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Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease*1
Abstract
The pathogenesis of alcohol-induced liver disease involves the adverse effects of ethanol metabolites and oxidative tissue injury. Previous studies indicated that covalent protein adducts with reactive aldehydes may be formed in alcohol consumers. To study the role of such protein adducts in the development of liver injury, we examined the sequential appearances of adducts of the ethanol metabolite acetaldehyde (AA) and of two products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenol (HNE), in ethanol-fed micropigs. Immunohistochemical stainings using specific antibodies that recognize epitopes of each adduct were performed from liver biopsy specimens obtained at 1, 5, and 12 months from micropigs fed either control diet (n = 5) or ethanol-containing diets (n = 5). After 1 month on the ethanol diet, AA and MDA adducts were observed primarily in the perivenous regions co-localizing with each other and coinciding with increased concentrations of serum aminotransferase markers of liver injury. HNE adducts were usually less intense and more diffuse, and were also seen in some biopsy specimens from control animals. Although the most intense staining reactions at 5 months remained in zone 3, a more widespread distribution was usually seen together with increased evidence of steatonecrosis and focal inflammation. In terminal biopsies at 12 months, perivenous fibrosis was present in three of five biopsy specimens. More extensive pericentral and intralobular fibrosis was noted in one micropig fed ethanol for 21 months. These studies demonstrate that covalent adducts of proteins with reactive aldehydes are formed in early phases of alcohol-induced liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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“Although many aberrant signaling pathways are found in the pathogenesis of liver diseases, elevated levels of adducts with AA, MDA, MAA, 4-HNE, and HER likely contribute to alcohol-induced cell injury214,215.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [214]
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Metadata
- Authors
- NIEMELA, O.
- Venue
- Hepatology
- Publisher
- Elsevier BV
- Published
- 1995-10
- Volume
- 22
- Issue
- 4
- Pages
- 1208-1212
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W4232204742
- Cited by
- 149
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 2
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hepatology (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA-06938)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK -35747)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- alcoholic liver disease, acetaldehyde, lipid peroxidation, malondialdehyde, 4-hydroxynonenal, protein adducts, reactive aldehydes, liver fibrosis, steatonecrosis, alcohol metabolism, oxidative tissue injury, micropigs, transaminases
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