Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats
Background/Aims: Doxorubicin-induced cardiac toxicity has been a major concern of oncologists and is considered the main restriction on its clinical application. Oxymatrine has shown potent anti-cancer, anti-fibrosis, and anti-oxidative effects. Recently, it has been reported that oxymatrine is prot...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Cell Physiol Biochem Press GmbH & Co KG
2017-09-01
|
Series: | Cellular Physiology and Biochemistry |
Subjects: | |
Online Access: | http://www.karger.com/Article/FullText/480471 |
_version_ | 1818253702315638784 |
---|---|
author | Yan-Yan Zhang Minhan Yi Yong-Pan Huang |
author_facet | Yan-Yan Zhang Minhan Yi Yong-Pan Huang |
author_sort | Yan-Yan Zhang |
collection | DOAJ |
description | Background/Aims: Doxorubicin-induced cardiac toxicity has been a major concern of oncologists and is considered the main restriction on its clinical application. Oxymatrine has shown potent anti-cancer, anti-fibrosis, and anti-oxidative effects. Recently, it has been reported that oxymatrine is protective against some cardiovascular diseases. In this study, we aimed to investigate the effects of oxymatrine on doxorubicin-induced cardiotoxicity in rat hearts and H9c2 cells. Methods: Creatine Kinase - MB (CK-MB) and Lactate Dehydrogenase (LDH) levels were determined using commercial kits. Biochemical indices reflecting oxidative stress, such as catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also analyzed with commercial kits. Mitochondrial reactive oxygen species (ROS) 2’,7’-dichlorofluorescin diacetate (DCFH-DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes, and apoptosis was measured using a commercial kit. Western blots were used to detect the level of expression of cleaved caspase-3. Results: Doxorubicin treatment significantly increased oxidative stress levels, as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species. Doxorubicin also increased pathological damage in myocardial tissue, myocardial ROS levels, and malonyldialdehyde levels, and induced apoptosis in myocardial tissues and H9c2 cells. All of these doxorubicin-induced effects were attenuated by oxymatrine. Conclusion: These in vitro and in vivo findings indicate that oxymatrine may be a promising cardioprotective agent against doxorubicin-induced cardiotoxicity, at least in part mediated through oxymatrine’s inhibition of cardiac apoptosis and oxidative stress. |
first_indexed | 2024-12-12T16:44:16Z |
format | Article |
id | doaj.art-3dc2391537034cc19a388e90f7819b29 |
institution | Directory Open Access Journal |
issn | 1015-8987 1421-9778 |
language | English |
last_indexed | 2024-12-12T16:44:16Z |
publishDate | 2017-09-01 |
publisher | Cell Physiol Biochem Press GmbH & Co KG |
record_format | Article |
series | Cellular Physiology and Biochemistry |
spelling | doaj.art-3dc2391537034cc19a388e90f7819b292022-12-22T00:18:30ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-09-0143262663510.1159/000480471480471Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in RatsYan-Yan ZhangMinhan YiYong-Pan HuangBackground/Aims: Doxorubicin-induced cardiac toxicity has been a major concern of oncologists and is considered the main restriction on its clinical application. Oxymatrine has shown potent anti-cancer, anti-fibrosis, and anti-oxidative effects. Recently, it has been reported that oxymatrine is protective against some cardiovascular diseases. In this study, we aimed to investigate the effects of oxymatrine on doxorubicin-induced cardiotoxicity in rat hearts and H9c2 cells. Methods: Creatine Kinase - MB (CK-MB) and Lactate Dehydrogenase (LDH) levels were determined using commercial kits. Biochemical indices reflecting oxidative stress, such as catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also analyzed with commercial kits. Mitochondrial reactive oxygen species (ROS) 2’,7’-dichlorofluorescin diacetate (DCFH-DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes, and apoptosis was measured using a commercial kit. Western blots were used to detect the level of expression of cleaved caspase-3. Results: Doxorubicin treatment significantly increased oxidative stress levels, as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species. Doxorubicin also increased pathological damage in myocardial tissue, myocardial ROS levels, and malonyldialdehyde levels, and induced apoptosis in myocardial tissues and H9c2 cells. All of these doxorubicin-induced effects were attenuated by oxymatrine. Conclusion: These in vitro and in vivo findings indicate that oxymatrine may be a promising cardioprotective agent against doxorubicin-induced cardiotoxicity, at least in part mediated through oxymatrine’s inhibition of cardiac apoptosis and oxidative stress.http://www.karger.com/Article/FullText/480471OxymatrineDoxorubicinCardiotoxicityApoptosisOxidative stress |
spellingShingle | Yan-Yan Zhang Minhan Yi Yong-Pan Huang Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats Cellular Physiology and Biochemistry Oxymatrine Doxorubicin Cardiotoxicity Apoptosis Oxidative stress |
title | Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats |
title_full | Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats |
title_fullStr | Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats |
title_full_unstemmed | Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats |
title_short | Oxymatrine Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats |
title_sort | oxymatrine ameliorates doxorubicin induced cardiotoxicity in rats |
topic | Oxymatrine Doxorubicin Cardiotoxicity Apoptosis Oxidative stress |
url | http://www.karger.com/Article/FullText/480471 |
work_keys_str_mv | AT yanyanzhang oxymatrineamelioratesdoxorubicininducedcardiotoxicityinrats AT minhanyi oxymatrineamelioratesdoxorubicininducedcardiotoxicityinrats AT yongpanhuang oxymatrineamelioratesdoxorubicininducedcardiotoxicityinrats |