Telmisartan decreases inflammation by modulating TNF-α, IL-10, and RANK/RANKL in a rat model of ulcerative colitis.

Abstract

BACKGROUND:

Telmisartan is an antihypertensive angiotensin II receptor blocker. This antihypertensive shows antiinflammatory activity.

PURPOSE:

In this study, the antiinflammatory activity of telmisartan was tested in an acetic acid (10%) model of ulcerative colitis (UC) in rats.

METHODS:

Rats were given 1, 3, and 5mg/kg/day of telmisartan orally for 3 days before induction of UC. The same doses were also administered 2 and 24h after induction. Rats from the non-colitis and non-treated colitis groups were administered vehicle (saline, 5 ml/kg) orally and another group received sulfasalazine (50mg/kg/day). Colons tissue was analyzed by macroscopic, by histopathology, by the immunohistochemical examination of RANKL/RANK pathway; by ELISA analysis of the levels of IL-10, TNF-α, myeloperoxidase (MPO) and malonaldehyde (MDA).

RESULTS:

Telmisartan at 5mg/kg reduced levels of MPO, MDA, TNF-α and increased of IL-10 (p<0.05). Additionally, telmisartan reduced macroscopic damage, number of ulcers, and inflammatory and histopathological processes such as neutrophil infiltration, changes in cytoarchitecture, and necrosis. Immunohistochemistry revealed down-regulation of nuclear factor-kappaB receptor/nuclear factor-kappaB ligand (RANK/RANKL) in groups treated with sulfasalazine or telmisartan.

CONCLUSION:

Telmisartan exerts beneficial effects in an acetic acid model of colitis in rats. These effects may be due to accelerated termination of the acute inflammatory phase, indicated by decreased TNF-α and increased production of IL-10 and low expression of RANKL and RANK.

• Authors: Gerlane C B Guerra, Aurigena A Araújo, George A Lira, Maryanne N Melo, Késia K O Souto, Daline Fernandes, Arthur L Silva, Raimundo F Araújo Júnior
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 67 Issue 3 Pg. 520-6 (Jun 2015) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 25933964 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• Benzimidazoles
• Benzoates
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Telmisartan

Topics

• Animals
• Benzimidazoles (therapeutic use)
• Benzoates (therapeutic use)
• Colitis, Ulcerative (drug therapy, metabolism, pathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Inflammation (drug therapy, metabolism, pathology)
• Interleukin-10 (physiology)
• RANK Ligand (physiology)
• Rats
• Rats, Wistar
• Receptor Activator of Nuclear Factor-kappa B (physiology)
• Telmisartan
• Tumor Necrosis Factor-alpha (physiology)