sc-236 and nimesulide

To investigate the effects of inhibitors of COX-1 or COX-2 on myometrial prostaglandin synthesis and on spontaneous contractions in human myometrium.. Cultured myometrial cells were incubated with SC 58560 (COX-1 selective inhibitor) or SC 58236 (COX-2 selective inhibitor), and the production of prostaglandins determined by ELISA. Spontaneously contracting strips of isolated gravid human lower segment myometrium were incubated with SC 58236, meloxicam, DFU, or nimesulide (COX-2 selective inhibitors), with SC 58560 (COX-1 selective inhibitor) or indomethacin (non-selective inhibitor).. SC 58236 inhibited the production of prostaglandins from myometrial cells, whereas SC 58560 had less effect. Nimesulide (100 microM) and indomethacin (300 microM) completely inhibited myometrial contractions, whereas meloxicam, DFU, SC 58236 and SC 58560 had less effect.. There was no relationship between the inhibition of prostaglandin production and the effects of the compounds on contractility. Myometrial prostaglandin synthesis does not seem to be essential for spontaneous contractility.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Female; Humans; Indomethacin; Isoenzymes; Meloxicam; Membrane Proteins; Myometrium; Organic Chemicals; Pregnancy; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pyrazoles; Sulfonamides; Thiazines; Thiazoles; Uterine Contraction

Both in experimental colitis and in inflammatory bowel disease, colonic eicosanoid generation is enhanced and may contribute to the pathogenesis of the inflammatory response.. To evaluate the effect of selective cyclo-oxygenase-2 (COX-2) inhibitors on the extent and severity of two models of experimental colitis.. Colitis was induced by intra-caecal administration of 2 ml 5% acetic acid or intra-colonic administration of 0.1 ml 3% iodoacetamide. Rats were treated intra-gastrically with nimesulide 2 x 10 mg/kg/day, or once with SC-236 6 mg/kg, and killed 1 or 3 days after damage induction. The colon was isolated, weighed, macroscopic damage was measured, and mucosal samples were obtained for histology and for determination of myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities and eicosanoid generation. The serum levels of thromboxane B2 (TXB2), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined.. Nimesulide significantly decreased the extent of colitis induced by acetic acid. Both nimesulide and SC-236 significantly decreased the extent of iodoacetamide-induced colonic damage. The decrease in the extent of colitis induced by nimesulide was accompanied by a significant decrease in mucosal MPO and NOS activities. Nimesulide and SC-236 decreased the enhanced colonic eicosanoid generation in acetic acid and iodoacetamide-induced colitis, and, in iodoacetamide-treated rats, nimesulide also decreased the elevated serum TNF-alpha and IL-1beta levels.. The effective nimesulide and SC-236-induced amelioration of the severity of the colitis in acetic acid and iodoacetamide-treated rats confirms the role of eicosanoids in their pathogenesis and suggests that COX-2 inhibitors may be of value in the treatment of inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis; Cyclooxygenase Inhibitors; Disease Models, Animal; Eicosanoids; Indomethacin; Inflammation; Interleukin-1; Male; Nitric Oxide Synthase; Peroxidase; Pyrazoles; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Sulfonamides; Tumor Necrosis Factor-alpha