Hepatoprotective efficacy of the use of oxymethyl uracil in various experimental models

Introduction. The formation of toxic liver damage is carried out with the participation of various mechanisms of pathological processes. Chemicals, drugs and alcohol play a significant role. Timely and correct selection of correction drugs will help reduce the risk of toxic organ damage. The aim of the study is a comparative assessment of the hepatoprotective activity of oxymethyluracil in the early stages of exposure to various toxic agents. Materials and methods. The studies were carried out on male outbred white rats with a single injection of hepatotoxicants (carbon tetrachloride, paracetamol, ethanol) and a correction drug - oxymethyl uracil - followed by the study of biochemical parameters 1 and 3 days after the introduction of the chemical agent. Results. As a result of the studies carried out, it was found that specific metabolic changes are noted already one day after exposure to toxicants in the body of animals. Correction of tetrachloromethane and paracetamol intoxication with oxymethyl uracil leads to the normalization of the functional state of hepatocytes. Conclusion. Oxymethyl uracil exhibits hepatoprotective properties already in the early stages of acute toxic liver damage (1-3 days), being most effective in tetrachloromethane and paracetamol intoxication.

Influence of Pancreo-Plant on the histological parameters of the liver in conditions of acute toxic hepatitis

Toxic liver damage is the most problematic for pharmacotherapy and, accordingly, the normalization of the patient’s condition. Most often, hepatotoxins include alcohol, drugs, household and industrial toxins, the effect of which on the liver leads to the development of hepatocyte necrosis. The peculiarity of drug toxic hepatitis is a wide range of clinical manifestations, the absence of unambiguous diagnostic methods, frequent poor prognosis, which makes toxic hepatitis one of the most difficult problems in clinical practice. A promising drug for the treatment of toxic liver damage is a multicomponent herbal remedy, which is currently produced by a domestic manufacturer in the form of a dietary supplement. The aim of the work is to study the effect of the herbal remedy Pancreo-Plant on the histological structure of the liver of rats, under conditions of subacute ethanol-tetrachloromethane intoxication. Materials and methods. A model of poisoning was formed and liver samples from nonlinear white rats were examined. The slides were examined under the light microscope Granum, photographing of microscopic images was carried out with Granum DCM 310 digital video camera. The photographs were processed on a computer using the Toup View program. Results. Micropreparations obtained from liver samples of rats under the condition of subacute ethanol-tetrachloromethane intoxication, were investigated. It has been proven that Pancreo-Plant helps to reduce necrotic manifestations, hydropic degeneration of hepatocytes, manifestations of steatosis, and signs of inflammation; it also stimulates carbohydrate metabolism in hepatocytes and improves regenerative manifestations. Conclusions. It was found that the investigated agent based on medicinal plant materials, when using the model of subacute ethanol-tetrachloromethane intoxication, exhibits a significant hepatoprotective effect. It normalizes the histological structure of hepatocytes, restores the processes of glycogen accumulation, and prevents the development of fatty degeneration of the liver.

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

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.

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

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.

Problems of formation of the toxic hepatopathy forming in the conditions of chronic fluoride intoxication of the body

Introduction. Aluminium production is characterized by the accumulation of impurities of various toxic and chemical compositions in the air of working areas, the predominant among which are fluoride compounds. The accumulation of fluorides in the body causes the development of osteoarticular and associated systemic pathology. The aim of the study was to evaluate the hygienic and medico-biological features of toxic liver damage in the conditions of chronic fluoride intoxication of the body. Material and methods. The hygienic working conditions of the workers of the primary professions in aluminium production were evaluated. The analysis of hepatobiliary dysfunction based on clinical and instrumental methods was carried out in 263 subjects with fluoride intoxication and a comparison group of 116 persons. Experimental studies of the morpho-functional liver state in modelling chronic fluoride intoxication were carried out based on toxicological, biochemical, pathomorphological methods with histological analysis of tissues. The toxic properties of sodium fluoride were studied in 117 white laboratory male rats with its peroral route intake into the body. Results. The qualitative composition of the air in the working areas in the electrolysis building was analyzed. The prevalence of pathological disorders of the biliary tract in metallurgists engaged in aluminium production was assessed. Clinical studies revealed a significant prevalence of toxic fluoride hepatopathy, fatty hepatosis, cholecystitis and other disorders in the group of patients with chronic fluoride intoxication. The harmful effect of sodium fluoride on hepatocytes, vessels of the portal tract was shown in an experiment. Hyperfunction of the reticuloendothelial system, Kupffer cell proliferation, irreversible destruction of hepatocytes, necrosis against the background of severe dystrophy, and decreased synthetic activity of the liver were determined. Conclusion. The structure of occupational diseases in the workers engaged in the aluminium production is dominated by hepatobiliary pathology caused by toxic liver damage with fluoride confirmed by experimental data on destructive violations of its morphostructure.

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

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).

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

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.

Study of antioxidant properties of suppositories with nicotinic acid in toxic liver damage

New medicinal forms of acid are proposed nicotine original composition: suppositories with nicotine acid and propolis extract and suppositories with nicotine acid and pyridoxine hydrochloride. In conditions of toxic liver lesions are shown to activate free – radical processes oxidation. Against the background of medicinal forms application with acid nicotine observed expressed antioxidant effect.

Evaluation of silymarin and berberine efficiencies in the self-emulsifying drug delivery systemin paracetamol-induced experimental toxic liver injury

The hepatoprotective properties of the silymarin and the plant alkaloid berberine combinationin experimental paracetamol-inducedliver damage were studied. Silymarin was obtained from milk thistle seeds. The conditions for extraction of flavonolignans (silymarin) were optimized. 70 % ethyl alcohol, ethyl acetate and water were used as extractants. It was shown that the optimal conditions for the extraction of flavonolignans in order to obtain the maximum yield of flavonolignans were alcohol extraction in a Soxhlet apparatus. The experiment showed that the combined of silymarin and berberine was greater than their individual actions, which most effectively permitted stabilization of hepatocyte membranes and prevented altering their integrity in paracetamol-induced toxic liver damage. The self-emulsifying system with silymarin and berberine to a greater extent a significant extent prevented dystrophic changes in hepatocytes and necrosis in liver tissue, reduced hyperfermentemia in rat blood serum, prevented disturbance in the activity of thioredoxin reductase and enzymes of the glutathione antioxidant system and there by more effectively prevented hepatocyte functional impairment.

Complex Therapy of Acute Poisoning by Thallium Compounds (Literature review and data from own research)

The Aim of the Research. Based on the analysis of modern literature data and our own research to substantiate the principles of rational complex therapy with acute poisoning by thallium compounds (Tl+) at different stages of intoxication. Materials and Methods. The analysis of literature data and our own researches is carried out and the principles of rational complex therapy with acute poisoning by thallium compounds at different stages of intoxication development are substantiated and the algorithm of doctors’ actions at suspicion of acute Tl+ poisoning is defined. Results and Conclusions. The principles of complex therapy of acute Tl+ poisonings substantiated, which includes antidote therapy, methods of extracorporeal treatment (plasmapheresis, hemosorption, hemodialysis), treatment of toxic encephalopolyradiculoneuropathy, neuropathic pain syndrome and toxic liver damage. The sequence of appearance of the main symptoms of intoxication at low and high doses of Tl+ is determined, which allows to assume poisoning by this toxicant. Key Words: thallium, acute poisoning, complex therapy.