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

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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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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgment

This study was supported by a grant from the Experimental Medicine Research Center, Tehran University of Medical Sciences (Grant No. 99-1-209-48299). The authors also want to thank the Iran National Science Foundation (INSF) for their kind support.

Funding

This study was supported by a grant from the Experimental Medicine Research Center, Tehran University of Medical Sciences (Grant No. 99-1-209-48299).

Author information

Author notes

  1. Armin Aryannejad and Mohammadreza Tabary have contributed equally to this work.

Authors and Affiliations

  1. Experimental Medicine Research Center, Tehran University of Medical Sciences, 13145-784, Tehran, Iran

    Armin Aryannejad, Mohammadreza Tabary, Nafise Noroozi, Baharnaz Mashinchi, Razieh Mohammad Jafari, Amir Rashidian & Ahmad Reza Dehpour

  2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Armin Aryannejad, Mohammadreza Tabary, Nafise Noroozi, Baharnaz Mashinchi, Amir Rashidian & Ahmad Reza Dehpour

  3. Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Setare Iranshahi

  4. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Tavangar

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Contributions

Study conception and design: AD; acquisition of data: AA, MT, NN, SMT; analysis and interpretation of data: AA, MT, AR, RM; drafting of the manuscript: AA, MT, BM, AD, SI; critical revision: AD, AR.

Corresponding author

Correspondence to Ahmad Reza Dehpour.

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The authors declare that they have no conflict of interest.

Ethics approval

All experiments were carried out according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8523, revised in 2011). All the study protocols were also approved by the Ethics in Medical Research Committee of Tehran University of Medical Sciences (No. IR.TUMS.MEDICINE.REC.1399.135) and were therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Aryannejad, A., Tabary, M., Noroozi, N. et al. Anti-inflammatory Effects of Ivermectin in the Treatment of Acetic Acid-Induced Colitis in Rats: Involvement of GABAB Receptors. Dig Dis Sci 67, 3672–3682 (2022). https://doi.org/10.1007/s10620-021-07258-x

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