Gastric damage induced by different doses of indomethacin in rats is variably affected by inhibiting iNOS or leukocyte infiltration

• Published in: Inflammation research 2008, Vol.57 (1), p.28-33
• Main Authors: Souza, M. H. L. P., Mota, J. M. S. C., Oliveira, R. B., Cunha, F. Q.
• Format: Article
• Language: English
• Subjects: Allergology; Animals; Biomedical and Life Sciences; Biomedicine; Dermatology; Dose-Response Relationship, Drug; Gastric Mucosa - drug effects; Immunology; Indomethacin - toxicity; Male; Neurology; Neutrophil Infiltration; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - physiology; Peroxidase - metabolism; Pharmacology/Toxicology; Rats; Rats, Wistar; Rheumatology
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-007-7089-z

. Aim: 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 . Conclusion: 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.