Unraveling the Time‐Dependent Effects of Ethanol on Liver Disease: Insights From a Mice Model
Year: 2026
Type: article
Abstract: Alcohol-associated liver disease (ALD) is a significant global health concern that is characterized by hepatic triglyceride accumulation and dysregulation with impairment of oxygen homeostasis. This study investigated the time-dependent effects of ethanol exposure on liver disease progression in 2-month-old male C57/BL6 mice. Mice were treated with ethanol (20% ethanol at 5 gm/kg.b.wt/day) for 2, 4, and 6 months, and blood biochemical markers, liver histopathology, and gene expression were evaluated. Results showed that ethanol exposure led to significant increases in thiobarbituric acid reactive substances (TBARS), protein carbonyls, plasma nitric oxide (NOx), C-reactive protein, and homocysteine, liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (γ-GT), lactate dehydrogenase (LDH) indicating oxidative stress and liver injury. Lipid profile analysis revealed increased total cholesterol and triglycerides, with decreased HDL-cholesterol. Moreover, reduced mitochondrial enzyme activity indicates dysfunction. Histopathology and qRT-PCR analysis showed increased CYP2E1, Bax, Bcl2, p53, caspase-3, caspase-9, and inducible nitric oxide synthase (iNOS) gene expression, leading to ROS/RNS generation. The miR-21 was upregulated, while miR-26a was downregulated, contributing to lipid metabolism dysregulation, pro-inflammation, and pro-fibrosis. These findings suggest that ethanol exposure causes triglyceride accumulation and cholesterol dysregulation, leading to oxidative stress, mitochondrial dysfunction, and hepatocellular injury. The dysregulation of miR-21 and miR-26a contributes to ALD progression. Markers of oxidative stress, miRNAs, and disrupted metabolic pathways may serve as potential biomarkers or therapeutic targets for early detection and intervention in ALD.
DOI: 10.1002/bab.70157
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7138234030