Tiron ameliorates acetic acid-induced colitis in rats : Role of TGF-β/EGFR/PI3K/NF-κB signaling pathway

Copyright © 2024 Elsevier B.V. All rights reserved..

BACKGROUND: Ulcerative colitis (UC), an ongoing inflammatory disorder of the colon, is marked by persistent mucosal surface irritation extending from the rectum to the near-proximal colon. Tiron is a synthetic analogue of vitamin E which is known to have antioxidant and anti-inflammatory effects in various animal models, so the goal of this study was to find out whether Tiron had any preventive impacts on UC inflicted by acetic acid (A.A) exposure in rats.

METHOD: Tiron (235 and 470 mg/kg) was administered intra-peritoneally for 2 weeks, and A.A (2 ml, 3 % v/v) was injected intra-rectally to cause colitis. Colon tissues and blood samples were then collected for measurement of various inflammatory and oxidative stress biomarkers.

RESULTS: Tiron administration significantly diminished lactate dehydrogenase (LDH), C-reactive protein (CRP), colon weight, and the weight/length ratio of the colon as compared to A.A-injected rats. Additionally, Tiron attenuated oxidative stress biomarkers. Tiron also enforced the levels of Glucagon-like peptide-1 (GLP-1) and trefoil factor-3 (TFF-3), while it greatly lowered the expression of nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interferon-γ (IFN-γ), and transforming growth factor-1(TGF-β1), phosphorylated epidermal growth factor receptor (P-EGFR), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) expression in colonic cellular structures. Furthermore, colonichistopathologic damages, revealed by hematoxylin and eosin (H&E) and Alcian Blue stain, were significantly decreased upon Tiron administration.

CONCLUSION: Tiron prevented A.A-induced colitis in rats via modulating inflammatory pathway TGF-β1/P-EGFR/PI3K/AKT/NF-κB, alongside managing the oxidant/antioxidant equilibrium, and boosting the reliability of the intestinal barrier.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:128

Enthalten in:

International immunopharmacology - 128(2024) vom: 15. Feb., Seite 111587

Sprache:

Englisch

Beteiligte Personen:

El Mahdy, Raghda N [VerfasserIn]
Nader, Manar A [VerfasserIn]
Helal, Manar G [VerfasserIn]
Abu-Risha, Sally E [VerfasserIn]
Abdelmageed, Marwa E [VerfasserIn]

Links:

Volltext

Themen:

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
4X87R5T106
Acetic Acid
Antioxidants
Biomarkers
EC 2.7.1.-
EC 2.7.1.137
EC 2.7.10.1
EC 2.7.11.1
ErbB Receptors
Journal Article
NF-kappa B
Phosphatidylinositol 3-Kinase
Phosphatidylinositol 3-Kinases
Phosphatidylinositol-3-Kinase
Protein Kinase B
Proto-Oncogene Proteins c-akt
Q40Q9N063P
Tiron
Transforming Growth Factor beta
Transforming Growth Factor beta1
Trefoil factor-3
Ulcerative colitis

Anmerkungen:

Date Completed 08.02.2024

Date Revised 08.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2024.111587

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36776413X