A novel insight into the cardiotoxicity of antineoplastic drug doxorubicin.
A novel insight into the cardiotoxicity of antineoplastic drug doxorubicin.
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DOI：
10.3390/ijms141121629
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发表时间：
2013-10-31
影响因子：
5.6
通讯作者：
Kizek R
中科院分区：
文献类型：
--
作者：
Heger Z;Cernei N;Kudr J;Gumulec J;Blazkova I;Zitka O;Eckschlager T;Stiborova M;Adam V;Kizek R
多柔比星是一种常用的化疗药物，用于治疗多种类型的癌症。关于阿霉素与心脏生物分子的相互作用知之甚少。严重的心脏毒性，包括扩张型心肌病，通常导致致命的充血性心力衰竭，可能是阿霉素化疗的结果。本研究的目的是确定暴露于阿霉素对心肌组织中主要氨基酸（脯氨酸、牛磺酸、谷氨酸、精氨酸、天冬氨酸、亮氨酸、甘氨酸、缬氨酸、丙氨酸、异亮氨酸、苏氨酸、赖氨酸和丝氨酸）变化的影响。进行了体外相互作用研究，以比较多柔比星应用前后心脏组织中的氨基酸谱。我们发现，阿霉素直接影响心肌氨基酸的代表性，即使在低浓度。此外，我们进行了一项相互作用研究，确定了每种分析氨基酸的断裂点。赖氨酸、精氨酸、β-丙氨酸、缬氨酸和丝氨酸被确定为最敏感的氨基酸。此外，我们还比较了阿霉素暴露前后心肌的氨基酸谱。与多柔比星相互作用后的氨基酸量显著降低（p = 0.05）。这一事实表明阿霉素能够诱导心肌中氨基酸的定量组成发生变化。此外，这证实了阿霉素和氨基酸之间的相互作用可能是另一个因素，最有可能负责阿霉素对心肌的不良反应。
Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine). An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05). This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.
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影响因子：
3.5
作者：
Holley, Aaron K.;Dhar, Sanjit Kumar;Xu, Yong;St Clair, Daret K.
通讯作者：
St Clair, Daret K.
影响因子：
--
作者：
Manocha, Bhavik;Margaritis, Argyrios
通讯作者：
Margaritis, Argyrios
影响因子：
5.7
作者：
Albright, CF;Graciani, N;Oliff, A
通讯作者：
Oliff, A
影响因子：
3.7
作者：
Eckman DM;Stacey RB;Rowe R;D'Agostino R Jr;Kock ND;Sane DC;Torti FM;Yeboah J;Workman S;Lane KS;Hundley WG
通讯作者：
Hundley WG
影响因子：
3.7
作者：
Feridooni T;Hotchkiss A;Remley-Carr S;Saga Y;Pasumarthi KB
通讯作者：
Pasumarthi KB