Anti-inflammatory activity of the leukotriene B4 receptor antagonist, SC-41930, in colitic cotton-top tamarins

Autor: R. Carson, S. W. Djuric, C. P. Anglin, D. L. Widomski, R. E. Walsh, D. J. Fretland, R. Hansard, M. Henke, N. Clapp
Rok vydání: 1994
Předmět:
Zdroj: Agents and Actions. 41:C254-C255
ISSN: 1420-908X
0065-4299
DOI: 10.1007/bf01987659
Popis: Cotton-top tamarins (CTTs) with histologically confirmed persistent and active colitis were given the leukotriene B4 (LTB4) receptor antagonist, SC-41930, (10 mg/kg BW, by gavage b.i.d.) for eight weeks. Anti-inflammatory activity was evaluated by colonic biopsy, stool consistency and the level of the lipid mediators LTB4 and prostaglandin E2 (PGE2) in rectal dialysates. Stool consistency did not improve with treatment but did not worsen. Blood chemistry (ALT, AST, LDH) and hematological parameters neither showed any untoward effects of SC-41930 treatment nor was there any effect on body weight. In rectal dialysate LTB4 levels were significantly reduced from pretreatment level of 4.87±1.46 ng/ml to 1.07±0.67 and 2.45±0.13 ng/ml at 4 and 8 weeks, respectively, and higher prostaglandin E2 (PGE2) over time. Histologically, 5/7 improved, 1/7 remained the same and 1/7 worsened. Oral SC-41930 treatment was safe and associated with an anti-colitic effect. The reduced LTB4 levels (affecting granulocyte degranulation and recruitment into tissues) and increased PGE2 (perhaps exerting a mucosal protective effect) may, in part explain the observed efficacy of this compound in active tamarin colitis. Use of the CTT model could provide insight into the inflammatory mediator contribution to idiopathic colitis and serve as a useful bridge between preclinical pharmacology and the assessment of these compounds in the medical management of human inflammatory bowel disease.
Databáze: OpenAIRE
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