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

This work was aimed to study COX-1 and COX-2 selectivity in 16 non-steroidal anti-inflammatory drugs (NSAIDs), at ulcerogenic doses in 2 experimental models: 1) provided subcutaneously (sc), after solid food(SF), (antrum ulcers and intestinal erosions); and 2) orally (O) (fundic and intestinal erosions). 17 groups of female Wistar rats (n = 7 each group), weighing 200 g, 36 h fasting with water ad libitum, were submitted to the following experiments: 1. SF (Cargill chow) during 1 h, and 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 the aforementioned drugs was 60 mg/kg; 8. aceclofenac (Ace); 9. 200 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. The drugs where administered by orogastric tubing to the same groups of fasting animals. After 24 h the animals were killed by ether overdose. Laparotomy was performed and the stomach and the small intestine was removed. The percentage of antum ulcer, and fundic and intestinal erosion (mm2) was tabulated by planimetry. Blood and histological samples were obtained. The NSAIDs Indo, Ibu, Ke, Ket, P and Te yielded an antrum ulcer area: 5-29% and intestinal erosion, 101-395 mm2, similar to Indo (p > 0.50). In contrast there were neither ulcers nor intestinal erosions with Mac, A, Di, E and Nap (p > 0.50). While there were absence of ulcers with Ace, Me, Na, Ni and Pa and slight intestinal erosion (0-23 mm2; p < 0.01). II. There were differences in the following oral (NAIDs: Ace, Me, NA, Ni and Pa, yielding 0-5% fundic erosion and 0-22 mm2 intestinal erosion (p < 0.001). The other NSADs yielded 33-90% fundic erosion and 116-550 mm2 intestinal erosion, similarly to Indo (p > 0.50). Leukocyte infiltrate in the gastrointestinal mucosa with all the NSADs, except Ibu and Pa. There was also neutrophilia (5000-20,000), but not with Ibu and Pa (700-1200). COX-2-COX-1 selectivity was demonstrated "in vivo" in aceclofenac, meloxicam, nabumetone, nimesulide and paracetamol.

Citation

O M Laudanno, J A Cesolari, J Esnarriaga, P Flaherty, J Vada, G Guastalli, P San Miguel, O A Bedini. In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats]. Acta gastroenterologica Latinoamericana. 1998;28(3):249-55

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PMID: 9773153

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