Effects of Mesalazine on Morphological and Functional Changes in the Indomethacin-Induced Inflammatory Bowel Disease (Rat Model of Crohn's Disease).
Morphological and functional changes have been investigated in the rat model of Crohn's disease. The inflammatory bowel disease was induced by indomethacin (1 × 10 mg/kg s.c. for 3 days). Morphological alterations were evaluated by macroscopic scoring system and on the base of histological changes in the small intestine. Functional activities were studied by determination of the intestinal and hepatic elimination of p-Nitrophenol (PNP) and its metabolites (PNP-glucuronide: PNP-G and PNP-sulfate: PNP-S) during the luminal perfusion of PNP. It was found that the indomethacin induced severe macroscopic changes (hyperaemia, petechia, bleeding, erosions, ulcerations) and significant histological alterations in the small intestine of rats which were definitely inhibited by mesalazine (1000 mg/kg by gastric tube for 3 days). Disappearance of PNP from the luminal perfusion solution was diminished by indomethacin which was corrected by administration of mesalazine. Significant depression was found in the luminal appearance of PNP metabolites by giving of indomethacin and these alterations could not be compensated by mesalazine.Hepatic elimination of PNP (biliary excretion of PNP and its metabolites) was decreased definitely by indomethacin which was - at least partly - compensated by mesalazine.The findings of the present study suggest that the indomethacin-induced inflammation in the small intestine represents a useful rat model of Crohn's disease. Morphological and functional alterations caused by indomethacin can be compensated by mesalazine.
Department of Pharmacology and Pharmacotherapy, Medical Faculty, University of Pécs, 12 Szigeti út, Pécs, Hungary.
Higin
H
Simon
Department of Pharmacology and Pharmacotherapy, Medical Faculty, University of Pécs, 12 Szigeti út, Pécs, Hungary.
Tamás
T
Fischer
Department of Pharmaceutical Chemistry, Pharmaceutical Faculty, University of Pécs, 2 Rókus utca, Pécs, Hungary.
Attila
A
Almási
Department of Pharmacology and Pharmacotherapy, Medical Faculty, University of Pécs, 12 Szigeti út, Pécs, Hungary. emil.fischer@aok.pte.hu.
Emil
E
Fischer
D000818:Animals; D003424:Crohn Disease / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D005965:Glucuronates / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D007421:Intestine, Small / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D009578:Nitrobenzenes / Q000494:pharmacology; D009596:Nitrophenols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D005965:Glucuronates; D009578:Nitrobenzenes; D009596:Nitrophenols; C049288:p-nitrophenol glucuronide; C023379:4-nitrophenyl sulfate; D019804:Mesalamine; D007213:Indomethacin; C024836:4-nitrophenol
Crohn’s disease; Indomethacin; Inflammatory bowel disease; Mesalazine; p-Nitrophenol