Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and nonalcoholic patients: Localization and association with progression of liver fibrosis†
Abstract
Acetaldehyde, the first product of ethanol oxidation, has been shown to stimulate collagen gene expression and to form protein-acetaldehyde adducts. Because little is known about these adducts in human liver tissue, we assessed, with an immunohistochemical procedure, the presence and location of acetaldehyde-protein adducts in liver biopsy specimens of alcoholic patients. In addition, we correlated the presence of adducts with the progression or subsequent occurrence of liver fibrosis. The group included 106 patients with high alcohol consumption (> 90 gm ethanol/day for the last 5 yr), 10 nonalcoholic patients with normal livers and 23 patients with other liver diseases. Sixty-four of the 106 alcoholic patients had a second liver biopsy, whose specimen was used to assess the progression of liver fibrosis. Polyclonal antibodies were produced against homologous low-density lipoprotein purified from rabbit serum and modified in vitro in the presence of acetaldehyde. Protein-acetaldehyde adducts could be detected by immunohistochemistry in biopsy specimens of 90 alcoholic patients (85%), in none of the 10 nonalcoholic patients with normal livers and in 65% of the patients with nonalcoholic liver disease. Acetaldehyde-modified epitopes were detected in the intracellular and extracellular compartment. Intracellular protein-acetaldehyde adducts were localized in the cytoplasm of hepatocytes with a more intense staining in zone 3. No correlation existed between the intensity of intr…
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Protein adducts contribute to lipid accumulation, inflammation, and fibrosis, playing a key role in the pathogenesis of various stages of ALD.
“Holstege et al. [41] demonstrated that protein adducts contribute to lipid accumulation, inflammation, and fibrosis, playing a key role in the pathogenesis of various stages of ALD.”
From Pathophysiological Aspects of Alcohol Metabolism in the Liver (2021) · cites this paper as [41]
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- Authors
- Holstege, A., Bedossa, P., Poynard, T., Kollinger, M., Chaput, J. C., Houglum, K., & Chojkier, M.
- Affiliations
- University of Regensburg (DE)
- Centre National de la Recherche Scientifique (FR)
- University of California San Diego (US)
- Venue
- Hepatology
- Published
- 1994-02
- Volume
- 19
- Issue
- 2
- Pages
- 367-374
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2161906863
- Cited by
- 80
- References
- 36
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- acetaldehyde, liver fibrosis, alcoholic liver disease, alcoholic hepatitis, liver cirrhosis, extracellular matrix, hepatocytes, fibrogenesis, collagen gene expression, alcohol metabolism, non-alcoholic liver disease, fibrosis progression, immunohistochemistry, polyclonal antibodies, low-density lipoprotein, liver biopsy
- MeSH terms
- Acetaldehyde, Adult, Antibody Specificity, Epitopes, Biopsy, Needle, Female, Humans, Immunohistochemistry, Liver, Liver Cirrhosis, Alcoholic, Liver Diseases, Male, Middle Aged, Prognosis
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