Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats
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Background and rationale for the study. Bacterial translocation is an important triggering factor of infection and mortality in cirrhosis. In a rat model using bile duct ligation (BDL), bacterial translocation appears within 24 h after ligation. The dynamic between TH1/TH2/TH17 cytokines and the integrity of the colonic mucosa in the context of cirrhosis is little known. This study aims to determine the link between bacterial translocation and intestinal inflammation in a cholestasis model. Additionally, alterations of the colonic mucus layer and the bacterial load were also addressed. RESULTS: Bacterial translocation detected by microbiological cultures and MALDI-TOF showed that Escherichia coli predominates in mesenteric lymph nodes of BDL rats. Intestinal bacterial load analyzed by qPCR indicates a dramatic Escherichia/Shigella overgrowth at 8 and 30 days post-BDL. IFN-γ, IL-4, and IL-17 evaluated by Western blotting were increased at 8 and 30 days in the small intestine. In the colon, in contrast, only IFN-γ was significantly increased. The colonic mucus layer and mucin-2 expression determined by Alcian blue staining and immunohistochemistry surprisingly showed an increase in the mucus layer thickness related to increased mucin-2 expression during the entire process of liver damage. Hepatic enzymes, as well as collagen I, collagen III, TNF-α, and IL-6 liver gene expression were increased. In conclusion, bacterial overgrowth associated with bacterial translocation is linked to the over-expression of IFN-γ, IL-4, IL-17 and mucin-2. These molecules might facilitate the intestinal permeability through exacerbating the inflammatory process and disturbing tight junctions, leading to the perpetuation of the liver damage.
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Increased mucus thickness has been observed after BDL, pointing to a role of mucins and likely mucus-degrading bacteria during cholestasis.
“Interestingly, increased mucus thickness has been observed after BDL34 pointing to a role of mucins and likely mucus-degrading bacteria during cholestasis.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [34]
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- Authors
- Said, M. M., Azab, S. S., Saeed, N. M., & El-Demerdash, E.
- Affiliations
- Ministry of Health and Population (EG)
- Ain Shams University (EG)
- Egyptian Russian University (EG)
- Venue
- Annals of Hepatology
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 17
- Issue
- 2
- Pages
- 307-317
- ISSN
- 1665-2681 (ISSN-L)
- OpenAlex
- W2791596265
- Cited by
- 65
- References
- 84
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 7 · 2018: 2
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Hepatology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- bacterial translocation, liver cirrhosis, bile duct ligation, intestinal inflammation, Escherichia coli, MUC2, colonic mucus layer, interferon-gamma, IL-17, IL-4, Th1/Th17 cytokines, intestinal permeability, tight junctions, cholestasis, liver fibrosis
- MeSH terms
- Gastrointestinal Microbiome, Animals, Cholestasis, Disease Models, Animal, Hepatitis, Interferon-gamma, Intestinal Mucosa, Intestines, Liver, Liver Cirrhosis, Lymph Nodes, Male, Permeability, Time Factors, Interleukin-4, Up-Regulation, Rats, Wistar, Bacterial Translocation, Interleukin-17, Mucin-2
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