Lipid peroxidation contributes to immune reactions associated with alcoholic liver disease
Open accessAbstract
Increasing evidence indicates the involvement of immune reactions in the pathogenesis of alcoholic liver disease. We have investigated whether ethanol-induced oxidative stress might contribute to immune response in alcoholics. Antibodies against human serum albumin modified by reaction with malondialdehyde (MDA), 4-hydroxynonenal (HNE), 2-hexenal, acrolein, methylglyoxal, and oxidized arachidonic and linoleic acids were measured by ELISA in 78 patients with alcoholic cirrhosis and/or hepatitis, 50 patients with nonalcoholic cirrhosis, 23 heavy drinkers with fatty liver, and 80 controls. Titers of IgG-recognizing epitopes derived from MDA, HNE, and oxidized fatty acids were significantly higher in alcoholic as compared to nonalcoholic cirrhotics or healthy controls. No differences were instead observed in the titers of IgG-recognizing acrolein-, 2-hexenal-, and methylglyoxal-modified albumin. Alcoholics showing high IgG titers to one adduct tended to have high titers to all the others. However, competition experiments showed that the antigens recognized were structurally unrelated. Anti-MDA and anti-HNE antibodies were significantly higher in cirrhotics with more severe disease as well as in heavy drinkers with cirrhosis or extensive fibrosis than in those with fatty liver only. We conclude that antigens derived from lipid peroxidation contribute to the development of immune responses associated with alcoholic liver disease.
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In hepatic Kupffer cells, 4-HNE adducts are present and activate infiltration of neutrophils into the liver, leading to activation of HSCs and an inflammatory cytokine response; these findings indicate a contributing role of MAA and 4-HNE adducts in promoting the hepatic immune response associated with ALD development.
“In hepatic Kupffer cells, 4-HNE adducts are also present and activate the infiltration of neutrophils into the liver, leading to the activation of HSCs and an inflammatory cytokine response226–228.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [228]
In advanced ALD with cirrhosis, 4-HNE and MDA adducts are found in greater amounts than in nonalcoholic liver cirrhosis and normal liver, suggesting involvement of 4-HNE and MDA adducts in promoting advanced ALD.
“In advanced ALD with cirrhosis, 4-HNE and MDA adducts are also found in greater amounts than in nonalcoholic liver cirrhosis and normal liver139,228, suggesting the involvement of 4-HNE and MDA adducts in promoting advanced ALD.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [228]
The average levels of MDA- and HNE-protein adducts in 50 alcoholic cirrhosis patients were significantly higher than those in a similar number of patients with nonalcoholic cirrhosis or healthy individuals.
“In fact, the average levels of MDA- and HNE-protein adducts in 50 alcoholic cirrhosis patients were significantly higher than those in a similar number of patients with nonalcoholic cirrhosis or healthy individuals [180].”
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“In fact, the average levels of MDA- and HNE-protein adducts in 50 alcoholic cirrhosis patients were significantly higher than those in a similar number of patients with nonalcoholic cirrhosis or healthy individuals [180].”
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- Authors
- Mottaran, E., Stewart, S. F., Rolla, R., Vay, D., Cipriani, V., Moretti, M., Vidali, M., Sartori, M., Rigamonti, C., Day, C. P., & Albano, E.
- Affiliations
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- Newcastle University (GB)
- Corresponding author
- Albano, Emanuele
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 32
- Issue
- 1
- Pages
- 38-45
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2045642603
- Cited by
- 145
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 9 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 9 · 2014: 11 · 2013: 5 · 2012: 5
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- lipid peroxidation, alcoholic liver disease, alcoholic cirrhosis, alcoholic hepatitis, oxidative stress, ethanol, malondialdehyde, 4-hydroxynonenal, oxidized fatty acids, autoantibodies, IgG, immune response, liver fibrosis, hepatic steatosis
- MeSH terms
- Acrolein, Adult, Aged, Ethanol, Aldehydes, Female, Humans, Immunoglobulin G, Liver Diseases, Alcoholic, Male, Malondialdehyde, Middle Aged, Oxidation-Reduction, Serum Albumin, Lipid Peroxidation, Arachidonic Acid, Oxidative Stress, Linoleic Acid
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