JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway

Author(s): Huan YUE^1, Runjing LI^3, Jiajia XU⁴, Weixin LIU¹, Ziyang ZHAO¹, Junxiao FENG¹, Rui SHI⁵, Dongkun XIE⁶, Zhenghao ZHANG², Xingjuan SHI¹
Affiliation(s): ¹School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China ²Department of Hematology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China ³Department of Geriatrics Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China ⁴The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China ⁵School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China ⁶State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi'an 710032, China
Corresponding email(s): Zhenghao ZHANG, zhangzhenghao123@sohu.com Xingjuan SHI, xingjuanshi@seu.edu.cn
Key Words: Rhein; Cardiotoxicity; Mitochondrial fission; Drp1; Akt

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Huan YUE^1*, Runjing LI^3*, Jiajia XU⁴, Weixin LIU¹, Ziyang ZHAO¹, Junxiao FENG¹, Rui SHI⁵, Dongkun XIE⁶, Zhenghao ZHANG², Xingjuan SHI¹. Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500658

@article{title="Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway",
author="Huan YUE^1*, Runjing LI^3*, Jiajia XU⁴, Weixin LIU¹, Ziyang ZHAO¹, Junxiao FENG¹, Rui SHI⁵, Dongkun XIE⁶, Zhenghao ZHANG², Xingjuan SHI¹",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2500658"
}

%0 Journal Article
%T Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway
%A Huan YUE^1*
%A Runjing LI^3*
%A Jiajia XU⁴
%A Weixin LIU¹
%A Ziyang ZHAO¹
%A Junxiao FENG¹
%A Rui SHI⁵
%A Dongkun XIE⁶
%A Zhenghao ZHANG²
%A Xingjuan SHI¹
%J Journal of Zhejiang University SCIENCE B
%P
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2500658"

TY - JOUR
T1 - Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway
A1 - Huan YUE^1*
A1 - Runjing LI^3*
A1 - Jiajia XU⁴
A1 - Weixin LIU¹
A1 - Ziyang ZHAO¹
A1 - Junxiao FENG¹
A1 - Rui SHI⁵
A1 - Dongkun XIE⁶
A1 - Zhenghao ZHANG²
A1 - Xingjuan SHI¹
J0 - Journal of Zhejiang University Science B
SP -
EP -
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2500658"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Mitochondrial dynamics, including mitochondrial fusion and fission, have been identified as a critical regulator of heart function. Doxorubicin (Dox) is a highly effective chemotherapeutic agent that has demonstrated broad-spectrum activity against a variety of tumor types, whereas its application is limited due to cardiotoxic effects. Rhein, a medicinal active ingredient found in rhubarb, possesses a wide range of pharmacological activities. However, whether it exerts a cardioprotective role in Dox-induced cardiotoxicity by regulating mitochondrial dynamics remains to be investigated. In this study, we found that Dox treatment promoted mitochondrial fission and elevated the expression of dynamin-related protein 1 (Drp1) in cardiomyocytes. In addition, Drp1 deletion reduced mitochondrial fission and mitochondrial ROS, and attenuated Dox-induced cardiotoxicity both in vitro and in vivo. Furthermore, rhein treatment rescued Dox-induced cardiac damage in vivo. Mechanistically, rhein attenuated Dox-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission and mitochondrial ROS in cardiomyocytes. Moreover, it alleviated the Dox-induced upregulation of Drp1 by activating phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In conclusion, our findings demonstrate that rhein attenuates Dox-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission and mitochondrial ROS via the PI3K/Akt pathway.

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