N-3 polyunsaturated fatty acids decrease levels of doxorubicin-induced reactive oxygen species in cardiomyocytes -- involvement of uncoupling protein UCP2
Journal
Journal of biomedical science
Journal Volume
21
Pages
101
Date Issued
2014
Author(s)
Abstract
BACKGROUND: Use of the chemotherapeutic drug doxorubicin (DOX) is associated with serious cardiotoxicity, as it increases levels of reactive oxygen species (ROS). N-3 polyunsaturated fatty acid dietary supplements can be of benefit to patients undergoing cancer therapy. The aims of this study were to determine whether DOX-induced cardiotoxicity is related to mitochondrial uncoupling proteins and whether eicosapentaenoic acid (EPA, C20:5 n-3) or docosahexaenoic acid (DHA, C22:6 n-3) affects DOX-induced cardiomyocyte toxicity.RESULTS: Treatment of H9C2 cells with DOX resulted in decreased cell viability and UCP2 expression. Treatment with 100 μM EPA or 50 μM DHA for 24 h resulted in a maximal mitochondria concentration of these fatty acids and increased UCP2 expression. Pretreatment with 100 μM EPA or 50 μM DHA prevented the DOX-induced decrease in UCP2 mRNA and protein levels, but these effects were not seen with EPA or DHA and DOX cotreatment. In addition, the DOX-induced increase in ROS production and subsequent mitochondrial membrane potential change (?ψ) were significantly attenuated by pretreatment with EPA or DHA.CONCLUSION: EPA or DHA pre-treatment inhibits the DOX-induced decrease in UCP2 expression, increase in ROS production, and subsequent mitochondrial membrane potential change that contribute to the cardiotoxicity of DOX.
SDGs
Other Subjects
antineoplastic antibiotic; doxorubicin; ion channel; mitochondrial protein; mitochondrial uncoupling protein 2; muscle protein; omega 3 fatty acid; reactive oxygen metabolite; cell line; cell survival; drug effects; heart mitochondrion; heart muscle cell; human; metabolism; mitochondrial membrane potential; pathology; Antibiotics, Antineoplastic; Cell Line; Cell Survival; Doxorubicin; Fatty Acids, Omega-3; Humans; Ion Channels; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Proteins; Muscle Proteins; Myocytes, Cardiac; Reactive Oxygen Species
Type
journal article