Dietary inorganic nitrate alleviates doxorubicin cardiotoxicity: Mechanisms and implications

Nitric Oxide - Biology and Chemistry

Volumn 26, Issue 4, 2012, Pages 274-284

  Xi, Lei ^a   Zhu, Shu Guang ^a   Das, Anindita ^a   Chen, Qun ^a   Durrant, David ^a   Hobbs, Daniel C ^a   Lesnefsky, Edward J ^a,b   Kukreja, Rakesh C ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Anthracycline; Cardioprotection; Cardiotoxicity; Mitochondria; Nitrate; Ventricular function

Indexed keywords

DOXORUBICIN; INORGANIC NITRATE; NITRIC ACID DERIVATIVE; NITRIC OXIDE SYNTHASE; NITRITE; PEROXIREDOXIN 5; REACTIVE OXYGEN METABOLITE; SODIUM NITRATE; UNCLASSIFIED DRUG;

ANTIOXIDANT ACTIVITY; APOPTOSIS; CARCINOGENESIS; CARDIOMYOPATHY; CARDIOTOXICITY; CARDIOVASCULAR RISK; CELL DAMAGE; CONFERENCE PAPER; DIET SUPPLEMENTATION; DIETARY INTAKE; ECHOCARDIOGRAPHY; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE NECROSIS; HEART PROTECTION; HYPOTENSION; INORGANIC NUTRIENT; LIPID PEROXIDATION; METHEMOGLOBINEMIA; MITOCHONDRIAL RESPIRATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEOMICS; RISK BENEFIT ANALYSIS; RISK REDUCTION;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; ANTIOXIDANTS; CARDIOTONIC AGENTS; CARDIOTOXINS; DIET; DOXORUBICIN; DRUG INTERACTIONS; HEART DISEASES; HUMANS; NITRATES;

ANIMALIA;

EID: 84861311670     PISSN: 10898603     EISSN: 10898611     Source Type: Journal    
DOI: 10.1016/j.niox.2012.03.006     Document Type: Conference Paper

References (98)

1. M.R. Bristow, J.W. Mason, M.E. Billingham, and J.R. Daniels Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization Ann. Intern. Med. 88 1978 168 175
2. P.K. Singal, and N. Iliskovic Doxorubicin-induced cardiomyopathy N. Engl. J. Med. 339 1998 900 905
3. S.M. Swain, F.S. Whaley, and M.S. Ewer Congestive heart failure in patients treated with doxorubicin - a retrospective analysis of three trials Cancer 97 2003 2869 2879
4. G. Minotti, P. Menna, E. Salvatorelli, G. Cairo, and L. Gianni Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity Pharmacol. Rev. 56 2004 185 229
5. K.B. Wallace Adriamycin-induced interference with cardiac mitochondrial calcium homeostasis Cardiovasc. Toxicol. 7 2007 101 107
6. D. Lebrecht, A. Kokkori, U.P. Ketelsen, B. Setzer, and U.A. Walker Tissue-specific mtDNA lesions and radical-associated mitochondrial dysfunction in human hearts exposed to doxorubicin J. Pathol. 207 2005 436 444
7. T. Simunek, M. Sterba, O. Popelova, M. Adamcova, R. Hrdina, and V. Gersl Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron Pharmacol. Rep. 61 2009 154 171
8. R.D. Olson, and P.S. Mushlin Doxorubicin cardiotoxicity - analysis of prevailing hypotheses FASEB J. 4 1990 3076 3086
9. C.F. Thorn, C. Oshiro, S. Marsh, T. Hernandez-Boussard, H. McLeod, T.E. Klein, and R.B. Altman Doxorubicin pathways: pharmacodynamics and adverse effects Pharmacogenet. Genomics 21 2011 440 446
10. J.G. Blanco, W.M. Leisenring, V.M. Gonzalez-Covarrubias, T.I. Kawashima, S.M. Davies, M.V. Relling, L.L. Robison, C.A. Sklar, M. Stovall, and S. Bhatia Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H: quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer Cancer 112 2008 2789 2795
11. X. Liu, Z. Chen, C.C. Chua, Y.S. Ma, G.A. Youngberg, R. Hamdy, and B.H. Chua Melatonin as an effective protector against doxorubicin-induced cardiotoxicity Am. J. Physiol. Heart Circ. Physiol. 283 2002 H254 H263
12. B.B. Hasinoff, D. Patel, and X. Wu The oral iron chelator ICL670A (deferasirox) does not protect myocytes against doxorubicin Free Radic. Biol. Med. 35 2003 1469 1479
13. B.B. Hasinoff, and D. Patel The iron chelator Dp44mT does not protect myocytes against doxorubicin J. Inorg. Biochem. 103 2009 1093 1101
14. S.G. Zhu, R.C. Kukreja, A. Das, Q. Chen, E.J. Lesnefsky, and L. Xi Dietary nitrate supplementation protects against doxorubicin-induced cardiomyopathy by improving mitochondrial function J. Am. Coll. Cardiol. 57 2011 2181 2189
15. L. Xi, S.G. Zhu, D.C. Hobbs, and R.C. Kukreja Identification of protein targets underlying dietary nitrate-induced protection against doxorubicin cardiotoxicity J. Cell. Mol. Med. 15 2011 2512 2524
16. S. Fogli, P. Nieri, and M.C. Breschi The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage FASEB J. 18 2004 664 675
17. D.M. Weinstein, M.J. Mihm, and J.A. Bauer Cardiac peroxynitrite formation and left ventricular dysfunction following doxorubicin treatment in mice J. Pharmacol. Exp. Ther. 294 2000 396 401
18. P. Pacher, L. Liaudet, P. Bai, J.G. Mabley, P.M. Kaminski, L. Virag, A. Deb, E. Szabo, Z. Ungvari, M.S. Wolin, J.T. Groves, and C. Szabo Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction Circulation 107 2003 896 904
19. M.J. Mihm, F. Yu, D.M. Weinstein, P.J. Reiser, and J.A. Bauer Intracellular distribution of peroxynitrite during doxorubicin cardiomyopathy: evidence for selective impairment of myofibrillar creatine kinase Br. J. Pharmacol. 135 2002 581 588
20. T. Katori, S. Donzelli, C.G. Tocchetti, K.M. Miranda, G. Cormaci, D.D. Thomas, E.A. Ketner, M.J. Lee, D. Mancardi, D.A. Wink, D.A. Kass, and N. Paolocci Peroxynitrite and myocardial contractility: in vivo versus in vitro effects Free Radic. Biol. Med. 41 2006 1606 1618
21. M.J. Kohr, J.P. Davis, and M.T. Ziolo Peroxynitrite increases protein phosphatase activity and promotes the interaction of phospholamban with protein phosphatase 2a in the myocardium Nitric Oxide 20 2009 217 221
22. J. Vasquez-Vivar, P. Martasek, N. Hogg, B.S. Masters, K.A. Pritchard Jr., and B. Kalyanaraman Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin Biochemistry 36 1997 11293 11297
23. S. Deng, A. Kruger, A. Schmidt, A. Metzger, T. Yan, U. Godtel-Armbrust, G. Hasenfuss, F. Brunner, and L. Wojnowski Differential roles of nitric oxide synthase isozymes in cardiotoxicity and mortality following chronic doxorubicin treatment in mice Naunyn Schmiedebergs Arch. Pharmacol. 380 2009 25 34
24. L.J. Ignarro Nitric oxide as a unique signaling molecule in the vascular system: a historical overview J. Physiol. Pharmacol. 53 2002 503 514
25. B. O'Murchu, V.M. Miller, M.A. Perrella, and J.C. Burnett Jr. Increased production of nitric oxide in coronary arteries during congestive heart failure J. Clin. Invest. 93 1994 165 171
26. R. Bolli Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research J. Mol. Cell. Cardiol. 33 2001 1897 1918
27. L. Xi, N.C. Jarrett, M.L. Hess, and R.C. Kukreja Essential role of inducible nitric oxide synthase in monophosphoryl lipid A-induced late cardioprotection: evidence from pharmacological inhibition and gene knockout mice Circulation 99 1999 2157 2163
28. Y. Guo, W.K. Jones, Y.T. Xuan, X.L. Tang, W. Bao, W.J. Wu, H. Han, V.E. Laubach, P. Ping, Z. Yang, Y. Qiu, and R. Bolli The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene Proc. Natl. Acad. Sci. USA 96 1999 11507 11512
29. A. Das, L. Xi, and R.C. Kukreja Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling J. Biol. Chem. 280 2005 12944 12955
30. F. Salloum, C. Yin, L. Xi, and R.C. Kukreja Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart Circ. Res. 92 2003 595 597
31. L. Xi, D. Tekin, E. Gursoy, F. Salloum, J.E. Levasseur, and R.C. Kukreja Evidence that NOS2 acts as a trigger and mediator of late preconditioning induced by acute systemic hypoxia Am. J. Physiol. Heart Circ. Physiol. 283 2002 H5 H12
32. 1 receptors: evidence from gene-knockout mice Circulation 102 2000 902 907
33. P.W. Fisher, F. Salloum, A. Das, H. Hyder, and R.C. Kukreja Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity Circulation 111 2005 1601 1610
34. F. de Nigris, M. Rienzo, C. Schiano, C. Fiorito, A. Casamassimi, and C. Napoli Prominent cardioprotective effects of third generation beta blocker nebivolol against anthracycline-induced cardiotoxicity using the model of isolated perfused rat heart Eur. J. Cancer 44 2008 334 340
35. A. Riad, S. Bien, D. Westermann, P.M. Becher, K. Loya, U. Landmesser, H.K. Kroemer, H.P. Schultheiss, and C. Tschope Pretreatment with statin attenuates the cardiotoxicity of doxorubicin in mice Cancer Res. 69 2009 695 699
36. S. Atar, Y. Ye, Y. Lin, S.Y. Freeberg, S.P. Nishi, S. Rosanio, M.H. Huang, B.F. Uretsky, J.R. Perez-Polo, and Y. Birnbaum Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2 Am. J. Physiol. Heart Circ. Physiol. 290 2006 H1960 H1968
37. U. Ikeda, M. Shimpo, M. Ikeda, S. Minota, and K. Shimada Lipophilic statins augment inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes J. Cardiovasc. Pharmacol. 38 2001 69 77
38. T. Lauer, M. Preik, T. Rassaf, B.E. Strauer, A. Deussen, M. Feelisch, and M. Kelm Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action Proc. Natl. Acad. Sci. USA 98 2001 12814 12819
39. M.T. Gladwin, N.J. Raat, S. Shiva, C. Dezfulian, N. Hogg, D.B. Kim-Shapiro, and R.P. Patel Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation Am. J. Physiol. Heart Circ. Physiol. 291 2006 H2026 H2035
40. E.A. Jansson, L. Huang, R. Malkey, M. Govoni, C. Nihlen, A. Olsson, M. Stensdotter, J. Petersson, L. Holm, E. Weitzberg, and J.O. Lundberg A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis Nat. Chem. Biol. 4 2008 411 417
41. J.L. Zweier, P. Wang, A. Samouilov, and P. Kuppusamy Enzyme-independent formation of nitric oxide in biological tissues Nat. Med. 1 1995 804 809
42. J.O. Lundberg, and M. Govoni Inorganic nitrate is a possible source for systemic generation of nitric oxide Free Radic. Biol. Med. 37 2004 395 400
43. A. Webb, R. Bond, P. McLean, R. Uppal, N. Benjamin, and A. Ahluwalia Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage Proc. Natl. Acad. Sci. USA 101 2004 13683 13688
44. K. Cosby, K.S. Partovi, J.H. Crawford, R.P. Patel, C.D. Reiter, S. Martyr, B.K. Yang, M.A. Waclawiw, G. Zalos, X. Xu, K.T. Huang, H. Shields, D.B. Kim-Shapiro, A.N. Schechter, R.O. Cannon III, and M.T. Gladwin Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation Nat. Med. 9 2003 1498 1505
45. N.S. Bryan, J.W. Calvert, J.W. Elrod, S. Gundewar, S.Y. Ji, and D.J. Lefer Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury Proc. Natl. Acad. Sci. USA 104 2007 19144 19149
46. M.R. Duranski, J.J. Greer, A. Dejam, S. Jaganmohan, N. Hogg, W. Langston, R.P. Patel, S.F. Yet, X. Wang, C.G. Kevil, M.T. Gladwin, and D.J. Lefer Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver J. Clin. Invest. 115 2005 1232 1240
47. K. Tsuchiya, Y. Kanematsu, M. Yoshizumi, H. Ohnishi, K. Kirima, Y. Izawa, M. Shikishima, T. Ishida, S. Kondo, S. Kagami, Y. Takiguchi, and T. Tamaki Nitrite is an alternative source of NO in vivo Am. J. Physiol. Heart Circ. Physiol. 288 2005 H2163 H2170
48. M. Gilchrist, P.G. Winyard, and N. Benjamin Dietary nitrate - good or bad? Nitric Oxide 22 2010 104 109
49. A.J. Webb, N. Patel, S. Loukogeorgakis, M. Okorie, Z. Aboud, S. Misra, R. Rashid, P. Miall, J. Deanfield, N. Benjamin, R. Macallister, A.J. Hobbs, and A. Ahluwalia Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite Hypertension 51 2008 784 790
50. J. Petersson, M. Carlstrom, O. Schreiber, M. Phillipson, G. Christoffersson, A. Jagare, S. Roos, E.A. Jansson, A.E.G. Persson, J.O. Lundberg, and L. Holm Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash Free Radic. Biol. Med. 46 2009 1068 1075
51. T.D. Presley, A.R. Morgan, E. Bechtold, W. Clodfelter, R.W. Dove, J.M. Jennings, R.A. Kraft, S.B. King, P.J. Laurienti, W.J. Rejeski, J.H. Burdette, D.B. Kim-Shapiro, and G.D. Miller Acute effect of a high nitrate diet on brain perfusion in older adults Nitric Oxide 24 2011 34 42
52. T. Sobko, C. Marcus, M. Govoni, and S. Kamiya Dietary nitrate in Japanese traditional foods lowers diastolic blood pressure in healthy volunteers Nitric Oxide 22 2010 136 140
53. M. Carlström, A.E. Persson, E. Larsson, M. Hezel, P.G. Scheffer, T. Teerlink, E. Weitzberg, and J.O. Lundberg Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension Cardiovasc. Res. 89 2011 574 585
54. G. Richardson, S.L. Hicks, S. O'Byrne, M.T. Frost, K. Moore, N. Benjamin, and G.M. McKnight The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans Nitric Oxide 7 2002 24 29
55. M. Carlström, F.J. Larsen, T. Nystrom, M. Hezel, S. Borniquel, E. Weitzberg, and J.O. Lundberg Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice Proc. Natl. Acad. Sci. USA 107 2010 17716 17720
56. V. Kapil, A.B. Milsom, M. Okorie, S. Maleki-Toyserkani, F. Akram, F. Rehman, S. Arghandawi, V. Pearl, N. Benjamin, S. Loukogeorgakis, R. Macallister, A.J. Hobbs, A.J. Webb, and A. Ahluwalia Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO Hypertension 56 2010 274 281
57. F.J. Larsen, B. Ekblom, K. Sahlin, J.O. Lundberg, and E. Weitzberg Effects of dietary nitrate on blood pressure in healthy volunteers N. Engl. J. Med. 355 2006 2792 2793
58. A.A. Kenjale, K.L. Ham, T. Stabler, J.L. Robbins, J.L. Johnson, M. VanBruggen, G. Privette, E. Yim, W.E. Kraus, and J.D. Allen Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease J. Appl. Physiol. 110 2011 1582 1591
59. M.E. Clementi, B. Giardina, E. Di Stasio, A. Mordente, and F. Misiti Doxorubicin-derived metabolites induce release of cytochrome C and inhibition of respiration on cardiac isolated mitochondria Anticancer Res. 23 2003 2445 2450
60. L.E. Solem, L.J. Heller, and K.B. Wallace Dose-dependent increase in sensitivity to calcium-induced mitochondrial dysfunction and cardiomyocyte cell injury by doxorubicin J. Mol. Cell. Cardiol. 28 1996 1023 1032
61. K.J. Davies, and J.H. Doroshow Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase J. Biol. Chem. 261 1986 3060 3067
62. J.H. Doroshow, and K.J. Davies Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical J. Biol. Chem. 261 1986 3068 3074
63. H. Nohl, L. Gille, and K. Staniek The exogenous NADH dehydrogenase of heart mitochondria is the key enzyme responsible for selective cardiotoxicity of anthracyclines Z. Naturforsch. C. 53 1998 279 285
64. J. Bergh Best use of adjuvant systemic therapies II, chemotherapy aspects: dose of chemotherapy-cytotoxicity, duration and responsiveness Breast 12 2003 529 537
65. J.M. Berthiaume, and K.B. Wallace Adriamycin-induced oxidative mitochondrial cardiotoxicity Cell Biol. Toxicol. 23 2007 15 25
66. A. van der Vliet, J.P. Eiserich, B. Halliwell, and C.E. Cross Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite. A potential additional mechanism of nitric oxide-dependent toxicity J. Biol. Chem. 272 1997 7617 7625
67. L. Chaiswing, M.P. Cole, W. Ittarat, L.I. Szweda, D.K. St Clair, and T.D. Oberley Manganese superoxide dismutase and inducible nitric oxide synthase modify early oxidative events in acute adriamycin-induced mitochondrial toxicity Mol. Cancer Ther. 4 2005 1056 1064
68. P.A. Meyers, R. Gorlick, G. Heller, E. Casper, J. Lane, A.G. Huvos, and J.H. Healey Intensification of preoperative chemotherapy for osteogenic sarcoma: results of the Memorial Sloan-Kettering (T12) protocol J. Clin. Oncol. 16 1998 2452 2458
69. J.F. Turrens Mitochondrial formation of reactive oxygen species J. Physiol. 552 2003 335 344
70. Q. Chen, A.K. Camara, D.F. Stowe, C.L. Hoppel, and E.J. Lesnefsky Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion Am. J. Physiol. Cell. Physiol. 292 2007 C137 C147
71. 2 emission from isolated heart mitochondria J. Biol. Chem. 286 2011 33669 33677
72. A.B. Witte, K. Anestal, E. Jerremalm, H. Ehrsson, and E.S. Arner Inhibition of thioredoxin reductase but not of glutathione reductase by the major classes of alkylating and platinum-containing anticancer compounds Free Radic. Biol. Med. 39 2005 696 703
73. R. Marouga, S. David, and E. Hawkins The development of the DIGE system: 2D fluorescence difference gel analysis technology Anal. Bioanal. Chem. 382 2005 669 678
74. J.C. Moore, J. Fu, Y.C. Chan, D. Lin, H. Tran, H.F. Tse, and R.A. Li Distinct cardiogenic preferences of two human embryonic stem cell (hESC) lines are imprinted in their proteomes in the pluripotent state Biochem. Biophys. Res. Commun. 372 2008 553 558
75. S.G. Rhee, H.Z. Chae, and K. Kim Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling Free Radic. Biol. Med. 38 2005 1543 1552
76. S.W. Kang, S.G. Rhee, T.S. Chang, W. Jeong, and M.H. Choi 2-Cys peroxiredoxin function in intracellular signal transduction: therapeutic implications Trends Mol. Med. 11 2005 571 578
77. F. Plaisant, A. Clippe, S.D. Vander, B. Knoops, and P. Gressens Recombinant peroxiredoxin 5 protects against excitotoxic brain lesions in newborn mice Free Radic. Biol. Med. 34 2003 862 872
78. I. Banmeyer, C. Marchand, A. Clippe, and B. Knoops Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide FEBS Lett. 579 2005 2327 2333
79. M. Trujillo, A. Clippe, B. Manta, G. Ferrer-Sueta, A. Smeets, J.P. Declercq, B. Knoops, and R. Radi Pre-steady state kinetic characterization of human peroxiredoxin 5: taking advantage of Trp84 fluorescence increase upon oxidation Arch. Biochem. Biophys. 467 2007 95 106
80. K. Abbas, J. Breton, C.R. Picot, V. Quesniaux, C. Bouton, and J.C. Drapier Signaling events leading to peroxiredoxin 5 up-regulation in immunostimulated macrophages Free Radic. Biol. Med. 47 2009 794 802
81. D.H. Perlman, S.M. Bauer, H. Ashrafian, N.S. Bryan, M.F. Garcia-Saura, C.C. Lim, B.O. Fernandez, G. Infusini, M.E. McComb, C.E. Costello, and M. Feelisch Mechanistic insights into nitrite-induced cardioprotection using an integrated metabolomic/proteomic approach Circ. Res. 104 2009 796 804
82. N.G. Hord, Y. Tang, and N.S. Bryan Food sources of nitrates and nitrites: the physiologic context for potential health benefits Am. J. Clin. Nutr. 90 2009 1 10
83. 2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans J. Appl. Physiol. 107 2009 1144 1155
84. S.J. Bailey, J. Fulford, A. Vanhatalo, P.G. Winyard, J.R. Blackwell, F.J. Dimenna, D.P. Wilkerson, N. Benjamin, and A.M. Jones Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans J. Appl. Physiol. 109 2010 135 148
85. F.J. Larsen, E. Weitzberg, J.O. Lundberg, and B. Ekblom Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise Free Radic. Biol. Med. 48 2010 342 347
86. F.J. Larsen, T.A. Schiffer, S. Borniquel, K. Sahlin, B. Ekblom, J.O. Lundberg, and E. Weitzberg Dietary inorganic nitrate improves mitochondrial efficiency in humans Cell Metab. 13 2011 149 159
87. A. Daiber, T. Gori, and T. Munzel Inorganic nitrate therapy improves doxorubicin-induced cardiomyopathy: a new window for an affordable cardiovascular therapy for everyone? J. Am. Coll. Cardiol. 57 2011 2190 2193
88. D.S. Powlson, T.M. Addisott, N. Benjamin, K.G. Cassman, T.M. de Kok, H. van Grinsven, J.L. L'hirondel, A.A. Avery, and C. van Kessel When does nitrate become a risk for humans? J. Environ. Quality 37 2008 291 295
89. R.L. Santarelli, F. Pierre, and D.E. Corpet Processed meat and colorectal cancer: a review of epidemiologic and experimental evidence Nutr. Cancer 60 2008 131 144
90. A. Milkowski, H.K. Garg, J.R. Coughlin, and N.S. Bryan Nutritional epidemiology in the context of nitric oxide biology: a risk-benefit evaluation for dietary nitrite and nitrate Nitric oxide 22 2010 110 119
91. G.M. McKnight, C.W. Duncan, C. Leifert, and M.H. Golden Dietary nitrate in man: friend or foe? Br. J. Nutr. 81 1999 349 358
92. A. Maekawa, T. Ogiu, H. Onodera, K. Furuta, C. Matsuoka, Y. Ohno, and S. Odashima Carcinogenicity studies of sodium nitrite and sodium nitrate in F344 rats Food Chem. Toxicol. 20 1982 25 33
93. D. Forman, S. Aldabbagh, and R. Doll Nitrates, nitrites and gastric cancer in Great Britain Nature 313 1985 620 625
94. S. Aldabbagh, D. Forman, D. Bryson, I. Stratton, and R. Doll Mortality of nitrate fertilizer workers Brit. J. Indust. Med. 43 1986 507 515
95. A. Ayebo, B.C. Kross, M. Vlad, and A. Sinca Infant methemoglobinemia in the Transylvania region of Romania Int. J Occup. Environ. Health 3 1997 20 29
96. W.A. Chow, T.W. Synold, M.L. Tetef, J. Longmate, P. Frankel, J. Lawrence, Z. Al Khadimi, L. Leong, D. Lim, K. Margolin, R.J. Morgan, J. Raschko, S. Shibata, G. Somlo, P. Twardowski, Y. Yen, and J.H. Doroshow Feasibility and pharmacokinetic study of infusional dexrazoxane and dose-intensive doxorubicin administered concurrently over 96 h for the treatment of advanced malignancies Cancer Chemother. Pharmacol. 54 2004 241 248
97. F.A. Burrows, and P.R. Hickey Perioperative complications in patients with anthracycline chemotherapeutic agents Can. Anaesth. Soc. J. 32 1985 149 157
98. F. Rossi, W. Filippelli, S. Russo, A. Filippelli, and L. Berrino Cardiotoxicity of doxorubicin - effects of drugs inhibiting the release of vasoactive substances Pharmacol. Toxicol. 75 1994 99 107