Tags

Type your tag names separated by a space and hit enter

Dietary nitrate supplementation protects against Doxorubicin-induced cardiomyopathy by improving mitochondrial function.

Abstract

OBJECTIVES

The aim of this study was to test the hypothesis that long-term dietary nitrate supplementation protects against doxorubicin-induced cardiomyopathy by improving ventricular function and reducing mitochondrial respiratory chain damage.

BACKGROUND

Doxorubicin is a powerful anthracycline antibiotic used to treat divergent human neoplasms. Its clinical use is limited because of severe cardiotoxic side effects. Dietary nitrate and nitrite are essential nutrients for maintenance of steady-state tissue levels of nitric oxide and may play a therapeutic role in diseases associated with nitric oxide insufficiency or dysregulation. Dietary nitrate and nitrite supplementation alleviates myocardial injury caused by ischemia-reperfusion and cardiac arrest-resuscitation.

METHODS

Adult male CF-1 mice were given a single dose of doxorubicin (15 mg/kg intraperitoneally), and left ventricular contractile function was assessed 5 days later using both echocardiography and pressure-volume Millar catheterization. A nitrate supplementation regimen (1 g/l sodium nitrate in drinking water) was started 7 days before doxorubicin injection and continued thereafter. Cardiomyocyte necrosis and apoptosis, tissue lipid peroxidation, and plasma nitrate and nitrite levels were assessed. In addition, mitochondrial complex I activity, oxidative phosphorylation capacity, and hydrogen peroxide generation were determined in parallel experiments.

RESULTS

Doxorubicin caused impairment of ventricular contractility and cell death, which were significantly reduced by nitrate supplementation (p < 0.05). These cardioprotective effects were associated with a significant decrease in tissue lipid peroxidation. Nitrate supplementation significantly preserved mitochondrial complex I activity and oxidative phosphorylation and attenuated hydrogen peroxide generation after doxorubicin treatment.

CONCLUSIONS

Long-term oral intake of inorganic nitrate attenuates doxorubicin-induced ventricular dysfunction, cell death, oxidative stress, and mitochondrial respiratory chain damage. Nitrate could be a promising therapeutic agent against doxorubicin-induced cardiotoxicity.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    VCU Pauley Heart Center, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia 23298-0204, USA.

    , , , ,

    Source

    MeSH

    Animals
    Antibiotics, Antineoplastic
    Cardiomyopathies
    Dietary Supplements
    Doxorubicin
    Electron Transport
    Male
    Mice
    Mitochondria, Heart
    Nitrates
    Nitrites
    Oxidative Phosphorylation
    Oxidative Stress

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    21596234

    Citation

    Zhu, Shu-Guang, et al. "Dietary Nitrate Supplementation Protects Against Doxorubicin-induced Cardiomyopathy By Improving Mitochondrial Function." Journal of the American College of Cardiology, vol. 57, no. 21, 2011, pp. 2181-9.
    Zhu SG, Kukreja RC, Das A, et al. Dietary nitrate supplementation protects against Doxorubicin-induced cardiomyopathy by improving mitochondrial function. J Am Coll Cardiol. 2011;57(21):2181-9.
    Zhu, S. G., Kukreja, R. C., Das, A., Chen, Q., Lesnefsky, E. J., & Xi, L. (2011). Dietary nitrate supplementation protects against Doxorubicin-induced cardiomyopathy by improving mitochondrial function. Journal of the American College of Cardiology, 57(21), pp. 2181-9. doi:10.1016/j.jacc.2011.01.024.
    Zhu SG, et al. Dietary Nitrate Supplementation Protects Against Doxorubicin-induced Cardiomyopathy By Improving Mitochondrial Function. J Am Coll Cardiol. 2011 May 24;57(21):2181-9. PubMed PMID: 21596234.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dietary nitrate supplementation protects against Doxorubicin-induced cardiomyopathy by improving mitochondrial function. AU - Zhu,Shu-Guang, AU - Kukreja,Rakesh C, AU - Das,Anindita, AU - Chen,Qun, AU - Lesnefsky,Edward J, AU - Xi,Lei, PY - 2010/08/06/received PY - 2011/01/07/revised PY - 2011/01/11/accepted PY - 2011/5/21/entrez PY - 2011/5/21/pubmed PY - 2011/8/13/medline SP - 2181 EP - 9 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 57 IS - 21 N2 - OBJECTIVES: The aim of this study was to test the hypothesis that long-term dietary nitrate supplementation protects against doxorubicin-induced cardiomyopathy by improving ventricular function and reducing mitochondrial respiratory chain damage. BACKGROUND: Doxorubicin is a powerful anthracycline antibiotic used to treat divergent human neoplasms. Its clinical use is limited because of severe cardiotoxic side effects. Dietary nitrate and nitrite are essential nutrients for maintenance of steady-state tissue levels of nitric oxide and may play a therapeutic role in diseases associated with nitric oxide insufficiency or dysregulation. Dietary nitrate and nitrite supplementation alleviates myocardial injury caused by ischemia-reperfusion and cardiac arrest-resuscitation. METHODS: Adult male CF-1 mice were given a single dose of doxorubicin (15 mg/kg intraperitoneally), and left ventricular contractile function was assessed 5 days later using both echocardiography and pressure-volume Millar catheterization. A nitrate supplementation regimen (1 g/l sodium nitrate in drinking water) was started 7 days before doxorubicin injection and continued thereafter. Cardiomyocyte necrosis and apoptosis, tissue lipid peroxidation, and plasma nitrate and nitrite levels were assessed. In addition, mitochondrial complex I activity, oxidative phosphorylation capacity, and hydrogen peroxide generation were determined in parallel experiments. RESULTS: Doxorubicin caused impairment of ventricular contractility and cell death, which were significantly reduced by nitrate supplementation (p < 0.05). These cardioprotective effects were associated with a significant decrease in tissue lipid peroxidation. Nitrate supplementation significantly preserved mitochondrial complex I activity and oxidative phosphorylation and attenuated hydrogen peroxide generation after doxorubicin treatment. CONCLUSIONS: Long-term oral intake of inorganic nitrate attenuates doxorubicin-induced ventricular dysfunction, cell death, oxidative stress, and mitochondrial respiratory chain damage. Nitrate could be a promising therapeutic agent against doxorubicin-induced cardiotoxicity. SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/21596234/Dietary_nitrate_supplementation_protects_against_Doxorubicin_induced_cardiomyopathy_by_improving_mitochondrial_function_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(11)00888-6 DB - PRIME DP - Unbound Medicine ER -