Coenzyme Q10 protects against doxorubicin-induced cardiomyopathy via antioxidant and anti-apoptotic pathway.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Dalia A Shabaan, Nora Mostafa, Manal M El-Desoky, Eetmad A Arafat
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引用次数: 4

Abstract

Doxorubicin (Dox) is an anthracycline antibiotic that treats a variety of malignancies. Unfortunately, its cardiotoxicity limits its therapeutic usefulness. Coenzyme Q10 (CoQ10) has effectively treated and prevented various cardiac diseases and toxicities. This study aimed to evaluate the possible antioxidative and anti-apoptotic cardioprotective effects of CoQ10 against doxorubicin-induced histopathological and molecular changes in cardiomyocytes. Twenty-eight adult Wistar rats were divided into positive control, negative control, Dox-treated group, and Dox+CoQ10-treated. On the 16th day after the start of treatment, the hearts of all rats were dissected, and the left ventricles were processed for histological evaluation; immunohistochemical staining with caspase-3 and inducible nitric oxide synthase (iNOS); ultrastructural examination of cardiomyocytes; molecular assessment of proapoptotic gene Bax and anti-apoptotic gene expression Bcl-2; and biochemical study of malondialdehyde (MDA). The Dox-treated group had disorganized cardiomyocytes with increased interstitial space, vacuolated cytoplasm, and multiple small-sized pyknotic nuclei. A significant increase in caspase-3 and iNOS immunoexpression was observed. Ultrastructurally, the mitochondria were large with abnormal shapes, vacuolated cytoplasm, multiple vacuoles and autophagosomes, collagen fibril accumulation, and multiple small hyperchromatic nuclei. The intercalated discs were disorganized with loss of desmosome junction. The cardiomyocytes also showed significantly increased MDA levels and upregulation of Bax/Bcl-2 gene expression ratio. Co-administration of CoQ10 resulted in significant improvement in the histopathological picture, with a significant decrease in caspase-3 and iNOS immunoexpression and downregulation of the Bax/Bcl-2 gene expression ratio. In conclusion, CoQ10 protects against Dox-induced cardiotoxicity through the regulation of proapoptotic and anti-apoptotic gene expression.

辅酶Q10通过抗氧化和抗凋亡途径预防阿霉素诱导的心肌病。
阿霉素(Dox)是一种治疗多种恶性肿瘤的蒽环类抗生素。不幸的是,它的心脏毒性限制了它的治疗作用。辅酶Q10 (CoQ10)有效地治疗和预防各种心脏疾病和毒性。本研究旨在评估辅酶q10对阿霉素诱导的心肌细胞组织病理和分子变化的可能的抗氧化和抗凋亡心脏保护作用。将28只成年Wistar大鼠分为阳性对照组、阴性对照组、Dox+ coq10处理组和Dox+ coq10处理组。治疗开始后第16天,解剖各组大鼠心脏,对左心室进行组织学观察;caspase-3和诱导型一氧化氮合酶(iNOS)免疫组化染色;心肌细胞超微结构检查;促凋亡基因Bax和抗凋亡基因Bcl-2的表达;丙二醛(MDA)的生化研究。dox治疗组心肌细胞组织紊乱,间质增大,细胞质空泡化,细胞核多发小体积缩小。观察到caspase-3和iNOS免疫表达显著升高。超微结构上,线粒体体积大,形状异常,细胞质空泡化,有多个空泡和自噬体,胶原纤维堆积,多小的深染核。间插椎间盘组织紊乱,桥粒连接处缺失。心肌细胞MDA水平明显升高,Bax/Bcl-2基因表达比明显上调。CoQ10联合给药显著改善了组织病理图像,caspase-3和iNOS免疫表达显著降低,Bax/Bcl-2基因表达比下调。综上所述,CoQ10通过调节促凋亡和抗凋亡基因的表达来抑制dox诱导的心脏毒性。
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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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