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[Preventive effect of misoprostol against nonsteroidal anti-inflammatory drug-induced enteropathy in mice]
Jinlian Jin1, Faming Wu1, Zhaozhao Xiao2
1Department of Gastroenterology, Third Clinical Medical College, Gezhouba Central Hospital, Yichang 443002, China.
Objective:
To investigate the preventive effect of misoprostol against non-steroidal anti-inflammatory drug (NSAID)-induced intestinal injury in mice.
Methods:
NSAID-induced intestinal injury model was established through diclofenac sodium. Sixty specific-pathogen-free (SPF) BABL/c male mice were randomly divided into the following five groups: normal, model and three misoprostol groups with different concentrations (200, 400, 800 μg/kg). Misoprostol was given to aforementioned three misoprostol groups by gavage once a day for 6 days. In the fourth day afternoon, 5 mg/kg (10 mL/kg) diclofenac was fed to all mice by gavage except for normal group. On the seventh day, all mice were sacrificed and intestinal permeability was detected using FITC labeled dextran. The intestinal tissues were taken for detecting the mRNA and protein expressions of intestinal glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and tumor necrosis factor alpha (TNF-α) through HE staining, reverse transcription PCR and Western blotting, respectively.
Results:
Compared with the normal group, intestinal mucosa in the model group was seriously damaged and intestinal permeability significantly increased. The intestinal mucosal villus degeneration, necrosis, shedding, and inflammatory cell infiltration occurred in the model group. Yet, intestinal mucosal injury in different misoprostol groups was less severe. Their intestinal mucosal permeability was improved. The expressions of GRP78 protein and TNF-α, CHOP mRNAs on intestine were significantly reduced compared with those of the model group.
Conclusion:
Misoprostol has preventive effect against NSAID-induced intestinal diseases.
Insights
Misoprostol effectively prevents non-steroidal anti-inflammatory drug (NSAID)-induced intestinal injury in mice. Treatment reduced intestinal permeability and key inflammatory markers, demonstrating a protective effect.
Area of Science:
- Gastroenterology
- Pharmacology
- Toxicology
Background:
- Non-steroidal anti-inflammatory drugs (NSAIDs) are common causes of gastrointestinal injury.
- NSAID-induced intestinal damage poses a significant clinical challenge.
- Preventive strategies against NSAID enteropathy are crucial.
Purpose of the Study:
- To evaluate the protective efficacy of misoprostol against NSAID-induced intestinal injury.
- To investigate the impact of misoprostol on intestinal permeability and molecular markers of injury.
- To determine the dose-dependent effect of misoprostol.
Main Methods:
- An NSAID-induced intestinal injury model was established in mice using diclofenac sodium.
- Mice were treated with varying doses of misoprostol (200, 400, 800 μg/kg).
- Intestinal permeability, histology, and expressions of GRP78, CHOP, and TNF-α were assessed.
Main Results:
- Diclofenac sodium induced significant intestinal mucosal damage and increased permeability.
- Misoprostol treatment dose-dependently ameliorated these effects.
- Misoprostol reduced the expression of GRP78, CHOP, and TNF-α in the intestinal tissue.
Conclusions:
- Misoprostol demonstrates a significant preventive effect against NSAID-induced intestinal injury.
- The findings suggest misoprostol as a potential therapeutic agent for NSAID enteropathy.
- Misoprostol mitigates NSAID-induced intestinal damage by reducing inflammation and improving barrier function.
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