Markers Of Cytolysis Research Articles

Conjugate of pyrimidine derivative, the drug xymedon with succinic acid protects liver cells.

The aim of the study was to investigate the hepatoprotective properties of the conjugate of the xymedon drug substance with succinic acid (1a). The study presents an in vitro comparative evaluation of the cytotoxicity and cytoprotective properties of 1a and succinic acid on a cell line of normal human hepatocytes Chang Liver, and in vivo investigation of the ability of 1a to restore liver from the toxic damage caused by CCl4 in Wistar rats. It was shown that the cytotoxicity of 1a was 19.9 ± 0.8 mmol/L, and that of succinic acid was 14.1 ± 0.2 mmol/L. Against the background of d-galactosamine exposure, the cytoprotective effect of 1a was found to be superior to that of succinic acid. It was shown that 1a caused a significant reduction in necrotic and steatosis changes in the liver and restoration of biochemical markers of cytolysis, as well as bilirubin metabolism and synthetic liver function.

“Hepatogenic diabetes” is an old term and new meaning

Introduction. Today, non-alcoholic fatty liver disease (NAFLD) is increasingly associated with the presence or risk of developing type 2 diabetes (D2). The term “hepatogenic diabetes”, proposed to refer to SD2 in patients with cirrhosis of the liver (CP), has acquired a new meaning, since this combination is of growing interest. The authors analyzed the current literature and summarized data on the pathogenesis, risk factors, and possible therapy of NAFLD.Objective: to evaluate the effectiveness of L-ornithine-L-aspartate (HEPA-Merz, Merz Pharma GmbH & Co) in combination with biguanides in the treatment of NAFLD patients in combination with D2.Materials and methods. The study included 30 patients aged 26 to 60 years with a verified diagnosis of NAFLD of varying degrees of activity in combination with D2. All patients were prescribed combination therapy with the drug HEPA-Merz (“Merz Pharma GmbH and Co”) at a dose of 3 grams 3 times a day in combination with biguanides. The examination was performed on the 1st, 28-th and 56-th days of treatment. In order to determine the effectiveness of therapy, we evaluated the dynamics of clinical symptoms (asthenovegetative, dyspeptic syndromes, pain syndrome in the ball system), biochemical parameters of liver function (changes in markers of cytolysis, cholestasis), lipidogram indicators, glucose levels, glycated hemoglobin, and ultrasound results of abdominal organs.Results. On day 56, asthenovegetative, dyspeptic and pain syndrome were stopped during therapy. Most patients showed a decrease in body weight from 3 to 5 kg. When evaluating changes in biochemical parameters on the 28-th day, the activity of ALT, AST, GGTP and glucose levels significantly decreased against the background of the therapy. On the 56th day of treatment, the activity of transaminases, bilirubin, GGTP and GFR in all patients were within the reference values.Conclusion. Understanding the multifactorial nature of NAFLD and the mechanisms of associated diseases, including D2, will allow us to assess the prognosis of the disease and prescribe adequate timely therapy. The effectiveness of the original ornithineaspartate (Merz Pharma GmbH & Co.) is manifested by a decrease in the processes of cytolysis of hepatocytes, normalization of lipid and carbohydrate metabolism.

Features of therapy of alcoholic liver disease in persons of young age

The aim of this study was to study the eff ects of using the infusion drug Remaxol in young patients with alcoholic liver disease.Materials and methods: the clinical and laboratory data of 80 young patients with alcoholic liver disease were analyzed, divided depending on the treatment regimen into 2 groups: the main (n = 44) who received Remaxol according to the scheme: 400 ml iv, drip, at a rate 40–60 drops per minute daily, course No. 5–10, and control (n = 36) — received basic therapy. In all patients, the dynamics in blood serum was studied: lipid peroxidation indices (malondialdehyde, diene conjugates), antioxidant protection enzymes (catalase, SOD, glutathione peroxidase), markers of cytolysis, cholestasis and lipid metabolism.Results: initially there was a significant increase in lipid peroxidation processes, accompanied by slight stimulation of the antioxidant system of the liver and pronounced signs of cytolysis and cholestasis. The inclusion of Remaxol in treatment regimens leads to a significant decrease in the level of malondialdehyde and diene conjugates, and the restoration of the antioxidant system (increase in catalase, SOD, and glutathione peroxidase). At the same time, a marked decrease in the syndromes of cytolysis and cholestasis was noted, which was accompanied by an improvement in the condition of the patients: cessation of nausea, restoration of appetite and sleep, and improvement of well-being.

Експериментальне дослідження кардіопротекторної дії 2-гідрокси-N-нафтален1-іл-2-(2-oксо-1,2-дигідро-індол-3-іліден)ацетаміду

Сучасні принципи лікування коморбідних пацієнтів із серцево-судинними захворюваннями та тяжкими психічними розладами спрямовані на обмеження поліпрагмазії. Тому перспективним є пошук препаратів полімодальної дії, здатних одночасно виявляти як кардіопротекторну, так і нейромодулювальну дію. У цьому аспекті привертають увагу похідні 2-оксоіндолін-3-гліоксилової кислоти, яким притаманний широкий спектр нейротропної активності. Мета дослідження – визначити вплив потенційного нейротропного засобу – 2-гідрокси-N-нафтален-1-іл-2-(2-oксо-1,2-дигідро-індол-3-іліден)-ацетаміду (умовна назва – сполука 18) – на перебіг експериментального ураження серця щурів. Досліди проведено на 38 статевозрілих рандомбредних білих щурах самцях. Адреналіновий міокардит моделювали шляхом одноразового підшкірного введення розчину адреналіну гідротартрату («Адреналін-Дарниця», розчин для ін’єкцій, 1,8 мг/мл, ФК «Дарниця», Україна) у дозі 1 мг/кг. Досліджувану речовину в дозі 12 мг/кг і препарат порівняння етилметилгідроксипіридину сукцинат («Армадин», розчин для для ін’єкцій, 50 мг/мл, ЗАТ «Лекхім-Харків», Україна) у дозі 100 мг/кг вводили внутрішньоочеревинно в лікувально-профілактичному режимі за 30 хв до і через 1 год після моделювання ураження міокарда. Функціональний стан міокарда оцінювали за показниками електрокардіограми. Виразність деструктивних процесів у серцевому м’язі визначали за активністю МВ-фракції креа тинфосфокінази, маркерних ферментів цитолізу – аспартатамінотрансферази та аланінамінотрансферази в плазмі крові щурів. Інтенсивність процесів пероксидного окиснення ліпідів визначали за вмістом активних продуктів, що реагують з тіобарбітуровою кислотою, у плазмі крові та гомогенаті міокарда щурів, стан антиоксидантної системи – за активністю супероксиддисмутази та каталази в гомогенаті міокарда. Досліджували морфологічний стан серця щурів. Встановлено, що адреналіновий міокардит у щурів супроводжується як функціональними (електрокардіографічними та біохімічними) змінами, так і дифузними морфологічними ознаками ішемії міокарда (спазм тонкостінних судин, венозний застій), дистрофії серцевого м’яза (набряк, втрата поперечної посмугованості) і некрозу кардіоміоцитів. У той самий час сполука 18 за умов адреналінового міокардиту чинить виразну кардіопротекторну дію, що її встановлено за відновленням електрокардіографічних показників і біохімічних індикаторів функціонального стану міокарда, а також морфологічно – за редукцією проявів ішемії та дистрофії серцевого м’яза тварин. Визначено також, що кардіопротекторний ефект сполуки 18 значно перевищує дію препарату порівняння етилметилгідроксипіридину сукцинату за експериментального адреналінового ураження серця щурів.

THERAPEUTIC PLASMAPHERESIS IN A COMPLEX TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS

The aim: To determine the pathogenetic expediency, efficiency and the place of therapeutic plasmapheresis in a complex treatment of patients with chronic hepatitis. Materials and methods: It was carried out the analysis of case histories of 77 patients. In the course of treatment, the patients were diagnosed with chronic toxic hepatitis (K.71). Diagnosis was exposed in accordance with the official documentation introduced by the Gastroenterological department of Sumy Regional Clinical Hospital CH"SRCH", Sumy Regional Infectious Diseases Clinical Hospital named after Krasovytsky ZY and Sumy Regional Center of Blood Service. Results: It was found that total protein indicator is the normal range and albumin after plasmapheresis and during conservative treatment. Markers of cytolysis and cholestasis are have great value may. The most significant changes were observed in rates indicating lesion of the hepatic parenchyma, including ALT, AsAT and alkaline phosphatase. In conservative treatment, the percentageof the alkaline phosphatase level improved by 31%, after the course of plasmapheresis - by 58%. The obtained figures of cholestasis indexes indicate the effectiveness of both methods of treatment, but treatment with plasmapheresis has a more expressed effect on the decrease of alkaline phosphatase level. The level of bilirubin improve on 38,8% after plasmapheresis and 65% in the comparison group. Conclusion: Inclusion in the complex therapy of chronic hepatitis plasmapheresis reduces the severity of cytolysis and cholestasis, increases remission and significantly improves clinical manifestations.

The Effect of 6-Hydroxy-2,2,4-Trimethyl-1,2-Dihydroquinoline on the Intensity of Free Radical Processes and Activity of Oxidative Metabolism Enzymes in Rats with Toxic Liver Injury

The effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of hepatocyte cytolysis (aspartate transaminase, alanine transaminase and gamma-glutamyl transpeptidase), parameters reflecting the state of oxidative status (intensity of biochemical luminescence and the content of conjugated dienes), and on activity of oxidative metabolism enzymes (aconitate hydratase, glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) was studied in rats with CCl4-induced liver injury. The results obtained in the course of this study demonstrate the ability of the test compound to reduce oxidative stress severity and the degree of liver cell damage, as well as to change activity of aconitate hydratase and NADP-generating enzymes towards control values. 6-Hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline was more effective in normalizing CCl4-induced changes of most analyzed parameters than carsil used as a reference compound. The tendency to normalize the state of oxidative status and enzyme activity of oxidative metabolism can be attributed to hepatoprotective and antioxidant properties of the test compound.

Alcoholic liver disease: a modern look at diagnosis and treatment

Alcohol is one of the leading etiological factors in liver damage. In alcoholic liver disease (ALD), hypoxia occurs due to an imbalance between the energy requirement of hepatocytes and energy production in the mitochondrial oxidative phosphorylation system. Diagnosis of ALD includes the taking of an anamnesis, questioning of patients, clinical examination data, laboratory and instrumental study. For the treatment of ALD, agents are used that protect cell membranes from oxidative stress factors and restore the energy potential of cells under conditions of tissue hypoxia. One such hepatotropic infusion is Remaxol®, the original polyionic succinatemethionine complex based on succinic acid. Aim of the study: to consider the effects of using Remaxol® infusion drug in the group of ALD patients. Materials and methods: treatment of 40 patients (male) with ALD was carried out, all of whom had a distinct history of the disease with regular and prolonged alcohol abuse. The duration of the disease in the group was 4.8 ± 0.7 years. Initially, all of them showed increased lipid peroxidation, depression of antioxidant protection, as well as pronounced sings of cytolysis, cholestasis and lipid metabolism. Then, all patients in the group were treated with Remaxol®. The course of treatment ranged from 5 to 10 daily intravenous drip infusions. After treatment, the parameters of lipid peroxidation malondialdehyde (MDA), diene conjugates (DC), enzymes of antioxidant system catalase (Cat), superoxide dismutase (SOD), glutathione peroxidase (GP), markers of cytolysis, cholestasis and lipid metabolism were again investigated in the serum of patients. Results of the study: a positive effect after monotherapy with Remaxol® was observed in 34 patients, which amounted to 85% of the group. They recorded a significant decrease in lipid peroxidation and a compensatory increase in antioxidant system enzymes. The indicators of cytolysis and cholestasis syndromes significantly decreased, lipid metabolism was restored, and the subjective status of patients improved. There were no side effects during the treatment with Remaxol® in the group of patients with ALD. Conclusions: It was noted that therapy with Remaxol® caused positive laboratory dynamics in 34 patients, which amounted to 85% of all treated patients with ALD. Thus, it has been shown that therapy with Remaxol® is an effective method of treating alcoholic liver disease.

Minimally-invasive technologies in the treatment of choledocholithiasis complicated by cholangitis and biliary sepsis

Minimally-invasive endoscopic technologies are used in the treatment of patients with choledocholithiasis with complicated cholangitis and biliary sepsis. 56 patients were treated for the period 2014–2018, aged 65,5 ± 15,18 years. ERCP was performed in 31 (55,3%) patients, in 13 (23,2%) – surgical intervention was performed without contrast of extrahepatic bile ducts. Papillotomy in 52 cases (96,4%) was performed by string papilloma and in 4 (7,1%) – by needle. In all cases, subtotal papilloprotectomy was performed, supplemented by balloon sphincteroplasty. In the I group, the patients included patients with acute cholangitis clinic, in group II patients with clinic of biliary sepsis, in the III group patients with purulent cholangitis clinic, biliary sepsis and septic shock.
 In the 1st and 2nd groups of patients, mortality was not observed. In the 3rd group, 3 patients died (37,5%). The rest of the patients are discharged from the hospital in a satisfactory condition. A decrease in the level of markers of hepatitis cytolysis (AlAT, AsAT, GGTP, L-FABP) was observe during surgical procedures without ERCP, indicating the toxic effect of contrast on the liver parenchyma. L-FABP is a highly informative marker for hepatocyte cytolysis and can be used as a criterion for hepatic insufficiency and prognosis of biliary sepsis. The high efficiency of transpacillary endoscopic surgical techniques in the treatment of cholangitis and biliary sepsis was noted.

Effect of angiolin on the functional state of the liver in experimental steatohepatitis

For a real impact on the functional state of the liver in steatohepatitis, the appointment of metabolic correctors is suggested. The aim of the study is to evaluate the effect of the biologically active compound angiolin on markers of cytolysis and liver function in experimental nonalcoholic steatohepatitis. Experimental studies were performed on 110 white, non-linear, mature male rats weighing 180–200 g at the start of the experiment. A model of non-alcoholic steatohepatitis was created, rats were maintained for 8 weeks on a high-calorie, high-cholesterol diet. After creating the model some of the animals were transferred to a standard semi-synthetic starch-casein diet and administered for 4 weeks the biologically active compound Angiolin. The activity of enzyme markers of cytolysis — alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGT) in serum was determined by standard methods. Liver biosynthetic function was assessed by the level of total protein and albumin. Statistical analysis of the obtained results was carried out with the use of the license program “STATISTICA 8” by Statsoft. After creating a model of non-alcoholic fatty liver disease in rats, an increase in body mass index occurred, high activity of ALT, AST, GGT was manifested and the concentration of total protein and albumin in the blood serum decreased compared to intact animals. An inverse correlation of mean strength was found between body mass index and total protein concentration as well as serum albumin. A strong inverse correlation between the value of ALT activity and the concentration of total protein and albumin in blood serum was established. The use of angiolin contributed to an increase in the concentration of total protein and albumin in the blood serum, an increase in the albumin / globulin coefficient, and a decrease in cytolysis. It was concluded that the biologically active compound angiolin positively affects the parameters of cytolysis and protein synthesis of the liver.

Effect of 4-Methyl-Phenyl Biguanide on Free Radical Homeostasis and Activity of Oxidative Metabolism Enzymes in Rats with Cardiovascular Pathology Developing against the Background of Rheumatoid Arthritis.

We studied the effect of 4-methyl-phenyl biguanide, a substance chosen by PASS software (Prediction of Activity Spectra for Substance), on oxidative status and activity of oxidation metabolism enzymes participating in limitation free radical processes (aconitate hydratase, glucose-6-phosphate dehydrogenase, and NADP-isocitrate dehydrogenase) in the heart and blood serum of rats with cardiovascular pathology developing against the background of experimental rheumatoid arthritis. Activity of cardiomyocyte cytolysis markers in rat blood serum was also measured. Normalization of the studied parameters under the influence of the test compound in animals with experimental pathology attests to its positive effects on metabolic and free radical processes.

ASSOCIATION OF INTESTINAL BACTERIAL OVERGROWTH AND DISEASES OF HEPATOBIARY TRACT

The aim. Find out the nature of the changes of the hepatobiliary system in patients with intestinal bacterial overgrowth and study the possible mechanisms of their association.Materials and methods. 148 patients with intestinal bacterial overgrowth and intestinal dysbiosis were examined. The level of total cholesterol, cholestasis and cytolysis markers was determined in the blood using the analyzer «Labsystems» (Finland). Intestinal bacterial overgrowth syndrome was assessed using a hydrogen breath test with lactulose on the LactophaH2 apparatus of AMA (St. Petersburg). Intestinal dysbiosis was determined by plating feces on nutrient media. Bile acids in bile were determined on the AmazonX mass spectrometer (Bruker Daltonik GmbH, Bremen, Germany). Ultrasound examination of the abdominal cavity performed with the apparatus «SHIMADZU SDN-500» (Japan). Liver elastography was performed using the AIXPLORER apparatus (France).Results. The syndrome of intestinal bacterial overgrowth in 67% of cases was established in the presence of ileocecal insufficiency, in 33% of cases — with preserved ileocecal function. The combination of intestinal bacterial overgrowth syndrome and intestinal dysbiosis was detected in 81,8% of patients. The majority of the examined patients showed clinical symptoms of damage the hepatobiliary system and intestines, which was confirmed by change laboratory parameters — increase the level of total cholesterol, markers of cholestasis and cytolysis compared with the control group. In the study of bile acids in bile, decrease free (mainlycholic) and increase conjugated (glycodesoxycholic, taurodesoxycholic, glycocholic, taurocholic) bile acids was observed compared with the control group. In general, patients with the syndrome of intestinal bacterial overgrowth revealed the presence of non-calculous cholecystitis — in 11,5% of cases, I stage of cholelithiasis — in 25,7%, II stage of cholelithiasis — in 18,9%, non-alcoholic fatty liver disease on stage steatosis and steatohepatitis — in 43,9% of cases.Conclusion. Intestinal bacterial overgrowth syndrome is the beginning of bacterial translocation, which is the triggering factor in inflammation of the liver and biliary tract. In turn, diseases of the hepatobiliary system contribute to the development of intestinal dysbiosis by reducing the synthesis of bile acids with antibacterial action, as well as violations of their excretion. Thus, strong association of intestinal bacterial overgrowth syndrome with damage to the hepatobiliary system has been established.

Effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on the intensity of free radical processes and the activity of oxidative metabolism enzymes under toxic liver injury in rats

The effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of hepatocytes cytolysis (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase), parameters reflecting the state of oxidative status (intensity of biochemical luminescence and the content of diene conjugates), and the activity of oxidative metabolism enzymes (aconitate hydratase, glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) was studied in rats with CCl4-induced liver injury. The results obtained in the course of the work demonstrated the ability of the test compound to reduce the severity of oxidative stress and liver cells damage, as well as to change the activity of aconitate hydratase and NADP-generating enzymes in the direction of control values. 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline was more effective in normalizing CCl4-induced changes of the analyzed parameters that Carsil used as a reference compound. The tendency to normalize the state of oxidative status and enzyme activity of oxidative metabolism can attributed to hepatoprotective and antioxidant properties of the tested compound.

Features of the course of manifest forms of acute hepatitis C

Aim. To identify clinical, epidemiological and laboratory-instrumental features of acute hepatitis C at the present stage according to the infectious hospital data.
 Methods. The study included 111 patients with acute hepatitis C aged from 18 to 79 years who were hospitalized in Republican Clinical Infectious Diseases Hospital named after A.F. Agafonov in 2011 - I quarter of 2017. Acute hepatitis C was diagnosed in accordance with the guidelines of the Ministry of Health of the Russian Federation.
 Results. In the study group, females aged 21 to 40 years, non-working, predominantly living in Kazan with medical transmission of infection (34 %) prevailed. The disease was mild and moderately severe (71 %). The icteric form was observed in 94 % of patients, in 3.6 % - with a cholestatic component. When comparing laboratory parameters, markers of cytolysis and cholestasis differed significantly in patients depending on the severity (p<0.001). Changes in the gallbladder walls (an ultrasound marker of cholestasis) were revealed in 21.4 % of patients. On specific examination, the viral RNA was detected in 100 % of patients. Analysis of serological markers revealed predominance of antibodies to core and NS3 proteins, M class antibodies were detected only in half of the patients. Specific antibodies were absent (“dark diagnostic window”) in 3 % of patients with mild and 6 % of moderate form of the disease.
 Conclusion. The feature of the course of acute viral hepatitis C was the predominance of moderate forms (71 %) with medical transmission of infection. Icteric forms of acute viral hepatitis C were diagnosed in 94 % of patients (in 3.6 % cases with the development of cholestatic component). PCR is a mandatory method of specific diagnosis of acute viral hepatitis C, and in case of a “dark diagnostic window” becomes the leading method.

Serum Aminotransferases and the Severity of Asthma

The serum enzymes are ideal diagnostic or prediction markers. Aspartate aminotransferase (AST), a mitochondrial and cytoplasmic enzyme, is one of the well-known markers of hepatic, myocardial or skeletal muscle cytolysis, while alanine aminotransferase (ALT) is mainly a hepatic cytoplasmic enzyme. The normal plasmatic values of AST and of ALT reflect a physiological cell turnover. Therefore, both high and low levels of serum liver enzymes might have a clinical significance. We have conducted a retrospective study targeting the association between the serum AST and ALT levels and the lung function impairment among patients with occupational asthma but without hepatic, cardiac, renal or muscular disorders. Our data show a significant relation (R = 0.54, p [0.05) between the parameters of obstructive ventilator syndrome and AST and ALT levels, respectively (R =0.42, p [0.05). If this relation is confirmed in prospective studies, serum AST and ALT could become useful markers in monitoring asthma patients.

Exchange disorders and their correction in patients with infected false joints of the tibia

The problem of treating infected false joints of the tibia is far from its final solution. Unsatisfa ctory results make additional studies necessary. The use of the revealed regularities in carrying out conservative therapy of false joints is a powerful reserve for obtaining good results.The data obtained by the authors indicate that protein-preserving therapy with the moments of performing sufficiently traumatic intervention in patients with infected tibial joints is pathogenetically grounded and provides a positive effect both on maintaining a stable level of its own plasma proteins and on reducing markers of cytolysis and proteolysis of its own tissues, Allowed to reduce the phenomenon of alteration, ensure maturation of bone regenerate and full bone callusand.Clinical observations indicate the safety and high efficacy of the proposed protein-preserving therapy in patients with infected false joints of the tibia.

A Screening Study of Hepatoprotective Activity of Liquid Extract from Common Tansy Tanacetum vulgare L. Herb in the setting of Subchronic Hepatitis in Rats

The number of patients with pathology of the hepatobiliary system is growing steadily every year, and the main etiological factors that cause the disease are action of drugs, organic solvents, salts of heavy metals, and environmental pollution. Regardless of etiology of hepatobiliary system diseases, given common features of their pathogenesis, the leading role in treatment belongs to hepatoprotectors. The aim of the study is to substantiate the existence of the hepatoprotective properties of liquid extract from common tansy (Tanacetum vulgare) herb. The task set is solved by studying hepatoprotective activity of liquid extract from common tansy herb on the model subchronic liver damage. A pathology model was reproduced by introduction of carbon tetrachloride in combination with alcohol. The liquid extract of common tansy herb tested was administered in the therapeutic mode at doses of 25, 50, 75, 100, and 150 mg/kg. Hepatoprotective activity was assessed by extract' effect on regulation of prooxidant-antioxidant imbalance and activity of transminases, cytolysis markers. A beneficial effect of liquid extract of common tansy herb on the course of subchronic toxic hepatitis at a dose-leader ? 75 mg/kg has been determined, as evidenced by increased content of reduced glutathione (1.4-fold) accompanied by significant decrease of transminases (1.3-fold) and decreased content of TBA-AP (1.5-fold). The mechanism of hepatoprotective action of liquid extract of common tansy herb is probably conditioned by binding of toxic free radicals and stabilizing of cell membranes by phenolic compounds present in its composition (luteolin, rutin, apigenin, apigenin-7-glucoside, hyperoside, chlorogenic, caffeic, ferulic, and gallic acids). Further studies of liquid extract of common tansy herb at a dose of 75 mg/kg aimed at development of a hepatoprotective agent is recommended.

Correction of toxic impact of anti-tuberculosis drugs on the liver in patients with first-time diagnosis of pulmonary tuberculosis

Introduction. The liver, being the main organ of detoxification, is experiencing the greatest burden in the process of chemotherapy. Disorders of the liver function in patients with respiratory tuberculosis can occur due to various factors, leading to the development of toxic reactions up to acute and chronic hepatitis. Numerous studies point to pronounced hepatotoxic effect of all anti-TB drugs and development of toxic hepatitis in patients treated with these drugs. This suggests the need to use hepatotropic drugs in complex treatment of TB.The aim of the study – to learn biochemical markers of liver function abnormalities in patients with newly diagnosed pulmonary tuberculosis and with severe intoxication syndrome before and two months after TB inpatient treatment, and the feasibility of using domestically-produced “Antral“ medication to treat functional disorders of the liver in these patients.Research methods. Two groups of people were involved in the study. Group I (control) consisted of evidently healthy donors, 27 individuals; Group II (31 individuals) consisted of patients with newly diagnosed pulmonary tuberculosis and with severe intoxication syndrome before and two months after of anti-TB therapy. This group was randomly divided into two subgroups: IIA(15 individuals), patients that only received standard anti-TB treatment and IIB (16 individuals), patients along with the standard anti-TB therapy received “Antral“ medication in the dose of 200 mg 3 times a day for the duration of treatment intensive phase. Results and Discussion. Results of the study indicate that when examining patients with pulmonary tuberculosis and severe intoxication syndrome markers of cytolysis and cholestasis should be measured prior to start of the treatment. With the increase of such indicators, in particular, ALT, AST, general and direct bilirubin, LDH, GGTP should be appointed hepatoprotector, in particular "Antral" drug. The use of this drug during the intensive phase of treatment normalizes the parameters of not only cytolytic but also cholestatic syndromes of liver function disorders in patients. Use of this medication in the treatment of tuberculosis contributed to ceasing release of the bacteria after intensive phase of treatment in 71.2 % of cases in subgroup IIB (43.9 % in subgroup IIA), and disappearance of clinical manifestations of intoxication in subgroup IIB in 79.8 % of cases (49.6 % in subgroup IIA). Significant reduction in markers of cytolysis and cholestasis was observed in patients that received “Antral“ medication during intensive phase of the treatment.Conclusions. Patients with newly-detected pulmonary tuberculosis and severe intoxication syndrome had significantly increased markers of cytolysis and cholestasis even before start of the treatment. “Antral“ is a medication with hepatoprotective action. Use of this medication alongside with the complex therapy of pulmonary tuberculosis contributed to normalization of liver function, significant reduction in the markers of cytolysis and cholestasis, faster termination of bacterial release and disappearance of clinical manifestations of intoxication.

Synthesis and primary evaluation of the hepatoprotective properties of novel pyrimidine derivatives

Based on the active ingredient of the drug Ximedon (1,2-dihydro-4,6-dimethyl-1-N-(2-hydroxyethyl)pyrimidone-2, referred below to as pyrimidine (I), novel derivatives containing biogenic acids: succinic, L-ascorbic, para-aminobenzoic, nicotinic, and L-2-amino-4-(methylthio)butanoic (L-methionine) acids have been synthesized. The parameters of acute toxicity (LD50) have been studied. The antitoxic effect of the compounds upon the injury by the hepatotropic poison carbon tetrachloride has been examined as the primary evaluation of their hepatoprotective properties. It has been found that, according to toxicological safety, the compounds synthesized belong to classes III and IV (moderately and little toxic compounds). The conjugates of pyrimidine (I) with ascorbic acid and methionine (LD50 more than 5400 mg/kg) are least toxic. Pyrimidine (I) and its derivatives possess the antitoxic activity upon acute poisoning with carbon tetrachloride; the combined injection of carbon tetrachloride with pyrimidine (I) or its derivatives leads to an increase in the survival of animals and the normalization of the integral functional parameters, weight and body temperature, which decrease upon toxic injury. In addition, pyrimidine (I) and some of its derivatives (conjugates with L-ascorbic, succinic, para-aminobenzoic, and nicotinic acids) decrease the weight coefficients of the liver and kidneys (the organ-to-body-weight ratio) and the activity of transaminases, the markers of hepatic cytolysis, which increase upon toxic injury with carbon tetrachloride. The area of the pathological injury of the liver by steatosis and necrosis decreases by the action of pyrimidine (I) and its novel derivatives (conjugates with L-ascorbic, succinic, and nicotinic acids) two to three times. Advantages of pyrimidine (I) and its novel derivatives over the hepatoprotective drug Thiotriazolin have been revealed.

Circadian peculiarities of antioxidant and membrane-protective properties of glutargin in acute chrono-determined paracetamol-induced hepatitis

Hepatobiliary system diseases take a leading position among diseases of the gastrointestinal tract. One of the main groups of drugs used for their treatment is hepatoprotectors. Active development of chronophysiology, chronopatology and chronopharmacology creates the possibility of determining chronoportraits of drugs. Considering the latter it allows significantly optimizing the pharmacotherapy. Aim. To assess the circadian dependence of the antioxidant and membrane-protective activity of glutargin. The choice of the drug as the object of our study was made due to its frequent use in clinical practice. Materials and methods. The study was conducted on the model of acute paracetamol-induced hepatitis in the following chronosimulated mode: in the morning (09.00), in the daytime (15.00), in the evening (21.00) and at night (03.00). The dose of paracetamol in the experiment was 1000 mg/kg in rats. Glutargin was administered in the therapeutic and preventive mode in the dose of 135 mg/kg, i.e. an hour before administration of paracetamol and 2 hours after it. Results. The study conducted revealed the peculiarities of dysinchronosis of the prooxidant-antioxidant balance and the activity of cytolysis markers depending on the period of the day, in which paracetamol-induced hepatitis was simulated; it allowed determining the peculiarities of their correction with glutargin. The most distinct decrease in the AlAT and AsAT activity when using glutargin was observed against the background of night and day simulation of hepatitis. It is probably due to the circadian peculiarities of antioxidant and membrane-stabilizing properties of this drug. Conclusions . The circadian regulation peculiarities of prooxidant-antioxidant balance obtained with glutargin against the background of paracetamol-induced hepatitis should be considered when developing a comprehensive chronoportrait of this drug.

СТАТЕВІ ВІДМІННОСТІ ПОКАЗНИКІВ ПРО-АНТИОКСИДАНТНОЇ СИСТЕМИ В МІОКАРДІ ЩУРІВ ЗА УМОВ ГІПЕРГОМОЦИСТЕЇНЕМІЇ

Гіпергомоцистеїнемія є незалежним фактором ризику патології серця та судин. Одним із механізмів кардіотоксичної дії високих концентрацій гомоцистеїну є оксидативний стрес. За умов гіпергомоцистеїнемії в міокарді розвивається про-антиоксидантний дисбаланс, який асоціюється з посиленням процесів вільнорадикального окиснення ліпідів та протеїнів. Однак статеві особливості впливу гіпергомоцистеїнемії на показники про-антиоксидантної системи в міокарді залишаються невивченими.Мета дослідження – оцінити вплив гіпергомоцистеїнемії на показники оксидативного стресу в міокарді та маркери цитолізу кардіоміоцитів у самців та самок щурів.Матеріал і методи. Досліди проведені на 40 білих лабораторних щурах обох статей масою 220–280 г. Модель гіпергомоцистеїнемії створювали шляхом введення тіолактону D, L-гомоцистеїну (Sigma, США) внутрішньошлунково в дозі 100 мг/кг маси протягом 28 діб. У міокарді визначали вміст H2S, активність NADPH-оксидази (КФ 1.6.3.1), супероксиддисмутази (КФ 1.15.1.1), вміст малонового діальдегіду (МДА), карбонільних груп білків (КГ). У сироватці крові оцінювали вміст гомоцистеїну, активність аспартатамінотрасферази (АСТ) та креатинфосфокінази (КФК). Статистичну обробку результатів проводили за допомогою програми SPSS Statistica 17.0.Результати. Тривале введення тіолактону гомоцистеїну супроводжується збільшенням вмісту гомоцистеїну в сироватці крові та зменшенням рівня гідроген сульфіду в міокарді у самців відповідно на 111 та 43,3 % (р˂0,05), а у самок – на 82,4 та 25,1 % (р˂0,05), порівняно з відповідним контролем.У самців з гіпергомоцистеїнемією зменшення активності супероксиддисмутази, а також зростання активності НАДФН-оксидази, вмісту МДА та КГ в міокарді становило відповідно 33,2; 52,7; 89,3 та 102 %, тоді як у самок зміни вказаних показників були меншими і становили 23,7; 33,3; 68,3 та 78,6 % відносно контролю.За умов гіпергомоцистеїнемії у самців розвивається більш виражений цитоліз кардіоміоцитів (активність АСТ та КФК у сироватці крові зростає відповідно на 39,2 та 42,5 % відносно контролю), ніж у самок (активність АСТ та КФК в сироватці крові зростає на 24,9 та 31,3 %).Висновки. Встановлено, що введення тіолактону гомоцистеїну протягом 28 діб викликає у самців більш істотне зменшення активності супероксиддисмутази та збільшення активності НАДФН-оксидази, процесів пероксидації ліпідів і протеїнів, ніж у самок. Поряд з цим у самців реєструється більш виразний цитоліз кардіоміоцитів, ніж у особин протилежної статі.