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

Abstract

BackgroundUse 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.ResultsTreatment 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.ConclusionEPA 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-014-0101-3) contains supplementary material, which is available to authorized users.

The impact of DRP1 on myocardial fibrosis in the obese minipig

“…Previous studies indicate that surplus palmitate induces ROS production, energy shortage, inflammation, ER stress and autophagy dysregulation and eventually causes mitochondrial dysfunction and triggers apoptosis . However, Hsu et al indicated the incorporation of fatty acid into subcellular fractions needs 24‐48 hours . Hence, in the future, DRP1 knockdown studies in cells must investigate the fatty acid composition of mitochondrial membranes as well as other mechanisms (eg ER stress, autophagy) with short‐term or long‐term palmitate stress to clarify the potential mechanism.…”

“…48,54 However, Hsu et al indicated the incorporation of fatty acid into subcellular fractions needs 24-48 hours. 55 Hence, in the future, DRP1 knockdown studies in cells must investigate the fatty acid composition of mitochondrial membranes as well as other mechanisms (eg ER stress, autophagy) with short-term or long-term palmitate stress to clarify the potential mechanism.…”

The role of pericardial adipose tissue in the heart of obese minipigs

“…To determine the fatty acid composition, lipids were extracted from the adipose tissue according to Hsu et al 13 Each sample (50 mg) plus 50 lg of 1,2-dinonadecanoylsn-glycero-3 phosphocholine (C19:0 PC; Avanti Polar Lipids Inc.; Alabaster, Alabama), as an internal standard was homogenized in a 2/1/0.75 (v/v/v) mixture of methanol/chloroform/water, centrifuged and the upper phase discarded. The lower phase was dried under nitrogen.…”

“…Components were identified by comparison of the retention time with those of authentic standards (Supelco 37 Comp. Fame Mix TM , Supelco Inc. Belletonte PA) 13.…”

Green Coffee Extract Protects H9C2 Cardiomyocytes from Doxorubicin Induced Apoptosis

“…One of the ways Doxorubicin is thought to mediate cardiac cell apoptosis is through the intrinsic pathway, initiated in the mitochondria. Hsu et al (2014) have demonstrated that Dox causes a loss of Δψm in H9C2 cardiomyocytes and restoration of Δψm by treatment with polyunsaturated fatty acids prevents cell death induced by Dox. Treatment with Dox caused loss of Δψm in the present study.…”