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)

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

The protective effect of 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A) and its two derivatives of 4-phenyl-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827B) and 4-(4-fluorophenyl)-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827C) on liver injury induced by carbon tetrachloride (CCl4) and orotic acid was studied using male rats. The approximate lethal doses were about 100 mg/kg for DT827A-treated animals and more than 800 mg/kg for the other two compounds-treated groups. Single oral administration of the three test compounds at the dose levels of 2 and 10 mg/kg 1 hour before CCl4 exposure revealed a protective effect on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in histopathological findings in livers in the order of DT827B-treated rats > DT827A-treated rats > DT827C-treated rats. Repeated oral administration of the compounds at the dose levels of 2 and 10 mg/kg/day for 10 consecutive days revealed a protective effect against liver injury on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in the order of DT827B-treated rats > DT827A-treated rats [symbol: see text] DT827C-treated rats. Simultaneous administration of the compounds at the dose level of 10 mg/kg/day together with a high sucrose diet containing orotic acid for 12 days revealed an inhibitory effect on fatty liver formation in the order of DT827B-treated rats > DT827C-treated rats > DT827A-treated rats. A hepatoprotective potential of the DT827 series compounds was suggested under the conditions of these studies, and DT827B was considered to be the most effective.
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PMID:Effect of 1,3-dithia-2-thioxo-cyclopent-4-ene and its derivatives on liver injury induced by carbon tetrachloride and orotic acid in rats. 944 51

The effects of carbon tetrachloride (CCl4) on the liver in spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) were investigated ultrastructurally in this study. Repetition of CCl4 treatment twice a week for four weeks, revealed liver cirrhosis in SHR, whereas, only bridging fibrosis was observed in the WKY, histologically, by reticulin silver impregnation. Scanning electron microscopy revealed that the liver surface of SHR was irregularly nodulated, while it was relatively smooth in case of the WKY. Transmission electron microscopy revealed that the mitochondria cristae were peripherally located in both strains. Vesicular change of the rough endoplasmic reticulum was observed to be more severe in SHR than in WKY. Further, local hypertrophy of the smooth endoplasmic reticulum and large lipid droplets were more easily observed in WKY than in SHR. The present results hence indicate that chronic chemical CCl4 intoxication induces severe ultrastructural organelle damage in hypertensive rats, leading to liver cirrhosis. On the other hand, CCl4 induced fatty liver and a relatively mild fibrosis were observed in normotensive rats. These findings suggest that the liver ultrastructural organelles are more susceptible to CCl4 in SHR than in WKY.
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PMID:Ultrastructural changes in liver damage induced by carbon tetrachloride in spontaneously hypertensive rats and Wistar-Kyoto rats. 968 7

Carbon tetrachloride-injected rats were given liquid diets with and without betaine for 7 d. Hepatic lipidosis was induced by 4 daily injections of carbon tetrachloride (CCl4). Animals were killed and their livers and blood taken for analysis of betaine, S-adenosylmethionine (SAM), betaine homocysteine methyltransferase (BHMT), triglyceride, alanine aminotransferase and aspartate aminotransferase. Liver samples were also processed and stained for histological examination. Supplemental betaine reduced triglyceride in the liver and centrilobular hepatic lipidosis induced by the CCl4 injections. In both the control and experimental groups receiving betaine, liver betaine, BHMT and SAM were significantly higher than in their respective groups not receiving betaine. This study provides evidence that betaine protects the liver against CCl4-induced lipidosis and may be a useful therapeutic and prophylactic agent in ameliorating the harmful effects of CCl4.
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PMID:Betaine reduces hepatic lipidosis induced by carbon tetrachloride in Sprague-Dawley rats. 977 59

The aim of the present work was to assess if the feeding of either the oil extract of Spirulina maxima or of its defatted fraction would prevent fatty liver development, induced in rats by a single intraperitoneal dose of carbon tetrachloride (CCl4). Liver and serum lipids were evaluated 4 days after treatment with this agent. Concentration of liver lipids did not differ in rats fed on a purified diet either without or with one of the fractions of Spirulina, except for total cholesterol, which showed a slight increase in the group receiving the oil extract of Spirulina. However, after CCl4 treatment, liver total lipids and triacylglycerols were significantly lower in rats fed on a diet containing any fraction of Spirulina (defatted or the oil fraction) than in rats without Spirulina in their diet. Furthermore, the increased liver cholesterol values, induced by CCl4 treatment, were not observed in rats receiving Spirulina. In addition, rats receiving whole Spirulina in their diet and treated only with the vehicle showed an increase in the percentage of HDL values. The changes in VLDL and LDL induced by CCl4 treatment were not observed in the whole Spirulina group. Furthermore, after CCl4 treatment the values of the liver microsomal thiobarbituric acid-reactive substances were lower in the whole Spirulina group than in the control group. These results support the potential hepatoprotective role of Spirulina.
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PMID:Studies on the preventive effect of Spirulina maxima on fatty liver development induced by carbon tetrachloride, in the rat. 1019 49

Eighty-five male Han-Wistar rats were arranged into three groups: CCl4-exposed rats, CCl4 + betaine-exposed rats, and control rats. To see the effect of betaine alone, five rats of the control and of the CCl4 + betaine groups were sacrificed after 7 days, before exposure to CCl4. After that, two of the groups (the CCl4 and CCl4 + betaine groups) were exposed to CCl4 (1 ml/kg per day subcutaneously [SC] for 4 consecutive days), and one of the groups (control group) was given olive oil (1 ml/kg per day SC for 4 consecutive days). At the start of the study (day 0), day 1, day 2, day 3, day 4, and 3 days after the last CCl4 and olive oil injections (day 7), samples of five rats per group were sacrificed, and the livers were taken for chemical analyses and histological examination. Oral betaine, after the acclimation period of a week, increased the number of mitochondria but not mitochondria size (day 0), compared with the case in control rats. Exposure to CCl4 resulted in centrilobular hepatic steatosis, and the administration of betaine significantly reduced this. Morphometric analyses also revealed that the addition of betaine increased the volume density of rough endoplasmic reticulum (RER) in the perinuclear areas of liver cell cytoplasm (day 7). Additionally, the administration of betaine prevented the reduction of Golgi complexes and mitochondrial figures in the cytoplasm observed after the exposures to CCl4. Also, the volume density of mitochondria was smallest in the CCl4-group, but the difference was not statistically significant. The results indicate that oral betaine either improves recovery or reduces the toxic effects of CCl4 on cell organelles in liver cells of male Han-Wistar rats.
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PMID:Reduction of carbon tetrachloride-induced hepatotoxic effects by oral administration of betaine in male Han-Wistar rats: a morphometric histological study. 1081 Sep 87

Microarray analysis of RNA from carbon tetrachloride (CCl4)-administered rat livers was performed at various time points to establish a global gene expression profile during injury and regeneration stages. A single dose of 1 ml/kg of CCl4 was given by ip injection, and the liver samples were obtained after 6, 24, 48 h, and 2 weeks. Histopathologic, biochemical, and immunohistochemical studies enabled the classification of the CCl4 effect into injury (6 and 24 h) and regeneration (48 h and 2 weeks) stages. The expression levels of 5180 clones on a custom rat gene microarray were analyzed and 587 clones yielded changeable gene expression on at least single time point. One hundred seventy-nine clones were classified as injury-specific clones, while 38 clones as regeneration-specific clones. Characteristic gene expression profiles could be associated with CCl4-induced gene expression with the disruption of lipid metabolism, which is known to cause the fatty liver induced by CCl4 treatment. In addition, induction of the transcripts for many ribosomal proteins was detected during the injury stage, particularly at the 24-h time point, despite the previous report of decreased protein synthesis rate upon CCl4 treatment. Several genes with known functions were also identified as CCl4-regulated genes. In conclusion, we established a global gene expression profile utilizing microarray analysis in rat liver upon acute CCl4 administration with a full chronological profile that not only covers injury stage but also later points of regeneration stage.
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PMID:Comprehensive analysis of differential gene expression profiles on carbon tetrachloride-induced rat liver injury and regeneration. 1596 42

Pretreatment with a methanolic extract of Ligularia fischeri var. spiciformis (Compositae) herb inhibited hepatotoxicities caused by CCl4, D-galactosamine (GalN), alpha-naphthylisothiocyanate (ANIT), and DL-ethionine in rats. An ethyl acetate (EtOAc) extract fractionated from the methanolic extract showed a strong inhibitory effect. A major component, 3,4-dicaffeoylquinic acid (DCQA), isolated from the methanolic extract was examined for antihepatotoxicity. Pretreatment with DCQA (5 and 10 mg/kg, p.o.) significantly reduced serum aminotransferases (alanine and aspartate), sorbitol dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, and lactate dehydrogenase activities during CCl4- or GalN-induced hepatotoxicity, suggesting that DCQA is a major principle for the antihepatotoxic activity of L. fischeri var. spiciformis. DCQA also partially restored bile flow and reduced total bilirubin and cholic acid concentrations in rats with ANIT-induced cholestasis. Treatment with DCQA inhibited the increase in triglyceride, cholesterol, and total lipids in DL-ethionine-induced fatty liver. These results support the traditionally held belief that this plant can be used for the treatment of jaundice and hepatic failure.
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PMID:In vivo antihepatotoxic effects of Ligularia fischeri var. spiciformis and the identification of the active component, 3,4-dicaffeoylquinic acid. 1617 46

The mechanism of carbon tetrachloride (CCl4)-induced hepatotoxicity, especially necrosis and fatty liver, has long been a challenging subject of many researchers from various fields over the past 50 years. Even though the mechanisms of tissue damages are different among chemicals and affected tissues, CCl4 has played a role as a key substance of tissue injury. A number of studies have been conducted and various hypotheses have been raised. As a result, several important basic mechanisms of tissue damages have emerged, involving metabolic activation, reactive free radical metabolites, lipid peroxidation, covalent binding and disturbance of calcium homeostasis. Recent studies also revealed inflammation and regeneration as important modification factors in the tissue injury. The author attempted to summarize the history of CCl4 research with some emphasis on the experiments done by the author and his colleagues. Their studies with isolated perfused rat liver suggest that covalent binding of CCl4 metabolites rather than lipid peroxidation has a significant role in the production of centrilobular necrosis following CCl4 administration. Further studies are necessary to unveil detailed mechanisms of hepatocyte necrosis induced by CCl4.
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PMID:[Learning toxicology from carbon tetrachloride-induced hepatotoxicity]. 1701 19


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