OBJECTIVETo investigate the expression of the lysosomal enzyme acid sphingomyelinase (ASMase) in alcohol-induced hepatic fibrosis using a rat model.

METHODSThe model of liver fibrosis was induced by administration of alcohol and high fat diet using 20 rats. Six rats given no alcohol and normal diet served as the control group. Real-time PCR, western blotting, and immunohistochemistry were used to evaluate fibrosis-related changes in the mRNA and protein expressions of ASMase.

RESULTSThe fibrotic liver tissues of the model rats showed significantly higher expression levels of ASMase than the non-fibrotic liver tissues of the control rats (P less than 0.05).

CONCLUSIONExpression of ASMase is increased in the fibrotic liver tissue of an alcohol-induced hepatic fibrosis rat model, suggesting that this lysosomal enzyme may contribute to development of this disease condition.

Animals ; Liver ; enzymology ; Liver Cirrhosis, Alcoholic ; enzymology ; Liver Cirrhosis, Experimental ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley ; Sphingomyelin Phosphodiesterase ; metabolism

Animals ; Female ; Liver ; enzymology ; Liver Cirrhosis, Experimental ; enzymology ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics

Female ; Glucuronosyltransferase ; biosynthesis ; genetics ; Hepatitis B, Chronic ; enzymology ; Hepatitis C, Chronic ; enzymology ; Hepatitis, Chronic ; enzymology ; Humans ; Liver Cirrhosis ; enzymology ; Male ; RNA, Messenger ; biosynthesis ; genetics

Telomerase is highly activated in human immortal cell lines and tumor tissues, whereas it is not activated in primary cell strains and many tumor-adjacent tissues. It is suggested that telomerase activation is one of the critical steps in malignant transformation. In the present study, the telomerase activity was investigated in hepatocellular carcinoma tissues and non-tumor liver tissues from Korean patients with chronic hepatitis and cirrhosis. Eighty two liver tissues (24 chronic hepatitis specimens, 34 cirrhosis specimens, and 24 hepatocellular carcinomas) were obtained from 23 chronic viral hepatitis patients, 19 cirrhosis patients (including 7 liver transplants), and 24 patients with hepatocellular carcinoma, of which the surrounding non-tumor liver tissues were available in 16 patients (1 chronic hepatitis and 15 cirrhosis). As negative controls, 3 normal liver tissues were included. Protein from liver specimens was purified by a detergent lysis method as described elsewhere, and telomerase activity was measured in 2 diluents of each sample (1:1 and 1:100) by a telomeric repeat amplification protocol (TRAP). Telomerase was strongly activated in 79% (19/24) of the hepatocellular carcinomas, while weakly in 8% (2/24) of the chronic hepatitis tissues and in 24% (8/34) of the cirrhosis tissues. All of 3 normal control livers showed no telomerase activation. No relationship could be observed between the enhancement of telomerase activity and tumor nature. None of the chronic heaptitis or cirrhosis patients with mild telomerase activation in the liver have developed hepatocellular carcinoma for at least 2 years of follow-up period. These results suggest that the strong enhancement of telomerase activity may be a critical part of hepatocarcinogenesis, although the exact mechanism of such high activation in hepatocellular carcinoma is not clear. In addition, further study will be necessary to clarify the reason why no telomerase activity detectable by a conventional TRAP can be seen in some hepatocellular carcinoma.
Adult ; Aged ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/enzymology* ; Cell Transformation, Neoplastic* ; Comparative Study ; Enzyme Activation ; Female ; Hepatitis, Chronic/enzymology ; Human ; Liver Cirrhosis/enzymology ; Liver Neoplasms/pathology ; Liver Neoplasms/enzymology* ; Male ; Middle Age ; Precancerous Conditions/enzymology* ; Telomerase/analysis*

Animals ; Immunohistochemistry ; In Situ Hybridization ; Liver ; enzymology ; pathology ; Liver Cirrhosis ; enzymology ; etiology ; pathology ; Male ; Matrix Metalloproteinase 2 ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

Animals ; Drugs, Chinese Herbal ; pharmacology ; Liver Cirrhosis, Experimental ; enzymology ; Male ; Pancreatic Elastase ; biosynthesis ; genetics ; Rats ; Rats, Wistar

Animals ; Cyclooxygenase 2 ; Humans ; Isoenzymes ; genetics ; physiology ; Liver ; enzymology ; Liver Cirrhosis ; etiology ; Liver Diseases, Alcoholic ; etiology ; Membrane Proteins ; Prostaglandin-Endoperoxide Synthases ; genetics ; physiology

BACKGROUND/AIMS: To investigate the degree of cyclooxygenase-2 (COX-2) protein expression in chronic hepatitis and cirrhosis. METHODS: COX-2 protein expression was evaluated in 43 cases of chronic hepatitis and 24 cases of cirrhosis using immunohistochemical techniques. The COX-2 immunohistochemical staining score was assessed using the scoring systems of Pazirandeh et al and Qiu et al. and each scoring system was based on a sum of the parameters of staining intensity and distribution. RESULTS: The mean COX-2 expression scores in chronic hepatitis and cirrhosis were 2.5 +/- 1.3 vs. 3.3 +/- 1.1 (p = 0.008), and 3.2 +/- 2.0 vs. 4.5 +/- 1.7 (p = 0.006), respectively, based on the Pazirandeh et al. and Qiu et al. scoring systems. The percentage samples of high COX-2 expression score (4 to 5) in chronic hepatitis and cirrhosis were 16.3% vs. 45.8% (p = 0.022), and 23.3% vs. 50% (p = 0.021), respectively, based on the two scoring systems. The mean COX-2 expression scores based on the severity of hepatic fibrosis scored using Ishak's modified staging system (fibrosis score 0 to 3 vs. 4 to 6) were 2.4 +/- 1.3 vs. 3.2 +/- 1.1 (p = 0.009), and 3.1 +/- 2.0 vs. 4.3 +/- 1.8 (p = 0.009), respectively, based on the two scoring systems. CONCLUSIONS: COX-2 expression was significantly higher in liver cirrhosis group than in chronic hepatitis. COX-2 expression scores according to Ishak's staging was significantly higher in the advanced fibrosis group. COX-2 may play a role in the progression of hepatic fibrosis.
Adult ; Aged ; Cyclooxygenase 2/analysis/*physiology ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Disease Progression ; Female ; Hepatitis, Chronic/enzymology ; Humans ; Immunohistochemistry ; Liver Cirrhosis/drug therapy/*enzymology ; Male ; Middle Aged

OBJECTIVESTo observe the function of heme oxygenase (HO) in the lung damage in hepatic cirrhosis rats.

METHODSLiver cirrhosis model rats were made by CCl4. Lung samples taken from normal and cirrhotic rats were examined for HO-1 and HO-2 protein and expression distribution with immunohistochemical staining and western blot.

RESULTSLiver cirrhosis model rats were successfully constructed. There was a notable increase of HO-1 staining (0.062+/-0.021 vs 0.185+/-0.044, t=11.24, P<0.01) and protein expression (0 vs 5294.92+/-46.02, t=11.45, P<0.01) in both vascular and bronchial smooth muscle cells and endothelium in cirrhotic rats, however, no statistical difference of HO-2 between cirrhotic and normal rats was observed.

CONCLUSIONThe HO-CO pathway is probably involved in the pathogenesis of lung damage in hepatic cirrhosis rats.

Animals ; Carbon Tetrachloride Poisoning ; Heme Oxygenase (Decyclizing) ; analysis ; biosynthesis ; Heme Oxygenase-1 ; Liver Cirrhosis, Experimental ; enzymology ; Lung ; enzymology ; Male ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUND/AIMS: An ideal noninvasive diagnostic test for hepatic fibrosis should be simple, inexpensive, and accurate. We aimed to find the simple marker for predicting hepatic fibrosis and to compare the accuracy of AST, platelet, AST/ALT ratio and AST to platelet ratio index (APRI) in chronic hepatitis B patients without clinical evidence of cirrhosis. METHODS: A total of one hundred and twenty-six chronic hepatitis B patients who underwent liver biopsy at the Ajou University Hospital from August 1998 to December 2003 were enrolled. Hepatic fibrosis was assessed using the Ludwig classification. Significant fibrosis was defined as fibrosis score of 3 or more. The AST/ALT ratio and APRI were calculated and correlations with hepatic fibrosis were analyzed. RESULTS: APRI showed a significant correlation (r=0.501, p=0.000) with hepatic fibrosis, and was superior to AST, AST/ALT ratio and platelet in predicting fibrosis. Patients with significant fibrosis (fibrosis stage 3, 4) can be identified to have APRI=1 with sensitivity 71.2% and specificity 70.3%. The sensitivity and specificity of an APRI = 1.5 for cirrhosis (stage 4) were 83.3% and 75.0%. CONCLUSIONS: Simple index using AST and platelet value can predict the presence of significant fibrosis and cirrhosis in chronic hepatitis B patients without clinical evidence of cirrhosis.
Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/*blood ; Female ; Hepatitis B, Chronic/blood/enzymology/*pathology ; Humans ; Liver/pathology ; Liver Cirrhosis/*pathology/virology ; Male ; *Platelet Count ; Sensitivity and Specificity