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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 8/2022

21-10-2021 | Chronic Inflammatory Bowel Disease | Original Article

Anti-inflammatory Effects of Ivermectin in the Treatment of Acetic Acid-Induced Colitis in Rats: Involvement of GABAB Receptors

Authors: Armin Aryannejad, Mohammadreza Tabary, Nafise Noroozi, Baharnaz Mashinchi, Setare Iranshahi, Seyed Mohammad Tavangar, Razieh Mohammad Jafari, Amir Rashidian, Ahmad Reza Dehpour

Published in: Digestive Diseases and Sciences | Issue 8/2022

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Abstract

Background

Recent investigations have proposed the potential role of gamma-aminobutyric acid (GABA) in regulating motility and immunity of the gastrointestinal system.

Aims

We aimed to investigate the anti-inflammatory effects of ivermectin (IVM) through GABAB receptors following acetic acid-induced colitis in rats.

Methods

In a controlled experimental study, we enrolled 78 male Wistar rats (13 groups; 6 rats/group). After colitis induction using acetic acid (4%), IVM, baclofen (a standard GABAB agonist) or the combination of both agents was delivered to rats orally (by gavage), with the same dosage continued for 5 days. The control group received the vehicle, and prednisolone (a standard anti-inflammatory agent) was administered in a separate group as the positive control. Colon samples were collected on the sixth day for histopathological evaluations and measurement of myeloperoxidase (MPO) activity, TNF-α levels, and p-NF-ĸB p65, COX-2 and iNOS expression levels.

Results

The greatest recovery was found after administering IVM 0.5, baclofen 0.5, or IVM 0.2 + baclofen 0.2 mg/kg/day (ulcer index [UI] = 1.4 ± 0.4, 1.7 ± 0.6, and 1.4 ± 0.3, respectively; p  < 0.001 vs. the control [UI = 6.5 ± 0.7]). Histopathological evaluations revealed a significant decrease in the inflammation severity in the three above-mentioned groups. P-NF-ĸB p65, COX-2, and iNOS expression, MPO activity, and TNF-α levels also decreased dramatically following treatment with IVM 0.5, baclofen 0.5, or the combination therapy (p < 0.001 vs. the control).

Conclusions

IVM exerted promising anti-inflammatory effects in treating acetic acid-induced colitis in rats. Its synergistic effect with baclofen also signified the possible involvement of GABAB receptors in this process.
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Metadata
Title
Anti-inflammatory Effects of Ivermectin in the Treatment of Acetic Acid-Induced Colitis in Rats: Involvement of GABAB Receptors
Authors
Armin Aryannejad
Mohammadreza Tabary
Nafise Noroozi
Baharnaz Mashinchi
Setare Iranshahi
Seyed Mohammad Tavangar
Razieh Mohammad Jafari
Amir Rashidian
Ahmad Reza Dehpour
Publication date
21-10-2021
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 8/2022
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-07258-x

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