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Various Liver Diseases (various + liver_diseases)
Selected AbstractsReview article: nuclear receptors and liver disease , current understanding and new therapeutic implicationsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009D. A. H. ELFAKI Aliment Pharmacol Ther,30, 816,825 Summary Background, The important role of nuclear receptors and their contribution to liver function in both physiological and pathological conditions has come to attention in recent years and has advanced our understanding of several liver diseases. These findings led to the introduction of targeting nuclear receptors as treatment strategies for various liver diseases. Aims, To review the new insights brought by the study of nuclear receptors to our understanding of the molecular basis of various liver diseases, and to summarize some of the recent studies that evaluated the efficacy of targeting nuclear receptor as a new approach in treating liver diseases. Methods, Review of articles, using PubMed and article references. Results, Nuclear receptor ligands in patients with liver diseases have been associated with a variety of toxicities. Some clinical results have not met the expectations predicted from animal experiments. Mechanistic explanations at the molecular level are needed for preventing toxicity and improving outcomes from nuclear receptor ligands. Conclusion, The use of various nuclear receptor ligands in liver diseases is a promising approach that can benefit many patients suffering from these devastating diseases. However, we are far from a full understanding of the molecular mechanisms by which these receptors work. [source] Hepatocyte growth factor protects against Fas-mediated liver apoptosis in transgenic miceLIVER INTERNATIONAL, Issue 10 2009Hideyuki Suzuki Abstract Background: Apoptosis via the Fas/Fas ligand signalling system plays an important role in the development of various liver diseases. The administration of an agonistic anti-Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors including hepatocyte growth factor (HGF) have been found to prevent apoptosis. Methods: In this study, we demonstrated the overexpression of HGF to have a protective effect on Fas-mediated hepatic apoptosis using a transgenic mice (Tg mice) model. Results: In HGF Tg mice, the elevation of alanine aminotransferase was dramatically inhibited at 12 and 24 h after the administration of 0.15 mg/kg anti-Fas antibody. HGF Tg mice showed a significantly lower number of apoptotic hepatocytes at 12 h compared with wild-type (WT) mice. Furthermore, 85% (six of seven) HGF Tg mice were able to survive after the administration of 0.3 mg/kg anti-Fas antibody, while none of the WT mice survived. The Bcl-xL expression was increased in HGF Tg mice, while there was no difference in the expression of Bax, Bid, Mcl-1 and bcl-2 between WT mice and HGF Tg mice. In addition, the HGF Tg mice showed more Akt phosphorylation than the WT mice both before and after the anti-Fas antibody injection. Conclusions: Taken together, our findings suggest that HGF protects against Fas-mediated liver apoptosis in vivo, and the upregulation of Bcl-xL via Akt activation may also play a role in the protective effects of HGF. [source] Expression of uncoupling protein-2 in biliary epithelial cells in primary biliary cirrhosisLIVER INTERNATIONAL, Issue 6 2002Eitaro Taniguchi Abstract:Background/Aims: Uncoupling proteins are thought to protect cells from oxidative stresses. Because uncoupling protein-2 is expressed in liver and reactive oxygen species are involved in pathogenesis of various liver diseases, this protein may protect liver cells from disease-associated oxidative stress. However, uncoupling protein-2 expression in human liver has not been examined. Methods: We investigated hepatic uncoupling protein-2 distribution in various liver diseases including primary biliary cirrhosis, autoimmune hepatitis, chronic viral hepatitis, and histologically normal liver by immunohistochemistry.Results: Uncoupling protein-2 was expressed in some hepatocytes, however, the degree of hepatocytic uncoupling protein-2 expression did not differ significantly among liver diseases and normal liver. Uncoupling protein-2 was abundant in biliary epithelial cells in primary biliary cirrhosis but not in other liver specimens. Enhanced uncoupling protein-2 expression in biliary epithelial cells was specific for primary biliary cirrhosis and did not result simply from cholestasis. The percentage of uncoupling protein-2 positive bile ducts in primary biliary cirrhosis patients treated with ursodeoxycholic acid was significantly lower than in untreated patients.Conclusions: These results suggest that uncoupling protein-2 is involved in the pathogenesis of primary biliary cirrhosis. [source] Quantitative ATP synthesis in human liver measured by localized 31P spectroscopy using the magnetization transfer experimentNMR IN BIOMEDICINE, Issue 5 2008A. I. Schmid Abstract The liver plays a central role in intermediate metabolism. Accumulation of liver fat (steatosis) predisposes to various liver diseases. Steatosis and abnormal muscle energy metabolism are found in insulin-resistant and type-2 diabetic states. To examine hepatic energy metabolism, we measured hepatocellular lipid content, using proton MRS, and rates of hepatic ATP synthesis in vivo, using the 31P magnetization transfer experiment. A suitable localization scheme was developed and applied to the measurements of longitudinal relaxation times (T1) in six healthy volunteers and the ATP-synthesis experiment in nine healthy volunteers. Liver 31P spectra were modelled and quantified successfully using a time domain fit and the AMARES (advanced method for accurate, robust and efficient spectral fitting of MRS data with use of prior knowledge) algorithm describing the essential components of the dataset. The measured T1 relaxation times are comparable to values reported previously at lower field strengths. All nine subjects in whom saturation transfer was measured had low hepatocellular lipid content (1.5,±,0.2% MR signal; mean,±,SEM). The exchange rate constant (k) obtained was 0.30,±,0.02,s,1, and the rate of ATP synthesis was 29.5,±,1.8,mM/min. The measured rate of ATP synthesis is about three times higher than in human skeletal muscle and human visual cortex, but only about half of that measured in perfused rat liver. In conclusion, 31P MRS at 3,T provides sufficient sensitivity to detect magnetization transfer effects and can therefore be used to assess ATP synthesis in human liver. Copyright © 2007 John Wiley & Sons, Ltd. [source] Ameliorative effects of pycnogenol® on carbon tetrachloride-induced hepatic oxidative damage in ratsPHYTOTHERAPY RESEARCH, Issue 11 2007Tai-Hwan Ahn Abstract This study evaluated the putative antioxidant activity of Pycnogenol® (PYC) against CCl4 -induced hepatic oxidative damage in Sprague-Dawley rats. A single oral dose of CCl4 (1.25 mL/kg) produced significantly increased levels of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities. In addition, increased malondialdehyde (MDA) concentration, reduced glutathione (GSH) content, and decreased catalase, superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were observed in the hepatic tissues. However, concomitant administration with PYC (10 or 20 mg/kg) significantly improved CCl4 -induced hepatic injury, as evidenced by the decline of serum AST and ALT activities in a dose dependent manner. Moreover, PYC reduced MDA concentration and increased GSH levels and catalase, SOD and GST activities in hepatic tissues, indicating that concomitant administration with PYC efficiently prevent the CCl4 -induced oxidative damage in rats. The free radical scavenging assay showed that PYC has a dose-dependent scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. These results indicate that PYC has an antioxidant effect against CCl4 -induced hepatic oxidative damage and is useful as a hepatoprotective agent against various liver diseases induced by oxidative stress. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||