Oral glutamine protects against acute doxorubicin-induced cardiotoxicity of tumor-bearing rats

Valentina K. Todorova, Yihong Kaufmann, Leah Hennings, Vicki Klimberg

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Doxorubicin (DOX), a widely used anticancer drug, has a dose-dependent cardiotoxicity, attributed mainly to free radical formation. The cardiomyocyte oxidative stress occurs rapidly after DOX treatment, resulting in harmful modifications to proteins, lipids, and DNA. Previous data showed that oral L-glutamine (Gln) prevented cardiac lipid peroxidation and maintained normal cardiac glutathione (GSH) levels in DOX-treated rats. Our aim in this study was to examine the effect of Gln on DOX-induced cardiac oxidative stress in a tumor-bearing host. Female Fisher344 rats with implanted MatBIII mammary tumors were randomized into 2 groups: a Gln group that received L-Gln (1 g.kg -1.d-1) (n = 10) via a Gln-enriched diet and/or gavage with 50% Gln suspension during the whole experiment and a control group that was fed the same diet formulation without Gln and/or were gavaged with water. All rats received a single injection of 12 mg/kg DOX and were killed 3 d later. GSH levels of hearts, livers, tumors, and blood, as well as cardiac histological alterations, lipid peroxidation, peroxinitrite levels, and caspase-3 activation were determined. Cardiac physiologic alterations were assessed by ultrasound imaging before and 3 d after DOX administration. The Gln supplementation resulted in lower cardiac lipid peroxidation and peroxintrite levels and elevated cardiac catalase enzyme activity and GSH compared with the controls, without affecting those of the tumors. DOX-induced alterations of the echocardiographic parameters were significantly reduced in the Gln-supplemented rats. These data indicate that Gln is able to reduce the oxidative damage of cardiomyocytes that occurs soon after DOX administration and thus protects the heart of a tumor-bearing host from DOX-induced cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)44-48
Number of pages5
JournalJournal of Nutrition
Volume140
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

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Glutamine
Doxorubicin
Neoplasms
Lipid Peroxidation
Heart Neoplasms
Cardiac Myocytes
Oxidative Stress
Diet
Cardiotoxicity
Cardiomyopathies
Caspase 3
Catalase
Free Radicals
Glutathione
Ultrasonography
Suspensions
Breast Neoplasms
Lipids
Control Groups
Injections

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Oral glutamine protects against acute doxorubicin-induced cardiotoxicity of tumor-bearing rats. / Todorova, Valentina K.; Kaufmann, Yihong; Hennings, Leah; Klimberg, Vicki.

In: Journal of Nutrition, Vol. 140, No. 1, 01.2010, p. 44-48.

Research output: Contribution to journalArticle

Todorova, Valentina K. ; Kaufmann, Yihong ; Hennings, Leah ; Klimberg, Vicki. / Oral glutamine protects against acute doxorubicin-induced cardiotoxicity of tumor-bearing rats. In: Journal of Nutrition. 2010 ; Vol. 140, No. 1. pp. 44-48.
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