title: N-3 polyunsaturated fatty acids decrease levels of doxorubicin-induced reactive oxygen species in cardiomyocytes -- involvement of uncoupling protein UCP2.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Hsiu-Ching
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, No, 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan. ronichen@ntu.edu.tw.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071246:Uncoupling Protein 2
chemical_list: D000903:Antibiotics, Antineoplastic; D015525:Fatty Acids, Omega-3; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D004317:Doxorubicin