Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver cell functional heterogeneity has been shown to persist in toxic CCl4 cirrhosis in growing rats, but the zonation observed in cirrhotic nodules may be different in other types of cirrhosis. To investigate this possibility, we looked at the zonal activities of two microsomal enzymes, glucose-6-phosphatase and NADPH dehydrogenase, in cirrhotic nodules from growing rats with chronic cholestasis. Zonal activities were measured by quantitative cytochemistry and microdensitometry. Liver cell heterogeneity was demonstrated, and we confirmed that the metabolic zonation is the mirror image of that observed in toxic cirrhosis, with periportal activity at the nodule periphery and perivenular activity at the nodule centers. Glucose-6-phosphatase activity was 2.06 times higher at the peripheries of the nodules than at the centers, whereas NADPH dehydrogenase activity at the nodule periphery was 72% of the nodule center activity. We conclude that a liver cell functional heterogeneity persists in biliary rat cirrhosis, with zonation the reverse of that previously found in toxic CCl4 cirrhosis.
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PMID:Liver metabolic zonation in rat biliary cirrhosis: distribution is reverse of that in toxic cirrhosis. 131 72

1. The systemic and splanchnic haemodynamic effects of pentifylline (40 mg/kg body weight intravenously) were assessed in rats with portal hypertension associated either with CCl4-induced cirrhosis (n = 13) or portal vein ligation (n = 13). 2. Heparinized catheters were placed into the portal vein, inferior vena cava, aorta and left ventricle with exits from the neck. Haemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabelled microspheres and the reference sample method in seven rats in each group; portal-systemic shunting was measured using microsphere injection in the ileo-colic vein in six rats in each group. 3. Forty-five minutes after injection, pentifylline had no effect on mean arterial pressure, cardiac output, peripheral resistance, portal venous flow, hepatic artery flow or portal-systemic shunting in either group of rats with portal hypertension. The drug lowered portal pressure (-18%) in cirrhotic rats, but not in portal-vein-ligated rats. 4. These data demonstrate that pentifylline lowers portal pressure in cirrhotic rats without affecting portal venous flow and portal-systemic shunting; this effect is possibly mediated by changes in intrahepatic resistance related to the effects of pentifylline on blood viscosity and/or on intrahepatic vasomotor tone.
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PMID:Systemic and splanchnic haemodynamic effects of pentifylline in rats with portal hypertension. 132 20

The role of spleen on inducing the portal hypertension and cirrhotic rat by carbon tetrachloride (CCl4) and ethyl alcohol was studied. Totally 412 male rats were divided randomly into four groups: group A (n = 42) underwent splenectomy before induction by CCl4; group B (n = 42) underwent splenectomy after induction by CCl4 and alcohol of 4 weeks; group C (n = 42) received sham-splenectomy and group D (n = 14) served as a control group. Free portal pressure (FPP), function of liver, the index of spleen (weight of spleen/weight of body) as well as the spleen and liver biopsy were evaluated at different time. The results showed that, in group C, the index of spleen and the area of splenic white pulp had significant increase. The degree of hepatic damage, the number of the infiltrating cells and the degree of hepatic fibrosis were significantly greater in sham-operated animals than in others (group A and B). These results suggested that the spleen should be an immunomodulatic organ in playing an exacerbation role of hepatic cirrhosis, and the effect of splenectomy be a preventive role against the induced rat liver cirrhosis, at least, at certain stage.
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PMID:[Effects of spleen on inducing portal hypertension and liver cirrhosis in rats]. 133 11

Reports of an increase in a serum epoxide hydrolase (sEH), immunochemically related to microsomal EH in humans and rats with hepatocellular carcinoma (HCC), suggested its use as a serum marker for this disease. We have now measured sEH levels (as either immunochemically determined content or enzyme activity) in a number of human and experimental models of liver disease. sEH was elevated above the normal range in at least 50% of individuals with HCC, including: 3 of 6 northern Californians; 4 of 7 Koreans with hepatitis B-associated HCC; hepatitis B-associated HCC in woodchucks; and male rats receiving chronic treatment with aflatoxin B1 or ciprofibrate. sEH was rarely elevated in other forms of chronic liver disease. Only 2 of 9 Koreans with hepatitis B-associated cirrhosis, 1 of 8 carriers, but none with chronic active hepatitis or infection with no apparent liver disease had elevated sEH. In addition, no elevations were found in woodchucks with noncancerous viral hepatitis. In aflatoxin B1- and M1-treated rats sEH was not elevated in those with only hyperplastic foci or hepatocellular adenomas, and in two rat initiation-promotion protocols sEH was elevated only in those rats which received the entire set of treatments. sEH was also increased during acute hepatotoxicity in rats treated with CCl4 or 1,2-dibromo-3-chloropropane. The mechanism of increase in sEH during hepatocarcinogenesis appears to be different from that of other markers of HCC, for in the Korean patients, there was no correlation between sEH concentrations and those of alpha-fetoprotein or ferritin, nor was there a correlation with alpha-fetoprotein concentrations in the aflatoxin-treated rats. Furthermore, the increase in sEH does not correlate with induction of microsomal EH in the liver of experimental animals. Studies to date indicate that sEH is selective for HCC and severe hepatonecrotic injury, and may be of some use in the diagnosis of HCC, particularly as a complement to other serum markers.
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PMID:Serum epoxide hydrolase (preneoplastic antigen) in human and experimental liver injury. 133 49

The modifying action of chronic liver injury on the process of hepatocarcinogenesis was investigated. To induce cirrhosis or fibrosis F344 rats received CCl4 alone or in combination with phenobarbital, either before (model 1) or after (model 2) the application of initiator, diethylnitrosamine (DENA). In these models, morphology, tumor incidence as well as polysubstrate monooxygenase system, gamma-glutamyltransferase (GGT) and glucose-6-phosphatase (G-6-Pase) were studied. The data presented show that in model 1 the tumor incidence was much lower than in rats treated with DENA alone. This reduction appeared to be associated with the decrease in cytochrome P450 content occurring in model 1 after DENA administration. Promotion of the hepatocarcinogenic process was observed when CCl4 injury followed the application of DENA (model 2). Comparison of marker enzymes in cirrhotic livers and in tumors either with or without cirrhosis indicated that changes in cytochrome P450 and G-6-Pase were rather the results of parenchymal damage, while GGT was elevated only in tumorous livers. In tumorous livers none of the xenobiotic metabolizing activities decreased as much as the cytochrome P450 content of the same samples. Thus conceivably the cytochrome P450 operates more rapidly in tumors than in normal livers.
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PMID:Modification of DENA-induced hepatocarcinogenesis by CCl4 cirrhosis. Comparison of the marker enzyme patterns. 135 Feb 34

The purpose of the present study was to determine the role of the systemic venous circulation in the hemodynamic alterations of the cirrhotic disease. Cardiac output (thermodilution; n = 8), mean circulatory filling pressure (balloon technique; n = 6), and blood volume (Evans blue dye; n = 7) were investigated in a rat model of liver cirrhosis without ascites induced by a 12-week individualized CCl4/phenobarbital treatment. Compared with control rats, conscious cirrhotic rats showed a hyperdynamic circulation characterized by normotension, high cardiac output (51 +/- 4.8 vs. 28.6 +/- 1.3 mL.min-1.100 g-1; P less than 0.01), and expanded blood volume (6.5 +/- 0.15 vs. 5.4 +/- 0.22 mL.100 g-1; P less than 0.05). There were no significant differences between control and cirrhotic rats in mean circulatory filling pressure (6.40 +/- 0.27 vs. 5.99 +/- 0.22 mm Hg, respectively) or in the pressure gradient for venous return (6.17 +/- 0.19 vs. 5.8 +/- 0.21 mm Hg, respectively). To further examine the venous tone, effective vascular compliance was estimated with the vascular filling-blood volume relationship by measuring the vascular filling before and after rapid changes in volume (+/- 8 mL.kg-1). Compliance was similar in both control and cirrhotic rats (3.15 +/- 0.26 and 3.41 +/- 0.21 mL.mm Hg-1), but the vascular filling-total blood volume relationship of the cirrhotic rats was displaced toward the volume axis. In conclusion, the increase in blood volume without changes in mean circulatory filling pressure (or venous tone) of the cirrhotic rats indicates a situation with venodilation and elevated total venous capacity; this is likely to be an important mechanism that could explain the hyperdynamic circulation of the cirrhotic disease.
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PMID:Increased total vascular capacity in conscious cirrhotic rats. 135 59

The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression, and significantly enhanced the induction of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions were not affected. Moreover, phenobarbital (PB) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model, no promotion influence being exerted after treatment with the non-carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural.
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PMID:Possible enhancing effect of the immunosuppressive agent, 6-mercaptopurine(6-MP) on focal lesion development in cirrhotic liver induced by carbon tetrachloride but not furfural in F344 rats. 135 82

DNA strand breaks (nicks) in non-parenchymal cells (NPCs) in CCl4-induced acute or chronic liver injury in rats were detected using an in situ nick translation method; their dynamic changes were analysed in relation to the proliferation pattern of hepatocytes and NPCs, as revealed by bromodeoxyuridine (BrdU)-uptake. In acute injury, hepatocyte proliferation started before centrilobular necrosis had occurred, whereas BrdU-labeled sinusoidal NPCs markedly increased only after centrilobular necrosis was apparent. DNA breakages in NPCs paralleled the proliferation pattern of these cells, suggesting that nicks are physiological, and reflect proliferation and activated gene expression. In chronic injury, liver cirrhosis developed after 9 weeks, but BrdU-labeling of hepatocytes was almost the same level as that in untreated liver. The number of BrdU-labeled NPCs showed only a slight increase, while those with DNA breakages were much more frequent in the cirrhotic stage, suggesting a significant role for NPCs in the fibrotic process. These results indicate that DNA strand breaks in NPCs act as a marker for activation states such as proliferation, differentiation and/or activated gene expression.
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PMID:Changes in DNA strand breaks in non-parenchymal cells following hepatocyte regeneration in CCl4-induced rat liver injury. 136 17

Development and regression of liver fibrosis and cirrhosis induced by CCl4 in male F-344 rats were strictly followed during and after an 8-week treatment. The relative amount of collagen was measured by morphometry and the number of glycosaminoglycan (GAG) containing fat storing cells was counted at each time point. The expression of proteoglycan genes (decorin, versican and BPG-5 HSPG) was studied in parallel with the development of cirrhosis. Collagen content of the liver as well as the number of GAG-containing mesenchymal (fat storing) cells increased in parallel until two weeks after the cessation of CCl4 treatment. Later, both the collagen content and the number of GAG-containing cells decreased in parallel and significantly. Proteoglycan gene expression in the nonparenchymal fraction of liver cells indicated an active proteoglycan synthesis in the course of the development of cirrhosis. It is concluded that modified Ito (fat storing) cells synthesize proteoglycans and play an important role in the formation of connective tissue fibers in liver fibrosis.
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PMID:Role of the modified (glycosaminoglycan producing) perisinusoidal fibroblasts in the CCl4-induced fibrosis of the rat liver. 138 23

We sought to study the immunogenicity of Type 3 pneumococcal capsular polysaccharide (PCP) antigen and the protective efficacy of Type 3 PCP antibodies in a rat model of cirrhosis. Cirrhosis with ascites was induced in male Sprague-Dawley rats by weekly gavage with CCl4. Cirrhotic and age-matched control rats were vaccinated with 25 micrograms of Type 3 PCP. Serum antibodies against Type 3 PCP were determined before vaccination and on postvaccination Days 5, 7, 10, 14, 21, 28, and 42 by radioimmunoassay. Maximum concentrations occurred at 7 days in cirrhotic rats and 10 to 14 days in control rats. Geometric mean Type 3 PCP antibody levels (ng AbN/ml) were higher in cirrhotic versus control rats before vaccination (75.9 versus 33.8; p = 0.011) and on post-vaccination Day 5 (626 versus 158; p = 0.008) and Day 7 (1,755 versus 493; p = 0.002). Postvaccination antibody from immunized control and cirrhotic animals provided passive immunity to Type 3 Streptococcus pneumoniae infection in mouse protection studies. Sham-immunized and PCP-immunized control and cirrhotic rats were challenged with 10(7) cfu Type 3 S. pneumoniae. Immunization was associated with a greater reduction in postchallenge mortality in control rats (91% reduced to 36%; p = 0.02) compared with cirrhotic rats (100% reduced to 83%; p = 1.0). Thus, the increased serum concentrations of functional, type-specific anticapsular antibody in vaccinated cirrhotic rats does not reverse their impaired resistance to Type 3 pneumococcal pneumonia.
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PMID:Effect of cirrhosis on the production and efficacy of pneumococcal capsular antibody in a rat model. 141 96


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