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

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.

Cardioprotective effect of linseed oil against isoproterenol-induced myocardial infarction in Wistar rats: a biochemical and electrocardiographic study

The present study was designed to evaluate the cardioprotective effect of Tunisian flaxseed oil (Linum usitatissimum) against isoproterenol-induced myocardial infarction in rats by studying hypertensive and cardiac damage markers especially electrocardiographic changes and troponin T serum level. In vitro, the extracted oil showed an important inhibition of angiotensin converting enzyme (ACE) with an IC50 = 85.96 μg/ml. According to chemical analysis, this extract is composed essentially of alpha linolenic acid (ALA), an n-3 polyunsaturated fatty acid (58.59 %). Male rats were randomly divided into three groups, namely control (C), isoproterenol (ISO), and isoproterenol-treated group with flaxseed oil (FO + ISO). Isoproterenol injection showed changes in ECG pattern, including ST-segment elevation (diagnostic of myocardial infarction), increase in the serum levels ofTroponin T and cardiac injury markers (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT)). However, Linum oil pre-co-treatment prevented almost all the parameters isoproterenol-induced myocardial infarction in rats. Results of the present study proved that flaxseed oil has a significant effect by heart protection against isoproterenol-induced myocardial infarction through beneficial effect of the important fraction of ALA