Gastric damage induced by different doses of indomethacin in rats is variably affected by inhibiting iNOS or leukocyte infiltration.
OBJECTIVE
To evaluate the effect of inhibiting inducible nitric oxide synthase (iNOS), by aminoguanidine, or leukocyte infiltration, by fucoidin, on gastropathy induced by two different doses of indomethacin in rats.


METHODS
Rats were treated with saline, aminoguanidine (50 or 100 mg.kg(-1), i. p.) or fucoidin (25 mg.kg(-1), i. v.). Indomethacin was then given at a dose of 5 or 20 mg.kg(-1). At the end of 3 h, macroscopic gastric damage and myeloperoxidase (MPO) activity were assessed.


RESULTS
Aminoguanidine reduced the gastric damage induced by indomethacin at 20 mg.kg(-1), but increased gastric MPO activity. However, aminoguanidine did not influence the gastric damage induced by indomethacin at 5 mg.kg(-1). Fucoidin prevented both the gastric damage and the increase in gastric MPO activity induced by indomethacin at 20 mg. kg(-1), but not at 5 mg.kg(-1).


CONCLUSIONS
Indomethacin at a dose of 20 mg.kg(-1), but not at 5 mg.kg(-1), induced gastropathy dependent on neutrophil infiltration and iNOS-generated NO.
Souza
M H L P
MH
Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Ceará, Brazil. souzamar@ufc.br
Mota
J M S C
JM
Oliveira
R B
RB
Cunha
F Q
FQ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000633:toxicity*; D008297:Male; D020556:Neutrophil Infiltration; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D007213:Indomethacin