In vivo selectivity of nonsteroidal antiinflammatory drugs and gastrointestinal ulcers in rats.
The aim of the present work was to study in vivo COX-2-COX-1 selectivity of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in two in vivo experimental models. Indomethacin, ibuprofen, nimesulide, aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol, piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and ketorolac were administered to female Wistar rats (N = 10 each group). In experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II, NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic gastric fundus area (65%) and erosive intestinal area (182 mm2), "in vivo" the NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where also ibuprofen and paracetamol not given neotrophilic infiltration. In conclusion, COX-2-COX-1 selectivity was demonstrated in vivo with the drugs aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol.
Laudanno
O M
OM
Department of Experimental Gastroenterology, Faculty of Médicine, UNR Rosario, Argentina.
Cesolari
J A
JA
Esnarriaga
J
J
San Miguel
P
P
Bedini
O A
OA
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005260:Female; D007279:Injections, Subcutaneous; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat