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Vol. 60, No. 3, 2000
Issue release date: April 2000

Effect of Nabumetone Treatment on Vascular Responses of the Thoracic Aorta in Rat Experimental Arthritis

Ülker S. · Önal A. · Hatip F.B. · Sürücü A. · Alkanat M. · Koşay S. · Evinç A.
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Abstract

Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg·kg–1·day–1, orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects.

Copyright © 2000 S. Karger AG, Basel



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References

  1. Brahn E: Animal models of rheumatoid arthritis. Clues to etiology and treatment. Clin Orthop 1991;265:42–50.

    External Resources

  2. Floman Y, Okon E, Zor R: The role of prostaglandin in experimental arthritis in the rat. Clin Orthop 1977;125:214–220.

    External Resources

  3. Issekutz AC, Movat HZ: The effect of vasodilator prostaglandins on polymorphonuclear leukocyte infiltration and vascular injury. Am J Pathol 1982;107:300–309.

    External Resources

  4. Simmons DL, Xie W, Chipman JG, Evett GE: Multiple cyclooxygenases: Cloning of a mitogen-inducible form; in Bailey JM (ed): Prostaglandins, Leukotrienes, Lipoxins and PAF. New York, Plenum Press, 1991, pp 67–78.
  5. Dandano P, Jeremy JY: Nonsteroidal anti-inflammatory drug therapy and gastric side effects; does nabumetone provide a solution? Drugs 1990;40(suppl 5):16–24.
  6. Dewitt DL, Meade EA, Smith WL: PGH synthase isoenzyme selectivity: The potential for safer nonsteroidal antiinflammatory drugs. Am J Med 1993;95(suppl 2A):40S–44S.
  7. Klein T, Nüsing RM, Pfeilschifter J, Ullrich V: Selective inhibition of cyclooxygenase. Biochem Pharmacol 1994;48:1605–1610.
  8. Çınar MG, Can C, Ülker S, Gök Ş, Çoker C, Soykan N, Koşay S, Evinç A: Effect of vitamin E on vascular responses of thoracic aorta in rat experimental arthritis. Gen Pharmacol 1998;31:149–153.
  9. Issekutz AC: Vascular responses during acute neutrophil emigration. Their relationship to in vivo neutrophil emigration. Lab Invest 1981;45:435–441.
  10. Fang ZY, Fontaine J, Unger PH, Berkenboom G: Alterations of the endothelial function of isolated aorta in rats with adjvuant arthritis. Arch Int Pharmacodyn Ther 1991;311:122–130.

    External Resources

  11. Pang L, Knox AJ: Effect of interleukin-1 beta, tumour necrosis factor-alpha and interferon-gamma on the induction of cyclo-oxygenase-2 in cultured human airway smooth muscle cells. Br J Pharmacol 1997;121:579–587.
  12. Tesfamariam B, Cohen RA: Role of superoxide anion and endothelium in vasoconstrictor action of prostaglandin endoperoxide. Am J Physiol 1992;262:H1915–H1919.

    External Resources

  13. Rofe AM, Philcox JC, Haynes DR, Coyle P: Wasting in adjuvant-induced arthritis and its relationship to plasma zinc, copper and liver metallothionein. Agents Actions 1994;42:60–62.

    External Resources

  14. Ohkawa F, Ikeda U, Kanbe T, Kawasaki K, Shimada L: Inflammatory cytokines and rat vascular tone. Clin Exp Pharmacol Physiol 1995;(suppl 1):S169–S171.
  15. Vane JR, Mitchell JA, Appleton I, Tomlinson A, Bishop-Bailey D, Croxtall J, Willoughley DA: Inducible isoforms of cyclooxygenase and nitric oxide synthase in inflammation. Proc Natl Acad Sci USA 1994;91:2046–2050.
  16. Goodwin JS: Are prostaglandins proinflammatory, antiinflammatory, both or neither? J Rheumatol Suppl 1991;28:26–29.
  17. Bensen W, Zizzo A: Newer, safer nonsteroidal anti-inflammatory drugs. Rational NSAID selection for arthritis. Can Fam Phys 1998;44:101–102.
  18. Roth SH: Endoscopy-controlled study of the safety of nabumetone compared with naproxen in arthritis therapy. Am J Med 1987;83(suppl 4B):25–30.
  19. Fleischmann RM: Clinical efficacy and safety of nabumetone in rheumatoid arthritis and osteoarthritis. J Rheumatol 1992;19(suppl 36):32–40.
  20. Melerange R, Gentry C, O’Connell C, Blower PR, Neil C, Kelvin AS, Toseland CDN: Antiinflammatory and gastrointestinal effects of nabumetone or its active metabolite, 6-methoxy-2-naphtylacetic acid (6MNA): Comparative studies with indomethacin. Dig Dis Sci 1992;37:1847–1852.
  21. Davies NM: Clinical pharmacokinetics of nabumetone. The dawn of selective cyclooxygenase-2. Clin Pharmacokinet 1997;33:403–416.


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