Search

Melanoma is one of the most aggressive tumors and is accompanied by the induction of local and systemic inflammatory responses. Combinations of chemotherapeutic agents with immunotherapy are therefore commonly used for melanoma treatment. A B16 melanoma model was used to study the tumor suppressive, immunostimulating, and hepatotoxic effects of a combination of a small double-stranded immunostimulatory RNA (isRNA) with 3'-trinucleotide overhangs and the cytotoxic drug dacarbazine compared with respective monotherapies. The drugs efficiently suppressed the tumor growth and acted synergistically. Histological and immunohistochemical examinations of tumor nodes showed that the combination of isRNA and dacarbazine significantly decreased mitotic activity and more efficiently increased apoptosis in tumor tissue as compared with either monotherapy. Regardless of the treatment regimen, signs of immune activation were observed in the spleen, including an increase in the number and diameter of lymphoid follicles and the volume density of the white pulp. Destructive changes were detected in the livers of nontreated animals with B16 melanoma. Administration of isRNA in combination with dacarbazine did not cause any additional damage to liver parenchyma, while stimulating regenerative processes in hepatic tissue of tumor-bearing animals.

Fibrates are well-known agonists of the PPAR family (peroxisome proliferator-activated receptors). This class of drugs is used for the treatment of dyslipidemia and atherosclerosis. Fenofibrate is one of the members of this class of synthetic PPARα receptor ligands. The oral administration of 0.3% fenofibrate caused a decrease in strength due to loss of body weight in laboratory animals when improving behavioural features. Analysis of the mitochondrial DNA of liver cells showed a genotoxic effect of fenofibrate, due to accumulation of reactive oxygen species, which could be attributed to activation of peroxisomal β-oxidation processes, as well as to the lack of increase in the expression of genes encoding antioxidant defense proteins. Treatment with fenofibrate did not cause brain mtDNA damage. It has been shown that fenofibrate induced mitochondrial β-oxidation in the brain, as indicated by the increased expression of the Acadm and Cpt1a and Ppargc1a and Ppara. The study found no effect of fenofibrate on the increase of mitochondrial biogenesis in brain and liver cells. Thus, we can conclude that fenofibrate significantly affects lipid metabolism in the liver and brain, but in the liver it is associated with an increase of oxidative stress, resulting in mtDNA oxidative damage. However, fenofibrate-induced increase in the expression of Ppargc1a is not associated with an increase of mitochondrial biogenesis. This is consistent with the recent suggestion that PGC-1α might not be a master regulator of mitochondrial biogenesis.

Objective: To provide a morphological evaluation of the effectiveness of incorporating remaxol into a treatment regimen for non-alcoholic fatty liver disease., Material and Methods: The investigation was conducted using 32 male C57BL/6 mice weighing 35-44 g, which were divided into 4 groups. In Group 1, eight mice were fed with a standard diet for 75 days; the animals from Groups 2 and 3 received a hypercaloric diet for the same period of time. The mice from Group 2 were euthanized immediately after the diet was stopped; and Group 3 was switched to the standard diet after 20 days of the recovery period. Group 4 included the mice that were, after a 75-day hypercaloric diet, were injected with remaxol at a dose of 25 ml/kg once daily every other day; the cycle consisted of 10 injections. Liver tissues were morphologically evaluated using Oil Red O-stained tissue specimens additionally stained with Mayer's hematoxylin on the cryostat sections applying a Zeiss Axio Imager. A2 microscope equipped with an Axiocam 506 color camera. The photographed images were processed using the ZEN 2.3 program ('Carl Zeiss', Germany)., Results: The morphological equivalent of liver improvement in mice that were injected and were not injected with remaxol was found to be normalization of the lobular structure, preservation of the structure and intralobular orientation of the hepatic tubules, and restoration of the width of the sinusoidal lumen. The degree of infiltration was much lesser than that in the group of experimental animals that did not additionally receive the drug., Conclusion: These histological signs may suggest that remaxol is effective in treating non-alcoholic fatty liver disease.

Eating mushrooms known to contain amatoxin is fraught with serious complications. The analysis of the relevant literature publications revealed no article with the description of the histological picture of the internal organs in the subjects intoxicated with amatoxin. It is known, however, that such poisoning is associated with the severe irreversible injuries to all intracellular protein structures the character of which depends on time. Specifically, acute amatoxin intoxication produces the well apparent clinical picture within 6 days after intake of the poison. It is characterized by acute renal and hepatic insufficiency in the combination with the injury to the conducting system of heart and the myocrardium itself. Thereafter, the disseminated intravascular coagulation (DIC) syndrome developed accompanied by the signs of progressive tissue hypoxia that ended in death on day 9. The histological study has demonstrated necrotic foci in the liver and oedematous hepatic stroma. Kidneys underwent multiple hemorrhages, necrosis of convoluted tubules and well apparent hydropic protein dystrophy of their epithelium. The adrenal glands showed up signs of necrosis and hemorrhage. It is concluded that poisoning with mushrooms (amatoxin) should be regarded as the most probable cause of the condition requiring differential diagnostics between acute gastroenteritis and renal insufficiency.

In recent years, the effectiveness of high-dose metformin (MF) to treat the endocrine and oncological diseases has been shown. However, the use of high-dose MF may be associated with the lactic acidosis and the liver dysfunctions. The aim of the work was to study the effect of long-term (10 days) oral administration of a relatively high dose of MF (600 mg/kg per day) into yellow C57Bl/6J (Ay/a) Agouti line mice with the melanocortin type obesity on the liver function, which was evaluated by the morphology of hepatocytes and the severity of steatosis, the expression of the inflammatory and apoptotic factors of and the activity of aminotransferases, as well as on the plasma lactate level in the animals. In Agouti line mice, MF (600 mg/kg per day) caused a decrease in the body and fat weight, led to the reduced hyperglycemia, hyperinsulinemia and hyperleptinemia, and restored the sensitivity to glucose and insulin. At the same time, in the liver of Agouti line mice treated with MF, the small-drop and large-drop fatty degeneration and the hydropic degeneration were attenuated, and the expression of pro-inflammatory IL-1β and pro-apoptotic Bax protein and the Bax/Bcl-2 ratio did not differ from the control C57Bl/6J (a/a) mice. In the blood of Agouti line mice treated with MF, the activity of alanine aminotransferase was normalized, and the lactate levels was increased, but to a moderate degree. It was concluded that the high-dose MF did not induce the lactic acidosis in Agouti line mice, and at the same time it restored the liver functions impaired in the melanocortin obesity. This allows us to consider the use of the high doses of MF as one of the possible ways to treat obesity and metabolic disorders that are associated with the hepatic steatosis.

Isatin (indol-2,3-dione) is an endogenous indole found in the brain, peripheral tissues and biological body fluids of humans and animals. Its wide spectrum of biological activity is realized via interaction with numerous isatin-binding proteins; these include proteins playing an important role in the development of neurodegenerative pathology. In the context of the neuroprotective effect, the effect of isatin is comparable to the effects of deprenyl, a pharmacological agent used for treatment of Parkinson's disease. In this study, the effects of the course of deprenyl (1 mg/kg) and isatin (20 mg/kg) administration for 21 days on the profile of the isatin-binding proteins of the liver of mice have been investigated. Proteomic profiling of liver isatin-binding proteins of control mice by means of 5-aminocaproylisatin as an affinity ligand resulted in identification of 105 proteins. Treatment of animals with a low dose of isatin slightly decreased (up to 91), while injections of deprenyl slightly increased (up to 120) the total number of isatin-binding proteins. 75 proteins were common for all three groups; they represented from 62.5% (in deprenyl treated mice) and 71% (in control mice), to 82% (isatin treated mice) of the total number of identified liver isatin-binding proteins. Proteomic analysis of the isatin-binding proteins of mice treated with isatin (20 mg/kg) or deprenyl (1 mg/kg) for 21 days revealed a representative group of proteins (n=30) that were sensitive to the administration of these substances. Taking into account the previously obtained results, it is reasonable to suggest that the change in the profile of isatin-binding proteins may be attributed to accumulation of isatin and deprenyl in the liver and interaction with target proteins prevents their subsequent binding to the affinity sorbent. In this context, the identified isatin-binding liver proteins of control animals that do not bind to the affinity sorbent (immobilized isatin analogue) after treatment of animals with either deprenyl or isatin appear to be specific targets directly interacting with isatin in vivo.

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

The objective of this researsh is to study the effects of Eminium Regelii phytopreparation (ERP) on immune status and free radical oxidation in the tissues of the adrenal glands and immunocompetent organs after combined exposure to 6 Gy dose of gamma irradiation and coal dust (remote period). The study was realized on 30 white laboratory male rats of the Wistar line, weighing 240±20g, that were divided into equal 3 groups: I group - intact, ІІ group - were exposured to combined effects of coal dust and gamma irradiation, III group - were exposured to combined effects and in parallel taking phytopreparation Eminium Regel. The animals of II and III groups were irradiated 90 days prior to the study at the TERAGAM 60Co radiotherapy unit ("ISOTREND spol. S.r.o.", Czech Republic) in dose of 6 Gy once. Experimental animals received phytopreparation of ER 2.5 mg/kg per day on calculate of body mass for 14 days. The results of the conducted studies showed that in the long-term period after the actions of the sublethal dose of gamma radiation and coal dust, significant changes were revealed that were characterized by a decrease in immunological reactivity, increased lipoperoxidation and inhibition of antioxidant defense activity of the organism. After exposure to ER, oxidative stress was alleviated, sufficient restoration of antioxidant protection and immune system indices, which were disrupted by the combined effects of a single high dose of radiation and a prolonged three-month inhalation of coal dust.

The lack of acceptable pharmacological approaches for restoration of the injured liver is associated with complex of mechanisms involved in hepatic regeneration and with difficulty of the target selection. The aim of this research was to study the hepatoprotective function of the extract from both the growing and regenerating liver containing a natural set of factors crucial for the hepatic restoration. Extracts from both regenerating liver of rats after 70% hepatic resection and the growing liver of neonatal pigs were obtained using own original technique. The set of resultant extracts was named as the hepatic regeneration set (HRS). HRS fractionation was carried out using the Toyopearl HW-50S sorbent. The efficiency of HRS and its fractions was estimated using a model of the mouse liver thioacetamide injury and monitoring hepatic enzyme activity in blood serum. The activities of AST and ALT in intact animals were 50 U/l and 80 U/l, respectively; after thioacetamide administration they increased to 2059±212 U/l and 4280±440 E/l, respectively (p<0.05). Treatment of injured animals with HRS from the rat regenerating liver resulted in a significant decrease of transaminase activities to 924±148 U/l (AST; p<0.05) and 1633±308 U/l (ALT; p<0.05). A similar effect was observed after treatment with HRS from the neonatal pig liver: the AST decreased to 937±138 U/l (p<0.05), while ALT activity decreased to 1710±237 U/l (p<0.05). HRs fractionation resulted in identification two active fractions characterized by much higher (8-29) hepatotropic effect that that of the whole extract. These fractions contained peptide/protein components with the range of molecular mass of 3-60 kDa (fraction 1) and 3-25 kDa (fraction 2a). Fraction 1 also contained some polynucleotides in fraction 1. Subsequent studies of these fractions exceeding the hepatotropic effect of original HRS is clearly needed to identify their individual components by immunochromatography methods, ELISA, MRM mass spectrometry and quantitative PCR.

MiR-21 is the most studied cancer-promoting oncomiR, which target numerous tumor suppressor genes associated with proliferation, apoptosis, and invasion. Here we have studied the synthesis of miR-21 and quantified the mRNA and protein levels for miR-21 potential target genes, i.e., Acat1, Armcx1, and Pten, in the livers of female Wistar rats after their treatment with either 1,1-trichloro-2,2-di(4-chlorophenyl)ethane (DDT) or benzo[a]pyrene (BP). The most important finding appears to be the significant decrease in the miR-21 level the day after treatment with DDT with subsequent rebound. These changes are accompanied by an increase and subsequent drop in the levels of mRNAs and proteins of the Acat1, Armcx1, and Pten genes. These observations indicate the involvement of miR-21 in the posttranscriptional regulation of the Acat1, Armcx1, and Pten genes in response to xenobiotics. We hypothesize that the toxic effects of xenobiotics may be indirect and may manifest by inducing epigenetic changes, particularly through the regulation of miRNAs and their target genes.

The aim of the study was to assess the hepatoprotective properties of the RNA-containing drug RN-13 on the model of acute CLL4 induced hepatitis in rats. To evaluate hepatoprotective properties of the RNA-containing drug RN-13 42 female rats were used. RN-13 increases the survival rate of animals with acute tetrachloromethane hepatitis. The hepatoprotective properties of RN-13 were confirmed by biochemical and morphological data. RN-13 helps to reduce the activity of alanine aminotransferase, which indicates its ability to limit cytolysis syndrome. Morphological studies confirm the ability of RN-13 to prevent destruction of liver tissue, preserve the radial structure of the hepatic lobes, and limit the development of hydropic and fatty degeneration.

The tolerability and efficiency of specific chemotherapy with albendazole were analyzed in 18 patients with cystic echinococcosis at various sites. The most common complication of albendazole treatment was its hepatotoxic effect. Al- bendazole chemotherapy during at least its 3 cycles was observed to be highly effective in preventing recurrent echinococ- cosis in children. If there were small-sized hydatid cysts in the liver and lung, there was a reduction in their number and sizes after 4-5 albendazole treatment cycles.

Reduced insulin sensitivity plays an important role in the pathogenesis of type II diabetes. Est-radiol increases sensitivity to insulin. Effect of estradiol may be due to the influence on gene expression, level of proteins or activity of insulin signaling pathway components and insulin target proteins. Effect of estradiol also may be due to the influence on GLUT4 translocation in the cell membrane. Effects of estradiol on insulin receptor substrate, phosphatidylinositol-3-kinase, protein kinase B, glucose transporter type 4, glucose-6-phosphatase most often examined. In this paper, data on the influence of estradiol on insulin sensitivity in liver, adipose and muscle tissues systematized in order to identify promising areas of research and new targets for pharmacological correction of insulin resistance.

The effect of combined administration of adrenaline (0.4 mg/kg, i.p.) and b1-blocker metoprolol (25 mg/kg) on the activity of glutathione peroxidase (GPO), glutathione reductase (GR), catalase, adenosine deaminase (AD), AMP deaminase (AMPD), 5¢-nucleotidase (5¢N), on the level ofmalonic dialdehyde (MDA) and conjugated dienes (CD) was investigated. In blood adrenaline administration to animals caused an increase in the activity of AMPD, AD, 5¢N and GPO, and the increase the level of CD in the blood increases. Metoprolol caused a more pronounced increase in the activity of blood AMPD, AD, 5'N and the amount of CD. In contrast to adrenaline, metoprolol decreased the MDA level of, and decreased the activity of GPO and catalase. Combined administration of metoprolol and adrenaline to animals was accompanied by an increase in the activity of AD, AMPD, 5¢N, a decrease in the activity of GR, GPO, catalase, and a decrease in MDA in the blood. In the heart, adrenaline injection was accompanied by an increase in the MDA level, a decrease in 5¢N activity and an increase in the ratio of the activities of the enzymes AD+AMPD/5¢N. Metoprolol injection reduced MDA and CD levels and the activity of GR and GPO. The combined administration of metoprolol and adrenaline in the heart was accompanied by activation of AD, AMPD and 5¢N, and a decrease in the amount of MDA and CD, and a decrease in the activity of GR, GPO, and catalase. In the liver adrenaline caused an increase in MDA and DC levels, activation of catalase, AD, AMPD, and 5¢N. Metoprolol caused a decrease in MDA and CD levels and activity of catalase and GPO, an increase in the activity of AD and AMPD in the liver. Combined administration of adrenaline and metoprolol reduced manifestations of the heart and liver oxidative stress response as compared with administration of adrenaline alone.

Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.

Administration of Aacetylsalicylic acid in children with viral infections (influence B, chickenpox) can be related with development of Reye syndrome - severe encephalopathy and liver insufficiency with mortality in 50% of cases. During Reye syndrome most important is deficiency of carnitine and hepatocyte damage. Decreased amount of carnitine impairs the energy function of mitochondria and gluconeogenesis as well as production of urea. As a result develops toxic encephalopathy and liver insufficiency. The goal of the research was assessment of efficacy of L-Carnitine, Corvitin and their combination on functional state of liver in experimental model of Reye Syndrome in rats. The study was performed on mature white male Wistar rates with body mass 150-180g. 50 rats were randomly divided into 5 groups (10 rats in each group). The model of Reye syndrome was induced in accordance with A.Vengersky's method. Intraperitoneal administration of 4-pentenoic acid was performed once daily during seven days, the used dosage was 20mg/kg. The treatment of toxic hepatitis was carried with intraperitoneal administration of L-Carnitine 300mg/kg, Corvitine 100mg/kg and concurrent administration of these drugs. Monotherapy with Corvitin and L-Carnitin successfully improved liver function and equally decreased indicators of hepatocyte's cytolyses and increased levels of glucose and urea. The markers of cholestasis was slightly more improved during use of L-Carnitine. Simultaneous use of both drugs was effective in rats with Reye syndrome, indicators of liver damage normalized and herewith, no mortality outcome was observed. The most pronounced hepatoprotective effect of concurrent administration of L-Carnitine and Corvitin may be due to synergic action of these drugs and such regime can be recommended for correction of liver function during Reye syndrome.

Radioprotective therapeutic effect of lyophilized extract ofAmaranthus retroflexus on the resistance of the albino laboratory male mice exposed to X-ray radiation at a one-time dose of LD(100/30) is studied. It was established that a 30-day use of a lyophilized extract of the vegetative parts of A. retroflexus at a dose of 50 mg/kg after X-ray exposure increases the survival rate of mice by 80%, enhances the recovery in the radiation period of the number of leukocytes, neutrophils, lymphocytes in the peripheral blood of the animals and the normalization of the intensity of peroxide oxidation of lipids in liver cells. Dose modification factor on the 5th day after irradiation, when using a lyophilized extract, was 1.5 according to the criterion of survival of mice.

The studies revealed specificity of morphologic changes in target organs, depending on acting occupational hazard. Evidences are that inhalation of coal rock dust causes irreversible sclerotic and degenerative changes mostly in lungs and bronchi even on 6th week of the experiment. In liver, changes in parenchyma and stroma are controlled by reparative processes by 9th week. Accumulation of sodium fluoride in the body causes irreversible necrotic changes mostly in liver, on 6th week of the intoxication. With that, morphologic changes in lungs and bronchi are minor, characterized by immune inflammation with degenerative changes only after the 9th week. Irrespective of the acting hazard, vascular changes are characterized by media and intima hypertrophy with endothelial dystrophy and hyalinosis since the 6th week of the experiment.

Analysis of the results of pharmacological phenotyping using antipyrine test prior to providing anesthesia for laparoscopic cholecystectomy showed that trimeperidine (promedol) dosing with allowance for the total oxidative capacity of liver and the patient mass allows the periods of post-anesthetic rehabilitation to be controlled. Clear algorithm of trimeperidine dosing based on established indices of the total oxidative capacity of liver and is yet nor developed because of restricted sampling set. The obtained results show expediency of using and studying antipyrine test as a simple, cheap, and informative method of individual anesthesia dosing for increasing the adequacy of general anesthesia.

Using bioinformatics analysis we selected microRNAs which could bind 3'-UTR-region of cytochrome P450 (CYP) genes. Three microRNA miR-21, -221, -222, their potential targets might be mRNA for CYP1A1, and two microRNA miR-143, miR-152 for CYP2B1 accordingly were selected for experimental verification. Expression level of these microRNAs in rat liver upon benzo(a)pyrene (BP), phenobarbital (PB), and DDT induction was determined using RT-qPCR method. In rats treated by both BP, and DDT the hepatic content of miR-21, -221, -222 significantly demonstrated a 2-3-fold decrease. The decrease in miR expression was accompanied by a considerable (5.5-8.7-fold) increase in the CYP1A1-mediated EROD activity. The expression of miR-143 remained unchanged after the PB treatment, while the expression of miR-152 increased by 2 times, however, the (10.5-fold) increase in PROD activity of CYP2B was much higher. In the DDT-treated liver PROD activity increased by 20 times, the expression of miR-152 didn't change, and the expression of miR-143 increased by 2 times. The bioinformatics analysis of interactions between microRNAs and targets showed that the studied miRs can potentially bind 3'-end of AhR, ESR1, GR, CCND1, PTEN mRNA. Thus, the expression profile of miR-21, -221, -222, -143, -152 might change under the xenobiotics exposure. In silico analysis confirmed, that microRNAs target not only cytochrome P450 mRNA but also other genes, including those involved in hormonal carcinogenesis, they also can be regulated with studied miRs.

In this study the effects of S-adenosylmethionine (SAM) on experimental hepatic fibrotic rats induced by carbon tetrachloride (CCl(4)) and ethanol and the relevant potential mechanisms were explored. Hepatic fibrotic rat models were established with CCl(4) diluted in olive oil being drunk with 10% ethanol in water. SAM was used both for prevention and treatment. Histological evaluation was carried out by hematoxylin-eosin (HE) and Masson staining of hepatic samples. Serum biochemical assays showed that alanine aminotransferase (ALT) was increased and albumin (ALB) was decreased by CCl(4) and ethanol, and both effects were suppressed by preventing and treating use of SAM. The model control rats got significantly higher scores in fatty degeneration, lobular inflammation, and hepatocyte ballooning. A significant improvement was observed in the SAM-prevented rats and SAM-treated rats, which was consistent with the change of fibrosis scoring in each group. Smad3 was induced by CCl(4) and ethanol in the model control group, which was significantly down regulated by SAM. SAM reduced both total Smad3 and phospho-Smad3 in vitro. SAM had a protective effect on hepatic fibrosis in rats induced by CCl(4) combined with ethanol and the down-regulation of activity and expression of Smad3 were involved in the potential mechanisms.

The results of surgical treatment of 137 patients, suffering obturation jaundice of non-tumoral etiology, were analyzed. In all the patients the cause of obturation jaundice was choledocholithiasis. Roncoleukin was infused intravenously additionally in a complex of therapy. A degree of hepatic dysfunction was determined, taking into account the cholestasis markers. In 23 patients purulent cholangitis have occurred on background of obturation jaundice. Concentration of cytokins TNF-α, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10 in sera were determined, using immunoassay analysis. The cytokins dysbalance severity preoperatively and dynamics of its changes have depended upon the hepatic dysbalance degree and presence of purulent cholangitis; a dysbalance is deeper, when the hepatic dysfunction is higher. Application of pathogenetically substantiated purposeful cytokinotherapy, including roncoleukin, have promoted the cytokins dysbalance elimination and improvement of the patients treatment results.

Sex steroids and corticol levels in Leibovitz's L-15 media samples after incubation of intact female and male sterlet (Acipenser rhutenus L.) tissue fragments and those if fishes treated with a superactive analogue of mammalian luteinising hormone-releasing hormone (LH-RH-A) were compared. 17,20β,21-trihydroxy-4-pregnen-3-one (20βS) levels were significantly higher in the media samples after incubation of ovarian follicles taken from females 5 h after treatment with LH-RH-A in comparison with 20βS levels in intact female samples. 20βS levels also increased after 1 μM progesterone (P4) adding to the media before incubation of ovarian follicles. Cortisol and testosterone levels in the media samples demonstrated the same tendency. Significant elevation of cortisol levels was observed in the blood serum samples of females 5 h after LH-RH-A treatment. The androgens (testosterone and 11-ketotestosterone) levels after incubation of testicular and liver fragments were high in the media samples in males who had high serum levels of these androgens before hormonal stimulation. Sex steroids and cortisol production was stimulated by P4 adding to the media before incubation of gonad fragments. 20βS media levels increased after P4 adding before incubation of liver fragments.

Aim: To evaluate the efficiency of Remaxol monotherapy in patients with nonalcoholic fatty liver disease (NAFLD) at the stage of steatohepatitis (SH)., Materials and Methods: The treatment of 156 patients with NAFLD at the stage of SH was analyzed. A study group included 84 patients who had received intravenous Remaxol, 400 ml, dropwise at a rate of 40-60 drops per minute once daily in the morning for 10 days; a control group of 72 patients had been treated with the conventional scheme., Results: During the treatment, the study group showed a rapider relief of the manifestations of asthenovegetative and dyspeptic syndromes and a reduction in the magnitude of biochemical manifestations of cytolytic and cholestatic syndromes than did the control group., Conclusion: Incorporation of Remaxol into the therapy regimen in patients with NAFLD at the stage of SH enhances the effectiveness of treatment.

Stable suspensions of NiO and/or Mn304 nanoparticles with average diameter 16,7?8,2 nm and 18,4?5,4 nm respectively, obtained via laser ablation of the metals with 99,99% purification in deionized water, were injected intraperitoneally into rats in dose of 0,5 mg or 0,25 mg three times per week up to 18 times separately or in various dose combinations. A group of rats received combined injections of nanoparticles in the highest dose or merely water with oral <> containing pectin, vitamins A, C and E, glutamate, glycine, N-acetylcysteine, selenium, iodine and polyunsaturated fatty acids of omega-3 class. Intoxication development was assessed through multiple functional parameters and histologic changes in liver, spleen, kidneys and brain. Nickel and manganese accumulation in these organs was measured-via various methods. Both types of metallic oxide nanoparticles appeared to be hazardous for body, but Mn304 caused more harm according to major nonspecific toxicity manifestations. Moreover, they caused more intense injury to caudate nucleus and hippocamp neurons - that can be considered as an experimental model of manganese parkinsonism. Mathematic analysis based on response pattern revealed ambiguity of the combined toxicity type, depending on the effects assessed and on its level. Due to the bioprotector complex, organic and systemic toxicity and genotoxicity of Mn304 and NiO nanoparticles combined were diminished.

The aim of the study was to increase the efficiency of the treatment of acute ethanol intoxication in patients with alcoholic fatty liver disease. The article presents the results which received during the investigation and treatment of 166 patients with acute ethanol in- toxication on the background of alcoholic fatty liver disease Patients were assessed by the severity scale APACHE-Il. Were studied the dynamics of clinical, laboratory, biochemical parameters, the state of the antioxidant system activity and lipid peroxidation. The study found the effect of the combination hepatoprotective drug remaxol on the many links of metabolism, which was confirmed by the dynamics of biochemical parameters. There was a quick correction of hyperlactatemia, an effective reduction of ALT activity, the absence of reduction of albumin and urea concentration in the somatic period of ethanol poisoning. Period of using remaxol there was improvement in the clinical course of the disease, which manifested by the reduce the incidence of delirium tremens and shorten the duration of treatment of patients.

Aim: The purpose of the research was to study the effectiveness of enteral insufficiency correction at an acute peritonitis by applying minimally invasive techniques, electrical stimulation and rehabilitation of the bowel and abdominal intestine using Remaxol drug., Material and Methods: The analysis of the results of clinical and laboratory examination and treatment of 110 patients with acute diffuse peritonitis. In the comparison group (62 patients) in the early postoperative period applied standardized treatment, including software reorganization of the abdominal cavity, in the study group (48 patients) -- a comprehensive treatment that includes software laparoscopic sanation abdominal electrical stimulation of the duodenum, and intra-abdominal (single dose, 200 ml), and intracolonic (200 ml, 2 times daily) administration Remaxol. It was noted a significant improvement in treatment outcomes, including reduced mortality by 2.3 times, the shortening of hospital stay by 1.3 times., Results: The major component of the positive effect of the developed scheme of therapy is its ability to promptly arrest the effects of enteral insufficiency, maintain the functional status of the liver. The relatively rapid recovery of motor and intestinal barrier function leads to a lowering of enteral insufficiency syndrome, which along with increased liver detoxification ability underlies the significant reduction of endogenous intoxication in three days. An important contribution to the effectiveness of the treatment makes intra and intracolonic administration Remaxol. The drug, possessing antioxidant, antihypoxic, hepatoprotective effects, contributes to the relatively rapid improvement of the barrier function of the peritoneum and intestines, detoxification ability of the liver recovery that significantly contributes to the relief of endogenous intoxication.

Rifapentine belongs to the most potent antituberculosis drugs. Nevertheless, there are some limitations for its clinical use because of the low aqueous solubility and side effects. A technological approach to development of rifapentine intravenous formulation based on human serum albumin was described earlier and its efficacy against experimental tuberculosis was estimated. Toxicological evaluation of that water-compatible form of rifapentine revealed its low acute toxicity (LD₅₀ 340 mg/kg). Chronic toxicity tests of both the oral substance and the injectable formulation of rifapentine demonstrated similar adverse effects. However, in contrast to the conventional oral formulations, the intravenous formulation of rifapentine had no gastrointestinal toxic effects or cardiotoxicity, thus suggesting its usefulness for clinical application.

Currently the problem of the impact of nanoparticles and nanomaterials on human health remains to be poorly understood. As in our studies of the impact of silver nanoparticles on rats liver as well in works of other researchers there were investigated morphofunctional indices under peroral exposure. Although all researchers took different sizes, doses and concentrations of silver nanoparticles, various exposure time and different stabilizers, the same effects had been obtained, which, however, were occurred under both different doses and time of exposure. However, it was interesting to compare the impact of silver nanoparticles with reference substance - silver sulfate on the mice liver with the previously evaluated effect produced on the rats ’ liver. By ourselves there was executed the morphological comparative evaluation of in vivo oral 2-weeks exposure of 4 concentrations (0.1; 5; 50 and 500 mg/l) of silver nanoparticles with size of 14 nm, stable arabian gum 1:7 by weight, and of 4 similar concentrations of silver sulfate on the liver of male mice СВАхС57В1/6 weighing 25-35g. 2 groups were considered as control: intact mice and mice received gum in water. Results of the exposure were assessed according to 10 morphological and functional indices. The impact of nanosilver was shown to initiate from its concentration of 50 mg/l and to express in the gain of the index of alteration of the cytoplasm of hepatocytes with the increasing in both severity of steatosis and the number of micronecroses, persisting at the same level at concentrations of 500 mg/l and with the elevation of the index of alteration of nuclei of hepatocytes, while the similar effect develops under the influence of silver sulfate at a concentration of 500 mg/l only. The remaining investigated morphofunctional indices did not differ significantly in all groups of mice. Unlike previously executed studies on rats, mice appeared to be sensitive to the effects of nano-silver more than to silver sulfate.

Aim: Comparative morphologic assessment of the liver tissue response to the preoperative infusion of octreotide and prednisolon after the major hepatic resection was studied in rats., Material and Methods: 25 male Wistar rats weighing 230--280 g were used. All rats underwent 70--80% hepatectomy. The rats were divided into three groups according to the infusions before hepatectomy: group 1 (n=7) -- received octreotide, group 2 (n=8) -- prednisolone, group 3 (n=10) -- 0.9% saline solution as the control. Histologic features of the remnant liver were evaluated in the sacrificied rats after 72 hours post-hepatectomy., Results: In the group 1 we observed more rapid decrease of edema and tendency to the accelerated regeneration process of hepatocytes., Conclusion: Octreotide infusion before the major hepatic resection may have protective effect on hepatocytes and accelerate the regeneration in the remnant liver.

Objective: To study the efficacy of remaxol addition in the treatment scheme of alcohol withdrawal syndrome., Material and Methods: Eighty patients with alcohol dependence and physical symptoms of alcohol withdrawal syndrome were enrolled. All patients received basic therapy in accordance to the applicable standards of treatment. The patients were randomized to remaxol introduced intravenously 2 times a day (morning and afternoon) in dose of 400 ml for 7 days (n=40) and saline with 25%-magnesium sulfate (10 ml) and 4% potassium chloride (10 ml) (n=40)., Results: The effectiveness of the inclusion of remaxol was expressed in a more rapid relief of asthenic syndrome, reduction of phenomena such as tension, dysphoria, headache and impaired coordination of samples. Patients treated with remaxol demonstrated a trend towards a more rapid reduction of the affective (p=0.08) and behavioral components (p=0.09) of the syndrome of pathological craving for alcohol. Hepatoprotective and detoxification properties of the drug were confirmed by the significant decline in ALT and AST activity to the 20th day of treatment. Significant positive changes in lipid metabolism (HDL to the 7th day of treatment) and a normalizing effect on the processes of tissue respiration were shown as well. No adverse effects were noted., Conclusion: The data obtained allow to recommend the inclusion of remaxol in the complex treatment regimens of alcohol withdrawal syndrome to improve the treatment efficacy.

The present study carried out on white male rats in experiments with the use of biochemical, radioimmunological, and electron- microscopic methods. It was shown that the combined treatment with potable mineral water (MV) and low-intensity electromagnetic radiation (LIEMR) of ultrahigh frequency (power density less than 1 pW/cm2, the frequency about 1000 MHz) facilitated the activation of metabolic and intracellular regenerative processes in the liver and testes. One of the advantages of the combined application of MV and LIEMR over the single-factor treatment manifested itself as the weakening of stress reactions, the increase in the frequency of the plastic processes, and the more harmonious development of different forms of intracellular regeneration. The results of the study provide a deeper insight ino the mechanisms underlying the combined actions of drinking mineral water and low-intensity electromagnetic radiation; also, they justify the application of these factors for the protection of the reproductive system and the entire body from stress-induced disorders.

Unlabelled: PERPOSE OF RESEARCH: to evaluate the effectiveness of Remaxol in patients with pervasive peritonitis., Materials and Methods: assessed the effectiveness of a balanced infusion of the drug (Remaxol) in the treatment of 44 patients agedfrom 18 to 50 years. Patients were devided into 2 groups by the method of envelopes. All patients received a comprehensive differential therapy: 21 patient 1 group consisting of infusion therapy in the postoperative period received Remaxol at a dose of 800 mg/day for 7 days., Results: the comporative assessment of indicators of systemic hemodinamics, oxygen transport, asid base status, glucose, lactose and free radical oxydation. Patients on the first background was used Remaxol have experiensed a more rapid relief of metabolic disorders, endotoxemia and hepatic dysfunction compared with the indices of the 2 group patients. Noted earlier stabilization of rudicators of systemic hemodynamics and oxygen transport. This has reduced the duration of respiratory and vasopressor suppot, early start ofparenteral intreduction in case the power (p < 0.05)., Conclusions: this study shows that use of the drug for the purpose of relief Remaxol hepatic dysfunction and prevention of drug liver toxicity in conditions ofperitonitis, after 48 hours of operation, provides a positive dynamics and stabilization ofparameters of central hemodynamics, contributing to the abolition of vasopressor support, and contributes to the effective utilization of oxygen, while providing antioxidant effect.

In this paper, the biological effects of diethylnitrosamine have been studied under controlled conditions of its metabolism in mice of different ages. The data presented indicate that diethylnitrosamine in a non-metabolized form exerts general toxic and hepatocarcinogenic effects while alkylating agents of this compound produce toxic liver injury. To our knowledge, the data presented impel to revise the general notion of an exceptional role of mutagenic activation in the carcinogenic effect of chemicals.

The influence of carbon monoxide on the blood and liver prooxidant-antioxidant parameters: lipid peroxidation products (conjugated dienes, malondialdehyde, Schiff bases) and antioxidant system parameters (catalase, retinol, α-tocopherol, glutathione) were investigated in rats during hepatic ischemia-reperfusion. Hepatic ischemia was induced by Pringle maneuver for 30 min, reperfusion period was 120 min. It is detected, that hepatic ischemia-reperfusion leads to intensification of lipid peroxidation with declining of antioxidant defense. Infusion of the donor CO before reperfusion period improves the prooxidant-antioxidant balance in the blood and liver. In conclusion, CO increases the antioxidant activity of the blood and liver, decreases lipid peroxidation processes, that's correct oxidative damages during hepatic ischemia-reperfusion.

In this paper in the bacterial Ames test we compared the mutagenicity of four aminoazo compounds, previously studied by other researchers and used for activation of rat liver enzymes, with the carcinogenicity in the rat liver. It was found that in the Ames test they have mutagenic activity, however, this activity does not correlate quantitatively with rat sensitivity to their hepatocarcinogenic action. Thus, the most active carcinogen 3'-methyl-4-dimethylaminoazobenzene causes mutations almost 2.5 times less than weakly carcinogenic ortho-aminoazotoluene, and exactly the same number of mutations as non-carcinogenic N,N-diethyl-4-aminoazobenzene.

The effect of melaxen on free radical processes and activity of superoxide dismutase and catalase in rats with type 2 diabetes mellitus (T2DM) has been investigated. It was established that melaxen administration to diabetic rats caused a decrease of the intensity of free radical processes as evidenced a decrease of the lipid peroxidation primary products content and biochemiluminescence parameters. The activity of the antioxidant enzymes changed towards normal values. These effects were probably induced by the correction of the melatonin level at the result of the melaxen action.

It was established in experiments on rats, that injection of opioid peptides DAGO (a selective igonist of opioid mu-receptors), DSLET (a selective agonist of opioid delta-receptors) or dynorpiin A (1-13) (a selective agonist of opioid kappa-receptors) decreased the stress-induced activatin of lipid peroxidation in liver tissue and plasma. A selective agonist of opioid mu-receptors) AGO manifested the most expressed activity. The using of investigating peptides caused the increase of superoxiddismutase activity in liver tissue. The reinforcement of catalase activity was )bserved in DSLET or dynorphin A (1-13). DAGO decreased its activity. The peptide effects of lifferent directions oncatalase activity in plasma were established. These effects can be explained y the stress-limiting action of peptides in entire organism, the peculiarities of opioid receptors spreading in liver tissue and by the influence of preceded load with non-complete oxidized sub stances after intensive swimming on the opioid receptor affinity.

Substances of a peptide nature isolated from the hepatopancreas of the king crab Paralithodes camtschaticus exhibited physicochemical properties and membranotropic and specific activities similar to those of membranotropic homeostatic tissue-specific bioregulators previously found in different mammalian and plant tissues. Their biological effect on vertebrate tissues was demonstrated on a model of roller organotypic cultivation of Pleurodeles waltl newt liver tissue.

We have studied the effect of berberine on the recovery processes of liver xenobiotic-metabolizing function during its compensatory growth after 70% partial hepatectomy. It was found the hepatic ability to metabolize foreign substances are not restored up to day 8. Administration of berberine (10 mg/kg intraperitoneally) for 6 days led to normalization of both cytochrome P450-dependent and flavin-containing monooxygenases. It is suggested that in the biotransformation of berberine involved not only cytochrome P450, but also flavin-containing monooxygenases.

Activity of the key enzyme of the cytochrome part of the respiratory chain--cytochrome oxidase, quantitative redistribution of mitochondrial cytochromes b, c1, c and aa3, activity of the key enzymes of cytochromes' heme metabolism--delta-aminolevulinate synthase and heme oxygenase under conditions of acetaminophen-induced hepatitis against the background of alimentary deprivation of protein were studied. It was found out, that under conditions of acetaminophen-induced hepatitis against the background of alimentary deprivation of protein, an inhibition of cytochrome oxidase activity and a decrease in the quantitative content of mitochondrial cytochromes against the background of the increase in the delta-aminolevulinate synthase and heme oxygenase activity are observed. In animals with toxic liver injury, maintained under conditions of alimentary deprivation of protein, a progressive decrease in the quantitative content of mitochondrial cytochromes b, c1, c and aa3 against the background. of the increase in heme oxygenase activity and preservation of delta-aminolevulinate synthase activity on the control level is identified. The conclusion was made, that alimentary deprivation of protein is a critical factor for the development of the disturbances of structural-functional integrity of the cytochromic part of the respiratory chain. The identified changes may be considered as one of the possible mechanisms of energy biotransformation system disturbances under conditions of alimentary deprivation of protein.

The study aims to clarify the influence of experimental cholestasis mother on the structure of the liver of young rats in early postnatal development (Day 2) and to explore the possibility of the correction of these disturbances with Ursofalk drug. Material was obtained from 30 outbred albino rat pups and studied using histological, histochemical, morphometric and electron microscopic methods. It was found that under the influence of maternal cholestasis, the liver of the offspring demonstrated the dilation of sinusoidal capillaries, the decreased activity of succinate dehydrogenase and increased activity of NADH dehydrogenase in hepatocyte cytoplasm, the development of significant ultrastructural abnormalities (disappearance of lipid droplets, accentuated heterogeneity of mitochondrial size and shape, increased number of lysosomes). The application of Ursofalk partially restored hepatocyte structure and metabolism.

Background: Benzo[a]pyrene (BaP) is the widespread environmental toxicant with carcinogenic activity. BaP undergoes metabolic activation in the liver microsomal monooxygenase system, and its regional lymph nodes act as peripheral filters, purifying lymph formed in the liver. It remains an open question about the significance of the integral liver and lymphatic system work in supporting processes of adaptation and resistance to the BaP effects., Objective: The purpose of our investigation was to study structural and metabolic changes in the liver and its lymph region in males Wistar rats weighing 180-220g., Methods: Animals of the experimental group (n =20) daily for 3 days was performed BaP injections: intraperitoneal with 2 mg per 100g of body weight in 0.2-0.3 ml of olive oil. Rats in the control group (n =20) received in the same mode of injection of olive oil. The light and electron microscopy morphometric study of the liver and its regional lymph nodes morphometric analysis were performed. The intensity of lipid peroxidation in the liver was measured by the number of diene conjugates (DC), ketotriene conjugates (KC) and malondialdehyde (MDA)., Results: Simultaneous increase of the hepatic sinusoids relative area and the specific area of the regional lymph nodes sinus system under the BaP effect was found. At ultrastructural level dilatation of the Disse spaces, filling of cell detritus and collagen fibers bundles of these spaces were noted. Damage of nuclear apparatus, balloon transformation of granular endoplasmic reticulum profiles were found in hepatocytes, condensation of the mitochondrial matrix was observed. The relative squares of B-dependent zones increased and T-dependentparacortical zone reduced in the regional lymph nodes. The increase in the content of KC and MDA in liver was identified., Conclusion: benzo[a]pyrene causes interrelated cascade of reactions in the liver and in its lymphatic region: a disturbance of the blood-lymph barrier morphological organization, and so obstruction of the lymphatic drainagefrom the organ. These promotes development of tissue hypoxia and apoptosis, protein synthesizing and energy cell apparatus disruptions, formation of lymphoid tissue temporary infiltrates in the liver.

The objective of the research was to study the effectiveness of including drug remaxol in the scheme of therapy for patients with decompensated cirrhosis of alcoholic etiology. A group of 29 patients with cirrhosis were treated in the ICU due to deterioration caused by growing phenomena of multiple organ failure. All patients received combined therapy depending on the general state. In addition, 12 patients (main group) received remaxol for 3-9 days (400-800 mL at a rate of 3 mL/min), 17 patients (control group) received essentiale (daily, 5.0 mL/20.0 mL blood of a patient intravenously). The inclusion of remaxol in the scheme of therapy increased the effectiveness of treatment, which was manifested by (i) decreasing severity of liver failure (transition from Class C to B on the Child-Pugh scale), (ii) reducing systemic inflammatory response and multiple organ failure (on the SOFA scale) with reliable half decline to 6.1 ± 1.7 points (p < 0.05), (iii) arresting pneumonia by the end of treatment in the ICU in 57.2% of patients and shortening ALV to 4.2 ± 0.7 days (p < 0.05). Owing to this treatment, the condition of all patients has been improved from decompensated to subcompensated, which allowed them to be transferred from ICU to therapy department in shorter time: remaxol group, within 7.5 ± 1.2 day; control group, within 9.4 ± 1.4 day (p = 0.05). In terms of prognosis and mortality rate (on the SAPS II scale), the state of patients was serious with poor prognosis of cirrhotic process, however, patients treated in the scheme with remaxol showed positive trend with 1.5-fld reduced negative dynamics (p < 0.05). The obtained data on clinical and laboratory efficacy along with good drug tolerance allow us to recommend the inclusion of remaxol in the scheme of treatment for patients with acute and chronic liver disease.

The data on the pharmacoeconomic research of the use of Remaxol in treatment of drug-associated liver injury due to the chemotherapy in cancer patients are presented. The costs-efficiency method was applied to two groups of the patients with drug-associated liver injury treated according to different schemes. The research showed economical benefits of the Remaxol use.

The aim of this work was to study the morphological changes of liver in common voles (Microtus arvalis Pallas) inhabiting the territories of brown coal deposition in Borodino coal opencast (Krasnoyarsk region) and on reclaimed dumps 10 and 20 years after its production. Trapping of the voles (10 animals in each group) living under natural conditions on each territory, was conducted for 30 days. Histological examination of the liver in all animals demonstrated degenerative changes and necrosis of hepatocytes, expressed to a various degree. Morphometric study has shown that the greatest changes in the structure of hepatic stroma and parenchyma took place in voles that lived in the dumps of coal, reclaimed 10 years before. It was found that in the animals of this group, the thickness of hepatocyte plates was increased 1.3 times, while the specific volume of necrotic hepatocytes was twice as much as this parameter in the animals that lived on intact territory.

Acute toxic alcoholic hepatitis continue to be relevant problem of modern medicine as a result of a significant spread of alcoholism in Ukraine and world. Aim - to explore the effect glutargin in blinding function of serum albumin and other indicators of functional state of liver in acute alcoholic toxic hepatitis in experiments on white rats. All animals were divided into four groups. The first (control group) consisted of 20 healthy intact animals, second - 17 rats with acute toxic alcoholic hepatitis, which was taken out of the experiment on the second day of its commencement, the third - 16 animals with similarly modeled pathology, which was taken out on the seventh day from the beginning of the experiment, fourth - 20 animals with acute toxic alcoholic hepatitis, which underwent correction of 4.0% solution glutargin during seven days. Shown, that blinding function of serum albumin, reduced in conditions studied pathology, take place pronounced biochemical signs of liver parenchyma. Under the influence of glutargin studied parameters significantly improved. In acute toxic alcoholic hepatitis significantly disturbing protein-synthetic liver function, occur phenomena cytolysis, suppressed blinding function of serum albumin with maximum expression on the second day of the experiment and with signs of recovery on the seventh day. Under the influence of glutargin upgraded indicators of blinding function of serum albumin: total protein, aminotransferase, alkaline phosphatase, total bilirubin. The activity of serum aspartate aminotransferase normalized and reached the level of control.

Aim: Study pharmacodynamic parameters of anti-viral effectiveness of a chemical compound NIOC-14 in experiments in mice infected with ectromelia virus (EV)., Materials and Methods: EV (K-1 strain) was obtained from the State Collection of Viral Infections and Rickettsioses Causative Agents of the State Scientific Centre of Virology and Biotechnology "Vector". Outbred ICR mice were intranasally infected with EV at a dose of 10 LD50 per animal (10 x 50% lethal doses/animal) and per orally received NIOC-14 or ST-246 as a positive control. Chemical compound NIOC-14 (7-[N'-(4-trifluoromethylbenzoyl)-hidrazincarbonyl]-tricyclo[3.2.2.0(2,4)]non-8-en-6-carbonic acid) was synthesized in Novosibirsk Institute of Organic Chemistry (NIOC). Anti-pox preparation ST-246, developed by SIGA Technologies Inc. (USA), was synthesized in NIOC using the technique described by the authors., Results: 50% effective doses against EV in vivo were shown not to differ significantly between the preparations NIOC-14 (3.59 μg/g mouse mass) and ST-246 (5.08 μg/g mouse mass). During determination of therapeutic window, administration of NIOC-14 to mice 1 day or 1 hour before EV infection, as well as 1, 2 and 4 days after EV infection and then for 9 days was found to ensure 100% animal survival. Administration of NIOC-14 as well as ST-246 resulted in the decrease relative to control of EV titers in lungs, nasal cavity, brains, liver, spleen, kidneys and pancreas., Conclusion: Anti-viral effectiveness of NIOC-14 against EV in vivo was thus comparable by all the studied pharmacodynamic parameters with anti-viral activity of anti-pox-virus preparation ST-246.

Type 2 diabetes mellitus complicated by steatohepatitis is accompanied by a decrease in aconitate hydratase activity, increase in the content of diene conjugates, decrease in the concentration of α-tocopherol, and change in the citrate level in the blood serum of patients, which is evidence of the development of oxidative stress as a result of the intensification of free radical oxidation of biosubstrates and decreasing degree of antioxidant defense of the organism. Combined therapy with melaxen provided a more significant change of the investigated parameters toward the norm (on the average by 36%, p 0.05) in comparison with basic treatment. This result was evidently associated with implementation of the antioxidant effect of melatonin, the level of which is corrected under the action of the drug employed.

Experimental data showing a significant role of enzyme NO-synthase type 2 and cytokine TNF-α enzymes in pathogenesis of CCl4-induced liver injury have been obtained by immunohistochemical assay. It is established that the hepatotoxic agent leads to an increase in NO-synthase 2 and TNF-α levels. The use of both studied phytoadaptogens (eleutherococcus extract and ginseng tincture) at a doses of 48.5 mg/kg and 47 mg/kg, respectively, and the reference drug karsil (100 mg/kg daily for 5 weeks) prevented to a significant degree the accumulation of enzyme NO-synthase 2 and the cytokine TNF-α, which is apparently one of the mechanisms of hepatoprotective action.