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8Antioxidant properties of remaxol in the conditions of cold stress
Dorovskikh V.A., Li O.N., Dorovskikh V.Y., ShtarbergM.A., SimonovaN.V., AnokhinaR. A., Kodintsev V. V.
Amur State Medical Academy, Department of Pharmacology, Blagoveshchensk, Russia
Summary:The results of the research focused on the crucial issue - protecting the body from stress and ecologically unfavorable environmental factors. The possibility of correction of free radical oxidation of lipid membranes by introducing remaksola. The effectiveness of the study medication at improving the body's resistance to stress conditions. Studied the antioxidant properties of remaksola in cold exposure. Clinical chemistry blood laboratory animals showed that the use of remaksola when exposed to low body temperature reduces the intensity of lipid peroxidation of membranes on increased activity of the main components of the antioxidant system of the body.
Keywords antioxidants, remaxol, cold stress, lipid peroxidation, experiment.
Hypoxia accompanies almost all tissue damage and disrupting the transfer of electrons leads to the uncoupling of oxidative phosphorylation and ATP synthesis violation against the enhanced decomposition of phospholipids and proteins, leading to the destruction of cellular structures, increasing the concentration of unsaturated fatty acids and lipid peroxidation. According to the uniformity of the body's response to hypoxia can be compared stressor damage. One of the triggering mechanisms of cellular response to hypoxia is to initiate the production of erythropoietin, which plays an important role in the formation mechanisms of transport of O2 in blood, forming a large number of red blood cells, the coordination mechanisms of pulmonary ventilation and cardiac output, O2 diffusion barriers, control of the local microcirculation and tissue changes the affinity of hemoglobin for oxygen.
Cold exposure, as a stressor, resulting in an increase in heat on the background of reducing the synthesis of ATP, which is the basis for the formation of tissue hypoxia, acidosis, accumulation of lipid peroxidation products. Therefore, an important aspect in the regulation of the effects of low temperatures on the body is the appointment Antihypoxanth drugs, stimulants, gene-mediated initiation of erythropoietin production, antioxidant drugs. Unfortunately, reducing the damaging effect of cold on the cell membrane and the formation of lipid peroxidation products, these drugs significantly reduce the time of cold adaptation. A promising direction in the correction of cold exposure is, in our opinion, the use of drugs based on succinic acid as the oxidation of the latter occupies an important place in the "output" of the energy of the Krebs cycle through the pronounced effect of succinate on a reverse electron transport in the mitochondrial ATPase, which in turn turn, adjusts the rate of phosphorylation.
Scientific and technological pharmaceutical company "Polisan" developed, and clinical bases of the Department of Anesthesiology and Intensive Care of the St. Petersburg Medical Academy of Postgraduate Education subjected to clinical testing various modifications preparations containing succinic acid: reamberin, remaksol, cytoflavin and others, opening prospects for the regulation of various types of stress effects, including cold. Part of the polyionic infusion of the drug "Remaksol" succinic acid - Xia is a product of the fifth and sixth substrate reactions of the Krebs cycle, performs control functions of living systems, has a powerful energy products, hypoxic, cardioprotective, disintoxicational action demonstrates ruet unusually high therapeutic effect in the presence of pathological process strengthens the processes of aerobic glycolysis and reduces the degree of oxidative processes in the Central Committee.
Materialsandmethods:
The experiment was carried out on white mongrel male rats weighing 150-180 g for 21 days. The animals were divided into 3 groups of 30 rats each: Group 1 - intact, the animals in this group were kept in standard vivarium conditions, group 2 - control, the animals were exposed to cold (-150C) in klimatokamere «Fentron» for 3 hours daily, 3 group - experimental animals just before cooling for 21 days remaksol intraperitoneally administered 100 mg / kg. The study was conducted at the same time in all groups for 21 days, animals were slaughtered by decapitation at 7, 14, 21 days of the experiment. Intensity of peroxidation was assessed by examining the content of lipid hydroperoxide, conjugated diene, malondialdehyde in plasma of animals and the activity of the main components of the AOC - ceruloplasmin and vitamin E. Statistical analysis of the results was performed using the parametric test «t» Student.
Theresultsofthestudyshowed that remaxol stabilizes lipid peroxidation in an experimental model of cold, it is confirmed by a significant decrease in the content of lipid peroxidation products: lipid hydroperoxide by 17%, 25%, 15% at 7, 14 and 21 of the experiment, respectively, conjugated diene by 23%, 29% and 24%, MDA by 19%, 30% and 22%.
Investigation of activity of the main components EPA has shown that administering remaxola ceruloplasmin level increases by 29%, 45%, 36% on days 7, 14 and 21 respectively of the experiment. The content of vitamin E when used in the experiment remaksola significantly increased by 19% by the end of the first week of the study by 16% - the end of the second 19% and - the end of the third. In turn, the investigation of the activity of antioxidant enzymes enabled state improving catalase 3%, 3% and 7%, 7, 14 and 21, respectively, and glucose-6-phosphate 1%, 15%, 12%, but the difference in these indicators were not significant.
Thus, the content of the main components of EPA (ceruloplasmin and vitamin E) in the blood serum of experimental animals experi - treated remaxol 100 mg / kg i.p. and reliably indicates the antioxidant activity of the drug, which stabilizes the processes of lipid peroxidation in cold stress conditions. In addition, tracing - is a direct correlation between antioxidant effect remaxola and duration of its use: the drug begins to act on the 7th day, the maximum efficiency occurs at the end of the second week of the experiment.
In general, the first to prove the effectiveness of the correction of cold stress in experimental drug administration "Remaxol", which allows us to recommend the drug for use in the treatment of diseases occurring against the backdrop of the lipid peroxidation.
Findings:
1. First experimental proof of the possibility of correction of cold stress by introducing a drug "Remaxol" containing succinic acid.
2. Intraperitoneal administration remaxola laboratory animals (rats) at a dose of 100 mg / kg decreased the intensity of lipid peroxidation of membranes induced by prolonged cold exposure, restoring the steady-state level of peroxidation products on the background of significant increase in activity of the main components of the AOC (ceruloplasmin and vitamin E).
3. Our study indicated recom - General to recommend remaxol as an antioxidant, as well as a regulator of adaptive reactions of the body at impact - action of low temperatures.
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