scholarly journals Proteins of allogeneic hepatocytes and pharmacological preparations for the correction of immunometabolic disorders in experimental liver pathology

2021 ◽  
Vol 7 (2) ◽  
pp. 83-99
Author(s):  
Ekaterina S. Litvinova ◽  
Nikolay N. Konoplya ◽  
Anastasiya A. Shulginova ◽  
Anastasiya V. Kharchenko
Keyword(s):  
Liver Damage ◽  
Alcohol Intoxication ◽  
Culture Fluid ◽  
Rat Hepatocytes ◽  
Ethanol Solution ◽  
Intragastric Administration ◽  
Newborn Mice ◽  
Male Wistar Rats ◽  
Toxic Liver Damage ◽  
Peroxidation Processes

Introduction: The relationship of numerous metabolic shifts, disorders of hepatocytes functional activity resulting from hypoxia and toxic liver damage with the function of the immune system has not been sufficiently studied so far, nor have the most effective methods of pharmacological correction been established. Materials and Methods: The studies were carried out on 603 mature male Wistar rats and 45 mice. Acute toxic liver damage (ATLD) was modeled by intramuscular introduction of carbon tetrachloride; acute liver ischemia (ALI) was caused by clamping the hepatoduodenal ligament for 20 minutes; chronic alcohol intoxication (CAI) was modeled by forced intragastric administration of 20% ethanol solution for 60 days. Isolation of xenogeneic (murine) and allogeneic (rat) hepatocytes from newborn mice and rats was carried out according to the method of Berry and Friend (1969); culture fluid of hepatocytes and its protein fractions were prepared according to our developed techniques. The obtained biological material was intraperitoneally introduced into the rats with ATLD, ALI, and CAI. Results and Discussion: In all the models of the liver damage, there developed morphological and biochemical signs of the liver damage, impaired congenital and adaptive immunity, oxidative stress, increased lipid peroxidation processes. Conclusion: The introduction of allogeneic hepatocytes, culture fluid obtained on their basis,and proteins isolated from it with MW less than 130 kDa to the recipients with toxic and ischemic liver damage more effectively corrects the pathologic changes in the liver in comparison with xenogeneic hepatocytes, their culture fluid and pharmacological preparations (combinations of Essentiale N and Hypoxenum or Heptral and Mexicor).

scholarly journals INVESTIGATION OF THE EFFECT OF ARTEMISIA L. HERB EXTRACTS ON THE PROGRESS OF THE TOXIC TETRACHLOROMETHANE LIVER DAMAGE

2020 ◽  
pp. 147-155
Author(s):  
R. A. Hrytsyk ◽  
O. A. Struk ◽  
V. M. Ivanochko
Keyword(s):  
Acute Toxicity ◽  
Liver Damage ◽  
Biochemical Parameters ◽  
Hepatoprotective Activity ◽  
Intragastric Administration ◽  
Artemisia Vulgaris ◽  
Artemisia Absinthium ◽  
Reference Drug ◽  
Toxic Liver Damage ◽  
Acute Toxic

Introduction. Artemisia L. genus species are the promising sources for the manufacturing of drugs with hepatoprotective activity. They are used as appetizing, anthelmintic, bactericidal, choleretic and anti-inflammatory re­medies. The pharmacological activity of Artemisia L. species is caused by the presence of different groups of biologically active substances. The aim of the study – to learn the acute toxicity and the effect of Artemisia absinthium and Artemisia vulgaris water-alcohol extracts on the progress of the toxic tetrachloromethane liver damage. Research Methods. The method of preclinical study of drugs safety was used to determine the acute toxicity. The investigation of hepatoprotective activity of Artemisia absinthium and Artemisia vulgaris extracts was performed using the model of acute tetrachloromethane hepatitis. Hepatoprotector of local manufacturer (“Silibor” tablets) was used as the reference drug. Results and Discussion. It was found that intragastric administration of Artemisia absinthium and Artemisia vulgaris extracts at the dose of 6000 mg/kg does not lead to the death of animals. There were no changes in the integral, hematological, biochemical parameters and in the morphological structure of the internal organs of experimental animals. It allows to characterize the extracts at this dose as almost non-toxic ones (V toxicity class, LD50>5000 mg/kg) according to the toxicity classification of substances. The results of Artemisia absinthium and Artemisia vulgaris extracts study indicate that they show the distinct hepatoprotective activity in condition of acute toxic liver damage. They suppress peroxide destructive processes and reduce the evolution of cytolysis syndrome and their effects are no inferior rather than the effect of tablets “Silibor”. Conclusions. The study of acute toxicity of Artemisia absinthium and Artemisia vulgaris extracts after their intragastric administration at the dose of 6000 mg/kg does not lead to the animals death. They were tidy and had the good appetite. The animals reacted adequately to sound and light stimulation. The processes of urination and defecation were unchanged. Breathing disorders and seizures were not observed. The investigated Artemisia ­absinthium and Artemisia vulgaris extracts demonstrate hepatoprotective activity in condition of acute toxic liver damage. This is proved by decreasing in the intensity of lipid peroxidation and in the toxicity of tetrachloromethane. Biochemical parameters of the animals’ blood and the liver homogenate became responded to the level of intact animals.

scholarly journals Pharmacological correction of metabolic disorders in experimental acute pancreatitis on the background of chronic alcohol intoxication

2018 ◽  
Vol 4 (4) ◽  
pp. 9-19
Author(s):  
Olga Bushmina ◽  
Svetlana Dolgareva ◽  
Alexander Konoplya ◽  
Aleksey Loktionov
Keyword(s):  
Acute Pancreatitis ◽  
Metabolic Disorders ◽  
Healthy Adult ◽  
Alcohol Intoxication ◽  
Ethanol Solution ◽  
Intragastric Administration ◽  
Chronic Alcohol ◽  
Ethanol Intoxication ◽  
Experimental Acute Pancreatitis ◽  
Chronic Alcohol Intoxication

Introduction. Acute pancreatitis and pre-existing diseases (chronic alcohol intoxication) are challenging issues of modern surgery in terms of frequency of deaths and the number of complications. Objective. To identify the best combination of immunomodulators, antioxidants and hepatoprotectors to correct immunometabolic disorders in acute destructive pancreatitis on the background of chronic alcohol intoxication (CAI). Materials and methods. Studies were conducted on 377 healthy adult Wistar rats weighing 150-200 g. Alcohol intoxication was modeled by forced intragastric administration of a 20% ethanol solution at a dose of 3 ml/kg or 2.92 g/kg at 24 hours for 5 days, 30 days (CAI-30) or 60 days (CAI-60). Acute destructive pancreatitis (ADP) was modeled after R.N. Wang et al. (1995), modified by S.A. Alekhin et al. (2006). The efficacy of combining Hepon (5 mg/kg, orally, at 24 hours, No. 14), Hypoxen (750 mg/kg, orally, at 24 hours, No. 14), Phosphogliv (800 mg/kg, orally, at 24 hours, No. 14), Glutoxim (20 mg/kg, intramuscularly, at 24 hours, No. 5), Mexidol (50 mg/kg, intraperitoneally, at 24 hours, No. 14) and Heptral (760 mg/kg, intraperitoneally, at 24 hours , No. 5) was examined in animals with ADP on the background of CAI-30 and CAI-60. Results and discussion. Different degrees of ethanol intoxication depending on time leads to the development of an impaired capacity of hepatocytes, as well as immune and metabolic disorders. The administration of Phosphogliv, Hypoxen and Hepon in case of CAI-30+ADP normalizes 12.1% and corrects 60.6% of the changed values. The combination of Heptral, Glutoxim and Mexidol normalizes 57.8% and corrects 42.4% of the values. In case of CAI-60+ADP, Phosphogliv, Hypoxen and Hepon normalizes 11.8% and corrects 38.2% of the values. The combination of Heptral, Glutoxim and Mexidol normalizes 17.6% and corrects 67.6% of the values, respectively. Conclusion. In case of ADP along with CAI-30 and CAI-60, the combination of Heptral, Glutoxim and Mexidol is more preferable than that of Phosphogliv, Hypoxen and Hepon.

scholarly journals CHANGE OF THE PROFILE OF EXPRESSION OF ADAPTIVE RESPONSE GENES IN TOXIC HEPATITIS OF DIFFERENT ETIOLOGY

2019 ◽  
Vol 98 (9) ◽  
pp. 1021-1025
Author(s):  
Denis O. Karimov ◽  
T. G. Kutlina ◽  
G. F. Mukhammadiyeva ◽  
Y. V. Valova ◽  
E. F. Repina ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Damage ◽  
Toxic Hepatitis ◽  
Alcohol Intoxication ◽  
Expression Profiles ◽  
Molecular Genetic ◽  
Liver Homogenate ◽  
Control Group ◽  
Mrna Levels ◽  
Toxic Liver Damage

Introduction. In Russia, the problem of toxic hepatitis is of great importance and relevance. The etiology of toxic hepatitis (industrial toxicants, drugs, ethanol) and, as a consequence, pathogenesis may have significant differences at the molecular genetic level. The aim of the study was to analyze the expression of genes involved in the response to toxic liver damage of various etiologies. Material and methods. Toxic hepatitis was modulated in male albino mongrel rats weighing 180-200 grams assigned to four groups (control group, carbon tetrachloride, paracetamol, ethanol). After 24 and 72 hours of paracetamol administration, rats were anesthetized and the mRNA levels of the Chek1, Gclc, Gstm1, Gstp1, Gstt1, Nfe2l2, Nqo1, Ripk1 genes in the liver homogenate were examined. Results. As a result of the analysis of the genes expression studied, the expression profile was found TO be differed depending on the etiology of toxic hepatitis. With carbon tetrachloride poisoning, an increase in the expression of the Nqo1 genes (p = 0.001), Gstm1 (p = 0.037) and a decrease in the expression of the Nfe2l2 genes (p = 0.004), Ripk1 (p = 0.004) was observed. With the liver damage by paracetamol and its metabolites, opposite to the expression of the Gstm1 gene (p = 0.001) decreased, and the expression of the Nfe2l2 (p = 0.009), Gclc (p = 0.001), Chek1 (p = 0.011) genes increased. During alcohol intoxication, there were no statistically significant changes in the expression profiles of the genes studied. Conclusion. the results obtained may indicate the involvement of various molecular genetic mechanisms in the process of response to toxic liver damage, depending on the etiology.

scholarly journals The use of immunomodulators, antioxidants and hepatoprotectors for the correction of the liver, erythrocites and the immune system disorders in chronic ethanol intoxication

2018 ◽  
Vol 64 (4) ◽  
pp. 360-367 ◽  
Author(s):  
S.A. Dolgareva ◽  
A.V. Sorokin ◽  
N.A. Konoplya ◽  
O.N. Bushmina ◽  
N.A. Bystrova ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Liver Damage ◽  
Alcohol Intoxication ◽  
Local Level ◽  
Ethanol Intoxication ◽  
Combined Use ◽  
Dependent Activity ◽  
Prothrombin Index ◽  
Toxic Liver Damage ◽  
Chronic Ethanol Intoxication

The effectiveness of three various combinations of an immunomodulator with an antioxidant and a membrane protector in the correction of metabolic and immune disorders has been studied in the experiment under 60-days ethanol intoxication. The development of such biochemical syndromes of the liver damage as cytolysis, intrahepatic, intracellular cholestasis, toxic liver damage by necrotic type, insufficiency of synthetic processes and inflammatory has been revealed. Oxidative stress development and the activation of lipid peroxidation on the systemic (blood plasma) and local level (erythrocytes) have been established. Suppression of adaptive immunity formation and phagocytic capabilities of neutrophils under the increase in their oxygen-dependent activity has been determined, which indicates the presence and possible progression of the inflammatory process at the systemic level. A disorder of erythrocytes metabolic activity, a decrease in stable metabolites of nitric oxide detected in blood plasma been revealed, indicating its uncompensated consumption, causing vasoconstriction and thrombosis, which can additionally arise due to the established increase in the prothrombin index. Combined use of “Longidasa”, “Mexicor”, “Essentiale forte N” or “Glutoxim”, “Mexidol”, “Heptral” was more effective in the correction of immune-metabolic disorders in chronic alcohol intoxication than “Hepon”, “Hypoxen” and “Phosphogliv”.

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.

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.

Occupational toxic liver damage

1986 ◽  
Vol 3 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Martin Døssing
Keyword(s):  
Liver Damage ◽  
Toxic Liver Damage

A novel fluorinated stilbene exerts hepatoprotective properties in CCl4-induced acute liver damage

2011 ◽  
Vol 89 (10) ◽  
pp. 759-766 ◽  
Author(s):  
Horacio Rivera ◽  
Martha S. Morales-Ríos ◽  
Wendy Bautista ◽  
Mineko Shibayama ◽  
Víctor Tsutsumi ◽  
...  
Keyword(s):  
Liver Damage ◽  
Inflammatory Responses ◽  
Acute Liver Damage ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Glutamyl Transpeptidase

There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl4)-induced acute liver damage. To achieve this, CCl4 (4 g·kg–1, per os) was administered to male Wistar rats, followed by either 2-fluoro-4′-methoxystilbene (FME) or 2,3-difluoro-4′-methoxystilbene (DFME) (10 mg·kg–1, per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl4 administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl4-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization.

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