title: Effect of COX-2 inhibitor lumiracoxib and the TNF-α antagonist etanercept on TNBS-induced colitis in Wistar rats.
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.
authors.affiliation: Department of Pathology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, UNIFESP, Sao Paulo, SP, Brazil.
authors.forename: Ana Paula Ribeiro
authors.initials: AP
authors.lastname: Paiotti
authors.forename: Daniel Araki
authors.initials: DA
authors.lastname: Ribeiro
authors.forename: Roseane Mendes
authors.initials: RM
authors.lastname: Silva
authors.forename: Patrícia
authors.initials: P
authors.lastname: Marchi
authors.forename: Celina Tizuko Fujiyama
authors.initials: CT
authors.lastname: Oshima
authors.forename: Ricardo Artigiani
authors.initials: RA
authors.lastname: Neto
authors.forename: Sender Jankiel
authors.initials: SJ
authors.lastname: Miszputen
authors.forename: Marcello
authors.initials: M
authors.lastname: Franco
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D004008:Diclofenac; D014302:Trinitrobenzenesulfonic Acid; D051546:Cyclooxygenase 2; D000068800:Etanercept; C473384:lumiracoxib