OBJECTIVETo establish a modified rat model of liver cancer with concurrent cirrhosis for the study of carcinogenesis characteristics and drug intervention of liver cancer.

METHODSFifty male Wistar rats weighing 100-120 g were randomly divided into normal control group (20 rats) and model group (30 rats). In the model group, the rats were subjected to intraperitoneal injection of 50 mg/kg DEN N-diethylnitrosamine (DEN) twice a week for 4 consecutive weeks, followed then by weekly injections for another 10 weeks. The control rats received injections of 0.1 ml saline in the same manner. At 2, 4, 8, 12, 14, and 18 weeks, 3 rats from each group were sacrificed for assessing tumor formation and liver cirrhosis.

RESULTSLiver cancer with concurrent cirrhosis was induced successfully after 14 weeks of DEN injections. At the 14th week, 3 out of the 5 rats were found to have cirrhosis and LC, and at the 18th week, all the 3 rats examined had cirrhosis and liver cancer. The total carcinogenesis rate in the rats was 75% at 18 weeks with an overall mortality of 33%.

CONCLUSIONThis approach to establishing rat models of liver cancer with concurrent cirrhosis requires simple operation, shortens the time of carcinogenesis, and ensures a high success rate of carcinogenesis and a low mortality rate. The carcinogenesis characteristics in this model are similar to those in human.

Animals ; Liver Cirrhosis, Experimental ; complications ; pathology ; Liver Neoplasms, Experimental ; etiology ; pathology ; Male ; Rats ; Rats, Wistar

Animals ; Bile Duct Diseases ; Liver Cirrhosis, Experimental ; Rats

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

BACKGROUND/AIMS: The reactive oxygen species from thioacetamide (TAA) induces rat liver cirrhosis that resembles the human disease, and it can serve as a suitable animal model for studying human liver cirrhosis. The aim of this study was to identify the molecular protein signatures via a proteomics approach with using a rat model with TAA-induced liver cirrhosis. METHODS: Male Wistar rats were treated with 0.3 g/L TAA in their drinking water. The animals were then sacrificed at 9 and 30 weeks after TAA administration. The development of liver cirrhosis was observed with histological study. The livers were processed for proteins extraction and the proteins were analyzed by 2-dimensional electrophoresis. The proteins were identified by matrix-assisted laser desorption ionizing time-of-flight mass spectrometry and this was validated by immunohistochemical staining. RESULTS: On the proteomics analysis of the liver tissues, a total of 88 proteins showed significant change in their expression between the controls and the cirrhotic rats. When the proteins were categorized by their function, they included ECM/cellular skeleton, cell proliferation/death signal, metabolism, DNA damage/stress and immune response related proteins. The level of expression gradually increased up to 30 weeks for interleukin-6 (IL-6) precursor, transforming growth factor-beta (TGF-beta) induced protein, TIMP-1 and MMP-9. Cytochrome P450 2B, which is required for the metabolic activation of TAA, also showed the same increasing pattern. In contrast, the expression level of the proteins did not show a significant change at 9 weeks, but this increased to 3-fold at 30 weeks for carbonic anhydrase VII, ras related protein Rab 6, Annexin A2, neurofibromatosis type 2 and aldehyde dehydrogenase. CONCLUSIONS: This study showed that there is a repertoire of proteins during the development of liver cirrhosis via TAA. In this model, IL-6, TGF-beta, MMP-9 and TIMP-1 were reconfirmed as the molecular signatures during the development of TAA-induced liver cirrhosis.
Thioacetamide ; Rats, Wistar ; Rats ; Proteomics ; Proteins/*metabolism ; Male ; Liver Cirrhosis, Experimental/*metabolism ; Liver/*metabolism ; Animals

Animals ; Cyclophilins ; metabolism ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; Rats ; Rats, Wistar

Animals ; Carbon Tetrachloride Poisoning ; Diabetes Mellitus, Experimental ; complications ; Liver Cirrhosis, Experimental ; chemically induced ; complications ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

Animals ; Leptin ; pharmacology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Superoxide Dismutase ; metabolism

Angiotensinogen ; metabolism ; Animals ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System

Animals ; Blood Proteins ; metabolism ; Liver Cirrhosis, Experimental ; blood ; diagnosis ; pathology ; Male ; Proteome ; Rats ; Rats, Sprague-Dawley

OBJECTIVESTo study the dynamic change of hepatic oval cells (HOC) in the process of rat liver cirrhosis formation induced by dimethylnitrosamine (DMN), and to explore its pathophysiology significance.

METHODSA rat cirrhosis model was established by using DMN. Microscopical and electronmicroscopical changes of HOC were examined. Thy1.1 was detected by immunohistochemical method at different times. The ratio of HOC was checked using image pattern analysis and Western blot. The number of HOC was counted microscopically.

RESULTSAt the 4th week after DMN administration, the liver fibrosis was at its peak, with false lobules formation combined with large areas of hemorrhage and necrosis. The fibrosis started to minimize at the 6th week, and also the inflammatory changes at the 8th week. Thy1.1 positive stained cells dispersed at the 2nd week; increased at the 4th week around fiber septa; reached its peak at the 6th week, then decreased at the 8th week. The results of image pattern analysis, cell counting under light microscope and Western blot were constant, with the highest cell numbers at the 6th week, and dropped at the 8th week. The ultrastructure of HOC was characterized by their small sized, oval nuclei, and higher nucleus/plasma ratio.

CONCLUSIONDuring the formation and reduction of rat cirrhosis caused by DMN, Thy1.1 stained HOC showed notable dynamic change, which may play an important role in the cirrhotic process.

Animals ; Dimethylnitrosamine ; Hepatocytes ; metabolism ; Liver Cirrhosis, Experimental ; metabolism ; Male ; Rats ; Rats, Wistar ; Thy-1 Antigens ; metabolism