RU2407401C2 - Dog feeding method - Google Patents

Abstract

FIELD: food industry.

SUBSTANCE: invention relates to domestic animals (in particular - dogs) feeding. The dog feeding method envisages additional introduction of selenopyran to the basic ration in an amount of 133 - 1200 mcg per 1 kg of the basic ration dry substance. The invention implementation enables dog health and life quality improvement due to optimisation of the processes of lipolysis, lipogenesis, lipid peroxidation and cholesterol metabolism.

EFFECT: invention usage enables immunogenesis stimulation (in cell and humoral forms), activation of the antioxidant-antiradical organism protection system, induction of the monooxygenase system eliminating exogenous organic and mineral xenobiotics from the organism and neutralisation of endogenously generated toxics and "refuses", reduction in concentration of lipid peroxidation products and atherogenic factors in blood as well as antiatherogenic factors concentration increase.

4 tbl, 1 ex

Description

The invention relates to the feeding of domestic animals, namely dogs.

The use of selenopyran in animal breeding methods is known in the prior art, in particular: piglets (RF patent No. 2 045200, 1995), poultry (RF patent No. 2038807, 1993), cows (RF patent No. 2212888, 2001), calves (patent RF number 2230523, 2004).

In accordance with the purpose of the invention, the method of feeding domestic animals (dogs, cats, etc.) described in patent RU 2163078 C1, 02.20.2001, providing a basic diet, can be indicated as the closest analogue.

A disadvantage of the known method of feeding dogs is that the use of even full-feed feed mixtures as the main diet does not provide for the regulation in the body of dogs of the ratio of lipolysis, lipogenesis, lipid peroxidation and cholesterol metabolism, which could help improve the health and quality of life of dogs.

In comparison with the inorganic and organic compounds of selenium widely used today, in the country and the world, selenopyran compares favorably with all existing selenium-containing preparations with a unique combination of low toxicity, metabolizability, followed by release and inclusion of selenium contained in it, and independent functional activity manifested by the molecule of selenopyran itself. Essentially, selenopyran, which entered the body, should be considered as a working prolonged form of selenium, as a metabolically active depot of selenium, with specific functions independently manifesting in the body.

Selenopyran is a broad-spectrum antioxidant, low-toxic organic compound containing selenium in an accessible, metabolizable form, a stimulator of cellular and humoral forms of immunity, an activator of antioxidant-antiradical defense systems, an adaptogenic antistress drug that induces a monoxigenase system of elimination of exogenous xenobiogenic organisms from the body and neutralization of endogenously formed toxins and “toxins” (see Galochkin V.A. New horizons of increase productivity and resistance of animals. Borovsk, 2000, p.90).

From the prior art it can be concluded: 1) selenopyran has never been used by anyone when feeding dogs; 2) when using selenopyran on other animal species, its effect on the lipid metabolism in the animal organism in general and on the ratio of cholesterol fractions, in particular, remained completely unexplored. The quality of life of animals and the degree of risk of cardiovascular diseases depend on these indicators.

Atherosclerosis is a chronic disease characterized by a specific lesion of the arteries of elastic and muscular-elastic types in the form of focal growths in their walls of connective tissue in combination with lipid infiltration of the inner membrane, which leads to organ and / or general circulatory disorders.

If atherosclerosis was previously associated with an increase in the concentration of lipids in the blood, now the term hyperlipidemia (hyperlipemia) is already gradually losing its significance and relevance of the clinical test. The concentration of total lipids and phospholipids in the blood is recognized as not quite informative criteria. Even the total concentration of cholesterol has limited value. It has already become generally accepted that it is important not the total amount of lipids of various fractions, but their ratio. The most striking integral indicator of metabolic disorders of lipoproteins is dyslipoproteinemia (DLP).

Back in the late 70s of the last century, WHO experts proposed abolishing the term hyperlipidemia and replacing it with the concept of dyslipidemia.

About half of the cholesterol in the body of omnivorous animals comes from food, and the rest of cholesterol of endogenous origin is synthesized in the liver.

Cholesterol is absolutely necessary for the synthesis of vitamin D, for the synthesis of all gonadal steroid hormones, male and female, for the synthesis of all corticosteroids, all bile acids, it is a component of all intracellular and intercellular membranes.

For health, not the total concentration of cholesterol is important, it is important to operate within the framework of the modern concept of DLP with the ratios of various fractions of lipids and cholesterols.

All modern diagnostic tests are based on the analysis of the balance (ratio) of different fractions of cholesterols - total cholesterol (cholesterol), high density lipoprotein cholesterol (HDL cholesterol), low density lipoprotein cholesterol (LDL cholesterol) and very low density lipoprotein cholesterol (cholesterol VLDL).

Currently, it is believed that indicators such as total lipids, total phospholipids, and even total cholesterol alone are asymptomatic, i.e. they do not have independent diagnostic value. They do not provide accurate diagnostic information about a specific disease, but only reflect a certain general state of lipid metabolism in the body and allow us to judge some trends, inclinations, and predispositions. Although it remains generally accepted that hypercholesterolemia is the most documented risk factor for coronary atherosclerosis.

Different variants of lipoprotein spectrum imbalance (DLP) are based on the specificity of lipoprotein metabolism. As the experience of the leading countries of the world shows, the prevention of atherosclerosis is based on this specific biochemical knowledge (for more than two decades now, the whole Western world has been fighting for low cholesterol milk, eggs, meat, etc.). It is here that people see both prevention and correction of DLP.

LDL is the most atherogenic for the following reasons. They transport about 66% of all plasma cholesterol, the cholesterol content in them can reach up to 50%. LDL along with HDL can penetrate the vascular wall through the endothelial barrier, but, unlike HDL, which is easily removed from the wall, helping to remove excess lipids, LDL is retained in it because it has selective affinity for glucose aminoglycans and smooth muscle cells. LDL is the main transport form of cholesterol for the needs of the cells of the vascular wall, and under pathological conditions it is a source of its accumulation in the vessel wall ("cholesterol plaques").

Studies of the last decade have allowed to decipher the biochemism of the pathogenesis of atherosclerosis of blood vessels. It has been established that for its development not only a violation of the spectrum and an increase in the level of blood LP are important, but the presence of modified (pathological) forms of LP is very important. The leading pathway for such a chemical transformation of drugs is the excessive peroxidation of lipids in their composition. As a result, there is a massive accumulation of cholesterol esters, the release of which into the intercellular space of the intima initiates the formation of atherosclerotic plaques.

The oxidation of low density lipoproteins is associated by most researchers with the development of atherosclerosis. Circulating monocytes destroy LDL molecules modified with active oxygen radicals with very high affinity; it is more than 10 times higher than with native LDL. These monocytes / macrophages penetrate into the subendothelial space and cause the first stage of atherogenesis, the so-called "fat strip", preceding the "cholesterol plaques". Antioxidants interrupt this process and effectively reduce the risk of occurrence, prevent and / or cure cardiovascular diseases. It was on this physiological effect of selenopyran that a calculation was made in the starting working hypothesis of the developed method of feeding dogs.

The mechanisms by which antioxidants inhibit LDL oxidation are still not fully understood. However, it is believed that they reduce the formation of free radicals, protect the LDL-α-tocopherol complex from oxidation, restore the oxidized LDL-α-tocopherol complex, and / or neutralize metal ions involved in oxidative reactions.

The close relationship between selenium and vitamin E known in the art indicates the high potential ability of selenopyran to prevent the peroxidation of low-density lipids and interrupt the first stage of atherogenesis. Therefore, selenopyran can be attributed to coronary protective factors.

It has now been proven that there is a direct relationship between the existing pathology, or the risk of atherosclerosis, and VLDL cholesterol and LDL cholesterol. These fractions are called atherogenic factors (contributing to the development of atherosclerosis). On the other hand, there is always an inverse relationship between the concentration of HDL cholesterol and atherosclerosis (this is an anti-atherogenic factor).

Thus, monitoring the ratio of the concentration of various fractions of cholesterol in the blood of animals is necessary to characterize the degree of functional activity of the metabolic systems of the body to prevent and neutralize metabolic situations associated with the risk of developing atherosclerosis, hypertension and other forms of cardiovascular failure.

The present invention is aimed at solving the technical problem of ensuring the regulation in the body of dogs of the ratio of lipolysis, lipogenesis, lipid peroxidation and cholesterol metabolism to improve the health and quality of life of dogs, achieved by optimizing the ratio of these processes.

The problem is solved in that the method of feeding dogs, according to the invention, includes the additional introduction of selenopyran into the main diet in an amount of from 133 to 1200 μg per kilogram of dry matter of the main diet.

The choice of the upper and lower limits of the content of selenopyran in the main diet of dogs (from 133 to 1200 μg per kilogram of dry matter of the main diet) was determined: 1) based on in-depth preliminary studies in vitro in the methyl oleate system to inhibit peroxidation reactions of selenopyran; 2) based on an analysis of the experience of using selenopyran in feeding various types of farm animals, poultry and cats; 3) on the basis of currently accepted standards for selenium nutrition, when calculated on the content of selenium in selenopyran (selenium is 25% of the mass of selenopyran), a decrease in the administered dose less than the lower used by us does not cause a biological effect, and an increase in the dose above the upper limit used by us is associated with a risk the development of hyperselenosis.

The advantage of the proposed method of feeding dogs over traditional ones is that when it is used, it stimulates immunogenesis (its cellular and humoral forms), activates the antioxidant-antiradical defense systems of the body, induces the monooxygenase system to eliminate exogenous xenobiotics of organic and mineral nature from the body and neutralize endogenously formed toxins and "slag", a decrease in the concentration in the blood of lipid peroxidation products, a decrease in rovi atherogenic factors antiatherogenic and increasing the concentration factor. Moreover, the technical result achieved is based on the influence of selenopyran on these processes in the dog’s body not known from the prior art.

The use of selenopyran supplements to the main complete diet of dogs (Pedigree Energy std.) To increase the functional activity of the immune, antioxidant and antiradical systems, to prevent the development of stress reactions and mitigate post-stress reactions, to reduce lipid peroxidation products in dogs blood, to reduce cholesterol fractions low density lipoproteins and very low density lipoproteins (LDL and VLDL), to increase the concentration of lipoprotein cholesterol fraction in the blood is high density (HDL), for the induction of a monooxygenase system for the elimination of xenobiotics, was not found in the patent and scientific literature.

Example 1

The experiment was conducted in the nursery "Red Star" (Dmitrov, Moscow region). The duration of the experiment is 2 months. Under the experiment there were 4 groups of adult dogs with 4 heads each.

1 group KD 149 Pedigree Energy std. - control, typical diet for adult dogs.

Group 2 KD 150 Pedigree Energy A - experimental, typical diet + 133 μg of selenopyran per 1 kg of dry matter feed.

Group 3 KD 151 Pedigree Energy B - experimental, typical diet + 400 μg of selenopyran per 1 kg of dry matter feed.

4 group KD 152 Pedigree Energy std. - experimental, typical diet + 1200 μg of selenopyran per 1 kg of dry matter of feed.

During the experiment, 3-fold blood sampling was performed (at the beginning, middle and end of the experiment, all blood samples were taken on an empty stomach, before the morning feeding of animals and 3 hours after it).

Table 1 The activity of enzymes in the blood of dogs The studied indicators Groups GPO GTF SOD P-450 ACT ALT First blood sample (start of experiment) 1 Group 498 ± 71 b01 ± 98 20.05 ± 6.20 4.63 ± 1.21 45.1 ± 9.9 30.2 ± 8.5 2 Group 507 ± 88 589 ± 102 18.55 ± 5.87 4.05 ± 1.37 42.7 ± 11.4 28.5 ± 8.8 3 Group 499 ± 91 b07 ± 97 19.34 ± 5.19 5.21 ± 1.44 47.0 ± 12.6 31.2 ± 9.0 4 Group 503 ± 95 590 ± 89 20.23 ± 7.16 4.72 ± 1.13 51 ± 15.0 34.6 ± 10.1 Second blood sample (1 month after the start of the experiment) 1 Group 481 ± 85 585 ± 95 19.28 ± 5.98 5.01 ± 0.99 55.4 ± 14.3 39.8 ± 9.5 2 Group 492 ± 89 610 ± 107 17.00 ± 5.31 6.50 ± 1.36 49.7 ± 12.8 37.6 ± 11.3 3 Group 508 ± 113 b12 ± 121 15.32 ± 4.98 7.39 ± 2.02 53.8 ± 16.0 41.2 ± 12.9 4 Group 519 ± 95 620 ± 104 13.68 ± 3.88 8.79 ± 2.62 58.9 ± 16.0 45.5 ± 13.6 Third blood sample (2 months after the start of the experiment) 1 Group 510 ± 92 608 ± 111 20.71 ± 5.14 4.84 ± 1.32 50.8 ± 15.0 33.0 ± 13.4 2 Group 522 ± 103 619 ± 97 15.59 ± 4.50 7.47 ± 1.58 45.3 ± 11.7 34.5 ± 12.1 3 Group 530 ± 89 627 ± 104 13.48 ± 4.22 8.58 ± 2.21 51.1 ± 12.8 36.1 ± 11.9 4 Group 536 ± 109 618 ± 121 10.87 ± 3.42 10.04 ± 2.56 54.5 ± 15.2 29.9 ± 12.0 Note
GPO - glutathione peroxidase selenium-containing, microns NADP oxidized / min / g
hemoglobin, substrate - hydrogen peroxide;
GTP - selenium-containing glutathione peroxidase (glutathione transferase), micron NADP oxidized / min / g hemoglobin, substrate - tert-butyl hydroperoxide;
SOD - superoxide dismutase - nmol of oxidized adrenaline / mg protein
P - 450 - cytochrome P - 450 - nmol of oxidized formaldehyde / mg protein
ACT - aspartate aminotransferase - IE / l
ALT - alanine aminotransferase - IE / l

The activity of two varieties of glutathione peroxidases (GPO), the leading enzymes of the antioxidant defense system of the body, was studied: - GPO 1 - KF 1.11.1.9 and GPO 2 - KF 2.5.1.18. GPOs are powerful antioxidant enzymes that are also involved in other functions: regulation of the biosynthesis of prostaglandins, prostacyclins, leukotrienes and thromboxanes. In glutathione peroxidase neutralization reactions of one peroxide molecule, two glutathione molecules are oxidized.

The main purpose of enzymes is to protect molecules and cellular structures, including biomembranes, from oxidative attack. The GPO family is represented by typical adaptive enzymes. Their activity can sharply increase under conditions of activation of oxidative stress reactions, which is necessary to eliminate foci of intense lipid peroxidation in the cell. Taking a direct part in the long-term regulation of lipid peroxidation, enzymes are an essential component of the antioxidant-antiradical system of body protection.

Even with sufficient selenium nutrition, the body is not able to completely insure itself against stressful situations of various etiologies. And any stress is accompanied by a sharp release of free radicals and the development of metabolic oxidative stress, with which the enzymatic and non-enzymatic links of the antioxidant defense system of the body are not always able to cope with joint actions. In such a metabolic situation, selenopyran will be very useful, since its molecule has glutathione-saving ability, transferring a proton and electron to oxidized glutathione and restoring it.

Since one glutathione peroxidase molecule in the active center contains 4 selenium atoms, without which the enzyme does not have catalytic activity, the information obtained is very interesting in terms of determining the dependence of the enzyme activity, as one of the main indicators of the availability of selenium in the body, on the concentration of selenium in animal blood. Based on the obtained material, it can be stated with a high degree of certainty that the concentration of selenium in the feed (including the control group) was not deficient.

As can be seen from the digital material summarized in Table 1, in two months of the experiment in four groups of experimental dogs that received three times different amounts of selenopyran, no significant and significant changes in the activity of glutathione peroxidase and glutathione transferase were detected.

The activity of HPO in experimental animals did not change, since the background content of selenium in the diet and the starting concentration of selenium in the body were quite high. In this situation, the enzyme activity reaches a plateau and the additional introduction of selenium is not able to increase it.

Analysis of the dynamics of the activity of superoxide dismutase and cytochrome P-450, also presented in table 1, eloquently confirms the judgments that selenopyran must be administered to animals and with a sufficient level of selenium in the diet. It also provides, against the background of nutrition sufficient for selenium, a very favorable effect in maintaining and strengthening the body's defenses and its general non-specific resistance.

In addition to immunostimulating, the specific detoxifying (neutralizing) function of selenopyran was clearly manifested. It consists in the activation of selenopyran enzymes of the monooxygenase system, in particular, the terminal portion of the microsomal electron transport pathway - cytochrome P-450, which is responsible for protecting the body from all exogenous xenobiotics of an organic and inorganic nature. This system is responsible not only for the metabolization and elimination of foreign substances from the body, constantly coming from the outside, but also for the neutralization and elimination of the body's constant natural metabolism satellites - endogenously formed toxic and harmful metabolic products ("waste"). If the activity of cytochrome P-450 in the control group of dogs remained almost at the initial level, then in the 2nd, 3rd and 4th experimental groups, 2 months after the start of feeding selenopyran, the activity of this enzyme increased by 54, 77 and 106 % respectively.

Throughout the experiment, a significant and reliable relationship was clearly observed between the amount of selenopyran introduced into the diet and the activity values of superoxide dismutase and cytochrome P-450. Moreover, and this was one of the most remarkable revealed facts, the activity of superoxide dismutase with an increase in the amount of selenopyran in the diet of dogs decreased by half. The dose-dependent effect of a decrease in the activity of superoxide dismutase relative to control confirms the lack of demand for the body in the high activity of the enzyme responsible for neutralizing the superreactive free oxygen radical - superoxidion. It was previously indicated that selenopyran is independently capable of performing the function of a metabolic trap of free radicals. This was confirmed in this experiment on dogs.

An equally pronounced dose-dependent response of the body to the concentration of selenopyran in the dogs ’diet is also traced in the magnitude of the activity of cytochrome P-450. However, the dynamics of the activity of this enzyme has a diametrically opposite direction, it increases significantly, almost doubles, demonstrating the increased potential ability of the dog’s body to neutralize and remove toxic products of both exogenous and endogenous origin.

The activity of both studied aminotransferases (Table 1) during the entire experiment did not undergo any logical and significant changes. All noted values fit into the framework of natural biological changes. This confirms the absence in experimental dogs of tension in the processes of transamination of amino acids and protein metabolism.

table 2 Biochemical blood parameters of dogs The studied indicators Groups MDA SH SS SH / SS Bilirubin conjug. Bilirubin is non-conjugate. First blood sample (start of experiment) 1 Group 2.91 ± 0.57 0.513 ± 0.09 0.223 ± 0.10 2.30 2.0 ± 0.61 2.8 ± 0.79 2 Group 2.85 ± 0.60 0.458 ± 0.07 0.237 ± 0.08 1.93 2.2 ± 0.70 2.5 ± 0.66 3 Group 2.93 ± 0.74 0.485 ± 0.13 0.246 ± 0.07 1.82 2.1 ± 0.65 2.7 ± 0.75 4 Group 2.88 ± 0.59 0.502 ± 0.16 0.252 ± 0.08 1.99 2.3 ± 0.65 2.6 ± 0.80 Second blood sample (1 month after the start of the experiment) 1 Group 2.90 ± 0.55 0.496 ± 0.11 0.217 ± 0.05 2.28 2.4 ± 0.75 2.9 ± 0.87 2 Group 2.79 ± 0.52 0.521 ± 0.09 0.203 ± 0.06 2.57 2.3 ± 0.60 2.7 ± 0.80 3 Group 2.48 ± 0.41 0.559 ± 0.11 0.188 ± 0.04 2.97 2.0 ± 0.49 2.5 ± 0.57 4 Group 2.41 ± 0.65 0.605 ± 0.15 0.172 ± 0.05 3.59 2.2 ± 0.60 2.6 ± 0.65 Third blood sample (2 months after the start of the experiment) 1 Group 2.92 ± 0.66 0.520 ± 0.08 0.233 ± 0.04 2.32 1.9 ± 0.55 2.4 ± 0.45 2 Group 2.70 ± 0.49 0.650 ± 0.11 0.220 ± 0.06 2.95 2.4 ± 0.76 3.0 ± 0.84 3 Group 2.33 ± 0.52 0.692 ± 0.10 0.200 ± 0.05 3.46 2.2 ± 0.60 2.3 ± 0.91 4 Group 2.29 ± 0.35 0.720 ± 0.17 0.187 ± 0.04 3.85 2.0 ± 0.61 2.4 ± 0.73 Note:
MDA - malondialdehyde, μm / ml of blood plasma;
SH - low molecular weight sulfhydryl groups (glutathione reduced + cysteine), μm / ml;
SS - low molecular weight disulfide groups (oxidized glutathione + cystine), mcm / ml;
TDS is the thiol disulfide ratio (SH / SS).
Bilirubin conjugate - conjugated bilirubin - μm / L
Unconjugated bilirubin - unconjugated bilirubin - μm / L

For many years, the concentration of malondialdehyde continues to remain a simple, reliable and universally recognized criterion for the ratio of antioxidant-prooxidant processes in any cell of the body. The growth of its content characterizes the inability of the body's protective systems to successfully cope with the processes of lipid peroxidation and oxygen oxidation along the one-electron pathway, during which the bulk of superreactive free radicals — undeoxidized oxygen products — are formed.

As can be seen from the digital material summarized in table 2, the concentration of malondialdehyde progressively and consistently decreased during the experiment, confirming the high capacity of the antioxidant systems of the body of experimental animals. This is confirmed by a regular and consistent decrease in the concentration of malondialdehyde in animal groups with increasing amounts of selenopyran. Thus, a strict inverse relationship between the amount of selenopyran introduced into the diet and the content of malondialdehyde in the blood has been demonstrated.

2 months after the start of the experiment, the concentration of malondialdehyde was 7, 20 and 22% lower in the 2nd, 3rd and 4th groups, respectively, than in the control. This information, based on the value of the indicator, which integrally characterizes the general state of peroxidation processes in dogs' organisms (a 20-percent decrease when 400 μg is introduced into the diet and a 22-percent decrease when 1200 μg of selenopyran is introduced into the diet), quite convincingly confirms the advisability of introducing 400 μg of selenopyran into adult diets 1 kg of feed. In other words, a 22% decrease in the concentration of lipid peroxidation products in dog blood compared with 20% cannot be considered justified, either biologically or economically, to increase the dose of selenopyran by a factor of three (from 400 to 1200 μg / kg feed) .

In the experiment, the concentration of bilirubins in the blood was studied (Table 2). Bilirubins are the breakdown products of hemoglobin and other chromoproteins, myoglobin, cytochromes, and heme-containing enzymes. The process of erythrocyte breakdown begins in the vascular bed, and ends in the cellular elements of the phage-citing mononuclear system (kupffer cells of the liver, connective tissue histocytes, plasma bone marrow cells).

After the release of hemoglobin from red blood cells, it is first converted to verdoglobin and then to biliverdin. Almost all of it is enzymatically restored to the bile pigment bilirubin. In the body of higher animals, which include the dog, with the breakdown of 1 g of hemoglobin, 34 mg of bilirubin is formed.

High concentrations of bilirubin in the blood are always accompanied by lesions of the central nervous system, foci of necrosis in the parenchymal organs, suppression of cellular immunity, and the development of anemia due to erythrocyte hemolysis.

The increased content of bilirubins in the blood and urine can be considered an early sign of damage to the liver parenchyma. Concentrations of bilirubins are also used in clinical practice, and they are really informative in a prognostic sense not only when they occur, but also as the pathological process attenuates: the level of bilirubin in the blood decreases.

All the information provided convincingly indicates a rather high prognostic and informational significance in the clinical diagnosis of this criteria group. When analyzing the material systematized in table 2, the fact of the absence of any pronounced regular changes in the concentration of conjugated and free bilirubin in the blood serum of dogs is noteworthy. This conclusion is true both individually for animals and in relation to the time of feeding, and on all four test diets. The fact that in all these cases the concentration of bilirubins slightly varied in the range that fit into the physiological norm for a given animal species indicates the absence of secretory-excretory and metabolic pathologies of the liver, secretory function of the pancreas, and intestinal absorption function. This circumstance confirms the physiological adequacy for dogs of different ages and different breeds of all three tested full-feed mixtures enriched with different doses of selenopyran when fed for two months.

An objective assessment of the body's adaptive reserves at the molecular level, the state of antioxidant protection, and mechanisms of nonspecific reactions to adverse environmental influences can be very successfully evaluated by the characteristics of the thiol disulfide system. Thiol disulfide ratio (TDS), i.e. the ratio of sulfhydryl to disulfide groups in blood serum serves as an important regulatory parameter and, at the same time, as a mobile diagnostic test for assessing nonspecific resistance of an organism. It can most informatively characterize the “buffer capacity” of the antioxidant system, both in norm and in pathology. The increased attention to this ratio and its classification as one of the most important regulatory parameters of the human and animal organism is due to the fact that thiol compounds (both low and high molecular weight), due to their ability to quickly but reversibly oxidize, turn out to be the most sensitive to adverse effects of different nature and intensity. In most pathologies of an infectious and non-infectious nature, including allergic conditions, and radiation damage, etc., a decrease in the content of SH-groups and an increase in the concentration of SS-groups are clearly observed. There is a very interesting hypothesis, according to which a very quick, easy and reversible formation of disulfide bonds is an adaptive mechanism invented by nature to protect sensitive membrane and intracellular structures from irreversible oxidative degradation.

The aforesaid is quite enough to recognize for glutathione the key role of the intracellular metabolite in the regulation of metabolism in normal and pathological conditions. It belongs to a special group of thiol antioxidants, has pronounced antitumor and radioprotective properties.

Therefore, initiating and supporting the reactions leading to the preservation of the restored thiol equivalents, the very same increases the body's adaptability and its resistance to the effects of a complex of adverse factors.

The severity of the disease, periods of exacerbation, exposure to adverse environmental factors, stressful situations in healthy people and animals correlate with the degree of decrease in the thiol disulfide ratio. The dynamics and magnitude of changes in the thiol-disulfide ratio (thiol-disulfide system) are a reflection of the development of an adaptive reaction and allow you to directly assess the level of nonspecific resistance of the body. An increase in the content of SH-groups and a decrease in SS-groups are associated with the active extraction of the reserve of low molecular weight thiols from the liver in response to the depletion of the blood redox system and the mobilization of body reserves for the restoration of oxidized thiols. In a number of diseases, a decrease in the SH / SS ratio was detected.

All systematized facts convincingly testify to the non-specific and universal nature of thiol changes when any extreme factors act on the body. Stress is characterized by a decrease in the content of thiol groups (and an increase in disulfides), which are considered as a significant criterion for the level of nonspecific resistance of the body.

The obtained experimental material (table 2) fully confirmed the correctness of the starting premises. New, very convincing and eloquent information was obtained for this group of indicators. The most remarkable circumstance is a progressive, substantial and significant increase in the concentration of sulfhydryl groups in all experimental groups of animals.

The dynamics of changes in the ratio of low molecular weight sulfhydryl and disulfide groups in the extracellular space (blood plasma) also quite convincingly and reliably confirmed the position on the positive effect of selenopyran as a glutathione-saving compound. The absolute values of the concentration of disulfide groups during the experiment in the blood of animals of the experimental groups decreased (by 6–20%), and the absolute values of the content of sulfhydryl groups in all three experimental groups increased (by 25–38%). As a result, the thiol-disulfide ratio in the blood plasma of experimental animals was higher than that in control animals. In animals of the 2nd, 3rd and 4th group, this index after two months of feeding selenopyran was 27, 43 and 66%, respectively, higher than in the control group.

Table 3 Biochemical blood parameters of dogs The studied indicators Groups Protein Hemoglobin Creatinine Glucose First blood sample (before feeding) 1 Group 51 ± 2.0 135 ± 4.6 95 ± 6.1 5.21 ± 0.6 2 Group 54 ± 1.7 140 ± 3.5 89 ± 4.4 4.99 ± 0.5 3 Group 57 ± 2.3 129 ± 4.2 86 ± 7.2 4.78 ± 0.9 4 Group 55 ± 2.2 137 ± 5.4 97 ± 6.6 5.07 ± 0.8 First blood sample (3 hours after feeding) 1 Group 53 ± 2.1 141 ± 7.5 127 ± 8.4 5.30 ± 0.7 2 Group 56 ± 1.7 125 ± 6.7 120 ± 7.1 5.01 ± 0.6 3 Group 55 ± 2.6 134 ± 5.9 131 ± 6.5 4.92 ± 0.4 4 Group 58 ± 2.3 143 ± 7.0 112 ± 5.5 4.99 ± 0.5 Second blood test (before feeding) 1 Group 55 ± 1.1 139 ± 6.5 90 ± 4.5 5.07 ± 0.8 2 Group 59 ± 2.2 142 ± 5.4 80 ± 5.1 4.98 ± 0.7 3 Group 56 ± 1.8 140 ± 6.7 84 ± 4.9 4.61 ± 0.5 4 Group 53 ± 1.5 136 ± 5.7 99 ± 6.0 4.48 ± 0.3 Second blood test (3 hours after feeding) 1 Group 54 ± 2.3 137 ± 5.9 147 ± 7.9 5.03 ± 0.4 2 Group 57 ± 2.0 150 ± 6.0 133 ± 12.3 5.34 ± 0.2 3 Group 50 ± 1.5 143 ± 5.5 102 ± 6.7 5.16 ± 0.3 4 Group 60 ± 3.1 138 ± 4.8 123 ± 5.5 4.95 ± 0.6 Third blood sample (before feeding) 1 Group 52 ± 1.5 124 ± 6.0 100 ± 4.9 5.05 ± 0.4 2 Group 52 ± 2.3 120 ± 4.9 92 ± 4.7 4.34 ± 0.2 3 Group 50 ± 1.9 141 ± 4.5 90 ± 5.5 4 Group 53 ± 2.6 110 ± 5.4 98 ± 6.0 4.76 ± 0.6 Third blood sample (3 hours after feeding) 1 Group 54 ± 1.1 131 ± 6.5 131 ± 6.5 5.02 ± 0.3 2 Group 58 ± 2.3 120 ± 6.0 125 ± 8.4 4.64 ± 0.1 3 Group 50 ± 1.9 141 ± 6.7 123 ± 6.0 4.36 ± 0.3 4 Group 54 ± 2.8 130 ± 5.8 115 ± 5.8 4.73 ± 0.5 Note: Hemoglobin - g / l .; Protein - g / l; Creatinine - mmol / L; Glucose - (mmol / L).

The concentration of hemoglobin in the blood (Table 3), making it possible to judge the antianemic properties of the diet and the hematopoietic function of the body, remained within the normal range. The glucose concentration reflects the energy supply of the diet, the availability of carbohydrates in the diet for metabolism, the state of insulin-glucagon and glycemic indices. Postprandial changes in glucose concentration were not detected in all test rations. In general, it was not possible to detect any significant and regular changes in the values of blood parameters, systematized in table 3. The stable values of this group of indicators confirmed the absence of deviations from the physiological norm in the dog’s body. The foregoing applies in full measure to the activity of aminotransferases and the concentration of bilirubins (Tables 1 and 2). All the noted values fit into the framework of natural biological fluctuations when feeding dogs for two months all three test doses of selenopyran.

Table 4 Biochemical blood parameters of dogs The studied indicators Groups Triacylglycerols Total cholesterol HDL cholesterol LDL cholesterol VLDL cholesterol First blood sample before feeding 1 Group 0.97 ± 0.07 5.01 ± 0.81 1.32 ± 0.06 3.25 ± 0.31 0.44 ± 0.06 2 Group 0.86 ± 0.06 4.90 ± 0.92 1.45 ± 0.04 3.06 ± 0.29 0.39 ± 0.05 3 Group 0.95 ± 0.08 5.22 ± 0.87 1.50 ± 0.03 3.30 ± 0.18 0.42 ± 0.04 4 Group 1.13 ± 0.09 4.95 ± 0.76 1.21 ± 0.05 3.21 ± 0.29 0.53-0.06 First blood sample, 3 hours after feeding 1 Group 1.37 ± 0.09 5.98 ± 0.89 1.49 ± 0.07 3.89 ± 0.40 0.60 ± 0.09 2 Group 1.20 ± 0.07 5.87 ± 0.77 1.54 ± 0.06 3.79 ± 0.28 0.54 ± 0.07 3 Group 1.48 ± 0.13 6.31 ± 1.02 1.66 ± 0.09 3.99 ± 0.37 0.66 ± 0.08 4 Group 1.39 ± 0.10 6.02 ± 0.95 1.40 ± 0.05 3.98 ± 0.30 0.64 ± 0.06 Second blood test, before feeding 1 Group 1.19 ± 0.18 5.20 ± 0.93 1.43 ± 0.06 3.23 ± 0.45 0.54 ± 0.06 2 Group 0.89 ± 0.08 4.71 ± 0.85 1.59 ± 0.08 2.72 ± 0.31 0.40 ± 0.05 3 Group 0.85 ± 0.07 4.53 ± 0.89 1.65 ± 0.07 2.49 ± 0.35 0.39 ± 0.04 4 Group 0.79 ± 0.09 4.42 ± 0.75 1.70 ± 0.08 2.40 ± 0.39 0.32 ± 0.03 Second blood sample, 3 hours after feeding 1 Group 1.39 ± 0.11 6.13 ± 1.02 1.56 ± 0.09 3.94 ± 0.60 0.63 ± 0.08 2 Group 1.25 ± 0.09 5.75 ± 0.99 1.67 ± 0.08 3.51 ± 0.45 0.57 ± 0.06 3 Group 1.28 ± 0.10 5.60 ± 1.11 1.82 ± 0.06 3.20 ± 0.42 0.58 ± 0.07 4 Group 1.10 ± 0.08 5.45 ± 0.87 1.90 ± 0.07 3.05 ± 0.39 0.50 ± 0.06 Third blood sample, before feeding 1 Group 1.08 ± 0.07 5.16 ± 1.03 1.49 ± 0.05 3.18 ± 0.41 0.49 ± 0.05 2 Group 0.80 ± 0.05 4.65 ± 0.91 1.78 ± 0.04 2.51 ± 0.33 0.36 ± 0.03 3 Group 0.75 ± 0.08 4.48 ± 0.83 1.80 ± 0.0b 2.34 ± 0.35 0.34 ± 0.02 4 Group 0.69 ± 0.07 4.30 ± 0.79 1.92 ± 0.03 2.07 ± 0.29 0.31 ± 0.02 Third blood sample, 3 hours after feeding 1 Group 1.45 ± 0.15 6.20 ± 1.02 1.65 ± 0.08 3.89 ± 0.62 0.66 ± 0.08 2 Group 1.18 ± 0.13 5.69 ± 0.88 1.85 ± 0.05 3.30 ± 0.55 0.54 ± 0.06 3 Group 1.20 ± 0.09 5.52 ± 0.95 1.97 ± 0.06 3.00 ± 0.51 0.55 ± 0.06 4 Group 1.05 ± 0.12 5.33 ± 0.7.9 2.10 ± 0.13 2.75 ± 0.46 0.48 ± 0.05 Note:
Triacylglycerols (TG) - μm / L;
Total cholesterol (cholesterol) - μm / L
High Density Lipoprotein Cholesterol (HDL) - μm / L
Low Density Lipoprotein Cholesterol (LDL) - μm / L
Very Low Density Lipoprotein Cholesterol (VLDL) - μm / L

In the control group of dogs, both the background (before feeding) and postprandial (after feeding) concentrations of total triglycerols (TG), total cholesterol (cholesterol), high density lipoprotein cholesterol (HLDPV), low density lipoprotein cholesterol (HLDP) and very low lipoprotein cholesterol density (HLPONP) throughout the experiment was within the range of natural fluctuations for this species of animal. In all three experimental groups of dogs within 1 month after the start of the experiment, a decrease in the concentration of TG, cholesterol, HLPNP and HLPONP was quite clearly observed, with a simultaneous increase in the concentration of HLPVP. Two months after the start of the experiment, the outlined specificity of the dynamics of all these indicators fully confirmed the identified trend. As a percentage of the 2nd, 3rd and 4th experimental groups, the concentration of TG 3 hours after feeding the dogs amounted to control in the groups of 81, 83 and 72%, respectively, the concentration of cholesterol - 92, 89 and 86%, the concentration of CLPN - 85, 77 and 71%, the concentration of HLPONP - 82, 83 and 72%, and the concentration of HLPVP - 121, 119 and 127%.

Thus, in dogs of the experimental groups, all factors mentioned as being related to atherogenic, i.e. contributing to the development of atherosclerosis decreased, and one factor attributed by clinicians to the number of anti-atherogenic, i.e. reducing the risk of cardiovascular disease, increased. The described dynamics of the concentration in the blood of dogs of experimental groups of studied lipids and cholesterol fractions allows us to conclude that selenopyran has a beneficial effect on lipid metabolism in the body of experimental animals. Moreover, direct experimental evidence for the antiatherogenic properties of diets with selenopyran was first obtained in this experiment. In other words, diets with selenopyran can be considered as reducing the risk of multiple pathologies of the cardiovascular system, as preventing these most serious and most common diseases.

Selenopyran, preventing lipid peroxidation, is able to interrupt the first stage of atherogenesis, which allows it to be attributed to coronary protective factors. The close relationship between selenium and vitamin E described by us indicates the high potential ability of selenopyran to prevent imbalances between different fractions of lipids and cholesterol, which are the main cause of the risk of a variety of disorders of the cardiovascular system.

Summing up all the experimental data obtained on the basis of zootechnical indicators, summarizing the quantitative dynamics of changes in triacylglycerols and the concentration of various cholesterol fractions, with data on the activity of superoxide dismutase, cytochrome P-450, the concentration of malondialdehyde and indicators of the thiol disulfide system, we can conclude the biological and economic feasibility of the developed method of feeding adult dogs, the main diet Pedigree Energy std. enriched with selenopyran . The rest of the complex of studied physiological and biochemical parameters, attributable to the number of clinical indicator criteria, as well as a complex of zootechnical indicators (feed intake, live weight, general well-being of animals, fecal consistency) also confirms the stated conclusion.

The extensive information available on the long-term use of selenopyran in cows, sows and their offspring, raised to adult animals, makes it possible to reasonably say that selenopyran, in addition to a short-term positive effect, also exhibits long-term positive effects.

Claims (1)

A method of feeding dogs, comprising the additional introduction of selenopyran in the main diet in an amount of from 133 to 1200 μg per kilogram of dry matter of the main diet.