Open Access

Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice

  • Authors:
    • Shuo Pang
    • Wei Dong
    • Ning Liu
    • Shan Gao
    • Jing Li
    • Xu Zhang
    • Dan Lu
    • Lianfeng Zhang
  • View Affiliations

  • Published online on: October 13, 2021     https://doi.org/10.3892/mmr.2021.12492
  • Article Number: 852
  • Copyright: © Pang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a member of the cytochrome P450 enzyme family and catalyzes the metabolism of various substrates. CYP2E1 is upregulated in multiple heart diseases and causes damage mainly via the production of reactive oxygen species (ROS). In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and knockdown of endogenous CYP2E1 can attenuate the pathological development of dilated cardiomyopathy (DCM). Nevertheless, targeted inhibition of CYP2E1 via the administration of drugs for the treatment of DCM remains elusive. Therefore, the present study aimed to investigate whether diallyl sulfide (DAS), a competitive inhibitor of CYP2E1, can be used to inhibit the development of the pathological process of DCM and identify its possible mechanism. Here, cTnTR141W transgenic mice, which developed typical DCM phenotypes, were used. Following treatment with DAS for 6 weeks, echocardiography, histological analysis and molecular marker detection were conducted to investigate the DAS‑induced improvement on myocardial function and morphology. Biochemical analysis, western blotting and TUNEL assays were used to detected ROS production and myocyte apoptosis. It was found that DAS improved the typical DCM phenotypes, including chamber dilation, wall thinning, fibrosis, poor myofibril organization and decreased ventricular blood ejection, as determined using echocardiographic and histopathological analyses. Furthermore, the regulatory mechanisms, including inhibition both of the oxidative stress levels and the mitochondria‑dependent apoptosis pathways, were involved in the effects of DAS. In particular, DAS showed advantages in terms of improved chamber dilation and dysfunction in model mice, and the improvement occurred in the early stage of the treatment compared with enalaprilat, an angiotensin‑converting enzyme inhibitor that has been widely used in the clinical treatment of DCM and HF. The current results demonstrated that DAS could protect against DCM via inhibition of oxidative stress and apoptosis. These findings also suggest that inhibition of CYP2E1 may be a valuable therapeutic strategy to control the development of heart diseases, especially those associated with CYP2E1 upregulation. Moreover, the development of DAS analogues with lower cytotoxicity and metabolic rate for CYP2E1 may be beneficial.
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December-2021
Volume 24 Issue 6

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Spandidos Publications style
Pang S, Dong W, Liu N, Gao S, Li J, Zhang X, Lu D and Zhang L: Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice. Mol Med Rep 24: 852, 2021.
APA
Pang, S., Dong, W., Liu, N., Gao, S., Li, J., Zhang, X. ... Zhang, L. (2021). Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice. Molecular Medicine Reports, 24, 852. https://doi.org/10.3892/mmr.2021.12492
MLA
Pang, S., Dong, W., Liu, N., Gao, S., Li, J., Zhang, X., Lu, D., Zhang, L."Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice". Molecular Medicine Reports 24.6 (2021): 852.
Chicago
Pang, S., Dong, W., Liu, N., Gao, S., Li, J., Zhang, X., Lu, D., Zhang, L."Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice". Molecular Medicine Reports 24, no. 6 (2021): 852. https://doi.org/10.3892/mmr.2021.12492