Energotropic effect of succinate-containing derivatives of 3-hydroxypyridine.

Succinate-containing derivatives of 3-hydroxypyridine, mexidol and proxypin, serve as succinate donors for the respiratory chain and contribute to activation of the succinate oxidase pathway of oxidation. Under conditions of hypoxia, these changes promote recovery of aerobic energy production, normalization of intracellular ATP concentration, and development of the antihypoxic effect. Succinate-free analogues of the test compounds exhibit no such properties. Both agents are considered as energotropic substances. The specific effect of these compounds is manifested in direct interaction with the respiratory chain and normalization of ATP synthesis under conditions of hypoxia/ischemia. The test compounds can be used for the correction of energy metabolism disorders during acute oxygen deficiency. Moreover, they can be used for the treatment of associated functional disturbances.

[Effect of occlusive cerebral ischemia on functional status of the internal organs]. / Vliianie okkliuzionnoi ishemii mozga na funktsional'noe sostoianie vnutrennikh organov.

Biochemical parameters characterizing visceral functions were measured in the plasma of rats with brain ischemia induced by double occlusion of the carotid arteries. Functional insufficiency of the viscera is gradually forming in the course of occlusive ischemia of the brain. Functional insufficiency of the liver was observed in animals with severe neurological deficiency and subsequent lethal outcome. In rats resistant to ischemia, visceral dysfunctions develop in a certain succession, starting from the pancreas and followed by the myocardium, liver, and kidneys.

[Brain bioenergetic parameters in rats with varying resistance to hypoxia]. / Bioénergeticheskie parametry mozga krys s raznoi rezistentnost'iu k gipoksii.

Spontaneous electrical activity, adenyl nucleotides' and cytochromes' contents, activity of respiratory chain enzymes complex in brain slices, homogenate and isolated mitochondria of rats, preliminary divided into non-resistant (NR) and high resistant (HR) animals by their sensitivity to hypobaric hypoxia have been investigated. It has been shown that in HR animals brain slices high resistant to hypoxia neurons and in NR brain slices non-resistant neurons predominate. ATP content and energetic charge in the HR animals brain slice were maintained at more high level than in NR. The reduction of NAD-depended way of oxidation in low pO2 conditions was greater in brain of NR than in HR animals. Activity of NADH-cytochrome C reductase (rotenon-sensitive) and Km for NADH in HR brain was more higher in the comparison with NR. These data indicate the main role of NADH-oxidase way in the formation of the individual brain resistance to hypoxia.

[The effect of the new nonsteroidal anti-inflammatory agent glucamine on oxidative phosphorylation processes]. / Vliianie novogo nesteroidnogo protivovospalitel'nogo sredstva gliukamina na protsessy okislitel'nogo fosforilirovaniia.

A study was made of the action of the nonsteroidal antiinflammatory agent glucamin on the processes of oxidation and phosphorylation (OP) in isolated mitochondria of the liver. It has been established that glucamin does not exhibit the properties of a separator in the explored concentrations (10(-2)-10(-7) M). Unlike the standard drug voltaren that separates OP processes, it slightly enhances interaction of liver mitochondria which oxidize NAD-dependent substrates. The effect of voltaren is dose-dependent, being pronounced to a greater measure when succinate is applied as a substrate of mitochondria oxidation.

[The correction of energy metabolism disorders in hypoxia by using vitamin K]. / Korrektsiia narushenii énergeticheskogo obmena pri gipoksii s pomoshch'iu vitamina K.

A study was made of the possibility of correcting respiratory chain function disorders in hypoxia by means of the naphthoquinone derivative vitamin K3. The antihypoxic activity of that compound is defined by its donor-acceptor properties and its capability to shunt the electron flow from NADH to CoQ. The effect is more pronounced in the tissues that oxidize mostly the NAD-dependent substrates which is related to rapid inactivation of the given enzymatic complex under hypoxia and correlates with low resistance of the cell using the NADH-oxidase pathway of oxidizing energy substrates to oxygen deficiency.

[Features of oxidative phosphorylation in brain mitochondria of rats with different sensitivity to oxygen insufficiency]. / Osobennosti okislitel'nogo fosforilovaniia v mitokhondriiakh mozga krys s razlichnoi chuvstvitel'nost'iu k kislorodnoi nedostatochnosti.

Oxidative phosphorylation parameters have been investigated in the isolated brain mitochondria of rats preliminary divided into non-resistant (NR) and high-resistant (HR) animals by their sensitivity to hypobaric hypoxia. During the NAD-dependent substrates oxidation it was shown that the identical effectiveness of the respiratory chain function in both groups of animals was reached at more tension of the oxidative processes. It has been established that at the identical effectiveness of the succinate oxidation by the brain mitochondria in both groups of animals compensatory potentialities of the succinate-oxidase pathway of oxidation is higher in the brain of the NR to hypoxia animals. It has been shown the regulated influence of the NAD-dependent pathway of oxidation activity on the succinate-oxidase site of respiratory chain. This influence is more expressed in the brain mitochondria of the NR animals that in the HR animals.