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Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction
Open accessAbstract
Doxorubicin (DOX) is a widely prescribed antineoplastic and although the precise mechanism(s) have yet to be identified, DOX-induced oxidative stress to mitochondrial membranes is implicated in the pathogenic process. Previous attempts to protect against DOX-induced cardiotoxicity with alpha-tocopherol (vitamin E) have met with limited success, possibly as a result of inadequate delivery to relevant subcellular targets such as mitochondrial membranes. The present investigation was designed to assess whether enrichment of cardiac membranes with alpha-ocopherol is sufficient to protect against DOX-induced mitochondrial cardiotoxicity. Adult male Sprague-Dawley rats received seven weekly subcutaneous injections of 2 mg/kg DOX and fed either standard diet or diet supplemented with alpha-tocopherol succinate. Treatment with a cumulative dose of 14 mg/kg DOX caused mitochondrial cardiomyopathy as evidenced by histology, accumulation of oxidized cardiac proteins, and a significant decrease in mitochondrial calcium loading capacity. Maintaining rats on the alpha-tocopherol supplemented diet resulted in a significant (two- to four-fold) enrichment of cardiac mitochondrial membranes with alpha-tocopherol and diminished the content of oxidized cardiac proteins associated with DOX treatment. However, dietary alpha-tocopherol succinate failed to protect against mitochondrial dysfunction and cardiac histopathology. From this we conclude that although dietary vitamin E supplementation enriches cardiac mitochondrial membranes with alpha-tocopherol, either (1) this tocopherol enrichment is not sufficient to protect cardiac mitochondrial membranes from DOX toxicity or (2) oxidative stress alone is not responsible for the persistent mitochondrial cardiomyopathy caused by long-term DOX therapy.
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Inefficient electron transfer through ETS complexes I and III increases superoxide anion half-life and H2O2 generation.
“inefficient electron transfer through ETS complexes I and III has been shown to increase the half-life of the superoxide anion and thus generation of the cellular H2O2 [7].”
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Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused?
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Doxorubicin‐Induced Cardiomyopathy in Children
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Metadata
- Authors
- Berthiaume, J. M., Oliveira, P. J., Fariss, M. W., & Wallace, K. B.
- Affiliations
- University of Minnesota (US)
- University of Coimbra (PT)
- University of Colorado Health (US)
- Corresponding author
- Berthiaume, J. M.
- Venue
- Cardiovascular Toxicology
- Published
- 2005
- Volume
- 5
- Issue
- 3
- Pages
- 257-268
- ISSN
- 1530-7905 (ISSN-L)
- OpenAlex
- W1966078661
- Cited by
- 101
- References
- 42
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 11 · 2021: 2 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 8 · 2012: 7
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Cardiovascular Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL58016, R01HL058016)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- doxorubicin, cardiotoxicity, alpha-tocopherol, vitamin E supplementation, oxidative stress, mitochondrial dysfunction, mitochondrial cardiomyopathy
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Body Weight, Calcium, Diet, Doxorubicin, Heart Diseases, Indicators and Reagents, Mitochondria, Heart, Muscle Proteins, Myocardium, Organ Size, Oxygen Consumption, Vitamin E, Vitamins, Rats, Sprague-Dawley, Oxidative Stress, Rats
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