2. • Cardiotoxicity
• Doxorubicin
• Calorie restriction
• Chemotherapy
• Cardiomyocytes
• Cardiomyopathy
• Cancer
• Ad libitum
• Anthracycline
• Lipid peroxidation
• Malondialdehyde
KEY TERMS
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3. INTRODUCTION
• Cancer accounted for 7.6 million deaths (13% of total) in 2008.
(World Health Organization, 2011; GLOBOCAN: Country Fast Stat.,
2008).
• Types of treatment include:
Chemotherapy, radiation therapy, surgery, and other alternative
methods of treatment
• Alternative methods of treatment are becoming more and more
popular.

4. PURPOSE
• The purpose of this study is to explore and analyze interventions that
may decrease the deleterious side effects of cancer treatment.
• Doxorubicin-Induced Cardiotoxicity.
• Calorie Restriction as an alternative method of treatment.

5. ANIMATION
DOX

6. O
O
O

7. Cell
E-
E-
E-
E-
E-
E-
E-
E-
E-

8. HYPOTHESIS
• Reduced caloric intake will directly affect the amount of ROS
produced and will therefore reduce the amount of MDA in rat heart
tissue.
• This should lead to reductions in doxorubicin-induced cardiotoxicity
due to an overall decrease in oxidative stress during chemotherapy
treatments.

9. BACKGROUND INFORMATION
Cancer Treatments
• Anthracyclines Drugs.
• Alkylating agents.
• Antimetabolites.
• Topoisomerase inhibitors.
• Mitotic inhibitors.
http://upload.wikimedia.org/wikipedia/commons/e/ee/Doxorubicin%E
2%80%93DNA_complex_1D12.png

10. CONT’D
• There are four different types of cardiotoxicity caused by
Anthracyclines:
Acute
Sub-chronic
Early-chronic
Delayed
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11. Fig. 2. Schematic overview of the pathways proposed to explain chronic anthracycline-induced cardiotoxicity. ANT – anthracycline, FADD –Fas-
associated death domain protein, iNOS – inducible nitric oxide synthase, MMP – matrix metalloproteinase, MnSOD – manganese (mitochondrial)
superoxide dismutase, mPTP – mitochondrial permeability transition pore, PS – phosphatidylserine, ROS – reactive oxygen species, RNS –
reactive nitrogen species, NO – nitric oxide, RyR – ryanodine receptor, SR – sarcoplasmic reticulum, TnT/I – troponin T/I
Picture taken from pg 158; Šimùnek, T, Štìrba, M., Popelová, O., Adamcová, M., Hrdina, R., Geršl, V. Anthracycline-induced cardiotoxicity:
Overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacological Reports. 2009; 61, 154–171

12. PAST RESEARCH
• CR has been shown to increase longevity. (Hursting, S., et al, 2003).
• CR and brain tumors.
• CR and mitochondria free radials.
http://www.crsociety.org/files/images/cr-youth.gif

13. METHODS AND MATERIALS
• Animal Care
• Calorie Restriction Protocol
• Tissue Preparation
• Myocardial lipid peroxidation
• Statistical Analysis

14. RESULTS
• No significant differences were found between groups of interest.
• The expected results.
• Decreased MDA concentration.

15. FIGURES
Treatment Group (n=
) MDA MeanS.D.
CR+SAL 5 5.175610 .887
CR+DOX 8 6.036585 .978
AL+SAL 7 6.808362 .631
AL+DOX 8 6.344512 .630
Table 1. Mean ± standard deviation (S.D.) of
each treatment group for malondialdehyde
(MDA) concentrations.

18. DISCUSSION
• Hypothesis not supported.
• What we expected.
• Implication of Calorie Restriction: Effectiveness
• Sample size.

19. CONCLUSION
• Doxorubicin-Induced Cardiotoxicity
• Purpose
• Hypothesis
• Findings
• Future research.
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lories/calorie-restriction-life-
extension.jpg
http://www.healthnewswebsite.com/img/anti
oxidants_fruit_Juice_dr.jpg
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s/default/files/exercise101.jpg

20. ACKNOWLEDGEMENTS
• Nathan Kirkley, Zabedah Saad, Nick True, Abby Davidson
• Noah Gibson, Reid Hayward
• Klaus Broeker, Karen Allnutt
• University of Northern Colorado
• Lori Ball
• Adolph Coors Foundation
• Bacon Family Foundation
• Edward Madigan Foundation
• FSI Alumni

21. WORKS CITED
Hursting, S., Lavigne, J., Berrigan, D., Perkins, S., & Barrett, J. C. (2003). Calorie
Restriction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability
to Humans. Annual Review of Medicine, 54, 131-152. Retrieved July 23, 2011, from
http://www.annualreviews.org/doi
Shelton, L., Huysentruyt, L., Mukherjee, P., Seyfried, T.(2010, July 23) Calorie
restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.
National Center for Biotechnology Information. Retrieved July 5, 2011, from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908744/?tool=pubmed
Šimùnek, T, Štìrba, M., Popelová, O., Adamcová, M., Hrdina, R., Geršl, V.
Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of
oxidative stress and free cellular iron. Pharmacological Reports. 2009; 61, 154–171
Singal, P., & Iliskovic, N. (1998). Doxorubicin-Induced Cardiomyopathy. New England
Journal of Medicine, 339, 900-905. Retrieved July 23, 2011, from
http://www.nejm.org/doi/full/10.1056/NEJM199809243391307