The article shows that the treckresan BAA derivative triastin can be recocorrected for the immunocorrection of women of the menopause with a diagnosis of breast cancer under the control of determining the concentration of serum iron- containing indicator proteins (lactoferrin and ferritin). Results from a study of lactoferrin and ferritin levels in menopausal women diagnosed with breast cancer when triastine was prescribed are shown. It was found that in the main group, the use of triastine in addition to the main course of treatment caused an earlier (by 7-10 days) concentration of LF — from 401,22±27,58 до 4089,32±119,04 ng/ml and F — from 29,1±1,5 ng/ml до 494,30±13,6 ng/ml, compared with the control group — 1295,37±28,61 ng/ml и 288,59±15,5 ng/ml, respectively.
The antiradical properties and biological activity of carnitine 2-ethyl-6-methyl-3-hydroxypyridine (СP) are investigated. The drug has strong antiradical activity. In the concentration range 10–6–10–9 M, CP prevents the activation of lipid peroxidation in the membranes of the liver mitochondria of mice incubated in a hypotonic medium. Such incubation causes a change in the fatty acid (FA) composition of the lipid component of mitochondrial membranes: the total relative percentage of 18:2ω6, 18:1ω9, and 22:6ω3 of the main FAs that make up cardiolipin decreased by 8.1
It was revealed that under the influence of the dietary supplement triastin, which includes trekrezan — tris-(2- hydroxyethyl)-ammonium-o-cresoxy-acetate andvarious additional components, prevents the consequences of excessive physicaloverload of the girls’ body in conditions of sports training. A comparative analysis of theeffects of dietary supplements showed that after the completion of courses of taking bothtrekrezan (analogue) and triastine, such indicators as MIC, Astrand Index, MET, DP SAO W 3 min VEM, BP recovery time, time of VEM, characterizing — stenting to physical activity, undergo statistically significant changes. The analysis of adaptive rearrangements under the influence of the biologically active additives studied by usallows us to substantiate a more effective system of complex influence in order to improvethe adaptation processes. The data obtained allow us to formulate a number of tasks forconducting systematic studies of the effects of triastine and similar dietary supplements.
The biological activity of 2-ethyl-6-methyl-3-hydroxypyridine carnitinate was studied. This substance exhibited high antiradical and antioxidant activity. It could indicate that 2-ethyl-6-methyl-3-hydroxypyridine carnitinate might have the ability to modulate stress-related alterations. The aim of this study was to examine the results supporting antistress property of this drug using a model of acute hypobaric hypoxia. Acute exposure to hypobaric hypoxia increased the rate of lipid peroxidation by 2.3 times, leading to changes in the content of C18 and C20 fatty acids in mitochondrial membranes: the double bond index of C18 fatty acids decreased by 18.2%, the content of 20:3ω3, 20: 2ω6 and 20:1ω9 dropped by 13%, 80% and 33%, respectively. These changes were accompanied by changes in the bioenergetic characteristics of mitochondria. The maximum rates of NAD-dependent substrate oxidation decreased by 28–35%. Administration of 2-ethyl-6methyl-3-hydroxypyridine carnitinate (10–6 mol/kg) to animals for 5 days suppressed lipid peroxidation, prevented changes in fatty acids composition of mitochondrial membranes, and, consequently, alterations in mitochondrial bioenergetics what most likely determined the anti-stress properties of the drug: 3.5–4.0-fold increase in life expectancy and 12–40% increase in the survival rate of mice under various types of hypoxia. The preparation was also able to enhance wheat seed germination and seedlings growth.
It is established that in the main group trekrezan application in addition to basic chemotherapy, caused earlier (for 7-10 days) increase in concentration of LF — from 396.32±24.82 to 4069.32±114.06 ng/ml and F — from 26.2±1.8 ng/ml to 439.47±16.3 ng/ml, in comparison with group of control — 1335.41±39.71 ng/ml and 279.47±14.3 ng/ml, respectively. At the same time, classical clinical effectiveness indicators (concentration of total protein, urea, hemoglobin, erythrocytes, leukocytes and blood lymphocytes) were normalized in the main group of patients.
The effect of the biologically active additive «Astragerm» on the activity of PGC-1-alpha was studied. The activating effect of astragerm on the expression of PGC-1-alpha in the «in vivo» system in rat muscle tissues was shown. Methods for quantitative assessment of mitochondria in tissues and analysis of the expression of genes included in the cascades of regulatory processes of energy metabolism were applied. Coordinated stimulation of tryptophanyl-tRNA synthetase gene expression, its non-canonical activity in the synthesis of the second messenger Ap3A, and expression of the PGC-1 alpha gene in «in vivo» systems under the action of astragerm was found, which indicates the unity of the mechanisms of energy regulation with the functions of protein synthesis and nonspecific immunity.
The problem of cardiovascular diseases, for example, atherosclerosis, justifies any attempts to identify the mechanisms of not only their formation, but also prevention and treatment, in particular with the use of drugs. In this regard, the purpose of the work was to study the possibility of using the dietary supplement Trekrevit during the treatment of patients with atherosclerosis with simvastatin. 45 men aged 22 to 35 years with signs of carotid artery sclerosis were examined. Patients of the main group, in addition to simvastatin, received Trekrevit for 10 months. It has been established that the addition of basic therapy with the dietary supplement trekrevit causes significant improvements in the characteristics of the walls of the carotid arteries in patients. It is also important that a previously unknown property of trekrevit has been established - to enhance and prolong the effect of simvastatin. This indicates the high effectiveness of combined treatment of patients with atherosclerosis.
The review article systematizes literature data on the possibilities of treatment with the help of representatives of a new class of chemical compounds — protatranes, liver lesions. It has been shown that the regenerative properties of the liver can be stimulated by silatranes — organosilicon esters of triethanolamine having a pentacoordinated structure, and trekrezan — the precursor of the entire class of protatranes. It has been shown that the use of protatranes for the correction of liver lesions stimulates the mitotic activity of hepatocytes, thus exerting a hepatoprotective effect.
The possibility of using the NO sodium μ2-dithiosulfato-tetranitrosyldiferrate tetrahydrate (TNIC-thio) as a drug preventing mitochondrial dysfunction under stress was studied. The properties of TNIC-thio were studied on the mitochondria of 5-day-old etiolated pea seedlings. The functional state of mitochondria was determined under conditions of heat shock (HS) and treatment of seedlings with TNIC-thio. Heat shock activated lipid peroxidation and led to swelling of mitochondria and changes in the content of C18 fatty acids (FAs): the C18 FA unsaturation index in mitochondrial membranes decreased from 1.42 ± 0.01 to 1.22 ± 0.01. Changes also took place in the C20 FA content: the 20:3ω6 content decreased by almost 43.6%, and the 20:0 content decreased by 1.3 times. The change in the pool of unsaturated FAs affected the bioenergetic characteristics of mitochondria: an almost 1.5-fold drop in the rates of oxidation of NAD-dependent oxidation substrates was shown. Treatment of pea seeds with 10 –6 M TNIC-thio was accompanied by prevention of lipid peroxidation (LPO), prevention of changes in the composition of FA membranes and mitochondrial morphology, and restoration of the bioenergetic characteristics of these organelles. The drug could help maintain the functional state of mitochondria under stress by preventing LPO. It perhaps resulted in the preservation of the efficiency of energy processes in the cell, which probably increased the organism’s resistance to changing environmental conditions.
New factors contributing to the processes of hormesis involving the peroxisome activator receptor coactivator 1 alpha gene (PGC-1α) and linking the mechanisms of energy regulation with the functions of protein synthesis were studied. Coordinated stimulation of the expression of the tryptophanyl-tRNA synthetase gene, its activity in the synthesis of the tertiary messenger aP3A and the expression of the PGC-1α gene in in vivo and in vitro systems, under the action of the immunostimulating and adaptogenic drug Trekrezan, was shown. It has been suggested that PGC—1α is a promising target for the therapeutic effect of drugs stimulating gene activity.
The data showing on an example only of one scientific school potential of a domestic chemic-pharmaceutical science are resulted. It is marked. Presence of two mainstreams — creation of original domestic preparations and food additives, and also development of medicines-generics taking place in Irkutsk institute of chemistry of the Russian Academy of Science. Affirms, that development of these most perspective directions keeps on enthusiasm devoted to the business and school experts of the highest class. It is recommended to integrate efforts of all experts within the limits of RAS.
Surveyed men aged 30 to 50 years. All patients received basic therapy with Enalapril 10 mg per day. Patients with AH, in addition to basic therapy, received Trekrezan in a dose of 300 mg / day for 21 days of the 2nd course for 6 months. The parameters of cardiac hemodynamics and psychophysiological state of patients with hypertension improved under the influence of Trekrezan.
28 young men aged 18 to 21 were examined. Main group received Trekrezan in a doze of 600 mg/day within 3 months. Trekrezan improved exchange parameters intimate hemodynamic and mental state with hypernension.
На моделях острой гипобарической гипоксии и острого алкогольного отравления исследованы антистрессовые свойства природного полифенола ресвератрола. Острая гипобарическая гипоксия и острое алкогольное отравление приводили к росту интенсивности перекисного окисления липидов в мембранах митохондрий печени мышей. Активация перекисного окисления липидов сопровождалась набуханием и изменениями в содержании жирных кислот С18 и С20-22 в составе общей липидной фракции мембран митохондрий. Индекс ненасыщенности С18-жирных кислот снижался на 7.5% (с 1.69 ± 0.01 до 1.52 ± 0.01. При этом соотношение (20:3ω6 + 20:5ω3)/22:6ω3 для жирных кислот в условиях острой гипобарической гипоксии уменьшалось с 0.23 ± 0.02 до 0.13 ± 0.01, что свидетельствовало о снижении метаболизма в эйкозаноидном цикле. Введение животным в течение пяти суток 210-5 моль/кг ресвератрола предотвращало изменения жирнокислотного состава, активацию перекисного окисления липидов и набухание митохондрий, что влияло на физиологические показатели. Предполагается, что адаптогенные свойства ресвератрола могут быть обусловлены предотвращением перекисного окисления липидов в мембранах митохондрий, что, вероятно, отражается на функциональном состоянии этих органелл, способствуя сохранению энергетического метаболизма клетки в условиях стресса.
The previously unknown ability of 2-(germatran-1-yloxy)ethylamine to affect the activity of alkaline phospholipase A2 was studied. Daily administration of an aqueous solution of 2-(germatran-1-yloxy)ethylamine for 2 months in an active substance dose of 10 mg per kg of animal body weight resulted in inhibition of the total activity of the alkaline phospholipase A2 of mononuclear cells. The results of the study can be used to correct the lipid metabolism in the development of hyperlipidemic disorders. This may extend the scope of applicability of the studied compound and lead to development of new pharmacological agents based on 2-(germatran-1-yloxy)ethylamine for the prevention and suppression of hyperlipidemias.
The intramuscular administration of the complex of tris(2-hydroxyethyl)amine with zinc bis[(2-methylphenoxy)acetate] (Zitrimin), as an aqueous solution in a dose of 10 mg (kg of animal weight) −1 for 2 months decreases activity of lysosomal lipolytic hydrolase (EC 3.1.1), cholesterol esterase (EC 3.1.1.13). Hence, the previously unknown feature of Zitrimin, that is, the ability to inhibit cholesterol esterase, attests to both structural and functional disorders of subcellular structures during development of atherosclerosis. The agents active towards such reactions can be useful in this case. Owing to the new properties, Zitrimin can be used to increase the vascular system stability to cholesterol during the atherosclerotic process. This expands the scope of applicability of this compound and gives prospects for development of new Zitrimin-based drugs for preventing the atherosclerotic vascular changes.
The previously unknown ability of Zitrimin, the complex of tris(2-hydroxyethyl)amine with zinc (ii) bis(2-methylphenoxyacetate), to affect the activity of acid lipase of the aortic intima was studied. Daily administration of an aqueous solution of the tris(2-hydroxyethyl)amine complex with zinc bis(2-methylphenoxyacetate) in a dose of 10 mg kg −1 for 3 months to rabbilts with experimental atherosclerosis was found to decrease the cholesterol and total lipid levels in the aortic tissue and to decrease the degree of aortic damage with atherosclerotic plaques. According to the results of enzymatic analysis, development of atherosclerosis is accompanied by 68% increase in the activity of acid lipase in the intima of the aorta compared to the control.
It was established that the administration of an aqueous solution of bis(µ-tartrato)di(μ-hydroxy) germanate (IV) triethanolammonium to animals daily for 2 months at a dose of the active substance of 10 mg/kg of the animal’s weight leads to inhibition of the total activity of the alkaline phospholipase A2 of mononuclear cells. The results of the study can be used to correct lipid metabolism in the development of disorders in hyperlipidemia. This makes it possible to expand the scope of use of the studied substance and create new pharmaceuticals based on bis(µ-tartrato)di(μ-hydroxy) germanate (IV) triethanolammonium prevent and inhibit the development of hyperlipidemia.