Apigenin-coated gold nanoparticles as a cardioprotective strategy against doxorubicin-induced cardiotoxicity in male rats via reducing apoptosis

Zeynab Sharifiaghdam; Seyed Mohammad Amini; Fereshteh Dalouchi; Amir Barzegar Behrooz; Yaser Azizi

doi:10.1016/j.heliyon.2023.e14024

Apigenin-coated gold nanoparticles as a cardioprotective strategy against doxorubicin-induced cardiotoxicity in male rats via reducing apoptosis

Heliyon. 2023 Feb 24;9(3):e14024. doi: 10.1016/j.heliyon.2023.e14024. eCollection 2023 Mar.

Authors

Zeynab Sharifiaghdam¹, Seyed Mohammad Amini², Fereshteh Dalouchi¹, Amir Barzegar Behrooz^{3

4}, Yaser Azizi^{1

5}

Affiliations

¹ Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
² Radiation Biology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
³ Nanobiotechnology Research Group, Department of Biochemistry, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang 43400, Malaysia.
⁴ Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Abstract

Aims: 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).

Main methods: 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).

Key findings: 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.

Significance: Api-AuNPs' anti-apoptotic activities provide cardioprotection against DIC. It has the potential to reduce cardiotoxicity and boost myocardial performance.

Keywords: Apigenin; Apoptosis; Cardiotoxicity; Doxorubicin; Gold nanoparticles.