Method for hepatic protection with api-phytocomposition

FIELD: medicine.

SUBSTANCE: method involves simulating hepatitis by 7-day alcoholisation in female rats. A hepatoprotective agent is presented by an api-phytocomposition in the form of an aqueous suspension of honey, lecithin and licorice root extract in the ratio of 10:2:1. The composition is introduced twice a day intragastrically before feeding in a dose of 200 mg/kg of body weight 5 days before ethanol introduction and for 7 days one hour before ethanol introduction.

EFFECT: effective treatment of hepatitis with no side effects.

1 ex, 1 tbl, 1 dwg

 

The invention relates to medicine, in particular to experimental pharmacology.

By well-known literary sources - lecithin (phosphatidylcholine and others) are major components of cell membranes and structures of hepatocytes. Their deficiency leads to the development of fatty infiltration of the liver, disturbances of choleresis, biliary excretion and functions of liver cells. Hepatoprotective effect of lecithins is based on the inhibition of processes of lipid peroxidation (LPO), which is considered as one of the leading pathogenetic mechanisms of development of liver lesions (Podymova S.D. Mechanisms of alcoholic liver injury and their correction essential phospholipids // Farmateka. - 2005. No. 14. S-31).

Known way to prevent liver damage during formation of the syndrome of combined dystrophic-degenerative changes of mesenchymal derivatives under local chronic inflammatory process and the means for its implementation (EN 2455988, publ. 20.07.2012), which is characterized by the fact that in a darkened room before going to sleep in the body is injected melatonin as an effective dose, for example, at a dose of 0.7-1.5 mg/kg of body weight, effective rate, for example, within 5-10 days.

The main disadvantage of this method is that the use of melatonin has a number of precautions, but it should not be used during the time of drivers of vehicles and people, professions related to high concentration of attention.

Closest to the claimed solution is the way hepatoprotective individual flavonoids (hesperidin, diosmin, flavianum, quercetin), Kars and dry extract (SE) of grass peas chopped off, according to the description of the experimental research in the dissertation on competition of a scientific degree of the doctor of biological Sciences on theme: "Hepatoprotective properties of flavonoids (pharmacodynamics and perspectives of a clinical study)" Dorking Mrs x, the Experiments were conducted on rats-females weight 170-240, Acute liver failure ethanol reproduced by the course of alcoholism rats by 2-fold intraperitoneal injection of a 33% solution of ethanol per day in a dose of 0.75 ml/100 g animal body weight for 7 days (Kushnerova NF, Sprygin VG, Fomenko S.E., and others, the Efficacy of the herbal preparation, deprim to restore the functional state of the liver after the defeat of ethyl alcohol // Hygiene and sanitation. 2002. No. 1). The investigated flavonoids, SE and Kars, the animals were injected daily for 12 days oral (intragastric) in the form of an aqueous suspension for 5 days prior to the introduction of ethanol, and then together with him (7 days) - at the same time before feeding the animals for 1 hour prior to the introduction of hepatotoxin (ethanol).

Main is not the com method is that quercetin belongs to clastogenic (genotoxic) compounds possessing the ability to destroy the DNA of cells (Snyder & Gillis, 2002); hesperidin and dio-Smin can cause symptoms of neuro-vegetative disorders; also diosmin is not recommended to persons under 18 years of age.

The task of the invention is to provide a method hepato-protection IPA-phytocomplex containing honey, lecithin, licorice root extract, eliminating the disadvantages of the known solutions.

The task is achieved by a method of hepatoprotective IPA-phytocomplex, including the reproduction of the model of acute alcoholic hepatitis and holding hepatoprotective means of natural origin that enter laboratory animal daily for 12 days, intragastrically in the form of an aqueous suspension for 5 days prior to the introduction of ethanol, and then together with him 7 days at the same time before feeding the animal for 1 hour prior to the introduction of ethanol 2 times a day, and as a means of natural origin used IPA-phytocomplex in the form of an aqueous suspension of honey, lecithin and extract of licorice root mass ratio 10:2:1, at a dose of 200 mg/kg of body weight of the animal.

Thus, the proposed method leads to a more pronounced correction alcoholic hepatitis than in the known solutions, as you entered the e lecithins (essential phospholipids) leads to inhibition of peroxidation processes in hepatocytes.

Moreover, an advantage of the proposed method is the absence of side effects observed in the reception of the above flavonoids, namely, genotoxicity and neuro-vegetative disorders, and is included in the IPA-creation of phyto compositions as korrigentami taste the licorice root extract and honey have a preventive effect of diseases of the upper respiratory tract and tonic properties.

The METHOD IS AS follows

Experiments conducted on rats-females weight 170-240 g of a 33% solution of ethanol injected intraperitoneally at a dose of 0.75 ml/100 g of animal body weight 2 times a day for 7 days. Aqueous suspension of honey, lecithin and licorice root extract (10:2:1) at a dose of 200 mg/kg animal body weight is injected every day, 2 times a day for 12 days, intragastrically (via probe) for 5 days prior to the introduction of ethanol, and then together with him (7 days) - at the same time before feeding the animals for 1 hour prior to the introduction of ethanol.

Evaluation of the effectiveness hepatoprotective action was performed according to the degree of normalization of biochemical indicators of pathological syndromes observed in the liver: cytolysis activity in serum Alt (alanine aminotransferase), AST (aspartate aminotransferase), KF (sour fosfotazy); cholestasis activity in serum alkaline phosphatase (alkaline FOSFA the cans), γ-GTP (γ-glutamyl transferase), the content of direct bilirubin (IB), mesenchymal inflammation - determination of protein fractions, ratio of albumins/globulins and thymol turbidity tests (TP) in serum; hepato-cellular failure, describing the state of the protein-synthetic and metabolic functions of liver markers of protein (the content of total protein, albumen fraction and activity HAE, the content of urea in blood serum), carbohydrate (glucose in the blood and glycogen in the liver) and lipid (cholesterol, tireotropin-releasing hormone (TRH) in the serum the content of the TWG and phospholipids (PL) in the liver) exchanges. The intensity of PAUL studied the content of TBA-active products in the liver and serum, diene conjugates (DC) in the liver, the intensity of spontaneous and Fe2+ - escortinbrisbane FLOOR in posthegemony fraction of the liver (PFI).

Statistical processing of results was performed using the parametric student's t-test to determine the arithmetic mean (M) and standard errors (m), non-parametric criterion of Mann-Whitney and linear correlation coefficient.

SPECIFIC EXAMPLE

As you know, alcoholic liver disease, in large part because of oxidative degradation of ethanol occurring in this organ (Cali is in AV, 2005, Lieber .S., 2005). Excessive intake of ethanol leads to the accumulation of acetaldehyde and increase the production of free radicals, which leads to increased FLOOR, the antioxidant depletion of resources and damage to biomembranes, which is determined by the concept of oxidative stress.

In the 7-day alcohol was observed increase of N-demethylase and NADPH-NT-reductase activities by 140% and 55% due to the induction of isoforms of cytochrome P450 2E I, involved in ethanol oxidation. At the same time revealed an increase in the intensity of the induced FLOOR PFI 130% and the content of TBA-active products in serum by 115%, while in the liver content of TBA-active products and DK was not significantly changed. This was accompanied by a drop in the efficiency of antioxidant defense (AOD) at various levels - decreased activity of superoxide dismutase (SOD) 40%, catalase by 50%G-S-T 38%, the content of glutathione GSH in 50%, as well as decreased activity of the main enzymes that supply redox equivalents for glutationreductase reactions: MDY - 45%, G-6-FDG - 75% and ICDH by 58%.

The revealed changes of biochemical parameters in the 7-day introduction 33% ethanol to rats-females testified to the development of liver damage with the manifestation of signs of cytolysis, cholestasis, mesenchymal, vospolenie and liver failure.

Researched IPA-a phytocomplex with alcoholic liver disease showed hepatoprotective properties. The restoration of the main indicators of pathological syndromes of treatment and prevention introduction IPA-creation of phyto compositions in acute alcoholic liver injury in rats are shown in table 1.

Table 1
Syndromes SubstanceCyto
Liz (Alat, ASAT, KF, A2)
Holes
the pelvis (alkaline phosphatase, γ-GTP, IB)
Mesenchymal
Noah inflammation (globulins, albumins/ globulins, TA)
Hepatic cell failure
protein synthetic function (total protein, albumin, HAE, urea)metabolic function (glucose CIV., glycogen pécs., The TWG CIV., TWG pécs., FL pécs)
Aqueous suspension of honey, lecithin, licorice root extract+++++++±++-++±+++++
% recoveryto 116.2 83,165,9107,9
Note "+" - a complete normalization of the indicator; "±" - incomplete normalization; "-" - no effect

The data in table 1 indicate that the use of IPA-creation of phyto compositions led to the restoration of the indicators syndromes cytolysis, cholestasis, mesenchymal inflammation, protein-synthetic and metabolic functions of the liver.

In acute alcoholic liver injury in rats, the proposed IPA-a phytocomplex in the form of an aqueous suspension of honey, lecithin, licorice root extract help normalize the intensity of SEX and the activity of antioxidant system (AOS) (figure 1). There was observed a complete normalization of the content of TBA-active products.

Thus, the results indicate a marked hepatoprotective in the model of acute alcoholic hepatitis in rats proposed IPA-phytocomplex.

How hepatoprotective IPA-phytocomplex, including the reproduction of the model of acute alcoholic hepatitis and holding hepatoprotective means of natural origin that enter laboratory animal daily for 12 days, intragastrically in the form of an aqueous suspension for 5 days prior to the introduction of ethanol, and then owls is local with him 7 days - at the same time before feeding the animal for 1 hour prior to the introduction of ethanol 2 times a day, characterized in that as a means of natural origin used IPA-phytocomplex in the form of an aqueous suspension of honey, lecithin and licorice root extract in the ratio 10:2:1, at a dose of 200 mg/kg animal body weight.



 

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