Cyclo-oxygenase-2 inhibitors ameliorate the severity of experimental colitis in rats

Background Both in experimental colitis and in inflammatory bowel disease, colonic eicosanoid generation is enhanced and may contribute to the pathoge nesis of the inflammatory response. Aims To evaluate the effect of selective cyclo-oxygenase-2 (COX-2) inhibito rs on the extent and severity of two models of experimental colitis. Methods Colitis was induced by intra-caecal administration of 2 mi 5% aceti c acid or intra-colonic administration of 0.1 mi 3% iodoacetamide, Rats wer e 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 wa s isolated, weighed, macroscopic damage was measured, and mucosal samples w ere obtained for histology and for determination of myeloperoxidase (MPO) a nd nitric oxide synthase (NOS) activities and eicosanoid generation. The se rum levels of thromboxane B-2 (TXB2), tumour necrosis factor-alpha (TNF-alp ha) and interleukin-1 beta (IL-1 beta) were determined. Results 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 col itis induced by nimesulide was accompanied by a significant decrease in muc osal MPO and NOS activities. Nimesulide and SC-236 decreased the enhanced c olonic eicosanoid generation in acetic acid and iodoacetamide-induced colit is, and, in iodoacetamide-treated rats, nimesulide also decreased the eleva ted serum TNF-alpha and IL-1 beta levels. Conclusions The effective nimesulide and SC-236-induced amelioration of the severity of the colitis in acetic acid and iodoacetamide-treated rats conf irms the role of eicosanoids in their pathogenesis and suggests that COX-2 inhibitors may be of value in the treatment of inflammatory bowel disease. for I Gastroenterol Hepatol 12:223-231 (C) 2000 Lippincott Williams & Wilki ns.