Method of relieving chemical liver injury of living body

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely physiology and experimental medicine, and may be used for preventing and relieving a chemical liver injury in a living body. That is ensured by an atmospheric hypoxic exposure which is started with standard 21% air oxygen to be gradually reduced to 12% at 3±0.25% a minute. That is followed by a -minute pause at 12% oxygen to be gradually increased to 30% at 3±0.25% a minute. That is followed by another 5-minute pause at 30% oxygen. Then, the oxygen content is gradually reduced to 21% at 3±0.25% a minute. The procedure is daily for 10-14 days.

EFFECT: method provides higher body adaptation ensured by the gradual variations of gas mixture oxygen.

2 tbl

 

The invention relates to physiology and regenerative veterinary medicine and medicine and can be used to eliminate chemical lesion of the liver of a living organism, as well as in research related to the study of the effect on a living organism, the effects of various physical factors.

The high sensitivity of the liver to chemical compounds is determined by several factors. First, substances which enter the body through the gastrointestinal tract, primarily, is received in the liver; thus, this is the first body standing in the way of the xenobiotic, nesorbiruyushchegosya in the internal environment of the body. Secondly, the liver is the main organ responsible for the metabolism of foreign substances. What if this biotransformation of xenobiotics is often associated with the formation of significant amounts of highly reactive intermediate products and the initiation of free-radical processes.

There is a method of physical therapy effects on a living organism passing through the skin of the animal or human electrical impulses that cause vibration subelectrode tissues (RF Patent No. 2325930, IPC A61N 1/36). The known method provides a number of positive effects on the superficial tissues of the living organism, but its effect on the internal'or the Ana is not installed.

There is a method of treatment of liver diseases of animals and humans, providing drug therapy in combination with physiotherapy impact in the form of abdominal decompression (RF Patent No. 2334499, A61G 10/02). However, it is known that medical therapy in some cases gives adverse reactions and various complications, including its combination with physiotherapy impact.

A known way to increase nonspecific adaptive capabilities of a person, characterized by exposure to hypoxic-gipertoksicheskaya gas mixtures by means of procedures, each of which consists of 6 hypoxic-gipertoksicheskaya cycles, where one cycle is a rotation normobaric hypoxic effects with a minimum of 10% oxygen content with normobaric gipertoksicheskaya impacts with maximum 30% oxygen (Patent RF №2289432, IPC AM 16/00). This method is used including to increase the resilience of the tissues of the liver, but this method is not devoid of possible negative effects of sudden changes in oxygen content in gas mixtures.

Closest to the invention, taken as a prototype, is a solution of the chemical destruction of the liver of a living organism, including the effects of breathing mixtures is (VP twerdochlib and others, "Stress damages the liver, lipid metabolism and the possible prerequisites for their prevention", issues in theoretical and clinical medicine // Collection of scientific works of scientists of the Orenburg medical Institute (Vol XXIX), Orenburg, 1994, p.122-127).

The objective of the invention is to improve the adaptive capacities of a living organism to changes in the oxygen content in gas mixtures. The technical result is achieved due to the stepless change of the oxygen content in gas mixtures.

The invention consists in achieving the mentioned technical result in the method, including the effects of breathing mixture. According to the invention spend normobaric hypoxic exposure, which started with the standard 21% oxygen content in the air and continuously reduce the oxygen content up to 12% with a rate of 3±0.25% in one minute, then give a 3-minute exposure at 12% oxygen, then infinitely increase the oxygen content up to 30% with a rate of 3±0.25% in one minute, then give a 5-minute exposure at 30% oxygen concentration, then stepless reduce the oxygen content up to 21% with a rate of 3±0,25% per minute, and the procedures carried out daily for 10-14 days.

The method is as follows

Hypoxic-GUI is toksicheskie gas mixture may be formed using a known device (Patent RF №2289432, IPC AM 16/00), equipped with a choke for regulating the rate of change of oxygen concentration in the gas mixture. Evaluation of the effectiveness of the elimination of chemical lesion of the liver of a living organism were carried out on laboratory animals, which were used Mature white rats-males line CD (Sprague-Dawley)received from SPE kennel laboratory animal fibh RAS (Pushchino), recommended in accordance with the International system of genetic standardization CRL (Steel V.O., ON the timing of exposure by modeling intoxications in Toxicological and epidemiological studies // Hygiene and sanitation. - 1996. No. 8. - P.70-72) for experimental research in the field of toxicology and pharmacology. Chemical lesion of the liver of animals was simulated in sub-chronic toxicity experiment using a mixture of hepatotropic poisons dissolved in drinking water - salt of chromium and benzene (Bianchi V., L. Celotti, G. Lanfranchi, Majone F., Marin, G., Montaldi, A., Sponza G., Tamino G., P. Venier, Zantedeschi A. et al. Genetic effects of chromium compounds. Mutat Res 117: 279-300 (1983)). Toxic load on the body of animals was calculated so that it was modeled concentration hepatotropic poisons, which occurs in real terms for a person to chemical industries. The study was conducted on 61 clinically healthy experimental animal wt is Oh 180-210 g to the beginning of the experiment. Just conducted three series of experiments, each of which was 2-3 groups of 7-8 animals. The control group consisted of 7 intact animals. In each series of experiments were evaluated as the effects of intoxication hepatotropic poisons and protective effects of adaptation of animals at different modes of oscillations in the concentration of oxygen in the breathing mixtures: from normoxia (21%) to moderate hypoxia (12%) and moderate hyperoxia (30%). Table 1 shows the distribution of animals in the experiment.

Table 1
The distribution of animals in the experiment.
SeriesGroups of experimental animalsDesignationThe number of animals in group
Series 11The group of animals treated with toxicants in 1 week1/17
2The group of animals treated with toxicants within 1 week amid adaptation to successive cycles "proposed method"1/27
3The group of animals treated with toxicants within 1 week amid adaptation to successive cycles "method-prototype1/37
Series 21The group of animals treated with toxicants in 2 weeks2/18
2The group of animals treated with toxicants within 2 weeks amid adaptation to successive cycles "proposed method"2/27
3The group of animals treated with toxicants within 2 weeks amid adaptation to successive cycles "method-prototype2/37
Series 31The group of animals treated with toxicants within 1 week after 2 weeks of adaptation to the cycles of the "proposed method"3/15
2The group of animals treated with toxicants within 2 weeks after 2-week course of adaptation to the iclam "proposed method" 3/26
ControlIntact animals7

In the first series - I group of animals consumed the solution of toxicants within one week. The second group of animals of the same series, consumed a toxic mix in the same doses in the background adaptation to fluctuations in breathing mixtures in the "proposed method". The third group in the same series group consumed a solution of toxicants in the same doses in the background adaptation mode "method prototype, applied as an intermediate control effectiveness of adaptation action.

In the second series - I group of animals consumed the solution of toxicants within two weeks. Group II in this series were subjected to intoxication simultaneously with a 2-week adaptation modes "proposed method", and group III received these toxicants in the same doses in the background of a 2-week adaptation modes "method prototype.

In the third series of the experiment group 1 animals received a solution of toxicants within 1 week after conducting a 2-week course pre-adaptation modes "proposed method", and the second group of animals consumed a toxic mixture for 2 weeks at the same dose after the performance of the 2-week course pre-adaptation modes "proposed method". Groups of experimental animals are forced to consume a toxic mixture instead of drinking water. The control group received drinking water without restrictions.

The definition of all biochemical parameters was performed using an automatic biochemical analyzer "Vitalit-1000" (Italy) using standard diagnostic kits of reagents "Cormay" (Poland), "Pliva-Lachema (Czech Republic).

As a result of prolonged exposure to toxins in the liver tissue inevitably formed damaging physiological structures, violated the biochemical processes of detoxification of xenobiotics. But, even short-term toxic effects of chemical substances lead to the violation of the natural biochemical processes prior to liver dysfunction. Initiation of free-radical processes, the binding of toxicants or their metabolites with proteins, nucleic acids and unsaturated fatty acids of cell membranes, disruption of plastic and bioenergetic processes - all of these metabolic processes in the liver proceed with participation of the relevant enzyme systems contained in hepatocytes. Their synthesis is one of the most important functions of the liver. Changes in the activity of enzymes accompanies any damage liver tissue. Organ-specific enzyme of the liver tissue is fructosamines aldolase (hereinafter TMA), activity in the blood increases in the early stages of damage to the membranes of hepatocytes when changing their viscosity and permeability. In recent years, an increasing importance in the diagnosis of liver disease and hepato-biliary tract acquires the determination of the activity of another organospecific for liver enzyme - transferase gamma-glutamic acid (hereinafter TGHK). This enzyme is important in the metabolism of amino acids in hepatocytes. In the cell, an enzyme localized in the membrane, lysosomes and cytoplasm, and membrane localization TGGC characteristic of hepatic cells with high secretory and excretory capacity. Total activity TGGC registered in the plasma, usually caused by excretion synthesized in liver enzymes and normal minor. Fermentee TGGC sharply increases at the early stages of damage of liver cells and can serve as a significant reflection of early trouble, caused by industrial toxins.

To perform the tasks of the experiment, prove toxic liver damage and adaptation of the effect of protection from the effects of toxicants in the blood serum of experimental animals was determined by the following biochemical parameters:

- fructose monophosphate-aldolase (FMA);

- transferase gamma-glutamine is islote (TGHK).

The results of determination in serum organ-specific activity of the enzymes is presented in summary table 2.

Table 2
Enzyme activity in the serum of experimental animals.
Series and groups of animalsThe activity of PMA (used)Activity TGGT (U/l)
Control0,8±0,061,64±0,06
1/12.0±0,072,08±0,09
2/11,3±0,064,87±0,05
1/21,0±0,041,48±0,06
2/20.5±0,022,45±0.08
1/32,7±0.030,78±0,04
2/31.85±0,031,08±0,05
3/11,25±0,021,66±0,09
3/21,55±0,021,92±0,2

When evaluating the results of this part of biochemical studies should pay special attention to fermentatio organ-specific enzymes MFA and TGGC in groups of animals (1/1 and 1/2)exposed intoxication mixture hepatotropic toxicants within 1 and 2 weeks. From the table it is seen that in the blood of animals these two groups have developed reliable organ-specific tissue liver hyperferritinemia.

Thus, experimentally validated a new principle of adaptation effects stepless changing oxygen level - Hypo - and hyperoxia. Adaptation mode stepless change of hypoxia and hyperoxia not only resulted in stabilization of membranes, but had a more pronounced effect than the adaptation mode of the method prototype. In addition, adaptive protection mode "proposed method" was formed much faster for 15 days, in contrast to the method prototype. When comparing methods known interval training (method prototype) and modified by us stepless adaptation effects in the "proposed method" in the experiment, it was shown that in the first case, the observed inhibition of some antioxidant enzyme systems in the liver. This fact may decree is to weak protective effect of this method on the liver cells.

When using adaptive variable effects in the "proposed method" working" continuously variable oscillating changes in the level of oxygen on both sides of normoxia, i.e. the use of infinitely recurring cycle, comprising the serial combination of moderate hypoxia and moderate hyperoxia.

Summarizing all the above, we can draw the following conclusions:

1) the effectiveness of adaptation is based on the selection conditions of its implementation, taking into account transpacificus, selecting the most sensitive organs to this effect and their adequate protection;

2) application of new types of adaptation impacts, based on the combination of continuously variable hypoxic and gipertoksicheskaya periods, allows you to increase the effectiveness of protection and reduce the time to reach the stage of long-term adaptation.

The obtained results can be used in research related to the study of the impact on the human impact of various physiotherapeutic factors for the prevention of chemical intoxication in an industrial environment and for the combined treatment of early lesions of the liver in persons working in conditions of high chemical load.

Solution chemical lesion of the liver of a living organization is mA including the effects of breathing mixture, characterized in that conduct normobaric hypoxic exposure, which started with the standard 21% oxygen content in the air and continuously reduce the oxygen content up to 12% with a rate of 3±0.25% in one minute, then give a 3-minute exposure at 12% oxygen, then infinitely increase the oxygen content up to 30% with a rate of 3±0.25% in one minute, then give a 5-minute exposure at 30% oxygen concentration, then stepless reduce the oxygen content up to 21% with a rate of 3±0,25% per minute at this procedure is carried out daily for 10-14 days.



 

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