Gastric damage induced by subchronic administration of preferential cyclooxygenase-1 and cyclooxygenase-2 inhibitors in rats.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known to induce gastrointestinal damage including bleeding, ulceration and perforation in humans and animals. The aim of this study was to compare the effects of two oxicams, preferential cyclooxygenase (COX)-1 or COX-2 inhibitors, on both gastric mucosa and some biological parameters (hematological, hepatic and renal) after subchronic administration (14 and 28 days) in rats. Neutrophil infiltration was also assessed. Equipotent doses of meloxicam (3.75 and 7.5 mg/kg) and piroxicam (5 and 10 mg/kg) were administered. Both drugs dose-dependently caused multiple gastric erosions and hemorrhage in rats after 14 and 28 days of administration. Treatment with meloxicam led to a higher gastric damage than with piroxicam on day 14 although these results were not significant. The levels of myeloperoxidase activity (as an index of neutrophil infiltration) were not changed compared with control after drug treatment. All the hematological parameters obtained after drugs administration for 14 and 28 days were in the range of normal values, and a significant increase in platelet levels could be observed in the group treated with 5 mg/kg of piroxicam for 14 days. Aspartate aminotransferase (AST or GOT) increased significantly after 14 days, but after 28 days the values returned to normality. Creatinine and urea did not undergo significant changes except for the piroxicam 14-day 5 mg/kg group, in which uremia increased significantly over normal values. In conclusion, our results show that meloxicam, a preferential COX-2 inhibitor, causes rates of gastric lesion comparable to those seen with traditional NSAIDs, without inducing important changes in biological parameters.
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain.
Isabel
I
Villegas
Catalina
C
Alarcón de la Lastra
M José
MJ
Martín
Virginia
V
Motilva
Carmen
C
La Casa García
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D008565:Membrane Proteins; D010894:Piroxicam / Q000008:administration & dosage / Q000009:adverse effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013843:Thiazines / Q000008:administration & dosage / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013843:Thiazines; D013844:Thiazoles; D010894:Piroxicam; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D000077239:Meloxicam