mobic and Colitis

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin synthesis by inhibiting cyclo-oxygenase 1 (COX-1) and/or cyclo-oxygenase 2 (COX-2). Different groups of NSAIDs, defined by their action on either COX-1 or COX-2, have been developed. Whether intestinal toxicity of preferential or selective COX-2 inhibitors is reduced compared with that of standard NSAIDs is controversial. We report the cases of two patients with self-limited colitis induced by preferential COX-2. We discuss the mechanisms of intestinal toxic effects of COX-2 preferential inhibitors from endoscopic and histological features of colitis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis; Cyclooxygenase Inhibitors; Female; Humans; Meloxicam; Middle Aged; Sulfonamides; Thiazines; Thiazoles

Whether intestinal toxicity of preferential or selective COX-2 inhibitors is reduced compared with that of standard NSAIDs is controversial. A 26-year-old woman presented with acute abdominal pain and bloody diarrhoea a few days after beginning meloxicam treatment. Endoscopic examination of the colon showed erythematous and ulcerative lesions involving 15 cm of the left colon. No aetiology has been found for colitis. Diarrhea disappeared 1 week after meloxicam was stopped. Total colonoscopy 3 months and 2 years later was normal. The role of meloxicam in the etiology of colitis was considered plausible. This report and a few other cases in the literature suggest that cyclooxygenase-2 selective non-steroidal anti-inflammatory drug inhibitor toxicity should be investigated in case of unexplained acute colitis.

Topics: Abdominal Pain; Adult; Analgesics, Non-Narcotic; Colitis; Colonoscopy; Cyclooxygenase 2 Inhibitors; Female; Humans; Meloxicam; Nefopam; Thiazines; Thiazoles; Tomography, X-Ray Computed

Inflammatory bowel diseases are associated with reduced colonic contractility and induction of cyclooxygenase-2. In this study a possible role of cyclooxygenase-2 in and the underlying mechanism of the reduced contractility were investigated in experimental colitis. The effects of meloxicam, a cyclooxygenase-2 selective inhibitor were examined on colonic contractility and MAP kinase p38 and ERK(1/2) expression. Colitis was induced in Sprague-Dawley male rats by intra-colonic instillation of trinitrobenzenesulphonic acid (TNBS; 40 mg/rat in 50 ethanol). The animals were divided into three groups. Group 1 (n=9) received meloxicam (3 mg/kg-day) gavage 1 h before and 1 day (Group 2) after induction of colitis. Group 3 (n=9) received phosphate buffered saline (PBS) in a similar manner and served as colitic control. The non colitic control animals received meloxicam in a similar manner. The animals were sacrificed after 5 days of treatment, colon was cleaned with PBS and colonic smooth muscle was obtained which was used in this study. Meloxicam treatment given 1 h before or 1 day after administration of colitis restored the reduced colonic contractility without affecting the sensitivity to carbachol. The levels of colonic smooth muscle IL-1beta mRNA, PGE(2), ERK(1/2), p38, malondialdehyde, myeloperoxidase activity and colonic mass were increased, whereas the body weight was decreased due to TNBS. The changes except colonic muscle mass and p38 expression were reversed by meloxicam treatment. These findings indicate that restoration of reduced colonic contractility by meloxicam is mediated by ERK(1/2), and that ERK(1/2) may serve as an important anti inflammatory target for treatment of colitis.

Topics: Animals; Blotting, Western; Carbachol; Colitis; Colon; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Gastrointestinal Motility; Isometric Contraction; Male; Malondialdehyde; Meloxicam; Muscle, Smooth; p38 Mitogen-Activated Protein Kinases; Peroxidase; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thiazines; Thiazoles; Trinitrobenzenesulfonic Acid

The effects of cyclooxygenase-2 (cox-2) inhibition by a cox-2 selective antisense phosphorothioated oligonucleotide (AS) and meloxicam were examined in experimental colitis.. Colitis was induced by trinitrobenzenesulphonic acid (TNBS) and acetic acid (Hac) separately in male Sprague-Dawley rats. Both groups of animals were treated daily intraperitoneally with AS and a mismatched control oligo (CO) (3 mg/kg), and orally with meloxicam (7.5 mg/kg) 1 h before induction of colitis. The animals were killed on day 4 (Hac) and on day 5 (TNBS). Tissue samples from colon, ileum, liver, kidney and spleen were collected for mRNA, myeloperoxidase activity (MPO), prostaglandin E2 (PGE2) estimation and for histology, and blood samples for PGE2, thromboxane B2 (TxB2) and TNF-alpha.. Both TNBS and Hac increased colonic MPO activity, PGE2 concentrations and infiltration of colonic wall by inflammatory cells. Serum levels of TNF-alpha were increased in both models, whereas PGE2 was increased only in TNBS colitis. Only meloxicam suppressed the level of PGE2 significantly below the basal level. The animals in both models also showed splenomegaly. The colitis-induced changes were significantly suppressed by the treatment of the test compounds but not by the CO. Cox-2 mRNA but not cox-1 was decreased by the AS, but not by meloxicam or in CO-treated colitic animals.. The findings demonstrate comparable beneficial effects of the cox-2 selective antisense oligonucleotide and meloxicam, which seem to be mediated by a combined inhibition of both PGE2 and TNF-alpha in the present models of colitis.

Topics: Animals; Colitis; Colon; Cyclooxygenase Inhibitors; Dinoprostone; Male; Meloxicam; Oligonucleotides, Antisense; Peroxidase; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thiazines; Thiazoles; Thromboxane B2; Tumor Necrosis Factor-alpha