Effect of COX-2 inhibitor lumiracoxib and the TNF-α antagonist etanercept on TNBS-induced colitis in Wistar rats.
Summary of "Effect of COX-2 inhibitor lumiracoxib and the TNF-α antagonist etanercept on TNBS-induced colitis in Wistar rats."
Crohn's disease (CD) is associated with gut barrier dysfunction. Besides the baseline barrier defect, a subgroup of patients also expresses an intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs. On the other hand, the anti-tumour necrosis factor alpha (TNF-α) treatment has brought benefits to these patients. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, and Etanercept (ETC), a TNF-α antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 47 Wistar rats were randomized into seven groups, as follows: (1) Sham: sham induced-colitis; (2)
TNBS:
nontreated induced-colitis; (3) Lumiracoxib control; (4) Lumiracoxib-treated induced-colitis; (5) ETC control; (6) ETC-treated induced-colitis; (7) Lumiracoxib-ETC-treated induced-colitis. Rats from groups 6 and 7 presented significant improvement of macroscopic and histopathological damages in the distal colon. The gene expression of COX-2 mRNA, as well of TNF-α mRNA, decreased significantly in groups 6 and 7 compared to the TNBS nontreated and lumiracoxib-treated groups. The treatment only with lumiracoxib did not reduce the inflammation on TNBS-induced experimental colitis. ETC attenuated the damage seen in the colon and reduced the inflammation caused by TNBS. Our results suggest that down-regulation of TNF-α and COX-2 resulted in a decrease in inflammation caused by TNBS and thus provided some protection from the colonic damage caused by TNBS.
Affiliation
Department of Pathology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, SP, Brazil.
Journal Details
This article was published in the following journal.
Name: Journal of molecular histology
ISSN: 1567-2387
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22426941
- DOI: http://dx.doi.org/10.1007/s10735-012-9400-8
Medical and Biotech [MESH] Definitions
Colitis, Microscopic
A condition characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. This syndrome was first described in 1980 by Read and associates. Subtypes include COLLAGENOUS COLITIS and LYMPHOCYTIC COLITIS. Both have similar clinical symptoms and are distinguishable only by histology.
Drug-induced Liver Injury, Chronic
Liver disease lasting six months or more, caused by an adverse drug effect. The adverse effect may result from a direct toxic effect of a drug or metabolite, or an idiosyncratic response to a drug or metabolite.
Vitamin U
A vitamin found in green vegetables. It is used in the treatment of peptic ulcers, colitis, and gastritis and has an effect on secretory, acid-forming, and enzymatic functions of the intestinal tract.
4,5-dihydro-1-(3-(trifluoromethyl)phenyl)-1h-pyrazol-3-amine
A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
Placebo Effect
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
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