Peptide Szeto‑Schiller 31 ameliorates doxorubicin‑induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway

Zhang,Li; Feng,Mengwen; Wang,Xuejun; Zhang,Hao; Ding,Jingjing; Cheng,Zijie; Qian,Lingmei

doi:10.3892/ijmm.2021.4896

Peptide Szeto‑Schiller 31 ameliorates doxorubicin‑induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway

Authors:
- Li Zhang
- Mengwen Feng
- Xuejun Wang
- Hao Zhang
- Jingjing Ding
- Zijie Cheng
- Lingmei Qian
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Affiliations: Department of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Internal Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Department of General Practice, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
Published online on: February 25, 2021 https://doi.org/10.3892/ijmm.2021.4896
Article Number: 63
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidative stress serves a key role in doxorubicin (DOX)‑induced cardiotoxicity. The peptide Szeto‑Schiller (SS)31 is an efficacious antioxidant with the capacity to reduce mitochondrial reactive oxygen species (ROS) levels and scavenge free radicals. Although SS31 is involved in the pathophysiological process of various cardiovascular diseases, the role of SS31 in DOX‑induced cardiotoxicity remains unclear. To explore the effects of SS31 in DOX‑induced cardiotoxicity, the present study first constructed DOX‑induced cardiotoxicity models, in which H9c2 cells were incubated with 1 µM DOX for 24 h and C57BL/6 mice were administered DOX (20 mg/kg cumulative dose). The results of various assays in these models demonstrated that SS31 exhibited a cardioprotective effect in vitro and in vivo by attenuating the level of ROS, stabilizing the mitochondrial membrane potential and ameliorating myocardial apoptosis as well as fibrosis following treatment with DOX. Mechanistically, the results of the present study revealed that the p38 MAPK signaling pathway was inhibited by SS31 in DOX‑treated H9c2 cells, which was associated with the cardioprotective function of SS31. In addition, P79350, a selective agonist of p38 MAPK, reversed the protective effects of SS31. Taken together, these results demonstrated the effects of SS31 on ameliorating DOX‑induced cardiotoxicity and indicated its potential as a drug for the treatment of DOX‑induced cardiotoxicity.

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