5-aminosalicylic acid improves indomethacin-induced enteropathy by inhibiting iNOS transcription in rats.
Nitric oxide has been implicated in the pathogenic mechanism of inflammatory bowel disease states. We evaluated indomethacin-induced enteropathy in rats, in relation to the expression of the inducible isoform of NO synthase (iNOS) using aminosalicylic acid (5-ASA), its isomer 4-ASA (10 or 50 mg/kg/day, po), and dexamethasone, an iNOS transcription inhibitor (3 mg/kg/day, sc). Enteropathy was induced by indomethacin (7.5 mg/kg/day, sc) for two days and the small intestine was examined for lesions over the next 14 days. Indomethacin-induced small-intestinal ulcer size, mucosal myeloperoxidase activity, iNOS expression and serum nitrite/nitrate levels were maximally increased by day 4 and gradually decreased by day 14. Treatment with 5-ASA, but not 4-ASA, decreased indomethacin-induced ulcer length, myeloperoxidase activity, serum nitrite/nitrate levels and iNOS expression at day 4. Dexamethasone had a greater effect than 5-ASA in reducing myeloperoxidase activity and ulcer length by 26 and 32%, respectively. Dexamethasone also reduced serum nitrate/nitrite and iNOS expression to their basal levels. In conclusion, inhibition of iNOS expression by 5-ASA appears to be associated with diminished intestinal ulceration in indomethacin-induced enteropathy.
Nandi
Jyotirmoy
J
Division of Gastroenterology, Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA. nandij@upstate.edu
Saud
Bipin
B
Zinkievich
J Michael
JM
Palma
David T
DT
Levine
Robert A
RA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015415:Biomarkers; D015153:Blotting, Western; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D007079:Ileitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D007213:Indomethacin / Q000633:toxicity; D007579:Jejunal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014158:Transcription, Genetic / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D019804:Mesalamine; D052247:Nitric Oxide Synthase Type II; D007213:Indomethacin