Blocking the Apelin Receptor (APJ) Attenuates TNBS-Induced Colitis in Rats

İlknur Birsen; Osman Sinen; Simla Su Akkan; İsmail Üstünel; V. Nimet İzgüt-Uysal

doi:10.58600/eurjther1883

Authors

İlknur Birsen Department of Chemistry, Faculty of Science, Akdeniz University, Antalya, Turkey https://orcid.org/0000-0002-8637-0250
Osman Sinen Department of Physiology, Faculty of Medicine, Akdeniz University, Antalya, Turkey https://orcid.org/0000-0002-3554-5604
Simla Su Akkan Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey https://orcid.org/0000-0002-2905-4083
İsmail Üstünel Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey https://orcid.org/0000-0002-3865-6457
V. Nimet İzgüt-Uysal Department of Physiology, Faculty of Medicine, Akdeniz University, Antalya, Turkey https://orcid.org/0000-0003-0513-5679

DOI:

https://doi.org/10.58600/eurjther1883

Keywords:

APJ, F13A, TNBS, ulcerative colitis, rat

Abstract

Objective: The apelinergic system, consisting of apelin, ELABELA, and the apelin receptor (APJ), has a wide range of roles in physiological and pathophysiological processes in tissues. The effects of increased apelin and APJ as an indicator of damage in inflammatory conditions or as a compensatory mechanism are not fully clear in inflammatory bowel disease (IBD). This study was designed to assess the role of APJ in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model.

Methods: Colitis in adult male Wistar rats were induced by intrarectally administered TNBS (30 mg b.w. in 50% ethanol). While the control group was treated with only saline to the colon, the TNBS+F13A and F13A groups received the APJ antagonist F13A (30 µg/kg/day, i.v.) for 3 days, starting immediately after TNBS or saline administration, respectively.

Results: A decrease in body weight and an increase in colon weight/length ratio and stool consistency score were observed in the TNBS group. TNBS caused an increase in the myeloperoxidase (MPO) activity and the number of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), as well as apelin production, leading to mucosal ulceration, necrosis, and submucosal edema in the colon. While F13A administration to the control did not cause any change in the colon, F13A administration immediately after TNBS greatly reduced the effects of TNBS.

Conclusion: APJ is involved in the development of damage in colitis induced by TNBS. F13A reduces the level of damage, inflammatory cell infiltration, and MPO enzyme activity. APJ may be a therapeutic target in IBD.

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