scholarly journals Determination of the activity of pyruvate kinase isoforms in normal conditions, in toxic liver damage and during the process of its regeneration

2021 ◽  
pp. 116-123
Author(s):  
A. G. Skuratov ◽  
A. N. Lyzikov ◽  
A. S. Shaforost ◽  
A. A. Zyatskov ◽  
N. M. Golubykh
Keyword(s):  
Pyruvate Kinase ◽  
Liver Damage ◽  
Intraperitoneal Administration ◽  
Mechanical Damage ◽  
Elisa Test ◽  
Reparative Regeneration ◽  
Laboratory Animals ◽  
Toxic Damage ◽  
Toxic Liver Damage

Objective. To evaluate the activity of pyruvate kinase (PK) isoforms in normal conditions, in toxic damage of the liver and during its regeneration.Materials and methods. An experimental study was carried out on 45 Wistar rats. Toxic liver damage was induced by the intraperitoneal administration of carbon tetrachloride. Mechanical damage was simulated by the surgical resection of the liver. The levels of PK isoforms R/L and M in the blood serum and liver tissue of the laboratory animals were measured with an ELISA test.Results. It has been found that the level of PK isoform M signifcantly increases in chronic toxic liver damage, which may indicate the activation of the processes of liver cell proliferation in response to the damaging effect of hepatotoxin (Mann-Whitney U Test: Z = 2.143; p = 0.032). After liver resection, the level of PK R/L, which characterizes the activation of glycolysis, increased and the level of pyruvate kinase M increased signifcantly, which reflected the processes of reparative regeneration in the liver.Conclusion. The serum level of PK isoforms may be used as a laboratory criterion for the activity of reparative regeneration processes, which can be used to evaluate the reparative potential of the liver in case of toxic or mechanical damage, as well as in chronic diffuse diseases.

Study of the effectiveness of herbal remedies for toxic liver damage in laboratory animals

2020 ◽  
Vol 1 (87) ◽  
pp. 117-122
Author(s):  
Elena Kuzminova ◽  
◽  
Marina Semenenko ◽  
Olga Vasiliadi ◽  
Andrey Koshchaev ◽  
...  
Keyword(s):  
Liver Damage ◽  
Herbal Remedies ◽  
Laboratory Animals ◽  
Toxic Liver Damage

scholarly journals Comparative Evaluation of Hepatoprotective Activities of Trigonella foenum-graecum (seeds), Cymbopogon proximus and Acacia nilotica on a model of acute carbon tetrachloride hepatitis in rats

2021 ◽  
pp. 172-177
Author(s):  
Abbas Abdelhamid Mutawakel ◽  
V. I. Inchina ◽  
T. V. Tarasova ◽  
G. G. Varvanina ◽  
I. E. Trubitsyna
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Damage ◽  
Blood Cells ◽  
Intraperitoneal Administration ◽  
Inflammatory Infiltration ◽  
Herbal Preparations ◽  
Water Extracts ◽  
Toxic Liver Damage ◽  
Different Doses ◽  
Acute Toxic

An experimental study of the beneficial effect of herbal preparations on acute toxic liver damage with carbon tetrachloride (CCl4) in animals was conducted The goal is to Compare the hepatoprotective effect of three water extracts of herbal preparations: (I) Trigonella foenum-graecum (seeds), (II) Cymbopogon proximus, (III) Asasia nilotica Material and methods. To simulate acute toxic liver damage, 50% CCl4 was administered once intraperitonally in doses of 0.6 ml, 0.3 ml, and 0.2 ml. Control groups: K1-1 group intact animals without injections; K2: groups 2, 3, 4. introduced saline solution (FR) without Ssl4 in the volume of 2 ml. Experimental groups: 5, 6, 7 and 8 studied the hepatoprotective properties of aqueous solutions of the studied drugs after intraperitoneal administration of Ssl4 or FR. Researched herbs: I, II, III, in different doses were administered 2 ml of an aqueous solution in breeding 1:10, observation period 5 days, the blood, for research stabilized solution of sodium citrate in the ratio of 1:10, studied the properties of blood cells hematological analyzer PCE-90Vet (USA). The content of total protein, albumin, total cholesterol, triglycerides, urea, creatinine and transaminase activity - ALT, AST-were recorded in the blood serum using an automatic analyzer of the company “ HUMASTAR 600 “(Germany)», Results and discussion. Water extracts of preparations I and II prevented the reduction of red blood cells and platelets, and activated the macrophage pool. All the herb extracts studied prevent platelet reduction, however, but do not bring them up to the indicators of intact animals. The use of solution III prevented the growth of the cytolysis enzyme-ALT. All studied extracts in acute carbon tetrachloride intoxication. they warned of an increase in hypertriglyceremia. The introduction of water extracts II, III in the 1:10 ratio prevented the development of necrotic changes in hepatocytes, inflammatory infiltration, manifestations of fatty dystrophy, and preserved the architectonics of the liver lobule.

scholarly journals CHRONOPHARMACOLOGICAL FEATURES OF SILIMARIN’S HEPATOPROTECTOCAL ACTIVITY UNDER PARACETAMOL HEPATITIS IN RATS

2020 ◽  
pp. 63-71
Author(s):  
K. O. Kalko ◽  
S. M. Drogovoz ◽  
O. Ya. Mishchenko ◽  
L. B. Ivantsyk ◽  
K. O. Dehtiarova ◽  
...  
Keyword(s):  
Liver Damage ◽  
Hepatoprotective Activity ◽  
Time Of Day ◽  
The State ◽  
Acute Liver Damage ◽  
Toxic Liver Damage ◽  
Antioxidant Protection System ◽  
Toxicity Of Drugs ◽  
Acute Toxic

Determination of dependence of the efficiency and toxicity of drugs on the time of day or season is one of the most promising areas of modern experimental and clinical pharmacology. The aim of the study. Aim is to identify features of daily rhythms of silymarin influence on the state of antioxidant/prooxidant and cytolytic processes (the leading link in the implementation of hepatoprotective activity) with paracetamol in rats under conditions of acute toxic liver damage. Materials and methods. Chronopharmacological action features of silymarin were studied by use of the generic drug "Karsil" as an example (Sopharma, Bulgaria) with paracetamol in rats under conditions of acute toxic liver damage. The state of the processes of POL-AOS was evaluated by the content of TBA-active products (TBA-AP), the content of recovered glutathione, the activity of SOD, catalase in hepatocytes, and the cytolytic processes by the activity of ALT in serum. Results. There was established a certain chronoarchitectonics of the rhythms of the antioxidant protection system and the activity of the processes of peroxidation in rats under physiological conditions, which was not disturbed by paracetamol on the background of acute liver damage (with the exception of level of acrophase catalase activity). The same dynamics and commonality of rhythms occurred on the background of the use of silymarin. The maximum display of silymarin hepatoprotective activity was observed under conditions of its use in the morning (09.00) and in the evening (21.00). Conclusions. The use of silymarin during periods of maximal display of its hepatoprotective activity, in the morning (09.00) and in the evening (21.00) may be the way to increase its bioavailability. Chronopharmacological features of silymarin activity have been established and should be taken into account when to conduct its further chronopharmacological studies.

scholarly journals SINUSOIDAL CELLS AND CYTOKINE RESPONSE IN THE TETRACHLOROMETHANE-INDUCED HEPATOTOXICITY AND AN APPROACH TO ITS CORRECTION

2019 ◽  
Vol 21 (5) ◽  
pp. 929-936
Author(s):  
Z. A. Shafigullina ◽  
I. G. Danilova ◽  
S. Yu. Medvedeva ◽  
V. A. Chereshnev ◽  
M. T. Abidov
Keyword(s):  
Liver Damage ◽  
Proinflammatory Cytokines ◽  
Local Level ◽  
System Level ◽  
Blood Monocytes ◽  
Sinusoidal Cells ◽  
Experimental Animals ◽  
Toxic Damage ◽  
Toxic Liver Damage

High occurence of liver diseases (toxic, viral hepatitis, liver failure, cirrhosis) requires urgent search of new methods for management of the hepatobiliary diseases. At the present time, the role of immune mechanisms in pathogenesis of diffuse toxic liver damage is not finally clarified. The model of toxic hepatitis induced by carbon tetrachloride (CCl4) is widely known, but this approach allows us to perform complex evaluation and develop the methods for adequate correction of liver disorders in experimental model, which is not always feasible in clinical setting.To design a model of diffuse toxic liver damage, the CCl4 oil solution was used, having been administered intraperitoneally to experimental animals, at a single dose of 50 mg per 100 g body mass. Aiming for correction of toxic liver damage, the injections of aminophthalhydrazide (APH) to experimental animals were carried out intramuscularly at the dose of 2 mg/kg over the terms of experiment. An evaluation of the role of sinusoidal cells (SC) and cytokine production at the local and systemic level were carried out in the model of toxic liver damage caused by CCl4 and its correction by APH treatment. In the course of developing diffuse toxic liver damage induced by CCl4, the production of proinflammatory cytokines TNFα, IL-1α and IL-18 was enhanced at the local level, whereas an increase in TNFα concentration was observed in blood plasma. Following aminophthalhydrazide (APH) administration, the concentrations of proinflammatory cytokines (TNFα and IL-18) decreased at system level, along with locally decreased levels of IL-6 and IFNγ.Changes in the functional state of immunocompetent cells, which include sinusoidal cells (SC), have a significant impact on the development of pathological processes in the liver. The results of our study presume that, over the early periods of toxic impact upon liver tissue, the number of SCs increases both due to influx of blood monocytes and mature macrophages from the peritoneal cavity that enter the injury site directly via mesothelial layer. The SCs provide phagocytosis of damaged hepatocytes and contribute to resolution of the inflammatory process.Modulation of the macrophage activities by APH contributes to increased amounts of SCs at the early stages, and stabilizes their quantities after 2 weeks of APH injections. Change in the numbers of liver SCs during toxic damage affects the production of cytokines. A direct effect of APH upon the SCs may change the production of regulatory factors and compensate the insufficient rate of recovery processes after the toxic damage.

scholarly journals Effect of combined transplantation of multipotent mesenchymal stromal cells and stellate liver cells on the morpho-functional state of the liver after adminitration of CCL4

2021 ◽  
pp. 48-55
Author(s):  
И.Ю. Маклакова ◽  
С.В. Цвиренко ◽  
В.В. Базарный ◽  
Д.Ю. Гребнев
Keyword(s):  
Carbon Tetrachloride ◽  
Functional State ◽  
Liver Damage ◽  
Stromal Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Repair System ◽  
Toxic Damage ◽  
Toxic Liver Damage

Цель исследования - изучение влияния сочетанной трансплантации мультипотентных мезенхимальных стромальных и звездчатых клеток печени на морфофункциональное состояние печени после ее токсического повреждения, вызванного введением CCl4. Задачи исследования: 1. Оценка морфометрических показателей печени после сочетанного введения мультипотентных мезенхимальных стромальных (ММСК) и звездчатых клеток печени (ЗКП) при токсическом повреждении печени CCl4. 2. Изучение влияния котрансплантации ММСК и ЗКП на биохимические показатели крови при токсическом повреждении печени CCl4. 3. Исследование активности системы репарации ДНК после введения ММСК и ЗКП при токсическом повреждении печени CCl4. Методика. Эксперименты выполнены на 63 белых лабораторных мышах-самцах в возрасте 7-8 мес. Токсический гепатит воспроизводили у всех животных внутрибрюшинным введением CCl4 (50 мкл/мышь), затем из них формировали опытную и контрольную группы. Животным опытной группы в латеральную хвостовую вену вводили суспендированные в 0,2 мл 0,9 % раствора NaCl ММСК, полученные из хориона плаценты мышей-самок (4 млн клеток/кг, 120 тыс клеток/мышь), и ЗКП - 9 млн клеток/кг (270 тыс клеток/мышь). Животным контрольной группы вводили в латеральную хвостовую вену 0,2 мл 0,9 % раствора NaCl. Внутривенные инъекции осуществляли однократно через 1 ч после введения CCl4. Использовлили ММСК 3-го пассажа. Трансплантированные ЗКП не подвергались культивированию. Исследовали влияние сочетанной трансплантации ММСК и ЗКП на морфофункциональное состояние печени на 1-е, 3-и, 7-е сут после введения CCl4. Результаты. Сочетанная трансплантация мультипотентных мезенхимальных стромальных и звездчатых клеток печени при токсическом поражении печени приводит к повышению митотической активности гепатоцитов, увеличению числа двуядерных гепатоцитов, повышению ядерно-цитоплазматического отношения. Введение стволовых клеток способствует снижению запрограммированной клеточной гибели гепатоцитов за счет повышения активности ферментов репарации семейства PARP. Заключение. Сочетанная трансплантации ММСК и ЗКП положительно влияет на морфофункциональное состояние печени в условиях ее токсического повреждения. Значимым механизмом восстановления морфофункционального состояния печени можно считать влияние трансплантируемых ММСК и ЗКП на систему репарации клеток. The aim of this study was to investigate the effect of combined transplantation of multipotent mesenchymal stromal and stellate liver cells on the morphofunctional state of the liver after toxic damage caused by carbon tetrachloride. Objectives of the study: 1. To evaluate changes in liver morphometric parameters after combined administration of multipotent mesenchymal stromal cells (MMSC) and hepatic stellate cells (HSC) in toxic liver damage. 2. To study the effect of cotransplantation of MMSC and HSC on changes in blood biochemical parameters in toxic liver damage. 3. To investigate the activity of the DNA repair system after the introduction of MMSC and HSC in toxic liver damage. Methods. The experiments were performed on 63 white laboratory male mice aged 7-8 mos. Toxic hepatitis was caused by intraperitoneal administration of carbon tetrachloride (CCl4) at a dose of 50 µl/mouse. The mice were divided into experimental and control groups. Animals of the experimental group were injected into the lateral caudal vein with MMSCs obtained from the chorion of the placenta of female mice and with HCP at doses of 4 million cells/kg (120 thousand cells/mouse) and 9 million cells/kg (270 thousand cells/mouse), respectively, suspended in 0.2 ml of 0.9% NaCl solution. Animals of the control group were injected with 0.2 ml 0.9 % NaCl into the lateral caudal vein. Intravenous injections were performed 1 hr after the administration of carbon tetrachloride. Rats were administered with MMSCs of the third passage. Transplanted HSC had not been subjected to cultivation. The effect of combined MMSC and HSC transplantation on the morpho-functional state of the liver was studied on the 1st, 3rd, and 7th days after administration of carbon tetrachloride. Results. The combined transplantation of multipotent mesenchymal stromal and hepatic stellate cells leads to an increase in the mitotic activity of hepatocytes, an increase in the number of binuclear hepatocytes, and an increase in the nuclear-cytoplasmic ratio. Administration of stem cells helps to reduce the programmed cell death of hepatocytes by increasing the activity of repair enzymes of the PARP family. Conclusion. Combined transplantation of MMSC and hepatic stellate cells (HSC) has a positive effect on the morphofunctional state of the liver in conditions of its toxic damage. A significant mechanism for the restoration of the morphological and functional state liver, the effect of transplanted MMSC and HSC on the cell repair system can be considered.

Determination of acute toxicity of Tiacyclin solution for injection in laboratory animals

2019 ◽  
Vol 331 (8) ◽  
pp. 25-27
Author(s):  
N.Y. Morozov ◽  
◽  
S.I. Tchukina ◽  
E.I. Koveshnikova ◽  
◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Laboratory Animals

ROLE OF THE STROMAL CELLULAR COMPONENT IN COMPENSATORY PROCESSES IN DIFFUSE LIVER DAMAGE

2018 ◽  
pp. 32-37 ◽  
Author(s):  
Z. A. Shafigullina ◽  
S. Yu. Medvedeva ◽  
I. G. Danilova
Keyword(s):  
Toxic Hepatitis ◽  
Intraperitoneal Administration ◽  
Sharp Decrease ◽  
Cellular Component ◽  
Ki 67 ◽  
Sinusoidal Cells ◽  
Toxic Damage ◽  
Stromal Component ◽  
Regeneration Processes

The aim of the study was to assess the role of the cellular component of the stroma in liver regeneration after its toxic damage. The experimental model of toxic hepatitis caused by intraperitoneal administration of tetrachloromethane (CCl4) showed that regeneration processes in the liver on the 3rd day are manifested in an increase in binuclear hepatocytes, Ki-67 + cells and hepatocytes dividing by mitosis. The reaction of the stromal component is expressed in an increase in the number of CD45 +, mast and sinusoidal cells (SC). On the 7th day of the development of toxic hepatitis the hepatocyte alteration increases, that is accompanied by a sharp decrease in the mitotic index and the number of Ki-67 + cells. In the stromal component there is a decrease in the number of sinusoidal cells, CD45 + and a significant increase in mast cells with a high secretion granule content.

EFFECT OF MMSC AND HSC ON REPARATIVE REGENERATION OF THE LIVER UNDER CONDITIONS OF ITS TOXIC DAMAGE

2020 ◽  
Vol 17 (3) ◽  
pp. 243-248
Author(s):  
I.Yu. Maklakova ◽  
◽  
V.V. Bazarniy ◽  
D.Yu. Grebnev ◽  
◽  
...  
Keyword(s):  
Dna Repair ◽  
Carbon Tetrachloride ◽  
Mitotic Activity ◽  
Liver Damage ◽  
Inflammatory Activity ◽  
Control Group ◽  
Nacl Solution ◽  
Repair Enzymes ◽  
Toxic Liver Damage ◽  
Hsc Transplantation

The aim of this study was to study the effect of combined MMSC and HSC transplantation on liver regeneration under conditions of toxic carbon tetrachloride damage. Materials and methods. The study was performed on white male mice with toxic liver damage by intraperitoneal administration of carbon tetrachloride at a dose of 50 µl per mouse once. An hour after modeling liver damage, placental MMSCs and HSCs were administered intravenously at a dose of 4 million cells/kg and 330 thousand cells/kg, respectively, suspended in 0.2 ml of 0.9% NaCl solution. Control group animals were given 0.9% NaCl solution-0.2 ml intravenously. On days 1, 3, and 7 after cell transplantation, changes in inflammatory activity in the liver were evaluated, and mitotic and apoptotic indices were determined. On the 7th day after the introduction of cells, the activity of DNA repair enzymes of the PARP family was analyzed. Results. Combined MMSC and HSC transplantation leads to a decrease in the index of inflammatory activity in the liver due to a decrease in necrosis, hepatocyte dystrophy, and a decrease in infiltration. As a result of the study, an increase in the activity of PARP repair enzymes was found, which led to a decrease in programmed cell death. Also, cotransplantation of MMSCs and HSCs was accompanied by increased mitotic activity of hepatocytes. Conclusion. Cotransplantation of MMSCs and HSCs under conditions of toxic liver damage reduces the inflammatory response, stimulates the mitotic activity of hepatocytes, and increases the activity of enzymes of the DNA repair system. Activation of the liver's reparative system, in turn, reduces the programmed death of hepatocytes.

scholarly journals Metabolic disorders, effects of obese genes and imbalance of fatty tissue hormones in patients after acute and chronic intoxication with pesticides

2018 ◽  
Vol 82-83 (2-3) ◽  
pp. 51-70 ◽  
Author(s):  
N.M. Bubalo ◽  
G.M. Balan
Keyword(s):  
Liver Damage ◽  
Metabolic Disorders ◽  
Acute Poisoning ◽  
Synthetic Pyrethroids ◽  
Fatty Tissue ◽  
Chronic Intoxication ◽  
Increased Risk ◽  
Tnf Α ◽  
Toxic Liver Damage ◽  
Tissue Hormones

The objective is to study the incidence of metabolic disorders and effects of obese genes in patients after acute and chronic intoxication with pesticides and to justify methods for evaluating their severity to optimize differentiated therapy and prevention. Material and methods. In 104 agricultural workers after acute poisoning with 2,4-D based herbicides, organophosphorus pesticides and synthetic pyrethroids, and 66 patients with chronic intoxication with pesticides in the initial period and a year later, parameters of oxidative stress, carbohydrate and fat metabolism were studied, depending on the development of toxic liver damage syndrome. In patients after acute poisoning with 2,4-D-based herbicides, imbalance of fatty tissue hormones — leptin, resistin, adiponectin and TNF-α — has also been studied. Conclusion. Dynamic observation has made it possible to establish that in those who have had acute and chronic intoxication with pesticides with toxic liver damage syndrome, metabolic disorders and effects of obese genes develop as the progression of hepatosteatosis develops. The increased level of fatty tissue hormones in the blood — leptin, resistin and TNF-α, at the background of a slight decrease in adiponectin levels in patients who have had poisoning with 2,4-D-based herbicides, allows predicting an increased risk of a progressive course of steatohepatosis and obesity, prevention of which is based on the long-term use of metformin and statins. Key words: metabolic disorders, effects of obese genes, imbalance of fatty tissue, acute and chronic intoxications, pesticides.

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