RU2290940C2 - Agent for correction of acute renal insufficiency in toxic hepatorenal syndrome induced by carbon tetrachloride and method for correction of acute renal insufficiency in toxic hepatorenal syndrome induced by carbon tetrachloride - Google Patents

Abstract

FIELD: experimental biology and medicine, hepatology, nephrology.

SUBSTANCE: invention proposes using extracts of porcine or human fetal adrenal gland cortex for correction of acute renal insufficiency in toxic hepatorenal syndrome caused by carbon tetrachloride (CCl₄). For realization for correction method involves carrying out course of subcutaneous injections of extract of porcine or human fetal adrenal gland cortex by 1 injection per 24 h in the dose 2.0-2.5 ml/kg of body mass by total course 10 every day injections. Using the proposed method provides enhancing effectiveness of regenerative processes in kidneys and reducing symptoms of adverse effects.

EFFECT: valuable medicinal properties of agent.

2 cl, 2 tbl

Description

The present invention relates to experimental biology and medicine, namely hepatology and nephrology, can be used to correct acute renal failure in the treatment of toxic hepatorenal syndrome caused by carbon tetrachloride poisoning (CCl ₄ ).

The widespread use of chemicals with pronounced nephrotoxicity in various spheres of human activity and a large number of toxic agents that can cause severe hemodynamic disturbances often lead to functional or destructive changes in the kidneys, combined by the term "toxic nephropathy". Patients with toxic nephropathy account for up to 20% among other patients with acute renal failure, concentrated in the renal centers, and despite the use of modern therapeutic measures, mortality still remains high - from 48.3% to 57%. The development and study of issues of renal pathology in acute poisoning are most often experimental in nature, and clinical observations of individual renal centers are few (Shimanko I.I.). Among the observed patients in the center for the treatment of poisoning Research Institute of Emergency Care. N.V. Sklifosovsky from 1964 to 1970. 54-60% had toxic nephropathy, and 9.8% developed acute renal failure. Most often, renal dysfunction was observed with oral poisoning of CCl ₄ (100%). In case of poisoning with vinegar essence - 86.5%, ethylene glycol - 84.2%, compounds of heavy metals and arsenic - 59.5%. Renal changes in CCl ₄ poisoning are classified as lower nephros nephrosis (Lucke), cholemic nephrosis (Allen), necronephrosis, (N.F. Kanypina and B.P. Darovsky).

However, Oliver et al described ruptures of the proximal tubules, and Allen indicated lesions in both the proximal and distal tubules. CCl ₄ is the strongest hepatotropic poison due to its ability to irreversibly bind to the lipid and protein components of microsomes, the endoplasmic reticulum and liver polysome, as well as the inactivation of certain enzymes. The toxic substance (CCl ₄ ) activation of liver lipid peroxidation has been proven. In the absence of such in the kidneys, the mechanism of action on the kidneys is not clear. L.N. Zimina and L.S. Agapova believe that changes in the kidneys are secondary as a result of damage to the liver (amino acids, crystals of organic acids, an increase in the osmotic concentration of intracellular fluid), which first causes hydropic and then protein dystrophy of the nephrothelium. In this regard, as well as proteinuria, lymphatic insufficiency and impaired water-electrolyte balance, reabsorption of nephrothelium occurs. The sequential development of changes (in the wake of the proximal) in the distal tubules and capsule reflects an adaptive reaction, compensation by various departments of nephrons. Immunological mechanisms seem to play a role in kidney damage. Indirectly, this is confirmed by the development of membranous glomerulopathy and the nature of the infiltrate around the cylinders. This is hepatic nephropathy of exotoxic etiology.

The severity of the course of hepatorenal syndrome is determined by liver damage. Inadequate hemodialysis aggravates liver damage. General and organ hyperhydration is observed - hyperhydration of the brain, kidneys ("glaucoma" of the kidneys), pulmonary hyperhydration. In the pathogenesis of kidney damage CCl _4, along with other factors, a certain role is given to disorders of regional renal circulation with the development of hypoxia of the cortical substance (A.G. Gorbushin et al.). In the early stages (6-24 hours), a diffuse spasm of the arterial bed of the kidneys develops, the intensity of which increases with a decrease in the diameter of the vessels and is most pronounced in the bringing arteries. Full resolution of spasm of the microarterial bed is observed by 7 days after poisoning. Spasm of the microarterial bed of the kidney leads to the development of hypoxia of the cortical substance, causing structural and functional disorders in the nephritis of the tubules. This is the basis for the introduction of funds that eliminate spasm of the arterial bed of the kidneys and provide early restoration of renal blood flow (N.N. Neznakomtsev).

In the clinical picture of acute both inhalation and oral poisoning of CCl ₄ , several leading syndromes are distinguished: toxic syndrome, hepato- and nephropathy, thrombohemorrhagic, hypertensive and hyperhydration.

Hyperhydration in case of carbon tetrachloride poisoning (CCl ₄ ), especially against the background of the development of acute renal failure (ARF), occurs in 76% of cases and can take the form of generalized or selective organ: cerebral edema, anasarca, ascites, and “moist lungs”. The most common manifestation of organ hyperhydration is glaucoma of the kidney with the effects of hydropic nephrosis, which is the main pathogenetic mechanism of acute renal failure in case of CCl ₄ poisoning. Symptoms of impaired water-salt metabolism accompany all types of acute renal failure. However, general and especially pulmonary is most common in cases of CCl ₄ poisoning. Among the various mechanisms, the effect of CCl ₄ on the body is generally accepted as the phenomenon of increased hydrophilicity of tissues (Shimanko I.I., Ilchenko L.A., Rimaliz B.U.).

The treatment of acute renal failure is complex and includes in the early period etiopathogenetic therapy aimed at eliminating the main clinical syndromes characteristic of each type of exogenous poisoning and stimulating diuresis.

Of great importance in the treatment of the initial period of acute renal failure is an early and vigorous struggle with pain and hypovolemic shock, accompanied by a violation of hemodynamics. This is achieved by repeated administration of drugs, antihistamines, anticholinergics, prolonged administration of the glucose-novocaine mixture, cardiac glucosides, hormonal drugs - prednisone 30-90 mg, hydrocortisone 125-175 mg, ACTH 40 units. With persistent pain syndrome, perirenal novocaine blockade is used. Polyglucin, dry plasma, 5% glucose are administered intravenously. With the elimination of hypovolemia, a blood transfusion is performed. In the oligoanuric period, measures aimed at correcting the water-electrolyte balance, acid-base balance, normalization of the nitrogen balance, the most effective of which is the use of the "artificial kidney" apparatus connected with an arteriovenous shunt, are of primary importance.

Of particular importance in the treatment of patients with various poisonings that cause kidney damage is preventive therapy, including: accelerated elimination of toxic substances from the body (gastric lavage, forced diuresis, early hemo- and peritonial dialysis, specific antidote therapy); symptomatic syndromic therapy is carried out, aimed at maintaining the basic vital functions of the body.

Essential help is provided by the umbilical vein bougienage and catheterization, which allows the constant delivery of medications through the portal system, which gives a pronounced clinical effect. Of the conservative methods of treatment, stimulation of diuresis (lasix 200-400 mg 4 times a day, furosemide), therapeutic diarrhea, hemodialysis, drainage of the thoracic lymphatic duct, exchange plasma replacement (Shimanko I.I., Ilchenko L.A., Rimalis B.Ts. .). Basic therapy in the polyuric stage of the disease with hepatorenal syndrome includes general bed rest, a diet taking into account the needs and tolerance of protein, carbohydrates, fats, salt, vitamins B1, B6. Differences in tactics are determined by the prevalence of liver or kidney damage. Corticosteroid therapy is carried out for a duration of 2 to 6 months, in doses of 40-80 mg of prednisone, a course of 2 weeks to 2 months (average 3 weeks) with a gradual decrease in dose by 2.5 mg every 2-3 days; anabolic steroids - retabolil, durabolil 50 mg 1 time in 10-15 days. Antihypertensives, diuretics - saluretics, spirolactone, osmotically active substances in normal hemodynamics (Shulutko B.I., 1976).

Glucocorticosteroid drugs are most important in the treatment of a number of diseases of the liver and kidneys. We can assume that today corticosteroid therapy is leading in the main forms of therapeutic pathology of the liver and kidneys. Only thanks to these means, many previously incurable diseases began to yield to therapy and more often give remissions. However, with most options for acute renal failure in the oligoanuric stage, corticosteroid therapy is contraindicated (Naumova V.I., Papayan A.V.). With secondary hemoliticouremic syndrome, it is still of paramount importance. Prednisone is prescribed in a daily dose of 3-5 mg / kg; the appearance of diuresis against this background can be an additional diagnostic diagnostic test, confirming the role of systemic vasculitis in the etiology of acute renal failure (Markova I.V. et al.). An unconditional indication for corticosteroid therapy is those forms of acute renal failure that arose as a result of toxic-allergic damage to the renal vessels in connection with hypersensitivity to drugs, with hemodynamic disorders associated with poisoning (Naumova V.I.). Severova A.E. draws attention to the appropriateness of using corticosteroids for diffuse drug nephritis. Theoretical prerequisites for treatment with corticosteroids are: a pronounced anti-inflammatory effect due to a decrease in vascular wall permeability, decreased exudation, activation of antifibrinolysin, inhibition of sweating of the liquid part of the blood into the inflammatory focus, suppression of cellular , inhibition of fibroplastic reactions, the growth of antibodies and gammaglobulins in the blood, the formation of histamine. Corticosteroids suppress local and general allergic reactions.

For the prototype of the present invention, a method for the correction of acute renal failure in hepatorenal syndrome induced in the experiment by carbon tetrachloride, including the action of a hormone-containing substance, namely a synthetic analogue of the hormone of the adrenal cortex of prednisolone by introducing it at a dose of 1 mg / kg of body weight with a general course of 2 weeks to several months. (B.I.Shulutko. Hepatorenal syndrome. Leningrad, Medicine, 1976, p. 166-167.

However, the prototype method has disadvantages. The observed increase in the processes of regeneration of the renal tubule epithelium is not effective enough, and therefore, sufficient recovery of urine outflow from the capsule space and removal of renal edema is not provided (see Tables 1, 2). In addition, prednisone has a number of side effects, namely, a negative effect on protein metabolism, a decrease in amino acid composition, increased blood pressure, impaired antibody production, the development of pseudo-diabetes, and even pancreatic cell damage, even true diabetes. Often there is a treatment-specific steroid syndrome of cushingism, sodium retention and excessive excretion of potassium, have a stimulating effect on gastric secretion and pepsin secretion, digesting ability of juice and ulceration while reducing mucus formation.

The objective of the invention is:

- expanding the arsenal of existing drugs for the correction of acute renal failure in hepatorenal syndrome;

- more effective strengthening of the processes of regeneration of the epithelium of the tubules and

- ensuring due to this recovery of the outflow of fluid (urine) from the capsule space, less compression of the glomerulus loops, removal of edema of the kidneys;

- reduction of side effects due to the fact that extracts of pork and fetal human adrenal glands contain much less concentration, which have side effects of the components.

The problem is achieved by the fact that they conduct a course of subcutaneous injections of the extract of the extract of the bark of pork or fetal human adrenal glands, 1 injection per day at a dose of 2.0-2.5 ml / kg body weight for a total course of 10 daily injections.

An experiment was conducted on 23 outbred rats, which were injected with a mixture of carbon tetrachloride (0.2 ml) with vegetable oil (0.1 ml) in an amount of 20 injections every other day to obtain toxic hepatorenal syndrome. After seeding, 6 animals underwent a 30% liver resection.

Subsequently, treatment was carried out with extracts of bark of pork or fetal adrenal glands of 0.5 ml per day in the amount of 2 injections (3 animals), 10 injections (10 animals). To compare the effect of treatment of toxic hepatorenal syndrome, 11 animals were injected with prednisolone in a volume of 0.5 ml (dose of 1 mg / kg weight) on an alcohol basis as well as adrenal cortex extracts: 4 animals 2 injections and 7 animals 10 injections. As a control, the liver and kidneys of intact animals (3 rats) were studied in 1 animal with toxic hepatorenal syndrome without treatment for 10 days after seeding. The other two died before the end of the experiment.

The extract of the extract of the pork and fetal adrenal cortex was obtained as follows: the adrenal glands of pigs and newborns (who died in childbirth) frozen in liquid nitrogen were crushed using a spinning top and subjected to ethanol extraction. Water-soluble compounds were removed by freezing. The resulting extract was transferred to alcohol, and then into an isotonic sodium chloride solution with a 10% concentration of ethyl alcohol. From 3 g of adrenal tissue, 1 ml of extract was obtained. The technical scheme for the production of the extract of the adrenal cortex extract is described in the literature (8). In 0.5 ml of extracts of pork adrenal cortex contained 65 nmol of hydrocortisone, 0.83 nmol of dehydroepiandrosterone and 0.1 nmol of progesterone. 0.5 ml of hydrocortisone, 1.15 nmol of dehydroepianrosterone and 0.45 nmol of progesterone were contained in 0.5 ml of fetal adrenal cortex extract.

Control animals were identical in weight and gender, as in the experimental groups.

Thus, the animals were divided into 9 groups:

Group 1 - intact

Group 2 - animals with toxic hepatorenal syndrome, received 2 injections of prednisolone,

Group 3 - animals with toxic hepatorenal syndrome, received 2 injections of the extract of pork adrenal cortex,

Group 4 - animals with toxic hepatorenal syndrome, liver resection, received 10 injections of prednisone,

Group 5 - an animal with toxic hepatorenal syndrome, liver resection, received 10 injections of the extract of the pork adrenal cortex,

6 group - animals with toxic hepatorenal syndrome without liver resection, received 10 injections of prednisone,

Group 7 - animals with toxic hepatorenal syndrome without liver resection, received 10 injections of pork adrenal cortex extract,

8 group - animals with toxic hepatorenal syndrome without liver resection, received 10 injections of fetal adrenal cortex extract,

Group 9 - an animal with toxic hepatorenal syndrome, 10 days after liver resection, without treatment.

Animals of all experimental groups were slaughtered after the end of the experiment. Pieces of the liver and kidneys taken during the slaughter of animals were fixed in a 10% solution of neutral formalin and embedded in paraffin. On histological sections of the liver stained with hematoxylin and eosin, the number of binuclear hepatocytes was counted, the results were expressed in ppm. For a more complete idea of the effectiveness of the therapeutic effect of the introduced substances, along with a visual description of the histologic drugs in the liver parenchyma, quantitative indicators of reparative processes were determined. For this purpose, the number of normal (NG) and dystrophic hepatocytes (DG) was calculated, followed by the calculation of the normalization coefficient of the parenchyma - KNP = NG / DG. The results were expressed in arbitrary units (cu) per test area of the drug. Dystrophic hepatocytes included non-nuclear cells with a torn cell membrane, as well as cells with a nucleus in a state of karyopiknosis and karyorexis. The measurements were carried out using morphometric grids of S. B. Stefanov using recommendations on the quantitative morphology of biopsy samples of the digestive organs (Solopaeva, Stefanov). The digital material was processed by the Student's method, the confidence interval of the fluctuation of the arithmetic mean value at p = 0.05 was determined by the formula and tables of RP Strelkov [10].

After histological sections of the kidneys stained with hematoxylin and iosin, after a general examination of the preparations, the size of the glomeruli and vascular body was determined using a morphometric ruler, the value of one division of which was verified by a micrometer. The total area of the glomerulus and vascular body was calculated using the formula S = π · 0.12 ² · a / 2 · b / 2, where π = 3.14, a is small size, b is large size, 0.12 ² is a constant recalculation of the magnification of the microscope; the value of one division of the ruler = 16.6 microns. The area of the glomerular capsule was determined by the difference between the areas of the glomerulus and vascular body.

The performed morphological studies of the liver in the same animals as the study of the kidneys showed a lesser severity of lesions with the addition of adrenal cortex extracts (Table 1). The content of normal hepatocytes was close to normal after a 10-day treatment with an extract of pork adrenal cortex (15.0 ± 0.81 cu against 8.2 ± 0.41 cu) in animals treated with prednisolone, p 4- 5 = 0.0022. Similar relations: the content of normal hepatocytes was observed in animals of groups 7 and 8 compared with group 6, p 6-7 = 0.005, p 6-8 = 0.0035. In the liver of animals treated with prednisolone, an increased content of dystrophically altered hepatocytes was noted after 2 injections of drugs (groups 2 and 3), although the difference in their content is not significant. More convincing were the differences in the content of dystrophically altered hepatocytes after 10 injections of prednisolone in group 6 (6.9 ± 0.54 cu) in comparison with the data in group 7 (3.6 ± 0.17 cu, p 6-7 = 0.0033) and in group 8 (4.37 ± 0.08 cu, p 6-8 = 0.0077).

The normalization coefficient of the liver parenchyma (KNP) was significantly reduced with toxic hepatorenal syndrome in groups of animals treated with prednisolone. After 10 injections of extracts of pork adrenal cortex, it corresponded to standard indicators in group 5 (3.8 ± 0.16) and in group 7 (3.92 ± 0.17) p 4-5 = 0.0012, p 6-7 = 0.0001. The content of binuclear hepatocytes reflecting parenchyma regeneration, hepatocyte division corresponded to standard values in animals after administration of extracts of pork adrenal cortex: 19.2 ± 0.42 ‰ in the third group, 20.3 ± 1.25 ‰ in the fifth group. On the contrary, in animals treated in comparable groups with prednisone, the content of binuclear cells was sharply reduced: 7.67 ± 0.01 ‰ in the second group, p 2-3 = 0.0001, 6.83 ± 2.13 ‰ in the fourth group, p 4 -5 = 0.0049. The lowest values for all studied parameters were observed in an animal with toxic hepatorenal syndrome, which remained untreated for 10 days after seeding with carbon tetrachloride.

When viewing the kidney preparations of animals with toxic hepatorenal syndrome caused by carbon tetrachloride, with subsequent resection of the liver and without it, marked changes were noted in all groups. In animals, an increase in the size of the glomeruli, the diameter of the proximal and distal tubules, collecting ducts, a decrease in the height of the epithelium of the tubules, karyorexis, necrosis and necrosis of the tubules, interstitial edema, stratification of the glomerulus loops (glomeruli), compression and decay of the glomerulus loops with accumulated fluid, and cellular infiltration, and cellular tubule epithelium regeneration.

The morphometric data of the glomeruli of the kidneys are presented in table 2. The area of the glomeruli was increased in all groups of experimental animals. The area of the glomerular vascular body differed in groups and depended significantly on the area of the capsule space. Injected drugs to animals had an effect on both components of the glomeruli. After 2-fold administration of prednisone, the glomerular body area in animals of the second group was increased (8026.9 ± 1880.1 μm ² ) against the norm, p1-2 = 0, while in animals of the third group that received extracts of pork adrenal cortex, its dimensions did not differ from the standards (6747.8 ± 1314.5 μm ² ) p1-3 = 0.0611. The differences between the second and third groups are highly significant p 2-3 = 0.0001. The space of the glomerular capsule also increased against the norm, but to a greater extent this was presented in animals of the third group who received 2 injections of extracts of pork adrenal glands (5510.9 ± 1642.2 μm ² ) p 1-2.3 = 0. The difference between the second and third groups is the same highly significant p 2-3 = 0. The increase in body size in animals of the second group is due to a smaller compression of the capsule with its liquid (primary urine) and reflects the greater anti-inflammatory effect of prednisolone, which reduces the increased permeability of the vascular wall than extracts of pork adrenal cortex.

When comparing the results of morphometric measurements of glomeruli in animals of the fourth and fifth groups treated for 10 days, we pay attention to the inverse ratios of the areas of the vascular body and capsular space, namely the increase in the body area after administration of extracts of the bark of the pork adrenal glands (8135.4 ± 2358 μm ² against 6736.3 ± 1946.2 μm ² ) p 4-5 = 0.008, p 3-5 = 0.0267. The decrease in glomerular body area with 10-day administration of prednisone was also significant in comparison with the second group of animals, p 2-4 = 0.0563. This can be explained by a faster restoration of tubule integrity with the introduction of extracts of pork adrenal cortex, while prednisolone inhibits regeneration. In this regard, the capsule space was reduced in animals treated with extracts of pork adrenal glands (3441.7 ± 1138.5 μm ² ), a decrease in the pressure of the liquid on the vascular body led to the smoothing of the previously compressed glomerulus loops, which is manifested by the multiplicity of the vascular body. The delay in repair of tubular epithelium with the introduction of prednisone contributed to a decrease in drainage of the tubules and compression of the glomerulus loops with liquid, and a decrease in their area.

The general pattern of slow recovery of the nephron with the introduction of prednisone is observed when comparing the data of 6.7 and 8 groups. With a 10-day administration of prednisone, the size of the glomerulus and its constituents (body and capsules) did not differ much from the data obtained in groups 4 and 5, with liver resection and those treated with prednisone, p 4-6 = 0.503, p 4-6 = 0.742, p 4- 6 = 0.667, respectively. Performance was better with the administration of extracts of pork adrenal cortex. They also did not differ from the indicators of the fifth group, p 5-7 = 0.402, p 5-7 = 0.754, p 5-7 = 0.561, respectively. But they were better, in essence, than in animals treated with prednisolone - larger body sizes and smaller capsule sizes p 6-7 = 0.0261.

The best results were obtained in animals that were injected with fetal adrenal cortex extract. The size of the glomeruli after a 10-day administration of the drug was significantly smaller than in animals of groups 6 and 7 (p 6.7-8 = 0), the vascular body (p 7-8 = 0.0001) and the capsule space ( p 6.7-8 = 0.0001). In animals that received 10 injections of extracts of fetal adrenal glands, the values of the areas of the renal glomerulus, body and capsule space, although they exceeded the standards, were very close to them and there were no statistical differences.

Thus, a comparative study of the therapeutic effect of various hormone-active substances on the dynamics of changes in the tissues of the liver and kidneys with toxic hepatorenal syndrome caused by carbon tetrachloride showed that the extracts of the pork and fetal adrenal cortex are inferior to prednisone only in an anti-inflammatory effect, which is reflected in a decrease in vascular permeability . However, extracts of the adrenal cortex better than prednisolone enhance the regeneration of hepatocytes and tubule epithelium than provide recovery of the outflow of fluid (urine) from the capsule space, less compression of the glomerulus loops, and removal of kidney edema, which is the most important pathogenetic link of toxic nephropathy in carbon tetrachloride poisoning . The results of the study allow us to offer extracts of bark of pork and fetal adrenal glands as a means for the treatment of toxic hepatorenal syndrome in combination with other therapeutic drugs.

The authors of the invention did not reveal in the sources of information information on the use of extracts of extracts of pork and fetal adrenal glands as a means for the treatment of hepatorenal syndrome.

Information sources

1. Gorbushin A.G. Change in kidneys due to carbon tetrachloride poisoning and their expert assessment. Abstract of dissertation for the degree of candidate of medical sciences, 1973.

2. Markova I.V., Nezhentsev M.V., Papayan A.V. Treatment of Kidney Diseases in Children (A Guide for Physicians). Sotis. St. Petersburg, 1994, p. 249.

3. Mashkovsky M.D. Medicines M., Medicine 1986, v. 1, 568-570.

4. Naumova V.I., Papayan A.V. Renal failure in children. Medicine, 1991, p. 81.

5. Strangers M.N. The role of changes in the structural components of the microarterial bed in the pathogenesis of kidney damage in carbon tetrachloride poisoning. Anesthesiology and resuscitation. 1979, 5, 51-53.

6. Rimalis B.Ts. Clinic, diagnosis and intensive care of hepatorenal syndrome in case of inhalation poisoning with carbon tetrachloride. Therapeutic Archive 1981, v. 53, No. 4, p. 93-98.

7. Rosenzweich P.E., Sander Yu.K. Technology of medicines and galenic drugs (Guide for pharmacists) Medicine. Leningrad branch 1967, 695-696.

8. Severova E.Ya. Medicinal kidney. Fundamentals of Nephrology, edited by Acad. Academy of Medical Sciences of the USSR E.M. Tareeva. Moscow, Medicine, 1972, v. 2, p. 682-685.

9. Solopaeva I.M., Stafanov S.V., Zhdanova T.F. Quantitative morphology of the digestive system (Methodological recommendations) Gorky, 1982, 16 pp.

10. Strelkov RB Method for calculating standard error and confidence interval in arithmetic means using tables. Sukhumi, Alashara, 1966, 12 pp.

11. Shimanko I.I. Nephropathy in acute exogenous poisoning, its conservative and surgical treatment. Abstract of dissertation for the degree of Doctor of Medical Sciences. Moscow, 1972.

Table 1
The effect of prednisolone and adrenal cortex extracts on liver morphometric parameters in toxic hepatorenal syndrome caused by CCl ₄ and liver resection. Rat number Group NG cu DG cu KNP Dual class ^_(0/00) 1 group n = 3 Intact 15.9 ± 0.41 4.0 ± 0.12 3.98 ± 0.06 20.33 ± 0.34 2 group Toxic 8.4 ± 0.176 5.1 ± 0.4 1.68 ± 0.09 7.67 ± 0.01 n = 4 Hepatitis + P2-3 = 0.021 p2-5 = 0.0469 P2-3 = 0.0001 P2-3 = 0.0001 Prednisone 2 p2-5 = 0.0015 P2-6 = 0.0437 p2-5 = 0.0003 p2-5 = 0.0005 injections p2-7 = 0.0025 P2-7 = 0.0151 P2-6 = 0.0039 P2-7 = 0.0016 p2-8 = 0.0014 p2-7 = 0,0003 P2-8 = 0.0084 P2-8 = 0.0001 3 group Toxic 12.25 ± 0.43 4,5 ± 0,18 2.75 ± 0.05 19.2 ± 0.42 n = 4 Hepatitis + pig 2 p3-4 = 0.0011 p3-6 = 0.0085 p3-4 = 0,0008 p3-4 = 0.0023 injections p3-5 = 0.0203 p3-7 = 0.0122 p3-5 = 0.0018 p3-6 = 0.0104 p3-6 = 0.0074 p3-6 = 0 p3-7 = 0.0011 p3-7 = 0.0015 p3-8 = 0.0001 p3-8 = 0.0037 4 group Toxic 8.2 ± 0.41 , 4.63 ± 0.15 1.81 ± 0.11 6.83 ± 2.13 n = 3 hepatitis + resection + p4-5 = 0.0022 p4-5 = 0.025 p4-5 = 0.0012 p4-5 = 0.0049 prednisone 10 p4-7 = 0.003 p4-6 = 0.018 p4-6 = 0.006 p4-7 = 0.0274 injection p4-8 = 0.0013 p4-7 = 0.0055 p4-7 = 0.0011 p4-8 = 0.0011 5 group Toxic 15.0 ± 0.81 4.03 ± 0.15 3.8 ± 0.16 20.3 ± 1.25 n = 3 Hepatitis + resection + p5-6 = 0.0027 p5-6 = 0.0054 p5-6 = 0.0001 p5-6 = 0.0014 pork 10 injection p5-8 = 0.0115 p5-7 = 0,0007 p5-8 = 0.0019 6 group Toxic 9, ± 0.83 6.9 ± 0.54 1.29 ± 0.04 10.4 ± 2.84 n = 4 hepatitis + p6-7 = 0.005 p6-7 = 0.0033 p6-7 = 0.0001 prednisone 10 p6-8 = 0.0035 p6-8 = 0.0077 p6-8 = 0 injection 7 group Toxic 13.86 ± 0.74 3.6 ± 0.17 3.92 ± 0.17 13.6 ± 0.64 n = 3 hepatitis + swine 10 p7-8 = 0.0099 p7-8 = 0.0082 p7-8 = 0.0069 injection 8 group Toxic 13.2 ± 0.35 4.37 ± 0.08 3.08 ± 0.06 10.5 ± 0.17 n = 3 hepatitis + fetal. 10 injection 9 group Toxic 7.4 5.7 1.71 4.75 n = 1 hepatitis + resection without treatment after 10 days Operational the control Indicated: NG - normal hepatocytes, DG - degenerated hepatocytes, KNP - coefficient of normalization of the parenchyma

table 2
The effect of prednisolone and adrenal cortex extracts on rat glomerular morphometric parameters in toxic hepatorenal syndrome caused by CCl ₄ and liver resection. No. Animal groups and injectable drugs Number of glomeruli Area in microns ² Glomerulus Glomerulus bodies Space
capsules one intact 60 8196.5 ± 1617.2 6279.2 ± 1293.3 1917.3 ± 910.9 Group P _{1-2,3,4,5,6,7,9} = 0 p _1-2,5,7 = 0 p _{1-2,3,4,5,6,7,9} = 0 n = 3 P _1-8 = 0.0001 p _1-4 = 0.128 p _l-8 = 0.003 p _1-6 = 0.001 p _1-8 = 0.0025 p _1-9 = 0.0015 2 Toxic hepatitis 60 11862.1 ± 2373.2 8026.9 ± 1880.1 3835.2 ± 1165.6 Group nephrosis + resection p _2-3 = 0.674 p _2-3 = 0,0001 p _2-3 = 0 n = 3 liver + prednisone p _2-4 = 0.233 p _2-4 = 0,0006 p _2-4 = 0.0019 2 injections p _2-9 = 0.0634 p _2-9 = 0 p _2-9 = 0 3 Toxic hepatitis nephrosis 60 12258.7 ± 2010.1 6747.8 ± 1314.5 5510.9 ± 1642.2 Group + liver resection + p _3-5 = 0.136 p _3-5 = 0,0003 p _3-5 = 0 n = 3 ext. pork bark p _3-9 = 0.283 p _3-9 = 0 p _3-9 = 0 above 2 injections four Toxic hepatitis nephrosis 60 11325.7 ± 2543.2 6736.3 ± 1946.2 4589.3 ± 1371.2 Group + liver resection + p _4-5 = 0.623 p _4-5 = 0,0008 p _4-5 = 0 n = 3 prednisone 10 p _4-6 = 0.0174 p _4-6 = 0.0612 p _4-6 = 0.0664 injection p _4-9 = 0.0047 p _4-9 = 0,0002 p _4-9 = 0 5 Toxic hepatitis nephrosis 60 11577.1 ± 2931.0 8135.4 ± 2358.5 3441.7 ± 1138.5 Group + liver resection + p _5-7 = 0.0151 p _5-7 = 0.0773 p _5-7 = 0.0196 n = 3 ext. pork adrenal. p _5-9 = 0.0266 p _5-9 = 0 p _5-9 = 0 10 injections 6 Toxic hepatitis 60 12512.2 ± 2882.1 7459.3 ± 2285.8 5052.8 ± 1404.7 Group nephrosis + prednisone p _6-7 = 0.54 p _6-7 = 0.001 p _6-7 = 0.0001 n = 3 10 injections p _6-9 = 0.668 p _6-8 = 0.565 p _6-8 = 0 7 Toxic hepatitis nephrosis 60 12829.3 ± 2669.9 8849.6 ± 2079.1 3979.7 ± 1355.1 Group + ext. pork bark p _7-8 = 0 p _7-8 = 0.0001 p _7-8 = 0 n = 3 adrenal gland 10 injections p _7-9 = 0.85 p _7-9 = 0 p _7-9 = 0 8 Toxic hepatitis nephrosis 60 9878.2 ± 2539.5 7163.9 ± 1756.7 2714.2 ± 1281.6 Group + ext. the cortex is fetal. p _8-9 = 0 p _8-9 = 0 p _8-9 = 0 n = 3 Adrenal gland 9 group Toxic hepatitis nephrosis + liver resection without treatment after 10 days 60 12738.4 ± 2798.8 5473.2 ± 1349.7 7265.1 ± 2798.8

Claims (2)

1. The use of extract extracts of the bark of pork or fetal human adrenal glands for the correction of acute renal failure in toxic hepatorenal syndrome induced by carbon tetrachloride. 2. A method for the correction of acute renal failure in toxic hepatorenal syndrome induced by carbon tetrachloride, including exposure to a hormone-containing substance, characterized in that a course of subcutaneous injections of the extract of the extract of the bark of pork or fetal human adrenal glands by 1 injection per day in a dose of 2.0-2, 5 ml / kg body weight for a total of 10 daily injections.