RU2029466C1 - Agent for increase of body mass, thymus, spleen and red marrow bone in animals - Google Patents

Abstract

FIELD: veterinary. SUBSTANCE: method involves addition of sodium succinate to the diet of mice at the diurnal dose 0.5-1 mmole/kg. After 30-31 days of preparation intake mice body mass is increased by 5-21%, index of thymus and spleen mass is increased by 19-82 and 42-47%, and DNA content in femoral bone marrow bone - by 10-34%. These inducible changes are stable for at least 15 days after cessation of preparation feeding to animals and their X-ray irradiation at the dose 3 Gr. EFFECT: increased effectiveness of agent proposed. 1 dwg, 3 tbl

Description

 The invention relates to biology and veterinary medicine and can be used to increase the gain of animals, as well as to increase the yield of raw materials used in the production of biologically active preparations of the thymus, spleen and red bone marrow.

 In medical and veterinary practice, anabolic steroids in combination with enhanced nutrition are used to increase body weight. However, anabolic steroids, being lipophilic and slowly metabolized, accumulate in the body during systemic use, cause a number of undesirable changes in reproductive functions, and also cause involution of lymphoid organs and toxic liver damage.

In order to stimulate blood formation in medical and veterinary practice, drugs are used - stimulants of leukopoiesis (sodium nucleinate, leucogen, pentoxyl, etc.), vitamins (folic acid, vitamin B ₁₂ , etc.), and trace elements (iron, zinc, cobalt, etc. ) However, these drugs are relatively expensive, and having the ability to stimulate the regeneration of damaged hematopoietic tissue, do not increase the mass of intact thymus, spleen and red bone marrow even with prolonged use.

 As a prototype, the author chose a method of increasing weight and body, which consists in introducing into the body anabolic steroid hormones such as retabolil, phenobolin, methandrostenolone, methylendrostenediol. This increases the mass of muscle tissue and the body as a whole. However, this method does not allow to solve the problem - simultaneously with the body weight of animals to increase the mass of thymus, spleen and red bone marrow. On the contrary, all drugs used in the prototype, possessing androgenic activity, have a thymolytic effect.

 The objective of the present invention is to increase the weight gain of animals while increasing the mass index of the lymphoid organs - thymus and spleen, as well as red bone marrow.

 The problem is solved by including sodium succinate in the diet of animals. Sodium succinate was previously used as a diuretic, laxative, antisclerotic, antacid, for removing patients from anesthesia and in experimental therapy of metabolic acidosis.

 In this method, the introduction of sodium succinate in the diet at a dose of 0.5-1 mmol / kg of body weight per day is optimal. In the range of daily doses, sodium succinate has an optimal effect on the increase in body weight in general, as well as on the increase in the mass of the thymus, spleen and red bone marrow of animals. In addition, doses of sodium succinate do not affect the taste of water when the drug is introduced into the daily diet in the form of a drink and, therefore, do not affect the amount of water consumed by animals.

 At doses less than 0.5 mmol / kg of body weight per day, an increase in body weight, thymus, spleen and red bone marrow is insignificant.

 At doses greater than 1 mmol / kg of body weight per day, animals refuse to drink or reduce water intake due to the poor taste properties of too concentrated sodium succinate solution. It is impossible to introduce doses of more than 1 mmol / kg of body weight per day with a small concentration of sodium succinate solution into the diet, since the animal refuses to consume such an amount of water.

 Sodium succinate is the sodium salt of succinic acid, a natural nutrient that is part of a number of natural foods, especially unripe berries and fruits. At present, succinic acid is produced on an industrial scale by chemical synthesis methods.

Succinic acid has low toxicity and versatile physiological activity in the body of animals, for which it is a normal metabolite. The dose of succinic acid that causes the death of 50% of the animals upon intraperitoneal administration (DM ₅₀ ) for mice is 22.9 mmol / kg. The manifestations of the physiological activity of succinic acid known from the literature are favorable for the body. Succinic acid and its salts are used as diuretics, laxatives, antisclerotic, antacids. Sodium salt of succinic acid (Soduxin drug) is used to remove patients from anesthesia and from a coma when poisoning with morphine, its derivatives and barbiturates. In the USSR, succinic acid is recommended for clinical trials as a therapeutic agent for diseases of the cardiovascular system.

 The invention is illustrated in the drawing, which reflects the dynamics of the body weight of mice in the process of consumption of sodium succinate in the form of a drinking solution in the specified daily dose. The abscissa axis shows the duration of animals' consumption of sodium succinate solution, the ordinate axis shows the group mean body weight (% of control). The shaded space indicates the confidence interval in the control group.

 Examples of the method.

 PRI me R 1. The experiments were carried out on receiving standard granular ad ad libitum male albino mice weighing 19-22 g, which were distributed in six groups with equal average body weight. The animals of the control group received distilled water, and the experimental groups received drinking solutions of succinic acid, sodium chloride, sodium succinate, potassium chloride and potassium succinate in an average daily dose of 1-2 mEq / kg. The concentration of solutions was chosen in accordance with GOST 2874-73 for drinking water according to the results of preliminary experiments in which it did not affect the water consumption of animals.

Weighing of mice by determining the mass of the thymus, spleen and bone marrow was performed on the 30th day of the experiment. As an indicator of the relative mass of the thymus and spleen, we used the mass index calculated by the formula
I = 1000a / b, where I is the mass index of the organ;
a is the mass of the organ, g;
b - body weight, g.

 The DNA content in 1 femur (an indicator proportional to the number of karyotic cells in the test sample) was used as an indicator of the mass of red bone marrow. DNA was determined by the Z.Dische method. The results are shown in table 1.

 Sodium chloride and sodium succinate had a significant effect on the body weight of mice (an increase of 5% to the control). The thymus mass index significantly increased under the influence of succinic acid (by 39%) and sodium succinate (by 19%). The spleen mass index increased in animals consuming sodium chloride (by 38%), sodium succinate (by 47%) and potassium succinate (by 30%). The DNA content in the bone marrow of the thigh increased only under the influence of sodium salts (by 34%). Thus, the totality of the studied parameters increased only in the group of animals treated with sodium succinate.

 PRI me R 2. Sodium succinate was included in the diet of albino mice weighing 21-23 g according to the method described in example No. 1. Animals were weighed daily. On the 1st, 4th, 7th, 13th, 14th, 21st and 31st days of the experiment, 10 mice from the experimental and control groups were used to determine the indices of the mass of internal organs and DNA content in the bone marrow of the femur. On the 31st day of the experiment, the drinking solutions in the experimental and control groups were replaced with tap water, and the animals were subjected to a general single x-ray irradiation in a dose of 3 Gy. On days 1, 3, 7, 10, and 15 after irradiation, the same indices were determined as before irradiation. The results are shown in table.2.

 A comparative study of the effect on the body weight, thymus, spleen and red bone marrow of mice of succinic acid, sodium chloride, sodium succinate, potassium chloride and potassium succinate in a daily dose of 1-2 mEq / kg body weight showed that of all these substances only sodium succinate caused an increase in all four indicators (Table 1).

 The increase in body weight, thymus and spleen of animals treated with sodium succinate as part of the diet is persistent (Table 2), since it persists for at least 15 days after stopping the administration of the drug and x-ray irradiation of animals at a dose of 3 Gy (radiation dose causing mice weight loss, aplasia of the thymus, spleen and bone marrow).

In all the experiments described, the consumption of drinking solutions of sodium succinate was not accompanied by toxic effects. According to the author, DM ₅₀ sodium succinate for male albino mice weighing 18-20 g is 52.8 mEq / kg body weight, which is 8% more than DM ₅₀ sodium chloride (49.0 mEq / kg body weight )

 PRI me R 3. Sodium succinate (sodium succinic) for twenty days was given to broiler chickens of both sexes daily with feed in three concentrations: 100, 500 and 2500 mg / kg, which corresponded to the average daily doses of 5-14, 25 -70 and 125-350 mg per 1 kg of body weight. Control animals under the same conditions as the experimental ones received mixed feed without the addition of sodium succinic acid. The data of periodic weighing of experimental chickens are presented in table.3.

 The use of sodium succinic acid was not accompanied by a significant change in the frequency of death of birds compared with the control (mortality of chickens during the tests was 115 and 117 in the control and experiment, respectively).

The tests performed allow us to draw the following conclusions:
The inclusion of sodium succinic acid in the diet of broiler chickens as a part of compound feed at concentrations of 100-2500 mg / kg causes an increase in the body weight of animals by 3-11% compared with the control.

 The highest increase in body weight of chickens was obtained by succinic sodium when it was included in the composition of compound feed at concentrations of 100 and 500 mg / kg.

 The use of sodium succinic acid as a feed additive in order to increase the gain of broiler chickens is appropriate.

Claims (1)

 MEANS FOR INCREASING WEIGHT OF THE BODY, THYMUS, SPLEEN AND RED BONE MARROW IN ANIMALS.  The use of sodium succinate as a means to increase body weight, thymus, spleen and red bone marrow in animals.

Images