Key result
Uridine pretreatment blunts myocardial injury in rats, cutting troponin I ~67% and preserving mitochondrial function.
Why the study?
Uridine and its phosphorylated derivatives regulate energy balance and tissue regeneration, but underlying mechanisms are unclear and its effect on isoprenaline-induced acute myocardial injury and mitochondrial dysfunction was unknown.
Does uridine pretreatment alleviate acute myocardial injury and mitochondrial dysfunction in a rat model of isoprenaline-induced stress cardiomyopathy?
Does uridine pretreatment alleviate acute myocardial injury and mitochondrial dysfunction in a rat model of isoprenaline-induced stress cardiomyopathy?
Uridine ameliorates acute isoprenaline-induced myocardial injury and mitochondrial malfunction in rats, potentially via activation of mitochondrial potassium recycling and decreased ROS generation.
Should not change clinical practice; hypothesis-generating for uridine in stress cardiomyopathy models and requires human validation.
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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Belosludtseva et al. (2023) studied Stress-induced cardiomyopathy (n=44). Uridine vs. Isoprenaline alone was evaluated on Serum cardiac troponin I concentration. Uridine pretreatment ameliorated acute isoprenaline-induced myocardial injury in rats, reducing serum troponin I by 67% and preserving mitochondrial function and ultrastructure.
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