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Cardiovascular & Hematological Agents in Medicinal Chemistry

Author(s): Justin Atiang Beshel*, Favour Nyoh Beshel, Justina Nwandimma Nwangwa, Idara Asuquo Okon, Clement Ikani Ejim and Daniel Udofia Owu

DOI: 10.2174/1871525718999200917114954

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Cardioprotective Role of Theobroma cacao against Isoproterenol-Induced Acute Myocardial Injury

Page: [75 - 80] Pages: 6

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Abstract

Background: Antioxidants are beneficial in myocardial infarction (MI). It is suggestive that Theobroma cacao (TC) with rich antioxidant properties can be of health benefits in myocardial injury.

Aim: The study investigated the effect of Theobroma cacao on cardioprotection in isoproterenol-induced myocardial infarction in rats.

Material and methods: Male Wistar rats divided into four groups of 6 rats were used for the study. In group 1, 0.9% normal saline placebo was administered via oral gavage to the control. Group 2 was the MI induced group that was given 100 mg/kg body weight isoproterenol subcutaneously twice at an interval of 24 hours. Group 3 was administered TC for 2 weeks at 100 mg/kg bodyweight via the oral route. Group 4 was pretreated with TC (100 mg/kg) via oral route for 2 weeks, immediately followed by the administration of 100 mg/kg body weight isoproterenol subcutaneously twice at an interval of 24 hours. The rats were sacrificed using chloroform anesthesia, and blood samples collected via cardiac puncture. The serum was analyzed for troponin level, lactate dehydrogenase (LDH), and malondialdehyde (MDA) level.

Results: The serum troponin, LDH, and MDA levels were found to be significantly (p<0.01) increased in the MI group compared with the control. Pretreatment with TC before MI induction significantly (p<0.01) prevented increased serum troponin, LDH, and MDA levels when compared with the MI group. There was also a significant (p<0.01) decrease in MDA in the TC group compared with the control.

Conclusion: These results suggest that Theobroma cacao protects against isoproterenol-induced myocardial injury, possibly by preventing oxidative stress and consequent lipid peroxidation.

Keywords: Acute myocardial infarction, isoproterenol, troponins, lactate dehydrogenase, malondialdehyde, Theobroma cacao, antioxidants.

Graphical Abstract

[1]
Reindl, M.; Reinstadler, S.J.; Feistritzer, H.J.; Mayr, A.; Klug, G.; Marschang, P.; Metzler, B. Acute myocardial infarction as a manifestation of systemic vasculitis. Wien. Klin. Wochenschr., 2016, 128(21-22), 841-843.
[http://dx.doi.org/10.1007/s00508-016-1051-4] [PMID: 27624326]
[2]
Haasenritter, J.; Stanze, D.; Widera, G.; Wilimzig, C.; Abu Hani, M.; Sonnichsen, A.C.; Bosner, S.; Rochon, J.; Donner-Banzhoff, N. Does the patient with chest pain have a coronary heart disease? Diagnostic value of single symptoms and signs-a meta-analysis. Croat. Med. J., 2012, 53(5), 432-441.
[http://dx.doi.org/10.3325/cmj.2012.53.432] [PMID: 23100205]
[3]
Rathore, V.; Singh, N.; Mahat, R. Risk factors for acute myocardial infarction: A review. Eurasian J. Med., 2018, 2(1), 1-7.
[http://dx.doi.org/10.14744/ejmi.2018.76486]
[4]
Richardson, W.J.; Clarke, S.A.; Quinn, T.A.; Holmes, J.W. Physiological implications of myocardial scar structure. Compr. Physiol., 2015, 5(4), 1877-1909.
[http://dx.doi.org/10.1002/cphy.c140067] [PMID: 26426470]
[5]
Liakos, M.; Parikh, P.B. Gender disparities in presentation, management, and outcomes of acute myocardial infarction. Curr. Cardiol. Rep., 2018, 20(8), 64.
[http://dx.doi.org/10.1007/s11886-018-1006-7] [PMID: 29909444]
[6]
Aydin, S.; Aydin, S. Irisin concentrations as a myocardial biomarker. Biomarkers in Cardiovascular Disease; Patel, V.B.; Preedy, V.R., Eds.; Springer: Dordrecht, 2016, pp. 489-504.
[http://dx.doi.org/10.1007/978-94-007-7678-4_3]
[7]
Danese, E.; Montagnana, M. An historical approach to the diagnostic biomarkers of acute coronary syndrome. Ann. Transl. Med., 2016, 4(10), 194.
[http://dx.doi.org/10.21037/atm.2016.05.19] [PMID: 27294090]
[8]
Mythili, S.; Malathi, N. Diagnostic markers of acute myocardial infarction. Biomed. Rep., 2015, 3(6), 743-748.
[http://dx.doi.org/10.3892/br.2015.500] [PMID: 26623010]
[9]
Feng, Q.Z.; Cheng, L.Q.; Li, Y.F. Progressive deterioration of left ventricular function in a patient with a normal coronary angiogram. World J. Cardiol., 2012, 4(4), 130-134.
[http://dx.doi.org/10.4330/wjc.v4.i4.130] [PMID: 22558493]
[10]
Åsgård, R.; Rytter, E.; Basu, S.; Abramsson-Zetterberg, L.; Möller, L.; Vessby, B. High intake of fruit and vegetables is related to low oxidative stress and inflammation in a group of patients with type 2 diabetes. Scand. J.Food Nutr., 2007, 51(4), 149-158.
[http://dx.doi.org/10.1080/17482970701737285]
[11]
Tang, G.Y.; Meng, X.; Li, Y.; Zhao, C.N.; Liu, Q.; Li, H.B. Effects of vegetables on cardiovascular diseases and related mechanisms. Nutrients, 2017, 9(8), 857.
[http://dx.doi.org/10.3390/nu9080857]
[12]
Moller, D.E.; Kaufman, K.D. Metabolic syndrome: a clinical and molecular perspective. Annu. Rev. Med., 2005, 56, 45-62.
[http://dx.doi.org/10.1146/annurev.med.56.082103.104751] [PMID: 15660501]
[13]
Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z. The metabolic syndrome. Lancet, 2005, 365(9468), 1415-1428.
[http://dx.doi.org/10.1016/S0140-6736(05)66378-7] [PMID: 15836891]
[14]
Ramaraj, R.; Chellappa, P. Cardiovascular risk in South Asians. Postgrad. Med. J., 2008, 84(996), 518-523.
[http://dx.doi.org/10.1136/pgmj.2007.066381] [PMID: 19017836]
[15]
Choudhary, M.; Tomer, V. Cardioprotective effect of nutraceuticals – the emerging evidences. Proc. Indian Natn. Sci. Acad., 2013, 79(4), 985-996.
[16]
Kumar, A.; Krishna, G.; Hullatti, P.; Akshara, T. Indian plants with cardioprotective activity–a review. Sys. Rev. Pharm., 2017, 8(1), 8-12.
[http://dx.doi.org/10.5530/srp.2017.1.3]
[17]
Viswanatha, G.L.S.; Vaidya, S.K.; Ramesh, C.; Krishnadas, N.; Rangappa, S. Antioxidant and antimutagenic activities of bark extract of Terminalia arjuna. Asian Pac. J. Trop. Med., 2010, 3, 965-970.
[http://dx.doi.org/10.1016/S1995-7645(11)60010-2]
[18]
Kris-Etherton, P.M.; Keen, C.L. Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr. Opin. Lipidol., 2002, 13(1), 41-49.
[http://dx.doi.org/10.1097/00041433-200202000-00007] [PMID: 11790962]
[19]
Kurosawa, T.; Itoh, F.; Nozaki, A.; Nakano, Y.; Katsuda, S.; Osakabe, N.; Tsubone, H.; Kondo, K.; Itakura, H. Suppressive effect of cocoa powder on atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic rabbits. J. Atheroscler. Thromb., 2005, 12(1), 20-28.
[http://dx.doi.org/10.5551/jat.12.20] [PMID: 15725692]
[20]
Murphy, K.J.; Chronopoulos, A.K.; Singh, I.; Francis, M.A.; Moriarty, H.; Pike, M.J.; Turner, A.H.; Mann, N.J.; Sinclair, A.J. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am. J. Clin. Nutr., 2003, 77(6), 1466-1473.
[http://dx.doi.org/10.1093/ajcn/77.6.1466] [PMID: 12791625]
[21]
Neukam, K.; Stahl, W.; Tronnier, H.; Sies, H.; Heinrich, U. Consumption of flavanol-rich cocoa acutely increases microcirculation in human skin. Eur. J. Nutr., 2007, 46(1), 53-56.
[http://dx.doi.org/10.1007/s00394-006-0627-6] [PMID: 17164979]
[22]
Tomaru, M.; Takano, H.; Osakabe, N.; Yasuda, A.; Inoue, K.; Yanagisawa, R.; Ohwatari, T.; Uematsu, H. Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice. Nutrition, 2007, 23(4), 351-355.
[http://dx.doi.org/10.1016/j.nut.2007.01.007] [PMID: 17350804]
[23]
Agwupuye, E.I.; Beshel, J.A.; Anosike, A.C.; Ezeanyika, L.U. Methanol extract of unfermented Theobroma cacao promotes normal lipid profile of wistar rats. Int. J. Trend Res., 2019, 3(3), 190-193.
[http://dx.doi.org/10.31142/ijtsrd21730]
[24]
Ramljak, D.; Romanczyk, L.J.; Metheny-Barlow, L.J.; Thompson, N.; Knezevic, V.; Galperin, M.; Ramesh, A.; Dickson, R.B. Pentameric procyanidin from Theobroma cacao selectively inhibits growth of human breast cancer cells. Mol. Cancer Ther., 2005, 4(4), 537-546.
[http://dx.doi.org/10.1158/1535-7163.MCT-04-0286] [PMID: 15827326]
[25]
Bruinsma, K.; Taren, D.L. Chocolate: food or drug? J. Am. Diet. Assoc., 1999, 99(10), 1249-1256.
[http://dx.doi.org/10.1016/S0002-8223(99)00307-7] [PMID: 10524390]
[26]
Abat, J.K.; Kumar, S.; Mohanty, A. Ethnomedicinal, Phytochemical and ethnopharmacological aspects of four medicinal plants of Malvaceae used in Indian traditional medicine: a review. Medicines (Basel), 2017, 4(4), 75.
[http://dx.doi.org/10.3390/medicines4040075] [PMID: 29057840]
[27]
Boarescu, P.; Chirila, I.; Bulboaca, A.; Parvu, A.; Gheban, D.; Bolboaca, S. Isoproterenol Induced Myocardial Infarction in Rats: Dose Identification. Clujul Med., 2018, 91, 6.
[28]
Gunjal, M.A.; Shah, A.S.; Wakade, A.S.; Juvekar, A.R. Protective effect of Moringa olifera Lam stem bark on serum lipids, marker enzymes and heart antioxidant parameters in isoproterenol induced cardiotoxicity in wistar rats. Indian J. Nat. Prod. Resour., 2010, 1(4), 485-492.
[29]
Nirmala, C.; Puvanakrishnan, R. Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Mol. Cell. Biochem., 1996, 159(2), 85-93.
[http://dx.doi.org/10.1007/BF00420910] [PMID: 8858558]
[30]
Jialal, I.; Sokoll, L.J. Clinical utility of lactate dehydrogenase: a historical perspective. Am. J. Clin. Pathol., 2015, 143(2), 158-159.
[http://dx.doi.org/10.1309/AJCTP0FC8QFYDFA] [PMID: 25596240]
[31]
Wessler, J.D.; Stant, J.; Duru, S.; Rabbani, L.; Kirtane, A.J. Updates to the ACCF/AHA and ESC STEMI and NSTEMI guidelines: putting guidelines into clinical practice. Am. J. Cardiol., 2015, 115(5)(Suppl.), 23A-28A.
[http://dx.doi.org/10.1016/j.amjcard.2015.01.004] [PMID: 25728971]
[32]
Kathyaini, R.; Gayatri, S.; Suleman, D. A study on Malondialdehyde as an oxidative stress marker in patients with myocardial infarction at a tertiary care centre. Natl. J. Lab. Med., 2017, 6(4), 13-16.
[33]
Korkmaz, S.; Radovits, T.; Barnucz, E.; Hirschberg, K.; Neugebauer, P.; Loganathan, S.; Veres, G.; Páli, S.; Seidel, B.; Zöllner, S.; Karck, M.; Szabó, G. Pharmacological activation of soluble guanylate cyclase protects the heart against ischemic injury. Circulation, 2009, 120(8), 677-686.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.870774] [PMID: 19667237]
[34]
Ittagi, S.; Merugumolu, V.; Siddamsetty, R. Cardioprotective effect of hydroalcoholic extract of Tecoma stans flowers against isoproterenol induced myocardial infarction in rats. Asian Pac. J. Trop. Dis., 2014, 1808(14), 60474-60476.
[http://dx.doi.org/10.1016/S2222-1808(14)60474-6]
[35]
Sudhakumari, A.; Javed, A.; Jaiswal, M.; Talkad, M.S.; Cardioprotective effects in methanolic extract of Evolvulus alsinoides Linn on isoproterenol-induced myocardial infarction in albino rats. IJBMSP, 2012, 2(2), 2049-4963.
[36]
Asdaq, S.M.; Inamdar, M.N. Pharmacodynamic interaction of garlic with hydrochlorothiazide in rats. Indian J. Physiol. Pharmacol., 2009, 53(2), 127-136.
[PMID: 20112816]
[37]
Siddiqui, M.A.; Ahmad, U.; Khan, A.A.; Ahmad, M.; Badruddeen, M.K.; Akhtar, J. Isoprenaline: a tool for inducing myocardial infarction in experimental animals. Int. J. Pharm., 2016, 6(2), 138-144.
[38]
Gaweł, S.; Wardas, M.; Niedworok, E.; Wardas, P. Malondialdehyde (MDA) as a lipid peroxidation marker. Wiad. Lek. (Warsaw, Poland : 1960), 2004, 57(9-10), 453-455.
[39]
Mastan, S.K.; Chaitanya, G.; Latha, B.T.; Srikanth, A.; Sumalatha, G.; Kumar, K.E. Cardioprotective effect of methanolic extract of Syzygium cumini seeds on isoproterenol- induced myocardial infarction in rats. Der Pharmacia Lettre, 2009, 1(1), 143-149.
[40]
Fujii, S.; Konishi, I.; Suzuki, A.; Okamura, H.; Okazaki, T.; Mori, T. Analysis of serum lactic dehydrogenase levels and its isoenzymes in ovarian dysgerminoma. Gynecol. Oncol., 1985, 22(1), 65-72.
[http://dx.doi.org/10.1016/0090-8258(85)90009-5] [PMID: 4018662]
[41]
Wei, B.; Jin, J.P. Troponin T isoforms and posttranscriptional modifications: Evolution, regulation and function. Arch. Biochem. Biophys., 2011, 505(2), 144-154.
[http://dx.doi.org/10.1016/j.abb.2010.10.013] [PMID: 20965144]
[42]
Anderson, P.A.; Malouf, N.N.; Oakeley, A.E.; Pagani, E.D.; Allen, P.D. Troponin T isoform expression in humans. A comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle. Circ. Res., 1991, 69(5), 1226-1233.
[http://dx.doi.org/10.1161/01.RES.69.5.1226] [PMID: 1934353]
[43]
Bodor, G.S. Biochemical markers of myocardial damage. EJIFCC, 2016, 27(2), 95-111.
[PMID: 27683523]
[44]
Anosike, C.A.; Iwunze, C.C. Effect of Theobroma cacao polyphenol on isoproterenol-induced myocardial infarction in wistar rats. J. Appl. Pharm. Sci., 2015, 5(7), 76-83.
[http://dx.doi.org/10.7324/JAPS.2015.50713]
[45]
Wang-Polagruto, J.F.; Villablanca, A.C.; Polagruto, J.A.; Lee, L.; Holt, R.R.; Schrader, H.R.; Ensunsa, J.L.; Steinberg, F.M.; Schmitz, H.H.; Keen, C.L. Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women. J. Cardiovasc. Pharmacol., 2006, 47(Suppl. 2), S177-S186.
[http://dx.doi.org/10.1097/00005344-200606001-00013] [PMID: 16794456]
[46]
McCullough, M.L.; Chevaux, K.; Jackson, L.; Preston, M.; Martinez, G.; Schmitz, H.H.; Coletti, C.; Campos, H.; Hollenberg, N.K. Hypertension, the Kuna, and the epidemiology of flavanols. J. Cardiovasc. Pharmacol., 2006, 47(Suppl. 2), S103-S109.
[http://dx.doi.org/10.1097/00005344-200606001-00003] [PMID: 16794446]
[47]
Taubert, D.; Roesen, R.; Schömig, E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch. Intern. Med., 2007, 167(7), 626-634.
[http://dx.doi.org/10.1001/archinte.167.7.626] [PMID: 17420419]
[48]
Gallus, S.; Tavani, A.; La Vecchia, C. Response to Chocolate, well-being and health among elderly men: chocolate and acute myocardial infarction in a case-control study from Italy. Eur. J. Clin. Nutr., 2009, 63(4), 588-589.
[http://dx.doi.org/10.1038/sj.ejcn.1602945] [PMID: 17957191]
[49]
Galleano, M.; Oteiza, P.I.; Fraga, C.G. Cocoa, chocolate, and cardiovascular disease. J. Cardiovasc. Pharmacol., 2009, 54(6), 483-490.
[http://dx.doi.org/10.1097/FJC.0b013e3181b76787] [PMID: 19701098]
[50]
Cheng, Y.C.; Sheen, J.M.; Hu, W.L.; Hung, Y.C. Polyphenols and oxidative stress in atherosclerosis-related ischemic heart disease and stroke. Oxid. Med. Cell. Longev., 2017, 2017, 8526438.
[http://dx.doi.org/10.1155/2017/8526438] [PMID: 29317985]
[51]
Ottaviani, J.I.; Heiss, C.; Spencer, J.P.E.; Kelm, M.; Schroeter, H. Recommending flavanols and procyanidins for cardiovascular health: Revisited. Mol. Aspects Med., 2018, 61, 63-75.
[http://dx.doi.org/10.1016/j.mam.2018.02.001] [PMID: 29427606]
[52]
Arteel, G.E.; Sies, H. Protection against peroxynitrite by cocoa polyphenol oligomers. FEBS Lett., 1999, 462(1-2), 167-170.
[http://dx.doi.org/10.1016/S0014-5793(99)01498-2] [PMID: 10580113]
[53]
Rein, D.; Paglieroni, T.G.; Wun, T.; Pearson, D.A.; Schmitz, H.H.; Gosselin, R.; Keen, C.L. Cocoa inhibits platelet activation and function. Am. J. Clin. Nutr., 2000, 72(1), 30-35. b
[http://dx.doi.org/10.1093/ajcn/72.1.30] [PMID: 10871557]
[54]
Zhu, Q.Y.; Holt, R.R.; Lazarus, S.A.; Orozco, T.J.; Keen, C.L. Inhibitory effects of cocoa flavanols and procyanidin oligomers on free radical-induced erythrocyte hemolysis. Exp. Biol. Med. (Maywood), 2002, 227(5), 321-329.
[http://dx.doi.org/10.1177/153537020222700504] [PMID: 11976402]
[55]
Heiss, C.; Dejam, A.; Kleinbongard, P.; Schewe, T.; Sies, H.; Kelm, M. Vascular effects of cocoa rich in flavan-3-ols. JAMA, 2003, 290(8), 1030-1031.
[http://dx.doi.org/10.1001/jama.290.8.1030] [PMID: 12941674]
[56]
Zhao, J.; Lahiri-Chatterjee, M.; Sharma, Y.; Agarwal, R. Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Carcinogenesis, 2000, 21(4), 811-816.
[http://dx.doi.org/10.1093/carcin/21.4.811] [PMID: 10753220]
[57]
Polovka, M.; Brezová, V.; Stasko, A. Antioxidant properties of tea investigated by EPR spectroscopy. Biophys. Chem., 2003, 106(1), 39-56.
[http://dx.doi.org/10.1016/S0301-4622(03)00159-5] [PMID: 14516911]
[58]
Rice-Evans, C. Flavonoid antioxidants. Curr. Med. Chem., 2001, 8(7), 797-807.
[http://dx.doi.org/10.2174/0929867013373011] [PMID: 11375750]