Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects
Lesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2021/8895376 |
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| author | Fabiola Cortes-Lopez Alicia Sanchez-Mendoza David Centurion Luz G. Cervantes-Perez Vicente Castrejon-Tellez Leonardo del Valle-Mondragon Elizabeth Soria-Castro Victoria Ramirez Araceli Sanchez-Lopez Gustavo Pastelin-Hernandez Wylly Ramses Garcia-Niño Maria Sanchez-Aguilar Luz Ibarra-Lara |
| author_facet | Fabiola Cortes-Lopez Alicia Sanchez-Mendoza David Centurion Luz G. Cervantes-Perez Vicente Castrejon-Tellez Leonardo del Valle-Mondragon Elizabeth Soria-Castro Victoria Ramirez Araceli Sanchez-Lopez Gustavo Pastelin-Hernandez Wylly Ramses Garcia-Niño Maria Sanchez-Aguilar Luz Ibarra-Lara |
| author_sort | Fabiola Cortes-Lopez |
| collection | DOAJ |
| description | Lesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, promotes beneficial activities counteracting cardiac injury. Therefore, the objective of this work was to determine the potential protective effect of fenofibrate in cardiomyocytes exposed to HG, H/R, and HG+H/R. Cardiomyocyte cultures were divided into four main groups: (1) control (CT), (2) HG (25 mM), (3) H/R, and (4) HG+H/R. Our results indicate that cell viability decreases in cardiomyocytes undergoing HG, H/R, and both conditions, while fenofibrate improves cell viability in every case. Fenofibrate also decreases ROS production as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH) subunit expression. Regarding the antioxidant defense, superoxide dismutase (SOD Cu2+/Zn2+ and SOD Mn2+), catalase, and the antioxidant capacity were decreased in HG, H/R, and HG+H/R-exposed cardiomyocytes, while fenofibrate increased those parameters. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) increased significantly in treated cells, while pathologies increased the expression of its inhibitor Keap1. Oxidative stress-induced mitochondrial damage was lower in fenofibrate-exposed cardiomyocytes. Endothelial nitric oxide synthase was also favored in cardiomyocytes treated with fenofibrate. Our results suggest that fenofibrate preserves the antioxidant status and the ultrastructure in cardiomyocytes undergoing HG, H/R, and HG+H/R preventing damage to essential macromolecules involved in the proper functioning of the cardiomyocyte. |
| format | Article |
| id | doaj-art-aa7200dbb9c940e7afef92f1148b5b46 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-aa7200dbb9c940e7afef92f1148b5b462025-02-03T05:57:35ZengWileyPPAR Research1687-47571687-47652021-01-01202110.1155/2021/88953768895376Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental EffectsFabiola Cortes-Lopez0Alicia Sanchez-Mendoza1David Centurion2Luz G. Cervantes-Perez3Vicente Castrejon-Tellez4Leonardo del Valle-Mondragon5Elizabeth Soria-Castro6Victoria Ramirez7Araceli Sanchez-Lopez8Gustavo Pastelin-Hernandez9Wylly Ramses Garcia-Niño10Maria Sanchez-Aguilar11Luz Ibarra-Lara12Department of Pharmacobiology, Center for Research and Advanced Studies of the National Polytechnic Institute, Calz. de los Tenorios 235, Col Granjas Coapa, Tlalpan, 14330 Mexico City, MexicoDepartment of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, MexicoDepartment of Pharmacobiology, Center for Research and Advanced Studies of the National Polytechnic Institute, Calz. de los Tenorios 235, Col Granjas Coapa, Tlalpan, 14330 Mexico City, MexicoDepartment of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, MexicoDepartment of Physiology, National Institute of Cardiology Ignacio Chávez, Mexico City, MexicoDepartment of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, MexicoDepartment of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chávez, Mexico City, MexicoDepartment of Experimental Surgery, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Col. Sección XVI, Tlalpan, 14080 Mexico City, MexicoDepartment of Pharmacobiology, Center for Research and Advanced Studies of the National Polytechnic Institute, Calz. de los Tenorios 235, Col Granjas Coapa, Tlalpan, 14330 Mexico City, MexicoDepartment of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, MexicoDepartment of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chávez, Mexico City, MexicoDepartment of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, MexicoDepartment of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, MexicoLesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, promotes beneficial activities counteracting cardiac injury. Therefore, the objective of this work was to determine the potential protective effect of fenofibrate in cardiomyocytes exposed to HG, H/R, and HG+H/R. Cardiomyocyte cultures were divided into four main groups: (1) control (CT), (2) HG (25 mM), (3) H/R, and (4) HG+H/R. Our results indicate that cell viability decreases in cardiomyocytes undergoing HG, H/R, and both conditions, while fenofibrate improves cell viability in every case. Fenofibrate also decreases ROS production as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH) subunit expression. Regarding the antioxidant defense, superoxide dismutase (SOD Cu2+/Zn2+ and SOD Mn2+), catalase, and the antioxidant capacity were decreased in HG, H/R, and HG+H/R-exposed cardiomyocytes, while fenofibrate increased those parameters. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) increased significantly in treated cells, while pathologies increased the expression of its inhibitor Keap1. Oxidative stress-induced mitochondrial damage was lower in fenofibrate-exposed cardiomyocytes. Endothelial nitric oxide synthase was also favored in cardiomyocytes treated with fenofibrate. Our results suggest that fenofibrate preserves the antioxidant status and the ultrastructure in cardiomyocytes undergoing HG, H/R, and HG+H/R preventing damage to essential macromolecules involved in the proper functioning of the cardiomyocyte.http://dx.doi.org/10.1155/2021/8895376 |
| spellingShingle | Fabiola Cortes-Lopez Alicia Sanchez-Mendoza David Centurion Luz G. Cervantes-Perez Vicente Castrejon-Tellez Leonardo del Valle-Mondragon Elizabeth Soria-Castro Victoria Ramirez Araceli Sanchez-Lopez Gustavo Pastelin-Hernandez Wylly Ramses Garcia-Niño Maria Sanchez-Aguilar Luz Ibarra-Lara Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects PPAR Research |
| title | Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects |
| title_full | Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects |
| title_fullStr | Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects |
| title_full_unstemmed | Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects |
| title_short | Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects |
| title_sort | fenofibrate protects cardiomyocytes from hypoxia reperfusion and high glucose induced detrimental effects |
| url | http://dx.doi.org/10.1155/2021/8895376 |
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