Abstract.
Background:
The pathogenesis of NSAID-induced enteropathy may involve dual inhibition of the cyclooxygenase (1 and 2) and a topical effect with sequential increased intestinal permeability, development of inflammation and ulcers. It has been suggested that nitric-oxide donating drugs cause significantly less gastrointestinal injury by counteracting for NSAID-induced reductions in blood flow.
Aims:
To compare the effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate], and naproxen on key pathogenic steps in NSAID-enteropathy in the rat.
Methods:
Single doses of AZD3582, naproxen (dose range 10-300 μmol/kg) or vehicle were given to male Sprague Dawley rats. Intestinal permeability (51CrEDTA) and intestinal inflammation (granulocyte marker protein) was quantitated and ulcer counts made.
Results:
Intestinal permeability (all doses) and inflammation (highest dose of the drugs) increased significantly from control levels following naproxen and AZD3582 and there was no significant difference between the drugs. Median ulcer counts were, however, significantly (p<0.01) lower with AZD3582 (4 ± 2) than with naproxen (17 ± 4).
Conclusions:
Naproxen and AZD3582 are equally associated with increased small intestinal permeability and inflammation, which is the consequence of their topical effect. The reduced small bowel ulcer counts with AZD3582 accords with the suggestion that vascular factors are the main driving force for NSAID-induced ulcer formation.
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
Received 9 October 2006; revised 27 January 2007; accepted 1 February 2007
Rights and permissions
About this article
Cite this article
Walley, M., Sigthorsson, G., Hotz-Behofsits, C. et al. The effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate], and naproxen on key pathogenic steps in NSAID-enteropathy in the rat. Inflammopharmacol 15, 119–123 (2007). https://doi.org/10.1007/s10787-007-1598-9
Issue Date:
DOI: https://doi.org/10.1007/s10787-007-1598-9