RU2424579C1 - Method for prevention of chronic toxic cardiopathy in experimental animals - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: in studying methods for prevention the injuries associated with chronic toxic action of heavy metals in experimental animals, a chronic molybdenum intoxication is simulated by a daily introduction of an ammonium molybdate solution through a probe in a stomach in a dose of 50 mg/kg on a metal base in which a unit of the solution 1 ml is equal to molybdenum 50 mg. Simultaneously every second day for two months, the natural sorbent yrlite-1 in the form 6% suspension is introduced in an animal through a probe into a stomach in an amount 2.5% of body weight. ^ EFFECT: effective prevention of chronic toxic cardiopathy by means of prescribed doses of a certain sorbent in excessive molybdenum body intake. ^ 2 tbl

Description

The invention relates to ecology, medicine, toxicology, experimental biology and can be used to study methods for the prevention of lesions in the chronic toxic effects of heavy metals, in particular molybdenum, on the functional state of the cardiovascular system.

Recently, the physiological effects of trace elements have been intensively studied in connection with their environmental pollution. It is known that the cardiovascular system undergoes one of the first toxic effects of molybdenum. The chronic effect of metal on the body leads to inhibition of the contractile function of the myocardium, worsening of central hemodynamics and coronary circulation (Bompart G., Christiane P., Prkvot D., 1990). The degree and nature of the damaging effect of molybdenum directly depends on the route of entry into the body and the concentration of metal in the cell (Pandey R., Kumar R., 2002). Questions related to the study of the distribution of metals in organs and tissues of the body, the mechanisms of their binding to the biocomponents of the cell, the degree of their fixation, as well as the search for means that accelerate their excretion are of certain scientific and practical interest.

There are many detoxicants that can remove non-ferrous metals from the body. We used natural sorbents of North Ossetia-Alania - Irlites. They have unique sorption, molecular sieve properties, catalytic and ion-exchange ability. The physicochemical parameters of irlite-1 make it possible to consider it as a potential enterosorbent with a wide spectrum of action, as an effective means for removing heavy metals, various toxins, and saturating it with microelements from the body.

The invention is aimed at solving the problem of developing a method for the prevention of chronic toxic cardiopathy in experimental animals.

The main technical result of the proposed invention is a significant reduction in the cardiotoxic effect of molybdenum in chronic poisoning by reducing the accumulation and increasing excretion of heavy metal from the body, which is confirmed by the results of morphofunctional studies of the heart.

To achieve this technical result, the claimed invention of a method for the prevention of chronic toxic cardiopathy in experimental animals with chronic molybdenum intoxication has the following significant features: the animals are injected with a natural sorbent Irlit-1 in the form of 6% suspension through the tube into the stomach in an amount of 2% every two days, 5% of body weight simultaneously with the daily administration of a solution of ammonium molybdate through a tube into the stomach at a dose of 50 mg / kg in terms of metal, in which 1 ml of solution per unit accounts for 50 mg of molybdenum.

The proposed method is characterized in that for the first time, the natural sorbent Irlit-1 is used to prevent chronic toxic cardiopathy in experimental animals with chronic poisoning with molybdenum (VI), by reducing the accumulation of metal and increasing its excretion from the body. Dosed administration of ammonium molybdate and a sorbent facilitates precise control of the dose-dependent effect.

Between the signs of the proposed method and the result, there is the following causal relationship: prophylactic administration of 6% suspension of natural zeolite - irlite-1 - through a probe into the stomach in an amount of 2.5% of body weight, every other day for two months simultaneously with intragastric administration of a molybdate solution ammonium, leads to a decrease in the intake of experimental animals of molybdenum and an increase in its elimination through the gastrointestinal tract, a decrease in tissue accumulation and a decrease in cardiotoxic effects of etnogo metal. The claimed method is effective, cost-effective and easily reproducible.

According to the information available to the authors, the set of essential features characterizing the essence of the claimed invention is not known, which allows us to conclude that the invention meets the criterion of "novelty."

The search results for known solutions in this and related fields have shown that the essence of the claimed invention does not follow explicitly from the prior art for specialists, since the above-mentioned possibility of obtaining a method for the prevention of chronic toxic cardiopathy in experimental animals is not revealed. Therefore, the invention meets the condition of patentability "inventive step".

The set of essential features characterizing the essence of the invention can be repeatedly used in medicine to obtain a result consisting in an effective and easily reproducible method for the prevention of chronic toxic cardiopathy in experimental animals, by reducing the accumulation and increasing excretion of molybdenum from the body during chronic poisoning, which allows us to conclude on the compliance of the invention with the criterion of "industrial applicability".

This method is as follows. To obtain a toxic substance, ammonium molybdate is dissolved in sterile distilled water in such a way that 50 mg of molybdenum (in terms of metal) falls per unit of solution equal to 1 ml. For every 100 g of rat weight, 0.1 ml of solution (5 mg of Mo) is injected, which is not a water load on the animal's body. By grinding and dissolving the zeolite Irlit-1 in water, a 6% aqueous suspension is prepared and introduced in an amount of 2.5% of body weight. A solution of ammonium molybdate is administered through a tube into the stomach at a dosage of 50 mg / kg daily 1 time per day for two months to two groups of animals (No. 1 and No. 2). At the same time, from the first day of the introduction of the metal, group 2 is injected a suspension of zeolite through the probe into the stomach every other day with the help of a refillable syringe with a specially curved needle on which the probe is worn.

At the end of the experiment, the rats were killed using thiopental. For histological studies, tissue samples of the heart were fixed in 10% neutral formalin, and then subjected to paraffin filling, followed by preparation of sections with a thickness of 7-8 microns. Sections were stained with hematoxylin and eosin. The sections were studied in transmitted light using a Mikmed-1 microscope under an magnification of 80 * 200 * 400.

The essence of the method is confirmed morphologically: in the drawing - myocardial tissue in chronic molybdenum intoxication against the background of the prophylactic administration of the natural sorbent Irlit-1. Brief description of the drawings: myocardial tissue with less pronounced histopathological changes - insignificant histiocytic infiltration of the stroma (1), moderate parenchymal dystrophy of tissue structures (2) with chronic intoxication with ammonium molybdate for 2 months. against the background of prophylactic administration of the sorbent Irlit-1.

The effectiveness of the proposed method is confirmed by the following experimental data.

Example. In the experiment, normotensive male rats weighing 200-300 g of the Wistar line were used. Two groups of animals every day for two months through a tube into the stomach were injected with a solution of ammonium molybdate at a dose of 50 mg / kg (No. 1 and No. 2). The controls were intact animals (No. 3). The natural sorbent Irlit-1 in the form of 6% suspension in the amount of 2.5% of body weight was administered through a probe into the stomach of group No. 2 every other day.

At the end of the experiment, under the conditions of intraperitoneal anesthesia with thiopental sodium, experimental animals measured mean arterial pressure (SBP) invasively (in a bloody manner). A plastic catheter was inserted into the right femoral artery, filled with a 10% heparin solution, which was then connected to the DDA electromeanometer. Registration was carried out on an MX-04 pressure gauge, data was printed out using an Epson JX-1050 printer. ECG was recorded in the II standard lead. Measurement of minute blood volume (IOC) was carried out by thermodilution. By special formulas, the cardiac index (SI), stroke index (UI), and specific peripheral vascular resistance (OSS) were calculated. Mathematical processing of the obtained results was performed by the method of variation statistics using Student's criterion.

Chronic molybdenum intoxication in experimental animals caused a significant decrease in mean blood pressure compared with the intact group (p <0.05) (Table 1.). Arterial hypotension in the experimental group of animals was associated with a significant decrease (p <0.001) in cardiac index (Table 2), despite the fact that the specific peripheral vascular resistance was significantly higher (p <0.001).

Table 1
The effect of Irlit-1 on the level of mean arterial pressure in chronic molybdenum intoxication Experience Conditions Stat indicator GARDEN (mmHg) Background M ± m 98.7 ± 1.2 Mo (VI) M ± m 94.9 ± 1.32 p * Mo (VI) + Irlit-1 M ± m 96.7 ± 2.2 p - Note: (*) - significant (p <0.05) change compared to the background.

table 2
The effect of irlite-1 on the values of the cardiac index in chronic molybdenum intoxication Experience Conditions Stat. indicator Cardiac Index (ml / 100 g) Background M ± m 44.69 ± 0.49 Mo (VI) M ± m 33.11 ± 0.68 p * Mo (VI) + Irlit-1 M ± m 35.23 ± 0.72 p * Note: (*) - significant (p <0.05) change compared to the background.

In rats treated with intragastric administration of ammonium molybdate sorbent Irlit-1, there was a restoration of SBP to the level of control animals. The restoration of SBP was due to an increase in the cardiac index (Table 2.). Thus, the studies showed that the prophylactic use of the natural sorbent Irlit-1 reduces the degree of manifestation of cardiac hemodynamic function disorders developing during molybdenum intoxication. Identified functional changes were confirmed by morphological studies.

Morphologically, in experimental animals with chronic molybdenum intoxication (2 months), parenchymal dystrophy, swelling of cardiomyocytes with focal loss of transverse striation, focal necrosis of cell groups were observed in the myocardium. In the stroma of the myocardium, interstitial edema, loosening of the interstitium and moderate lymphohistiocytic infiltrates were noted. Pathological changes most intensely manifested mainly subendo- and subepicardial, in groups of muscle cells located along the venous knee of the capillaries and small veins.

When Irlit-1 was prescribed in the animal myocardium, the above-described pathological pattern was revealed histologically, which is characteristic of toxic cardiopathy in the form of dystrophic and discirculatory changes, but less severe in severity compared to the group of animals treated with ammonium molybdate in isolation (see drawing). In addition, hyperplasia of immunocompetent myocardial cells was noted as a manifestation of the compensatory-adaptive reaction of the body to damage to cellular structures.

From the above it follows that the use of the natural sorbent Irlit-1 is an effective way to prevent chronic toxic cardiopathy with excessive intake of molybdenum in the body in experimental animals.

Claims (1)

A method for the prevention of chronic toxic cardiopathy in experimental animals, characterized in that the animals are injected with a natural sorbent Irlit-1 in the form of 6% suspension through a tube into the stomach in an amount of 2.5% of body weight every other day at the same time as daily administration of a molybdate solution ammonia through a probe into the stomach, at a dose of 50 mg / kg in terms of metal, in which 50 mg of molybdenum per unit of solution equal to 1 ml.

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