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Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase
BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) and mitogen-activated protein (MAP) kinase play an important role in the development of myocardial reperfusion injury. In this study, we examined whether treatment with alpha-lipoic acid (ALA) before reperfusion could prevent myocardial reperf...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Korean Society of Cardiology
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771824/ https://www.ncbi.nlm.nih.gov/pubmed/19949619 http://dx.doi.org/10.4070/kcj.2009.39.9.359 |
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author | Oh, Seok Kyu Yun, Kyeong Ho Yoo, Nam Jin Kim, Nam-Ho Kim, Min-Sun Park, Byung-Rim Jeong, Jin-Won |
author_facet | Oh, Seok Kyu Yun, Kyeong Ho Yoo, Nam Jin Kim, Nam-Ho Kim, Min-Sun Park, Byung-Rim Jeong, Jin-Won |
author_sort | Oh, Seok Kyu |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) and mitogen-activated protein (MAP) kinase play an important role in the development of myocardial reperfusion injury. In this study, we examined whether treatment with alpha-lipoic acid (ALA) before reperfusion could prevent myocardial reperfusion injury in vivo. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to a 45-minute left anterior descending coronary artery ligation followed by 45- or 10-minute reperfusion. ALA was administered 10 minutes prior to reperfusion. The infarct size ratio of the infarct area to the ischemic area at risk, was measured based on 10, 25, 50, and 100 mg/kg of ALA, with propidium iodide (PI) fluorescence. Apoptosis was evaluated by TdT-mediated dUDP nick end labeling (TUNEL) staining. The generation of intracellular ROS was evaluated using the fluorogenic probe, dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA). Western blot analysis was performed for MAP kinase (pERK 1/2 and pJNK 1/2) activity. RESULTS: The infarct size, according to ALA dose, was significantly suppressed 29.1% with ALA 25 mg/kg (p<0.0001), 41.5% with 50 mg/kg (p<0.05), and 41.4% with 100 mg/kg (p<0.05) compared to the controls (54.3%). However, the results were not significantly different with 47.2% of the ALA 10 mg/kg (p=0.192). A few apoptotic nucleoli were detected in the ALA 25 mg/kg group, but were frequently detected in the control group. The ROS generation was significantly suppressed (p<0.0001), the activity of pERK 1/2 was significantly increased (p<0.05) and the activity of pJNK 1/2 was significantly decreased (p<0.05) in the ALA 25 mg/kg group compared to the controls. CONCLUSION: The results of this study suggested that adequate doses of ALA before reperfusion was effective for the prevention of myocardial reperfusion injury in vivo. This cardioprotective activity of ALA might be associated with an anti-apoptotic effect of ALA via suppression of ROS generation, increase of pERK 1/2 and decrease of pJNK 1/2 activity. |
format | Text |
id | pubmed-2771824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Korean Society of Cardiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-27718242009-11-30 Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase Oh, Seok Kyu Yun, Kyeong Ho Yoo, Nam Jin Kim, Nam-Ho Kim, Min-Sun Park, Byung-Rim Jeong, Jin-Won Korean Circ J Original Article BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) and mitogen-activated protein (MAP) kinase play an important role in the development of myocardial reperfusion injury. In this study, we examined whether treatment with alpha-lipoic acid (ALA) before reperfusion could prevent myocardial reperfusion injury in vivo. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to a 45-minute left anterior descending coronary artery ligation followed by 45- or 10-minute reperfusion. ALA was administered 10 minutes prior to reperfusion. The infarct size ratio of the infarct area to the ischemic area at risk, was measured based on 10, 25, 50, and 100 mg/kg of ALA, with propidium iodide (PI) fluorescence. Apoptosis was evaluated by TdT-mediated dUDP nick end labeling (TUNEL) staining. The generation of intracellular ROS was evaluated using the fluorogenic probe, dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA). Western blot analysis was performed for MAP kinase (pERK 1/2 and pJNK 1/2) activity. RESULTS: The infarct size, according to ALA dose, was significantly suppressed 29.1% with ALA 25 mg/kg (p<0.0001), 41.5% with 50 mg/kg (p<0.05), and 41.4% with 100 mg/kg (p<0.05) compared to the controls (54.3%). However, the results were not significantly different with 47.2% of the ALA 10 mg/kg (p=0.192). A few apoptotic nucleoli were detected in the ALA 25 mg/kg group, but were frequently detected in the control group. The ROS generation was significantly suppressed (p<0.0001), the activity of pERK 1/2 was significantly increased (p<0.05) and the activity of pJNK 1/2 was significantly decreased (p<0.05) in the ALA 25 mg/kg group compared to the controls. CONCLUSION: The results of this study suggested that adequate doses of ALA before reperfusion was effective for the prevention of myocardial reperfusion injury in vivo. This cardioprotective activity of ALA might be associated with an anti-apoptotic effect of ALA via suppression of ROS generation, increase of pERK 1/2 and decrease of pJNK 1/2 activity. The Korean Society of Cardiology 2009-09 2009-09-30 /pmc/articles/PMC2771824/ /pubmed/19949619 http://dx.doi.org/10.4070/kcj.2009.39.9.359 Text en Copyright © 2009 The Korean Society of Cardiology http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Oh, Seok Kyu Yun, Kyeong Ho Yoo, Nam Jin Kim, Nam-Ho Kim, Min-Sun Park, Byung-Rim Jeong, Jin-Won Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase |
title | Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase |
title_full | Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase |
title_fullStr | Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase |
title_full_unstemmed | Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase |
title_short | Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase |
title_sort | cardioprotective effects of alpha-lipoic acid on myocardial reperfusion injury: suppression of reactive oxygen species generation and activation of mitogen-activated protein kinase |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771824/ https://www.ncbi.nlm.nih.gov/pubmed/19949619 http://dx.doi.org/10.4070/kcj.2009.39.9.359 |
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