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3 Biotech

, 9:147 | Cite as

Beetroot juice alleviates isoproterenol-induced myocardial damage by reducing oxidative stress, inflammation, and apoptosis in rats

  • Mohammad RaishEmail author
  • Ajaz Ahmad
  • Mushtaq Ahmad Ansari
  • Khalid M. Alkharfy
  • Abdul Ahad
  • Altaf Khan
  • Naushad Ali
  • Majid A. Ganaie
  • Mohammed Abbas Ali Hamidaddin
Original Article
  • 57 Downloads

Abstract

Beetroot (Beta vulgaris L.) juice (BRJ) is a good source of betalain (betacyanins and betaxanthin) pigments and exhibits antioxidant, anti-inflammatory, and chemo-preventive activities in vitro and in vivo. The current study was performed to determine the cardioprotective effect of BRJ on lipid peroxidation, antioxidant defense, functional impairment, and histopathology in rats with isoproterenol (ISP)-induced myocardial injury. Myocardial ischemia was induced by ISP (85 mg/kg) s.c. injection at 24 h intervals, followed by oral administration of BRJ for 28 days at doses of 150 and 300 mg/kg. ISP-induced myocardial damage was confirmed by an increase in heart weight to body weight ratio, % infarction size, serum cardiac indices (AST, ALT, GGT, ALP, LDH and CK-MB), and histological alterations in the myocardium. Pretreatment with BRJ (150 and 300 mg/kg) followed by ISP induction reduced oxidative/nitrosative stress and restored the cardiac endogenous antioxidants in rats. ISP augmented cardiac inflammatory cytokines (TNF-α, IL-6 and IL-10), myeloperoxidase activity, NF-κB DNA binding and protein expression of NF-κB (p65), and the hyperlipidemia level was significantly reduced by the BRJ pretreatment. Furthermore, the BRJ pretreatment significantly reduced caspase-3, Bax, and MMP-9 protein expression, enhanced the Bcl-2 antiapoptotic protein expression, alleviated the extent of histological damage, myonecrosis, and edema, and maintained the architecture of cardiomyocytes. These findings suggest that BRJ pretreatment mitigates cardiac dysfunction and structural damages by decreasing oxidative stress, inflammation, and apoptosis in cardiac tissues. These results further support the use of BRJ in traditional medicine against cardiovascular diseases.

Keywords

Beetroot juice Isoproterenol Oxidative stress Myocardial injury Cardioprotection 

Abbreviations

BRJ

Beetroot juice

MI

Myocardial infarction

ISP

Isoproterenol

b.w

Body weight

LPO

Lipid peroxidation

AST

Aspartate transaminase

LDH

Lactate dehydrogenase

CK-MB

Creatine kinase-MB isoenzyme

MDA

Malondialdehyde

TP

Total protein

CAT

Catalase

SOD

Superoxide dismutase

NP-SH

Non-protein sulphydydryl group

MPO

Myeloperoxidase

NO

Nitric oxide

OD

Optical density

s.c

Sub-cutaneous

TNF-α

Tumor necrosis factor-α

IL-6

Interleukin-6

IL-10

Interleukin-10

NF-κB

Nuclear factor kappa B

Notes

Acknowledgements

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through the Research Group Number, RG-1438-081.

Compliance with ethical standards

Conflict of interest

The author(s) declare no conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

  1. Aebi H (1974) Catalase. Methods in enzymatic analysis, vol 2. Academic, CheimeGoogle Scholar
  2. Agrawal YO, Sharma PK, Shrivastava B, Ojha S, Upadhya HM, Arya DS, Goyal SN (2014) Hesperidin produces cardioprotective activity via PPAR-gamma pathway in ischemic heart disease model in diabetic rats. PLoS One 9(11):e111212.  https://doi.org/10.1371/journal.pone.0111212 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Al-Yahya M, Raish M, AlSaid MS, Ahmad A, Mothana RA, Al-Sohaibani M, Al-Dosari MS, Parvez MK, Rafatullah S (2015) ‘Ajwa’ dates (Phoenix dactylifera L.) extract ameliorates isoproterenol-induced cardiomyopathy through downregulation of oxidative, inflammatory and apoptotic molecules in rodent model. Phytomedicine.  https://doi.org/10.1016/j.phymed.2015.10.019 CrossRefPubMedGoogle Scholar
  4. Asselbergs FW, Tervaert JW, Tio RA (2004) Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 350(5):516–518 (author reply 516–518) CrossRefGoogle Scholar
  5. Assmann G (1979) A fully enzymatic colorimetric determination of HDL-cholesterol in the serum. Internist 20:559–567PubMedGoogle Scholar
  6. Chilton RJ (2004) Pathophysiology of coronary heart disease: a brief review. J Am Osteopath Assoc 104(9 Suppl 7):S5–S8PubMedGoogle Scholar
  7. Curtis KJ, O’Brien KA, Tanner RJ, Polkey JI, Minnion M, Feelisch M, Polkey MI, Edwards LM, Hopkinson NS (2015) Acute dietary nitrate supplementation and exercise performance in COPD: a double-blind, placebo-controlled, randomised controlled pilot study. PLoS One 10(12):e0144504.  https://doi.org/10.1371/journal.pone.0144504 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Du H, Hao J, Liu F, Lu J, Yang X (2015) Apigenin attenuates acute myocardial infarction of rats via the inhibitions of matrix metalloprotease-9 and inflammatory reactions. Int J Clin Exp Med 8(6):8854–8859PubMedPubMedCentralGoogle Scholar
  9. El Gamal AA, AlSaid MS, Raish M, Al-Sohaibani M, Al-Massarani SM, Ahmad A, Hefnawy M, Al-Yahya M, Basoudan OA, Rafatullah S (2014) Beetroot (Beta vulgaris L.) extract ameliorates gentamicin-induced nephrotoxicity associated oxidative stress, inflammation, and apoptosis in rodent model. Mediat Inflamm 2014:983952.  https://doi.org/10.1155/2014/983952 CrossRefGoogle Scholar
  10. Fan Q, Chen M, Fang X, Lau WB, Xue L, Zhao L, Zhang H, Liang YH, Bai X, Niu HY, Ye J, Chen Q, Yang X, Liu M (2013) Aging might augment reactive oxygen species (ROS) formation and affect reactive nitrogen species (RNS) level after myocardial ischemia/reperfusion in both humans and rats. Age (Dordr) 35(4):1017–1026.  https://doi.org/10.1007/s11357-012-9421-y CrossRefGoogle Scholar
  11. Frantz S, Kelly RA, Bourcier T (2001) Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes. J Biol Chem 276(7):5197–5203.  https://doi.org/10.1074/jbc.M009160200 CrossRefPubMedGoogle Scholar
  12. Georgiev VG, Weber J, Kneschke EM, Denev PN, Bley T, Pavlov AI (2010) Antioxidant activity and phenolic content of betalain extracts from intact plants and hairy root cultures of the red beetroot Beta vulgaris cv. Detroit dark red. Plant Foods Hum Nutr 65(2):105–111.  https://doi.org/10.1007/s11130-010-0156-6 CrossRefPubMedGoogle Scholar
  13. Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281(5381):1309–1312CrossRefGoogle Scholar
  14. Hirotani S, Otsu K, Nishida K, Higuchi Y, Morita T, Nakayama H, Yamaguchi O, Mano T, Matsumura Y, Ueno H, Tada M, Hori M (2002) Involvement of nuclear factor-kappa B and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyocyte hypertrophy. Circulation 105(4):509–515CrossRefGoogle Scholar
  15. Hobbs DA, George TW, Lovegrove JA (2013) The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies. Nutr Res Rev 26(2):210–222.  https://doi.org/10.1017/S0954422413000188 CrossRefPubMedGoogle Scholar
  16. Joris PJ, Mensink RP (2013) Beetroot juice improves in overweight and slightly obese men postprandial endothelial function after consumption of a mixed meal. Atherosclerosis 231(1):78–83.  https://doi.org/10.1016/j.atherosclerosis.2013.09.001 CrossRefPubMedGoogle Scholar
  17. Kalogeris T, Bao Y, Korthuis RJ (2014) Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol 2:702–714.  https://doi.org/10.1016/j.redox.2014.05.006 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Kaptoge S, Seshasai SR, Gao P, Freitag DF, Butterworth AS, Borglykke A, Di Angelantonio E, Gudnason V, Rumley A, Lowe GD, Jorgensen T, Danesh J (2014) Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J 35(9):578–589.  https://doi.org/10.1093/eurheartj/eht367 CrossRefPubMedGoogle Scholar
  19. Kim HE, Dalal SS, Young E, Legato MJ, Weisfeldt ML, D’Armiento J (2000) Disruption of the myocardial extracellular matrix leads to cardiac dysfunction. J Clin Invest 106(7):857–866.  https://doi.org/10.1172/JCI8040 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kujala TS, Vienola MS, Klika KD, Loponen JM, Pihlaja K (2002) Betalain and phenolic compositions of four beetroot (Beta vulgaris) cultivars. Eur Food Res Technol 214(6):505–510.  https://doi.org/10.1007/s00217-001-0478-6 CrossRefGoogle Scholar
  21. Laine G, Allen S (1991) Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function. Circ Res 68(6):1713–1721CrossRefGoogle Scholar
  22. Lawrence T (2009) The nuclear factor NF-kappa B pathway in inflammation. Cold Spring Harbor Perspect Biol 1(6):a001651.  https://doi.org/10.1101/cshperspect.a001651 CrossRefGoogle Scholar
  23. Lee CH, Wettasinghe M, Bolling BW, Ji LL, Parkin KL (2005) Betalains, phase II enzyme-inducing components from red beetroot (Beta vulgaris L.) extracts. Nutr Cancer 53(1):91–103.  https://doi.org/10.1207/s15327914nc5301_11 CrossRefPubMedGoogle Scholar
  24. Li H, Liang J, Castrillon DH, DePinho RA, Olson EN, Liu Z-P (2007) FoxO4 regulates tumor necrosis factor alpha-directed smooth muscle cell migration by activating matrix metalloproteinase 9 gene transcription. Mol Cell Biol 27(7):2676–2686CrossRefGoogle Scholar
  25. Lord-Fontaine S, Averill-Bates DA (2002) Heat shock inactivates cellular antioxidant defenses against hydrogen peroxide: protection by glucose. Free Radic Biol Med 32(8):752–765CrossRefGoogle Scholar
  26. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMedPubMedCentralGoogle Scholar
  27. Lundberg JO, Weitzberg E, Gladwin MT (2008) The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7(2):156–167.  https://doi.org/10.1038/nrd2466 CrossRefPubMedGoogle Scholar
  28. Maulik SK, Kumar S (2012) Oxidative stress and cardiac hypertrophy: a review. Toxicol Mech Methods 22(5):359–366.  https://doi.org/10.3109/15376516.2012.666650 CrossRefPubMedGoogle Scholar
  29. Moris D, Spartalis M, Tzatzaki E, Spartalis E, Karachaliou GS, Triantafyllis AS, Karaolanis GI, Tsilimigras DI, Theocharis S (2017) The role of reactive oxygen species in myocardial redox signaling and regulation. Ann Transl Med 5(16):324.  https://doi.org/10.21037/atm.2017.06.17 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Oecd (1994) OECD guidelines for the testing of chemicals. Organization for Economic, ParisGoogle Scholar
  31. Ojha S, Golechha M, Kumari S, Arya DS (2012) Protective effect of Emblica officinalis (amla) on isoproterenol-induced cardiotoxicity in rats. Toxicol Ind Health 28(5):399–411.  https://doi.org/10.1177/0748233711413798 CrossRefPubMedGoogle Scholar
  32. Peskin AV, Winterbourn CC (2000) A microtiter plate assay for superoxide dismutase using a water-soluble tetrazolium salt (WST-1). Clin Chim Acta 293(1–2):157–166CrossRefGoogle Scholar
  33. Raish M (2017) Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-kappa B signaling pathway. Int J Biol Macromol 97:544–551.  https://doi.org/10.1016/j.ijbiomac.2017.01.074 CrossRefPubMedGoogle Scholar
  34. Rona G, Kahn DS, Chappel CI (1963) Studies on infarct-like myocardial necrosis produced by isoproterenol: a review. Rev Can Biol 22:241–255PubMedGoogle Scholar
  35. Sahu BD, Putcha UK, Kuncha M, Rachamalla SS, Sistla R (2014) Carnosic acid promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress and apoptosis in mice. Mol Cell Biochem 394(1–2):163–176.  https://doi.org/10.1007/s11010-014-2092-5 CrossRefPubMedGoogle Scholar
  36. Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS (2002) Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol 34(4):379–388CrossRefGoogle Scholar
  37. Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205CrossRefGoogle Scholar
  38. Seropian IM, Toldo S, Van Tassell BW, Abbate A (2014) Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J Am Coll Cardiol 63(16):1593–1603CrossRefGoogle Scholar
  39. Singleton VL, Orthofer R, Lamuela-Raventos RM (1999) [14] Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods Enzymol 299C:152–178CrossRefGoogle Scholar
  40. Spodick DH (2004) Decreased recognition of the post-myocardial infarction (Dressler) syndrome in the postinfarct setting: does it masquerade as “idiopathic pericarditis” following silent infarcts? Chest 126(5):1410–1411.  https://doi.org/10.1378/chest.126.5.1410 CrossRefPubMedGoogle Scholar
  41. Tesoriere L, Fazzari M, Angileri F, Gentile C, Livrea MA (2008) In vitro digestion of betalainic foods. Stability and bioaccessibility of betaxanthins and betacyanins and antioxidative potential of food digesta. J Agric Food Chem 56(22):10487–10492.  https://doi.org/10.1021/jf8017172 CrossRefPubMedGoogle Scholar
  42. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76(9):4350–4354CrossRefGoogle Scholar
  43. Upaganlawar A, Gandhi C, Balaraman R (2009) Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats. Plant Foods Hum Nutr 64(1):75–80.  https://doi.org/10.1007/s11130-008-0105-9 CrossRefPubMedGoogle Scholar
  44. Vali L, Stefanovits-Banyai E, Szentmihalyi K, Febel H, Sardi E, Lugasi A, Kocsis I, Blazovics A (2007) Liver-protecting effects of table beet (Beta vulgaris var. rubra) during ischemia-reperfusion. Nutrition 23(2):172–178.  https://doi.org/10.1016/j.nut.2006.11.004 CrossRefPubMedGoogle Scholar
  45. Van Vleet J, Ferrans V, Herman E (2002) Cardiovascular and skeletal muscle systems. Handb Toxicol Pathol 2:363–455CrossRefGoogle Scholar
  46. Vulic JJ, Cebovic TN, Canadanovic-Brunet JM, Cetkovic GS, Canadanovic VM, Djilas SM, Saponjac VTT (2014) In vivo and in vitro antioxidant effects of beetroot pomace extracts. J Funct Foods 6:168–175.  https://doi.org/10.1016/j.jff.2013.10.003 CrossRefGoogle Scholar
  47. Winkler BWC, Schroecksnadel K, Schennach H, Fuchs D (2005) In vitro effects of beet root juice on stimulated and unstimulated peripheral blood mononuclear cells. Am J Biochem Biotechnol 1:180–185CrossRefGoogle Scholar
  48. Wybraniec S (2005) Formation of decarboxylated betacyanins in heated purified betacyanin fractions from red beet root (Beta vulgaris L.) monitored by LC-MS/MS. J Agric Food Chem 53(9):3483–3487.  https://doi.org/10.1021/jf048088d CrossRefPubMedGoogle Scholar
  49. Zhou R, Xu Q, Zheng P, Yan L, Zheng J, Dai G (2008) Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. Eur J Pharmacol 586(1–3):244–250CrossRefGoogle Scholar

Copyright information

© King Abdulaziz City for Science and Technology 2019

Authors and Affiliations

  • Mohammad Raish
    • 1
    Email author
  • Ajaz Ahmad
    • 2
  • Mushtaq Ahmad Ansari
    • 3
  • Khalid M. Alkharfy
    • 2
  • Abdul Ahad
    • 1
  • Altaf Khan
    • 3
  • Naushad Ali
    • 5
  • Majid A. Ganaie
    • 4
  • Mohammed Abbas Ali Hamidaddin
    • 6
  1. 1.Department of PharmaceuticsCollege of Pharmacy, King Saud UniversityRiyadhSaudi Arabia
  2. 2.Department Clinical Pharmacy, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  3. 3.Department Pharmacology and Toxicology, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  4. 4.Department Pharmacology and Toxicology, College of PharmacyPrince Sattam Bin Abdulaziz UniversityAlkharajSaudi Arabia
  5. 5.Quality Assurance Unit, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  6. 6.Department Pharmaceutical Chemistry, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia

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