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Objective: To evaluate the effect of monocarbonyl analogues of curcumin on changes in the processes of mitophagy and mitochondrial biogenesis in the cerebral cortex of rats with experimental Alzheimer's disease., Material and Methods: Alzheimer's disease was modeled in Wistar rats of both sexes by injection of β-amyloid fragments into the hippocampus of the animal. Compounds (1E, 4E)-1.5-bis (3.4.5-trimethoxyphenyl) penta-1.4-diene-3-one (AZBAX4 code) and (1E, 4E)-1.5-bis (2.4.6-trimethoxyphenyl) penta-1.4-diene-3-one (AZBAX6 code) at a dose of 20 mg/ kg (orally) and the reference drug donepezil at a dose of 50 mg/kg (orally) were administered for 30 days, after which changes in the activity of succinate dehydrogenase, cytochrome-c oxidase and citrate synthase as enzymatic biomarkers of mitochondrial biogenesis and mitophagy, respectively, were evaluated in the mitochondrial fraction of the cerebral cortex., Results: The administration of AZBAX4 and AZBAX6 compounds led to an increase in the activity of succinate dehydrogenase; cytochrome-c oxidase, as well as citrate synthase in relation to the same indicators of the group of untreated animals. The use of the analyzed compounds was equally effective in both female and male rats. At the same time, it should be noted that the analyzed compounds significantly exceeded the activity level of the reference donepezil., Conclusion: AZBAX4 and AZBAX6 contribute to an increase in the intensity of mitochondrial biogenesis and mitophagy reactions in the cerebral cortex of rats with Alzheimer's disease, which makes them potentially effective neuroprotective compounds.

Objective: To evaluate an effect of ethylmethylhydroxypyridine succinate and ethylmethylhydroxypyridine malate on changes in mitochondrial function under experimental focal cerebral ischemia., Material and Methods: Focal cerebral ischemia was modeled in Wistar rats by thermocoagulation of the middle cerebral artery. Ethylmethylhydroxypyridine succinate («Mexidol») and ethylmethylhydroxypyridine malate («Ethoxidol») were injected into the tail vein 30 minutes after ischemia simulation and then for 3 days at doses of 50 mg/kg, 100 mg/kg and 150 mg/kg. After 72 hours, changes in neurological deficits, aerobic and anaerobic respiration activity, the concentration of mitochondrial hydrogen peroxide and apoptosis-inducing factor, as well as the activity of succinate dehydrogenase and cytochrome c oxidase in brain tissue supernatants were assessed., Results: The course administration of ethylmethylhydroxypyridine succinate and ethylmethylhydroxypyridine malate dose-dependently contributed to a decrease in the concentration of mitochondrial hydrogen peroxide and apoptosis-inducing factor in the brain tissue. The restoration of mitochondrial energy function was also shown with the use of ethylmethylhydroxypyridine succinate in all studied doses, while the administration of ethylmethylhydroxypyridine malate led to the restoration of mitochondrial-dependent energy production only at higher doses (100 mg/kg and 150 mg/kg)., Conclusion: The effect of malic acid and succinic acid salts of ethylmethylhydroxypyridine on the change in the redox and apoptosis-regulating function of mitochondria does not depend on the type of anion, whereas the change in the energy function of mitochondria is associated with the salt residue included in the drug structure and its dosage.

Objective: To evaluate the effect of ten pyrimidine-4-H1-OH derivatives on the change in the activity of mitochondrial respiratory chain complexes and tricarboxylic acid cycle enzymes in rats under experimental brain ischemia., Material and Methods: Cerebral ischemia in rats was modeled by irreversible occlusion of the middle cerebral artery. Two hundred and sixty male Wistar rats were administered studied compounds at a dose of 50 mg/kg (orally) and the reference - L-carnitine at a dose of 200 mg/kg (orally) for 72 hours after ischemia modeling (once a day). The activity of mitochondrial complexes (I, II, IV and V) was evaluated by the respirometric method. The activity of complex III and the enzymes of the tricarboxylic acid cycle (aconitase, citrate synthase, α-ketoglutarate dehydrogenase) was evaluated by spectrophotometric method. The analysis was performed in the mitochondrial fraction of the animal brain., Results: The use of pyrimidine-4-H1-OH derivatives containing a conjugated double bond and substituted phenol in the side chain, equally with the reference, contributed to the restoration of the activity of respiratory complexes and enzymes of the tricarboxylic acid cycle. The use of the remaining test compounds did not have a significant effect on the change in the estimated indicators., Conclusion: It is possible to assume the relevance of further study of pyrimidine-4-H1-OH derivatives as neuroprotective agents of metabolic action.

It was studied the effect of two natural compounds with polyphenol structure, green tea polyphenols (Sigma-Aldrich) and catechol hydrate (Sigma-Aldrich) in a dose of 100 mg/kg, on the vasodilating function of endothelium in brain vessels of rats with model ischemic damage. The focal ischemia was modeled by occlusion of the right middle cerebral artery. The vasodilating function of endothelium was estimated from NO synthesis modification determined by means of the Doppler sonography technique. It was established that at the focal brain ischemia leads to the pronounced endothelial dysfunction that is confirmed by the suppressed reactivity of brain vessels to the action of a vasodilating factor (acetylcholine, Ach) and by development of the L-arginine paradox phenomenon. Upon the treatment with polyphenolic compounds studied, the ability of brain vessels to vasodilatation upon ACh introduction is retained. The observed blood flow enhancement (relative to negative control group) in response to the introduction of L-arginine significantly decreases upon the administration of green tea polyphenols and catechol hydrate (by a factor of 3.15 and 2.29, respectively). This result, in turn, gives grounds to assume that the polyphenolic compounds studied possess endothelium protecting properties.