5-aminosalicylic acid improves indomethacin-induced enteropathy by inhibiting iNOS transcription in rats.

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Nandi J, Saud B, Zinkievich JM, Palma DT, Levine RA

5-aminosalicylic acid improves indomethacin-induced enteropathy by inhibiting iNOS transcription in rats.

Dig Dis Sci. 2008 Jan;53(1):123-32. Epub 2007 May 15.

PubMed ID

17503181 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drugs

Mesalazine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dexamethasone	Nitric oxide synthase, inducible	Protein	Humans	Unknown	Negative modulator	Details
Dexamethasone acetate	Nitric oxide synthase, inducible	Protein	Humans	Unknown	Negative modulator	Details
Mesalazine	Nitric oxide synthase, inducible	Protein	Humans	Unknown	Inhibitor	Details