N-3 polyunsaturated fatty acids decrease levels of doxorubicin-induced reactive oxygen species in cardiomyocytes -- involvement of uncoupling protein UCP2

Journal of Biomedical Science

Ming-Fong Chen¹  Ching-Yi Chen²  Hsiu-Ching Hsu¹ 

[1] Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S Rd, Taipei, Taiwan;Present address: 50, Lane 155, Sec 3, Keelung Rd, Taipei 106, Taiwan

关键词: UCP2;    ROS;    Doxorubicin;    DHA;    EPA;   

Others  :  1146116
DOI  :  10.1186/s12929-014-0101-3

 received in 2014-07-22, accepted in 2014-10-31,  发布年份 2014

【 摘 要 】

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 ?M EPA or 50 ?M DHA for 24 h resulted in a maximal mitochondria concentration of these fatty acids and increased UCP2 expression. Pretreatment with 100 ?M EPA or 50 ?M 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 (??) 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.

【 授权许可】

   
2014 Hsu et al.; licensee BioMed Central Ltd.

【 图 表 】

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