The DOI matches its Crossref record.
Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration
Open accessAbstract
Acetaldehyde and the lipid peroxidation-derived aldehyde malondialdehyde (MDA), are reactive compounds that are generated during ethanol metabolism in the liver, and both aldehydes have been shown to be capable of binding to proteins and forming stable adducts. Because similar concentrations of MDA and acetaldehyde can coexist in the liver during ethanol oxidation, protein adduct formation in the presence of both of these aldehydes was studied under both in vitro and in vivo conditions. When proteins were incubated in the presence of both MDA and acetaldehyde, MDA caused a marked and concentration-dependent increase in the stable binding of acetaldehyde to proteins. Maximum stimulation of binding occurred at approximately a fourfold molar excess of MDA relative to acetaldehyde when concentrations of 1.0 mmol/L and 0.1 mmol/L were tested. The formation of highly fluorescent product or products was associated with the MDA stimulation of acetaldehyde binding, indicating that new and distinct products were being generated. These hybrid adducts of MDA and acetaldehyde have been designated as MAA adducts. An affinity-purified polyclonal antibody was produced that specifically recognized MAA epitopes on proteins and did not cross-react with carrier proteins or proteins modified with either acetaldehyde or MDA alone. A quantitative competitive enzyme-linked immunosorbent assay (ELISA) was developed and detected the presence of MAA-modified proteins in liver cytosol from ethanol-fed rats but not in pair-fed controls. Quantification of the data from the competitive ELISA indicated the presence of approximately 75 pmoles protein-bound MAA per milligram liver cytosol proteins of the ethanol-fed animals. These results indicate that acetaldehyde and MDA can react together in a synergistic manner and generate hybrid adducts (MAA-adducts) and further suggest that MAA adducts may represent a major species of adducts formed in the liver during ethanol metabolism in vivo .
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Interactions between acetaldehyde or MDA and cellular proteins lead to the formation of MAA adducts, which are highly stable and resistant to rapid degradation178,179.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [178]
Citations
Cited by
Sorted by citations
Items 201–246 of 246
Stellate Cells in Alcoholic Hepatitis
Mandal, P., & Nagy, L. E. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800134-9.00010-5 · Cited by 3
Cooperative Aldehyde Chemistry Maps an Orthogonal Lysine Reactivity Landscape
Galindo, A. V., Sihag, P., Talbott, J. M., & Raj, M. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c01030 · Cited by 2
Martinez, L. R., García-Moreno, C., Pérez‐Pampín, E., et al. (2023) · Arthritis Research & Therapy · doi:10.1186/s13075-023-03180-x · Cited by 2
“These adducts are highly immunogenic and differ from adducts separately formed by MDA or AA [13–15].”
BackgroundTorres, S., Segalés, P., de la Rosa, L. C., García‐Ruiz, C., & Fernández-Checa, J. C. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_56 · Cited by 3
Disease and Therapy: A Role for Oxidants
Trinidad, E. M. M., Gutirrez, S. L. D. I., Tllez, A. M., & Lpez, M. (2013) · InTech eBooks · doi:10.5772/51994 · Cited by 2
Protective effect of black tea on integral membrane proteins in rat liver
Szachowicz‐Petelska, B., Skrzydlewska, E., & Figaszewski, Z. A. (2011) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2011.08.003 · Cited by 2
Pranoto, H., & Nugrahalia, M. (2020) · JURNAL BIOSAINS · doi:10.24114/jbio.v6i2.17938 · Cited by 2
“Peningkatan peroksidasi lipid menyebabkan kerusakan jaringan dan kegagalan mekanisme pertahanan antioksidan untuk mencegah pembentukan radikal bebas yang berlebihan serta menimbulkan respon imun (Alagammalet al., 2013; Tuma et al., 1996).”
BackgroundRole of non-Genetic Risk Factors in Exacerbating Alcohol-related organ damage
Osna, N. A., Bhatia, R., Thompson, C. M., Batra, S. K., Sushil Kumar, K., Cho, Y., Szabó, G., Molina, P. E., Weinman, S. A., Ganesan, M., et al. (2020) · Alcohol · doi:10.1016/j.alcohol.2020.05.002 · Cited by 2
Bode, C., Bode, J. C., Hahn, E. G., Rossol, S., Schäfer, C., & Schuppan, D. (2002) · Springer eBooks · doi:10.1007/978-3-642-56253-2_16 · Cited by 2
Mechanisms of Alcohol-Mediated Cancer
Mueller, S. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_73 · Cited by 1
Zhou, W., Aripova, N., Johnson, H. J., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1648290 · Cited by 1
“Once formed, MAA adducts have been demonstrated to act as potent immunogens, capable of eliciting strong innate and adaptive immune responses, tolerance loss, and the formation of anti-MAA antibody (12 – 14).”
Self-citationSwaminathan, K., Kumar, S., Clemens, D. L., & Dey, A. (2013) · Toxicology Research · doi:10.1039/c3tx50016k · Cited by 1
Albano, E., & Vidali, M. (2005) · Elsevier eBooks · doi:10.1016/b978-012564370-2/50096-9 · Cited by 1
Chen, J., Petersen, D. R., Schenker, S., et al. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb02023.x · Cited by 1
Sergent, O., Podechard, N., Aliche-Djoudi, F., & Lagadic‐Gossmann, D. (2013) · Nutrition Clinique et Métabolisme · doi:10.1016/j.nupar.2013.10.003 · Cited by 1
“[27] Tuma DJ, Thiele GM, Xu D, Klassen LW, Sorrell MF.”
BackgroundAutoantibodies in Rheumatoid Arthritis
Andrade, F., Darrah, E., & Rosen, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-31696-5.00056-5 · Cited by 1
Vagts, D. A. (2007) · Springer eBooks · doi:10.1007/978-3-540-33734-8_1 · Cited by 1
Shanmugam, N., Rajaram, S., Ekambaram, M., Rajendran, R., Ramasamy, Y., & Balasubramanian, A. (2022) · International Journal of Basic & Clinical Pharmacology · doi:10.18203/2319-2003.ijbcp20220413 · Cited by 1
The Ubiquitin–Proteasome System in Alcohol–Induced Pathology
Donohue, T., & French, S. (2005) · Elsevier eBooks · doi:10.1016/b978-012564370-2/50082-9 · Cited by 1
Oxidative Activation of Transcription Factor Pathways by Cigarette Smoke Oxidants
Stavridis, J. C. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6704-4_5 · Cited by 1
Role of Oxidative Stress in Alcohol-Induced Mitochondrial Dysfunction
Bailey, S. M. (2005) · Elsevier eBooks · doi:10.1016/b978-012564370-2/50091-x · Cited by 1
Viitala, K. (1998) · Cited by 1
Delgado, R. C., & Alcedo, S. P. (2002) · Progresos de Obstetricia y Ginecología · doi:10.1016/s0304-5013(02)75839-1 · Cited by 1
Diametric Effects of Acetaldehyde on Factor VII and Factor IX Function
Sabol, D. A., Basista, M. H., Brecher, A. S., et al. (1999) · Cited by 1
Aripova, N., Duryee, M. J., Hunter, C. D., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4125936 · Cited by 1
Self-citationVykoukal, J., Chen, Y., Hong, M. J., Zuo, M., Krishna, H., Katayama, H., Irajizad, E., Wu, R., Léon-Letelier, R. A., Dennison, J. B., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.04.587899 · Cited by 1
“35,36 Leveraging EV proteomic profiles, we additionally evaluated for aldehyde protein adduction.”
MethodAlcohol and Cancer: Biological Basis
Singletary, K. W. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-627-6_31
The Immune Response in the Pathogenesis of Alcoholic Liver Disease
Klassen, L. W., & Thiele, G. M. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-518-3_25 · Cited by 1
“Tuma and co-workers have shown the formation of hybrid adducts with acetaldehyde and MDA, designated MAA adducts, in livers of ethanol-fed rats (39, 40 ).”
BackgroundSelf-citationWorrall, S. (2001) · Steinkopff eBooks · doi:10.1007/978-3-642-96008-6_7
Worrall, S. (2003) · CRC Press eBooks · doi:10.1201/9780203507636.ch13
The Effect of Diet on Protein Modification by Ethanol Metabolites
Worrall, S. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-047-2_9
Thiele, G. M., & Klassen, L. W. (2009) · doi:10.1002/9783527628100.ch4
Self-citationA Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation
Hill, G. E., Gasanova, I., & Thiele, G. M. (2014) · Open Journal of Anesthesiology · doi:10.11648/j.ja.20140201.11
Self-citationShort Communication Ethanol Promotes Intestinal Tumorigenesis in the MIN Mouse 1
Roy, H. K., Gulizia, J. M., Karolski, W. J., et al. (2002)
Self-citationWatt, K. D. S., & Sorrell, M. F. (2004) · doi:10.1007/978-1-4615-6502-4_9
Self-citationSinger, P. D. M. D. H. C. M. M. V., & Teyssen, P. D. M. S. (2005) · Springer eBooks · doi:10.1007/3-540-26446-9_20
Modulation of Immunity and Viral-Host Interactions by Alcohol
Thiele, G. M., Szabó, G., Kovacs, E. J., et al. (2002) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200212000-00018
Self-citationA Mechanism for Inhaled Anesthetic-Induced Solid Organ Injury: Inflammation
Hill, G. E., Gasanova, I., & Thiele, G. M. (2014) · Open Journal of Anesthesiology · doi:10.4236/ojanes.2014.43012
“Fluorescence measurements were obtained on post dialysis samples using a Perkin Elmer (Norwalk, CT) LS-5B spectrophotofluorometer attached to a Perkin Elmer GP-100 graphics printer as previously described [15].”
BackgroundMethodInfluentialSelf-citationIntravenous Glutathione: A Promising Therapy for the Alcoholic Liver Disease
Adarsh, C. K. (2024) · Journal of Medical Science And clinical Research · doi:10.18535/jmscr/v12i03.02
The Adaptive Immune System and Liver Toxicity
Holt, M. R., & Ju, C. H. (2010) · Elsevier eBooks · doi:10.1016/b978-0-08-046884-6.01030-7
Alcohol Metabolism and Its Implications for Cancer
Murray, G. J., Brooks, P. J., & Zakhari, S. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0040-0_4
“Malondialdehyde MDA French et al. (1993), Niemela et al. (1994) 4-Hydroxynonenal HNE Kamimura et al. (1992) Malondialdehyde–acetaldehyde hybrid MAA Tuma et al. (1996) Hydroxyethyl radical HER Moncada et al. (1994) Crotonaldehyde Cr Brooks and Theruvathu (2005)”
BackgroundMethodPeriodontitis and Rheumatoid Arthritis—Mechanistic Evidence
Bartold, P. M., Cheah, C. W., & Vaithilingam, R. D. (2026) · Journal of Periodontal Research · doi:10.1111/jre.70132
Aging, liver, and alcohol-associated liver disease
Liu, T., Zheng, Z., Sun, H., Wang, X., & Gao, Y. (2026) · Hepatobiliary Communications · doi:10.1016/j.hbc.2026.100005
Fang, C., Xie, Q., Peng, L., et al. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.6c04195
Metadata
- Authors
- Tuma, D. J., Thiele, G. M., Xu, D., Klassen, L. W., & Sorrell, M. F.
- Affiliations
- United States Department of Veterans Affairs (US)
- ORCID
- Venue
- Hepatology
- Published
- 1996-04
- Volume
- 23
- Issue
- 4
- Pages
- 872-880
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2021937351
- Cited by
- 245
- References
- 0
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 12 · 2021: 6 · 2020: 7 · 2019: 2 · 2018: 8 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 18 · 2012: 8
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01aa004961-18)
- National Institute on Alcohol Abuse and Alcoholism (AA-04961, AA07818)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Keywords
- acetaldehyde, malondialdehyde, protein adducts, alcohol metabolism, liver, lipid peroxidation, polyclonal antibodies, competitive ELISA, liver cytosol
- MeSH terms
- Acetaldehyde, Ethanol, Animals, Enzyme-Linked Immunosorbent Assay, Liver, Male, Malondialdehyde, Protein Binding, Rabbits, Serum Albumin, Bovine, Rats, Wistar, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
