Home About us Contact
|
Home About us Contact | ||
|
|
||
Hepatic Fibrogenesis (hepatic + fibrogenesi)
Selected AbstractsA yellow bullet against the drivers of hepatic fibrogenesis,HEPATOLOGY, Issue 2 2008Ralf Weiskirchen Ph.D. No abstract is available for this article. [source] Matrix metalloproteinase inhibitor, CTS-1027, attenuates liver injury and fibrosis in the bile duct-ligated mouseHEPATOLOGY RESEARCH, Issue 8 2009Alisan Kahraman Aim:, Excessive matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of acute and chronic liver injury. CTS-1027 is an MMP inhibitor, which has previously been studied in humans as an anti-arthritic agent. Thus, our aim was to assess if CTS-1027 is hepato-protective and anti-fibrogenic during cholestatic liver injury. Methods:, C57/BL6 mice were subjected to bile duct ligation (BDL) for 14 days. Either CTS-1027 or vehicle was administered by gavage. Results:, BDL mice treated with CTS-1027 demonstrated a threefold reduction in hepatocyte apoptosis as assessed by the TUNEL assay or immunohistochemistry for caspase 3/7-positive cells as compared to vehicle-treated BDL animals (P < 0.01). A 70% reduction in bile infarcts, a histological indicator of liver injury, was also observed in CTS-1027-treated BDL animals. These differences could not be ascribed to differences in cholestasis as serum total bilirubin concentrations were nearly identical in the BDL groups of animals. Markers for stellate cell activation (,-smooth muscle actin) and hepatic fibrogenesis (collagen 1) were reduced in CTS-1027 versus vehicle-treated BDL animals (P < 0.05). Overall animal survival following 14 days of BDL was also improved in the group receiving the active drug (P < 0.05). Conclusion:, The BDL mouse, liver injury and hepatic fibrosis are attenuated by treatment with the MMP inhibitor CTS-1027. This drug warrants further evaluation as an anti-fibrogenic drug in hepatic injury. [source] Expression of intercellular adhesion molecule-1 in hepatic stellate cellsJOURNAL OF DIGESTIVE DISEASES, Issue 1 2000Lu Lungen OBJECTIVE: To explore the expression of intercellular adhesion molecule-1 (ICAM-1) in hepatic stellate cells (HSC). METHODS: Via in situ perfusion with proteinase and collagenase and density-gradient centrifugation with Nycodenz, HSC were isolated and cultured from the livers of both normal Wistar rats and the livers of rats treated with carbon tetrachloride. Expression of ICAM-1 in HSC was detected by an immunohistochemistry assay and reverse transcription,polymerase chain reaction (RT-PCR). RESULTS: No ICAM-1 was expressed in the freshly isolated HSC of normal rats, but ICAM-1 was found in primary cultures of HSC at day 10 and in secondary cultures of HSC at day 7. Additionally, the intensity of the expression increased over time. Expression of ICAM-1 was observed in freshly isolated HSC from the livers of rats treated with carbon tetrachloride. CONCLUSIONS: Expression of ICAM-1 is related to the activation of HSC, hepatic inflammation and hepatic fibrogenesis. [source] Biochemical markers of hepatic fibrogenesis: Single measurements are not reliable enough to replace liver biopsyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2000Jacob George No abstract is available for this article. [source] Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride-induced hepatic fibrosis in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2003Tzung-Yan Lee ABSTRACT Carbon tetrachloride (CCl4) is metabolized by cytochrome P450 to form a reactive trichloromethyl radical that triggers a chain of lipid peroxidation. These changes lead to cell injury, and chronic liver injury leads to excessive deposition of collagen in liver, resulting in liver fibrosis. The aim of this study was to evaluate the effects of long-term Salvia miltiorrhiza administration in CCl4 -induced hepatic injury in rats. Salvia miltiorrhiza (10, 25 or 50 mg kg,1 twice a day) was given for 9 weeks, beginning at the same time as the injections of CCl4. Rats receiving CCl4 alone showed a decreased hepatic glutathione level and an increased glutathione-S-transferase content. The hepatic thiobarbituratic acid-reactive substance levels were increased. CCl4 also caused a prominent collagen deposition in liver histology that was further supported by the increased hepatic mRNA expression of transforming growth factor-,1, tissue inhibitor of metallproteinase-1 and procollagen I. Salvia miltiorrhiza administration led to a dose-dependent increase in hepatic glutathione levels and a decrease in peroxidation products. Additionally, it reduced the mRNA expression of markers for hepatic fibrogenesis. In conclusion, long-term administration of Salvia miltiorrhiza in rats ameliorated the CCl4 -induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis. [source] Lack of association of iron metabolism and Dupuytren's diseaseJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2008J Hnanicek Abstract Background,Iron accumulation as seen in genetic haemochromatosis is a major cause of hepatic fibrogenesis. A link between chronic liver disease and Dupuytren's disease (DD) is well established, especially in alcoholics. Aim The aim of the present study was to test the hypothesis that iron accumulation might cause fibrosis of the palmar aponeurosis leading to DD. Patients and methods We examined iron metabolism, mutations of the HFE gene, serum cholesterol, alcohol consumption, presence of chronic liver disease, diabetes and history of severe manual work in a group of 90 patients who had undergone surgery for a severe form of DD. The tissue removed during surgery was histologically examined to confirm the diagnosis of DD. For a control group, we used 33 healthy subjects with similar profiles. Results The DD group consisted of 82 men and 8 women. Chronic liver disease was found in 27% of DD patients, compared with 6.1% of control subjects (P = 0.013). A history of hand traumatization was present in 33% of DD patients vs. 15% of control subjects (P = 0.048). Excessive alcohol consumption was present in 35.5% of DD patients compared with 15.1% of controls (P = 0.029). None of the other tested parameters, including the prevalence of HFE gene mutations, showed a significant difference between the two groups. Conclusions Iron accumulation does not play a major role in the pathogenesis of DD. However, sex, age, manual labour and alcohol consumption are risk factors for progression of DD. We observed a high incidence of chronic liver disease in patients with DD. [source] Hypoxia potentiates transforming growth factor-, expression of hepatocyte during the cirrhotic condition in rat liverLIVER INTERNATIONAL, Issue 6 2004Won-II Jeong Abstract: Background/Aims: Many studies have reported that hypoxia might be associated with angiogenesis and fibrogenesis, and the level of transforming growth factor-,1 (TGF-,1) was increased in fibrotic liver and maximal at cirrhosis. Therefore, we examined the expression of TGF-,1, phosphorylated-Smad2/3 (p-Smad2/3) of the TGF-, immediate down stream signaling system and hypoxic status during hepatic fibrogenesis. Methods: Fibrosis of rats was induced by carbon tetrachloride. Collagens were detected with Azan stain. Immunohistochemistry and immunoblotting was used. Results: TGF-,1 was mainly produced by hypoxic hepatocytes at cirrhosis although myofibroblasts (MFBs) and macrophages producing TGF-,1 were decreased. Moreover, distribution of p-Smad2/3 in hepatocytes was consistent with those of hypoxic hepatocytes regardless of MFBs. Furthermore, in recovery, most MFBs disappeared, whereas positive reactions of p-Smad2/3 still existed in the hepatocytes of hypoxic areas. Therefore, TGF-,1 expression in hepatocytes might have been associated with hypoxia. Conclusions: We put forward the hypothesis that TGF-,1 is mainly produced by MFBs and macrophages at early and middle stages of fibrotic processes, but it is predominantly released by hypoxic hepatocytes in the last fibrotic stage or cirrhosis. [source] | ||||||||||