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The Protective Effect of Uridine on Metabolic Processes in the Rat Myocardum during its Ischemia/Reperfusion Injury

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Abstract—

The experimental study of the cardioprotective effect of uridine, the metabolic precursor of the endogenous activator of mitochondrial ATP-dependent K+-channels (mitoKATP-channels), was performed using the model of myocardial ischemia/reperfusion injury (I/RP) in rats. Ischemia for 30 min followed by reperfusion for 120 min resulted in a significant decrease in the ATP and phosphocreatine (PCr) content, intensification of lipid peroxidation (LPO), and inhibition of the antioxidant system (AOS) in cardiomyocytes. Intravenous administration of uridine (30 mg/kg) had a protective effect on the myocardial metabolism in the zone of I/RP. It prevented the I/RP-induced decrease of ATP and PCr, limited LPO processes, evaluated by the content of lipid hydroperoxides (LHP) and conjugated dienes (CD), and improved the AOS state by, preventing a decrease of superoxide dismutase (SOD) activity and increasing the content of reduced glutathione (GSH). The intravenous injection of mitoKATP-channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg, 5 min before uridine) eliminated the ability of uridine to maintain the ATP level and to exhibit its positive effect on the intensity of the LPO and activity of AOS. The data obtained suggest that the activation of mitoKATP-channels plays an important role in the mechanism of the cardioprotective effect of uridine in the myocardial I/RP.

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Authors and Affiliations

  1. Institute of Experimental Medicine (IEM), ul. Akad. Pavlova 12, 197376, St. Petersburg, Russia

    V. V. Bul’on, E. N. Selina & I. B. Krylova

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  1. V. V. Bul’on
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  2. E. N. Selina
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  3. I. B. Krylova
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Correspondence to I. B. Krylova.

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The experimental work was performed in accordance with the provisions of the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes [25] and was approved by the IEM Ethics Committee.

The authors declare that they have no conflict of interest.

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Translated by A. Medvedev

Abbreviations used: ADav—mean arterial pressure; AOS—antioxidant system; CD—conjugated dienes; GSH—reduced glutathione; 5-HD—5-hydroxydecanoate; HPLC—high performance liquid chromatography; HR—heart rate; I/RP—ischemia/reperfusion injury; LCA—left coronary artery; LHP—lipid hydroperoxides; LPO—lipid peroxidation; mitoKATP channels—mitochondrial ATP dependent K+ channels; PCr—phosphocreatine; ROS—reactive oxygen species; SOD—superoxide dismutase; UDP—uridine diphosphate.

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Bul’on, V.V., Selina, E.N. & Krylova, I.B. The Protective Effect of Uridine on Metabolic Processes in the Rat Myocardum during its Ischemia/Reperfusion Injury. Biochem. Moscow Suppl. Ser. B 14, 33–37 (2020). https://doi.org/10.1134/S1990750820010072

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  • DOI: https://doi.org/10.1134/S1990750820010072

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