The leukocyte recruitment inhibitor, NPC 15669 accelerates healing in acetic acid-induced colitis.
The therapeutic efficacy of the leukocyte recruitment inhibitor, NPC 15669 (N-[9H-(2,7-dimethylfluoren-9-yl-methoxy)carbonyl]-L-leucine), was evaluated through the time course of acetic acid colitis in rats. Intrarectal (i.r.) administration of dilute acetic acid produced intense inflammation of the colon, neutrophil infiltration, hemorrhage, necrosis and denuding of epithelium. Myeloperoxidase (MPO) accumulation increased approximately 40-fold (by day 1) and significant resolution of the disease occurred by day 9. When NPC 15669 (10 mg/kg, i.r.) was administered 24 h after acid, MPO accumulation and colonic lesion scores were significantly inhibited (days 3-9) and histological examination revealed the absence of hemorrhage, epithelial cell regeneration and complete restoration of the mucosal architecture. Thus, NPC 15669 prevents colonic damage and promotes healing of ulcers, even when administered at the peak of the inflammatory response.
Lowe
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Scios Nova Inc., Baltimore, MD 21224.
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D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; C071244:N-(9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl)leucine; D009195:Peroxidase; D007930:Leucine; D019342:Acetic Acid