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)

Effects of inhibitors of arachidonic acid (AA) metabolism on the development of fatty liver, cirrhosis, glutathione-S-transferase placental form (GST-P)-positive nodules and the generation of 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid-reactive substances (TBARS), caused by a choline-deficient, L-amino acid-defined (CDAA) diet, were examined in male Fischer 344 rats by feeding CDAA diets supplemented with the inhibitors for 12 and 30 weeks. Acetylsalicylic acid (ASA) (at doses of 0.1 and 0.2%) and p-bromophenacylbromide (BPB) (0.1 and 0.2%) were used as inhibitors of, respectively, cyclo-oxygenase and phospholipase A2, and quercetin (QU) (0.75 and 1.5%) and nordihydroguaiaretic acid (NDGA) (0.1 and 0.2%) as inhibitors of lipoxygenase. None of the inhibitors affected the development of fatty liver caused by the CDAA diet. ASA at a doe of 0.2% almost completely prevented the appearance of cirrhosis, GST-P-positive nodules, 8-OHdG and TBARS in seven out of 11 (63.7%) rats. BPB at a dose of 0.2% also exerted inhibitory effects on all of these lesions but to a lesser extent than ASA. QU and NDGA exerted inhibitory effects limited to the GST-P-positive nodule case. The results indicate that a perturbed AA metabolism, particularly of the cyclo-oxygenase pathway, derived secondarily from depletion of labile methyl groups or phosphatidylcholine, might play key roles in the cirrhosis, hepatocarcinogenesis and oxidative stress caused by a CDAA diet. The results also indicated a possible involvement of the lipoxygenase pathway in hepatocarcinogenic processes.
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PMID:Inhibition by acetylsalicylic acid, a cyclo-oxygenase inhibitor, and p-bromophenacylbromide, a phospholipase A2 inhibitor, of both cirrhosis and enzyme-altered nodules caused by a choline-deficient, L-amino acid-defined diet in rats. 863 Nov 32

It is shown that chronic hepatobiliary pathology is associated with a fall in spontaneous metabolite conjugation related to reduced concentration of hepatic glutathione. There was also enhanced activity of glutathione-dependent enzymes. This indicates progress of compensatory processes associated with mobilization of detoxication phase 2, i.e. stimulation of conjugation processes under depression of cytochrome P-450 system. The authors ascertain high informative value of hepatic glutathione transferase in assessment of disease activity in patients with chronic active hepatitis and hepatic cirrhosis.
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PMID:[The clinical significance of the liver glutathione system in chronic lesions]. 917 70

The effects of green tea extract (GTE) on exogenous and endogenous models of rat liver carcinogenesis using diethylnitrosamine (DEN) and a choline-deficient, L-amino acid-defined (CDAA) diet were studied. For the exogenous carcinogenesis study, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal dose of 200 mg/kg body weight of DEN, partially hepatectomized at week 3, and administered GTE at doses of 0, 0.01 and 0.1% in the drinking water from week 2 for 10 weeks. For the endogenous carcinogenesis study, rats were fed the CDAA diet and simultaneously given GTE for 12 weeks. All rats were killed at the end of week 12. After DEN-initiation, the apparent numbers of glutathione S-transferase placental form-positive foci, assayed as putative preneoplastic lesions, were decreased by the administration of GTE, though their sizes were not altered. In contrast, GTE did not significantly reduce the numbers of the lesions induced by the CDAA diet or affect their sizes. While the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, were reduced by the GTE administration in both experimental models, GTE did not protect against the CDAA-diet-associated liver tissue damage in terms of either histology or plasma marker enzyme levels. We conclude that, while GTE may be a possible chemopreventive agent for nitrosamine-initiated hepatocarcinogenesis in the absence of chronic hepatocyte damage, it does not significantly inhibit lesion development in hepatocarcinogenesis associated with the CDAA diet, a cirrhosis-associated model.
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PMID:Inhibition by green tea extract of diethylnitrosamine-initiated but not choline-deficient, L-amino acid-defined diet-associated development of putative preneoplastic, glutathione S-transferase placental form-positive lesions in rat liver. 919 26

Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, the effect of which leads to liver damage.
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PMID:The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function. 924 25

Previously, we have reported that aspirin, a cyclooxygenase (COX) inhibitor, can prevent the fibrosis, cirrhosis and generation of oxidative DNA damage, and the associated development of glutathione-S-transferase placental form (GST-P)-positive preneoplastic liver nodules, caused by a choline-deficient, L-amino acid-defined (CDAA) diet in rats. In the present study, in order to elucidate the role of COX pathway in liver lesion-induction by a CDAA diet, the modulatory effects of other distinct chemical classes of COX inhibitors were examined. A long-acting example, piroxicam (PIRO) (at doses of 0.01, 0.02, 0.04 and 0.06%) and the short-acting ibuprofen (IBU) (at doses of 0.02, 0.04 and 0.06%) and indomethacin (IND) (at doses of 0.005 and 0.008%) were administered in the CDAA diet to male F344 rats, and animals were killed after 12 and 30 weeks. In another experiment, IND was given in drinking water at doses of 0.001, 0.002 and 0.004%. None of the inhibitors affected the development of fatty liver caused by a CDAA diet, but PIRO at doses higher than 0.04%, strongly inhibited the development of GST-P-positive and neoplastic nodules as well as fibrosis, cirrhosis and formation of 8-hydroxydeoxyguanosine (8-OHdG) adducts. IBU at the highest dose also exhibited similar but much less pronounced inhibitory effects. With IND, there was only a tendency for inhibition with no clear dose-dependence. The results together with our previous findings, indicate that relatively strong COX inhibitors, acting irreversibly like aspirin or for extended periods like PIRO, can prevent the endogenous hepatocarcinogenesis associated with a CDAA diet, although not the development of a fatty liver, suggesting that an augmented COX pathway might play key roles in the causation of liver lesions in this model.
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PMID:Inhibition by piroxicam of oxidative DNA damage, liver cirrhosis and development of enzyme-altered nodules caused by a choline-deficient, L-amino acid-defined diet in rats. 936 1

Intensive regeneration of cholangia and cholangioles, fibrosis, microglobular cirrhosis, vacuolar and granular dystrophy, and necrosis of hepatocytes were found in the liver of rats 36 days after ligation of the common bile duct. Lipid peroxidation was activated, the activity of the mono-oxidase system was inhibited in maintained function of glucuro- and glutathione transferase. Essentiale (per os in starch mucilage, 1 ml/kg. for 35 days) increased the activity of cytosol glutathione-S-transferase and normalized the decreased blood plasma antioxidant activity. Combination of essentiale with cordiamin (nikethamide) and viatmin E (50 mg/kg for 35 days) considerably activated the mono-oxigenase, glucoro- and glutathione transferase systems of the liver: the free-radical processes became less intense. The structure of the liver improves insignificantly in both methods of treatment.
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PMID:[The action of Essentiale and its combination with cordiamine and vitamin E on the processes of xenobiotic biotransformation and lipid peroxidation and on liver structure in rats with cholestasis]. 957 9

The nonenzymatic conjugation of metabolites is decreased in chronic diseases of the liver, which is caused by decreased concentration of glutathione. The activities of glutathione enzymes are increased, this indicating the development of compensatory processes of mobilization of the second phase of detoxication, that is, increased conjugation under conditions of suppression of the cytochrome P-450 system. Measurement of liver glutathione transferase is a highly informative test for assessing the activity of the pathological process, particularly important in patients with chronic active hepatitis and cirrhosis of the liver.
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PMID:[Activities of glutathione enzymes in liver biopsy specimens in chronic lesions of hepatocytes]. 962 74

Effects of inhibitors of arachidonic acid (AA) cascade on the development of fatty liver, cirrhosis, glutathione S-transferase placental form (GST-P)-positive preneoplastic nodules, neoplastic nodules and generation of 8-hydroxydeoxyguanosine (8-OHdG), caused by a choline-deficient, L-amino acid-defined (CDAA) diet, were examined in Fischer 344 male rats by feeding CDAA diet supplemented with the inhibitors for 12 and 30 weeks. None of the inhibitors affected fatty liver. Among cyclooxygenase (COX) inhibitors, an irreversibly acting acetylsalicylic acid and a long-acting piroxicam, and to a much lesser extent the short-acting ibuprofen but not indomethacin, inhibited the development of cirrhosis, GST-P-positive and neoplastic nodules and generation of 8-OHdG. A phospholipase A2 inhibitor p-bromophenacylbromide (BPB) also exerted similar but lesser extent of inhibitory effects. Lipoxygenase inhibitors quercetin and nordihydroguiaretic acid inhibited GST-P-positive nodules but not cirrhosis or 8-OHdG. Present results suggest that perturbed AA cascade, particularly augmented COX pathway, might play key roles in the causation of liver lesions in the CDAA diet model.
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PMID:Prevention by inhibitors of arachidonic acid cascade of liver carcinogenesis, cirrhosis and oxidative DNA damage caused by a choline-deficient, L-amino acid-defined diet in rats. 967 12

Biological tests are important for the diagnosis and the follow-up of viral chronic hepatitis. The viral hepatitis C is by far the most frequent. The etiologic diagnosis is based on serological or immunological tests which have good sensitivity and specificity, and may be completed by molecular biological methods. In contrast, the tests for the evaluation of the activity (necrosis and inflammation) and of the fibrosis are less informative than the histological study. The diagnosis and prognosis interpretation of the aminotransferases are well known, but other tests as alpha glutathione S-transferase or orosomucoid are also proposed for evaluation of the activity. Some parameters as PIIINP or hyaluronic acid may be useful in the diagnosis and follow-up of fibrogenesis, fibrosis and cirrhosis but some new molecules, as the metalloproteinases and their inhibitors, are presenting interesting future prospects. Biological tests also contribute to the diagnosis of an associated extra-hepatic pathology and of a possible hepatocellular carcinoma occurring on the cirrhotic liver.
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PMID:[Role of biology in the follow up of viral hepatitis]. 976 16

The effect of carbon tetrachloride (CCl4) on aflatoxin B1 (AFB1)-induced enzyme altered hepatic foci has been examined in young male Fischer rats given AIN-76A diet. A single i.p. dose of AFB1 (0.2 mg/kg body wt) was given to rats 24 h after partial hepatectomy. Two weeks later, CCl4 (0.8 ml/kg body wt) was injected i.p. once a week for 9 weeks. Animals were sacrificed 24 h after the last dose of CCl4 and glutathione S-transferase placental form (GST-P) and gamma-glutamyl transpeptidase (GGT) positive hepatic foci were analyzed by immunohistochemical and histochemical methods, respectively. Ten weeks after AFB1 dosing, treatment with CCl4 increased the number of AFB1-induced enzyme altered foci several fold and produced a ten to twenty-fold increase in area and volume. GST-P was more sensitive than GGT in detecting AFB1-induced enzyme altered foci. Treatment with AFB1 or CCl4 produced mild hepatic fibrosis in zones 1 and 3 respectively, whereas both treatments produced severe fibrosis in zones 1 to 3 areas. Treatment with CCl4 after AFB1 dosing lowered hepatic GSH levels by 20% and increased lipid peroxidation by 40%. It appears that CCl4, by being an effective enhancer of AFB1-induced enzyme altered hepatic foci in the rat, may mimic cirrhosis observed in human hepatocellular carcinoma.
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PMID:Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride. 989 47


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