The neurotrophic properties of magnesium comenate were studied under standard conditions and under conditions of oxidative stress. It was found that magnesium comenate has a stimulating effect on the neurotrophic processes of the spinal ganglia under normal conditions and under conditions of oxidative stress. Under standard conditions, magnesium comenate exhibits neurotrophic activity at a concentration of 0.0001 mM, under conditions of oxidative stress, magnesium comenate exhibits neurotrophic activity at concentration 0.1 mM.

The effects of prolonged (42 day) consumption of deuterium-depleted water by rats on the functional state of their central nervous system under normal conditions and under conditions of normobaric hypercapnic hypoxia have been studied. The consumption of deuterium-depleted water both under normal conditions and after exposure to oxidative stress contributed to a significant reduction in emotional anxiety in animals. Prolonged consumption of deuterium-depleted water before experimental hypoxia (amnesic factor) helped animals to maintain their ability to learn and memory at the control level, i.e., it exerted a pronounced protective antiamnesic effect. Under normal conditions, deuterium-depleted water does not affect the learning ability of animals.

The effects of prolonged (42 days) addition of deuterium-depleted water into rat’s diet on the functional state of the central nervous system in normal conditions and under conditions of normobaric hypoxia with hypercapnia were studied. It was also established that the use of deuterium-depleted water both in normal conditions and after exposure to oxidative stress contributes to a significant reduction in the emotional anxiety of animals. Prolonged use of deuterium-depleted water before hypoxic exposure (amnestic effect) helps to maintain learning and memory at the control level, i.e. it has a pronounced protective antiamnestic effect. In normal conditions, deuterium-depleted water does not affect the learning ability of animals.

The effect of deuterium-depleted water on oxidative processes in the rat brain under physiological or hypoxic conditions was studied. The results obtained by a tissue culture method that characterize the functional parameters of neurons under stress are also presented. Results on free radical processes in the rat brain tissues demonstrated that consumption of deuterium-depleted water over 2 weeks has a stress effect. The long-term consumption of deuterium-depleted water caused activation of non-specific protective systems. The effect of a saline solution prepared with deuterium-depleted water on a cerebellar tissue culture was also studied. When incubation occurred in a saline solution based on deuterium-depleted water, glucose deprivation and temperature stress (39°C) were found to result in increased cell death in the neuronal culture. The neuron death rates under physiological conditions were similar in the case of both 150 and 50 ppm deuterium. At the same time, the mitochondrial membrane potential of cerebellar neurons decreased in the deuterium-depleted medium. Thus, incubation of cerebellar neurons in the deuterium-depleted saline solution had no cytoprotective effect.

Проведено сравнительное исследование влияния коменовой кислоты и нового нейропротекторного фармакологического средства – кальциевой соли коменовой кислоты на окислительные процессы и антиоксидантную систему головного мозга в условиях иммобилизационного стрессового воздействия. Установлено, что применение коменовой кислоты и её кальциевой соли в дозе 4 мг/кг в условиях стрессового воздействия препятствует развитию окислительных процессов в головном мозге стрессированных мышей, способствует нормализации механизмов антиоксидантной защиты. При этом показатели антиоксидантной защиты (каталаза, глутатионпероксидаза, глутатионредуктаза и GSH) у этих животных практически не отличаются от таковых в контроле. В норме кальциевая соль коменовой кислоты и коменовая кислота влияния на эти показатели практически не оказывают. В условиях стресса коменат кальция вызывает более выраженное, в сравнении с коменовой кислотой, снижение активации перекисного окисления липидов.

Using the model of cultured spinal ganglia, we demonstrated high neurotrophic activity of comenic acid and its derivatives potassium comenate and calcium comenate both under normal conditions and during oxidative stress. Calcium comenate in the norm as well as potassium and calcium comenates during oxidative stress demonstrate greater neurotrophic potency than comenic acid.

This paper reports an analysis of the effects of sodium comenate on neurite growth from spinal ganglia under the conditions of hydrogen peroxide-induced oxidative stress and on the glutathione antioxidant system in the brain of mice exposed to immobilization stress. It has been demonstrated that sodium comenate at the concentrations of 0.1–0.001 mM stimulates the growth of neurites from spinal ganglia exposed to oxidative stress. The most profound stimulatory effect was observed with 0.001 mM sodium comenate. The administration of sodium comenate at doses of 1, 2, and 4 mg/kg contributed to the maintenance of the GSH content and glutathione peroxidase and glutathione reductase activities at the physiologically normal state level under stress conditions. The results of the study of neurotrophic and antioxidant effects of sodium comenate in oxidative stress suggest that this compound is a highly efficient neuroprotector.

Potassium comenate and comenic acid exhibit manifest and virtually identical antioxidant activity under conditions of hypoxia with hypercapnia. The effects of these drugs on conditioned reflex training with positive reinforcement differ significantly. Potassium comenate promotes retention of the learning capacity and memory in hypoxic rats at the level of intact control, that is, exhibits a pronounced protective antiamnestic effect, while comenic acid only facilitates training of the conditioned reflex with positive reinforcement.

Изучено влияние нового фармакологического соединения кальциевой соли коменовой кислоты (CaK) на генерацию активных форм кислорода в модельной системе ЦФЛ (цитрат фосфатный буфер с добавлением люминола), на токсичность глутамата в диссоциированных культурах нейронов мозжечка крыс, а также его влияние на ростовые процессы культивируемых нейронов спинальных ганглиев эмбрионов кур в условиях окислительного стресса в сравнении с коменовой кислотой (КК). Установлено, что CaK повышает устойчивость культивируемых нейронов мозжечка к глутаматной цитотоксичности, проявляет выраженный нейротрофический эффект — защищает нейроны спинальных ганглиев эмбрионов кур от окислительного воздействия перекиси водорода, значительно снижает содержание свободных радикалов в модельной системе ЦФЛ (на 64,6 %, p < 0,001). Антиокислительные свойства CaK практически не отличаются от КК, в тоже время максимальный нейропротекторный эффект CaK проявляется в более низких (1 и 10 мкМ), чем КК (1000 мкМ) концентрациях, а нейротрофическое действие, в отличие от КК, в более широком диапазоне концентраций: CaK — 0,01 и 0,001 мМ, КК — 0,01 мМ.

The effects of potassium comenate on functional state of CNS in mice and rats were studied in the open-field and hole-board tests under control conditions and after acute exposure to hypoxia–hypercapnia. The effects of potassium comenate on CNS were also studied in rodents subjected to propofol-induced sleep. Preliminary administration of 4 mg/kg potassium comenate for 3 days attenuated the posthypoxic changes in behavioral reactions (emotional anxiety/reactivity). The pronounced stress-protective effect of potassium comenate was observed both on days 1 and 14 after exposure to hypoxia–hypercapnia. Under normal conditions, potassium comenate moderated behavioral reactions and augmented somniferous effect of propofol. We hypothesized that the antihypoxic effect of potassium comenate is determined by its stress-protective and sedative potencies.

We studied antioxidant protective effect of comenic acid and potassium comenate in doses of 2, 4, and 8 mg/kg under conditions of oxidative stress in the brain of mice exposed to immobilization stress. Administration of potassium comenate and comenic acid in the above doses for 3 days before stress prevented the development of oxidative processes in the brain of stressed animals. The antioxidant effect of potassium comenate more pronounced.

The study demonstrated neuroprotective action of novel chemical agent, potassium salt of comenic acid, against the glutamate-induced cytotoxicity on the model of cultured cerebral neurons. Potassium comenate (0.001-1.0 mM) significantly decreased the rate of glutamateinduced neuronal death. The highest viability of the cultured neurons during postglutamate time was observed when potassium comenate was applied in a concentration of 0.1 mM.

The influence of a new substance, lithium salt of comenic acid, on the oxidative processes in the brain of animals under the conditions of acute and long combined stress has been investigated. It is established that lithium comenate (1 and 2 mg/kg) exhibits pronounced dose-dependent antioxidative stress-protective effect, which is manifested in suppression of the hyperproduction of free radicals and depression of the content of malonic dialdehyde (a secondary product of lipid peroxidation) in the brain of stressed animals. The maximum antioxidative stress protection effect under the conditions of acute and long combined stress has been observed for lithium salt ofcomenic acid in a dose of 2 mg/kg.

We studied the state of the antioxidant glutathione system ( activity of glutathione peroxidase, glutathione reductase, and content of GSH and GSSG) and the level of lipid peroxidation in the brain of newborn rats, as well as the intensity of neurite growth in the cultured spinal ganglia of these animals after prenatal treatment with lead acetate. Daily addition ( 6 mg/kg) or single addition on the 18th day of pregnancy ( 200 mg/kg) of lead acetate to food of pregnant females resulted in a considerable decrease in the activity of the glutathione system and increase in the levels of GSSG and malonic dialdehyde in the brain tissue. The lead intoxication also inhibited neurite growth in cultured ganglia. In addition, the permanent presence of lead acetate (0.02 mM) in the cultures of ganglia of intact rats on the second and third days in vitro also led to inhibition of neurite growth. The data obtained indicate that oxidative stress, which results in decreased antioxidant activity, may be one of the main mechanisms that underlie toxic injury of central and peripheral neurons after prenatal action of lead.

The influence of peptide fractions, discharged of kumys (SK) and a sour milk of Mechnikov (PMS) on some parameters of immunity experimental animal, transferred a stress is investigated. The outcomes of examinations have shown, that SK promotes correction of immune violations called by action of a stress. So the introduction SK animal one day prior to a stress renders expressed immunoregulatory an operation on a content of neutrocytes and metabolism in them, depending from Oxygenium, promotes a raise of number of T lymphocytes in a blood animal transferred a stress. The peptide fraction, discharged of a sour milk of Mechnikov (PMS) does not render essential influence on the above-stated parameters.