Cardioprotective Effect of Mango and Kinnow Peel Extracts on Doxorubicin-induced Cardiotoxicity in Albino Rats

Cardioprotective Effect of Mango and Kinnow Peel Extracts on Doxorubicin

Authors

  • Muhammad Naeem Safdar Food Science and Product Development Institute, National Agricultural Research Centre, Islamabad, Pakistan , Institute of Food Science and Nutrition, University of Sargodha, Sargodha, Pakistan
  • Tusneem Kausar Institute of Food Science and Nutrition, University of Sargodha, Sargodha, Pakistan
  • Muhammad Nadeem Institute of Food Science and Nutrition, University of Sargodha, Sargodha, Pakistan
  • Saqib Jabbar Food Science and Product Development Institute, National Agricultural Research Centre, Islamabad, Pakistan
  • Salman Ahmed Department of Food Science and Technology, The University of Agriculture, Peshawar, Pakistan
  • Touqeer Taj Ecotoxicology Research Institute, National Agricultural Research Centre, Islamabad, Pakistan
  • Fatima Tufail Food Science and Product Development Institute, National Agricultural Research Centre, Islamabad, Pakistan
  • Waqas Mehmood Department of Food Science and Technology, The University of Agriculture, Peshawar, Pakistan

Keywords:

Polyphenols, peel extracts, cardioprotective activity, doxorubicin, histopathology

Abstract

Different dose levels of mango (Mangifera indica L.) and kinnow (Citrus reticulate L.) peel extracts were administered to rats for 60 days and myocardial infarction was induced by administering doxorubicin (DOX) injection 2.5 mg/kg body weight (BW) intraperitoneal in six equal doses on alternate days from 50th to 60th day. Cardiac biomarkers lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB fraction (CKMB), creatine phosphokinase (CPK), lipid profile (triglycerides, cholesterol,high density lipoprotein (HDL)) and low density lipoprotein (LDL), renal function activities (blood urea nitrogen, creatinine, uric acid) in serum and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) in heart tissues were estimated. Histopathological studies were carried out for cardiac tissues of the studied rat groups. Mango and kinnow peel polyphenolic extracts at medium dose (i.e., 150 mg/kg BW) and high dose (i.e., 300 mg/kg BW) exhibited significant protection against doxorubicin induced myocardial infarction. Maximum cardioprotective activity was exhibited by groups pre-treated with 300 mg/kg of peel extracts, especially mango peel extracts, which maintained the membrane integrity of myocardial tissues, lowered the DOX-induced hyperlipidemia, nephrotoxicity and significantly restored the activity of cardiac endogenous antioxidant enzymes. Histopathological studies of cardiac tissues verifield the cardioprotective activity of both peels extracts at medium and high dose levels. Thus, mango and kinnow peel extracts have cardioprotective potential at medium and high dose levels.

References

Solsona, C., T.B. Kahn, C.L. Badilla, C.A. Zaldiernas, J. Blasi, J.M. Fernandez, & J.A. Cebollada. Altered thiol chemistry in human

amyotrophic lateral sclerosis-linked mutants of superoxide dismutase 1. The Journal of Biological Chemistry 289: 26722–26732 (2014).

Markkanen, E., U. Meyer, & G.L. Dianov. DNA damage and repair in schizophrenia and autism: implications for cancer comorbidity and beyond. International Journal of Molecular Sciences 17(6): E856 (2016) doi: 10.3390/ijms17060856.

Peiró, C., T. Romacho, V. Azcutia, L. Villalobos, E. Fernández, J.P. Bolaños, S. Moncada, & C.F. Sánchez-Ferrer. Inflammation, glucose, and

vascular cell damage: the role of the pentose phosphate pathway.Cardiovascular Diabetology 15: 82 (2016).

Huang, W.J., X. Zhang, &W.W. Chen. Role of oxidative stress in Alzheimer's disease (Review). Biomedical Reports 4: 519-522 (2016).

Piccolo, R., G. Giustino, R. Mehran, &S. Windecker. Stable coronary artery disease: revascularisation and invasive strategies. The

Lancet 386: 702-713 (2015).

Lala, A., & A.S. Desai. The role of coronary artery disease in heart failure. Heart Failure Clinics 10: 353-365 (2014).

Leifert, W.R., & M.Y. Abeywardena. Cardioprotective actions of grape polyphenols.Nutrition Research 28: 729-737 (2008).

Li, A.N., S. Li, Y.J. Zhang, X.R. Xu, Y.M. Chen, & H.B. Li. Resources and biological activities of natural polyphenols. Nutrients 6: 6020-6047

(2014).

Keevil, J.G., H.E. Osman, J.D. Reed, & J.D. Folts. Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. The Journal of Nutrition 130: 53-56 (2000).

Nunes, M.A., F. Pimentel, A.S.G. Costa, R.C. Alves, & M.B.P.P. Oliveira. Cardioprotective properties of grape seed proanthocyanidins: An

update. Trends in Food Science and Technology 57: 31-39 (2016).

Masibo, M., & Q. He. Major mango polyphenols and their potential significance to human health. Comprehensive Reviews in Food Science and Food Safety 7: 309-319 (2008).

Senevirathne, M., Y.J. Jeon, J.H. Ha, & S.H. Kim. Effective drying of citrus by-product by high speed drying: A novel drying technique and their antioxidant activity. Journal of Food Engineering 92: 157-163 (2009).

Franke, A.A., R.V. Cooney, S.M. Henning, & L.J. Custer. Bioavailability and antioxidant effects of orange juice components in humans. Journal of Agriculturaland Food Chemistry 53: 5170-5178 (2005).

Abdel-Raheem, I.T., & A.A. Abdel-Ghany. Hesperidin alleviates doxorubicin-induced cardiotoxicity in rats. Journal of the Egyptian

National Cancer Institute 21: 175-184 (2009).

Kumar, S., R. Marfatia, S. Tannenbaum, C. Yang, & E. Avelar. Doxorubicin-induced cardiomyopathy 17 years after chemotherapy. Texas Heart Institute Journal 39: 424-427 (2012).

Jing, L., L. Li, J. Zhao, J. Zhao, Z. Sun, & S. Peng. Zinc-induced metallothionein overexpression prevents doxorubicin toxicity in cardiomyocytes by regulating the peroxiredoxins. Xenobiotica 46: 715-725 (2016).

Kumral, A., M.S. Tekkeşin, V. Olgac, S.D. Abbasoglu, U. Turkoglu, & M. Uysal. Effect of olive leaf extract treatment on doxorubicininduced cardiac, hepatic and renal toxicity in rats. Pathophysiology 22: 117-123 (2015).

Barry, E., J.A. Alvarez, R.E. Scully, T.L. Miller, & S.E. Lipshultz. Anthracycline-induced cardiotoxicity: Course, pathophysiology,

prevention and management. Expert Opinion on Pharmacotherapy 8: 1039-1058 (2007).

Alyane, M., L. Kebsa, H. Boussenane, H. Rouibah, & M. Lahouel. Cardioprotective effects and mechanism of action of polyphenols extracted from propolis against doxorubicin toxicity. Pakistan Journal of Pharmaceutical Sciences 21: 201-209 (2008).

Cecen, E., T. Dost, N. Culhaci, A. Karul, B. Ergur, & M. Birincioglu. Protective effects of silymarin against doxorubicin-induced toxicity. Asian Pacific Journal of Cancer Prevention 12: 2697-2704 (2010).

Srivastava, P.Beneficial effect of dietary squalene supplementation on experimentally induced cardiomyopathy in rats. International Journal of Research in Pharmaceutical and Biomedical Sciences 3: 525-533 (2015).

Bimakr, M., R.A. Rahman, F.S. Taip, N.M. Adzahan, Z.I. Sarker, & A. Ganjloo. Ultrasoundassisted extraction of valuable compounds

from winter melon (Benincasa hispida) seeds. International Food Research Journal 20: 331-338 (2013).

Singleton, V.L., R. Orthofer, &R.M. LamuelaRaventos. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods in Enzymology 299: 152-178 (1999).

Salvador, M..J., E.O. Ferreira, S.U. MertensTalcott, W.V. De Castro, V. Butterweck, H. Derendorf, & D.A. Dias. Isolation and HPLC

quantitative analysis of antioxidant flavonoids from Alternanthera tenella Colla. Zeitschrift Für Naturforschung C 61: 19-25 (2006).

Bhupati, L.V.S., S. Muvvala, & P. Shashank. Protective effect of Vitis vinifera in doxorubicininduced oxidative stress in rats- A preliminary study. International Journal of Advances in Pharmacy Medicine and Bioallied Sciences 2: 7-14 (2014).

Thomas, L. Clinical Laboratory Diagnostics: Use and Assessment of Clinical Laboratory Results, Ist ed. TH-Books Verlagsgesellschaft, Frankfurt, Germany (1998).

Rosalki, S.B. An improved procedure for serum creatine phosphokinase determination. Journal of Laboratory and Clinical Medicine 69: 696-705 (1967).

Cole, T.G., S.G. Klotzsch & J.R. McNamara. Measurement of triglyceride concentration. In: Handbook of Lipoprotein Testing, 2nd ed. Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.), AACC Press, Wahington, USA, p. 207-220 (2000).

Artiss, J.D. & B. Zak. Measurement of cholesterol concentration. In: Handbook of Lipoprotein Testing, 2nd ed. Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.), AACC Press, Wahington, USA, p. 189-206 (2000).

Nauck, M., D. Wiebe & G.R. Warnick. Measurement of high density lipoprotein cholesterol. In: Handbook of Lipoprotein Testing, 2nd ed., Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.). AACC Press, Wahington, USA, p. 221-244 (2000).

Bachorik, P.S. Measurement of low density lipoprotein cholesterol. In: Handbook of Lipoprotein Testing, 2nd ed., Rifai, N., G.R.

Warnick & M.H. Dominiczak (Ed.). AACC Press, Wahington, USA, p. 245-264 (2000).

First, M.R. Renal Function. In: Clinical Chemistry; Theory, Analysis, Correlation, 4th ed. Kaplan, L.A., A.J. Pesco & S.C. Kazmierczak (Ed.). Mosby, St. Louis, USA, p. 477-491 (2003).

Kono, Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Archives of Biochemistry and Biophysics 186: 189-195 (1978).

Aebi, H. Catalase in vitro. In: L. Packer (Ed.) Methods in Enzymology. Elsevier, Orlando, p. 121-126 (1984).

Rotruck, J., A. Pope, H. Ganther, A. Swanson, D.G. oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods in Enzymology 299: 152-178 (1999).

Salvador, M..J., E.O. Ferreira, S.U. MertensTalcott, W.V. De Castro, V. Butterweck, H. Derendorf, & D.A. Dias. Isolation and HPLC

quantitative analysis of antioxidant flavonoids from Alternanthera tenella Colla. Zeitschrift Für Naturforschung C 61: 19-25 (2006).

Bhupati, L.V.S., S. Muvvala, & P. Shashank. Protective effect of Vitis vinifera in doxorubicininduced oxidative stress in rats- A preliminary study. International Journal of Advances in Pharmacy Medicine and Bioallied Sciences 2: 7-14 (2014).

Thomas, L. Clinical Laboratory Diagnostics: Use and Assessment of Clinical Laboratory Results, I st ed. TH-Books Verlagsgesellschaft, Frankfurt, Germany (1998).

Rosalki, S.B. An improved procedure for serum creatine phosphokinase determination. Journal of Laboratory and Clinical Medicine 69: 696-705 (1967).

Cole, T.G., S.G. Klotzsch & J.R. McNamara. Measurement of triglyceride concentration. In: Handbook of Lipoprotein Testing, 2nd ed. Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.), AACC Press, Wahington, USA, p. 207-220 (2000).

Artiss, J.D. & B. Zak. Measurement of cholesterol concentration. In: Handbook of Lipoprotein Testing, 2nd ed. Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.), AACC Press, Wahington, USA, p. 189-206 (2000).

Nauck, M., D. Wiebe & G.R. Warnick. Measurement of high density lipoprotein cholesterol. In: Handbook of Lipoprotein Testing, 2nd ed., Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.). AACC Press, Wahington, USA, p. 221-244 (2000).

Bachorik, P.S. Measurement of low density lipoprotein cholesterol. In: Handbook of Lipoprotein Testing, 2nd ed., Rifai, N., G.R.

Warnick & M.H. Dominiczak (Ed.). AACC Press, Washington, USA, p. 245-264 (2000).

First, M.R. Renal Function. In: Clinical Chemistry; Theory, Analysis, Correlation, 4th ed. Kaplan, L.A., A.J. Pesco & S.C. Kazmierczak (Ed.). Mosby, St. Louis, USA, p. 477-491 (2003).

Kono, Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Archives of Biochemistry and Biophysics 186: 189-195 (1978).

Aebi, H. Catalase in vitro. In: L. Packer (Ed.) Methods in Enzymology. Elsevier, Orlando, p. 121-126 (1984).

Rotruck, J., A. Pope, H. Ganther, A. Swanson, D.G. oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods in Enzymology 299: 152-178 (1999).

Salvador, M..J., E.O. Ferreira, S.U. MertensTalcott, W.V. De Castro, V. Butterweck, H. Derendorf, & D.A. Dias. Isolation and HPLC

quantitative analysis of antioxidant flavonoids from Alternanthera tenella Colla. Zeitschrift Für Naturforschung C 61: 19-25 (2006).

Bhupati, L.V.S., S. Muvvala, & P. Shashank. Protective effect of Vitis vinifera in doxorubicininduced oxidative stress in rats- A preliminary study. International Journal of Advances in Pharmacy Medicine and Bioallied Sciences 2: 7-14 (2014).

Thomas, L. Clinical Laboratory Diagnostics: Use and Assessment of Clinical Laboratory Results, I st ed. TH-Books Verlagsgesellschaft, Frankfurt, Germany (1998).

Rosalki, S.B. An improved procedure for serum creatine phosphokinase determination. Journal of Laboratory and Clinical Medicine 69: 696-705 (1967).

Cole, T.G., S.G. Klotzsch & J.R. McNamara. Measurement of triglyceride concentration. In: Handbook of Lipoprotein Testing, 2nd ed. Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.), AACC Press, Wahington, USA, p. 207-220 (2000).

Artiss, J.D. & B. Zak. Measurement of cholesterol concentration. In: Handbook of Lipoprotein Testing, 2nd ed. Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.), AACC Press, Wahington, USA, p. 189-206 (2000).

Nauck, M., D. Wiebe & G.R. Warnick. Measurement of high density lipoprotein cholesterol. In: Handbook of Lipoprotein Testing, 2nd ed., Rifai, N., G.R. Warnick & M.H. Dominiczak (Ed.). AACC Press, Wahington, USA, p. 221-244 (2000).

Bachorik, P.S. Measurement of low density lipoprotein cholesterol. In: Handbook of Lipoprotein Testing, 2nd ed., Rifai, N., G.R.

Warnick & M.H. Dominiczak (Ed.). AACC Press, Wahington, USA, p. 245-264 (2000).

First, M.R. Renal Function. In: Clinical Chemistry; Theory, Analysis, Correlation, 4th ed. Kaplan, L.A., A.J. Pesco & S.C. Kazmierczak (Ed.). Mosby, St. Louis, USA, p. 477-491 (2003).

Kono, Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Archives of Biochemistry and Biophysics 186: 189-195 (1978).

Aebi, H. Catalase in vitro. In: L. Packer (Ed.) Methods in Enzymology. Elsevier, Orlando, p.

Rotruck, J., A. Pope, H. Ganther, A. Swanson, D.G. Hafeman, & W. Hoekstra. Selenium: biochemical role as a component of glutathione peroxidase. Science 179: 588-590 (1973).

Patel, S.S., N.K. Verma, B. Rathore, G. Nayak, A.K. Singhai, & P. Singh. Cardioprotective effect of Bombax ceiba flowers against acute adriamycininduced myocardial infarction in rats. Revista Brasileira de Farmacognosia 21: 704-709 (2011).

Prabhu, S., M. Jainu, K. Sabitha, & C.S. Devi. Cardioprotective effect of mangiferin on isoproterenol induced myocardial infarction in

rats. Indian Journal of Experimental Biology 44: 209-215 (2006).

Abirami, M., & U. Kanagavalli. Cardioprotective effect of grapeseed proanthocyanidin on doxorubicin induced myocardial injury in rats. International Journal of Pharmacy and Life Sciences 4: 2288–2293 (2013).

Sivakumar, R., R. Rajesh, S. Buddhan, R. Jeyakumar, D. Rajaprabhu, B. Ganesan, & R. An. Antilipidemic effect of chitosan against

experimentally induced myocardial infarction in rats. Journal of Cell and Animal Biology 1: 71-77 (2007).

Barter, P., J. Kastelein, A. Nunn, R. Hobbs, & F.F.E. Board. High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions. Atherosclerosis 168: 195-211(2003).

Shakya, M., P. Paliwal, S. Patil, B. Koti, & A. Swamy. Cardioprotective effect of 'Qolest'a polyherbal formulation against doxorubicin

induced cardiotoxicity in wistar rats. International Journal of Research in Pharmacy and Science 1: 85-100 (2011).

Jahan, N., K. Rahman, S. Ali, M.R. Asi, & A. Akhtar. Cardioprotective potential of gemmomodified extract of Terminalia arjuna

against chemically induced myocardial injury in rabbits. Pakistan Veterinary Journal 32: 255-259 (2012).

Baniya, S., D.R. Dhananjaya, A. Acharya, B. Dangi, & A. Sapkota. Cardioprotective activity of ethanolic extract of Citrus grandis (L.) osbek peel ondoxorubicin and cyclophosphamide induced cardiotoxicity in albino rats. International Journal of Pharmaceutical Sciences and Drug Research 7: 354-360 (2015).

Borghi, C., F.M. Verardi, I. Pareo, C. Bentivenga, & A.F. Cicero. Hyperuricemia and cardiovascular disease risk. Expert Review of Cardiovascular Therapy 12: 1219-1225 (2014).

Pasalic, D., N. Marinkovic, & L. Feher-Turkovic. Uric acid as one of the important factors in multifactorial disorders–facts and controversies. Biochemia Medica 22: 63-75(2012).

Shafik, A.N., M.M. Khodeir, & M.S. Fadel. Animal study of anthracycline-induced cardiotoxicity and nephrotoxicity and evaluation of protective agents. Journal of Cancer Science and Therapy 3: 96-103 (2011).

Karthikeyan, K.,B.S. Bai, & S.N. Devaraj. Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced

myocardial injury in rats. International Journal of Cardiology 115: 326-333 (2007).

Davey, M.S., & C.W. Atlee. Inotropic and cardioprotective effect of Terminalia Paniculata roth bark extract in doxorubicin induced

cardiotoxicity in rats. International Journal of Research in Ayurveda and Pharmacy 2: 869-875 (2011).

Kulkarni, J., & A.V. Swamy. Cardioprotective effect of gallic acid against doxorubicin-induced myocardial toxicity in albino rats. Indian Journal of Health Sciences 8: 28-35 (2015)

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Published

2017-09-21

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Safdar, M. N. ., Kausar, T., Nadeem, . M. ., Jabbar, S. ., Ahmed, . S. ., Taj, . T., Tufail, . F., & Mehmood, . W. (2017). Cardioprotective Effect of Mango and Kinnow Peel Extracts on Doxorubicin-induced Cardiotoxicity in Albino Rats: Cardioprotective Effect of Mango and Kinnow Peel Extracts on Doxorubicin. Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences, 54(3), 219–235. Retrieved from http://ppaspk.org/index.php/PPAS-B/article/view/394

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Vol. 54 No. 3 (2017)

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Research Articles

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