ETHANOL-INDUCED ALTERATIONS IN CARDIAC ENZYMESâ€“AMELIORATIVE EFFECT OF THESPESIA POPULNEA LEAF EXTRACT
Objective: This study covers the estimation of changes in cardiac enzymes such as ATPases and antioxidant enzymes following ethanol-administration in rats, and the possible ameliorative effect of leaf extract of the plant Thespesia populnea (TP) on these changes.
Methods: Male adult Wistar rats were divided into 10 groups of six rats each. Vehicle controls received 5% gum acacia. Experimental groups received ethanol (20%, 2g/kg); or TP leaf extract (200 mg/kg and 400 mg/kg respectively); or vitamin E (25 mg/kg); or carvedilol (1 mg/kg) per orally every morning for 6 w, individually as well as in combination with ethanol. Following this, changes in the activities of Na+ ATPase, Ca2+ATPase, Mg2+ATPase, and antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were determined in the heart tissue and compared with those in vehicle control.
Results: Ethanol (20%, 2g/kg) treatment caused a reduction from the vehicle control in activities of all the examined enzymes, with minimal reduction in Mg2+ ATPase activity (29.26%) and maximal reduction in CAT activity (71.05%). With TP leaf extracts of 200 and 400 mg/kg, vitamin E and carvedilol individually, the vehicle controls showed percent changes in enzyme activities ranging from â€’8.24% for Mg2+ ATPase activity to+109.39% for Na+ ATPase activity caused by carvedilol. When administered along with ethanol, TP leaf extracts, vitamin E and carvedilol reversed the effect of ethanol to various degrees and brought back the enzyme activities to near vehicle control levels. While recovery with 200 mg Thespesia leaf extract was less, ranging from 24.1% for Mg2+ATPase activity to 190.91% for CAT activity, 400 mg Thespesia extract effected a greater recovery, with a minimum of 48.19% for Mg2+ ATPase activity and a maximum of 222.73% for CAT activity, as compared with ethanol-treated rats as controls. These effects could be interpreted in terms of the adverse effects of ethanol on cardiac function and the ameliorative effects, primarily the antioxidant potential, of TP leaf extracts, vitamin E and carvedilol.Conclusion: The restoration of enzyme activities with TP leaf extract may promote recovery of cardiac tissue from oxidative damage. Results from the current study indicate that treatment with TP leaf extract reduces ethanol-induced oxidative stress in rat heart and hence may help prevent cardiac damage.
2. Inkielewicz I, Rogowska M, Krechniak J, Gdansk P. Lipid peroxidation and antioxidant enzyme activity in rats exposed to fluoride and ethanol. Fluoride 2006;39:53â€“9.
3. Nicholas ASH, Jun R. Short-term acetaldehyde exposure depresses ventricular myocyte contraction: the role of cytochrome P450 oxidase, xanthine oxidase, and lipid peroxidation. Alcohol Clin Exp Res 2003;27:577-83.
4. Rubin E, Rottenberg H. Ethanol-induced injury and adaptation in biological membranes. Fed Proc 1982;41:2465â€“71.
5. Kono Y, Fridovich I. Superoxide radical inhibits catalase. J Biol Chem 1982;57:5751-4.
6. Saravanan R, Prakasam A, Ramesh B, Pugalendi KV. Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in ethanol-treated Wistar rats. J Med Food 2004;5:197-204.
7. Luczaj W, Waszkiewicz E, Skrzydlewska E, Roszkowska-Jakimiec W. Green tea protection against age-dependent ethanol-induced oxidative stress. J Toxicol Environ Health Part A 2004;67:595-606.
8. Luczaj W, Stankiewicz-Kranc A, Milewska E, Roszkowska-Jakimiec W, Skrzydlewska E. Effect of sweet grass extract against oxidative stress in rat liver and serum. Food Chem Toxicol 2012;50:135-40.
9. Durga M, Nathiya S, Devasena T. Protective role of fenugreek leaf extract and quercetin against petrol exhaust nanoparticle induced lipid peroxidation and oxidative stress in rat erythrocytes in vitro. Asian J Pharm Clin Res 2015;8:237-41.
10. Akilandeswari V, Sekkizhar M, Sylvia Santhakumari A, Nirmala P. Nephroprotective effect of lycopene in hyperglycemia induced oxidative stress in male Wistar rats. Int J Curr Pharm Res 2015;7:77-9.
11. Deepa Philip C, Indira Kumari R, Lavanya B. Phytochemical analysis, the antioxidant and antimicrobial activity of white and pink Psidium guajava Linnaeus. Int J Curr Pharm Res 2015;7:29-31.
12. Warrier PK, Nambiar VPK, Ramankutty C. Indian medicinal plants-4. Vol. 5. Chennai: Orient Longman Ltd; 1994.
13. Milbrodt M, Konig WA, Hausen BM. 7-hydroxy-2,3,5,6-tetrahydro-3,6,9-trimethylnaphtho[1,8-b,c] pyran-4,8-dione from Thespesia populnea. Phytochemistry 1997;45:1523-5.
14. Sathyanarayana T, Sarita T, Balaji M, Ramesh A, Boini MK. Antihyperglycemic and hypoglycemic effect of Thespesia populnea fruits in normal and alloxan-induced diabetes in rabbits. Saudi Pharm J 2004;12:107â€“11.
15. Haja Sherief S, Moideen K, Sengottuvelu S, Sivakumar T. Anti-diabetic effect of methanolic extract of Thespesia populnea flower and leaf in normal and alloxan-induced diabetic rats. Int J Res Ayurveda Pharm 2011;2:936-9.
16. Shirwaikar A, Kumar AV, Krishnanand BR, Sreenivasan KK. Chemical investigation and antihepatotoxic activity of Thespesia populnea. Int J Pharmacogn 1995;33:305â€“10.
17. Ilavarasan R, Vasudevan M, Anbazhagan S, Venkataraman S, Sridhar SK. Hepatoprotective activity of Thespesia populnea bark extracts against carbon tetrachloride-induced liver toxicity in rats. Nat Prod Sci 2003a;9:83â€“6.
18. Ilavarasan R, Vasudevan M, Anbazhagan S, Venkataraman S. Antioxidant activity of Thespesia populnea bark extracts against carbon tetrachloride-induced liver injury in rats. J Ethnopharmacol 2003b;87:227â€“30.
19. Rastogi RP, Mehrotra BN. Compendium of Indian Medicinal Plants. Vol. 5. Lucknow, CDRI, New Delhi: Publication and Information Directorate; 1979.
20. Tokyoshima C. How Ca2+- ATPase pumps ions across the sarcoplasmic reticulum membrane. Biochim Biophys Acta 2009;1793:941-6.
21. Pushpakiran G, Mahalakshmi K, Viswanathan P, Anuradha CV. Taurine prevents ethanol-induced alterations in lipids and ATPases in rat tissues. Pharmacol Rep 2005;57:578-87.
22. Gonzalez-Calvin JL, Saunders JB, Williams R. Effects of ethanol and acetaldehyde on hepatic plasma membrane ATPases. Biochem Pharmacol 1983;32:1723â€“8.
23. Pallavi S, Ambuj Bhushan J, Rama Shanker D, Mohammad P. Reactive oxygen species, oxidative damage, and antioxidative defence mechanism in plants under stressful conditions. J Bot 2012:1-26. Doi:10.1155/2012/217037
24. Ichikawa I, Kiyama S, Yoshioka T. Renal antioxidant enzymes: their regulation and function. Kidney Int 1994;45:1â€“9.
25. Sharma M, Kishore K, Gupta SK, Joshi S, Arya D. Cardioprotective potential of Ocimum sanctum in isoproterenol induced myocardial infarction in rats. Mol Cell Biochem 2001;225:75-83.
26. Elakkiya S, Ananthi T. Studies on anti-inflammatory activity of Thespesia populnea Linn. on the drug induced male albino rats. J Chem Pharm Res 2011;3:473-7.
27. Sahitya Chetan P, Shanmugam RK, Sangeetha LR, Pavan NK, Saritha P, Murali Mohan P, et al. Alterations in antioxidant enzyme activities and oxidative damage in alcoholic rat tissues: protective role of Thespesia populnea. Food Chem 2012;132:150â€“9.
28. Agrawal SS, Paridhavi M. Herbal drug technology. Hyderabad: Universities Press (India) Private Limited; 2007.
29. Makkar HP, Bluemmel M, Borowy NK, Becker K. Gravimetric determination of tannins and their correlations with chemical and protein precipitation methods. J Sci Food Agric 1993;61:161â€“5.
30. Zhishen J, Mengcheng T, Jianming W. The determination of flavonoids contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 1999;64:555â€“9.
31. Ghosh MN. Fundamentals of experimental pharmacology. 2nd ed. Calcutta: Scientific Book Agency Publisher; 1984.
32. Husain K, Somani SM. The response of cardiac antioxidant system to alcohol and exercise training in the rat. Alcohol 1997;14:301-7.
33. Fritz PJ, Hamrick ME. Enzymatic analysis of adenosine triphosphatase. Enzymologia 1966;30:57-64.
34. Desaiah D, Ho IK. Effect of acute and continuous morphine administration on catecholamine-sensitive adenosine triphosphatase in mouse brain. J Pharmacol Exp Ther 1979; 208:80-5.
35. Lowry OH, Lopez JA. The determination of inorganic phosphate in the presence of labile phosphate esters. J Biol Chem 1946;162:421-8.
36. Phillips TD, Hayes AW. Effects of patulin on ATPase in the mouse. Toxicol Appl Pharmacol 1977;42:175-88.
37. McIlwain H. Chemical exploration of the brain: a study of ion movement and cerebral excitability. Amsterdam: Elsevier Publishing Co; 1963.
38. Misra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay of SOD. J Biol Chem 1972;247:3170-5.
39. Aebi H. Oxido reductases acting on groups other than CHOH: Catalase. In: Colowick SP, Kaplan NO, Packer L. editors. Methods in Enzymology. London: Academic Press; 1984. p. 121-5.
40. Beckemeier ME, Bora PS. Fatty acid ethyl esters: potentially toxic products of myocardial ethanol metabolism. J Mol Cell Cardiol 1998;30:2487â€“94.
41. Zhang Y, Ren J. Autophagy in ALDH2-elicited cardioprotection against ischemic heart disease: slayer or saviour? Autophagy 2010;6:1212â€“3.
42. Rappas M, Niwa H, Zhang X. Mechanisms of ATPases--a multi-disciplinary approach. Curr Protein Pept Sci 2004;5:89-105.
43. Upaganlawar A, Gandhi H, Balaraman R. Effect of green tea and vitamin E combination on isoproterenol induced myocardial infarction in rats. Plant Foods Hum Nutr 2009;64:75-80.
44. Upaganlawar A, Balaraman R. Cardioprotective effects of Lagenaria siceraria fruit juice on isoproterenol-induced myocardial infarction in Wistar rats: A biochemical and histo-architecture study. J Young Pharm 2011;3:297-303.
45. Bing RJ. Effect of alcohol on the heart and cardiac metabolism. Fed Proc 1982;41:2443-6.
46. Rosario SepÃºlveda M, Mata AM. The interaction of ethanol with reconstituted synaptosomal plasma membrane Ca2+- ATPase. Biochim Biophys Actaâ€“Biomembr 2004;1665:75â€“80.
47. Bondy SC. Ethanol toxicity and oxidative stress. Toxicol Lett 1992;63:227â€“9.
48. Prince PSM, Dhanasekar K, Rajakumar S. Vanillic acid prevents altered ion pumps, ions, inhibits Fas-receptor and caspase mediated apoptosis-signaling pathway and cardiomyocyte death in myocardial infarcted rats. Chem Biol Interact 2015;232:68â€“76.
49. Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, et al. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 1990;51:283â€“97.
50. Shanmugam KR, Mallikarjuna K, Kesireddy N, Chen CY, Kuo CH, Sathyavelu RK. Ginger feeding protects against renal oxidative damage caused by alcohol consumption in rats. J Renal Nutr 2011;21:263â€“70.
51. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S. The antioxidant vitamins and cardiovascular disease: a critical review of epidemiologic and clinical trial data. Ann Intern Med 1995;123:860-72.
52. Upaganlawar A, Gandhi H, Balaraman R. Effect of vitamin E alone and in combination with lycopene on biochemical and histopathological alterations in isoproterenol-induced myocardial infarction in rats. J Pharmacol Pharmacother 2010;1:24-31.
53. Dandona P, Karne R, Ghanim H, Hamouda W, Aljada A, Magsino CH. Carvedilol inhibits reactive oxygen species generation by leukocytes and oxidative damage to amino acids. Circulation 2000;101:122â€“4.
54. Nakamura K, Kusano K, Nakamura Y. Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation 2002;105:2867â€“71.
55. Yuan Z, Shioji K, Kihara Y, Takenaka H, Onozawa Y, Kishimoto C. Cardioprotective effects of carvedilol on acute autoimmune myocarditis: anti-inflammatory effects associated with the antioxidant property. Am J Physiol Heart C 2004;286:83â€“90.
56. Sharma M, Kishore K, Gupta SK, Joshi S, Arya D. Cardioprotective potential of Ocimum sanctum in isoproterenol induced myocardial infarction in rats. Mol Cell Biochem 2001;225:75-83.
57. Kalyanaraman B, Joseph J, Kalivendi S, Wang S, Konorev E, Kotamraju S. Doxorubicin-induced apoptosis: implications in cardiotoxicity. Mol Cell Biochem 2002;234â€“5:119â€“24.
58. Solomon S, Muruganantham N, Senthamilselvi MM. The antioxidant and anti-inflammatory activity of Thespesia populnea (Flowers). Pharmacophore 2015;6:53-9.