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The challenge of liver disease is predominantly found in developing countries due to the use of drugs, parasites, alcohol, bacteria, and viruses. To overcome this challenge, Combretum indicum var. B plant has been identified as potential hepatoprotector. Therefore, this study aimed to screen compounds in C. indicum var. B flowers with the potential to be CYP2C9 enzyme inhibitors using pharmacophore and molecular dynamic methods. The compounds contained in the C. indicum var. B flowers were extracted and screened based on pharmacophore, drug-likeness, absorption probability, docking, and molecular dynamics. The screening results showed that there were five compounds with potential as hepatoprotector and docking obtained the ranking based on their lowest binding energies. These compounds included 6-quanolinecarboxylic acid, ellagic acid, 2- (2-thienyl)-4H-chromen-4-one, N-[4-(diethylamino)phenyl]-N'-phenylurea, and AMPA, with binding energies of -5.52, -8.93, -7.04, -6.16, and -5.54 kcal/mol, respectively. Based on the results, the most potential compound as hepatoprotector was N-[4-(diethylamino)phenyl]-N'- phenylurea. [ABSTRACT FROM AUTHOR]

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

The preservation of poultry stock can be improved by incorporating therapeutic and preventive agents, including hepatoprotectors, into the diet. This study aimed to evaluate the effect of an experimental drug containing hepatoprotectors on the health of broiler chickens. The research sought to identify the potential of the preparation to enhance liver function and overall poultry stock survival. The study was conducted from 2023 to 2024 at Odesa State Agrarian University. Investigations were carried out to assess the effects of the experimental preparation in the following doses: 1.0 g/kg body weight (therapeutic dose), 2.0 g/kg body weight (double therapeutic dose), and 5.0 g/kg body weight (fivefold therapeutic dose) over 30 days. The experiment was conducted on 500 Cobb 500 broiler chickens aged 1 to 40 days. Additionally, biochemical blood parameters were measured and analysed using a Polish biochemical selective automatic analyser, the Hitachi 902. Studies have established that the optimal dose of the experimental drug for hepatosis in broiler chickens is 1.0 g/kg body weight. After administration of the drug, the serum bilirubin content decreased by 27.3%, lactate dehydrogenase activity decreased by 17.1%, aspartate aminotransferase activity decreased by 16.4%, alanine aminotransferase activity decreased by 19.3%, and vitamin A content increased by 25.6%, while the phagocytic activity of pseudoeosinophils increased by 23.1%. The results of the studies have proven that the experimental drug normalises liver function, positively affects the biochemical composition of blood, promotes growth, provides protection and natural resistance of the broiler organism, and even improves the quality of poultry products. Based on the above, it is necessary to improve methods for early diagnosis of liver function disorders in poultry and apply effective methods for correcting metabolic processes

Hepatobiliary disorders contribute significantly to the structure of morbidity, causes of disability and mortality of the world’s population. Therefore, the search for and development of effective and safe hepatoprotective agents for the pharmacotherapy thereof remains a problematic issue. This article presents a pharmacological profile for each of the active ingredients of the composite phytopharmaceutical Dipana, and reviews the evidence for its effectiveness and safety in chronic hepatobiliary disorders.

The preservation of poultry stock can be improved by incorporating therapeutic and preventive agents, including hepatoprotectors, into the diet. This study aimed to evaluate the effect of an experimental drug containing hepatoprotectors on the health of broiler chickens. The research sought to identify the potential of the preparation to enhance liver function and overall poultry stock survival. The study was conducted from 2023 to 2024 at Odesa State Agrarian University. Investigations were carried out to assess the effects of the experimental preparation in the following doses: 1.0 g/kg body weight (therapeutic dose), 2.0 g/kg body weight (double therapeutic dose), and 5.0 g/kg body weight (fivefold therapeutic dose) over 30 days. The experiment was conducted on 500 Cobb 500 broiler chickens aged 1 to 40 days. Additionally, biochemical blood parameters were measured and analysed using a Polish biochemical selective automatic analyser, the Hitachi 902. Studies have established that the optimal dose of the experimental drug for hepatosis in broiler chickens is 1.0 g/kg body weight. After administration of the drug, the serum bilirubin content decreased by 27.3%, lactate dehydrogenase activity decreased by 17.1%, aspartate aminotransferase activity decreased by 16.4%, alanine aminotransferase activity decreased by 19.3%, and vitamin A content increased by 25.6%, while the phagocytic activity of pseudoeosinophils increased by 23.1%. The results of the studies have proven that the experimental drug normalises liver function, positively affects the biochemical composition of blood, promotes growth, provides protection and natural resistance of the broiler organism, and even improves the quality of poultry products. Based on the above, it is necessary to improve methods for early diagnosis of liver function disorders in poultry and apply effective methods for correcting metabolic processes. [ABSTRACT FROM AUTHOR]

The aim of the work was to analyze the current research state of phenylpropanoids as a special specific class of biologically active compounds and the prospects for their use for the development of medicines and biologically active food additives.Materials and methods. The scientific data for the period from 1968 to 2023 were studied in the databases of Scopus, ScienceDirect, PubMed, Google Scholar, e-library.ru, ResearchGate – a scientific information network. Herewith, the following keywords were used: “phenylpropanoids”, “antioxidants”, “hepatoprotectors”, “immunomodulators”, “organoprotectors”, “anxiolytics”, “adaptogens”, “preventive medicine”, “sanogenesis”, “medicines”, “biologically active food additives”, “sports medicine” and their English-language analogues.Results. This scientific research examines the main stages and results of studying the class of phenylpropanoids in the following aspects: a chemical structure and classification, biosynthesis and its role in the biogenesis of other classes of phenolic compounds, their distribution, biological and pharmacological activity in the plant world, the search for plant sources and their use in medicine and pharmacy. The existing and potential applications of phenylpropanoids for preventive and therapeutic purposes are discussed.Conclusion. The analysis of the scientific publications on the pharmacognostic and biomedical studies of the medicinal plants containing phenylpropanoids, substantiates the expediency of considering them as an autonomous specific class of biologically active compounds. The organoprotective profile of their action and a wide range of specific pharmacological activities of phenylpropanoids are connected by common links of the sanogenesis in the “prooxidant–antioxidant” system. The choosing of promising plant sources for the development of medicines and biologically active compounds with specified properties is justified from the dependence position of “chemical composition – structure of compounds – spectrum of activity”.

5-Alkyl-substituted derivatives of 1-(2-hydroxyethyl)-4,6-dimethyl-1H-pyrimidin-2-one (1) are synthesized for the first time. Pyrimidine 1 is an active pharmaceutical ingredient of the burn drug Xymedon, which has pronounced hepatoprotective properties. The cytotoxicity and cytoprotective properties of the synthesized pyrimidines against the Chang Liver cell line of hepatocytes are evaluated. It is shown that the introduction of an alkyl substituent into the pyrimidine ring of Xymedon have a significant negative impact on the hepatoprotective properties. [ABSTRACT FROM AUTHOR]

Currently, polymorbidity is characteristic not only for gerontological patients, but also for persons of young and middle age, which is due to the peculiarities of modern lifestyle. In this context, diseases connected pathophysiology are of particular interest, since in this case the therapeutic treatment strategies based on the existing nosological approach may not give a proper positive result. At the same time, prescribing drugs with positive pleiotropic properties plays a very important role, as it allows to influence several pathophysiological mechanisms at once and avoid polypragmasy. In this article we consider a clinical case demonstrating the features of management tactics of a young polymorbid patient with arterial hypertension, obesity and nonalcoholic fatty liver disease, in whom the addition of ursodeoxycholic acid to the complex of therapeutic interventions gave positive effects not only in reducing the severity of liver steatosis, but also in terms of cardiovascular and metabolic disorders.

Background. An analysis of published results on the chemical structure, pharmacodynamics and pharmacokinetics of hepatoprotective agents, as well as their practical application, shows that a holistic view on the pharmacology of hepatoprotective agents is yet to be developed. Thus, the relationship between antioxidant activity and the effectiveness of reducing hepatocyte cytolysis remains unclear. Another difficult question concerns indications for the application of hepatoprotectors, selection of a particular drug and treatment duration.Objectives. To investigate the effects of hepatoprotective agents with different mechanisms of action on the indicators of oxidative metabolism in the blood of patients with alcoholic hepatitis.Methods. Four groups of patients were involved in the study. The 1st group consisted of relatively healthy male patients (n = 15). The remaining groups (10 individuals in each) were represented by patients with moderate alcoholic hepatitis. Patients of the 2nd group received remaxol; patients of the 3rd group received ademetionine; patients of the 4th group received ursodeoxycholic acid. Prior to and following treatment, the indicators of cytolysis and oxidative stress in blood were determined. Statistical data processing was carried out using the StatPlus v 7 (AnalystSoft Inc.) software package.Results. According to the observed changes in the cytolytic syndrome marker enzymes, all three hepatoprotectors under study expressed comparable efficacy. After treatment according to any of the applied schemes, the ALT and AST activity in the blood plasma decreased by 56–68% and 75–81%, respectively, compared to their initial values. In comparison with the control group, the total antioxidant activity of the blood plasma decreased by 20–27%; the content of TBA-reactive products in the erythrocyte suspension increased by 61–87%. The remaxol, ademethionine or ursodeoxycholic acid therapy led to a partial normalization of the abovementioned parameters without significant differences between the experimental groups. The concentration of reduced glutathione in the erythrocyte suspension and the content of thiol groups in the blood plasma of patients were reduced in comparison with the control group by 16% and 26%, respectively. After therapy, these indicators also increased by 12–15%, although no predominant effect of either of the studied hepatoprotectors was revealed.Conclusion. The conducted comparative study indicated the absence of a specific antioxidant effect among the pharmacological mechanisms of action of remaxol, ademethionine and ursodeoxycholic acid. In this regard, further research should be carried out to investigate the effect of hepatoprotective drugs on pathobiochemical changes and to analyse a relationship between the antioxidant effect and the efficacy of reducing the level of hepatocyte cytolysis.

The article deals with a review of the current literature on the clinical use of hepatoprotectors in drug-induced liver injury. The literature was searched in Scopus, Web of Science, PubMed and other databases. Risk factors, pathogenetic mechanisms of li­ver damage, international diagnostic criteria and treatment for drug-induced liver injuries are considered. Clinical and pharmacological approaches to the choice of hepatoprotectors for the management of drug-induced liver injury are substantiated. The positive effects of ademetionine, a hepatoprotector, are highlighted — choleretic, cholekinetic, regenerating, antioxidant and antitoxic. In accordance with the principles of evidence-based medicine, it has been found that the indisputable advantage of ademetionine in the comprehensive treatment of drug-induced liver injury is its high clinical effectiveness as a mean of pathogenetic treatment of cholestasis, hepatocellular lesions and their combinations.

Scientific data on the pharmacodynamics of dry extracts of Bupleurum aureum and Salsola collina L. based on the results of studying the antimicrobial effect and the similar effect of co-trimoxazole when they are used together have been supplemented. The investigated phytoextracts do not show antimicrobial properties, but they do not change the antimicrobial effect of co-trimoxazole when they are used in combination. The aim of the study was to experimentally investigate the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establish the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when used together. Materials and methods. The research was conducted in May 2016. Screening of the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establishing of the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when they are used together was carried out in the laboratory of the Department of Microbiology of the National Pharmaceutical University, which has a certificate of attestation 045/14 dated 28.10.2014. For determination of antimicrobial activity, the agar diffusion method ("well" method), which is based on the ability of medicinal substances to penetrate the agar layer, was used. A set of reference strains of microorganisms was used: S. aureus ATCC 6538, E. coli ATCC 8739, P. aeruginosa ATCC 9027, B. subtilis ATCC 6633, C. albicans ATCC 10231. Petri dishes were filled with two layers of solid nutrient medium. The lower layer - 10 ml of melted "cold" AGV agar (medium No. 3), the upper layer - nutrient medium for the corresponding test strain. After cooling the lower layer of agar, three thin-walled steel cylinders (inner diameter -- 6.0±0.1 mm, height - 10.0±0.1 mm) were placed on it at an equal distance from each other and from the edge of the cup. The top layer was poured around the cylinders -- 13.5 ml of agar, melted and cooled to 45-48°c, mixed with the seed dose of the test microorganism (1.5 ml of microbial suspension, the concentration corresponding to the type of microorganism). After cooling the upper layer of agar, the cylinders were removed with sterile tweezers and 0.25-0.3 ml of the studied drug was added to the resulting wells. The results were recorded after 24 h by measuring the zone of growth inhibition, including the diameter of the wells. Measurements were made with an accuracy of 1 mm, while focusing on the complete absence of visible growth. The obtained data were analyzed using the methods of variational statistics. The significance level is p<0.05. The studied plant extracts of Bupleurum aureum (aqueous and alcoholic) and Salsola collina L. (aqueous and alcoholic) were used in doses of 0.005 mg/ml and 0.01 mg/ml, which corresponded to doses of 5 mg/kg and 10 mg/kg. Experimental data were also processed by parametric (Newman-Keuls) and non-parametric (Mann- Whitney) methods of variational statistics, using the Statistica 6.0 statistical software package; differences were considered statistically significant at p<0.05. Results. At the final stage, the determination of the antimicrobial effect of water and alcohol extracts of Bupleurum aureum and Salsola collina L. at doses of 1 mg/ml and 5 mg/ml was carried out, and the effect of BAS of these extracts on the antimicrobial effect of co-trimoxazole when used together was determined. In the course of the study, it has been established, that the addition of the above-mentioned extracts to the co-trimoxazole formulation does not affect its initial antimicrobial properties. Conclusion. Today, drug-induced liver injury remains one of the most important problems of hepatology and pediatrics, pharmacological science pays a lot of attention to the search for new effective and harmless drugs with a hepatoprotective effect, and the improvement of existing drugs is primarily aimed at increasing their specificity and reducing side effects related to the pharmacological properties of the drug. Currently, there is increasing interest in medicinal plants as a source of various biologically active substances (BAS), which provide a wide spectrum of pharmacological action of the agent, which allows to immediately affect various links of the pathogenesis of liver diseases. The analysis of scientific sources made it possible to establish that medicinal products of plant origin, thanks to BAS, possess polymodality of effects and reveal a versatile complex effect on the course of pathological processes in the body. Most drugs are characterized by good tolerability, absence of withdrawal syndrome and toxicity to parenchymal organs. Medicinal plants are used not only as monopreparations, but also in combination with synthetic drugs and as raw materials for obtaining BAS [ABSTRACT FROM AUTHOR]

The paper describes an in-depth in vitro and in vivo comparative study of hepatoprotective properties of some "doubled" derivatives of 4,6-dimethyl-1,2-dihydro-1-(2-hydroxyethyl)pyrimidin-2-one (the drug xymedon 1), in which the moieties of 1 are linked by ester bridges with different numbers of methylene groups (succinate (2a), adipate (2b), and suberate (2c)). The effect of "doubled" derivatives of compound 1 on the cell cycle of Chang Liver cell line was determined. The hepatoprotective properties of compounds 2a and 2b were studied in vivo in Wistar rats. Compounds 2a—c were found to restore the proliferative activity of Chang Liver cells in the presence of the d-galactosamine toxicant. Compounds 2a and 2b were effective over the widest concentration range and were more active than 2c. Compound 2b was most effective, causing a maximum increase in the percentage of cells in the G2/M phase of the cell cycle, in the concentration range from 62.5 to 250 µmol L−1, similarly to compound 1. According to in vivo studies, "doubled" derivatives 2a and 2b had less pronounced hepatoprotective properties than parent compound 1: an effect similar to that of 1 was attained at doses exceeding the minimum effective dose of xymedon (0.24 mg kg−1) by factors 7.5 and 2.7, respectively. [ABSTRACT FROM AUTHOR]

The article is devoted to the clinical effectiveness of the complex treatment of maxillofacial phlegmon in patients with liver pathology. To date, the problem of prevention and treatment of surgical infectious diseases in dentistry is one of the topical issues. According to the literature data, more than 50% of surgical complications of odontogenic infection are caused by the background pathology: cardiovascular and respiratory system diseases, diabetes mellitus, kidney and liver diseases. Particularly, the incidence of viral hepatitis "B" infection in hospital and clinical settings has increased sharply recently. The problem of surgical infections is nowadays an important and urgent one. Purulent-septic diseases annually affect millions of people and in the mortality structure of the population from infectious pathology occupy the leading place in all developed countries of the world, with a steady increase in the number of patients with abscesses and phlegmons of maxillofacial area. Many questions of etiology, pathogenesis, prevention and treatment of purulent inflammatory processes of the maxillofacial region are still unresolved, which explains the constant interest and attention of researchers to them [1,3,7,9]. Meanwhile, it is known that acute inflammatory processes of the maxillofacial region often develop with reduced immunological reactivity of the body, and the course of the disease and the likelihood of complications are largely determined by the initial immunity parameters [2,4,5,12]. The aim of the study was. To create the complex treatment program for patients with acute progressive inflammatory diseases of maxillofacial region in patients with hepatitis B. The analysis of 52 cases of maxillofacial region abscesses in patients with viral hepatitis B was performed. It was found out that in purulent-inflammatory processes of the maxillofacial area the causative agents are aerobic, anaerobic odontogenic and periodontal infection, which prevail in immunity decrease and occurrence of endogenic intoxication syndrome as well as accumulation of lipid peroxidation, which in turn leads to the liver functional activity failure. [ABSTRACT FROM AUTHOR]

Aim: the aim of the research is a pharmacological study of the original extracts of corn silk. Materials and methods. The object of the study were 4 original extracts of corn silk, obtained by extraction with water and ethanol of different concentrations, namely: aqueous extract of corn silk (ACSE), extract of corn silk, extracted with ethanol 30 % (ECSE 30 %), extract of corn silk, extracted with ethanol 50 % (ЕCSЕ 50 %), extract of corn silk, extracted with ethanol 70 % (ЕCSЕ 70 %). A screening study of the antioxidant properties of corn silk extracts was carried out in vitro using models of spontaneous and ascorbate-induced lipid peroxidation (LPO) in rat liver homogenate. Results. As can be seen from the given data, ECSE 50 % at a dose of 20 mg/kg showed a pronounced protective effect on the hepatotoxicity of TСM. Its use led to a probable restoration of the bile-forming function of the liver against the background of tetrachloromethane hepatitis: in response to an increase in the cholesterol content (by 43 %, p<0.05), the content of bile acids increased 2 times (p<0.05), as a result of which cholate -cholesterol ratio approached the level of indicators of intact animals, the rate of bile secretion normalized. Based on the analysis of the results of the study, it can be concluded, that in terms of bile-forming and choleretic activity on the tetrachloromethane hepatitis model, ECSE 50 % was not inferior to silibor and superior to quercetin (р<0.05). Conclusions. Biologically active substances of corn silk affect not only the diffusion and filtration processes of the liver parenchyma, but also the biosynthesis and transport of its organic components, that is, they affect the bile-forming function [ABSTRACT FROM AUTHOR]

The aim of research was to study the oxidized dextran protection effect against hepatic parenchyma defect at combinated acute and chronic toxicity of ethyl alcohol and tetrachloromethane solutions. Materials and methods. 150 male Wistar rats were injected by toxicants with intraperitoneal administration: 50 % CCl4 in olive oil solution and 5 % oxidized dextran (OD) aqueous solution with molecular weight 40 kDa and peroral 6.5 % ethyl alcohol aqueous solution. Tetrachloromethane was injected once a day, and then only ethyl alcohol aqueous solution was administrated 1 time per day during 3 days. The ethyl alcohol aqueous solution was not administered on the days of the of tetrachlomethane and OD injections. OD has been administered from the 1st day of the toxicants injection till 60 days. OD without toxicants has been injected for the next 30 days. Results and discussion. In animals that were injected only with toxicants, hepatocytes were in a state of vacuolar dystrophy, which occupied slightly more than 40 % of the organ parenchyma, and hepatocytes in a state of necrosis, which occupied from 37 to 28 % of the parenchyma at different periods of observation. The OD inclusion in the scheme for the prevention of necrotic complications reduced them from 3 to 4 times more than in animals that did not receive OD. The data obtained indicate the OD high hepatoprotective effectiveness.

Introduction. Liver diseases with all the variety of clinical manifestations have common pathogenetic links at the cellular level. The group of hepatoprotective agents is represented by drugs that exhibit versatile mechanisms for protecting liver cells from the effects of damaging factors, the main of which are membrane-stabilizing, antioxidant, regenerative, detoxifying, choleretic and anti-inflammatory effects. The high therapeutic and hepatoprotective effectiveness of modern drugs is largely due to their metabolic effects, as well as their ability to bind free radicals and reactive oxygen species in the cell.Text. The purpose of this work is to form an analytical review of the literature on the assortment and concepts of improving the dosage forms of hepatoprotective agents. According to the analysis and systematization of modern publications devoted to the use of hepatoprotectors in the treatment of liver diseases, it is shown that it is necessary to develop new formulations and combinations of biologically active substances with the manifestation of versatile mechanisms of hepatoprotection, as well as to improve the composition and manufacturing technologies of existing traditional therapies. One of the current trends is the use of new substances in the development of traditional and innovative dosage forms. The search for biologically active molecules with antioxidant, antiradical and membrane-stabilizing activity that can be considered as effective hepatoprotectors continues. An integral task of pharmaceutical development is the creation of bioavailable drugs that have a prolonged effect and minimal side effects. A promising direction in pharmaceutical technology is the development of innovative drugs for the directed transport of biologically active molecules to the affected organ.Conclusion. As a result of the analysis of modern data, priority directions for the development and improvement of existing formulations based on modern approaches to the production of innovative dosage forms are identified. The relevance of improving the dosage forms of hepatoprotectors presented on the pharmaceutical market is shown. Of particular interest is the development of innovative targeted delivery systems with effective and safe hepatoprotectors in various combinations, including those based on cinnamic acid derivatives.

The article deals with a review of the current literature on the clinical use of hepatoprotectors in drug-induced liver injury. The literature was searched in Scopus, Web of Science, PubMed and other databases. Risk factors, pathogenetic mechanisms of liver damage, international diagnostic criteria and treatment for drug-induced liver injuries are considered. Clinical and pharmacological approaches to the choice of hepatoprotectors for the management of drug-induced liver injury are substantiated. The positive effects of ademetionine, a hepatoprotector, are highlighted — choleretic, cholekinetic, regenerating, antioxidant and antitoxic. In accordance with the principles of evidence-based medicine, it has been found that the indisputable advantage of ademetionine in the comprehensive treatment of drug-induced liver injury is its high clinical effectiveness as a mean of pathogenetic treatment of cholestasis, hepatocellular lesions and their combinations. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the features of the organization of therapy for patients with HIV-associated tuberculosis (TB/HIV) and the effectiveness of pharmacotherapeutic approaches under the conditions of penitentiary institutions. Materials and methods: the data on the incidence and effectiveness of specialized medical care for TB/HIV patients were analyzed for a ten-year period in the population of penitentiary institutions of the Federal Penitentiary Service of one of the subjects of the Central Federal District of the Russian Federation. Therapy and examination of patients with TB/HIV was carried out in accordance with regulatory documents and using generally accepted diagnostic methods. The patients consulted the staff of the departments of the FSBEI HE KSMU to verify the diagnosis and correct treatment regimens. Results: the analysis showed that, despite the stabilization of the TB epidemic situation, the epidemiological indicators for comorbid TB/HIV are increasing in the penitentiary health sector, which is due to an increase in the number of HIV-infected patients. In order to intensify the treatment of patients with TB/HIV in the population of the penitentiary system, it is necessary to give priority to social and sanitary prevention, primarily in risk groups — HIV-infected and individuals with residual lung changes. The inclusion of Remaxol in the therapy regimens for TB/HIV patients promotes rapid relief of hepatotoxic reactions and, as a consequence, increases the effectiveness of the primary therapy, which is illustrated by clinical observation.

High incidence of liver disease is one of the major problems for health care in the world. Today, etiotropics such as vaccines, antivirals, etc. are used to prevent and treat liver diseases. In addition, medicines for additional treatment of liver diseases, so-called hepatoprotectors, are often used in medical practice. Hepatoprotectors vary in both chemical composition and mechanism of action and target to increase liver resistance to adverse factors. The aim of the study was to provide a comprehensive analysis of Ukrainian pharmaceutical market in the framework of the group of hepatoprotectors and its price range. Materials and methods. The study was carried out grounding on the data provided by State Register of Medicines of Ukraine, International Classification of Diseases 11 issue (МКХ-11, ICD-11), entered into force on June 18, 2018 by the Order of Health Ministry of Ukraine № 892 dated 18.04.2019. “About Approval of the Eleventh Issue of the National Formulary of Medicines and Making It Available”, National List of Essential Medicines, approved by the Cabinet of Ministers of Ukraine № 333 dated 25.03.2009 (on 07.05.2019), and analytical system of the pharmaceutical market “Farmstandard” by Morion company for the period between 2019 and the first half of 2020. During investigation, systemic, structural, logical practices and method of summarization were used. Results. The results of the research show that the domestic market for hepatoprotectors is saturated enough. It embraces both Ukrainian producers and foreign firms, mainly from India, Germany, France, Italy, China, Switzerland. The analysis of the changes in the prices for drugs of this group shows that during the period between 2017–2020 there was a significant increase in the prices of all drugs in the submitted sub-groups, which can be attributed to currency market instability. The structural analysis of the hepatoprotectors shows that the subgroup A05A X10, namely the combined drugs, constitutes the majority (57, 51, 67, 55 names according to studied year). The smallest subgroup is A05B A06 Ornithine oxyglurate (no names of medicine were registered by domestic producers in 2017). The activity of domestic producers should be noted. The proportion of Ukrainian preparations in this segment is 86.20 %, 84.12 %, 68.00 %, 56.79 % (first half of 2020) (according to years under consideration). Conclusions. The range analysis conducted for the period between 2017–2020 (first half-year) shows saturation of the domestic pharmaceutical market with hepatotropic drugs. Structural analysis conducted reveals that the pharmaceutical market in Ukraine is dominated by Ukrainian medicines, in particular from 56.79 % to 86.20 % (according to years under consideration). Price trend analysis shows low availability of imported products for some sub-groups: during 2019–2020, in sub-group A05A A02 Ursodeoxycholic acid price ranged from 1207.57 to 2376.15 UAH, and A05B A06 Ornithine oxyglurate it ranged from 1397.99 to 2557.55 UAH respectively.

Background: Considerable attention is currently drawn to inflammation as one of the main risk factors in the development of colon cancer. The aggravation of endogenous intoxication under conditions of the oncological process is observed concurrently with the development of inflammatory processes in the body. [19]. The objective need for cytostatic therapy occurs under the development of colorectal cancer to inhibit tumor growth. It has been substantiated that cytostatic therapy can cause almost all known forms of hepatic diseases, which leads to the necessitate use of adjunct medication to eliminate the adverse effects of the cytostatics.Material and methods: The experimental studies were conducted on white rats kept on a standard diet in the vivarium conditions. All procedures were performed in compliance with the regulations of «The European Convention for the protection of vertebrate animals used for experimental and other scientific purposes». The carcinogen 1,2-dimethylhydrazine.(DMH) was injected subcutaneously in the interscapular region at a dose of 7,2 mg/kg of body weight once a week for 30 weeks. The medication Xeloda was daily administered by an intragastric route at a dose of 134 mg/kg of animal’s body weight for 21 days, starting immediately after 7-month modeling of the oncological process. The hepatoprotector Glutargin was administered to eliminate adverse effects of thecytostatic upon the liver at a dose of 130 mg / kg for 21 days after modeling the oncological process and effect of the cytostatic agent Xeloda. Levels of pro- and anti-inflammatory interleukins in blood serum were determined by immunoenzyme technique. The endogenous intoxication level was measured through the accumulation of middle molecules in the blood serum.Results and Discussion: It was established that the concentration of markers of endogenous intoxication in the blood serum - middle molecules of both fractions (with the predominance of branched-chain and aromatic amino acids) increased within seven months of dimethylhydrazine administration, reaching the peak concentration over the last month of the conducted experiment (the increase was 2.9 and 2, 8 times, respectively). The augmented concentration of pro-inflammatory IL-6 (by 3,6 times), as well the decreased concentration of anti-inflammatory IL-4 (by 50%) were determined within the same experimental period, indicating the development of inflammatory processes under conditions of colon cancer in rats. The cytostatic agent Xeloda, administered for 21 days, exacerbated the revealed disorders after the adenocarcinoma modeling. An even greater increase in the content of middle molecules, as well as the imbalance in the levels of cytokines, were observed after the administration of cytostatic. The level of pro-inflammatory cytokine was exaggerated by 28% compared to the experimental group of animals with dimethylhydrazine-induced carcinogenesis for 7 months. The hepatoprotector Glutargin, administered to eliminate adverse effects of the cytostatic, evidenced its efficacy under these conditions. The use of the hepatoprotector caused the decrease in the concentration of IL-6 by 1,7 times compared to the animals with induced adenocarcinoma administered the medication Xeloda, which indicates the inhibition of inflammatory processes under the pathological process.Conclusions: It has been evidenced that administration of the hepatoprotector Glutargin leads to the normalization of the studied parameters in rats with induced carcinogenesis that were administered the cytostatic agent Xeloda, indicating the prospects of further research of its effect on inflammatory processes and indicators of endogenous intoxication in the dynamics of colorectal cancer development.

Aim.To provide modern view on atherogenic disorders in the blood lipid spectrum, the principles of lipid-lowering therapy prescription in certain groups of patients, the safety issues of statin therapy in patients with chronic liver diseases. Materials and methods.The data of 55 scientific sources published in the Russian and foreign press in 19882020 were analyzed. Results.It is known that atherogenic dyslipidemia is a key factor in pathogenesis of atherosclerotic cardiovascular diseases. Various disorders in blood lipids and lipoproteins are identified. In this regard, there are certain recommendations for the analysis of lipids and lipoproteins in certain situations. The issues of interpreting extreme deviations from normal values of the blood lipid spectrum are discussed. Patient groups with different levels of the cardiovascular risk, which determines prescription of lipid-lowering therapy, are presented. Statins are the first line of lipid-lowering therapy for both the correction of dyslipidemia and the prevention of cardiovascular complications. The article discusses the tactics of prescribing statins in special groups of patients, their safety issues. It considers promising ways for increasing statins tolerability in patients with chronic liver diseases, primarily with non-alcoholic fatty liver disease, by adding of combined hepatoprotector. Conclusions.Generally, modern tactics of statins prescription are based on dyslipidemia characteristics and the patients cardiovascular risk level. Moreover, statins are clinically effective in special patient groups and have a good tolerability profile.

Antioxidants of natural origin are considered as possible agents for prevention and treatment of liver diseases. Marine algae and in particular their extracts and obtained from them sulfated polysaccharides are significant sources of natural antioxidants. The recent data on the effect of the extracts and sulfated polysaccharides of seaweed on the functional activity of the liver with injuries induced by CCl4, some drugs (paracetamol, diclofenac), N-nitrosocompounds, aflatoxin are presented in the review.Particular attention is paid to the effect of sulfated polysaccharides and in particular fucoidans on the functional activity of the liver in patients with chronic viral hepatitis C. Fucoidan is highly safe and active not only as an antioxidant but also as an inhibitor of HCV replication, has antiinflammatory and immunomodulating effects. The data of the review allow to conclude that seaweed extracts and sulfated polysaccharides may be a basis for development of new generation drugs in the future for the treatment and prevention of liver diseases.

Efficient chemotherapy of tuberculosis patients could be complicated by hepatoprotective responses to antituberculosis drugs. The frequency and nature of the response depend on the drug and the genotypical and phenotypical characteristics of its metabolism in the patients, that should be considered while choosing the hepatoprotector. The liver injury was induced by the reserve antituberculosis drugs in experiments on rats with various acetylation phenotypes. Analysis of the clinicobiochemical and morphological indices revealed differences in the liver injury simulation: prevalence of the cytolytic mechanism in slow acetylators vs. the rapid ones.

The study of pharmacological properties and experimental substantiation of application possibilities of the plum fruits extracts in the treatment of the gastrointestinal tract and hepatobiliary system diseases is relevant, because plum is source of phenolic compounds with a wide range of action and is used in folk medicine for treating diseases of digestive system. The aim of the present work was an experimental study of anti free radical activity by lipid peroxidation indicators and antioxidant properties by the antioxidant system (AOS) indicators of two Plum extracts, detecting the most effective extract and determining its effective dose. The objects of research were extracts obtained from the fresh plum fruits: plum extract containing fibers (PEF) and extract containing plum polysaccharide complex (PEPC). Research methods: pharmacological (modeling of alcoholic damage to rat liver), biochemical (determination of the level of diene conjugates, TBA-AP, lipid hydroxyperoxides, reduced glutathione and α-tocopherol in rat liver homogenate) and statistical (using the program «Statistica 6.0», Student’s t-test). Experimental data on the study of the anti free radical properties of the plum extracts showed inhibitory effects on lipid peroxidation, reducing the content of diene conjugates, TBAs, and lipid hydroxyperoxides under conditions of alcoholic liver damage. Regarding the effect of the investigated extracts on the markers of the antioxidant system of hepatocytes, there was an increase in the content of reducing glutathione and α-tocopherol on the alcoholic hepatitis model. The fiber-containing extract (PEF) was the most effective in normalizing the functional state of the liver at a dose of 200 mg/kg. Thus, it was determined that an effective dose of extract with fibers (PEF) was 200 mg/kg. The investigated effects of PEF in 200 mg/kg exceeded the effects of PEPS at the tested doses and were at the level of activity of reference drug «Silibor» in the dose of 25 mg/kg. Anti free radical and antioxidant properties of the PEF are probably related to its chemical composition namely phenolic compounds (anthocyanins and hydroxycinnamic acids). Considering the results of screening, the most promising subject for further in-depth pharmacological study is plum extract PEF at dose 200 mg/kg.

Hepatobiliary system diseases represent an important medical and social problem due to increasing morbidity rates worldwide. Liver and biliary diseases are characterized by complex pathophysiology as well as by multi- and comorbidity. The treatment of such diseases necessitates multitarget drug development. The effectiveness of current drugs in the treatment of hepatobiliary disorders remains low and the incidence of side-effects are profound. This actualizes the search and development of highly effective hepatoprotectors with a low incidence of side effects. Medicinal plants potentially constitute a sourse of such preparations. The review summarizes the data concerning mechanisms of hepatoprotective and immunomodulatory effects of medicinal plants and their phytoconstituents. The prospects for the development and use of herbal remedies in the treatment of hepatobiliary diseases are outlined.

The rationale for this study is the controversial data regarding the efficacy of hepatoprotectors and antioxidants for lipid profile correction in non-alcoholic fatty liver disease, the prevalence of which is increasing especially in association with diabetes mellitus. We examined 100 non-alcoholic fatty liver disease patients (40–75 years old) with concomitant type 2 diabetes mellitus (n = 73) or without it (n = 27), the groups were standardized by age and gender. In patients with non-alcoholic fatty liver disease with diabetes mellitus we revealed significantly higher rates of total cholesterol, triglycerides and atherogenic factor in association with a significantly lower high-density lipoproteins level versus the group of patients without concomitant diabetes. We recommended the modification of lifestyle as basic management of their condition to all patients, hypoglycemic therapy with metformin to persons with concomitant diabetes mellitus and rosuvastatin to patients with non-alcoholic fatty liver disease without diabetes. In addition, 25 patients received essential phospholipids (2 caps. 3 times a day) and omega-3 polyunsaturated fatty acids (1000 mg per day) for 3 months; 26 patients – α-lipoic acid (600 mg daily) for 3 months, 22 patients received rosuvastatin (10 mg daily), 27 patients with non-alcoholic fatty liver disease without diabetes mellitus received rosuvastatin (10 mg daily). We evaluated the treatment efficiency after 3 months treatment, and the remote consequences – 12 months after the start of combined treatment. After 3 months, the alanine-aminotransferase rate had decreased by 15.1% in the group taking combined essential phospholipids and ω3-polyunsaturated fatty acids and by 12.9% in the group taking alpha-lipoic acid, which was significantly larger than in the rosuvastatin group (7.5%); gamma-glutamate transpeptidase level decreased by 16.7%, 18.7% and 9.4% respectively indicating anticholestatic and hepatoprotective effect of both proposed treatment combinations. The same tendency of cytolysis and cholestasis processes inhibition was observed after 12 months as well. In conclusion, the combination of standard treatment with antioxidant and hepatoprotective agents (omega-3 polyunsaturated fatty acids with essential phospholipids or only alpha-lipoic acid) promotes both cytolysis and cholestasis syndromes inhibition in non-alcoholic fatty liver disease patients with concomitant type 2 diabetes mellitus.

Data on assessment of lecithin preparation effect on liver toxicity experimentally induced in laboratory animals are presented. Experiments were carried out in rats kept under similar conditions that had been subjected to quarantine in animal facilities and demonstrated no apparent disease manifestations. The animals were divided into groups based on paired counterparts’ principle. Acute toxic damage of liver was induced by single administration of carbon tetrachloride (0.3 mg/kg of body weight). The rats demonstrated the following apparent signs of intoxication on day 2 after administration: anorexia, depression, dyspnea, fever.Per os administration of rape lecithin at a dose of 1 ml/kg of body weight one hour before hepatotoxicant administration and then daily for subsequent 30 days reduces intoxication manifestations and improves survivability of the rats. Pharmacological effect of lecithin includes biochemical characteristics improvement and functional state of liver of laboratory animals with experimentally induced acute hepatitis. Obtained data may provide grounds for application of lecithins as hepatoprotectors of natural origin in the form of biologically active supplements or active ingredients of pharmaceuticals intended for hepatic disease treatment in animals.

"Double" derivatives of the drug Xymedon (1,2-dihydro-4,6-dimethyl-1-N-(hydroxyethyl)pyrimidone-2), hereafter referred to as pyrimidine (I), in which the pyrimidine (I) molecules are joined by an alkyl(xylylenyl)dionate bridge have been synthesized. Primary data on the hepatoprotective activity of five "double" pyrimidine (I) derivatives with different numbers of methylene groups and a meta-xylylene fragment in the ester bridge have been obtained on normal human hepatocytes of the Chang Liver cell line. The cytotoxicity and the cytoprotective properties of the new compounds against the background of exposure to d-galactosamine at a concentration of 150 mmol/L have been determined, their effect on the cell cycle compared with that of the initial pyrimidine (I) has been studied, and the dependence of the biological properties of the derivatives on their structure has been established. [ABSTRACT FROM AUTHOR]

The hepatoprotective activity of 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-one was studied in vivo using a model of CCl4-induced acute toxic hepatitis. It was found that this compound affected indices determining the level of free-radical oxidation, i.e., levels of malondialdehyde (MDA) and diene conjugates (DC), and the activities of the key antioxidant enzymes superoxide dismutase (SOD) and catalase. Hepatoprotective activity was analyzed using the activity levels of the enzymes alanine aminotransferase (AlAT), aspartate aminotransferase (AsAT), and alkaline phosphatase and the bilirubin level. The mechanism of the antioxidant activity was determined from the effect of this compound on the expression levels of the gene katG encoding catalase-hydroperoxidase I and the gene sodA encoding Mn-superoxide dismutase. It was found that 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]-cinnolin-3-one exhibited antioxidant activity by increasing the SOD and catalase levels. [ABSTRACT FROM AUTHOR]

The effect of the Xymedon conjugate with methionine on blastema regeneration in Schmidtea mediterranea planarians was investigated. It was established that the preparation has low toxicity towards planarians, which is evidenced by its CL50 values (lethal concentration). The results of the vital computer morphometry and flow cytofluorometry confirm that Xymedon with methionine induces regeneration at high concentrations only: 0.01 g/100 mL, 0.05 g/100 mL, and 0.1 mg/100 mL. Low concentrations of the preparation have no influence on blastema regeneration in planarians. [ABSTRACT FROM AUTHOR]

The article describes the current views on the pathogenesis of nonalcoholic fatty liver disease and a short overview of possible methods of therapy. The main mechanisms of antioxidant action of ademetionine in the treatment of NAFLD and the analysis of the evidence base of its effectiveness are discussed. We present clinical cases of a positive impact of ademetionine in NAFLD patients.

Liver cirrhosis is the consequence of chronicisation and of the evolution of untreated liver diseases. The complexity of the disease and the complications it can cause have been and are still intensively researched, aiming to discover new therapies or improve existing ones for the effective management of liver cirrhosis. Currently, the treatment used is directed against the cause that caused the disease, if it is known; in advanced cases, liver transplantation is the only valid therapeutic option. Hepatoprotectors that are currently on the market are numerous, having as common properties the antioxidant, anti-inflammatory, stabilizing properties of the hepatocytic membrane; A few examples: the ethanolic extract of Curcuma longa, the extract from the plant called Sophora flavescens, the extract of Glycyrrhiza glabra, silymarin (extracted from Sylibum marianum), the extract of Ganoderma lucidum, etc. Liver cirrhosis is accompanied by generalized hypovitaminosis, so supplementing the diet with hydro- and liposoluble vitamins is mandatory. Protein-caloric malnutrition can be prevented by a hyperprotein diet, especially beneficial being the supplementation with branched-chain amino acids, which are also applicable in the prophylaxis and treatment of hepatic encephalopathy. Nanoparticles are a state-of-the-art therapeutic option, proving increased bioavailability, for example polydopamine nanoparticles loaded with l-arginine have been tested as therapy in liver cirrhosis. Among the innovative treatment directions in liver cirrhosis are hybrid products (e.g. hybrid polymer nanoparticles loaded with caffeic acid), cell cultures and artificial or bioartificial liver support.

A salt-like conjugate of xymedone with para-aminobenzoic acid in a series of pyrimidine derivatives was synthesized, and its hepatoprotective properties were studied. The compound studied exhibits a cytoprotective effect at a concentration of 25 μmol L-1 enhancing the viability of normal human hepatocyte cells of the Chang Liver line by 2.1 times against the background of the impact of the d-galactosamine toxicant, which was shown by experiments in vitro. The cytotoxicity of the compound (IC50) is 20.7 mmol L-1. The data indicating the hepatoprotective effect most pronounced at the early stages of therapy were obtained in experiments in vivo performed according to the therapeutic scheme on the model of CCl4-induced toxic hepatitis. The ability of the conjugate to exert reparative and protective effects was found, since the surface area of destructive-degenerative and necrotic injuries revealed in hematoxylin- and eosin-stained sections on the third day of intraperitoneal administration of the studied compound in a dose of 0.7 mg kg-1 decreased by 1.5 times. The areas of detection of lipid inclusions in frozen sections stained with Sudan black decreased by four times on the third day at a dose of 1.7 mg kg-1, whereas the decrease was 3.2 times on the seventh day at a dose of 0.7 mg kg-1 compared to the control group of animals administrated with saline. According to the biochemical parameters, positive effects on the secretory and synthetic functions of the liver, bilirubin metabolism, and metabolism of iron and magnesium were observed during the treatment of animals with the conjugate. [ABSTRACT FROM AUTHOR]

This article deals with the data on therapy of 130 patients who suffered chronic hepatic diseases (metabolic, viral) and by various reasons received the hepatoprotector and the immune modulator Laenneс. The high effectiveness of patients therapy by steatohepatites (alcoholic and non-alcoholic) was shown. In patients with chronic viral hepatitis B and C, who received antiviral therapy Leannec was used successfully to overcome antiviral therapy resistance, to reduce therapy side effects (high fever, muscular weakness, pancytopenia). Laennec allows overcoming these side effects and anemia therapy resistance in patients who suffered from chronic hepatitis at the hepatic cirrhosis stage.

In current work examination of 150 obese women with normal body weight was conducted. Peculiarities of pregnancy period and delivery are described. The structure of developed complications, as well as prevalence of nonalcoholic fatty liver disease among them are presented. It is revealed, that in 52% of pregnant women with obesity ultrasound signs of fatty degeneration of the liver are present. However, typical changes in blood biochemical analysis are detected only in 12% of patients. Thus, management of pregnancy in obese women should includeliver ultrasound examination. And in case of evaluation of fatty liver distrophyhepatoprotectors and membrane stabilizers with low fatty diet should be indicated.

Nonalcoholic fatty liver disease is a chronic disease uniting steatosis, nonalcoholic steatohepatitis and cirrhosis. Nonalcoholic fatty liver disease is associated with obesity and is a component of metabolic syndrome, thus increasing cardiometabolic risk and affecting the prognosis and duration of life of patients. The review tells about the mechanisms, symptoms, diagnosis and treatment of nonalcoholic fatty liver disease.

The article deals with the treatment of nonalcoholic fatty liver disease as a complication in patients with complex cardiovascular disease and type 2 diabetes mellitus. The data from the studies on the effect of Hepa-Merz® on the functional state of the liver, endothelium, blood rheology, the state of the capillary circulation, endotoxemia markers and clinical status in these patients are presented. The findings confirm the possibility of the influence of Hepa-Merz® on the functional disorders of the liver in patients with complex cardiovascular disease and type 2 diabetes mellitus.

The aim of review. To keep doctors and population in the picture of alcohol abuse issues and to acquaint with treatment approach at alcoholic disease, to prove necessity of primary and secondary prophylaxis.Key points. Alcoholism control efforts should be directed first of all on prevention of this disease. Primary prophylaxis is necessary for decrease or stop of alcohol consumption. It is required to educate population and to unveil myths about safe, and the more so useful dozes of alcohol. Secondary prophylaxis includes application of specific therapy with application of metabolic agents (hepatoprotectors).Conclusion. Alcohol is the main etiological factor of liver cirrhosis in Russia. Prompt change of situation with alcohol abuse is required for reduction of morbidity and mortality. Preventive actions should be directed on change of embedded stereotypes of doctors and population in relation to alcohol intake.

Introduction: Influence of the endogenous opioid system on the liver has not been studied enough. To understand the damaging effects of stress on the liver and the hepatoprotective effects of opioids, a study was performed on stress-resistant and stress-susceptible animals. Materials and methods: The investigation was performed on 725 Wistar male-rats. Various types of stress were modeled: acute immobilization stress of various duration (3, 6 and 12 hours), chronic stress of limited mobility, swimming stress and traumatic stress (resection of 70% of the liver). Agonists of various types of opioid receptors in equimolar doses were injected to stressed animals at equimolar doses: DAGO - a mu-receptor agonist - at a dose of 6.3 mcg/kg, DSLET - a delta-receptor agonist - at a dose of 10 mcg/kg, and kappa receptor agonist dynorphin A (1-13) - at a dose of 20.1 mcg/kg. Results and discussion: The stress-limiting action of the studied opioids is characterized by the reduced hepatocyte dystrophy, microcirculation correction, a decreased concentration of lipid peroxidation metabolites, a suppressed cytolytic syndrome, a stimulated synthetic ability of the liver, and is more pronounced in stress- susceptible animals. The greatest stress-protective effect is shown after administering dynorphin A (1-13) in immobilization stress, and DAGO - in swimming stress. Dynorphin A (1-13) and DAGO manifested the most pronounced effect on the liver regeneration after resection. A preliminary stress simulation accelerates liver regeneration at the initial stage after resection. Conclusion: The hepatoprotective effect of opioids in stress depends on the typological peculiarities of animals. The results obtained offer a challenge of synthesizing new hepatoprotectors. [ABSTRACT FROM AUTHOR]

Silybin (Slb) and ursodeoxycholic acid (UDCA) are hepatoprotectors used in the pathogenetic therapy of liver and biliary tract. However, low bioavailability of these drugs restricts their application. In order to solve this problem, Slb and UDCA were incorporated into polymer carriers based on polylactic acid and poly(lactic-co-glycolic acid) by nanoprecipitation. The polymeric forms obtained according to the developed and optimized method are nanoparticles with a size from 100 to 200 μm. In vitro experiments showed a 1.5-2-fold higher hepatoprotective activity of Slb- and UDCA-containing polymeric nanoparticles compared to free substances. [ABSTRACT FROM AUTHOR]

We studied circadian rhythms of activity of hepatoprotectors (Antral, Carsil, and glutargin) under conditions of acute paracetamol-induced hepatitis simulated in the morning, afternoon, evening, and at night (09.00, 15.00, 21.00, and 03.00). Antral and Carsil exhibited similar chronoprofiles with the maximum hepatoprotective activity at 09.00 and 21.00, while glutargin exhibited circadian pattern opposite and its activity was maximum at 15.00 and 03.00. [ABSTRACT FROM AUTHOR]

Aim: To develop of antidysbiotic and antiphlogistic actions of quertulin on rat tissues at he toxic hepatitis. Materials and methods: The hepatitis was made with hydrazine sulfate. Antidysbiotic action was estimated by the correlation of urease and lysozyme, antiphlogistic action was estimated by depression of the levels of elastase and malonic dialdehide (MDA). Quertulin (quercetin + inulin + citrate Ca) was introduced per os in dose of 300 mg/kg in duration 14 days. The objects of investigation were liver, kidney, gum, mucosa of check, intestine and colon, serum. Results: The toxic hepatitis were made the raising levels of urease, elastase, MDA and depressing level of lysozyme. Quertulin was depressed of levels of urease, elastase, MDA and was raised of lysozyme level. Conclusion: The toxic hepatitis was developed dysbiosis and inflammation in the rat tissues. Quertulin was made antidysbiotic and antiphlogistic actions, much expressed in colon.