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Induced Hepatitis (induced + hepatitis)
Selected AbstractsRole of 2B4-mediated signals in the pathogenesis of a murine hepatitis model independent of Fas and V,14 NKT cellsIMMUNOLOGY, Issue 1pt2 2009Hiroshi Furukawa Summary Concanavalin A (Con A)-induced hepatitis is a T-cell-mediated murine experimental model of autoimmune hepatitis. Mice lacking V,14 NKT cells were found to be less sensitive to this hepatitis and the MRL/Mp- Faslpr/lpr (MRL/lpr; i.e. Fas deficient) mice were also less sensitive. We report herein that MRL/Mp- Faslpr/lpr - Saprpl/, (MRL/lpr/rpl) mice lack V,14 NKT cells and are deficient in the Fas antigen but sensitive to Con A-induced hepatitis. The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. We previously reported new mutant mice found among MRL/lpr mice and revealed that SAP deficiency led to the regression of autoimmune phenotypes in mutant MRL/lpr/rpl mice. It was also revealed that CD4+ and CD8+ T cells were effector cells and that blockade of 2B4, one of the SLAM family receptors, inhibited the induction of hepatitis in MRL/lpr/rpl mice. These data suggest that signals mediated by molecules other than SAP from 2B4 in T cells played important roles in the induction of hepatitis in MRL/lpr/rpl mice. [source] Lactoferrin protects against concanavalin A-induced liver injury in miceLIVER INTERNATIONAL, Issue 4 2010Hao Yin Abstract Background: Liver diseases, caused by viral infection, autoimmune conditions, alcohol ingestion or the use of certain drugs, are a significant health issue, as many can develop into liver failure. Lactoferrin (Lac) is an iron-binding glycoprotein that belongs to the transferrin family. Owing to its multiple biological functions, Lac has been evaluated in a number of clinical trials to treat infections, inflammation and cancer. Aim: The present study aims to reveal a profound hepatoprotective effect of Lac, using a mouse model of Concanavalin A (Con A)-induced hepatitis, which mimics the pathophysiology of human viral and autoimmune hepatitis. Method: C57Bl/6J mice were injected with bovine Lac following Con A challenge. The effects of Lac on interferon (IFN)-, and interleukin (IL)-4 expression were determined. The roles of Lac on T-cell apoptosis and activation, and leukocytes infiltration were examined. Result: The data demonstrated that the protective effect of Lac was attributed to its ability to inhibit T-cell activation and production of IFN-,, as well as to suppress IL-4 production by hepatic natural killer T cells. Conclusion: These findings indicate a great therapeutic potential of Lac in treating in treating inflammatory hepatitis and possibly other inflammatory diseases. [source] P-selectin mediates leukocyte rolling in concanavalin-A-induced hepatitisLIVER INTERNATIONAL, Issue 5 2005Sandra March Abstract: Concanavalin- A (Con-A)-induced hepatitis is an experimental model of human autoimmune hepatitis characterized by leukocyte activation and infiltration of the liver. The aim of the present study was to evaluate the role of P-selectin on leukocyte,endothelial interactions within the hepatic microvasculature in response to Con-A. Methods: The study was performed in P-selectin-deficient mice and wild-type mice pretreated with anti-P-selectin blocking monoclonal antibody (mAb) or vehicle. After 2 h of Con-A (20 mg/kg i.v.) or PBS administration, leukocyte rolling and adhesion and the index of sinusoidal perfusion were evaluated using the intravital microscopy technique in the liver. Apoptosis was determined by flow cytometry analysis of caspase-3 activity assayed on freshly isolated hepatocytes. Results: Con-A induced a significant increase in leukocyte rolling, mainly located at the central venule (2.1±0.4 vs 0.6±0.2 cells/min in wild-type mice treated with vehicle) and less marked, but still significant, in portal venules. This was associated with a significant increase in leukocyte adhesion. In P-selectin-deficient mice treated with Con-A, leukocyte rolling in portal and central venules was markedly reduced. However, leukocyte adhesion was only partially attenuated. A few sinusoids were perfused in wild-type mice treated with Con-A (26%). The percentage of perfused sinusoids was significantly higher in P-selectin-deficient mice (45%; P<0.05 vs wild-type). Similar effects were noted after the simultaneous injection of Con-A and anti-P-selecting mAb in wild-type mice. After Con-A treatment, apoptosis was markedly reduced in isolated hepatocytes of P-selectin-deficent mice (37±7% vs 75±5% in wild type). Conclusion: The results of this intravital microscopy study clearly demonstrate that P-selectin is involved in the initial leukocyte rolling that leads to the development of Con-A-induced liver injury. [source] Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in sprague-dawley ratsPHYTOTHERAPY RESEARCH, Issue 9 2010Chung Mu Park Abstract The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl4 control, and two DLWE groups (0.5 and 2,g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl4 (50% CCl4/olive oil; 0.5,mL/kg bw) was administered 24,h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl4 -induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl4 administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly elevated Fas and TNF-? mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl4 -induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl4. Copyright © 2010 John Wiley & Sons, Ltd. [source] Hepatoprotective activity of aqueous,methanol extract of Artemisia vulgarisPHYTOTHERAPY RESEARCH, Issue 2 2005Anwarul Hassan Gilani Abstract The effect of a crude extract of the aerial parts of Artemisia vulgaris (Av.Cr) was investigated against D -galactosamine (D -GalN) and lipopolysaccharide (LPS) induced hepatitis in mice. Co-administration of D -GalN (700 mg[sol ]kg) and LPS (1 µg[sol ]kg) significantly (p < 0.05) raised the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice in the toxin group compared with the values in the control group. Pre-treatment of mice with different doses of Av.Cr (150,600 mg[sol ]kg) significantly (p < 0.05) reduced the toxin-induced rise in plasma ALT and AST. The hepatoprotective effect was further verified by histopathology of the liver, which showed improved architecture, absence of parenchyma congestion, decreased cellular swelling and apoptotic cells, compared with the findings in the toxin group of animals. These findings scientifically validated the traditional use of Artemisia vulgaris for various liver disorders. Copyright © 2005 John Wiley & Sons, Ltd. [source] | ||||||||||