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Switching to a low-fat diet attenuates the intensified doxorubicin cardiotoxicity associated with high-fat feeding

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Abstract

Purpose

A high-fat diet has been shown to exacerbate the cardiotoxicity associated with the chemotherapy drug doxorubicin (DOX); however, it is unknown whether switching from a high-fat diet to a low-fat diet can attenuate the intensified DOX cardiotoxicity. The purpose of this study was to investigate the effects of a low-fat diet on DOX-induced cardiotoxicity in rats previously fed a high-fat diet.

Methods

Male rats were randomly assigned to consume a Western diet or a low-fat diet for 6 weeks. Western diet-fed rats were then further randomized to switch to the low-fat diet (WD-LF) or continue with the Western diet (WD). One week later, WD-LF and WD received 1 mg/kg DOX per day for 10 consecutive days and continued with their diets (WD-LF + DOX, WD + DOX). LF was further randomized to receive 1 mg/kg DOX per day for 10 consecutive days (LF + DOX) or saline injections as a control (LF + SAL). Four weeks following the first injection, cardiac function was analyzed, and left ventricles were analyzed for cardiotoxicity indices.

Results

When compared to LF + SAL and LF + DOX, WD + DOX exhibited an enhanced cardiotoxicity as evidenced by reduced septal wall thickness, fractional shortening, and sarco-endoplasmic reticulum Ca2+ ATPase expression as well as increased left ventricular cavity dimensions, lipid peroxidation, and β-myosin heavy-chain expression. This exacerbated cardiotoxicity was not observed in WD-LF + DOX.

Conclusions

Switching to a low-fat diet 1 week prior to, during, and following DOX treatment attenuated the exacerbated cardiotoxicity observed in the previously Western diet-fed rats.

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Acknowledgments

This work was supported by UNC Provost’s Research, Dissemination, & Faculty Development funding to DSH.

Conflict of interest

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Authors and Affiliations

  1. School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, 80639, USA

    David S. Hydock, Carole M. Schneider & Reid Hayward

  2. Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO, USA

    David S. Hydock, Carole M. Schneider & Reid Hayward

  3. Department of Athletics, National Taiwan University, Taipei, Taiwan

    Chia-Ying Lien

  4. Department of Exercise and Rehabilitative Sciences, Slippery Rock University, Slippery Rock, PA, USA

    Brock T. Jensen

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  1. David S. Hydock
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  2. Chia-Ying Lien
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Correspondence to David S. Hydock.

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Hydock, D.S., Lien, CY., Jensen, B.T. et al. Switching to a low-fat diet attenuates the intensified doxorubicin cardiotoxicity associated with high-fat feeding. Cancer Chemother Pharmacol 71, 1551–1560 (2013). https://doi.org/10.1007/s00280-013-2154-5

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  • DOI: https://doi.org/10.1007/s00280-013-2154-5

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