Histology and Cell Biology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansurah, Egypt.
Tissue Barriers. 2023 Jan 2;11(1):2019504. doi: 10.1080/21688370.2021.2019504. Epub 2021 Dec 23.
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.
多柔比星（阿霉素）是一种蒽环类抗生素，可用于治疗多种恶性肿瘤。遗憾的是，其心脏毒性限制了它的治疗用途。辅酶 Q10（CoQ10）已有效治疗和预防多种心脏疾病和毒性。本研究旨在评估 CoQ10 对多柔比星诱导的心肌细胞组织病理学和分子变化的可能抗氧化和抗细胞凋亡的心脏保护作用。将 28 只成年 Wistar 大鼠分为阳性对照组、阴性对照组、多柔比星处理组和多柔比星+CoQ10 处理组。在开始治疗的第 16 天，解剖所有大鼠的心脏，并处理左心室进行组织学评估；用 caspase-3 和诱导型一氧化氮合酶（iNOS）进行免疫组织化学染色；超微结构检查心肌细胞；评估促凋亡基因 Bax 和抗凋亡基因 Bcl-2 的表达；以及丙二醛（MDA）的生化研究。多柔比星处理组的心肌细胞排列紊乱，细胞间间隙增大，细胞质空泡化，多个小固缩核。caspase-3 和 iNOS 免疫表达显著增加。超微结构显示，线粒体形状异常，细胞质空泡化，多个空泡和自噬体，胶原纤维积累，多个小染色质深核。闰盘排列紊乱，桥粒连接丢失。心肌细胞的 MDA 水平也显著升高，Bax/Bcl-2 基因表达比值上调。辅酶 Q10 的联合给药导致组织病理学图片显著改善，caspase-3 和 iNOS 免疫表达显著降低，Bax/Bcl-2 基因表达比值下调。总之，CoQ10 通过调节促凋亡和抗凋亡基因表达来保护多柔比星诱导的心脏毒性。
