Method for increasing body adaptability under thermal stress

FIELD: medicine.

SUBSTANCE: cytoflavin is administered into laboratory animals (rats) daily immediately before overheating in an air laboratory thermostat at +40±1-2°C for 45 minutes. The preparation is administered intraperitoneally in a dose of 100 mg/kg of body weight for 14 days.

EFFECT: higher body adaptability by increasing antioxidant activity and reducing a rate of lipid peroxidation products accumulation with underlying thermal exposure.

4 tbl

 

The invention relates to medicine, in particular to pharmacology, and can be used to enhance the adaptive capacity of the organism in conditions of exposure to heat and to find application in experimental medicine and clinical practice. Stay in high ambient temperature leads to a decrease in the consumption of tissue oxygen reduction activity of some redox enzymes, increase the intensity of processes of lipid peroxidation of biomembranes. Hyperthermia, and other extreme environmental factors that can cause change in the biochemical status indicators, characteristic of the stress response [1].

To improve adaptive capacity of the organism used medicinal tonic action (psychostimulants-adaptogens) [2] based on multivariate influence on the processes of metabolism, an important feature is the presence of adaptogenic and antioxidant activity [3]. A method of increasing the adaptive and compensatory abilities of the body, including the course of daily sessions of 20-30 minutes of inspiration and hypercapnic hypercapneic-hypoxic gas mixtures on the basis of atmospheric air at constant nitrogen composition [4]. The disadvantage of this method is mandatory nalitch�e special equipment for cooking and inspired gas mixtures.

It is also known the use of plant preparations of Eleutherococcus dose of 1 DG/kg to facilitate thermal adaption of animals daily for 28 days immediately before the overheating of animals for 45 minutes in an incubator laboratory air TVL-(St. Petersburg) at a temperature of +40±1-2°C with the observance of adequate conditions of humidity and ventilation [1]. This technical decision taken by us as a prototype.

The object of the present invention is to expand the Arsenal of tools that enhance the adaptive capacity of the organism in thermal (oxidative) stress in terms of reducing the duration of the course correction and enhancement of persistent pharmacological effect.

The task is solved by developing a new method of enhancing the adaptive capacity of the organism in conditions of heat stress, contributing to the activation of processes of lipid peroxidation of membranes, the introduction of the drug Cytoflavin production Polysan St. Petersburg (Registration number: R-003135/01 from 21.11.2008). The drug Cytoflavin is a solution for parenteral administration (pharmacotherapeutic group: metabolic means), which is composed of the following active ingredients (per 1 l solution): succinic acid - 100 g; nicotinamide 10 g; riboxinum (�of nothin) - 20 g; Riboflavin mononucleotide - 2, intravenous drug Cytoflavin is activated aerobic metabolism of cells, increases the stability of membranes of nerve and glial cells to the effects of ischemia, improves coronary and cerebral blood flow, metabolic processes are activated in the CNS [5].

The invention consists in that in the method of increasing the adaptive capacity of the organism in conditions of heat stress, including daily administration of the drug immediately before the overheating of animals for 45 minutes in an incubator laboratory air at a temperature of +40±1-2°C with the observance of adequate conditions of humidity and ventilation, the animals administered the drug Cytoflavin intraperitoneally at a dose of 100 mg/kg for 14 days.

The implementation of the method. Experimental animals (rats or mice) in standard conditions of vivarium, daily immediately before a long period of overheating in the unit laboratory air TVL-(St. Petersburg) at a temperature of +40±1-2°C for 45 minutes with the observance of adequate conditions of humidity (45%) and ventilation administered drug Cytoflavin intraperitoneally at a dose of 100 mg/kg for 14 days.

On 15ththe day of the experiment animals were killed by decapitation.

The results were reported at sootnoshenie� the content of peroxidation products (lipid hydroperoxides, diene conjugates, malonic dialdehyde) and the main components of AOS (glucose-6-phosphate dehydrogenase, catalase, ceruloplasmin, vitamin E) in the blood and lung tissue compared to animals of control group treated with standard parametric methods using t-student criterion.

Method allowed to improve the adaptive capacity of the organism, based on the increase of antioxidant activity and reducing the degree of accumulation of products of radical character and lipid peroxides in mice and rats on the background of thermal effects, in terms of reducing the duration of the course correction of the processes of peroxidation up to 14 days in comparison with the prototype.

Investigated the content of products of lipid peroxidation (lipid hydroperoxides, diene conjugates, malonic dialdehyde) and the main components of AOS (glucose-6-phosphate dehydrogenase, catalase, ceruloplasmin, vitamin E) in plasma and lung tissue of control and experimental groups.

As a result of the conducted researches the content of lipid hydroperoxides in the blood of animals fed on the background of thermal effects of Cytoflavin, significantly lower by 18.4% compared to animals of control group (p<0.01), diene conjugates - 23.6% (p<0.01), malondialdehyde - 22.6% (p<0.01) (table 1).

Table 1The content of peroxidation products in blood plasma of rats subjected to thermal effects during administration of the drug CytoflavinGroups of animalsDigestion of lipids (nmol/ml)Diene conjugates (nmol/ml)Malonic dialdehyde (nmol/ml)The control group (heat)33,8±0,947,5±2,06,2±0,3Experimental group27,6±1,436,3±1,14,8±0,2(heat + Cytoflavin)p<0.01p<0.01P<0.01

In the blood of experimental animals, the activity of glucose-6-phosphate dehydrogenase were significantly higher by 15.4% compared with the control group rats (p<0,05), catalase - 26.9% (p<0.01), the content of ceruloplasmin by 22.8% (p<0.01), the level of vitamin E - by 23.2% (p<0.01) (table 2).

Table 2
The content of the main components of EPA in plasma of rats subjected to thermal effects during administration of the drug Cytoflavin
Groups of animalsGlucose-6-phosphatedehydrogenase (µmol NADPH l-1with-1)Catalase (µmol H2O2g-1with-1)Ceruloplasmin (mg/ml)Vitamin E (µg/ml)
The control group (heat)5,5±0,368,0±4,919,4±0,533,2±1,8
Experimental group6,5±0,293,0±2,625,1±1,543,2±0,9
(heat + Cytoflavin)p<0,05p<0.01p<0.01P<0.01

In the lung tissue of experimental group of animals the content of lipid hydroperoxides were significantly lower at 23.2% compared with the control (p<0,05), diene conjugates by 20.6% (p<0,05), malondialdehyde - 30% (p<0,001) (table 3).

Table 3
The content of peroxidation products in lung tissue of rats subjected to thermal effects during administration of the drug Cytoflavin
Groups of animalsDigestion of lipids (nmol/g)Diene conjugates (nmol/g)Malonic dialdehyde (nmol/g)
The control group (heat)68,2±3,745,2±2,66,5±0,3
Experimental group52,4±3,035,9±0,84,6±0,2
(heat + Cytoflavin)p<0,05p<0,05p<0,001

The activity of glucose-6-phosphate dehydrogenase in lung tissue of experimental group animals were significantly higher by 12.4% relative to control rats (p<0,05), catalase by 23% (p<0,05), the content of ceruloplasmin by 15% (p<0.01), the level of vitamin E by 20.6% (p<0.01) (table 4).

Table 4
The content of the main components And�With in the lung tissue of rats subjected to thermal effects during administration of the drug Cytoflavin
Groups of animalsGlucose-6-phosphatedehydrogenase (µmol NADPH g-1with-1)Catalase (µmol H2O2g-1with-1)Ceruloplasmin (mg/g)Vitamin E (µg/g)
The control group (heat)5,7±0,273,6±5,719,9±0,732,9±1,9
Experimental group6,5±0,195,6±3,823,2±0,541,4±1,1
(heat + Cytoflavin)p<0,05p<0,05p<0.01P<0.01

Thus, experimentally stabilising action of the drug Cytoflavin on the processes of lipid peroxidation in biomembranes under heat stress, based on the decrease in the content of peroxidation products and increased activity of the major components of the antioxidant system in the blood plasma and lung tissue of animals, Thu� give grounds to recommend Cytoflavin to the application to enhance adaptive capacity of the organism against the background of exposure to high temperatures.

The technical result of the invention is to expand the range of possible indications for use of the drug Cytoflavin and reducing the duration of the course correction peroxidation processes during thermal exposure up to 14 days in comparison with the prototype in terms of injecting Cytoflavin, possessing antioxidant activity, and improving adaptive capacity of the organism.

Sources of information

1. Shapovalenko N. With. Pharmacological regulation of cold and heat exposure in the experiment: author. dis. Cand. honey. Sciences. - Vladivostok, 2011. - 24 p.

2. Vengerovsky A. I. Lectures on pharmacology for physicians and pharmacists. - 3-e Izd., revised. and add. textbook. - M.: Institute of Physico-mathematical literature, 2006. - P. 387-388.

3. Simonova N. In. Herbal in correction of processes of lipid peroxidation of membranes, induced by ultraviolet irradiation: author. dis. Dr. Biol. Sciences. - Blagoveshchensk, 2012. - 46 p.

4. Agadzhanyan N. And., Mangostin J. N., Levkin S. F. a Method of increasing the adaptive and compensatory abilities of the body. - RF patent for the invention №2187341. - Posted: 20.08.2002.

5. Agathine A. S. Collection of articles on the use of the drug Cytoflavin. - St. Petersburg, 2006. - 104 p.

A method of increasing the adaptive capacity of the organism in conditions of warm�of the wind stress, includes daily administration of the drug to rats just before it is overheating within 45 minutes in an incubator laboratory air at a temperature of +40±1-2°C with the observance of adequate conditions of humidity and ventilation, characterized in that the rats administered the drug Cytoflavin intraperitoneally at a dose of 100 mg/kg for 14 days.



 

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