Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.
Stem Cell Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt.
Cell Biochem Biophys. 2024 Jun;82(2):1353-1366. doi: 10.1007/s12013-024-01289-7. Epub 2024 May 14.
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.
多柔比星（DOX）是化疗的基石。然而，它具有剂量依赖性的心脏毒性事件，限制了其临床应用。本研究旨在研究多柔比星（DOX）在地奥司明（DIO）存在下作为抗癌药物对 MCF-7 细胞系的疗效，并评估 DIO 在体内对 DOX 心脏毒性的保护作用。体外研究旨在建立 DIO 存在时 DOX 细胞毒性的保存。体内研究在 42 只成年雌性 Wistar 大鼠上进行，将它们等分为 6 组；对照组、DIO（100mg/kg）、DIO（200mg/kg）、DOX（20mg/kg，单次腹腔注射）、DIO（100mg/kg）+DOX，DIO 口服（100mg/kg）30 天，然后给予单次 DOX 剂量和 DIO（200mg/kg）+DOX，DIO 口服（200mg/kg）30 天，然后给予 DOX。体外研究表明，DIO 存在时 DOX 对 MCF-7 的细胞毒性活性得以保存。体内研究表明，DOX 改变了心电图（ECG）参数。此外，它还导致 CK-MB、cTnT 和 LDH 血清水平以及 MDA、IL-1β 的心脏含量显著升高，同时 IL-10 和 SOD 水平显著降低。此外，DOX 组心脏组织中 Bax、TNF-α 和 HIF-1α 的表达显著上调，同时 Bcl-2 mRNA 的表达显著下调。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学结构。相反，DIO 预处理可以改善 ECG 参数，抑制 IL-1β 并增强 IL-10，促进 SOD 活性并抑制 MDA。此外，在 DIO 预处理大鼠中还证明了 Bax、TNF-α、HIF-1α 的下调和 Bcl-2 的上调。此外，心脏组织的组织病理学检查表明，DIO 对保护心脏组织学结构有积极影响。DIO 被建议用于保护 DOX 引起的急性心脏毒性，而不影响抗肿瘤活性。
