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PHARMASPIRE - Volume 10, Issue 2, April - June, 2018

Pages: 87-94

Date of Publication: 14-Jun-2022

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Histoarchitectural and biochemical investigation of cardiac myocytes in rat model of isoproterenol-induced myocardial infarction with the exploration of boswellic acid

Author: Lavdeep Beniwal , Deepa Khanna , Rajesh Dudi , Sidharth Mehan

Category: Pharmaceutics


Myocardial infarction is a condition in which loss of myocytes takes place due to prolonged ischemic condition and adrenergic overactivation. Isoproterenol, a synthetic catecholamine and a non-selective β-adrenergic agonist, is often employed in high dose to induce experimental myocardial infarction in order to study cardioprotective anti-infarct effects of pharmacological interventions. Induction of high oxidative stress in the heart is one of key events that could contribute to isoproterenol-induced experimental myocardial infarction. Boswellic acids have potent anti-inflammatory properties, and it has been shown to be beneficial against various inflammatory disorders. In addition to its anti-inflammatory action, boswellic acids have a potent antioxidant potential. However, the protective effect of boswellic acids (250mg/kg, p.o.) on experimentally induced myocardial infarction has not been investigated. Therefore, the present study has been designed to investigate the effect of boswellic acids against isoproterenol-induced (85 mg/kg, s.c.) myocardial infarction in rats. The present study provides experimental evidence that boswellic acids augmented the myocardial antioxidant enzyme level, preserved histoarchitecture, and improved cardiac performance by changing marker level following isoproterenol administration.

Keywords: Boswellic acid, inflammation, isoproterenol, myocardial infarction, oxidative stress


1. Kalra BS, Roy V. Efficacy of metabolic modulator in ischemic heart diseases: An overview. J Clin Pharmacol 2012;52:292-305.

2. Veinot TC, Bosk EA, Unnikrishnan KP, Iwashyna TJ. Revenue relationships and routines: The social organization of acute myocardial infarction patient transfers in the United States. Soc Sci Med 2012;75:1800-10.

3. Vakeva AP, Agah A, Rollins SA, Matis LA, Li L, Stahl GL. Myocardial infarction and apoptosis after myocardial ischemia and reperfusion: Role of the terminal complement components and inhibition by anti-C5 therapy. Circulation 1998;97:2259-67.

4. Ellison KE, Gandhi G. Optimising the use of beta-adrenoceptor antagonists in coronary artery disease. Drugs 2005;65:787-97.

5. Horimoto M, Takenaka T, Igarashi K, Fujiwara M, Batra S. Coronary spasm as a cause of coronary thrombosis and myocardial infarction. Jpn Heart J 1993;34:627-31.

6. Martin JF, Kristensen SD, Mathur A, Grover EL, Choudry FA. The causal role of megakaryocyte-platelet hyperactivity in acute coronary syndromes. Nat Rev Cardiol 2012;9:658-70.

7. Ueda S, Yamagishi S, Matsui T, Jinnouchi Y, Imaizumi T. Administration of pigment epithelium-derived factor inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction. Am J Pathol 2011;178:591-98.

8. Yang CH, Sheu JJ, Tsai TH, Chua S, Chang LT, Chang HW, et al. Effect of tacrolimus on myocardial infarction is associated with inflammation ROS MAP kinase and akt pathways in mini-pigs. J Atheroscler Thromb 2013;20:9-22.

9. Sahna E, Deniz E, Bay-Karabulut A, Burma O. Melatonin protects myocardium from ischemia-reperfusion injury in hypertensive rats: Role of myeloperoxidase activity. Clin Exp Hypertens 2008;30:673-81.

10. Upaganlawar A, Gandhi H, Balaraman R. Isoproterenol induced myocardial infarction: Protective role of natural products. J Pharmacol Toxicol 2011;6:1-17.

11. Mann DL, Kent RL, Parsons B, Cooper G 4th. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 1992;85:790-804.

12. Communal C, Singh K, Pimentel DR, Colucci WS. Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 1998;98:1329-34.

13. Neye N, Enigk F, Shiva S, Habazettl H, Plesnila N, Kuppe H, et al. Inhalation of NO during myocardial ischemia reduces infarct size and improves cardiac function. Intensive Care Med 2012;38:1381-91.

14. Karthikeyan K, Bai BR, Gauthaman K, Sathish KS, Devaraj SN. Cardioprotective effect of the alcoholic extract of Terminalia arjuna bark in an in vivo model of myocardial ischemic reperfusion injury. Life Sci 2003;73:2727-39.

15. Karthikeyan K, Bai BR, Devaraj SN. Grape seed proanthocyanidins ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes: An in vivo study. Life Sci 2007;81:1615-21.

16. Nandav M, Ojha SK, Joshi S, Kumari S, Arya DS. Oringa oleifera leaf extract prevents isoproterenol-induced myocardial damage in rats: Evidence for an antioxidant antiperoxidative and cardioprotective intervention. J Med Food 2009;12:47-55.

17. Bloom S, Davis DL. Calcium as mediator of isoproterenol-induced myocardial necrosis. Am J Pathol 1972;69:459-70.

18. Rathore N, John S, Kale M, Bhatnagar D. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res 1998;38:297-303.

19. Rajadurai M, Prince PS. Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in wistar rats: Biochemical and histopathological evidences. Toxicology 2006;228:259-68.

20. Krohn K, Rao MS, Raman NV, Khalilullah M. High-performance thin layer chromatographic analysis of anti-inflammatory triterpenoids from Boswellia serrata. Roxb Phytochem Anal 2001;12:374-76.

21. Gupta I, Parihar A, Malhotra P, Singh GB, Lüdtke R, Safayhi H, et al. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res 1997;2:37-43.

22. Gupta I, Gupta V, Parihar A, Gupta S, Lüdtke R, Safayhi H, et al. Effects of Boswellia serrata gum resin in patients with bronchial asthma: Results of a double-blind placebo-controlled 6-week clinical study. Eur J Med Res 1998;3:511-4.

23. Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med 2001;67:391-95.

24. Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges RZ. Therapy of active crohn disease with Boswellia serrata extracts H 15. Gastroenterology 2001;39:11-7.

25. Sharma A, Upadhyay J, Jain A, Kharya MD, Namdeo A, Mahadik KR. antioxidant activity of aqueous extract of Boswellia Serrata. J Chem Bio Phy Sci 2011;1:60-71.

26. Yin MC, Lin MC, Mong MC, Lin CY. Bioavailability distribution and antioxidative effects of selected triterpenes in mice. J Agric Food Chem 2012;60:7697-70.

27. Parikh V, Singh M. Possible role of adrenergic component and cardiac mast cell degranulation in preconditioning-induced cardioprotection. Pharmacol Res 1999;40:129-37.

28. Fishbein MC, Meerbaum S, Rit J, Lando U, Kanmatsuse K, Mercier JC, et al. Early phase acute myocardial infarct size quantification: Validation of the triphenyltetrazolium chloride tissue enzyme staining technique. Am Heart J 1981;101:593-600.

29. Sharma NK, Mahadevan N, Balakumar P. Adenosine transport blockade restores attenuated cardioprotective effects of adenosine preconditioning in the isolated diabetic rat heart: Potential crosstalk with opioid receptors. Cardiovasc Toxicol 2013;13:22-32.

30. Ohkawa H, Ohishi N, Ya K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.

31. Ma FX, Liu LY, Xiong XM. Protective effects of lovastatin on vascular endothelium injured by low density lipoprotein. Acta Pharmacol Sinica 2003;24:1027-32.

32. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.

33. Boyne AF, Ellman GL. A methodology for analysis of tissue sulfhydryl components. Anal Biochem 1972;46:639-53.

34. Rona G, Chappel CI, Balazs T, Gaudry R. An infarct like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. Arch Pathol 1959;67:443-5.

35. Ponnian SM, Sundaresan R, Koothan D. Protective effects of vanillic acid on electrocardiogram lipid peroxidation antioxidants proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats. Eur J Pharmacol 2011;688:233-40.

36. Zhou R, Xu Q, Zheng P, Yan L, Zheng J, Dai G. Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. Eur J Pharmacol 2008;586:244-50.

37. Karthick M, Stanely MP. Preventive effect of rutin a bioflavonoid on lipid peroxides and antioxidants in isoproterenol-induced myocardial infarction in rats. J Pharm Pharmacol 2006;58:701-7.

38. Sudhira B, Nargis A. Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats. Bangladesh J Pharmacol 2007;2:55-60.

39. Haleagrahara N, Varkkey J, Chakravarthi S. Cardioprotective effects of glycyrrhizic Acid against isoproterenol-induced myocardial ischemia in rats. Int J Mol Sci 2011;12:7100-13.

40. Kannan MM, Quine SD. Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electro cardiological biochemical and histological study. Eur J Pharmacol 2011;654:5.

41. Nigam PK. Biochemical markers of myocardial injury. Indian J Clin Biochem 2007;22:10-7.

42. Verma S, Devaraj S, Jialal I. C-reactive protein promotes atherothrombosis. Circulationulation 2006;113:2135-250.

43. Chun O, Chung S, Song W. Estimated dietary flavonoid intakes and major food sources of U.S. adults. J Nutr 2006;137:1244-52.

44. Li H, Xie YH, Yang Q, Wang SW, Zhang BL, Wang JB, et al. Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats. PLoS One 2012;7:e48872.