[In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats]

摘要: UNLABELLED This work was aimed to study COX-1 and COX-2 selectivity in 16 non-steroidal anti-inflammatory drugs (NSAIDs), at ulcerogenic doses 2 experimental models: 1) provided subcutaneously (sc), after solid food(SF), (antrum ulcers intestinal erosions); 2) orally (O) (fundic erosions). METHODS 17 groups of female Wistar rats (n = 7 each group), weighing 200 g, 36 h fasting with water ad libitum, were submitted the following experiments: 1. SF (Cargill chow) during 1 h, then sc: 1.1 ml saline; 2. diclofenac (Di); 3. indomethacine (Indo); 4. Ketorolac (Ke); 5. meloxicam (Mel); 6. Pyroxicam (P); 7. tenoxicam (T). The dose for aforementioned 60 mg/kg; 8. aceclofenac (Ace); 9. mg/kg nimesulide (Ni); 10. mefenamic acid (Mac); 11. aspirin (A); 12. etodolac (E); 13. ibuprophen (Ibu); 14. nabumetone (Na); 15. naproxene (Nap); 16. ketoprophen (Ket); 17. paracetamol (Pa), 500 mg/kg. II. where administered by orogastric tubing same animals. After 24 animals killed ether overdose. Laparotomy performed stomach small intestine removed. percentage antum ulcer, fundic erosion (mm2) tabulated planimetry. Blood histological samples obtained. RESULTS NSAIDs Indo, Ibu, Ke, Ket, P Te yielded an antrum ulcer area: 5-29% erosion, 101-395 mm2, similar Indo (p > 0.50). In contrast there neither nor erosions Mac, A, Di, E Nap While absence Ace, Me, Na, Ni Pa slight (0-23 mm2; p HISTOLOGY Leukocyte infiltrate gastrointestinal mucosa all NSADs, except Ibu Pa. There also neutrophilia (5000-20,000), but not (700-1200). CONCLUSIONS COX-2-COX-1 demonstrated "in vivo" aceclofenac, meloxicam, nabumetone, paracetamol.