Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel
Abstract The effect of uridine on the myocardial ischemic and reperfusion injury was investigated. A possible mechanism of its cardioprotective action was established. Two rat models were used: (1) acute myocardial ischemia induced by occlusion of the left coronary artery for 60 min; and (2) myocard...
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| Format: | Article |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-96562-7 |
| _version_ | 1818991910424936448 |
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| author | Irina B. Krylova Elena N. Selina Valentina V. Bulion Olga M. Rodionova Natalia R. Evdokimova Natalia V. Belosludtseva Maria I. Shigaeva Galina D. Mironova |
| author_facet | Irina B. Krylova Elena N. Selina Valentina V. Bulion Olga M. Rodionova Natalia R. Evdokimova Natalia V. Belosludtseva Maria I. Shigaeva Galina D. Mironova |
| author_sort | Irina B. Krylova |
| collection | DOAJ |
| description | Abstract The effect of uridine on the myocardial ischemic and reperfusion injury was investigated. A possible mechanism of its cardioprotective action was established. Two rat models were used: (1) acute myocardial ischemia induced by occlusion of the left coronary artery for 60 min; and (2) myocardial ischemia/reperfusion with 30-min ischemia and 120-min reperfusion. In both models, treatment with uridine (30 mg/kg) prevented a decrease in cell energy supply and in the activity of the antioxidant system, as well as an increase in the level of lipid hydroperoxides and diene conjugates. This led to a reduction of the necrosis zone in the myocardium and disturbances in the heart rhythm. The blocker of the mitochondrial ATP-dependent potassium (mitoKATP) channel 5-hydroxydecanoate limited the positive effects of uridine. The data indicate that the cardioprotective action of uridine may be related to the activation of the mitoKATP channel. Intravenously injected uridine was more rapidly eliminated from the blood in hypoxia than in normoxia, and the level of the mitoKATP channel activator UDP in the myocardium after uridine administration increased. The results suggest that the use of uridine can be a potentially effective approach to the management of cardiovascular diseases. |
| first_indexed | 2024-12-20T20:17:46Z |
| format | Article |
| id | doaj.art-91dce8832b204e19896e31278e998607 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:17:46Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-91dce8832b204e19896e31278e9986072022-12-21T19:27:40ZengNature PortfolioScientific Reports2045-23222021-08-0111111310.1038/s41598-021-96562-7Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channelIrina B. Krylova0Elena N. Selina1Valentina V. Bulion2Olga M. Rodionova3Natalia R. Evdokimova4Natalia V. Belosludtseva5Maria I. Shigaeva6Galina D. Mironova7Department of Neuropharmacology, Federal State Budgetary Scientific Institution, Institute of Experimental MedicineDepartment of Neuropharmacology, Federal State Budgetary Scientific Institution, Institute of Experimental MedicineDepartment of Neuropharmacology, Federal State Budgetary Scientific Institution, Institute of Experimental MedicineDepartment of Neuropharmacology, Federal State Budgetary Scientific Institution, Institute of Experimental MedicineDepartment of Neuropharmacology, Federal State Budgetary Scientific Institution, Institute of Experimental MedicineLaboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics of Russian Academy of SciencesLaboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics of Russian Academy of SciencesLaboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics of Russian Academy of SciencesAbstract The effect of uridine on the myocardial ischemic and reperfusion injury was investigated. A possible mechanism of its cardioprotective action was established. Two rat models were used: (1) acute myocardial ischemia induced by occlusion of the left coronary artery for 60 min; and (2) myocardial ischemia/reperfusion with 30-min ischemia and 120-min reperfusion. In both models, treatment with uridine (30 mg/kg) prevented a decrease in cell energy supply and in the activity of the antioxidant system, as well as an increase in the level of lipid hydroperoxides and diene conjugates. This led to a reduction of the necrosis zone in the myocardium and disturbances in the heart rhythm. The blocker of the mitochondrial ATP-dependent potassium (mitoKATP) channel 5-hydroxydecanoate limited the positive effects of uridine. The data indicate that the cardioprotective action of uridine may be related to the activation of the mitoKATP channel. Intravenously injected uridine was more rapidly eliminated from the blood in hypoxia than in normoxia, and the level of the mitoKATP channel activator UDP in the myocardium after uridine administration increased. The results suggest that the use of uridine can be a potentially effective approach to the management of cardiovascular diseases.https://doi.org/10.1038/s41598-021-96562-7 |
| spellingShingle | Irina B. Krylova Elena N. Selina Valentina V. Bulion Olga M. Rodionova Natalia R. Evdokimova Natalia V. Belosludtseva Maria I. Shigaeva Galina D. Mironova Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel Scientific Reports |
| title | Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel |
| title_full | Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel |
| title_fullStr | Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel |
| title_full_unstemmed | Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel |
| title_short | Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel |
| title_sort | uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia reperfusion by activating the mitochondrial atp dependent potassium channel |
| url | https://doi.org/10.1038/s41598-021-96562-7 |
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