Tags

Type your tag names separated by a space and hit enter

Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction.
Cardiovasc Toxicol 2005; 5(3):257-67CT

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, University of Minnesota Medical School, Duluth, MN 55812, USA. jberthi1@d.umn.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16244371

Citation

Berthiaume, J M., et al. "Dietary Vitamin E Decreases Doxorubicin-induced Oxidative Stress Without Preventing Mitochondrial Dysfunction." Cardiovascular Toxicology, vol. 5, no. 3, 2005, pp. 257-67.
Berthiaume JM, Oliveira PJ, Fariss MW, et al. Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. Cardiovasc Toxicol. 2005;5(3):257-67.
Berthiaume, J. M., Oliveira, P. J., Fariss, M. W., & Wallace, K. B. (2005). Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. Cardiovascular Toxicology, 5(3), pp. 257-67.
Berthiaume JM, et al. Dietary Vitamin E Decreases Doxorubicin-induced Oxidative Stress Without Preventing Mitochondrial Dysfunction. Cardiovasc Toxicol. 2005;5(3):257-67. PubMed PMID: 16244371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. AU - Berthiaume,J M, AU - Oliveira,P J, AU - Fariss,M W, AU - Wallace,K B, PY - 2005/10/26/pubmed PY - 2006/1/6/medline PY - 2005/10/26/entrez SP - 257 EP - 67 JF - Cardiovascular toxicology JO - Cardiovasc. Toxicol. VL - 5 IS - 3 N2 - 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. SN - 1530-7905 UR - https://www.unboundmedicine.com/medline/citation/16244371/Dietary_vitamin_E_decreases_doxorubicin_induced_oxidative_stress_without_preventing_mitochondrial_dysfunction_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=16244371.ui DB - PRIME DP - Unbound Medicine ER -