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Anti-Inflammatory Effects of Ivermectin in the Treatment Of Acetic Acid-Induced Colitis in Rats: Involvement of Gabab Receptors Publisher Pubmed



Aryannejad A1, 2 ; Tabary M1, 2 ; Noroozi N1, 2 ; Mashinchi B1, 2 ; Iranshahi S3 ; Tavangar SM4 ; Mohammad Jafari R1 ; Rashidian A1, 2 ; Dehpour AR1, 2
Authors
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Authors Affiliations
  1. 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, 13145-784, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: Digestive Diseases and Sciences Published:2022


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. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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