Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway

Copyright: © Zhan et al..

Doxorubicin (DOX) stimulates the generation of reactive oxygen species, thereby impairing mitochondrial functions. Angiotensin-converting enzyme inhibitors (ACEIs) have been identified to exhibit protective effects on cardiovascular diseases. The present study aimed to test the hypothesis that an ACEI benazepril hydrochloride (HCl) may protect against DOX-induced cardiotoxicity. The DOX injury model was established using rat embryonic cardiac myoblast cells (H9c2 cell line) treated with DOX in vitro. H9c2 cells were treated with benazepril-HCl, DOX or a mixture of DOX and benazepril-HCl to measure the activities of myocardial enzymes including lactate dehydrogenase (LDH), superoxide dismutase, catalase and glutathione peroxidase, in addition to the concentration of malondialdehyde in the culture medium. Cells without any treatment were used as a control. DOX treatment increased the levels of activity of myocardial enzymes in H9c2 cells compared with those in the untreated control cells. Additionally, co-treatment with benazepril-HCl significantly reduced the levels of apoptosis occurring due to DOX-mediated cellular damage. The mechanistic experiment revealed that pretreatment with benazepril-HCl counteracted the DOX-induced oxidative stress and suppressed the activation of apoptosis via the PI3K/Akt signaling pathway. By contrast, an Akt inhibitor (MK2206) inhibited the protective effects of benazepril-HCl against DOX-induced H9c2 cell injury, as revealed by increased LDH release in H9c2 cells. These results suggested that benazepril-HCl may potentially be administered as an adjuvant for DOX in long-term clinical use.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

Experimental and therapeutic medicine - 22(2021), 4 vom: 07. Okt., Seite 1082

Sprache:

Englisch

Beteiligte Personen:

Zhan, Lan [VerfasserIn]
Wang, Xiangxiu [VerfasserIn]
Zhang, Yanjing [VerfasserIn]
Zhu, Guonian [VerfasserIn]
Ding, Yu [VerfasserIn]
Chen, Xuemei [VerfasserIn]
Jiang, Wei [VerfasserIn]
Wu, Sisi [VerfasserIn]

Links:

Volltext

Themen:

Apoptosis
Benazepril hydrochloride
Cardiotoxicity
Doxorubicin
H9c2 cells
Journal Article
Oxidative stress

Anmerkungen:

Date Revised 28.08.2021

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.3892/etm.2021.10516

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM329903381