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Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
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  11. Protective Effect Of Dimethyl Fumarate Against Ethanol-provoked Gastric Ulcers In Rats Via Regulation Of Hmgb1/tlr4/nf-κb, And Pparγ/sirt1/nrf2 Pathways: Involvement Of Mir-34a-5p

Protective effect of dimethyl fumarate against ethanol-provoked gastric ulcers in rats via regulation of HMGB1/TLR4/NF-κB, and PPARγ/SIRT1/Nrf2 pathways: Involvement of miR-34a-5p

Eman M Elbaz1, Amina A S Abdel Rahman2, Amira A El-Gazar3

  • 1Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.

Archives of Biochemistry and Biophysics
|July 25, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Dimethyl fumarate (DMF) effectively heals gastric ulcers in rats by reducing inflammation and oxidative stress. This study suggests DMF could be a new treatment for gastric ulcers by restoring the gastric mucosal barrier.

Area of Science:

  • Gastroenterology
  • Pharmacology
  • Molecular Biology

Background:

  • Gastric ulcers (GU) are linked to disruptions in the gastric mucosal barrier's homeostasis.
  • Understanding protective mechanisms is crucial for developing effective GU treatments.

Purpose of the Study:

  • To investigate the gastroprotective effects of dimethyl fumarate (DMF) on ethanol-induced gastric ulcers in rats.
  • To elucidate the underlying molecular mechanisms of DMF's action.

Main Methods:

  • Rats were pretreated with DMF (80 mg/kg) or omeprazole (20 mg/kg) for two weeks.
  • Gastric ulcers were induced using oral ethanol administration.
  • Macroscopic, microscopic, biochemical, and molecular analyses were performed.

Main Results:

Keywords:
Dimethyl fumarateGastric ulcerHMGB1Nrf2

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  • DMF significantly reduced gastric damage, secretion, acidity, and ulcer area while increasing mucus production.
  • DMF upregulated miR-34a-5p, suppressed HMGB1, and reduced inflammatory responses.
  • DMF enhanced antioxidant defenses via the PPARγ/SIRT1/Nrf2 pathway and mitigated apoptosis.

Conclusions:

  • Dimethyl fumarate demonstrates significant gastroprotective effects against ethanol-induced gastric ulcers in rats.
  • DMF acts by attenuating inflammation, oxidative stress, and apoptosis, restoring gastric mucosal barrier integrity.
  • DMF shows potential for repurposing as a novel therapeutic agent for gastric ulcers.
miR-34a-5p