Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic lipid peroxidation in vivo or in vitro as measured by UV absorption spectra of microsomal lipids or by production of TBA-reacting substances by whole liver homogenates, was studied after acute or during prolonged administration of ethanol. No evidence of peroxidative derangement of liver microsomal lipids in vivo was detected in either experimental situation, while the production of TBA-reacting substances by pooled liver homogenates incubated in vitro appeared slightly increased. Treatment with reduced glutathione (GSH and 2-mercaptopropionylglycine (2-MPG) was able to reduce fatty liver in acute and prolonged ethanol dosing, as well as the production of TBA-reacting compounds. Similar effects were obtained with 3-amino-1,2,4-triazole which was assayed only in acute experiments. By contrast, hepatic triglyceride accumulation induced by a single intoxicating dose of ethanol was not affected by preventive treatment with pyrazole which seemed to act as a pro-oxidant agent as far as the production of TBA-reacting substances is concerned. The role of lipid peroxidation as a pathogenic mechanism for acute and chronic ethanol-induced hepatotoxicity is discussed in relation to the action of anti-oxidant compounds which are active in preventing liver injury. It is concluded that lipid peroxidation is unlikely to be an important mechanism in alcohol hepatotoxicity.
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PMID:Ethanol-induced hepatotoxicity; experimental observations on the role of lipid peroxidation. 72 5

Hepatic glutathione (GSH) S-transferase (GST) activity and the tissue distribution of a cationic GST were investigated in biopsy liver samples obtained from patients with alcoholic liver diseases. GST activities in alcoholic fatty liver were significantly high, whereas those in cirrhosis were significantly low compared with normal liver. In fatty liver, immunohistochemically, the staining of the enzyme was strongly positive in hepatocytes around intensive fatty metamorphosis. Then, using experimental chronic alcohol-fed rats, the changes in hepatic GST and GSH peroxidase (GPx) activities and lipid peroxide (LPO) and GSH contents in alcoholic fatty liver were evaluated. Hepatic GST isoenzymes were analyzed and tissue distribution of cationic and neutral GSTs was also investigated. Liver GSH content decreased at two weeks and increased at six weeks. Liver LPO content was elevated at four and six weeks and cytosolic GPx activity was enhanced at four weeks. Cytosolic GST activity was enhanced at six weeks. The cationic and neutral GST isoenzyme pattern was unchanged compared with normal liver. Immunohistochemically, the distribution and intensity of the staining of GSTs were essentially unchanged. There was no evidence of an increase in the GST isoenzyme with selen-independent GPx activity. However, GSTs were strongly stained in the hepatocytes with fatty droplets. Thus, in alcoholic fatty liver, hepatic GST and GPx activities are thought to be enhanced by different mechanisms. The elevated GPx activity may relate to the production of LPO. However, the enhancement of GST activity may result from some other causes which include the enzyme induction.
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PMID:Glutathione S-transferase in alcoholic fatty liver. 177 80

Orotic acid-induced fatty livers were examined by biochemical and immunohistochemical approaches. Lipid peroxide levels by the thiobarbituric acid method and glutathione-peroxidase (GSH-PO) activity in the liver homogenates from orotic administered rats were similar to those of controls. Immunohistochemical localization of GSH-PO in orotic acid-induced fatty liver was mainly observed in the portal zone of the hepatic lobules. This staining pattern of GSH-PO was similar to that of the controls. No remarkable changes in GSH-PO staining patterns were detected in orotic acid-induced fatty liver. Our data strongly suggested that no lipid peroxidation is actively involved in the genesis of fatty liver due to the administration of orotic acid, and GSH-PO a protective enzyme against lipid peroxidation, was not inhibited by orotic acid-induced fatty liver.
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PMID:Biochemical and immunohistochemical analysis of orotic acid-induced fatty liver. 181 53

Preliminary data on the liver damage following combined treatment with paracetamol and carbon tetrachloride in the rat are reported. Administration of a single dose of paracetamol (2000 mg/kg, os) was followed after 1 hour by an intraperitoneal injection of CCl4 (1.0 ml/Kg). Experiments in parallel were performed in rat given paracetamol or CCl4 alone. Our results indicate paracetamol induces a drastic decrease of hepatic GSH that appears in relation with a marked production of TBA-reacting compounds in liver tissue, while CCl4 does not modify the hepatic content of GSH and provokes a slight increase of TBA-reacting substances. Preventive treatment with paracetamol of rats intoxicated after 1 hour with carbon tetrachloride results in a partial protection against fatty liver and necrosis following haloalkane poisoning. On the other hand, the combined treatment with both the hepatotoxins was followed by a minor decrease of GSH. These data are discussed in considering a possible interaction of the two chemicals at the site of their activation.
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PMID:[Liver damage after paracetamol and carbon tetrachloride administration]. 744 87

Hydrazine hepatotoxicity in vivo, as manifested by triglyceride accumulation, depletion of ATP and reduced glutathione (GSH) was shown to be dose related. The effect of pretreatment of rats with various inhibitors and inducers of cytochrome P450 on these dose-response relationships was investigated. Pretreatment with the inhibitor piperonyl butoxide increased triglyceride accumulation whereas pretreatment with the inducers phenobarbital and beta-naphthoflavone (BNF) resulted in reduced triglyceride accumulation. Pretreatment with the inducers acetone and isoniazid also enhanced triglyceride accumulation. Only phenobarbital pretreatment also significantly reduced GSH and ATP depletion. A linear correlation was found between hepatic glutathione and ATP levels in non-pretreated animals given various doses of hydrazine. However, exponential relationships were found between hepatic triglycerides and both hepatic ATP and glutathione. The results suggest that i) the hepatotoxicity of hydrazine can be modulated by inducing or inhibiting particular isoenzymes of cytochrome P450, ii) ATP and GSH depletion may not be directly involved in the development of fatty liver.
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PMID:Influence of inducers and inhibitors of cytochrome P450 on the hepatotoxicity of hydrazine in vivo. 809 26

The glutathione (GSH) S-transferases are believed to have dual functions as hepatic detoxifying enzymes and intrahepatic binding proteins. Little is known about their alterations in human liver diseases. Therefore, we have studied the relationship between the enzyme activity and rose bengal (RB) binding in hepatic cytosol and plasma indocyanine green (ICG) kinetics in patients with various liver diseases. The enzyme activity was measured in samples of hepatic cytosol obtained from 52 patients. In addition, the content of cationic and neutral transferases was estimated in 17 biopsy samples by densitometry of Coomassie blue stained sodium dodecyl sulphate polyacrylamide gel electrophoretograms. RB binding studies also were performed on cytosol samples. ICG kinetic parameters were determined using the two-compartment open model in 17 patients who were given the dye (0.5 mg kg-1) intravenously. Correlations between the enzyme activity and liver function tests, content of the enzyme, RB binding and ICG kinetic parameters were evaluated. The following results were obtained. (1) The enzyme activities were high in alcoholic liver disease, fatty liver and Gilbert's syndrome, and low in cirrhosis. (2) The enzyme activities were positively correlated with serum cholinesterase activity, serum albumin level and hepaplastin test, and negatively correlated with ICG retention rate at 15 min. (3) The enzyme activity, its content and RB binding affinity of the cytosol were positively correlated with each other. (4) The enzyme activity was positively correlated with hepatic ICG distribution volume. These results are consistent with the role of the GSH S-transferases as ligandins in intracellular storage of dyes.
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PMID:Relationship between content of hepatic glutathione S-transferases and the kinetics of indocyanine green elimination in various liver diseases. 825 11

The effects of CP and antioxidants on fatty liver hemorrhagic syndrome (FLHS) in Japanese quail hens were studied. In Experiment 1, four treatments were arranged as a 2 x 2 factorial; dietary CP (18 or 24%) and reduced glutathione (GSH, 0 or 120 mg/kg diet) were the major variables, but cysteine and other amino acids were higher in the 24% CP diets. Negative control (NC1) and positive control (PC1) diets were also evaluated. In Experiment 2, the effects of vitamin E (VE) and GSH were evaluated in the presence and absence of adequate dietary sulfur amino acids. Negative control (NC2) and positive control (PC2) diets were used. In both experiments, liver hemorrhage was most severe in quail fed the diets that were formulated to induce hepatic steatosis and limit oxidant defense capability. Liver hemorrhage was least severe in quail fed the diets that were formulated to minimize liver lipid accumulation and support oxidant defenses. Histological evaluation of affected quail livers showed changes consistent with FLHS in chicken hens. In Experiment 1, neither CP concentration nor GSH supplementation influenced liver hemorrhage. In Experiment 2, liver hemorrhagic score was reduced from 3.8 to 2.7 (P < or = .05) by adding VE to the basal diet. The PC2 diet further depressed liver score to only 2.0 (P < or = .05). The data clearly show that Japanese quail are susceptible to FLHS and indicate that a combination of lipotropic and antioxidant nutrients is protective against hemorrhage, even when lipogenic demands are maximized by feeding diets devoid of added fat.
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PMID:Effect of dietary protein and selected antioxidants on fatty liver hemorrhagic syndrome induced in Japanese quail. 826 98

Arsenazo III (AIII) (100 mg/kg ip in saline) administration to Sprague-Dawley male rats 30 min before or 6 or 10 hr after CCl4 [1 ml/kg ip as a 20% (v/v) solution in olive oil] significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as demonstrated either by histology or by determination of isocitric acid dehydrogenase in plasma. AIII did not modify the CCl4 concentrations reaching the liver, the intensity of the covalent binding of CCl4-reactive metabolites to hepatic microsomal lipids, or the CCl4-promoted lipid peroxidation process at either 1 or 3 hr of poisoning. AIII administration enhanced glutathione (GSH) levels in liver and significantly prevented the CCl4-induced minor decreases in GSH content and the CCl4-induced increases in calcium content at 24 hr of intoxication. AIII treatment further enhanced the CCl4-induced decreases in body temperature of the poisoned rats. Results suggest that AIII's preventive effects might be related to its very well-known calcium-chelating properties, but that additional factors related to AIII's ability to increase GSH content in liver or to decrease body temperature of CCl4-intoxicated animals may also play a role.
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PMID:Prevention of CCl4-induced liver necrosis by the calcium chelator arsenazo III. 851 46

We have shown that urinary taurine level may be used as a biomarker of pathological and biochemical lesions. Detection of changes in the urinary concentration of this low molecular weight metabolite indicates biochemical lesions which may also be associated with pathological damage. Hepatotoxic compounds such as CCl4, galactosamine and thioacetamide that cause hepatic necrosis and compounds such as hydrazine and ethionine that cause fatty liver all result in elevated urinary taurine levels in rats. However compounds which do not cause liver damage, such as cycloheximide, also raise urinary taurine levels. All of these substances are known to or are believed to inhibit protein synthesis. Conversely, compounds which increase protein synthesis, such as phenobarbital and clenbuterol, significantly decrease urinary taurine levels. Compounds which interfere with hepatic GSH synthesis will also change urinary taurine levels. Thus, depletion of GSH with diethyl maleate or phorone decreases urinary taurine whereas inhibition of GSH synthesis with compounds such as buthionine sulphoximine increases urinary taurine levels. In isolated hepatocytes in vitro, leakage of taurine occurs in response to cytotoxic compounds such as hydrazine and allyl alcohol. However, total taurine levels were increased by the hepatotoxicant CCl4. Taurine synthesis is decreased by depletion of GSH with allyl alcohol in isolated hepatocytes. Therefore taurine levels are an important potential biomarker for biochemical lesions induced by chemicals both in vivo and in vitro, in particular changes in protein and GSH synthesis.
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PMID:Changes in taurine as an indicator of hepatic dysfunction and biochemical perturbations. Studies in vivo and in vitro. 891 50

A rapid and reproducible model of fatty liver in rats was developed by injecting corn oil (s.c.). In preliminary experiments, the mortality due to acute ethanol intoxication was significantly higher in this model of acutely fattened animals. Lipid peroxidation is a process that involves free radicals and consumes as substrate unsaturated fatty acids, which are present in great amounts in corn oil. Thus, in this work we explored whether the acute loads of corn oil increased hepatic lipid peroxidation. The three markers of cellular oxidative stress measured in fatty livers from rats injected with corn oil were: the production of thiobarbituric acid-reactive substances (TBARS), liver content of triacylglycerides (TAG), and total glutathione (GSH-GSSG). All were significantly modified. We also studied the effect of butylated hydroxytoluene (BHT), a free radical scavenger frequently used in the food industry to prevent lipid oxidation, and found that it prevented the effect of corn oil on TBARS and TAG but enhanced the depletion of GSH-GSSG caused by the acute administration of large loads of corn oil.
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PMID:Butylated hydroxytoluene prevents hepatic damage induced by food oil. 943 24


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