Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart

Background: Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mitochondria have been shown to pl...

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Main Authors: Siriporn C. Chattipakorn, Savitree Thummasorn, Jantira Sanit, Nipon Chattipakorn
Format: Journal
Published: 2018
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84904509817&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/45397
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spelling th-cmuir.6653943832-453972018-01-24T06:09:50Z Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart Siriporn C. Chattipakorn Savitree Thummasorn Jantira Sanit Nipon Chattipakorn Background: Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mitochondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arrhythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods: Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore (mPTP) blocker, cyclosporine A (CsA), and an inner membrane anion channel (IMAC) blocker, 4'-chlorodiazepam (CDP), were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential change and mitochondrial swelling were determined as indicators of cardiac mitochondrial function. Results: Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS production. Conclusions: Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of cardiac mitochondrial dysfunction caused by severe oxidative stress. ©2014 JGC All rights reserved. 2018-01-24T06:09:50Z 2018-01-24T06:09:50Z 2014-01-01 Journal 16715411 2-s2.0-84904509817 10.3969/j.issn.1671-5411.2014.02.014 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84904509817&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/45397
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description Background: Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mitochondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arrhythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods: Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore (mPTP) blocker, cyclosporine A (CsA), and an inner membrane anion channel (IMAC) blocker, 4'-chlorodiazepam (CDP), were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential change and mitochondrial swelling were determined as indicators of cardiac mitochondrial function. Results: Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS production. Conclusions: Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of cardiac mitochondrial dysfunction caused by severe oxidative stress. ©2014 JGC All rights reserved.
format Journal
author Siriporn C. Chattipakorn
Savitree Thummasorn
Jantira Sanit
Nipon Chattipakorn
spellingShingle Siriporn C. Chattipakorn
Savitree Thummasorn
Jantira Sanit
Nipon Chattipakorn
Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart
author_facet Siriporn C. Chattipakorn
Savitree Thummasorn
Jantira Sanit
Nipon Chattipakorn
author_sort Siriporn C. Chattipakorn
title Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart
title_short Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart
title_full Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart
title_fullStr Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart
title_full_unstemmed Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart
title_sort phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84904509817&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/45397
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