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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]

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]

"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]

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]

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]

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 (LD) 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 (LD 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims We aimed to explore the effectiveness of preventive usage of hepatoprotectors in patients with tuberculosis ( TB) receiving anti- TB treatment. Methods With stratified cluster sampling strategy, a prospective cohort with 4488 sputum smears positive pulmonary TB patients was established from 52 counties of four regions in China. During anti- TB treatment, prescriptions of hepatoprotectors were documented in detail, and liver enzymes were routinely monitored. Anti- TB drug-induced liver injury ( ATLI) was assessed based on liver enzymes following the criteria of American Thoracic Society. The incidence of ATLI between the preventive usage group and reference group was compared by propensity score adjusted Cox proportional hazard analysis. Preexisting diseases, history of liver disease, hepatitis B surface antigen status, primary/re-treatment of TB, income per year, and liver enzymes before anti- TB treatment were included in the propensity score model. Results After 6-9 months of follow-up and monitoring, 4304 patients sustained in our cohort. Two thousand seven hundred fifty-two (63.9%) patients preventively took hepatoprotectors with a median course of 183 days. Most frequently used drugs were Hu Gan Pian, silymarin, glucurone, and inosine. Two thousand one hundred forty-four (77.9%) patients took those drugs more than 6 months. Sixty-nine (2.4%) patients of preventive usage group and 37 (2.5%) of reference group experienced ATLI, respectively. Statistical significances were not found by propensity score analysis for the association between using hepatoprotectors (hazard ratio[HR] = 0.99, 95% confidence interval [ CI]: 0.65-1.52), using hepatoprotectors in the whole course ( HR = 0.94, 95% CI: 0.60-1.48), using Hu Gan Pians, silymarin, glucurone, and inosine with ATLI occurrence. Conclusions No preventive effect of hepatoprotectors was observed in patients receiving anti- TB treatment. [ABSTRACT FROM AUTHOR]

The hepatoprotective properties of humic acids from lowland peat of Tomsk region were studied experimentally. It was established that native humic acids of peat (HAP) exhibited pronounced hepatoprotective activity against acute CCl hepatitis. The results showed that intragastric injection of HAP prevented damage from CCl to the metabolic and morphologic parameters of rat liver. The rates of lipoxidation and destruction of hepatocyte membranes and the manifestation of cytolytic syndrome decreased substantially. Liver excretory function improved. Fibrous structures did not develop in livers of experimental animals. The hepatoprotective action of HAP may be due to their pronounced antioxidant properties. [ABSTRACT FROM AUTHOR]

Xymedon (1-(β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine), a regeneratory and wound-healing drug, exhibited hepatoprotective activity in laboratory animals with experimental toxic hepatitis. Oral drug reduced the severity of toxic involvement of the liver induced by CCl and reduced animal mortality. Xymedon promoted recovery of the blood biochemical parameters characterizing the liver status. [ABSTRACT FROM AUTHOR]

Phospholipid hepatoprotectors essentiale, eplir, and their combinations with succinic acid decreased the relative content of apoptotic lymphocytes and granulocytes in the blood, content of TNF-α, total and indirect bilirubin, and activities of transaminases and alkaline phosphatase and increase the content of IL-10 in rats with experimental intoxication induced by isoniazid and paracetamol. A combination of eplir and succinic acid was most effective in preventing the development of leukocyte apoptosis. [ABSTRACT FROM AUTHOR]

Hepatoprotective properties of a new pyrimidine derivative - L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one, synthesized on the basis Xymedon, were assessed in white rats exposed to CCl4. The compound under study administered prior to exposure to CCl reduced the deviation of biochemical parameters from reference values and severity of structural and morphological changes in liver, when compared to the control. Hepatoprotective properties of the studied compound were more pronounced than those of Xymedon. [ABSTRACT FROM AUTHOR]

The effects of polyphenol-containing hepatoprotectors of plant origin, i.e., an extract of the Russian thistle and silymarin, on liver metabolism after paracetamol-induced damage were studied in rats. Both hepatoprotectors decreased the signs of paracetamol hepatotoxicity and promoted recovery of the major functions of the liver. Russian thistle extract and to a lesser extent silymarin prevented the formation of lipid peroxidation products, i.e., diene conjugates, Schiff bases, and malondialdehyde, in the liver, produced reductions in blood aminotransferases, y-glutamyltranspeptidase, acid and alkaline phosphatases, and phospholipase A levels, decreased the total bilirubin concentration, and activated the detoxification of bilirubin, phenols, and ammonia. [ABSTRACT FROM AUTHOR]