Cardioprotective Effect of 2-Ethyl-3-Hydroxy-6-Methylpyridinium 2-Nitroxysuccinate Against Adrenaline/Hydrocortisone-Induced Myocardial Ischemia in Mice: Modulation of Free-Radical Processes in Biomembranes and Monoamine Oxidase A Activity.

Autor: Faingold II; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia. ifaingold@mail.ru., Smolina AV; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Soldatova YV; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Poletaeva DA; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Balakina AA; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Sashenkova TE; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Allayarova UY; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Prikhodchenko TR; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Blokhina SV; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Makartseva LA; Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution 'Petrovsky National Research Centre of Surgery', 3 Tsyurupy Street, Moscow, 117418, Russia., Areshidze DA; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia.; Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution 'Petrovsky National Research Centre of Surgery', 3 Tsyurupy Street, Moscow, 117418, Russia., Varfolomeev VN; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia., Mishchenko DV; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia.; Medicinal Chemistry Research and Education Center, Moscow Region State University, 24 Vera Voloshina Street, Mytishchi, Moscow Region, 141014, Russia., Kotelnikova RA; Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences (FRC PCP MC RAS), Academician Semenov avenue 1, Chernogolovka, Moscow Region, 142432, Russia.
Jazyk: angličtina
Zdroj: Cell biochemistry and biophysics [Cell Biochem Biophys] 2024 Mar; Vol. 82 (1), pp. 235-245. Date of Electronic Publication: 2023 Dec 08.
DOI: 10.1007/s12013-023-01203-7
Abstrakt: Oxidative stress (OS) plays a key role in the development of cardiovascular diseases (CVD) in three major ways: reactive oxygen species (ROS)-induced reduction of nitric oxide (NO) bioavailability, ROS-induced inflammation and ROS-induced mitochondrial dysfunction. Oxidation of lipid molecules under the action of ROS leads to damage to membrane structures, changes the functioning of membrane-bound enzymes, and impairs membrane permeability and stability. An increase in OS results in the occurrence of endothelial dysfunction and drug tolerance, side effects, requiring discontinuation of drugs. All of these are significant problems of cardiotherapy. Therefore, the search for new alternative NO donors continues. The present research was aimed at studying the protective effect of 2-ethyl-3-hydroxy-6-methylpyridinium 2-nitroxysuccinate (NS) on the cardiovascular system on mouse myocardial ischemia (MI) model. The NS hybrid molecule includes a synthetic vitamin B6 analog 2-ethyl-3-hydroxy-6-methylpyridine (an antioxidant) and 2-nitroxysuccinic acid (a source of nitric oxide). Using the electron paramagnetic resonance (EPR) method and biochemical methods, we showed that the pronounced ability of NS to release NO is favorably combines with the capacity to prevent OS due to mechanisms such as suppression of the lipid peroxidation (LPO) process, antiradical activity and inhibition of the mitochondrial membrane-bound monoamine oxidase A (MAO-A). Using histological methods, we established that the administration of NS (10 mg/kg, i.p.) reduces the number of ischemic fibers and protects cardiomyocytes against ischemia injury. Thus, the complex protective effect allows us to consider NS as an alternative NO donor and a candidate for the development of a new pharmaceutical agent for the treatment of CVD.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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