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Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity
Arsenic trioxide (ATO) is used as a therapeutic agent in the treatment of acute promyelocytic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. The cardio-protective effect of salvianolic acid A (Sal A) against ATO cardiotoxicity has been report...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954107/ https://www.ncbi.nlm.nih.gov/pubmed/29867492 http://dx.doi.org/10.3389/fphar.2018.00487 |
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author | Zhang, Jing-yi Wang, Min Wang, Rui-ying Sun, Xiao Du, Yu-yang Ye, Jing-xue Sun, Gui-bo Sun, Xiao-bo |
author_facet | Zhang, Jing-yi Wang, Min Wang, Rui-ying Sun, Xiao Du, Yu-yang Ye, Jing-xue Sun, Gui-bo Sun, Xiao-bo |
author_sort | Zhang, Jing-yi |
collection | PubMed |
description | Arsenic trioxide (ATO) is used as a therapeutic agent in the treatment of acute promyelocytic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. The cardio-protective effect of salvianolic acid A (Sal A) against ATO cardiotoxicity has been reported. However, the distinct role of the mitochondria in the cardio-protection of Sal A is not understood. The aim of this study was to determine whether Sal A preconditioning protects against ATO-induced heart injury by maintaining cardiac mitochondrial function and biogenesis. For the in vivo study, BALB/c mice were treated with ATO and/or Sal A. For the in vitro study, we determined the effects of ATO and/or Sal A in H9c2 cardiomyocytes. Our results showed that ATO induced mitochondrial structural damage, abnormal mitochondrial permeability transition pore (mPTP) opening, overproduction of mitochondrial reactive oxygen species (ROS), and decreased the ATP content. Sal A pretreatment alleviated the ATO-induced mitochondrial structural and functional damage. In this study, ATO decreased the expression level of the peroxisome proliferator activator receptor gamma-coactivator 1 (PGC-1α) and disrupted the normal division and fusion of mitochondria. Sal A pretreatment improved the dynamic balance of the damaged mitochondrial biogenesis. Moreover, the combination treatment of Sal A and ATO significantly enhanced the ATO-induced cytotoxicity of SGC7901, HepaRG, K562 and HL60 cells in vitro. These results indicated that Sal A protects the heart from ATO-induced injury, which correlates with the modulation of mitochondrial function, and the maintenance of normal mitochondrial biogenesis. |
format | Online Article Text |
id | pubmed-5954107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59541072018-06-04 Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity Zhang, Jing-yi Wang, Min Wang, Rui-ying Sun, Xiao Du, Yu-yang Ye, Jing-xue Sun, Gui-bo Sun, Xiao-bo Front Pharmacol Pharmacology Arsenic trioxide (ATO) is used as a therapeutic agent in the treatment of acute promyelocytic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. The cardio-protective effect of salvianolic acid A (Sal A) against ATO cardiotoxicity has been reported. However, the distinct role of the mitochondria in the cardio-protection of Sal A is not understood. The aim of this study was to determine whether Sal A preconditioning protects against ATO-induced heart injury by maintaining cardiac mitochondrial function and biogenesis. For the in vivo study, BALB/c mice were treated with ATO and/or Sal A. For the in vitro study, we determined the effects of ATO and/or Sal A in H9c2 cardiomyocytes. Our results showed that ATO induced mitochondrial structural damage, abnormal mitochondrial permeability transition pore (mPTP) opening, overproduction of mitochondrial reactive oxygen species (ROS), and decreased the ATP content. Sal A pretreatment alleviated the ATO-induced mitochondrial structural and functional damage. In this study, ATO decreased the expression level of the peroxisome proliferator activator receptor gamma-coactivator 1 (PGC-1α) and disrupted the normal division and fusion of mitochondria. Sal A pretreatment improved the dynamic balance of the damaged mitochondrial biogenesis. Moreover, the combination treatment of Sal A and ATO significantly enhanced the ATO-induced cytotoxicity of SGC7901, HepaRG, K562 and HL60 cells in vitro. These results indicated that Sal A protects the heart from ATO-induced injury, which correlates with the modulation of mitochondrial function, and the maintenance of normal mitochondrial biogenesis. Frontiers Media S.A. 2018-05-09 /pmc/articles/PMC5954107/ /pubmed/29867492 http://dx.doi.org/10.3389/fphar.2018.00487 Text en Copyright © 2018 Zhang, Wang, Wang, Sun, Du, Ye, Sun and Sun. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zhang, Jing-yi Wang, Min Wang, Rui-ying Sun, Xiao Du, Yu-yang Ye, Jing-xue Sun, Gui-bo Sun, Xiao-bo Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity |
title | Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity |
title_full | Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity |
title_fullStr | Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity |
title_full_unstemmed | Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity |
title_short | Salvianolic Acid A Ameliorates Arsenic Trioxide-Induced Cardiotoxicity Through Decreasing Cardiac Mitochondrial Injury and Promotes Its Anticancer Activity |
title_sort | salvianolic acid a ameliorates arsenic trioxide-induced cardiotoxicity through decreasing cardiac mitochondrial injury and promotes its anticancer activity |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954107/ https://www.ncbi.nlm.nih.gov/pubmed/29867492 http://dx.doi.org/10.3389/fphar.2018.00487 |
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