Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation

Acta Pharmaceutica Sinica. B
Jing LuPei-qing Liu

Abstract

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of Rheum palmatum L., is considered to play a broad role in a variety of biological processes. However, the effects of CHR׳s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide (3AB) and ABT888. Ectopic expression of PARP1 effectively blocked this CHR׳s cardioprotection against DOX-induced cardiomyocyte injury in H9C2 cells. Furthermore, pre-administration with both CHR and 3AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague-Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.

Citations

Dec 15, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Junjie YinXudong Wei
May 16, 2020·Frontiers in Physiology·Zhenhong FuYundai Chen
Dec 17, 2020·Frontiers in Pharmacology·Roodabeh Bahramsoltani, Roja Rahimi
Mar 7, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jian GaoJianxin Chen
Jul 12, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Cun LiuChanggang Sun
Jun 8, 2021·Acta Pharmaceutica Sinica. B·Zhenzhen LiPeiqing Liu
Jul 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Pushkar Singh RawatUmashanker Navik

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Methods Mentioned

BETA
light microscopy
PARylation

Software Mentioned

Quantity One
EVOS FL

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