Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction
Abstract Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of...
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doaj-4822e11dae67459f93b0a8a97da64a992021-07-11T11:29:19ZengNature Publishing GroupScientific Reports2045-23222021-07-0111111410.1038/s41598-021-93234-4Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunctionAnand Ramalingam0Siti Balkis Budin1Norsyahida Mohd Fauzi2Rebecca H. Ritchie3Satirah Zainalabidin4Program of Biomedical Science, Centre of Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan MalaysiaProgram of Biomedical Science, Centre of Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan MalaysiaDrug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan MalaysiaHeart Failure Pharmacology, Baker Heart and Diabetes InstituteProgram of Biomedical Science, Centre of Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan MalaysiaAbstract Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resveratrol (a sirtuin activator) , on nicotine-induced cardiac remodeling and dysfunction. Sprague–Dawley rats were administered 0.6 mg/kg nicotine daily with 0.7 mg/kg mitoTEMPO, 8 mg/kg resveratrol, or vehicle alone for 28 days. At the end of the study, rat hearts were collected to analyze the cardiac structure, mitochondrial ROS level, oxidative stress, and inflammation markers. A subset of rat hearts was perfused ex vivo to determine the cardiac function and myocardial susceptibility to ischemia–reperfusion injury. Nicotine administration significantly augmented mitochondrial ROS level, cardiomyocyte hypertrophy, fibrosis, and inflammation in rat hearts. Nicotine administration also induced left ventricular dysfunction, which was worsened by ischemia–reperfusion in isolated rat hearts. MitoTEMPO and resveratrol both significantly attenuated the adverse cardiac remodeling induced by nicotine, as well as the aggravation of postischemic ventricular dysfunction. Findings from this study show that targeting mitochondrial ROS with mitoTEMPO or resveratrol partially attenuates nicotine-induced cardiac remodeling and dysfunction.https://doi.org/10.1038/s41598-021-93234-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anand Ramalingam Siti Balkis Budin Norsyahida Mohd Fauzi Rebecca H. Ritchie Satirah Zainalabidin |
spellingShingle |
Anand Ramalingam Siti Balkis Budin Norsyahida Mohd Fauzi Rebecca H. Ritchie Satirah Zainalabidin Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction Scientific Reports |
author_facet |
Anand Ramalingam Siti Balkis Budin Norsyahida Mohd Fauzi Rebecca H. Ritchie Satirah Zainalabidin |
author_sort |
Anand Ramalingam |
title |
Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction |
title_short |
Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction |
title_full |
Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction |
title_fullStr |
Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction |
title_full_unstemmed |
Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction |
title_sort |
targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-07-01 |
description |
Abstract Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resveratrol (a sirtuin activator) , on nicotine-induced cardiac remodeling and dysfunction. Sprague–Dawley rats were administered 0.6 mg/kg nicotine daily with 0.7 mg/kg mitoTEMPO, 8 mg/kg resveratrol, or vehicle alone for 28 days. At the end of the study, rat hearts were collected to analyze the cardiac structure, mitochondrial ROS level, oxidative stress, and inflammation markers. A subset of rat hearts was perfused ex vivo to determine the cardiac function and myocardial susceptibility to ischemia–reperfusion injury. Nicotine administration significantly augmented mitochondrial ROS level, cardiomyocyte hypertrophy, fibrosis, and inflammation in rat hearts. Nicotine administration also induced left ventricular dysfunction, which was worsened by ischemia–reperfusion in isolated rat hearts. MitoTEMPO and resveratrol both significantly attenuated the adverse cardiac remodeling induced by nicotine, as well as the aggravation of postischemic ventricular dysfunction. Findings from this study show that targeting mitochondrial ROS with mitoTEMPO or resveratrol partially attenuates nicotine-induced cardiac remodeling and dysfunction. |
url |
https://doi.org/10.1038/s41598-021-93234-4 |
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