major cause of liver injury, progressing from hepatic steatosis to inflammation, necrosis, and fibrosis. Protein kinase C epsilon (PRKCε) has been implicated in alcohol-induced hepatic steatosis; however, its contribution to subsequent inflammatory and necrotic injury remains unclear. The present study investigated the differential role of PRKCε in chronic ethanol-induced liver injury using an experimental animal model. Mice were maintained on a high-fat diet and treated with either saline or PRKCε antisense oligonucleotides (ASO) for four weeks, followed by ethanol exposure. Hepatic lipid accumulation, fatty acid synthase (FAS), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), inflammation, necrosis, and fibrin deposition were evaluated. PRKCε ASO treatment significantly attenuated ethanol-induced hepatic lipid accumulation and prevented the ethanol-mediated increase in FAS expression. Furthermore, PRKCε inhibition completely suppressed the elevation of TNF-α expression associated with ethanol exposure. Despite these effects, PRKCε ASO administration did not significantly reduce chronic ethanol-induced hepatic inflammation or necrosis. Similarly, the ethanol-induced upregulation of PAI-1 and accumulation of fibrin were unaffected by PRKCε inhibition. These findings indicate that PRKCε plays an important role in alcohol-induced hepatic steatosis and associated metabolic alterations but is not the primary mediator of chronic inflammatory and necrotic liver injury. The persistence of PAI-1 elevation and fibrin deposition despite PRKCε inhibition suggests that these pathways may independently contribute to progression of alcohol-induced hepatic damage. Thus, targeting multiple pathological pathways may provide a more effective strategy for preventing chronic alcohol-related liver injury.

Esculin attenuates cholestatic liver injury and fibrosis in bile duct-ligated rats by modulating oxidative stress, inflammatory responses, and fibrogenic mediators

The anti-obesity and hepatoprotective effects of bacterial cyclodipeptides in a rat obesity model involve aquaporins, inflammatory factors, and GAB1 modulation

Dexpanthenol Attenuates High-Fructose Corn Syrup-Induced Hepatic Injury in Young Adult Rats by Modulating Oxidative Stress, Apoptosis, and Inflammasome-Associated Pyroptotic Signaling

It is suggested that DEX attenuates HFCS-induced liver injury through a multi-target mechanism involving suppression of oxidative damage, apoptosis, and inflammasome-associated pyroptotic signaling in young adult rats.

Colchicine attenuates myocardial inflammation, endothelial dysfunction, and apoptosis in a rat model of alcohol-related cardiac damage.