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PLOS ONE  2009 

Blueberry-Enriched Diet Protects Rat Heart from Ischemic Damage

DOI: 10.1371/journal.pone.0005954

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Objectives to assess the cardioprotective properties of a blueberry enriched diet (BD). Background Reactive oxygen species (ROS) play a major role in ischemia-related myocardial injury. The attempts to use synthetic antioxidants to block the detrimental effects of ROS have produced mixed or negative results precipitating the interest in natural products. Blueberries are readily available product with the highest antioxidant capacity among fruits and vegetables. Methods and Results Following 3-mo of BD or a regular control diet (CD), the threshold for mitochondrial permeability transition (tMPT) was measured in isolated cardiomyocytes obtained from young male Fischer-344 rats. Compared to CD, BD resulted in a 24% increase (p<0.001) of ROS indexed tMPT. The remaining animals were subjected to a permanent ligation of the left descending coronary artery. 24 hrs later resulting myocardial infarction (MI) in rats on BD was 22% less than in CD rats (p<0.01). Significantly less TUNEL(+) cardiomyocytes (2% vs 9%) and 40% less inflammation cells were observed in the myocardial area at risk of BD compared to CD rats (p<0.01). In the subgroup of rats, after coronary ligation the original diet was either continued or switched to the opposite one, and cardiac remodeling and MI expansion were followed by serial echocardiography for 10 weeks. Measurements suggested that continuation of BD or its withdrawal after MI attenuated or accelerated rates of post MI cardiac remodeling and MI expansion. Conclusion A blueberry-enriched diet protected the myocardium from induced ischemic damage and demonstrated the potential to attenuate the development of post MI chronic heart failure.


[1]  Weisfeldt ML, Zweier J, Ambrosio G, Becker LC, Flaherty JT (1988) Evidence that free radicals result in reperfusion injury in heart muscle. Basic Life Sci 49: 911–919.
[2]  Zweier JL, Duke SS, Kuppusamy P, Sylvester JT, Gabrielson EW (1989) Electron paramagnetic resonance evidence that cellular oxygen toxicity is caused by the generation of superoxide and hydroxyl free radicals. FEBS Lett 252: 12–16.
[3]  Zweier JL, Kuppusamy P, Williams R, Rayburn BK, Smith D, et al. (1989) Measurement and characterization of postischemic free radical generation in the isolated perfused heart. J Biol Chem 264: 18890–18895.
[4]  Ambrosio G, Flaherty JT (1992) Effects of the superoxide radical scavenger superoxide dismutase, and of the hydroxyl radical scavenger mannitol, on reperfusion injury in isolated rabbit hearts. Cardiovasc Drugs Ther 6: 623–632.
[5]  Ambrosio G, Zweier JL, Duilio C, Kuppusamy P, Santoro G, et al. (1993) Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J Biol Chem 268: 18532–18541.
[6]  Villari B, Ambrosio G, Golino P, Ragni M, Focaccio A, et al. (1993) The effects of calcium channel antagonist treatment and oxygen radical scavenging on infarct size and the no-reflow phenomenon in reperfused hearts. Am Heart J 125: 11–23.
[7]  Griendling KK, FitzGerald GA (2003) Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS. Circulation 108: 1912–1916. Review.
[8]  Griendling KK, FitzGerald GA (2003) Oxidative stress and cardiovascular injury: Part II: animal and human studies. Circulation 108: 2034–2040.
[9]  Zorov DB, Juhaszova M, Sollott SJ (2006) Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta 1757: 509–517.
[10]  Vanden Hoek TL, Li C, Shao Z, Schumacker PT, Becker LB (1997) Significant levels of oxidants are generated by isolated cardiomyocytes during ischemia prior to reperfusion. J Mol Cell Cardiol 29: 2571–2583.
[11]  Kevin LG, Camara AK, Riess ML, Novalija E, Stowe DF (2003) Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion. Am J Physiol 284: H566–574.
[12]  Bandyopadhyay D, Chattopadhyay A, Ghosh G, Datta AG (2004) Oxidative stress-induced ischemic heart disease: protection by antioxidants. Curr Med Chem 11: 369–387.
[13]  Cozma LS (2004) The role of antioxidant therapy in cardiovascular disease. Curr Opin Lipidol 15: 369–371.
[14]  Chen JK, Chow SE (2005) Antioxidants and myocardial ischemia: reperfusion injuries. Chang Gung Med J 28: 369–377.
[15]  Papaharalambus CA, Griendling KK (2007) Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med 17: 48–54.
[16]  Prior RL, Cao G, Prior RL, Cao G (2000) Analysis of botanicals and dietary supplements for antioxidant capacity: a review. J AOAC Int 83: 950–956.
[17]  Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, et al. (1999) Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 19: 8114–8121.
[18]  Bickford PC, Gould T, Briederick L, Chadman K, Pollock A, et al. (2000) Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats. Brain Res 866: 211–217.
[19]  Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, et al. (2003) Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci 6: 153–162.
[20]  Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545: 51–64. Review.
[21]  Lau FC, Bielinski DF, Joseph JA (2007) Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J Neurosci Res 85: 1010–1017.
[22]  Sweeney MI, Kalt W, MacKinnon SL, Ashby J, Gottschall-Pass KT (2002) Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutr Neurosci 5: 427–431.
[23]  Duffy KB, Spangler EL, Devan BD, Guo Z, Bowker JL, et al. (2008) A blueberry-enriched diet provides cellular protection against oxidative stress and attenuates a kainate-induced learning impairment in rats. Neurobiol Aging 29: 1680–1689.
[24]  Shukitt-Hale B, Lau FC, Carey AN, Galli RL, Spangler EL, et al. (2008) Blueberry polyphenols prevent kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutrit Neurosci 11: 172–182.
[25]  Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, et al. (2003) Erythropoietin reduces myocardial infarction and left ventricular functional decline following coronary artery ligation in rats. Proc Natl Acad Sci USA 100: 11612–11617.
[26]  Ahmet I, Krawczyk M, Heller P, Moon C, Lakatta EG, Talan MI (2004) Beneficial effects of chronic pharmacologic manipulation of ?-adrenoreceptor subtype signaling in rodent dilated ischemic cardiomyopathy. Circulation 110: 1083–1090.
[27]  Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan M (2005) Cardioprotection by intermittent fasting in rats. Circulation 112: 3115–3121.
[28]  Youdim KA, Shukitt-Hale B, MacKinnon S, Kalt W, Joseph JA (2000) Polyphenolics enhance red blood cell resistance to oxidative stress: in vitro and in vivo. Biochim Biophys Acta 1523: 117–122.
[29]  Goyarzu P, Malin DH, Lau FC, Taglialatela G, Moon WD, et al. (2004) Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Nutr Neurosci 7: 75–83.
[30]  Capogrossi MC, Kort AA, Spurgeon HA, Lakatta EG (1986) Single adult rabbit and rat cardiac myocytes retain the Ca2+- and species-dependent systolic and diastolic contractile properties of intact muscle. J Gen Physiol 88: 589–613.
[31]  Juhaszova M, Zorov DB, Kim S-H, Pepe S, Fu Q, et al. (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113: 1535–1549.
[32]  Zorov DB, Filburn CR, Klotz LO, Zweier JL, Sollott SJ (2000) Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med 192: 1001–1014.
[33]  Briel M, Nordmann AJ, Bucher HC (2005) Statin therapy for prevention and treatment of acute and chronic cardiovascular disease: update on recent trials and metaanalyses. Curr Opin Lipidol 16: 601–605. Review.
[34]  Shepherd J (2006) Who should receive a statin these days? Lessons from recent clinical trials. J Intern Med 260: 305–319. Review.
[35]  Ward S, Lloyd Jones M, Pandor A, Holmes M, Ara R, et al. (2007) A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess 11: 1–178.
[36]  Hillsdon M, Thorogood M, Murphy M, Jones L (2004) Can a simple measure of vigorous physical activity predict future mortality? Results from the OXCHECK study. Public Health Nutr 7: 557–562.
[37]  Akita Y, Otani H, Matsuhisa S, Kyoi S, Enoki C, et al. (2007) Exercise-induced activation of cardiac sympathetic nerve triggers cardioprotection via redox-sensitive activation of eNOS and upregulation of iNOS. Am J Physiol 292: H2051–2059.
[38]  Marini M, Lapalombella R, Margonato V, Ronchi R, Samaja M, et al. (2007) Mild exercise training, cardioprotection and stress genes profile. Eur J Appl Physiol 99: 503–510.
[39]  Kitsis RN, Narula J (2008) Introduction-cell death in heart failure. Heart Fail Rev 13(2): 107–109).
[40]  Joseph JA, Shukitt-Hale B, Casadesus G, Fisher D (2005) Oxidative stress and inflammation in brain aging: nutritional considerations. Neurochem Res 30: 927–935. Review.
[41]  Lau FC, Bielinski DF, Joseph JA (2007) Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J Neurosci Res 85: 1010–1017.
[42]  Minghetti L, Levi G (1998) Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol 54: 99–125. Review.
[43]  Egger T, Schuligoi R, Wintersperger A, Amann R, Malle E, et al. (2003) Vitamin E (alpha-tocopherol) attenuates cyclo-oxygenase 2 transcription and synthesis in immortalized murine BV-2 microglia. Biochem J 370(Pt 2): 459–467.
[44]  Hope Smith S, Tate PL, Huang G, Magee JB, Meepagala KM, et al. (2004) Antimutagenic activity of berry extracts. J Med Food 7: 450–455.
[45]  Neto CC (2007) Cranberry and blueberry: evidence for protective effects against cancer and vascular diseases. Mol Nutr Food Res 51: 652–664. Review.
[46]  Yi W, Fischer J, Krewer G, Akoh CC (2005) Phenolic compounds from blueberries can inhibit colon cancer cell proliferation and induce apoptosis. J Agric Food Chem 53: 7320–7329.
[47]  Martineau LC, Couture A, Spoor D, Benhaddou-Andaloussi A, Harris C, et al. (2006) Anti-diabetic properties of the Canadian lowbush blueberry Vaccinium angustifolium Ait. Phytomedicine 13: 612–623.
[48]  Li S, Li X, Rozanski GJ (2003) Regulation of glutathion in cardiac myocytes. J Mol Cell Cardiol 35: 1145–1152.
[49]  Das UN (2003) Insulin: an endogenous cardioprotector. Curr Opin Crit Care 9: 375–383. Review.
[50]  Diaz R, Paolasso EA, Piegas LS, Tajer CD, Moreno MG, et al. (1998) Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Circulation 98: 2227–2234.
[51]  Zhang HX, Zang YM, Huo JH, Liang SJ, Zhang HF, et al. (2006) Physiologically tolerable insulin reduces myocardial injury and improves cardiac functional recovery in myocardial ischemic/reperfused dogs. J Cardiovasc Pharmacol 48: 306–313.
[52]  Juhaszova M, Rabuel C, Zorov DB, Lakatta EG, Sollott SJ (2005) Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res 66: 233–244. Review.


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