[Protective effect of uridine on metabolic processes in rat myocardum during its ischemia/reperfusion damage]
- PMID: 31666412
- DOI: 10.18097/PBMC20196505398
[Protective effect of uridine on metabolic processes in rat myocardum during its ischemia/reperfusion damage]
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 (I/RP) in rats. Ischemia for 30 min followed by reperfusion for 120 min resulted in a significant decrease in ATP and phosphocreatine (PC) content, intensification of lipid peroxidation (LPO), and inhibition of the antioxidant system (AOS) in cardiomyocytes. Uridine in a dose of 30 mg/kg, administered intravenously prior to reperfusion, had a protective effect on myocardial metabolism in the I/RP zone. It prevented the decrease of ATP and PC, limited the LPO processes, evaluated by the content of lipid hydroperoxides and conjugated dienes, and improved the AOS state by, preventing the decrease of superoxide dismutase (SOD) activity and increasing the content of reduced glutathione (GSH). The mitoKATP-channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) 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 obtained data allow us to conclude that activation of mitoKATP-channels play an important role in the mechanism of the cardioprotective effect of uridine in I/RP damage of myocardium.
Provedeno éksperimental'noe izuchenie kardioprotektornogo deĭstviia uridina – metabolicheskogo predshestvennika éndogennogo aktivatora mitokhondrial'nykh ATP-zavisimykh K+-kanalov (mitoKATP-kanalov) uridindifosfata (UDP) na modeli ishemii/reperfuzii (I/RP) miokarda u krys. Ishemiia dlitel'nost'iu 30 min s posleduiushcheĭ reperfuzieĭ v techenie 120 min privodila k znachitel'nomu umen'sheniiu soderzhaniia makroérgicheskikh soedineniĭ, intensifikatsii protsessov perekisnogo okisleniia lipidov (POL) i ugneteniiu antioksidantnoĭ sistemy (AOS) v kardiomiotsitakh. Uridin v doze 30 mg/kg, vvedennyĭ zhivotnym vnutrivenno za 5 min do reperfuzii, okazyval zashchitnoe deĭstvie na metabolizm miokarda v zone I/RP. On predotvrashchal padenie urovnia ATP i kreatinfosfata, ogranichival protsessy lipoperoksidatsii, snizhaia soderzhanie gidroperekiseĭ lipidov i dienovykh kon"iugatov, i uluchshal sostoianie AOS, prepiatstvuia padeniiu aktivnosti superoksiddismutazy i povyshaia soderzhanie vosstanovlennogo glutationa. Blokator mitoKATP-kanalov 5-gidroksidekanoat (5-GD, 5 mg/kg), vvedennyĭ vnutrivenno za 5 min do in"ektsii uridina, ustranial sposobnost' preparata sokhraniat' zapasy ATP i blokiroval ego polozhitel'nyĭ éffekt v otnoshenii ogranicheniia intensivnosti POL i aktivatsii AOS. Poluchennye dannye pozvoliaiut zakliuchit', chto v mekhanizmakh kardioprotektornogo éffekta uridina pri reperfuzionnom povrezhdenii miokarda vedushchaia rol' prinadlezhit mitoKATP-kanalam.
Keywords: ischemia/reperfusion; mitochondrial ATP-dependent K+-channels; myocardium; uridine.