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Place of publication:
a journal of neurology and psychiatry named after S.S. Korsakova, 2023, T. 123, No. 12

Summary:
Purpose of the study. To study the effect of ethyl-hydroxypyridine of the succinate (EMGPS) on the anti-Bolar effect of the non-election inhibitor of cyclooxygenase (COO) of the sodium diclofenac and selective chief-2 ethrioxib inhibitor on the models of acute visceral and somatic pain and evaluate the possibility of using EMGPS in combination with the inhibitors of the TSU for the reduction their doses with the preservation of anti -Bolar efficiency . Material and methods. The effect of EMGPS was studied with a single oral effect on anti-Bolar effects of non-steroidal anti-inflammatory drugs (NSAIDs): a non-melting inhibitor of the diclofenac sodium and selective TSOG-2-2 etrica inhibitor-on the models of acute visceral (vinegar croching test) and somatic pains (formalin tests the one Hyperalgesia with inflammation) in an experiment on mice and rats. Results. On the model of acute visceral pain in EMGPS mice (25–100 mg/kg) does not have a significant effect on its severity, but enhances the anti -Bolea effect of sodium diclofenac (0.5 mg/kg) and ethricoxib (1 mg/kg). In the formalin test in rats that simulates pain during operational cuts (injury), EMGPS (25 mg/kg) increases the severity of the anti -folly action of TSOG inhibitors (1 mg/kg) primarily due to a decrease in pain in the acute phase, due to the effect of formalin on afferent neurons . On the model of mechanical hyperalgesia in rats caused by exudative inflammation after injection of the Karraginan solution in the paw, the EMGPS enhances the effect of diclofenac to a greater extent than ethricoxib. Conclusion. The data obtained indicate the appropriateness of clinical study of the use of EMGPS in combination with NSAIDs for visceral and somatic pain in order to evaluate its ability to increase the therapeutic effect of NSAIDs. Keywords: ethylmethylhydroxypyridine succinate, non -steroidal anti -inflammatory drugs, visceral pain, somatic pain, mouse, rats.

Place of publication:
a journal of neurology and psychiatry named after S.S. Korsakova, 2022, T. 122, No. 8, Issue. 2

Summary:
Purpose of the study. The study of the role of oxidative stress in the development of disorders that occur with hemorrhagic stroke (GI), and the assessment of the influence of Mexidol on neurological and cognitive disorders with the analysis of the relationship of therapeutic effects of the drug with its antioxidant effect. Material and methods. The study was carried out on sexually mature out-and-aids weighing 260–280 g. The Gi model was created by destruction of brain tissue in the Capsula Interna with the introduction of blood damage to the place. On the 1st, 7th and 14th day after the modeling of GI in rats, death, neurological deficit (McGrow scale, a rotating rod, TVS), convulsive syndrome, violation of cognitive functions were recorded, a quantitative analysis of the indicators of oxidative stress with the assessment of TBK-active (thiobarbituric acid - TBK) products in blood plasma and homogenates of the cortex of the brain of rats. Mexidol was introduced after surgery in the first 3 days at a dose of 150 mg/kg intra-abdominal, then (from 4 to 14 days)-75 mg/kg inward. Results. Mexol in rats with GI significantly increases survival, reduces the severity of the neurological deficit on the McGROW scale (manners, paresis of 1-4 limbs, paralysis of the lower extremities, lateral position), eliminates convulsive attacks, restores violation of movement coordination (TVS) and improves training processes and improves training processes and improves learning processes and improves memory. Mexidol normalizes the concentrations of TBK-active products in the blood of animals and homogenes of the cortex of the brain of rats 1 and 7 days after the GI. Conclusion. The data obtained indicate the role of oxidative stress in the development of violations with the GI and the ability of Mexidol to weaken the neurological deficit, convulsive manifestations and cognitive disorders for GI, which limits the manifestations of oxidative stress. All this substantiates the significance of the use of Mexidol in patients with GI and determines the features of its therapeutic effects. Key words: hemorrhagic stroke, intracerebral hematoma, oxidative stress, Mexidol, neurological deficit, convulsions, cognitive disorders.

Place of publication: a journal of neurology and psychiatry named after S.S. Korsakova / vol. 120, No. 1, 2020

Resume

The purpose of the study . Studying the ability of the drug Mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats.
Material and methods. In the cerebral cortex of young (3 months; n = 216) and aging (6, 9, 12 and 15 months; n = 168), outbred rats by Western-Blot Analysis, the level of expression of cerebral mitochondriogenesis protein-markers with course use of Mexidol (20, 40, 100 mg/kg; 20 days; intra-abdominal).
Results. For the first time, it was shown that the exchange rate of Mexidol in doses of 40 and 100 mg/kg is accompanied by a dose-dependent induction of SUCNR1 sucnr1 and mitochondrial biogenesis proteins: PGC-1α transcriptional coactivator, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUFV2, SDHA, CYT B, COX2) and ATP-syntase (ATP5A) in the cerebral cortex of outbred rats of young and aging age. Mexol-dependent oven-sequences of subunits of mitochondrial enzymes and PGC-1α are noted only with the course use of the drug.
Conclusion. The data obtained indicate the ability of Mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, influence one of the key pathogenetic links in the development of disorders during aging and neurodegenerative diseases.

Keywords: aging, mitochondrial dysfunction, Mexidol, succinate receptor, cerebral mitochondria-
genesis, transcription coactivator PGC-1α

Information about the authors:
Kirova Yu.I. -https://orcid.org/0000-0002-2436-3661; E-mail: Bioenerg@mail.ru
Shakova F.M. -https://orcid.org/0000-0002-0494-2500; E-mail: shakova.fatima@yandex.ru
Germanova E.L. -https://orcid.org/0000-0003-1191-8477; E-mail: Elgerm@mail.ru
Romanova G.A. -https://orcid.org/0000-0003-0090-351x; E-mail: romanovaga@mail.ru
Voronina T.A. -https://orcid.org/0000-0001-7065-469x; voroninata38@gmail.com

How to quote:
Kirova Yu.I., Shakova F.M., Germanova E.L., Romanova G.A., Voronina T.A. The influence of Mexidol on cerebral mitochondrio-
nonse at a young age and in aging. Journal of neurology and psychiatry named after S.S. Korsakova. 2020; 120 (1): 55-62. https://doi.org/10.17116/
jnevro202012001155

Place of publication:
a journal of neurology and psychiatry named after S.S. Korsakova, 2020, T. 120, No. 4

Summary:
Purpose of the study. Studying the influence of Mexidol on cognitive and motor functions disturbed during aging, the threshold of convulsive reaction, body weight and life expectancy in the old rat smams of the Vistar line. Material and methods. In a long experiment, a violation of cognitive functions (a test of conditional reflex of passive avoidance), motor disorders (tests of a rotating rod and pulling on the crossbar), a convulsive threshold (a test of subcutaneous administration of the pentilentetrazole), an animal mass and life expectancy were evaluated in a long experiment. Mexidol in the form of a 0.15% solution that replaced drinking water, rats received 2 courses of 2 months: at the age of 18-20 and 22-24 months. The dose of Mexidol consumed by the rat was 40–75 mg/kg/day. Results. Mexol in the old rat smams of the Vistar line with prolonged course use improves training, preservation and reproduction of a memorable trace in the test of conditional reflex of passive avoidance, increases the convulsive threshold and improves muscle tone and coordination of movements disturbed during aging, and increases life expectancy. The use of Mexidol allows us to prevent a significant increase in body weight, characteristic of aging. Conclusion. Mexidol reduces the severity of the cognitive and neurological deficiency that occurs during aging in the rats of the Vistar line, increases the threshold of convulsive reaction and increases life expectancy, which is determined by its ability to influence mitochondrioogenesis and antioxidant properties. Keywords: aging, Mexidol, life expectancy, memory violation, neurological deficit, convulsive threshold.

The purpose of the study.

The study of the influence of Mexidol on the dynamics of rats of rats after light or dark deprivation on the swimming dough model with load, as well as an assessment of the state of glycolytic processes in these conditions. Material and methods. The experiment was performed in the spring on 70 rats of the Wistar line. Three groups (30 animals) were in the natural conditions of lighting. One group was not exposed to any influences. Two other groups were presented with physical activity and 30 minutes before it was administered intramuscularly either a physiological solution or Mexidol. Four other groups (40 individuals) 10 days were in the conditions of dark or light deprivation before the presentation of physical activity and received either a physiological solution or Mexidol before the test after the abolition of deprivation. The physical activity model has been chosen a method of forced swimming rats with an additional load daily for 5 days. In the blood serum, the lactate level was determined by the colorimetric method.

Results and conclusion.

Mexol increased the performance of rats in a swimming test in natural lighting conditions and with light desinghronosis, contributed to the formation of cross adaptation to physical exertion under natural lighting conditions and prolonged this condition under the conditions of desinchronosis, did not change the content of lactate in the blood of rats after physical activity in the natural conditions of lighting and dark -skinned deprivation and prevented it light deprivation.

Key words: Mexidol, light and dark deprivation, performance, lactate.

Summary:
Purpose of the study. To study the influence of the original domestic drug Mexidol on the expression of the transcription factor NRF2 in the cores of the cells of the frontal cerebral cortex with one -way occlusion of the general carotid artery. Material and methods. The work was done on 64 sexually mature rats of the Vistar line. The expression of NRF2 was determined by the immunohymic method. Results and conclusion. A single intra -Brushyne administration of Mexidol per 1 kg of body weight of the animal and its course oral administration per 1 kg of mass 3 times a day for 14 days did not affect the expression of the NRF2 factor. Unilateral occlusion of the general carotid artery increased the expression of NRF2 after 4 hours and on the 5th day after modeling occlusion. The oral administration of 100 mg of Mexidol per 1 kg of mass 3 times a day for 14 days before and after modeling ischemia increased the expression of NRF2 after 4 hours and on the 12th day compared to the norm indicators, as well as after 4 hours and on the 12th A day compared with the values ​​of the control of occlusion. Thus, it was established that Mexidol increases the expression of NRF2 in the frontal cortex of the rats of rats not in normal conditions, but with unilateral occlusion of the general carotid artery. Keywords: Mexidol, NRF2, ethylmethylhydroxypyridine succinate, ischemia, occlusion of the general carotid artery.

Place of publication:
Journal of Neurology and Psychiatry, 10, 2017

Summary:
Purpose of the study. To study the influence of Mexidol (ethylmethylhydroxypyridine of succinate) on the expression of the factor induced by hypoxia (HIF-1α), in the bark of the frontal lobe of the large hemispheres of the brain during its ischemia. Material and methods . The work was done on 64 sexually mature rats of the Vistar line. The expression of HIF-1α was determined immunohymic chemically. Results and discussion. It was established that a single intra-Brush administration of Mexidol at a dose of 120 mg/kg of mass and its course oral administration at a dose of 100 mg/kg of mass 3 times a day for 14 days does not affect the expression of the HIF-1α factor. Unilateral occlusion of the general carotid artery increases the expression of HIF-1α after 4 hours from the moment of occlusion. The oral introduction of Mexidol at a dose of 100 mg/kg of mass 3 times a day for 14 days before and after ischemia, increases the expression of HIF-1α after 4 and 12 hours compared with the norms of the norm on the 5th day compared to the values ​​of occlusion control. Thus, it was established that Mexidol increases the expression of HIF-1α in the frontal cortex of the rats of rats not in normal conditions, but with unilateral occlusion of the general carotid artery.

Place of publication:
neurology, neuropsychiatry, psychosomatics, 2017, No. 9

Summary:
The purpose of the study is a comprehensive assessment by means of pharmacinformation profiling of all possible effects of mexidol molecules, alfoseta choline, piracetam, glycine, semax in accordance with anatomical and therapy-chemical classification. Material and methods. Hemoreactomic, pharmacinformation and geronto -informational analyzes of the properties of molecules are based on a chemorectic methodology. For chemoreactic analysis, information from the databases Pubchem, HMDB and String was used; For pharmacinformation analysis - information from the international classification of ATX and a combined data selection from the TTD (Therapeutic Target Database), Supertarget, Matador (Manually Annoted Targets and Drugs Online Resource) and PDTD (Potential Drugs Database); For gerontoinformation analysis, data on the heroroprotective action of individual substances from the Pubchem database and the literature on Heroproteus from the Pubmed base, collected through the system of artificial intelligence. Results and discussion. Mexidol is characterized by a maximum set of positive effects (a drug for the treatment of central nervous system diseases, cardiovascular pathology, metabolic disorders, which has anti-inflammatory and anti-infectious properties, etc.). Mexidol and glycine predict the smallest frequencies of such side effects as itching, constipation, paresthesia, vomiting, etc. Geronto -information assessments of changes in the life expectancy of model organisms showed that Mexidol helps to increase the average life expectancy of C. Elegans (by 22.7 ± 10%) , Drosophiles (by 14.4 ± 15%) and mice (by 14.6 ± 3%, control drugs - not more than 6.1%). Conclusion. The results of the study indicate the high potential of Mexidol for use as a hero of the Heroprotector.

Place of publication:
a journal of neurology and psychiatry, 1, 2017; Ext. 2

Summary:
Purpose of the study. Comparative chemorectic analysis of the Mexidol molecule (ethylmethylhydroxypyridine succinate) with control molecules (alpha alphascerate, piracetam, glycine, semax). Material and methods . Comparisons of the chemical structure of Mexidol with molecules in the database of human metabolism and molecules in the databases of drugs. More than 40,000 compounds given in the HMDB (Human Metabolome Database) were used as a human metabolism. Results and conclusion. Hemorestom analysis showed that Mexidol can be an agonist of acetylcholine and gamut-a receptors; anti -inflammatory agent, the effects of which occur due to inhibiting the synthesis of pro -inflammatory prostaglandins; neuroprotective agent with neurotrophic properties; coagulation inhibitor; sugar -lowering and hyalipidemic agents. Mexol molecules are distinguished by a more pronounced safety profile (less impact on serotonin, dopamine and adrenergic receptors, a lower degree of interaction with potassium potatoes, Mao enzymes and p450 cytochromas). The results of modeling allow at the molecular level to clarify the mechanism of action of the Mexidol molecule.

Place of publication:
Journal of Neurology and Psychiatry, 8, 2014

Summary:
The purpose of the study is to study the penetration of Mexidol through the hematoencephalic barrier (GEB) in different parts of the brain and mitochondria of cells. Material and methods. Used the drug Mexol LLC NPK Pharmasoft (Russia). They studied the penetration of large hemispheres, cerebellum, thalamus and oblong brain into the fabric and the distribution between mitochondrial and cytoplasmic fractions of nerve cells. The concentration of Mexidol in the blood plasma and brain tissue was analyzed by the method of highly effective liquid chromatography. Results and conclusion. It was established that Mexidol penetrates through the GEB into different parts of the brain of rats. Its greatest concentration is determined in the fabric of the bark of large hemispheres. Inside the nerve cells of Mexidol is found both in the cytoplasmic and mitochondrial fractions. Keywords: Mexidol, Pharmacokinetics, Hematoencephalic Barrier, Big Hses, Mozheschok, Thalamus, Minuted Brain, Mitochondria, Highly Effective Liquid Chromatography.

Place of publication:
Bulletin of experimental biology and medicine, 2006, Appendix 1

Summary:
the influence of Mexidol in different doses in the dynamics of the development of experimental toxic hepatitis according to indicators of hydration and free radical oxidation in the blood and liver tissue has been studied. A positive and dose-dependent effect of Mexidol on the studied physicochemical processes in the blood and liver tissue in the experiment is established, its use in patients with diffusion liver diseases is theoretically substantiated. Key words: hepatology, intoxication, free radical processes, Mexidol.

Place of publication:
Bulletin of experimental biology and medicine, 2006, Appendix 1

Summary:
on the model of experimentally caused intracerebral post -traumatic hematoma (hemorrhagic stroke), rats have established that the drug Mexidol is effective at a dose of 100 mg/kg (course - 7 days). The drug statistically reliably reduced the number of neurological disorders (paresis, manners), increased animal survival, improved the processes of learning and memory of rats with hemorrhagic stroke, as well as their motor activity. Key words: Mexidol, hemorrhagic stroke, neurological status, memory

Place of publication: Farmatek magazine Special Psychiatry / Neurology / 2016

Mexidol is an original domestic drug. The article describes the history of the creation of the drug, outlines modern ideas about its pharmacokinetics (including data on the penetration of Mexidol into mitochondria, as well as its effect on the activity of cytochroma-R450 isform 3A4 and protein-conveyor glycoprotein-r) and pharmacodynamics. From a biochemical point of view, the appropriateness of the use of Mexidol with hypoxia of the brain, the development of oxidative stress, with glutamate exaytotoxicity is substantiated. The comparison of Mexidol and its generics, as well as studies proving the safety of this drug, are presented.

Keywords: Mexidol, ethylmethylhydroxypirinate, pharmacokinetics, pharmacodynamics, safety

Place of publication:
a journal of neurology and psychiatry, No. 12, 2012

Summary:
Mexidol (2-El-methyl-3-gydro Xipina Ridina Succinate)-a domestic original antioxidant and anti-hyphyxant, created at the Research Institute of Pharmacology of the RAMS in the mid-80s. Mexol consists of two related and functionally significant compounds: 2-ethyl-6-methyl-3-hydroxypyridine and amber acid. The presence of 3-hydroxypyridine in the structure of Mexidol provides a complex of its antioxidant and membranotropic effects, the ability to reduce glutamate excanitotoxicity, modulate the functioning of receptors, which fundamentally distinguishes Mexol from other preparations containing amber acid. The presence of succinate in the structure of Mexidol distinguishes it from Emoxypin and other 3-oxypyridine derivatives, since the succinate is functionally significant for many processes occurring in the body and, in particular, is a substrate for increasing energy metabolism in the cell.

Place of publication:
Pharmacate, No. 6, 2009

Summary:
The article presents viewing data on pharmacological effects and pharmacokinetics of Mexidol. Neuroprotective, anti -hypic, anti -ischemic, nootropic, anti -stress, anxiolytic, anticonvulusal, anti -alcohol, anti -anatherogenic, heroesidal action of Mexidol is considered. Particular attention is paid to the effects of Mexidol in the treatment of diseases occurring with neurodegeneration, primarily acute and chronic disorders of cerebral circulation. Information is presented about the polycomponent mechanism of action of Mexidol, the important links of which are its antioxidant, membrane effects, the ability to modulate the functioning of receptors and membrane -raised enzymes, as well as restore the neurotransmitted balance.

Year of publication: 2004

Summary:
in recent years, close attention of pharmacologists and clinicians as promising drugs that effectively regulate oxidation and peroxidation processes attracted compounds of heteroamatic phenols, in particular, 3-oxypyrin derivatives. 3-oxypyridine derivatives (3-OP) belong to the simplest heterocyclic analogues of aromatic phenols and in this regard show antioxidant and anti-radical properties. They are structural analogues of the compounds of the Vitamin B6 group (pyridoxol, pyridoxal and pyridoxamine), playing an important role in the life of the body. The synthesis and analysis of the physicochemical properties of a number of original derivatives of 3-Op was carried out by L.D. Smirnov, K.M. Dyumaev, V.I. Kuzmin, and their pharmacological study was carried out in the laboratory of psychopharmacology of the Research Institute of Pharmacology of the Russian Academy of Sciences under the guidance of a honored science figure of Professor T.A. Voronina.