Thrombopoietin ameliorates doxorubicin-induced toxicities in H9c2 myocardiocytes by inhibiting oxidative stress through the SIRT1/p38 MAPK signaling pathway

Abstract

Objective: To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1 (SIRT1) signaling pathway. Methods: H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay. The protein expressions of SIRT1 and p38 MAPK were measured by Western blot. RT-qPCR was also used to determine SIRT1 mRNA expression. In addition, intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated. Results: Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability. It also increased SIRT1 and decreased p-p38 MAPK protein expressions. In addition, thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress, and enhanced antioxidant enzyme activities. However, silencing SIRT1 abrogated the protective effects of thrombopoietin, as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels. Conclusions: Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway. However, its protective effects need to be further verified in animal tests.

Keywords

Doxorubicin / Thrombopoietin / Oxidative stress / Sirtuin 1 / Cardiotoxicity

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

This study was supported by the Natural Science Foundation of Hainan Province High-level Talent Project (grant number 820RC644) and Innovative Research Projects for Postgraduate Students at Hainan Medical University (grant number HYYS2022B08).

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

XHZ and YH contributed to data curation, investigation, and visualization. XHZ wrote the original draft. BCC planned the experimental protocols, ensuring that each step effectively supported the validation of our research hypotheses. MYZ, CCZ, HYJ, and LFL contributed to the final version of the manuscript. HW and MX supervised the project.

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