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The aim of the study. To evaluate the effect of succinic acid derivatives on changes of mitochondrial function in rats under cerebral ischemia conditions. Materials and methods. In this work, the effect of succinic acid, ethylmethylhydroxypyridine succinate, and acetylaminosuccinic acid at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg (per os) on the change of the neuronal mitochondria function was studied. Cerebral ischemia was reproduced by the Tamura method. The following parameters were evaluated: changes in aerobic/anaerobic metabolism, mitochondrial membrane potential, the opening rate of the mitochondrial pore of transitional permeability and the activity of apoptotic systems. Results. During the study, it was found that the use of the test-compounds at doses of 100 mg/kg and 200 mg/kg contributed to an increase in ATP-generating activity, as well as the maximum respiration level and respiratory capacity, while accompanied by a decrease in the intensity of anaerobic metabolism reactions. Also, upon administration of the test succinic acid derivatives, an increase in the mitochondrial membrane potential and latent opening time of the mitochondrial pore transitional permeability were observed. Moreover, the activity of caspase-3 and apoptosis-inducing factor on groups treated by test objects at doses of 100 mg/kg and 200 mg/kg was significantly lower than that in untreated animals. Conclusion. The studied succinic acid derivatives contribute to the restoration of mitochondrial function in cerebral ischemia conditions, while the most effective dose can be considered to be 100 mg/kg.

The aim of the study was to assess the effect of certain derivatives of cinnamic acids on changes of the tricarboxylic acid cycle enzymes activity under experimental cerebral ischemia. Materials and methods. Brain ischemia was modeled by irreversible right-sided coagulation of the middle cerebral artery. Test compounds: 4-hydroxy-3,5-ditretbutyl cinnamic acid, coumaric, coffee, synapic, cinnamic, 4-hydroxycinnamic and ferulic acids, as well as a reference drug — succinic acid was administered at a dose of 100 mg / kg per os for 3 days after the reproduction of ischemia. Then, changes in the activity of aconitase, citrate synthase, and α-ketoglutarate dehydrogenase were evaluated in the supernatant of the brain. Results. The use of all the studied compounds and the reference drug helped to restore the activity of enzymes of the tricarboxylic acid cycle. The most pronounced results were obtained when animals were treated by 4-hydroxy-3,5-ditretbutyl cinnamic acid, against the background of which the activity of citrate synthase was higher than in animals treated by succinic, coumaric, coffee, synapic and ferulic acids by 1.53 ( p < 0.05), 1.41 ( p < 0.05), 1.4 ( p < 0.05), 1.46 ( p < 0.05) and 1.41 ( p < 0.05) times, respectively. Also, with the administration of 4-hydroxy-3,5-ditretbutyl cinnamic acid, the activity of aconitase was higher compared to rats that were administered with succinic, coumaric, coffee, synapic and ferulic acids by 2.47 ( p < 0.05), 2.49 ( p < 0.05), 3.44 ( p < 0.05), 2.59 ( p < 0.05) and 1.9 ( p < 0.05) times, respectively. Conclusion. The administration of the studied in this work cinnamic acid derivatives helps to restore the activity of citrate synthase, aconitase, and α-ketoglutarate dehydrogenase in rats under conditions of cerebral ischemia. The most pronounced changes in the activity of enzymes were obtained with the iadministration of 4-hydroxy-3,5-ditretbutyl cinnamic acid.

Nowdays it is established that ischemic brain damage like ischemic stroke is one of the leading cause of death and disability in the population that assumes relevance development of anti-ischemic drugs. The work studied the anti-hypoxic and anti-ischemic effect of 7 plant extracts. Antihypoxic activity was assessed on models of hypobaric, hypercapnic, histotoxic, hematotoxic hypoxia. Anti-ischemic activity of test-extracts was studied on the focal cerebral ischemia model. Administration of Tagetes patula, Gaillardia pulchella, Sorbaria sorbifolia, Grossularia reclinata, Ribes nigrum, Rubus caesius and Lysimachia punctata extracts contributed to the necrosis zone reduction by 56.6% (p

Background and Purpose: Ischemic stroke remains one of the leading causes of death in the population. In addition, mitochondrial dysfunction is an essential part of the pathogenesis of cerebral ischemia and is a promising pharmacotherapeutic target. Experimental Approach: the work was performed on male Wistar rats, which were simulated cerebral ischemia by irreversible occlusion of the middle cerebral artery. 4-hydroxy-3,5-di-tret-butyl cinnamic acid (25 mg/kg, 50 mg/kg and 100 mg/kg) was injected intraperitoneally for 3 days after ischemia (daily). On the 4th day of the experiment, the changes of rat’s cognitive functions in the Morris water maze test, cellular respiration processes, the activity of the mitochondrial respiratory chain complexes and citrate synthase activity, the intensity of oxidative stress and apoptosis reactions were assessed. Key Results: it was found that the administration of 4-hydroxy-3,5-di-tret-butyl cinnamic acid at doses of 25 mg/kg and 50 mg/kg practically equivalently promotes the restoration of aerobic metabolism reactions and the activity of the mitochondrial respiratory chain complexes, decrease of the intensity of oxidative stress reactions and apoptosis, as well as an increase in the activity of citrate synthase. As a result, the restoration of mitochondrial function in the hippocampal cells contributed to the restoration of the animal’s spatial memory. Conclusion and Implications: a study showed that 4-hydroxy-3,5-di-tret-butyl cinnamic acid at doses of 25 mg/kg and 50 mg/kg has a neuroprotective effect on hippocampal neurons under conditions of permanent occlusion of the middle cerebral artery, realized by restoration of mitochondrial function.

Background and objectives: To evaluate the effect of a new pyrimidine derivative on the change of mitochondrial function in experimental chronic traumatic encephalopathy. Materials and methods: The study was performed on male mice of the BALB/c line (acute toxicity was assessed) and male rats of the Wistar line, which were modeled chronic traumatic encephalopathy by the method of free fall of the load (weight 150 g from a 50 cm height). The injury to rats was reproduced once a day for 7 days. Further, cognitive functions, changes in sensorimotor deficiency, cerebral blood flow, neuron-specific enolase(NSE), S100&beta, glial fibrillary acidic protein (GFAP) (in blood serum) and &beta, amyloid, adenosine triphosphate (ATP) (in brain tissue supernatant) were evaluated. Mitochondrial respiration was also measured. Choline alfoscerate (100 mg/kg) was used as a reference drug. Results: The study found that the use of a new pyrimidine derivative contributed to the preservation of the mitochondrial respirometric function and cognitive functions in rats. In addition, against the administration of test-object marked increase in the concentration of ATP, the velocity of cerebral blood flow was 4.2 times (p &lt, 0.05) and 35.6% (p &lt, 0.05), respectively, as well as reduced concentration and GFAP, NSE, S100&beta, &beta, amyloid and sensorimotor deficit at 2.7 (p &lt, 0.05) times, 2 times (p &lt, 0.05), 2.4 times (p &lt, of 30.4% (p &lt, 0.05 and 46.5% (p &lt, 0.05), respectively. The LD50 (per os) for the test-object was 4973.56 &plusmn, 573.72 mg/kg. Conclusion: Based on the obtained data, high therapeutic efficacy and low systemic toxicity of the application are assumed 4-{2-[2-(3,4-dimethoxyphenyl)-vinyl]-6-ethyl-4-oxo-5-phenyl-4H-pyrimidine-1-Il}benzsulfamide in chronic traumatic encephalopathy.

Conducted research devoted to the study of potential mechanisms of action implementation endotelioproteсtion 4-hydroxy- 3,5-di-tretbutyl cinnamic acid in experimental conditions simulated cerebral ischemia in rats. The research found that the cerebral ischemia in rats is accompanied by the development of endothelial dysfunction, expressed in increasing the concentration of asymmetric dimethylarginine, nNOS, iNOS and PKC, as well as reducing the concentration of eNOS. Introduction of sulodexide (to a greater extent compared with thioctic acid and mexidol restores endothelial function in conditions of brain ischemia in rats. The use of 4-hydroxy-3,5-di-tretbutyl cinnamic acid helped reduce the concentration of ADMA, nNOS, iNOS and PKC on 83.9% (p >0.05), 60.6% (p >0.05), 61. 9% (p >0.05), 108.6% (p >0.05), respectively, as well as improve the content of eNOS at 114.2% (p >0.05), thereby contributing to the correction that has developed in conditions cerebral ischemia, endothelium dysfunction