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Toxic effects of the anticancer drug epirubicin in vitro assayed in human erythrocytes.
Toxicology in Vitro ( IF 3.2 ) Pub Date : 2020-08-13 , DOI: 10.1016/j.tiv.2020.104964
Karla Petit 1 , Mario Suwalsky 1 , José R Colina 1 , David Contreras 2 , Luis F Aguilar 3 , Malgorzata Jemiola-Rzeminska 4 , Kazimierz Strzalka 4
Affiliation  

Epirubicin is a cytotoxic drug used in the treatment of different types of cancer and increasing evidence suggests that its target is cell membranes. In order to gain insight on its toxic effects, intact red blood cells (RBC), human erythrocyte membranes and molecular models were used. The latter consisted in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes found mainly in the outer and inner monolayers of the human erythrocyte membrane, respectively. The results obtained by X-ray diffraction displayed that epirubicin induced structural perturbations in multilayers of DMPC. Differential scanning calorimetry (DSC) showed that epirubicin disturbed the thermotropic behavior of both DMPC and DMPE vesicles, whereas fluorescence spectroscopy demonstrated alterations in the fluidity of DMPC vesicles and the erythrocyte membrane. Scanning electron microscopy (SEM) revealed that epirubicin changed the normal discoid form of RBC to echinocytes and stomatocytes. Electron paramagnetic resonance (EPR) disclosed that this drug induced conformational changes in the erythrocyte membrane proteins. These findings demonstrate that epirubicin interacts with lipids and proteins of the human erythrocyte membrane, effects that might compromise the integrity and function of cell membranes. This is the first time that its toxic effects on the human erythrocyte membrane have been described.



中文翻译:

在人类红细胞中体外测定抗癌药物表柔比星的毒性作用。

表柔比星是一种细胞毒性药物,用于治疗各种类型的癌症,越来越多的证据表明,它的靶标是细胞膜。为了深入了解其毒性作用,使用了完整的红细胞(RBC),人红细胞膜和分子模型。后者由二豆蔻酰磷脂酰胆碱(DMPC)和二豆蔻酰磷脂酰乙醇胺(DMPE)的双层组成,磷脂类分别主要存在于人红细胞膜的外单层和内单层中。通过X射线衍射获得的结果表明,表柔比星引起了DMPC多层中的结构扰动。差示扫描量热法(DSC)显示,表柔比星干扰了DMPC和DMPE囊泡的热致行为,而荧光光谱显示DMPC囊泡和红细胞膜的流动性发生了变化。扫描电子显微镜(SEM)显示,表柔比星将正常的盘状形式的红细胞变成了棘突细胞和口气细胞。电子顺磁共振 EPR 公开了该药物诱导红细胞膜蛋白的构象变化。这些发现表明,表柔比星与人红细胞膜的脂质和蛋白质相互作用,这种作用可能会损害细胞膜的完整性和功能。这是首次描述了其对人红细胞膜的毒性作用。

更新日期:2020-08-18
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