[Neuroprotective Mechanisms of the Ubiquinol Action in Experimental Focal Ischemia]

Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.

Ishemicheskiĭ insul't – odno iz naibolee sotsial'no-znachimykh zabolevaniĭ, kharakterizuiushchikhsia narusheniem mozgovogo krovoobrashcheniia s ochagovym povrezhdeniem tkani golovnogo mozga i narusheniem ego funktsiĭ. Nesmotria na uspekhi sovremennoĭ farmakologii, vozmozhnosti farmakoterapii insul'ta ostaiutsia ogranichennymi, i aktual'nym iavliaetsia poisk novykh lekarstvennykh preparatov neĭroprotektornogo deĭstviia, sposobnykh predotvratit' gibel' kletok golovnogo mozga. V dannoĭ rabote provedeno izuchenie neĭroprotektornoĭ aktivnosti ubikhinola v sostave innovatsionnoĭ formy na modeli neobratimoĭ 24 ch ishemii golovnogo mozga u krys s otsenkoĭ mekhanizmov ego neĭroprotektornogo deĭstviia. Pri vnutrivennom vvedenii v doze 30 mg/kg v ostrom periode 24 ch neobratimoĭ fokal'noĭ ishemii golovnogo mozga ubikhinol okazyval priamoe neĭroprotektornoe deĭstvie, kharakterizuiushcheesia umen'sheniem ob"ema ochaga nekroza tkani golovnogo mozga. Zashchitnyĭ éffekt ubikhinola obuslovlen sposobnost'iu prepiatstvovat' razvitiiu okislitel'nogo stressa za schet priamogo antiradikal'nogo deĭstviia putem predotvrashcheniia rosta lipidnykh gidroperekiseĭ v tkani mozga, prilezhashcheĭ k ochagu nekroza, snizheniia skorosti okisleniia lipidov v plazme krovi na fone povysheniia obshcheĭ antioksidantnoĭ aktivnosti kak v mozge, tak i krovi éksperimental'nykh zhivotnykh. V éksperimentakh in vitro pokazana sposobnost' ubikhinola predotvrashchat' gibel' neĭronov pervichnoĭ kul'tury kory bol'shikh polushariĭ golovnogo mozga krysy v usloviiakh 4 ch gliukozo-kislorodnoĭ deprivatsii s 20 ch reoksigenatsieĭ.

Keywords: antioxidants; focal cerebral ischemia; neuroprotection; ubiquinol.