Abstract：
Doxorubicin (DOX) is the cornerstone of chemotherapy. However, it has dose-dependent cardiotoxic events that limit its clinical use. This study was intended to investigate the efficiency of DOX as an anti-cancer against the MCF-7 cell line in the presence of diosmin (DIO) and to appraise the protective impact of DIO against DOX cardiotoxicity in vivo. In vitro study was carried out to establish the conservation of DOX cytotoxicity in the presence of DIO. In vivo study was conducted on 42 adult female Wistar rats that were equally allocated into 6 groups; control, DIO (100 mg/kg), DIO (200 mg/kg), DOX (20 mg/kg, single dose i.p.), DIO (100 mg/kg) + DOX, received DIO orally (100 mg/kg) for 30 days, then administrated with a single dose of DOX and DIO (200 mg/kg) + DOX, received DIO orally (200 mg/kg) for 30 days, then administrated with DOX. In vitro study showed preservation of cytotoxic activity of DOX on MCF-7 in the presence of DIO. In vivo study indicated that DOX altered electrocardiograph (ECG) parameters. Also, it yielded a significant rise in CK-MB, cTnT and LDH serum levels and cardiac contents of MDA, IL-1β; paralleled by a significant drop in cardiac IL-10 and SOD. Moreover, significant upregulation of Bax, TNF-α, and HIF-1α, in concomitant with significant downregulation of Bcl-2 mRNA in cardiac tissue have been recorded in the DOX group. Furthermore, histopathological description of cardiac tissues showed that DOX alters normal cardiac histoarchitecture. On the opposite side, DIO pretreatment could ameliorate ECG parameters, suppress IL-1β and enhanceIL-10, promote activity of SOD and repress MDA. Additionally, downregulation of Bax, TNF-α, HIF-1α and upregulation of Bcl-2 have been demonstrated in DIO-pretreated rats. Furthermore, the histopathological examination of cardiac tissues illustrated that DIO had a favorable impact on the protection of heart histoarchitecture. DIO is suggested for protection against acute cardiotoxicity caused by DOX without affecting antitumor activity.
摘要：
多柔比星（DOX）是化疗的基石。然而,它具有剂量依赖性心脏毒性事件,限制了其临床应用.这项研究旨在研究在地奥司明（DIO）存在下DOX作为抗MCF-7细胞系的抗癌效率，并评估DIO对体内DOX心脏毒性的保护作用。进行体外研究以建立在DIO存在下DOX细胞毒性的保守性。对42只成年雌性Wistar大鼠进行了体内研究，这些大鼠平均分为6组；对照组，DIO（100mg/kg），DIO（200mg/kg），DOX（20mg/kg，单剂量i.p.)，DIO（100mg/kg）+DOX，口服DIO（100mg/kg）30天，然后给予单剂量的DOX和DIO（200mg/kg）+DOX，口服DIO（200mg/kg）30天，然后用DOX管理。体外研究表明，在DIO存在下，DOX对MCF-7的细胞毒活性得以保留。体内研究表明，DOX改变了心电图（ECG）参数。此外，它产生了显著的CK-MB上升，血清cTnT和LDH水平和心脏MDA含量，IL-1β；与心脏IL-10和SOD显着下降平行。此外，Bax的显着上调，TNF-α,和HIF-1α，在DOX组中，伴随着心脏组织中Bcl-2mRNA的显着下调。此外，心脏组织的组织病理学描述表明，DOX改变了正常的心脏组织结构。在对面，DIO预处理可以改善心电参数，抑制IL-1β和增强IL-10，促进SOD活性并抑制MDA。此外,下调Bax，TNF-α,在DIO预处理的大鼠中已经证明了HIF-1α和Bcl-2的上调。此外，心脏组织的组织病理学检查表明DIO对心脏组织结构的保护具有有利的影响。建议DIO用于保护由DOX引起的急性心脏毒性而不影响抗肿瘤活性。
