Cytochrome P450 as possible link between Mallory-Denk body formation in DDC-intoxicated mouse liver and human steatohepatitis.

Cornelia Stumptner, Karoline Fechter, Kurt Zatloukal, Helmut Denk

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Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

4 authors.

Cornelia StumptnerDiagnostic and Research Institute of Pathology, Center of Molecular Biomedicine, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria.

Karoline FechterDiagnostic and Research Institute of Pathology, Center of Molecular Biomedicine, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria.

Kurt ZatloukalDiagnostic and Research Institute of Pathology, Center of Molecular Biomedicine, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria.

Helmut DenkDiagnostic and Research Institute of Pathology, Center of Molecular Biomedicine, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria. helmut.denk@medunigraz.at.ORCID http://orcid.org/0000-0001-6959-0828

Funding

Bundesministerium für Bildung, Wissenschaft und Forschung 2023-0.752.780 (2023-2028)

6 · The paper itself

Abstract

Mallory-Denk bodies (MDBs) are hepatocytic inclusions in alcohol-related (ASH) and metabolic dysfunction-associated (MASH) steatohepatitis as well as in some other apparently etiologically different chronic human liver disorders. They are experimentally induced in mouse liver by chronic intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Like in human diseases, mouse liver MDBs consist of stress proteins as major components indicating their relationship to chronic cellular stress. Mouse livers at different stages of DDC intoxication, recovery, and re-intoxication were analyzed with regard to cytochrome P450 (CYP) expression, enzyme activity, oxidative stress, and anti-oxidative response. mRNAs of cytochrome P450 2A5 (CYP2A5), heme oxygenase-1 (Hmox-1), and the ubiquitin-binding adapter protein p62/sequestosome1 (p62) were significantly elevated by DDC treatment. CYP2A5 protein correlated at the cellular level with the presence of MDBs, and CYP2A5-related coumarin 7-hydroxylase (COH) activity was increased in relation to MDB expression. A functional relationship between CYP2A5 and Hmox-1 activity was established by the identification of bilirubin as a potent inhibitor of the production of reactive oxygen species (ROS) by CYP2A5. Moreover, CYP2E1 as well as CYP2A6, which are induced in human steatohepatitis, showed similar H

Indexed as

Cytochrome P-450 Enzyme SystemDihydropyridinesFatty LiverLiverMallory BodiesAnimalsAryl Hydrocarbon HydroxylasesCytochrome P450 Family 2Disease Models, AnimalHeme Oxygenase-1HumansMaleMiceMice, Inbred C57BLOxidative StressPyridines3,5-diethoxycarbonyl-1,4-dihydrocollidineAryl Hydrocarbon HydroxylasesCyp2a5 protein, mouseCytochrome P-450 Enzyme SystemCytochrome P450 Family 2DihydropyridinesHeme Oxygenase-1PyridinesAlcohol-related steatohepatitis (ASH)BilirubinCYP2A5Metabolic dysfunction-associated steatohepatitis (MASH)Oxidative stressReactive oxygen species (ROS)

Identifiers

PMID41168377

DOI10.1007/s00428-025-04290-4

PMCPMC13264601

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.