ArticleGastroenterology2010
Gender dimorphic formation of mouse Mallory-Denk bodies and the role of xenobiotic metabolism and oxidative stress.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- Cytochrome P450 as possible link between Mallory-Denk body formation in DDC-intoxicated mouse liver and human steatohepatitis.Virchows Archiv : an international journal of pathology · 2026Article
- Animal Models of Porphyria with Hepatic Involvement.Seminars in liver disease · 2025Review
- Vitamin D supplementation ameliorates ductular reaction, liver inflammation and fibrosis in mice by upregulating TXNIP in ductular cells.Nature communications · 2025Article
- SQSTM1/p62 and Hepatic Mallory-Denk Body Formation in Alcohol-Associated Liver Disease.The American journal of pathology · 2023Review
- BALB.NCT-Molecular genetics and metabolism reports · 2023Article
- Review
- Liver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling.JCI insight · 2020Article
- Normal and fibrotic liver parenchyma respond differently to irreversible electroporation.HPB : the official journal of the International Hepato Pancreato Biliary Association · 2019Article
- Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury.Cellular and molecular gastroenterology and hepatology · 2019Review
- Loss of hepatocyte β-catenin protects mice from experimental porphyria-associated liver injury.Journal of hepatology · 2019Article
- Keratin 18-deficiency results in steatohepatitis and liver tumors in old mice: A model of steatohepatitis-associated liver carcinogenesis.Oncotarget · 2016Article
- A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence.International journal of molecular sciences · 2016Review
- Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.PloS one · 2016Article
- Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.PloS one · 2016Article
- Absence of keratin 8 or 18 promotes antimitochondrial autoantibody formation in aging male mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Ambient Light Promotes Selective Subcellular Proteotoxicity after Endogenous and Exogenous Porphyrinogenic Stress.The Journal of biological chemistry · 2015Article
- Modulation of cytoskeletal dynamics by mammalian nucleoside diphosphate kinase (NDPK) proteins.Naunyn-Schmiedeberg's archives of pharmacology · 2015Review
- CD73 (ecto-5'-nucleotidase) hepatocyte levels differ across mouse strains and contribute to mallory-denk body formation.Hepatology (Baltimore, Md.) · 2013Article
- Lamin aggregation is an early sensor of porphyria-induced liver injury.Journal of cell science · 2013Article
- Wnt/β-catenin signaling protects mouse liver against oxidative stress-induced apoptosis through the inhibition of forkhead transcription factor FoxO3.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsMallory-Denk bodies (MDBs) are keratin (K)-rich cytoplasmic hepatocyte inclusions commonly associated with alcoholic steatohepatitis. Given the significant gender differences in predisposition to human alcohol-related liver injury, and the strain difference in mouse MDB formation, we hypothesized that sex affects MDB formation.
methodsMDBs were induced in male and female mice overexpressing K8, which are predisposed to MDB formation, and in nontransgenic mice by feeding the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). MDB presence was determined by histologic, immunofluorescence, and biochemical analyses and correlated to liver injury using serologic and pathologic markers. Cytoskeletal and metabolic liver protein analysis, in vitro metabolism studies, and measurement of oxidative stress markers and protoporphyrin-IX were performed.
resultsMale mice formed significantly more MDBs, which was attenuated modestly by estradiol. MDB formation was accompanied by increased oxidative stress. Female mice had significantly fewer MDBs and oxidative stress-related changes, but had increased ductular reaction protoporphyrin-IX accumulation, and MDB-preventive K18 induction. Evaluation of the microsomal cytochrome-P450 (CYP) enzymes revealed significant gender differences in protein expression and activity in untreated and DDC-fed mice, and showed that DDC is metabolized by CYP3A. The changes in CYPs account for the gender differences in porphyria and DDC metabolism. DDC metabolite formation and oxidative injury accumulate on chronic DDC exposure in males, despite more efficient acute metabolism in females.
conclusionsGender dimorphic formation of MDBs and porphyria associate with differences in CYPs, oxidative injury, and selective keratin induction. These findings may extend to human MDBs and other neuropathy- and myopathy-related inclusions.
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Registered trials
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.