Potentiation of Indomethacin-Induced Anti-Inflammatory Response by Montelukast in Formalin-Induced Inflammation in Rats

  • Ali Asghar Hemmati Department of Pharmacology and Toxicology, School of Pharmacy, AND Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. and Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  • Behnam Ghorbanzadeh Mail Department of Pharmacology and Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  • Mohammad Amin Behmanesh Department of Histology, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Keywords:
Formalin, Inflammation, Indomethacin, Leukocyte, Montelukast

Abstract

The leukotrienes and prostaglandins are biologically active metabolites derived from arachidonic acid. The leukotrienes have a role in inflammatory diseases such as allergic rhinitis, inflammatory bowel disease and asthma. Montelukast, a cysteinyl leukotriene receptor antagonist, is claimed to be effective in asthma. The present study aimed to assess the role of cysteinyl leukotriene receptor antagonist on peripheral inflammation and whether montelukast treatment enhances the anti-inflammatory effect of indomethacin. Anti-inflammatory response was measured using a plethysmometer. Histopathologic examination for leukocyte accumulation was done. Montelukast (0.5-2mg/kg, i.p.) produced a significant anti-inflammatory effect in dose dependent manner against formalin-induced rat paw oedema at 1h but not in 3 and 5 h. When indomethacin (5 mg/kg, i.p) was co-administered with montelukast (1 mg/kg, i.p), the anti-inflammatory effects of indomethacin were significantly increased as compared to the per se effect at 3 and 5 hour after formalin challenge. In histopathology it has been found that combination therapy significantly decreased migration of leucocytes into the site of inflammation. These results show that montelukast has anti-inflammatory properties in peripheral tissue and markedly potentiates the anti-inflammatory activity of indomethacin at 3 and 5 h. It is expected that combination of montelukast with cyclooxygenase inhibitor would prove to be a novel approach to manage complex inflammatory conditions.

References

Finch CE. Developmental origins of aging in brain and blood vessels: an overview. Neurobiol Aging 2005;26:281–91.

Caruso C, Lio D, Cavallone L, Franceschi C. Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci. 2004;1028:1-13.

Paoletti R, Gotto AMJ, Hajjar DP. Inflammation in atherosclerosis and implications for therapy. Circulation 2004;109: III20–III6.

Rus H, Niculescu FI. Inflammation, aspirin, and therisk of cardiovascular disease. N Engl J Med 1997;337(6):423–4.

Firestein GS. Inhibiting inflammation in rheumatoid arthritis. N Engl J Med 2006;354(1):80–2.

Klegeris A, McGeer EG, McGeer PL. Therapeutic approaches to inflammation in neurodegenerative disease. Curr Opin Neurol 2007;20(3):351–7.

Libby P, Plutzky J. nflammation in diabetes mellitus: roleof peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gammaagonists. Am J Cardiol 2007;99(4A):27B-40B.

Yan SF, Ramasamy R, Schmidt AM. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Clin Pract Endocrinol Metab 2008;4(5):285-93.

Tsirpanlis G. Inflammation in atherosclerosis and other conditions: a response to danger. Kidney Blood Press Res 2005;28(4):211-7.

Nathan C. Points of control in inflammation. Nature 2002;420(6917):846–52.

Heller A, Koch T, Schmeck J, Van Ackern K. Lipid mediators in inflammatory disorders. Drugs 1998;55(4):487–96.

Nakadate T, Yamamoto S, Iseki H, Sonoda S, Takemura S, Ura A, Hosoda Y, Kato R. Inhibition of 12-Otetradecanoylphorbol-

-acetate-induced tumor promotion by nordihydroguaiaretic acid, a lipoxygenase inhibitor, and p-bromophenacylbromide, a phospholipase A2 inhibitor Gann 1982(73):841–3.

Parker CW. Lipid mediators produced through the lipooxygenase pathway. Annu Rev Immunol 1987;5:65-84.

Chung KF, Barnes PJ. Zafirlukast (Accolate). Drugs Today 1998;34(4):375–88.

Vianna EO, Martin RJ. Recent innovations in asthma therapy. Drugs Today 1998;34(4):341–51.

Weisberg SC. Pharmacotherapy of asthma in children with special reference to leukotriene receptor antagonists Pediatr Pulmonol 2000;29(1):46–61.

Jain NK, Singh A, Kulkarni SK. Analgesic, antiinflammatory and ulcerogenic activity of a zinc–naproxen complex in mice and rats. Pharm Pharmacol Commun 1999;5:599-602.

Radhofer-Welte S, Rabasseda X. Lornoxicam, a new potent NSAID with an improved tolerability profile Drugs Today 2000;36(1):55–76.

Chung KF. Leukotriene receptor antagonists and biosynthesis inhibitors: potential breakthrough in asthma therapy. Eur Respir J 1995;8(7):1203–13.

Levine JD, Lau W, Kwiat G, Goetzl EJ. Leukotriene B4 produces hyperalgesia that is dependent on polymorphonuclear leukocytes. Science 1984;225(4663):743–5.

Nickerson-Nutter CL, Medvedeff ED. The effect of leukotriene synthesis inhibitors in models of acute and chronic inflammation. Arthritis Rheum 1996;39(3):515–21.

Yamauchi K, Tanifuji Y, Pan LH, Yoshida T, Sakurai S, Goto S, Kuroda S, Kobayashi H, Inoue H. Effects of pranlukast, a leukotriene receptor antagonist, on airway inflammation in mild asthmatics. J Asthma 2001;38(1):51-7.

Feldman M, McMahon AT. Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal antiinflammatory drugs, with less gastrointestinal toxicity? Ann Intern Med 2000;132(2):134–43.

Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999;340(24):1888–99.

How to Cite
1.
Hemmati AA, Ghorbanzadeh B, Behmanesh MA. Potentiation of Indomethacin-Induced Anti-Inflammatory Response by Montelukast in Formalin-Induced Inflammation in Rats. Acta Med Iran. 51(10):675-680.
QRcode
Section
Articles