Sharifiaghdam Zeynab, Amini Seyed Mohammad, Dalouchi Fereshteh, Behrooz Amir Barzegar, Azizi Yaser
Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Radiation Biology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Heliyon. 2023 Feb 24;9(3):e14024. doi: 10.1016/j.heliyon.2023.e14024. eCollection 2023 Mar.
Cardiotoxicity is associated with doxorubicin (DOX), an effective anticancer drug. Apigenin has cardioprotective properties; it may be employed as a capping and reducing agent in synthesizing gold nanoparticles (AuNPs). This study examined the cardioprotective impact of AuNPs synthesized with apigenin (Api) in DOX-induced cardiotoxicity (DIC).
Api-AuNPs were synthesized in a single pot without needing additional reagents for reducing gold ions or stabilizing the NPs. The cytotoxicity of Api-AuNPs on H9c2 heart cells was subsequently determined using the MTT assay. In the animal investigation, 40 male rats were randomly assigned to one of four groups: control, cardiotoxicity (DOX), DOX treated with apigenin (DOX + Api), or DOX treated with Api-AuNPs (DOX + Api-AuNPs). To examine heart function, echocardiography was conducted. Blood samples were obtained to evaluate injury indicators (Lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), Cardiac Troponin I (cTn-I), Alanine transaminase (ALT), and Aspartate transaminase (AST)). The heart was removed under general anesthetic, weighed, and preserved in formalin solution. Six micrometer-thick cardiac tissue sections were stained with hematoxylin, eosin (H&E), and immunohistochemistry to identify cardiomyocyte apoptotic markers (Bax, Bcl-2, and caspase3).
Api-AuNPs have an average size of 21.4 ± 11.6 nm and are stable in physiological environments. Api-AuNPs therapy substantially reduced body and heart weight loss compared to the DOX group. Injury indicators were reduced dramatically by Api-AuNPs treatment. Api-AuNPs inhibited myocardial apoptosis via modulating Bax, caspase3, and Bcl-2 and ameliorating tissue damage caused by DOX.
Api-AuNPs' anti-apoptotic activities provide cardioprotection against DIC. It has the potential to reduce cardiotoxicity and boost myocardial performance.
心脏毒性与阿霉素（DOX）有关，阿霉素是一种有效的抗癌药物。芹菜素具有心脏保护特性；它可在合成金纳米颗粒（AuNPs）时用作封端和还原剂。本研究考察了用芹菜素（Api）合成的AuNPs对阿霉素诱导的心脏毒性（DIC）的心脏保护作用。
在单锅中合成Api-AuNPs，无需额外试剂来还原金离子或稳定纳米颗粒。随后使用MTT法测定Api-AuNPs对H9c2心脏细胞的细胞毒性。在动物研究中，40只雄性大鼠被随机分为四组之一：对照组、心脏毒性组（DOX）、用芹菜素治疗的DOX组（DOX + Api）或用Api-AuNPs治疗的DOX组（DOX + Api-AuNPs）。为检查心脏功能，进行了超声心动图检查。采集血样以评估损伤指标（乳酸脱氢酶（LDH）、肌酸激酶同工酶MB（CK-MB）、心肌肌钙蛋白I（cTn-I）、谷丙转氨酶（ALT）和谷草转氨酶（AST））。在全身麻醉下取出心脏，称重，并保存在福尔马林溶液中。对6微米厚的心脏组织切片进行苏木精、伊红（H&E）染色和免疫组织化学染色，以鉴定心肌细胞凋亡标志物（Bax、Bcl-2和caspase3）。
Api-AuNPs的平均粒径为21.4±11.6纳米，在生理环境中稳定。与DOX组相比，Api-AuNPs治疗显著减轻了体重和心脏重量的损失。Api-AuNPs治疗显著降低了损伤指标。Api-AuNPs通过调节Bax、caspase3和Bcl-2抑制心肌细胞凋亡，并改善了DOX引起的组织损伤。
Api-AuNPs的抗凋亡活性为DIC提供了心脏保护作用。它有可能降低心脏毒性并改善心肌性能。
