RU2110269C1 - Method of stimulation of protein-synthesizing liver function after its resection in experiment - Google Patents

Abstract

FIELD: biology, medicine. SUBSTANCE: method involves the use of chorionic gonadotropin with mussel food hydrolysate simultaneously. Method can be used for treatment of liver damages accompanying with decrease of protein-synthesizing function. EFFECT: enhanced protein-synthesizing function of liver due to the total protein synthesis increase.

Description

 The invention relates to biology and medicine and can be used to treat liver lesions, accompanied by a decrease in the protein-synthetic function of the organ.

 It is known that with liver lesions of various etiologies, the protein-synthetic function of this organ is often violated, the correction of which is essential in the treatment of liver diseases. In this regard, the search for drugs that enhance the synthesis of protein in the liver is important and relevant.

 Known stimulants of protein synthesis are some anabolic steroids, such as metaandrostenolone, phenobolin, retabolil, silabolin. But their use is accompanied by hepatomegaly and jaundice, allergization of the body and expression of androgenic effect. All this limits the use of these anabolic steroids in order to enhance the protein-synthetic functions of the liver (MD Mashkovsky. Medicines, vol. 1.-M .: Medicine, 1985, p. 603-608).

 Chorionic gonadotropin, which has the ability to stimulate protein synthesis in the liver, was selected as the prototype of the invention (I.M.Solopaeva. Stimulation of the regeneration of normal and pathologically altered liver. Diss. For work. Academician of medical sciences, Gorky, 1969).

 However, the action of gonadotropin chorionic (GC) is less effective.

 The aim of the invention is to enhance the protein-synthetic function of the liver.

 This goal is achieved by the simultaneous use of GC and hydrolysis from food mussels (MIGI-K) for the first time as a means to stimulate the protein-synthetic function of the liver.

 Thus, the present invention meets the criteria of "novelty" and "inventive step", because a new, previously unknown application of GC preparations with MIGI-K was found, and the new field of use of the complex of these drugs does not obviously follow from the previously known properties of MIGI-K and its complex with GC and is based on the new property of these drugs established by the authors of this application.

 GC has previously been used to treat endocrine pathology.

 It is used (M. D. Mashkovsky. Medicines. M: 1985, p. 536-537) with a decrease in the function of the sex glands, due to a violation of the hypothalamus and pituitary gland. The drug is indicated in patients with interstitial-pituitary insufficiency (Beat Simonds, Skien syndrome, panhypopituitarism of any etiology, andipozogenital dystrophy, pituitary dwarfism with the phenomena of sexual infantilism, hypogonadotropic hypogonadism with the phenomena of eunuchoidism and late ovarian dysfunction), development, with habitual and threatening abortion in the first trimester of pregnancy, with dysfunctional uterine bleeding in women of childbearing age, with bilateral cr ptorhizme after surgery with signs evnuhoidizma. The drug is used for the differential diagnosis of primary and secondary hypogonadism in men.

 The hydrolyzate from food mussels (MIGI-K) is a known substance authorized as a food additive, which was approved by the USSR M3 (N 143-5 / 109-12 of 09.15.89).

 When studying the effect of GC in complex with MIGI-K administered after liver resection, it turned out that the amount of total protein in rat liver 24 and 48 hours after surgery and administration of the GC complex with MIGI-K was 48.39 ± 0.52 and 56 , 18 ± 0.89 g%, respectively, and significantly (P less than 0.01) differed from the amount of total protein in the liver of control animals that underwent only liver resection for the same study period (30.02 ± 0.27 and 25.14 ± 0.89 1%), of the total protein in the liver of rats received after GC resection (34.96 ± 0.33 and 34.80 ± 0.92 g%, respectively, 24 and 48 hours after re projection liver and GC administration, but also on the amount of total protein in the liver of rats that received only after resection MIGI-K - 39.48 ± 0.42 and 41.06 ± 0.85 g%) (see Table)...

 The study used 80 male white infertile rats that underwent liver resection in the amount of 65-70% of the organ mass.

 The operated animals were divided into 4 groups: 1 group - 20 control operated rats; Group 2 — 20 control rats obtained by GC immediately after liver resection subcutaneously 1 time per day at a dose of 75 - 85 IU per 100.0 animal body weight immediately after and the next day after liver resection; Group 3 - 20 rats who received immediately after resection into the stomach MIGI-K at the rate of 0.3 ml of a 33% aqueous solution; Group 4 - 20 rats treated immediately after liver resection and the day after it GC in combination with MIGI-K. GC was administered subcutaneously 1 time per day at a dose of 75 - 85 IU per 100.0 body weight. MIGI-K was also injected immediately after resection of the liver into the stomach through a tube at the rate of 3.0 ml of a 33% aqueous solution. There were no animal deaths after drug administration.

GC is administered at a dose of 75 ED-85 per 100.0 body weight because such a dose of the hormone gives a biological effect (ed. St. N 1081466)
The experiment used 80 males of white outbred rats. An experimental animal undergoes liver resection in the amount of 65-70% of the mass of the organ. After the operation, the animal is immediately injected through a tube into the stomach with 3.0 ml of a 33% solution of MIGI-K and GC subcutaneously 1 time at a dose of 75 - 85 PIECES per 100.0 per body weight. Then MIGI-K and the hormone are administered in the same dose and in the same manner 24 hours after liver resection. Liver resection was used in these experiments as a way of trauma, damage to the liver and animals after liver resection. Animals that received GC after liver resection or MIGI-K were control. Slaughter of animals of all groups was carried out after 24 and 48 hours. Removing the liver, a homogenate was prepared in an environment of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in accordance with 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 Thus, the results show that after 1 and 2 days after the simultaneous administration of GC and MIGI-K at the indicated doses and the indicated rate to the animals after liver damage in the form of resection of it in the amount of 65-70% of the organ mass, reliable (P less than 0, 01) an increase in the amount of total liver protein in comparison with the effect of liver resection or the introduction of GC after liver resection or the introduction of MIGI-K after liver resection.

 Example 1. In rat N 82, 24 hours after liver resection, the amount of total protein in the liver tissue was determined. For this, a homogenate is prepared from liver tissue in an environment of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in a ratio of 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 The amount of total protein in rat liver tissue N 82 was found to be 30.76 g%.

 Example 2. In rat N 94, the total amount of protein in the liver tissue was determined 24 hours after liver resection and GC administration. For this, a homogenate was prepared from liver tissue in an environment of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in accordance with 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 In rat N 94, the protein content in the liver tissue was 34.01 g%.

 Example 3. In rat N 104, the total amount of protein in the liver tissue was determined 24 hours after liver resection and MIGI-K administration. For this, a homogenate was prepared from liver tissue in an environment of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in a ratio of 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 In rat N 104, the amount of total protein was 40.45 mg g%.

 Example 4. In rat N 114, the total amount of protein in the liver tissue was determined 24 hours after resection of the liver and administration of the GC complex with MIGI-K. For this, a homogenate was prepared from liver tissue of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in a ratio of 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 The amount of total protein in the liver tissue in rat N 114 was equal to 49.38 g%.

 Example 5. In rat No. 5, the total amount of protein in the liver tissue was determined 48 hours after liver resection. For this, a homogenate was prepared from liver tissue of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in a ratio of 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 It turned out that the total protein content in liver tissue in rat N 5 was equal to 25.76 g%.

 Example 6. In rat No. 18, the total amount of protein in the liver tissue was determined 48 hours after liver resection and GC injections. For this, a homogenate was prepared from liver tissue of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in accordance with 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 It turned out that the total protein content in the liver tissue in rat N 18 was 34.41 g%.

 Example 7. In rat No. 45, the total amount of protein in the liver tissue was determined 48 hours after liver resection and MIGI-K administration. For this, a homogenate was prepared from liver tissue of the following composition: 0.25 M sucrose, Tris-HCl pH 7.4 in accordance with 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 In rat N 45, the amount of total protein (turned out to be equal to 40.11 g%.

 Example 8. In rat No. 57, the total amount of proteins in the liver tissue was determined 48 hours after liver resection and GC administration in combination with MIGI-K. For this, a homogenate was prepared from liver tissue of the following composition: 0.25 M sucrose, Tris-HCl sucrose, Tris-HCI pH 7.4 in accordance with 1 g of tissue + 9.0 ml of medium. In the resulting homogenate, the protein content was determined according to Lowry and expressed in g%.

 In rat N 57, the amount of total protein was 57 g%.

 Positive effect. The use of GC simultaneously with MIGI-K leads to a significant stimulation of protein-synthetic liver function, which is expressed in a significant increase compared to animals in the control groups of the amount of total protein in the liver tissue in rats receiving GC simultaneously with MIGI-K after liver resection. This effect can be used in the treatment of liver lesions that accompany a decrease in the protein-synthetic function of this organ.

Claims (1)

 A method of stimulating the protein-synthetic function of the liver after resection in an experiment, comprising administering immediately after resection of the gonadotropin a chorionic and biologically active substance, characterized in that the hormonal gonadotropin is administered subcutaneously at a dose of 75 - 85 IU / 100 g body weight per day, and as biologically active substances use MIGI-K, which is administered intragastrically at a dose of 3 ml of a 33% aqueous solution per day.

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