352 research outputs found

    Proteolytic system activity dysfunction in case of experimental liver cirrhosis

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    Experimental data presented are devoted to influence of the alpha-lipoic acid and tivortin on activity of proteolytic enzymes in conditions of experimental liver cirrhosis in rats. Experimental model of CCl4-induced liver cirrhosis was shown to be accompanied by the proteolysis system activation. Both pharmacological compounds were shown to reveal the similar normalising effect resulting in the normalisation of proteolytic activity starting 6 hours after the disease induction. The therapeutic efficiency of the alpha-lipoic acid is higher than that of tivortin in case of their single administration in the modelled condition. The data obtained showed the pathogenetic importance of the proteolytic system activation in case of the experimental liver cirrhosis. The data is also an experimental background for prospects of using the tested pharmacons in the pathogenetically oriented complex correction of liver functioning in clinical conditions

    Mesenchymal stem cell-based Smad7 gene therapy for experimental liver cirrhosis

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    BackgroundBone mesenchymal stem cells (MSCs) can promote liver regeneration and inhibit inflammation and hepatic fibrosis. MSCs also can serve as a vehicle for gene therapy. Smad7 is an essential negative regulatory gene in the TGF-β1/Smad signalling pathway. Activation of TGF-β1/Smad signalling accelerates liver inflammation and fibrosis; we therefore hypothesized that MSCs overexpressing the Smad7 gene might be a new cell therapy approach for treating liver fibrosis via the inhibition of TGF-β1/Smad signalling.MethodsMSCs were isolated from 6-week-old Wistar rats and transduced with the Smad7 gene using a lentivirus vector. Liver cirrhosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) for 8 weeks. The rats with established liver cirrhosis were treated with Smad7-MSCs by direct injection of cells into the main lobes of the liver. The expression of Smad7, Smad2/3 and fibrosis biomarkers or extracellular matrix proteins and histopathological change were assessed by quantitative PCR, ELISA and Western blotting and staining.ResultsThe mRNA and protein level of Smad7 in the recipient liver and serum were increased after treating with Smad-MSCs for 7 and 21 days (P

    The parameters of cardiac rhythm in individuals of different age under the influence of physical activity

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    The research of the regularities of the adaptation's process of the organism associated with environment change is one of the most important problems of modern physiology and medicine. The given theme is actual nowadays, as it promotes the development of sports, helps to reach or improve sports achievements. The obtained results are used for the prevention and treatment of many diseases; allow us to identify opportunities for physiological mechanisms

    H-Ras Oncogene Expression and Angiogenesis in Experimental Liver Cirrhosis

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    Background. Proto-oncogenes, particularly ras, may not only affect cell proliferation but also contribute to angiogenesis by influencing both proangiogenic and antiangiogenic mediators. The aim of this study was to investigate whether any relationship exists between ras expression and angiogenesis during diethylnitrosamine- (DEN-) induced experimental liver fibrosis. Materials and Methods. Liver cirrhosis was induced in rats by intraperitoneal injections of DEN. The animals were sacrificed 2 weeks after the last administrations and a hepatectomy was performed. Masson’s trichrome staining was used in the evaluation of the extent of liver fibrosis. The vascular density in portal and periportal areas was assessed by determining the count of CD34 labeled vessel sections. For quantitative evaluation of H-ras expression, in each section positive and negative cells were counted. Results. In fibrotic group H-ras expression was higher than that in nonfibrotic group and was more widespread in cirrhotic livers. Friedman’s test showed that there was a significant correlation between H-ras expression and VD (P<0.01). Conclusion. The results of this descriptive study reveal that H-ras expression gradually increases according to the severity of fibrosis and strongly correlates with angiogenesis

    Methylthioadenosine phosphorylase gene expression is impaired in human liver cirrhosis and hepatocarcinoma

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    Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine and adenine salvage pathways. In mammals, the liver plays a central role in methionine metabolism, and this essential function is lost in the progression from liver cirrhosis to hepatocarcinoma. Deficient MTAP gene expression has been recognized in many transformed cell lines and tissues. In the present work, we have studied the expression of MTAP in human and experimental liver cirrhosis and hepatocarcinoma. We observe that MTAP gene expression is significantly reduced in human hepatocarcinoma tissues and cell lines. Interestingly, MTAP gene expression was also impaired in the liver of CCl4-cirrhotic rats and cirrhotic patients. We provide evidence indicating that epigenetic mechanisms, involving DNA methylation and histone deacetylation, may play a role in the silencing of MTAP gene expression in hepatocarcinoma. Given the recently proposed tumor suppressor activity of MTAP, our observations can be relevant to the elucidation of the molecular mechanisms of multistep hepatocarcinogenesis

    Renal Effects of the Novel Selective Adenosine A1 Receptor Blocker SLV329 in Experimental Liver Cirrhosis in Rats

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    Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (−36.5%, p<0.05), especially in those receiving furosemide (−41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis

    Вплив блокади опіоїдних рецепторів на співвідношення холатів у жовчі щурів із експериментальним алкогольним гепатитом

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    Показано, что при воздействии этанола уменьшается синтез желчных кислот, в частности угнетается гидроксилирование желчных кислот. Применение налокс она в условиях экспериментального алкогольного гепатита у крыс вызывает угнетение гидроксилирования и конъюгации желчных кислот.It is shown that ethanol decreases the synthesis of bile acids, in particular, inhibited the hydroxylation of bile acids. The use of naloxone in experimental alcoholic hepatitis in rats causes inhibition of hydroxylation and conjugation of bile acids

    Активность катепсина D при экспериментальном циррозе печени и при введении координационных соединений меди и препарата бактериального происхождения BioR

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    This paper investigates the influence of the copper coordination compounds CMT-28, CMT-67 and of the bacterial remedy BioR on the cathepsin D activity in liver in experimental cirrhosis. The activity of cathepsin D was also detected electron-histochemicaly in the liver during the regression of experimental hepatic cirrhosis. The result suggests that the coordinative compound CMT-67 used in combination with the bacterial remedy BioR has a pronounced stimulating effect on the enzymatic hydrolysis of the extracellular matrix under the action of cathepsin D and contributes to a more efficient breakdown of the excessive fibrous tissue in liver. It was determined that the active cathepsin D is localized intracellularly in the lysosomes of hepatocytes, macrophages, fibroblasts and endothelial cells, as well as extracellularly on the collagen fibrils near the parenchymal and mezenchymal cells. In addition to its participation in the intracellular proteolysis, cathepsin D is secreted by the hepatocytes and connective tissue cells to the extra-cellular space and participates in the extracellular breakdown of the fibrous tissue.Было изучено влияние координационных соединений меди CMT-28, CMT-67 и препарата бактериального происхождения BioR на активность катепсина D в печени при экспериментальном циррозе. Активность катепсина D была также выявлена электронно-гистохимически в печени при регрессии экспериментального цирроза. Результаты свидетельствуют о том, что координационное соединение меди CMT-67, введенное в комбинации с препаратом бактериального происхождения BioR, имеет выраженное стимулирующее влияние на ферментативный гидролиз внеклеточного матрикса под влиянием катепсина D и способствует более эффективному распаду фиброзной ткани в печени.Было выявлено, что активный катепсин D локализуется внутриклеточно в лизосомах гепатоцитов, макрофагов и эндотелиальных клеток, а также внеклеточно – на коллагеновых волокнах вблизи паренхимальных и мезенхимальных клеток. Таким образом, помимо участия во внутриклеточном протеолизе, катепсин D секретируется гепатоцитами и клетками соединительной ткани во внеклеточное пространство и участвует во внеклеточном распаде фиброзной ткани
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