Open Access

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

  • Authors:
    • Lan Zhan
    • Xiangxiu Wang
    • Yanjing Zhang
    • Guonian Zhu
    • Yu Ding
    • Xuemei Chen
    • Wei Jiang
    • Sisi Wu
  • View Affiliations

  • Published online on: July 29, 2021     https://doi.org/10.3892/etm.2021.10516
  • Article Number: 1082
  • Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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October-2021
Volume 22 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhan L, Wang X, Zhang Y, Zhu G, Ding Y, Chen X, Jiang W and Wu S: Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway. Exp Ther Med 22: 1082, 2021.
APA
Zhan, L., Wang, X., Zhang, Y., Zhu, G., Ding, Y., Chen, X. ... Wu, S. (2021). Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway. Experimental and Therapeutic Medicine, 22, 1082. https://doi.org/10.3892/etm.2021.10516
MLA
Zhan, L., Wang, X., Zhang, Y., Zhu, G., Ding, Y., Chen, X., Jiang, W., Wu, S."Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway". Experimental and Therapeutic Medicine 22.4 (2021): 1082.
Chicago
Zhan, L., Wang, X., Zhang, Y., Zhu, G., Ding, Y., Chen, X., Jiang, W., Wu, S."Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway". Experimental and Therapeutic Medicine 22, no. 4 (2021): 1082. https://doi.org/10.3892/etm.2021.10516