Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction
Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11<i>H</i>-indeno [1,2-<i>b&...
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/714 |
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| author | Mark B. Plotnikov Galina A. Chernysheva Vera I. Smol’yakova Oleg I. Aliev Tatyana I. Fomina Lyubov A. Sandrikina Irina V. Sukhodolo Vera V. Ivanova Anton N. Osipenko Nina D. Anfinogenova Andrei I. Khlebnikov Dmitriy N. Atochin Igor A. Schepetkin Mark T. Quinn |
| author_facet | Mark B. Plotnikov Galina A. Chernysheva Vera I. Smol’yakova Oleg I. Aliev Tatyana I. Fomina Lyubov A. Sandrikina Irina V. Sukhodolo Vera V. Ivanova Anton N. Osipenko Nina D. Anfinogenova Andrei I. Khlebnikov Dmitriy N. Atochin Igor A. Schepetkin Mark T. Quinn |
| author_sort | Mark B. Plotnikov |
| collection | DOAJ |
| description | Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11<i>H</i>-indeno [1,2-<i>b</i>]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI. |
| first_indexed | 2024-03-11T06:54:13Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:54:13Z |
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| series | Biomedicines |
| spelling | doaj.art-216f2644432a467b9703cf6cf31007dc2023-11-17T09:44:32ZengMDPI AGBiomedicines2227-90592023-02-0111371410.3390/biomedicines11030714Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial InfarctionMark B. Plotnikov0Galina A. Chernysheva1Vera I. Smol’yakova2Oleg I. Aliev3Tatyana I. Fomina4Lyubov A. Sandrikina5Irina V. Sukhodolo6Vera V. Ivanova7Anton N. Osipenko8Nina D. Anfinogenova9Andrei I. Khlebnikov10Dmitriy N. Atochin11Igor A. Schepetkin12Mark T. Quinn13Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, RussiaDepartment of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, RussiaDepartment of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, RussiaDepartment of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, RussiaDepartment of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, RussiaDepartment of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, RussiaDepartment of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, RussiaDepartment of Morphology and General Pathology, Siberian State Medical University, 634050 Tomsk, RussiaDepartment of Pharmacology, Siberian State Medical University, 634050 Tomsk, RussiaCardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634012 Tomsk, RussiaKizhner Research Center, Tomsk Polytechnic University, 634050 Tomsk, RussiaKizhner Research Center, Tomsk Polytechnic University, 634050 Tomsk, RussiaDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USADepartment of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USAActivation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11<i>H</i>-indeno [1,2-<i>b</i>]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI.https://www.mdpi.com/2227-9059/11/3/714cardioprotective activityc-Jun N-terminal kinase inhibitor11<i>H</i>-indeno[1,2-<i>b</i>]quinoxalin-11-one oximeheart failureinfarct sizemyocardial infarction |
| spellingShingle | Mark B. Plotnikov Galina A. Chernysheva Vera I. Smol’yakova Oleg I. Aliev Tatyana I. Fomina Lyubov A. Sandrikina Irina V. Sukhodolo Vera V. Ivanova Anton N. Osipenko Nina D. Anfinogenova Andrei I. Khlebnikov Dmitriy N. Atochin Igor A. Schepetkin Mark T. Quinn Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction Biomedicines cardioprotective activity c-Jun N-terminal kinase inhibitor 11<i>H</i>-indeno[1,2-<i>b</i>]quinoxalin-11-one oxime heart failure infarct size myocardial infarction |
| title | Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction |
| title_full | Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction |
| title_fullStr | Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction |
| title_full_unstemmed | Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction |
| title_short | Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction |
| title_sort | cardioprotective effects of a selective c jun n terminal kinase inhibitor in a rat model of myocardial infarction |
| topic | cardioprotective activity c-Jun N-terminal kinase inhibitor 11<i>H</i>-indeno[1,2-<i>b</i>]quinoxalin-11-one oxime heart failure infarct size myocardial infarction |
| url | https://www.mdpi.com/2227-9059/11/3/714 |
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