The DOI matches its Crossref record; 245 of the 245 references it cites were found in a registry or an index.
Pathogenesis of alcoholic liver disease: Role of oxidative metabolism
Open accessAbstract
Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility.
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“An accumulating body of evidence indicates that acetaldehyde activates HSCs in ALD by inducing oxidative stress [60].”
From Pathophysiological Aspects of Alcohol Metabolism in the Liver (2021) · cites this paper as [60]
In the citing paper
“In addition to individual AA and MDA adducts, MAA adducts (AA-MDA-protein hybrid adducts) are found in HSCs, liver sinusoidal endothelial cells, and Kupffer cells in ALD models.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [222]
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Metadata
- Authors
- Ceni, E., Mello, T., & Galli, A.
- Affiliations
- University of Florence (IT)
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2014-12-21
- Volume
- 20
- Issue
- 47
- Pages
- 17756-17772
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC4273126
- OpenAlex
- W1456504179
- Cited by
- 521
- References
- 245
- Citations by year
- 2026: 42 · 2025: 39 · 2024: 58 · 2023: 75 · 2022: 56 · 2021: 59 · 2020: 47 · 2019: 38 · 2018: 40 · 2017: 21 · 2016: 25 · 2015: 21
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- alcoholic liver disease, acetaldehyde, reactive oxygen species, alcoholic fatty liver, alcoholic hepatitis, liver fibrosis, hepatocellular carcinoma, hepatic stellate cells, collagen synthesis, AMPK, autophagy, lipid peroxidation, lipopolysaccharide translocation, intestinal barrier, Kupffer cells, natural killer cells, innate immunity, adaptive immunity, DNA adducts, DNA methylation
- MeSH terms
- Acetaldehyde, Ethanol, Animals, Humans, Immunity, Innate, Liver, Liver Diseases, Alcoholic, Oxidation-Reduction, Prognosis, Risk Factors, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Disease Progression, Adaptive Immunity
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