Telmisartan decreases inflammation by modulating TNF-α, IL-10, and RANK/RANKL in a rat model of ulcerative colitis.
BACKGROUND
Telmisartan is an antihypertensive angiotensin II receptor blocker. This antihypertensive shows antiinflammatory activity.


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Biophysical and Pharmacology, UFRN, Natal, Brazil.
Gerlane C B
GC
Guerra
Department of Biophysical and Pharmacology, Post Graduation Program in Public Health/Post Graduation Program in Pharmaceutical Science, UFRN, Natal, Brazil.
Aurigena A
AA
Araújo
Department of Morphology, Post Graduation Program in Health Science UFRN, Natal, Brazil.
George A
GA
Lira
Department of Pharmaceutical Science, Post Graduation Program in Pharmaceutical Science, UFPE, Recife Pe, Brazil.
Maryanne N
MN
Melo
Department of Textile Engineer, UFRN, Natal, Brazil.
Késia K O
KK
Souto
Department of Nutrition, Post Graduation Program in Technology and Science of Food, UFPB, Paraiba, Brazil.
Daline
D
Fernandes
Department of Pharmacology Science, UFRN, Natal, Brazil.
Arthur L
AL
Silva
Department of Morphology, Post Graduation Program in Functional and Structural Biology/Post Graduation Program in Health Science, UFRN, Natal, Brazil. Electronic address: araujojr@cb.ufrn.br.
Raimundo F
RF
Araújo Júnior
D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000502:physiology*; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D001562:Benzimidazoles; D001565:Benzoates; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000077333:Telmisartan
Angiotensin II receptor blockers; Antiinflammatory; Immunohistochemical; Rats