Comparative study of cardioprotective effects of uridine-5′-monophosphate and uridine-5′-triphosphate during the early periods of acute myocardial ischemia

Bul'on, V. V.; Крылова, И. Б.; Rodionova, Olga M.; Selina, Elena N.; Евдокимова, Н. Р.; Sapronov, N. S.

doi:10.1007/s10517-007-0323-4

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Recent data revealed that a higher level of plasma uridine reduces the tendency for atrial fibrillation and can be associated with a decreased atherosclerosis risk [48,49]. Our previous studies indicated that under ischemia and reperfusion conditions, uridine supplementation prevents myocardial redox dyshomeostasis and heart rhythm disorders [29,30]. A growing body of evidence suggests that uridine can induce tissue recovery and decrease pro-inflammatory cytokine levels in various models of cardiac injury and cell pathologies [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…Uridine treatment can significantly decrease the levels of oxidative stress and inflammation in in vitro and in vivo models [33,51]. The positive effects of uridine against myocardial oxidative stress and inflammation may be associated with the activation of the mitoK ATP channel and normalization of the activity of antioxidant defense systems [29,30,33].…”

Section: Discussionmentioning

confidence: 99%

“…Using the ISO overstimulation model, we show that uridine is capable of restoring mitochondrial ultrastructure and function in the context of acute cardiomyocyte injury. In our experimental setting, the dose of uridine was evaluated based on our previous studies on other models of pathologies associated with oxidative stress and the data available in the literature [29,30,[33][34][35]56]. This dosage was well tolerated by control rats, without side effects during the follow-up period.…”

Section: Discussionmentioning

confidence: 99%

“…Uridine, a pyrimidine nucleoside containing uracil and ribose, is mostly known as a precursor for RNA; however, this nucleoside and its derivatives also play an essential role in the regulation of energy balance and oxidative phosphorylation [25,26], systemic metabolism [25], glycogen synthesis [27,28], membrane integrity, and normal cardiac function [29][30][31]. Recent insights into global transcriptomic and proteomic profiling in murine models suggest that uridine can promote the process of tissue repair and regeneration by modulating the metabolic processes [32].…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Uridine on Structural and Functional Rearrangements in Heart Mitochondria after a High-Dose Isoprenaline Exposure Modelling Stress-Induced Cardiomyopathy in Rats

Belosludtseva,

Pavlik,

Mikheeva

et al. 2023

IJMS

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The pyrimidine nucleoside uridine and its phosphorylated derivates have been shown to be involved in the systemic regulation of energy and redox balance and promote the regeneration of many tissues, including the myocardium, although the underlying mechanisms are not fully understood. Moreover, rearrangements in mitochondrial structure and function within cardiomyocytes are the predominant signs of myocardial injury. Accordingly, this study aimed to investigate whether uridine could alleviate acute myocardial injury induced by isoprenaline (ISO) exposure, a rat model of stress-induced cardiomyopathy, and to elucidate the mechanisms of its action related to mitochondrial dysfunction. For this purpose, a biochemical analysis of the relevant serum biomarkers and ECG monitoring were performed in combination with transmission electron microscopy and a comprehensive study of cardiac mitochondrial functions. The administration of ISO (150 mg/kg, twice with an interval of 24 h, s.c.) to rats caused myocardial degenerative changes, a sharp increase in the serum cardiospecific markers troponin I and the AST/ALT ratio, and a decline in the ATP level in the left ventricular myocardium. In parallel, alterations in the organization of sarcomeres with focal disorganization of myofibrils, and ultrastructural and morphological defects in mitochondria, including disturbances in the orientation and packing density of crista membranes, were detected. These malfunctions were improved by pretreatment with uridine (30 mg/kg, twice with an interval of 24 h, i.p.). Uridine also led to the normalization of the QT interval. Moreover, uridine effectively inhibited ISO-induced ROS overproduction and lipid peroxidation in rat heart mitochondria. The administration of uridine partially recovered the protein level of the respiratory chain complex V, along with the rates of ATP synthesis and mitochondrial potassium transport, suggesting the activation of the potassium cycle through the mitoKATP channel. Taken together, these results indicate that uridine ameliorates acute ISO-induced myocardial injury and mitochondrial malfunction, which may be due to the activation of mitochondrial potassium recycling and a mild uncoupling leading to decreased ROS generation and oxidative damage.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Uridine on Structural and Functional Rearrangements in Heart Mitochondria after a High-Dose Isoprenaline Exposure Modelling Stress-Induced Cardiomyopathy in Rats

Belosludtseva,

Pavlik,

Mikheeva

et al. 2023

IJMS

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Antiarrhythmic Effect of Uridine and Uridine-5’-Monophosphate in Acute Myocardial Ischemia

et al. 2014

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Experiments on rats with acute myocardial ischemia accompanied by early postocclusive arrhythmias have shown normalizing, energy-stabilizing, and antiarrhythmic effects of uridine and uridine-5'-monophosphate. The drugs decreased lactate and restored reserves of glycogen and creatine phosphate depleted by ischemia. Uridine and uridine-5'-monophosphate significantly decreased the severity of ventricular arrhythmias. Both drugs reduced the incidence and duration of fibrillation. Uridine -5'-monophosphate demonstrated most pronounced antifibrillatory effectiveness. We hypothesize that the antiarrhythmic effect of the drugs is determined by their capacity to activate energy metabolism.

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Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel

Крылова

Selina

Bulion

et al. 2021

Sci Rep

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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.

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Comparative study of cardioprotective effects of uridine-5′-monophosphate and uridine-5′-triphosphate during the early periods of acute myocardial ischemia

Cited by 4 publications

References 9 publications

Protective Effect of Uridine on Structural and Functional Rearrangements in Heart Mitochondria after a High-Dose Isoprenaline Exposure Modelling Stress-Induced Cardiomyopathy in Rats

Protective Effect of Uridine on Structural and Functional Rearrangements in Heart Mitochondria after a High-Dose Isoprenaline Exposure Modelling Stress-Induced Cardiomyopathy in Rats

Antiarrhythmic Effect of Uridine and Uridine-5’-Monophosphate in Acute Myocardial Ischemia

Uridine treatment prevents myocardial injury in rat models of acute ischemia and ischemia/reperfusion by activating the mitochondrial ATP-dependent potassium channel

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