RU2418586C2 - Method of correcting failures in reproductive organs caused by high temperature - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to experimental medicine, namely to gynecology, and can be used for correction of failures in reproductive organs, caused by carrying out controlled total-body hyperthermia (CTBH). For this purpose, after CTBH impact melatonin is introduced into animal organism.

EFFECT: method ensures prevention of spasm of ovarian arteries; reduction of venous congestion severity and normalisation of venous blood flow; reduction of severity of lymph flow and folliculogenesis failures on the 7-th day; as well as ensures restoration of volume density of yellow bodies of ovaries, which are at the proliferation and vascularisation stage; reduction of degree of severity of decrease of volume density of ovary yellow bodies that are at the stages of glandular metamorphosis and growth; reduction of degree of severity of degeneration and atresia of yellow bodies that are at the stage of reverse development.

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Description

The invention relates to medicine, more specifically to gynecology.

We give the information known from the prior art:

a) on the means for the correction of disorders in the reproductive organs;

b) the means used for hyperthermia;

c) on the areas of application of melatonin.

A) Means for the correction of disorders in the reproductive organs

A known method for correcting violations of the reproductive function of the ovaries in animals, which consists in the fact that they sequentially affect the millimeter-wave electromagnetic radiation at a frequency of the molecular spectrum of atmospheric oxygen or nitric oxide on the biological points of the ovaries and the genitourinary area for 1-2 minutes per area every day 5-7 days (RU 2007107901).

There is a method of correcting reproductive dysfunction in patients suffering from chronic inflammatory diseases of the uterus and appendages, which consists in the fact that patients are prescribed internal and external (baths and gynecological irrigation at 36-38 ° C, exposure 15 min) intake of mineral water from the Slavyanovsky source, and also peloid therapy in the form of applications for the “panty” zone t 40-42 ° C, exposure time 15-20 min and vaginal tampons t 40-45 ° C, exposure time 20-25 min, for a course of 8-10 procedures, alternating every other day ( RU 2006116203).

Caused by various factors, disorders in the reproductive organs are specific. The above inventions are not intended to correct disorders in the reproductive organs caused by high temperature.

B) The following drugs are known for hyperthermia:

- a method of providing emergency care when overheating the body, which consists in eliminating the source of heat and the victim receives a heliox mixture for breathing, containing 40% oxygen, at a temperature of 4-6 ° C (RF 2002133290);

- a tool that increases the body's resistance to overheating and is sodium oxybutyrate in the composition with relanium. The tool affects the central nervous and cardiovascular systems (RF 2096035);

- hydrazide (1,2,4-triazino [5,6-b] indolyl-3-thio) acetic acid, which increases resistance to hyperthermia and has antiarrhythmic activity. In an overheating climate (40 ° C, 30% humidity), the new compound increases resistance to hyperthermia with a degree of protection of 60% for animals and has a pronounced antiarrhythmic activity, 2 times the duration of action of the drug trimecaine at a dose of 2-10 times less than for trimecaine (SU 1487415);

- dihydrochloride 3- (2-morpholinoethylthio) -1,2,4-triazino [5,6-b] indolyl-5-acetamide, accelerating the recovery process after physical exertion, increasing resistance to hyperthermia, with antihypoxic activity. The protection coefficient of the new compound against hypoxia 1.4; against hyperthermia, the degree of protection of animals is 53% against 30% for bemitil, and the degree of recovery after physical activity in comparison with the control increases by 142% (RF 1498021).

The above funds affect the central nervous and cardiovascular systems of the body, increase resistance to overheating, but are not intended to correct disorders in the reproductive organs.

C) The following areas of application of melatonin are known:

- to increase the resistance and productivity of farm animals in veterinary implantable preparations, synthetic melatonin or synthetic melatonin and a tranquilizing (psychotropic) drug are used with the following mixture,%: melatonin 10-40, cyacrine-EO (polymer) 89.95-55, 5, a plasticizer 0.05-4.5 or: melatonin 7-25, a psychotropic agent (e.g. phenazepam) 7-25, cyacrine-EO (polymer) 85.95-45.5, a plasticizer 0.05-4.5 (RF 2001135563);

- to regulate the biological rhythm of animals and accelerated maturation of hair in fur animals in implantable veterinary preparations, which include the active substance melatonin or melatonin mixed with psychotropic substances, a biodegradable polymer base and plasticizer. Two medicinal compositions of a veterinary preparation of the following composition are claimed,%: a) melatonin 10-40, cyacrine-EO (polymer) 89.95-55.5, plasticizer 0.05-4.5, b) melatonin 7-25, psychotropic drug 7-25, cyacrine-EO (polymer) 85.95-45.5, plasticizer 0.05 - 4.5 (RF 2096044);

- as part of an agent with antistress, nootropic, antiviral and immunostimulating effects, containing synergistically active ingredients: DSIP nonapeptide with the amino acid sequence Trp-Ala-Gly-Asp-Ala-Ser-Gly-Glu and genetically engineered alpha-interferon (reaferon) in the ratio of DSIP - 1 mg reaferon - 1103-1104 ME. The tool may additionally contain glycine, dipeptide carnosine and melatonin, in a weight ratio of 1 mg: DSIP - 1 glycine - (20-40), carnosine - (3-30), melatonin - (10-50), reaferon - (1103- 1104) ME (RF 2001115934);

- N-acetyl-5-methoxytryptamine (melatonin) or melatonin in combination with other antihypertensives is used to treat arterial hypertension. The tool does not have undesirable side effects, effectively reduces blood pressure and is especially effective for the treatment of elderly patients (RF 2134108);

- to stimulate meiosis of germ cells, the indicated cells are introduced in vivo, ex vivo or in vitro to an effective amount of a compound that causes the accumulation of endogenous substance that activates meiosis to the level at which meiosis is induced. The compound that causes the accumulation of the endogenous substance that activates meiosis is melatonin (RF 97116491);

- in a pharmaceutical composition containing, as an active ingredient, at least one substance that inhibits NO synthetase and at least one substance that traps reactive forms of oxygen, and optionally a pharmaceutically acceptable carrier, wherein, as a scavenger, reactive forms of oxygen melatonin can be used (RF 9910679);

- for the treatment of alexithymia (recognition disorders and descriptions of their own feelings) with angina pectoris, patients aged 55-60 years old are prescribed melatonin in a dose of 1.5 mg once a day at night for 10 days in addition to the standard treatment of angina pectoris, which reduces the level of alexithymia , improves sleep, leads to the cessation of angina attacks at night (RF 2203053);

- for the treatment of atopic dermatitis, antihistamines, detoxification therapy, local glucocorticoid-containing ointments and an immunomodulatory drug, the pineal gland hormone melatonin, are given in a dose of 3 mg at 21.00 hours on a 21-day course. The method provides the effectiveness of treatment by reducing the level of IgE (RF 2268737);

- to reduce the risk of breast cancer by lengthening the follicular phase of the menstrual cycle and its overall duration, which is ensured by the daily administration of melatonin in an effective dose, including in combination with progestogen and / or estrogen (RU 2067001);

- to prevent conception by inhibiting ovulation in women of childbearing age, melatonin is prescribed in a daily dose of 2 - 1000 mg per 70 kg of body weight or a composition containing a mixture of melatonin in an amount of 2 - 1000 mg and a progestogen in an amount of 7.5 - 2500 mg, or a mixture of melatonin and estrogen in an amount of 2-100 mg, or a mixture of melatonin, progestogen and estrogen according to various schemes (RF 2114621);

- for the treatment of sleep disorders, derivatives of melatonin are used (RF 2146140);

- the use of melatonin to activate a hypothalamus in a subject to increase the level of growth hormone releasing hormone (GHRH) in the blood serum, which in turn leads to an increase in the secretion of growth hormone (GH) and a subsequent increase in the level of insulin-like growth factor 1 (IGF-1 ) in the blood serum, for the preparation of a therapeutic composition for treating symptoms of fatigue and exhaustion in people, “burnout” syndrome, chronic fatigue syndrome, depression, Alzheimer's disease, directly irritated syndrome intestine, osteoporosis, type 2 diabetes or for therapy aimed at slowing aging, immune therapy, or for stimulating recovery after physical training, or to increase growth and increase immunity in animals (RF 2006114757);

- the use of melatonin for the treatment of drug addiction, as well as patients with symptoms of dependence, or immunity, or addiction to drugs of the benzodiazepine group (RF 97113435, RF 2182001);

- the use of melatonin in a pharmaceutical composition comprising at least one antipsychotic compound and melatonin in an amount effective to reduce the intensity of the manifestation or prevent symptoms of the development of tardive dyskinesia (EA 004057).

The authors did not find any publications that would investigate the ability of melatonin to correct high-temperature disorders in the reproductive organs.

Disclosure of invention

The essence of the proposed method for the correction of disorders in the reproductive organs caused by high temperature (general controlled hyperthermia - hereinafter OAG) is that after exposure to OAG, melatonin is introduced into the body. Melatonin prevents spasm of the ovarian arteries; reduces the severity of venous stasis and normalizes venous blood flow; reduces the severity of lymph flow disorders. Melatonin reduces the severity of folliculogenesis disorders on the 7th day. Melatonin restores the bulk density of the corpus luteum of the ovaries, which are at the stage of proliferation and vascularization; reduces the severity of the fall in bulk density of the yellow bodies that are at the stages of glandular metamorphosis and flowering; reduces the severity of the processes of degeneration and atresia of the corpus luteum, which are at the stage of reverse development.

List of figures

Figure 1. Bulk density of ovarian arteries,%.

Figure 2. The bulk density of the venous vessels of the ovary,%.

Figure 3. Bulk density of the lymphatic vessels of the ovary,%.

Figure 4. Bulk density of primary follicles,%.

Figure 5. Bulk density of tertiary follicles,%.

6. Bulk density of atretic follicles,%.

7. Bulk density of corpus luteum (proliferation and vascularization stage),%.

Fig. 8. Bulk density of the corpus luteum (stage of glandular metamorphosis).

Fig.9. Bulk density of yellow bodies (heyday),%.

Figure 10. Volumetric density of yellow bodies (stage of reverse development),%.

The implementation of the invention

In the experiment, 155 sexually mature female Wistar rats (3 months old) with a body weight of 180-200 grams were used. Animals were kept in vivarium conditions at an air temperature of 20-22 ° C with a standard diet and free access to water. Taking into account the influence of biological rhythms on living objects, all experiments were carried out in the winter-spring period at the same time from 10 to 12 hours.

Rats were divided into 7 groups: one group was intact, control (animals of this group were not exposed to OAG), three control groups with OCA (animals were subjected to OAG, and then they were injected with saline) and three experimental groups with OAG (animals were exposed to OAG, and then they were given melatonin). Melatonin was administered to animals in the regimen indicated below. In the same mode, physiological saline was injected. Additional group information is provided below:

1st group - control intact, number of animals - 20;

2nd group - control with OUG (OUG + saline), animals were withdrawn from the experiment on the 3rd day, the number of animals - 21,

3rd group - control with OUG (OUG + saline), animals were withdrawn from the experiment on the 7th day, the number of animals - 21,

4th group - control with OUG (OUG + saline), animals were withdrawn from the experiment on the 14th day, the number of animals - 21,

5th group - experimental: OUG + melatonin, animals were removed from the experiment on the 3rd day, the number of animals - 25,

6th group - experimental: OUG + melatonin, animals were removed from the experiment on the 7th day, the number of animals - 25,

7th group - experimental: OUG + melatonin, animals were removed from the experiment on the 14th day, the number of animals - 22.

Animals at the stage of the diestrus of the astral cycle were subjected to general controlled hyperthermia in accordance with the Method of Experimental Modeling of General Hyperthermia in Small Laboratory Animals (Efremov A.V., Pakhomova Yu.V., Pakhomov E.A., Ibragimov R.Sh. , Shorina G.N. Patent of the Russian Federation No. 2165105).

Experimental groups of animals were injected with melatonin ICN Biomedical inc. Given the duration of the estrous cycle of rats, the first administration of melatonin was carried out on the day of hyperthermia, then on the next 2 days (in the evening after sunset, once a day). The introduction of melatonin can be carried out over a longer period, for example within 7 days, to provide a more pronounced therapeutic effect.

A working solution of melatonin was prepared as follows. A melatonin preparation was taken as a source (uterine), in which 13.8 mg of melatonin was contained in 1.5 ml of an alcohol solution. To 0.25 ml of a mother liquor containing 2.3 mg of melatonin, 5 ml of physiological saline was added. Melatonin is administered in doses of 0.05-5.0 mg / kg, providing a therapeutic effect. In the experiment, each experimental animal was injected subcutaneously with 0.2 ml of physiological saline with melatonin (0.1 mg of melatonin), which corresponds to the average value in the above dose range; each control animal of groups 2-4 was injected subcutaneously with 0.2 ml of physiological saline.

To conduct a morphological study, the animals were taken out of the experiment under ether anesthesia in accordance with the Rules for the work using experimental animals (Order of the USSR Ministry of Health of 08/12/1977) on days 3, 7, 14 after the OUG. As an object of histological examination, ovaries were used, the samples of which were fixed in a 10% solution of neutral formalin, dehydrated in a series of alcohols of increasing concentration and enclosed in paraffin. Slices 5-6 μm thick were prepared on a sled microtome, which were stained with Mayer hematoxylin, eosin and examined under a binocular microscope at 70x magnification (objective 10, eyepiece 7).

For morphometric analysis, we used a square test system mounted in the microscope eyepiece and consisting of 11 transverse and 11 longitudinal lines and 121 points. When conducting morphometry used a semi-automatic recording device. The volume densities of the main structural and tissue elements of the ovaries (primordial, primary, secondary, tertiary, atretic follicles and corpus lutes, as well as the spiral arteries, venous plexus vessels and lymphatic vessels of the cerebral ovary layer) were calculated by the method of point counting and the dynamics of their bulk density by 3 , 7, 14 days from the conduct of the OAG.

Morphometric digital data were processed by the method of variation statistics using the statistical package STATISTICA 5. To determine the statistical differences between the compared means, the Student criterion was used, the differences were considered significant at p <0.05.

A study of the effectiveness of the correction of morphofunctional changes in the vascular bed of the cerebral layer of the ovary of rats with melatonin that occurs in CVI showed the following with respect to various categories of vessels.

Arteries

Arterial bulk density on the 3rd day after exposure to OAG remains at the control level; on the 7th day it decreases (almost twice); on the 14th day it is also lower than in group 1 (table 1, figure 1).

With the introduction of melatonin, the bulk density of the arteries on the 3rd, 7th, 14th day after the OAG remains at the level of control group 1 (table 1, figure 1).

Veins

The bulk density of veins on the 3rd day after exposure to OAG increases (2.5 times), by the 7th day it decreases to the level of control group 1, by the 14th day it decreases to 38% of the control value (in group 1) ( table 1, figure 2).

With OAG, followed by correction with melatonin, the bulk density of veins on the 3rd day increases, but not as much as in group 2 (by 30%); on the 7th and 14th day corresponds to the level of control group 1 (table 1, figure 2).

Lymphatic vessels

1. The bulk density of the lymphatic vessels on the 3rd day after the OAG significantly increases in relation to the control group 1 (4.6 times); by the 7th day there is a decrease in the bulk density of the lymphatic vessels, however, it is still significantly higher (2 times) than in the control group 1; by the 14th day, the bulk density decreases to the level of control (table 1, figure 3).

When melatonin is corrected, the volume density of lymphatic vessels on the 3rd day increases with respect to the intact control not so much as in group 2 (1.6 times), by the 7th day it decreases to the level of control group 1, by 14- m days there was a further decrease to 60% from the level of group 1. The differences between groups 5 and 2, 6 and 3, 7 and 4 were significant at p <0.05 (table 1, figure 3).

Thus, the introduction of melatonin after exposure to OAG causes the following effects:

1) prevents arterial spasm;

2) corrects dystonia of venous vessels: reduces the severity of venous stagnation on the 3rd day, normalizes venous blood flow on the 7th and 14th day;

3) reduces the severity of lymphostasis on the third day, normalizes lymph flow on the 7th day.

When studying changes in the follicular apparatus of the ovaries after exposure to OAG at the stages of primordial, secondary and tertiary follicles, the effect of melatonin administration is not observed. With regard to primary and atretic follicles, the following was revealed.

1. The bulk density of primary follicles on the 3rd day after overheating decreases (up to 43% of the level of control group 1), by the 7th day there was a further decrease to 6%, and by the 14th day the bulk density of primary follicles is restored to 55 % of the value in the control group 1 (table 2, figure 4).

When melatonin is corrected, changes in the bulk density of primary follicles on the 3rd day and 14th day after exposure are similar to the above, and on the 7th day the decrease in bulk density is not as significant as in the corresponding group of animals with saline (up to 33% of the level control). The difference between groups 6 and 3 is significant (table 2, figure 4).

2. Bulk density of tertiary follicles on the 3rd day after exposure to OAG corresponds to their bulk density in control group 1; on the 7th day there is a decrease of 60%; by the 14th day, the bulk density increases to values that exceed the control level by 33% (Table 2, FIG. 5).

After administration of melatonin, the bulk density of tertiary follicles on the 3rd day slightly increases; by the 7th day its increase was noted, exceeding the control level by 66%; by the 14th day, the bulk density of tertiary follicles is reduced and is already 66% of the level of the control group. The differences between groups 2 and 5, 3 and 6, 4 and 7 are significant (table 2, figure 5).

3. The bulk density of atretic follicles on the 3rd day after OAG significantly increases (3 times); on the 7th day there is a sharp increase in bulk density by 25 times; by the 14th day, a slight decrease in the bulk density of atretic follicles was noted. With correction by melatonin on the 3rd day, there is also a significant increase in the bulk density of atretic follicles; by day 7, an increase in bulk density is less pronounced compared to group 3 with a significant difference between groups 6 and 3; by the 14th day, the bulk density of atretic follicles is comparable to their bulk density in group 4 (Table 2, FIG. 6).

Thus, with the introduction of melatonin after exposure to OAG at the stages of primary, tertiary and atretic follicles, a positive effect is observed on the 7th day after OAG and that folliculogenesis disorders for this period are much less pronounced.

The effect of melatonin on various stages of development of the corpus luteum of the ovaries of rats is as follows.

1. The bulk density of the corpus luteum of the ovary in the proliferation and vascularization stage on the 3rd day after the OAG remains at the initial level; by the 7th day it decreases to zero, and by the 14th day it is restored to 42% of the initial value. After exposure to melatonin, the volume density of the corpus luteum in the proliferation and vascularization stage on the 3rd day also remains at the initial level, decreases to zero by the 7th day, and is restored to the control level by the 14th day (Table 2, Fig. 7 )

2. Bulk density of corpus luteum in the stage of metamorphosis decreases by 3 days to 30% of the control level, by 7 days it drops to zero, and by the 14th day it is restored to 14% of control. When corrected with melatonin, a slight decrease in the volume density of the yellow bodies on the 3rd day after OAG to 70% of the control level is noted; on the 7th day, a further decrease to 12% is recorded, and by the 14th day there is an increase in the volume density of yellow bodies to values of 37% of the initial level. The experimental data for groups 5 and 2, 6 and 3, 7 and 4 have significant differences (table 2, Fig. 8).

3. Similar changes are characteristic for yellow bodies in their heyday: on the 3rd day - a decrease in bulk density by 3.2 times; by the 7th day there is a further decrease to zero, which persists on the 14th day. After the introduction of melatonin, the bulk density of the corpus luteum decreases on the 3rd day significantly less - 1.8 times the level of control; on the 7th day there was a further decrease to 11% of the control level; by the 14th day - restoration to 34% of the initial values, the differences between groups 5 and 2, 6 and 3, 7 and 4 are significant (Table 2, Fig. 9).

4. The bulk density of the corpus luteum in the stage of reverse development on the 3rd day after the OAG increases by 1.5 times. On the 7th day, the excess of the control level is already 5.6 times (27.41% versus 4.91% in control group 1). On the 14th day, the bulk density decreases to the level of 3 days. When melatonin corrected, changes in the volume density of yellow bodies in the reverse development stage on the 3rd and 14th day are similar to the above, on the 7th day - only 2.2 times higher than the level of control group 1. The difference between groups 3 and 6 is significant ( table 2, figure 10).

Thus, the introduction of melatonin after exposure to OAG affects the yellow bodies of the ovaries of rats at all stages of development and leads to the following effects:

1) in the stage of proliferation and vascularization on the 14th day, melatonin restores the bulk density of the corpus luteum of the ovaries to the initial level;

2) at the stages of glandular metamorphosis and flowering, a positive effect from the administration of melatonin is observed at all times after the CVL and is manifested in a less sharp decrease in the volume density of yellow bodies on the 3rd, 7th and 14th days;

3) the positive effect of the introduction of melatonin on the corpus luteum in the heyday is observed at all times after the OAG and manifests itself in a less sharp drop in bulk density;

4) the positive effect of the introduction of melatonin on the corpus luteum in the stage of reverse development is observed on the 7th day and manifests itself in a less sharp increase in their bulk density.

Table 1
Bulk density of the vessels of the cerebral layer of the ovaries at different times after total controlled hyperthermia V _V ,% (M ± m) Ovarian structure The control Hyperthermia + saline Hyperthermia + melatonin 3 days 7 days 14 days 3 days 7 days 14 days 1st group. 2nd gr. 3rd gr. 4th gr. 5th gr. 6th gr. 7th gr. Arteries 0.73 ± 0.11 0.73 ± 0.13 0.39 ± 0.08 ^{* #} 0.48 ± 0.09 ^{* #} 0.79 ± 0.14 0.67 ± 0.11 ^# 0.84 ± 0.15 ^# Veins 2.66 ± 0.20 6.83 ± 0.60 ^{* #} 2.44 ± 0.33 1.01 ± 0.17 ^{* #} 3.47 ± 0.26 ^{* #} 2.69 ± 0.27 2.69 ± 0.34 ^# Lymphatic vessels 1.37 ± 0.13 6.25 ± 0.61 ^{* #} 2.88 ± 0.36 ^{* #} 1.74 ± 0.24 ^# 2.16 ± 0.25 ^{* #} 1.15 ± 0.17 ^# 0.84 ± 0.15 ^{* #} * - significance of differences compared with control (group 1), p <0.05
# - significance of differences between groups 2 and 5, 3 and 6, 4 and 7, p <0.05.
V _V is the bulk density, i.e. the fraction of the volume of the investigated structure v in unit volume of tissue V.

table 2
Bulk density of ovarian structures V _V ,% (M ± m) Ovarian structure The control Hyperthermia + saline Hyperthermia + melatonin 3 days 7 days 14 days 3 days 7 days 14 days 1st group. 2nd gr. 3rd gr. 4th gr. 5th gr. 6th gr. 7th gr. Primary follicles 0.51 ± 0.04 0.22 ± 0.01 ^* 0.03 ± 0.002 ^{* #} 0.28 ± 0.02 ^* 0.22 ± 0.02 ^* 0.17 ± 0.01 ^{* #} 0.24 ± 0.03 ^* Tertiary follicles 6.49 ± 0.62 6.60 ± 0.32 ^# 2.61 ± 0.22 ^{* #} 8.64 ± 0.62 ^{* #} 7.67 ± 0.51 ^# 10.80 ± 0.95 ^{* #} 4.28 ± 0.46 ^{* #} Atretic bodies 0.60 ± 0.05 1.96 ± 0.16 ^{* #} 15.04 ± 1.30 ^{* #} 11.06 ± 1.08 ^* 2.41 ± 0.18 ^{* #} 5.8 ± 00.60 ^{* #} 10.86 ± 0.92 ^* The corpus luteum proliferate. and vascularization. 13.28 ± 1.34 14.72 ± 1.30 0 ^* 5.63 ± 0.40 ^{* #} 12.88 ± 1.1 0 ^* 12.51 ± 1.10 ^# The corpus luteum glandular metamorphosis 16.22 ± 1.46 4.65 ± 0.36 ^{* #} 0 ^{* #} 2.21 ± 0.09 ^{* #} 11,47 ± 1,00 ^{* #} 1.96 ± 0.25 ^{* #} 5.94 ± 0.46 ^{* #} Yellow body heyday 3.06 ± 0.25 0.95 ± 0.08 ^{* #} 0 ^{* #} 0 ^{* #} 1.66 ± 0.12 ^{* #} 0.34 ± 0.04 ^{* #} 1,04 ± 0,08 ^{* #} Corpus luteum reverse development 4.91 ± 0.20 7.17 ± 0.52 * 27.41 ± 2.45 ^{* #} 8.26 ± 0.71 ^* 8.45 ± 0.75 ^* 10.36 ± 0.80 ^{* #} 8.16 ± 0.49 ^* * - significance of differences compared with control (group 1), p <0.05
# - significance of differences between groups 2 and 5, 3 and 6, 4 and 7, p <0.05

Claims (1)

A method for correcting disorders in the reproductive organs caused by general controlled hyperthermia (OUG) in the experiment, which consists in the fact that after exposure to the OAG, melatonin is introduced into the body of the animal.

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