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Effect of COX-2 inhibitor lumiracoxib and the TNF-α antagonist etanercept on TNBS-induced colitis in Wistar rats

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Abstract

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.

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Acknowledgments

This work was supported by the FAPESP and CAPES. DAR is a recipient of a CNPq fellowship. The authors wish to express their gratitude to Profa. Dra. Silvia Regina Caminada de Toledo, Indhira Dias Oliveira of the Pediatric Oncology Institute IOP/GRAACC of the Federal University of Sao Paulo, UNIFESP, SP, Brazil and Profa. Dra. Nora Manoukian Forones of the Division of Gastroenterology, Universidade Federal de Sao Paulo, Escola Paulista de Medicina, UNIFESP, SP, Brazil, for the technical assistance.

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Authors and Affiliations

  1. Department of Pathology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, SP, Brazil

    Ana Paula Ribeiro Paiotti, Daniel Araki Ribeiro, Patrícia Marchi, Celina Tizuko Fujiyama Oshima, Ricardo Artigiani Neto & Marcello Franco

  2. Department of Biosciences, Universidade Federal de Sao Paulo, UNIFESP, Av Ana Costa 95, Santos, SP, 11060001, Brazil

    Daniel Araki Ribeiro

  3. Division of Gastroenterology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, UNIFESP, Santos, SP, Brazil

    Roseane Mendes Silva & Sender Jankiel Miszputen

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  1. Ana Paula Ribeiro Paiotti
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Correspondence to Daniel Araki Ribeiro.

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Paiotti, A.P.R., Ribeiro, D.A., Silva, R.M. et al. Effect of COX-2 inhibitor lumiracoxib and the TNF-α antagonist etanercept on TNBS-induced colitis in Wistar rats. J Mol Hist 43, 307–317 (2012). https://doi.org/10.1007/s10735-012-9400-8

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  • DOI: https://doi.org/10.1007/s10735-012-9400-8

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