EFFECT OF TERMINALIA CHEBULA (HARAD) FRUIT EXTRACT ON CARDIOTOXICITY IN STREPTOZOTOCIN INDUCED DIABETIC RATS
Objective: The aim of the study was to explore the protective activity of Terminalia chebula fruit extract on cardiotoxicity in streptozotocin (STZ) induced diabetic rats.
Methods: The animals were divided into eight groups of five each and were fed with high fat diet (HFD) except sham control, diabetic control and isoproterenol control. Diabetes was induced by administering single intraperitoneal (i. p.) injection of STZ (0.05 g/kg) in all groups except sham and isoproterenol control and was confirmed by testing blood glucose level after 48 h. Rats were pretreated with ethanolic extract of Terminalia chebula (0.25& 0.5 g/kg/d; per oral (p. o.)), pioglitazone (0.01 g/kg/d), carvedilol (0.002 g/kg/d) and normal saline throughout the study period (14 days). Cardiotoxicity was induced by the administrating two subcutaneous (s. c) injection of isoproterenol (ISO) (0.085 g/kg) at an interval of 24 h. Troponin was checked to confirm cardiotoxicity. The evaluation parameters include initial and final blood glucose level, change in body weight, food efficiency ratio (FER), heart weight-body weight ratio, biochemical estimations and histopathological studies.
Results: Pretreatment with Terminalia chebula produced significant (p<0.01) decrease in blood glucose level and heart weight-body weight ratio. It significantly decrease the elevated activity of the cardiac marker enzymes, alanine transaminase (ALT), lactate dehydrogenase (LDH), creatinine kinase (CK-MB) (p<0.01), similar to the standard drug carvedilol in isoproterenol injected rats. Pretreatment with Terminalia chebula showed absence of troponin and lesser degree of necrosis, edema, and myofibrillar degeneration.
Conclusion: Terminalia chebula has significant cardioprotective action against cardiotoxicity in STZ induced diabetic rats, which is comparable with standard drugs i.e., pioglitazone and carvedilol.
2. Albini A, Pennesi G, Donatelli F, Cammarota R, Flora SD, Noonan DM. Cardiotoxicity of anticancer drugs: the need for Cardio-Oncology and Cardio-Oncological prevention. J Natl Cancer Inst 2010;102:14â€“25.
3. What are the signs and symptoms of coronary heart disease? Available from: URL: http://www.nhlbi.nih.gov/2014. [Last accessed on 10 May 2015]
4. Ferdinandy P, Schulz R, Baxter GF. Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning and postconditioning. Pharmacol Rev 2007;59:418â€“58.
5. Nesto WR. Correlation between cardiovascular disease and diabetes mellitus: current concepts. Am J Med 2004;116 Suppl 5:11â€“22.
6. Papaccio G, Pisanti FA, Latronico MV, Ammendola E, Galdieri M. Multiple low dose and single high dose treatments with streptozotocin do not generate nitric oxide. J Cell Biochem 2000;77:82-91.
7. Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003;17 Suppl 1:24-38.
8. Wexler BC. Myocardial infarction in young vs old male rats: pathophysiologic changes. Am Heart J 1978;96 Suppl 1:70-80.
9. Todd GL, Cullan GE, Cullan GM. Isoproterenol-induced myocardial necrosis and membrane permeability alterations in the isolated perfused rabbit heart. Exp Mol Pathol 1980;33 Suppl 1:43-54.
10. Wexler BC. Protective effects of propanolol in isoproterenol induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats. Atherosclerosis 1973;18:11-42.
11. Young IS, Purvis JA, Lightbody JH, Adgey AA, Trimble ER. Lipid peroxidation & antioxidant status following thrombolytic therapy for acute myocardial infarction. Eur Heart J 1993;14:1027-33.
12. Tilak JA, Devasagayam TP. Cardioprotective and other beneficial effects of some indian medicinal plants. J Clin Biochem Nutr 2006;38:9-18.
13. Gupta PC. Biological and pharmacological properties of Terminalia chebula retz (haritaki)-An overview. Int J Pharm Pharm Sci 2012;4 Suppl 3:62-8.
14. Kaur S. The in vitro cytotoxic and apoptotic activity of Triphala-an Indian herbal drug. J Ethnopharmacol 2005;97:15â€“20.
15. Devani U, Pandita N, Kachwala Y. Evaluation of inhibitory activity of Vitex nirgundo and Terminalia chebula by alpha amylase inhibiton assay in management of diabetes. Asian J Plant Sci Res 2013;3 Suppl 2:6-14.
16. Singh MP, Sharma CS. Wound healing activity of Terminalia Chebula in experimentally induced diabetic rats. Int J PharmTech Res 2009;1 Suppl 4:1267-70.
17. Factor SM, Bhan R, Minase T, Wolinsky H, Sonnenblick EH. Hypertensive-Diabetic cardiomyopathy in the rat an experimental model of human disease. Am J Pathol 1981;102 Suppl 2:219-28.
18. Lee SJ, Zhang GF, Sung NJ. Hypolipidemic and hypoglycemic effects of Orostachys japonicus A. Berger extracts in streptozotocin-induced diabetic rats. Nutr Res Pract 2011;5 Suppl 4:301-7.
19. Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening. Pharmacol Res 2005;52 Suppl 4:313â€“20.
20. Ansari MN, Bhandari U, Pillai KK. Protective role of curcumin in myocardial oxidative damage induced by isoproterenol in rats. Hum Exp Toxicol 2007;26 Suppl 12:933-8.
21. Vijaya C, Ramanathan M, Suresh B. Lipid lowering activity of ethanolic extract of leaves of Aegle marmelos in Hyperlipidaemic models of Wistar Albino Rats. Indian J Exp Biol 2009;47:182-5.
22. Rona G, Kahn DS, Chappel CI. Study on the healing of cardiac necrosis in the rat. Am J Pathol 1961;39 Suppl 4:473-89.
23. Goyal S, Siddiqui MK, Siddiqui KM, Arora S, Mittal R, Joshi S, et al. Cardioprotective effect of 'Khamira abresham hakim arshad wala' a unani formulation in isoproterenol-induced myocardial necrosis in rats. Exp Toxicol Pathol 2010;62 Suppl 1:61-74.
24. Panda VS, Naik SR. Cardioprotective activity of Ginkgo biloba Phytosomes in isoproterenol-induced myocardial necrosis in rats: A biochemical and histoarchitectural evaluation. Exp Toxicol Pathol 2008;60 Suppl 5:397-404.
25. Seth SD, Maulik M, Katiyar CK, Maulik SK. Role of Lipistat in protection against isoproterenol induced myocardial necrosis in rats: a biochemical and histopathological study. Indian J Physiol Pharmacol 1998;42 Suppl 1:101-6.
26. Wei Y, Wu J, Cai F, Xiang J, Zha W, Fan D, et al. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. Plos One 2012;7 Suppl 12:52013.
27. Milano CA, Allen LF, Rockman HA, Dolber PC, Mcminn TR, Chien KR, et al. Enhanced myocardial function in transgenic mice overexpressing beta-2 adrenergic receptor. Science 1994;264:582-6.
28. Kumar GP, Arulselvan P, Kumar DS, Subramanian SP. Anti-diabetic activity of fruits of terminalia chebula on Streptozotocin induced diabetic rats. JHS 2006;52 Suppl 3:283â€“91.
29. Suchalatha S, Shyamala Devi CS. Protective effect of Terminalia chebula against experimental myocardial injury induced by isoproterenol. Indian J Exp Biol 2004;42 Suppl 2:174-8
30. Wang HJ, Jin YX, Shen W, Neng J, Wu T, Li YJ, et al. Low dose streptozotocin (STZ) combined with high energy intake can effectively induce type 2 diabetes through altering the related gene expression. Asia Pac J Clin Nutr 2007;16:1412â€“7.
31. Nigam PK. Biochemical markers of myocardial injury. Indian J Clin Biochem 2007;22 Suppl 1:10-7.