Evaluation of clopidogrel on acute and sub-acute models of inflammation in male Wistar rats
Keywords:
Clopidogrel, Aspirin, Carrageenan, InflammationAbstract
Background: Atherosclerosis and its complications remain the major cause of death and premature disability. Atherogenesis involves elements of inflammation, a process that now provides a unifying theme in the pathogenesis of the disease. Anti-platelet drugs are currently used in the treatment of atherosclerosis and its complications. Our study evaluated the influence of clopidogrel on acute and sub-acute models of inflammation in male Wistar rats.
Methods: Male Wistar rats (150-200 g) were divided into three groups, i.e. control, aspirin and clopidogrel (n=6 animals in each group). The effect of clopidogrel administered orally on inflammation was studied using acute (carrageenan-induced rat paw edema) and sub-acute (cotton pellet granuloma and histopathological examination of grass piths) models. Experiment was conducted according to the Committee for the Purpose of Control and Supervision on Experiments on Animals guidelines. Analysis was done using one-way ANOVA followed by post-hoc test of Dunnets. p<0.05 was considered as statistically significant.
Results: Clopidogrel showed significant inhibition of rat paw edema in acute model (p<0.01) and granuloma dry weight, in sub-acute model of inflammation when compared to control (p<0.01). Histopathological examination of grass pith revealed markedly reduced fibroblasts, granulation tissue, fibrous tissue and collagen in clopidogrel group when compared to control.
Conclusion: Clopidogrel exhibited a significant anti-inflammatory activity in acute and sub-acute models of inflammation.
References
Park K. Park’s Textbook of Preventive and Social Medicine. 20th Edition. Jabalpur: M/s Banarsidas Bhanot Publishers; 2009: 325.
Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, et al. Harrison’s Principles of Internal Medicine. 17th Edition. New York: McGraw Hill Publishers; 2008: 1501, 1549-52.
Libby P, Okamoto Y, Rocha VZ, Folco E. Inflammation in atherosclerosis: transition from theory to practice. Circ J. 2010;74(2):213-20.
Steinhubl SR, Badimon JJ, Bhatt DL, Herbert JM, Lüscher TF. Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease. Vasc Med. 2007;12:113-22.
Laurence DR, Bacharach AL. Evaluation of Drug Activities: pharmacometrics. Volume 2. New York, London: Academic Press Inc.; 1964.
Sweetman SC. Martindale the Complete Drug Reference. 36th Edition. London: Pharmaceutical Press; 2009: 23, 1316, 1409, 1420.
Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc Soc Exp Biol Med. 1962;111:544-7.
Gupta SK. Drug Screening Methods. 2nd Edition. New Delhi: Jayapee Brothers Medical Publishers (P) Ltd.; 2009: 488-9.
Turner RA. Screening Methods in Pharmacology. New York, London: Academic Press Inc.; 1965.
Patil PA, Kulkarni DR. Effect of antiproliferative agents on healing of dead space wounds in rats. Indian J Med Res. 1984;79:445-7.
Molero L, López-Farré A, Mateos-Cáceres PJ, Fernández-Sánchez R, Luisa Maestro M, Silva J, et al. Effect of clopidogrel on the expression of inflammatory markers in rabbit ischemic coronary artery. Br J Pharmacol. 2005;146(3):419-24.
Klinkhardt U, Bauersachs R, Adams J, Graff J, Lindhoff-Last E, Harder S. Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease. Clin Pharmacol Ther. 2003;73(3):232-41.
Xiao Z, Théroux P. Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome. J Am Coll Cardiol. 2004;43(11):1982-8.
Sharis PJ, Cannon CP, Loscalzo J. The antiplatelet effects of ticlopidine and clopidogrel. Ann Intern Med. 1998;129(5):394-405.
Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med. 1999;340(2):115-26.
