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

Male Fischer 344 (F344) rats were treated with phenobarbital + carbon tetrachloride (CCl4) for 16 weeks to induce liver cirrhosis. Another group of rats received 50 mg/kg iv suramin once a week for 16 weeks. The third group of rats was treated with both phenobarbital + CCl4 and suramin. After 16 weeks of suramin treatment, a massive periportal infiltration composed of macrophages, many of them containing glycosaminoglycans in their cytoplasm, mast cells, and other inflammatory cells were observed. This lesion was added to the liver cirrhosis caused by CCl4 in the group treated with suramin and CCl4. The changes in glycosaminoglycan metabolism caused by suramin did not influence the CCl4 cirrhosis. Since suramin has been reported to be a prototype of a new generation of antitumor compounds, we suggest caution in the use of chronic suramin treatment, especially in patients with livers which are already damaged.
 ...
PMID:Liver damaging effect of suramin in normal and carbon-tetrachloride treated rats. 178 Jun 43

The effect of D-penicillamine (Pe) on liver fibrosis-cirrhosis induced by chronic CCl4 and phenobarbital (Pb) administration in Fischer 344 male rats was studied. Morphometric analysis did not reveal a decrease in the amount of connective tissue fibers after Pe-treatment. Compared to the CCl4 and Pb-treated control groups, Pe had no significant effect on the concentrations of hydroxyproline, a parameter of collagen degradation, either; however, it increased the glycosaminoglycan concentrations. Lymphocyte stimulation by Con-A in the Pe-treated groups did not differ from that of the CCl4 and Pb-treated ones. According to our studies, Pe-treatment was ineffective in rats with liver fibrosis-cirrhosis induced by CCl4 and Pb administration. It seems that Pe can be effective only in the cirrhosis types accompanied by a considerable copper accumulation due to suppression of the toxic effects of copper.
 ...
PMID:The effect of D-penicillamine on CCl4-induced experimental liver cirrhosis. 178 39

The time-course of some alterations produced in erythrocytes during the onset of CCl4-induced liver cirrhosis was studied in rats. Erythrocyte membranes were isolated to measure Na+, K+ and Ca+2-ATPase activities. Membrane lipid composition was determined to calculate the cholesterol/phospholipid ratio and serum samples were used to measure lipoperoxidation. The results demonstrated that as CCl4 treatment progressed, serum lipoperoxidation and membrane cholesterol/phospholipid ratio increased while ATPase activities decreased. ATPase activities in red blood cells of cirrhotic rats were 50% below normal values but those determined in cells of animals treated simultaneously with CCl4 + silymarin were significantly improved. Silymarin co-treatment also preserved the normal cholesterol/phospholipid ratio in the membranes. Our results suggest that the measure of ATPase activities in erythrocytes membranes could be a simple, safe and useful early marker of liver damage and also valuable to test the effectiveness of a given drug therapy.
 ...
PMID:Erythrocyte defects precede the onset of CCl4-induced liver cirrhosis. Protection by silymarin. 184 33

To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
 ...
PMID:In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. 184 94

A common model for producing experimental liver cirrhosis is the administration of CCl4 to phenobarbital (PhB)-stimulated rats. However, concern may arise due to the complex actions of PhB upon liver metabolism. This study examined the role of PhB in the production of CCl4-induced liver cirrhosis in the rat. In addition, regenerative capacity of the liver after partial hepatectomy (PH) or portal branch ligation (PBL) was studied in cirrhotic rats, rats treated with CCl4 alone, and in PhB-treated controls. In rats given PhB throughout the CCl4-induction period, ascitic form of micronodular cirrhosis was found in 93% with only 3% mortality. In contrast, rats pretreated with PhB for only 2 weeks followed by CCl4 alone for 18 weeks did not develop liver cirrhosis. In most of the cirrhotic rats, PH induced hepatic regeneration associated with improved liver histology. PBL was less effective. Treatment with PhB alone for 10 weeks resulted in liver atrophy and reduced hepatic regenerative capacity. Impaired regeneration response was also found in rats treated with CCl4 alone. In conclusion, treatment with PhB throughout the CCl4-induction period seems necessary for the production of liver cirrhosis in rats. However, prolonged treatment with PhB alone results in liver atrophy and an impaired regenerative response. Therefore, though necessary for the cirrhotic model, PhB by itself has negative hepatotrophic influences which questions the thoroughness of the PhB/CCl4 experimental model.
 ...
PMID:Liver cirrhosis in rats: regeneration and assessment of the role of phenobarbital. 192 73

The experimental model of liver cirrhosis induced by intragastric administration of CCl4 reproduces not only the histological picture of the postnecrotic cirrhosis but also its pathophysiological features. Corrosion casts of livers affected by CCl4-induced cirrhosis show the loss of the lobular pattern. Once the cirrhosis has completely developed, the whole microvascular bed appears to be composed of groups of sinusoid nodules of diameters varying between 0.3 and 1.5 mm.. Pre- and post-sinusoidal vessels and anastomoses between the former and the latter are mainly located at the perinodular spaces. This microvascular situation modifies the normal perfusion gradient within the parenchyma. Nevertheless, it can allow a still viable function.
 ...
PMID:The hepatic microcirculation in experimental cirrhosis. A scanning electron microscopy study of microcorrosion casts. 194 31

Glucose homeostasis and fatty acid metabolism are abnormal in patients with cirrhosis. To assess the metabolic response to starvation in an animal model of cirrhosis, glycogen and fuel metabolism were characterized in rats with CCl4-induced cirrhosis studied 2 wk after 10 weekly doses of CCl4. Plasma concentrations of glucose and beta-hydroxybutyrate were not different between fed CCl4-treated and control rats, but plasma nonesterified fatty acid concentrations were higher in cirrhotic animals (0.25 +/- 0.01 vs. 0.39 +/- 0.04 mmol/L; p less than 0.05). After 12 hr of starvation, the plasma nonesterified fatty acid concentration had reached 0.58 +/- 0.04 mmol/L in CCl4-treated rats, compared with 0.38 +/- 0.04 mmol/L in control rats (p less than 0.05). The redistribution of the hepatic carnitine pool toward acylcarnitines, which is characteristic of starvation, was complete after fasting for 12 hr in the CCl4-treated rats, compared with the 24 hr required in control rats. In fed cirrhotic rats, liver glycogen content per gram liver was decreased by 64% compared with control rats (30.0 +/- 5.1 vs. 10.8 +/- 1.1 mg/gm liver wet wt; p less than 0.05). After 12-hr fasting, hepatic glycogen content had fallen to 14.3 +/- 3.9 and 4.8 +/- 0.4 mg/gm liver wet wt (p less than 0.05) in control and cirrhotic animals, respectively. To further characterize the status of glycogen metabolism in cirrhotic livers, activities of glycogen synthase and glycogen phosphorylase were determined. Hepatic active and total glycogen phosphorylase activities normalized to hepatocellular content were unaffected by CCl4 treatment, whereas total glycogen synthase activity was increased by 45%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Decreased hepatic glycogen content and accelerated response to starvation in rats with carbon tetrachloride-induced cirrhosis. 195 69

In order to explore the cellular source(s) and the behaviour of the collagenolytic activity previously described in rat liver homogenates, in the reversibility of experimental cirrhosis of the liver, enriched suspensions of hepatocytes and of sinusoidal liver cells were obtained by a procedure which employs low EDTA concentrations and no bacterial collagenase. Cell suspensions were prepared from three different groups of animals: 1) normal controls, 2) rats with CCl4-induced cirrhosis of the liver, and 3) rats with swine serum-induced cirrhosis of the liver. Animals were sacrificed in each group upon completion of treatment and also after 3, 6 and 12 months. In each liver wet weight and collagen concentration were determined, and collagenolytic activity of both enriched cell suspensions was measured separately. In addition, histological studies of liver tissue and ultrastructural examination of cell suspensions were performed by standard procedures. Enriched suspensions of both normal hepatocytes and sinusoidal liver cells display Ca2(+)-dependent collagenolytic activities. Both cell suspensions obtained from each of the two types of cirrhotic livers show normal or slightly increased average levels of collagenase activity at the time of treatment discontinuation, when average liver collagen content ranges from 6 to 10-fold over normal, suggesting that the normal collagenase/collagen ratio is disturbed and that collagenolytic activity is deeply decreased in relation to the actual liver collagen load.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Collagenase of hepatocytes and sinusoidal liver cells in the reversibility of experimental cirrhosis of the liver. 198 May 58

To study alterations in host defense mechanisms that enhance pneumococcal virulence, a model of Streptococcus pneumoniae pneumonia was developed in cirrhotic rats. Cirrhosis, with or without ascites, was produced in rats by intragastric administration of carbon tetrachloride (CCl4). Histopathologic and laboratory studies demonstrated that CCl4-induced cirrhosis was similar to alcoholic cirrhosis in humans. Cirrhotic rats were more susceptible to type 3 pneumococcal pneumonia induced by intratracheal challenge than controls, and the presence of ascites was associated with the lowest LD50. More cirrhotic rats with ascites had bacteremia and elevated levels of circulating capsular antigen after challenge compared with cirrhotic rats without ascites or controls. Pulmonary clearance of pneumococci was markedly reduced in rats with cirrhosis and ascites and was associated with reduced serum complement levels. This model may be useful in further studies of the pathogenesis and therapy of pneumococcal infections in the compromised host.
 ...
PMID:Pneumococcal pneumonia in a rat model of cirrhosis: effects of cirrhosis on pulmonary defense mechanisms against Streptococcus pneumoniae. 198 56

In the course of experimental CCl4-induced cirrhosis, an increase of the membrane-associated factor stimulating 3T3 cells' proliferation in vitro was observed. Gel filtration showed an approximate molecular mass of 150 kDa. Extraction of growth stimulatory activity by liver perfusion in situ demonstrated a peripheral plasma membrane protein localization. The activity increased with an increasing number of CCl4 treatments, reaching a maximum at the tenth intoxication, faster than the proliferation of connective tissues. Cessation of treatment caused a decrease in activity to the level of untreated liver, although the amount of fibroblast-like cells remained large, which is evidence in favour of an hepatocyte origin of the factor.
 ...
PMID:A correlation between liver plasma membrane-associated stimulatory activity (PMASA) and experimental cirrhosis formation. 199 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>