Hsu, Hsiu-ChingHsiu-ChingHsuCHING-YI CHENMING-FONG CHEN2019-12-192019-12-19201414230127https://scholars.lib.ntu.edu.tw/handle/123456789/435608https://www.scopus.com/record/display.uri?eid=2-s2.0-84925883556&doi=10.1186%2fs12929-014-0101-3&origin=inward&txGid=cc124d132055c823b719e7529d507f31BACKGROUND: 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.en[SDGs]SDG3antineoplastic 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 Speciesjournal article10.1186/s12929-014-0101-3254075162-s2.0-84925883556https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84925883556&doi=10.1186%2fs12929-014-0101-3&partnerID=40&md5=e0392b7b1fa3ea00adee9fc66466acc9