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Sample records for carbon tetrachloride-induced liver

  1. Hepatoprotective effect of Centella asiatica (L in carbon tetrachloride-induced liver injury in rats

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    Antony B

    2006-01-01

    Full Text Available The present study was conducted to evaluate the hepatoprotective effects of the Centella asiatica extract in carbon tetrachloride-induced liver injury in rats. Sprague Dawley rats were treated with alcohol extract of Centella asiatica orally in two doses (20 and 40 mg/kg/day for 3 mo along with intraperitoneal injection of carbon tetrachloride (1 ml/kg. Biochemical parameters such as serum total protein, albumin and marker enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were estimated both before and after the experiment. Histopathological studies of liver were also carried out to confirm the biochemical changes. Carbon tetrachloride-induced hepatotoxic effects were evident by a significant (p < 0.05 increase in the serum marker enzymes and a decrease in the total serum protein and albumin. Administration of extract of Centella asiatica effectively inhibited these changes in a dose-dependent manner; maximum effect was with 40 mg/kg. Histopathological examination of liver tissue corroborated well with the biochemical changes. Hepatic steatosis, hydropic degeneration and necrosis were observed in carbon tetrachloride-treated group, while these were completely absent in the treatment group. Centella asiatica extract exhibited hepatoprotective action against carbon tetrachloride-induced liver injury. This effect is attributed to the presence of asiaticoside (14.5% in the extract.

  2. Transcriptome Analysis of the Effects of Gomisin A on the Recovery of Carbon Tetrachloride-Induced Damage in Rat Liver

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    Choi, Young Mi; Choi, In Soo; Lee, Sang Mong; Hwang, Dae Youn; Choi, Young Whan; Park, Young Hoon

    2011-01-01

    Gomisin A possesses a hepatic function-facilitating property in liver-injured rats. Its preventive action on carbon tetrachloride-induced cholestasis is due to maintenance of the function of the bile acids-independent fraction. To investigate alterations in gene expression after gomisin A treatment on injured rat liver, DNA microarray analyses were performed on a Rat 44K 4-Plex Gene Expression platform with duplicated reactions after gomisin A treatment. We identified 255 up-regulated and 230...

  3. Transcriptome analysis of the effects of gomisin a on the recovery of carbon tetrachloride-induced damage in rat liver.

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    Choi, Young Mi; Choi, In Soo; Lee, Sang Mong; Hwang, Dae Youn; Choi, Young Whan; Park, Young Hoon

    2011-06-01

    Gomisin A possesses a hepatic function-facilitating property in liver-injured rats. Its preventive action on carbon tetrachloride-induced cholestasis is due to maintenance of the function of the bile acids-independent fraction. To investigate alterations in gene expression after gomisin A treatment on injured rat liver, DNA microarray analyses were performed on a Rat 44K 4-Plex Gene Expression platform with duplicated reactions after gomisin A treatment. We identified 255 up-regulated and 230 down-regulated genes due to the effects of gomisin A on recovery of carbon tetrachloride-induced rat liver damage. For functional characterization of these genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes biochemical pathways analyses were performed. Many up-regulated or down-regulated genes were related to cell cycle or focal adhesion and cell death genes, respectively. Our microarray experiment indicated that the liver repair mechanism induced by gomisin A was strongly associated with increased gene expressions related to cell cycle and suppression of the gene expression related in cell death.

  4. Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice.

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    Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D

    2010-06-01

    The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

  5. Contribution of mononuclear bone marrow cells to carbon tetrachloride-induced liver fibrosis in rats

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    Bao-Qiang Cao; Ji-Zong Lin; Yue-Si Zhong; Shao-Bin Huang; Nan Lin; Zhao-Feng Tang; Rui Chen; Peng Xiang; Rui-Yun Xu

    2007-01-01

    AIM:To study the inhibitory effect of mononuclear bone marrow cell (BMC) transplantation on carbon tetrachloride (CCIt) -induced liver fibrosis in rats.METHODS:Rat liver fibrosis models were induced by CCN and alcohol administration. After 8 wk,twenty rats were randomly allocated into treatment group (n = 10) and control group (n = 10). BMC were infused into the rats in treatment group via the portal vein,while heparinized saline was infused in control group. CCU was hypodermically injected into the rats twice a week for 4 wk. At the end of wk 12,all rats were humanely sacrificed. Liver samples were taken and stained with HE or Masson trichrome. The general conditions,liver fibrSsis (hydroxyproline and collagen fibre) and liver pathological grades in rats were evaluated.± 128.8μg/g in treatment group,and 596.0 ± 341. 8μg/g in control group.The percentage of collagen fibre was 3.75% ± 0.98% in treatment group and 5.02% ± 0.44% in control group.There was a significant difference berween the two groups (P<0.05).Liver pathological grade decreased from grade Ⅳ to grade Ⅲ partially in treatment group (P<0.05) with no obvious improvement in control group (P<0.05).There was a significant difference between treatment group and control group(P<0.05).CONCLUSION: Transplantation of BMC can improve liver fibrosis due to chronic liver injury in rats.

  6. Hydrogen sulfide attenuates carbon tetrachloride-induced hepatotoxicity, liver cirrhosis and portal hypertension in rats.

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    Gang Tan

    Full Text Available BACKGROUND: Hydrogen sulfide (H(2S displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H(2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H(2S in carbon tetrachloride (CCl(4-induced hepatotoxicity, cirrhosis and portal hypertension. METHODS AND FINDINGS: Sodium hydrosulfide (NaHS, a donor of H(2S, and DL-propargylglycine (PAG, an irreversible inhibitor of cystathionine γ-lyase (CSE, were applied to the rats to investigate the effects of H(2S on CCl(4-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2S, hepatic H(2S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4 significantly reduced serum levels of H(2S, hepatic H(2S production and CSE expression. NaHS attenuated CCl(4-induced acute hepatotoxicity by supplementing exogenous H(2S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, hyaluronic acid (HA, albumin, tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6 and soluble intercellular adhesion molecule (ICAM-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA expression. PAG showed opposing effects to NaHS on most of the above parameters. CONCLUSIONS: Exogenous H(2S attenuates CCl(4-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H(2S may present a promising approach, particularly for its prophylactic effects, against liver

  7. Total Flavonoids from Mimosa Pudica Protects Carbon Tetrachloride-Induced Acute Liver Injur y in Mice

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    QIU Zhen-qin; CAI Lei; CHEN Da-shuai

    2015-01-01

    Objective:To observe the protective effect of total lfavonoids from Mimosa pudica on carbon tetrachloride (CCl4)-induced acute liver injury in mice. Methods:CCl4-induced acute liver injury model in mice was established. The activity of ALT and AST, the content of serum albumin (Alb) and total antioxidant capacity (T-AOC) were determined. The content of malondiadehyde (MDA) was measured and the activity of superoxide dismutase (SOD) was determined. The histopathological changes of liver were observed. Results:Compared with CCl4 model group, each dose group of total lfavonouida from Mimosa pudica could reduced the activity of ALT and AST in mice obviously (P<0.01), indicating they had remarkably protective effect on CCl4-induced acute liver injury in mice. High and middle dose groups of total lfavonouida from Mimosa pudica could increase the content of Alb in mice (P<0.01). Each dose group of total lfavonouida from Mimosa pudica could enhance the level of T-AOC (P<0.01), and lower the content of liver homogenate MDA, but enhance the activity of SOD in a dose-depended manner (P<0.01).

  8. Protection effect of kallistatin on carbon tetrachloride-induced liver fibrosis in rats via antioxidative stress.

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    Xiaoping Huang

    Full Text Available Prolonged inflammation and oxidative stress are emerging as key causes of pathological wound healing and the development of liver fibrosis. We have investigated the effects of recombinant human kallistatin, produced in Pichia. pastoris, on preventing carbon tetrachloride (CCl4-induced liver fibrosis in rats. Daily administration of kallistatin prevented development of CCl4-induced liver fibrosis, which was evidenced by histological study. In all kallistatin treated rats, activation of hepatic stellate cells (HSC as assessed by s-smooth muscle actin staining was attenuated, TGF- β1 expression was inhibited, class I serum biomarkers associated with the process of fibrogenesis, such as hyaluronic acid, laminin, and procollagen III, were lowered, compared with that in the model control group. Furthermore, residual hepatic functional reserve was improved by kallistatin treatment. CCl4 induced elevation of malondialdehyde level and reduced superoxide dismutase activity in the liver, while kallistatin reduced these oxidative parameters. We also investigated the effects of kallistatin on rat primary HSC and LX-2, the human HSC cell line. Kallistatin scavenged H2O2-induced ROS in the LX-2 cells, and suppressed the activation of primary HSC. These results suggest recombinant human kallistatin might be a promising drug candidate for therapeutic intervention of liver fibrosis.

  9. Effect of WeiJia on carbon tetrachloride induced chronic liver injury

    Institute of Scientific and Technical Information of China (English)

    Pik-Yuen Cheung; Jay Chun; Hsiang-Fu Kung; Meng-su Yang; Qi Zhang; Ya-Ou Zhang; Gan-Rong Bai; Marie Chia-Mi Lin; Bernard Chan; Chi-Chun Fong; Lin Shi; Yue-Feng Shi

    2006-01-01

    AIM: To study the effect of WeiJia on chronic liver injury using carbon tetrachloride (CCl4) induced liver injury animal model.METHODS: Wistar rats weighing 180-220g were randomly divided into three groups: normal control group (Group A), CCl4 induced liver injury control group (Group B) and CCl4 induction with WeiJia treatment group (Group C). Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCl4 in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week,Group C rats also received daily intraperitoneal injection of WeiJia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week (4 male, 3 female), and eighth week (4 male, 3 female) respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid (HA), type Ⅳ collagen (CIV), γ-glutamyl transferase (γ-GT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) immunohistochemistry were also performed.RESULTS: CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and Y-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L (P0.05) respectively, similar to normal control group (Group A), but significantly different from CCl4 induced liver injury control group (Group B). An increase in PCNA and decrease in a-SMA expression level was also observed.CONCLUSION: WeiJia could improve liver function and reduce liver fibrosis

  10. Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis.

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    Kang, Jung-Woo; Hong, Jeong-Min; Lee, Sun-Mee

    2016-05-01

    Liver fibrosis leads to liver cirrhosis and failure, and no effective treatment is currently available. Growing evidence supports a link between mitochondrial dysfunction and liver fibrogenesis and mitochondrial quality control-based therapy has emerged as a new therapeutic target. We investigated the protective mechanisms of melatonin against mitochondrial dysfunction-involved liver fibrosis, focusing on mitophagy and mitochondrial biogenesis. Rats were treated with carbon tetrachloride (CCl4) dissolved in olive oil (0.5 mL/kg, twice a week, i.p.) for 8 wk. Melatonin was administered orally at 2.5, 5, and 10 mg/kg once a day. Chronic CCl4 exposure induced collagen deposition, hepatocellular damage, and oxidative stress, and melatonin attenuated these increases. Increases in mRNA and protein expression levels of transforming growth factor β1 and α-smooth muscle actin in response to CCl4 were attenuated by melatonin. Melatonin attenuated hallmarks of mitochondrial dysfunction, such as mitochondrial swelling and glutamate dehydrogenase release. Chronic CCl4 exposure impaired mitophagy and mitochondrial biogenesis, and melatonin attenuated this impairment, as indicated by increases in mitochondrial DNA and in protein levels of PTEN-induced putative kinase 1 (PINK1); Parkin; peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α); nuclear respiratory factor 1 (NRF1); and transcription factor A, mitochondrial (TFAM). CCl4-mediated decreases in mitochondrial fission- and fusion-related proteins, such as dynamin-related protein 1 (DRP1) and mitofusin 2, were also attenuated by melatonin. Moreover, melatonin induced AMP-activated protein kinase (AMPK) phosphorylation. These results suggest that melatonin protects against liver fibrosis via upregulation of mitophagy and mitochondrial biogenesis, and may be useful as an anti-fibrotic treatment.

  11. Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice

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    Cheng, Ni; Wu, Liming; Zheng, Jianbin; Cao, Wei

    2015-01-01

    Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity. PMID:26508989

  12. Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice

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    Ni Cheng

    2015-01-01

    Full Text Available Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity.

  13. Hepatoprotective effects of Bupleurum exalatum extracts against carbon tetrachloride induced liver injury in rats

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    s Roozbehi

    2015-03-01

    Full Text Available Background & aim: Some of natural and synthetic products have antioxidant properties which protect the liver against the destructive factors. This study aimed to investigate the effect of Bupleurum exelatum (B. exalatum extracts on rat liver. Material and method: This experimental study was conducted at Yasouj University of Medical Sciences in 2013 on 50 healthy adult male Wistar rats. Animals were randomly divided into five equal groups: the normal group (receiving, olive oil, control and experiment groups receiving different dose of carbon tetrachloride and olive oil. The experiment group was given daily doses of 75, 150 and 300 mg per Kg of B. exalatum extract by gavage respectively. After two months, the liver enzymes, total protein, albumin and bilirubin in animal’s sera were measured. Data were analyzed by the SPSS software, using ANOVA and tuky-test. Result: The toxicant significantly (P < 0.05 increased the levels of ALT, AST, ALP, TB, DB, and decrease the level of TP and ALB. Oral administration of B. exalatum extracts showed a significant (P < 0.05 decrease in all the elevated serum and significant increase (P < 0.05 in TP and ALB levels at all usage doses. These results indicate the maximum recovery was observed in 300 mg/kg/day. The histopathological changes i.e. fatty changes, necrosis etc were partly or fully prevented in animals treated with the extracts. Conclusion: These findings suggest that the extract of B. exalatum possessed hepatoprotective activity, which could be linked to their phytochemical constituents and antioxidant activity this therefore requires further in-depth studies.

  14. Protective effects of polydatin from Polygonum cuspidatum against carbon tetrachloride-induced liver injury in mice.

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    Hong Zhang

    Full Text Available Polydatin is one of main compounds in Polygonum cuspidatum, a plant with both medicinal and nutritional value. The possible hepatoprotective effects of polydatin on acute liver injury mice induced by carbon tetrachloride (CCl(4 and the mechanisms involved were investigated. Intraperitoneal injection of CCl(4 (50 µl/kg resulted in a significant increase in the levels of serum aspartate aminotransferase (AST, alanine aminotransferase (ALT and hepatic malondialdehyde (MDA, also a marked enhancement in the expression of hepatic tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β, cyclooxygenase-2 (COX-2, inducible nitric oxide synthase (iNOS and nuclearfactor-kappa B (NF-κB. On the other hand, decreased glutathione (GSH content and activities of glutathione transferase (GST, superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GPx were observed following CCl(4 exposure. Nevertheless, all of these phenotypes were evidently reversed by preadministration of polydatin for 5 continuous days. The mRNA and protein expression levels of hepatic growth factor-beta1 (TGF-β(1 were enhanced further by polydatin. These results suggest that polydatin protects mice against CCl(4-induced liver injury through antioxidant stress and antiinflammatory effects. Polydatin may be an effective hepatoprotective agent and a promising candidate for the treatment of oxidative stress- and inflammation-related diseases.

  15. Ameliorative effect of Ganoderma lucidum on carbon tetrachloride-induced liver fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Wen-Chuan Lin; Wei-Lii Lin

    2006-01-01

    AIM: To investigate the effects of Reishi mushroom,Ganoderma lucidum extract (GLE), on liver fibrosis induced by carbon tetrachloride (CCl4) in rats.METHODS: Rat hepatic fibrosis was induced by CCl4.Forty Wistar rats were divided randomly into 4 groups:control, CCl4, and two GLE groups. Except for rats in control group, all rats were administered orally with CCl4(20%, 0.2 mL/100 g body weight) twice a week for 8weeks. Rats in GLE groups were treated daily with GLE (1 600 or 600 mg/kg) via gastrogavage throughout the whole experimental period. Liver function parameters,such as ALT, AST, albumin, and albumin/globulin (A/G)ratio, spleen weight and hepatic amounts of protein,malondiladehyde (MDA) and hydroxyproline (HP) were determined. Histochemical staining of Sirius red was performed. Expression of transforming growth factor β1(TGF-β1), methionine adenosyltransferase (MAT1) 1A and MAT2A mRNA were detected by using RT-PCR.RESULTS: CCl4 caused liver fibrosis, featuring increase in plasma transaminases, hepatic MDA and HP contents,and spleen weight; and decrease in plasma albumin,A/G ratio and hepatic protein level. Compared with CCl4group, GLE (600, 1 600 mg/kg) treatment significantly increased plasma albumin level and A/G ratio (P< 0.05)and reduced the hepatic HP content (P<0.01). GLE (1600 mg/kg) treatment markedly decreased the activities of transaminases (P< 0.05), spleen weight (P< 0.05) and hepatic MDA content (P<0.05); but increased hepatic protein level (P<0.05). Liver histology in the GLE (1600 mg/kg)-treated rats was also improved (P<0.01).RT-PCR analysis showed that GLE treatment decreased the expression of TGF-β1 (P< 0.05-0.001) and changed the expression of MAT1A (P<0.05-0.01) and MAT2A (P< 0.05-0.001).CONCLUSION: Oral administration of GLE significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.

  16. Xanthohumol prevents carbon tetrachloride-induced acute liver injury in rats.

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    Pinto, Carmen; Duque, Antonio L; Rodríguez-Galdón, Beatriz; Cestero, Juan J; Macías, Pedro

    2012-10-01

    Xanthohumol (XN), a prenyl flavonoid present in beer, prevents the acute hepatic injury induced by carbon tetrachloride (CCl4) in rats. Pre-treatment of rats with XN significantly reduced the increased liver weight observed in CCl4-intoxicated rats, normalised the increased values of plasma lactate dehydrogenase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities and reduced the incidence of histopathological alterations produced by CCl4. The oxidative stress induced by CCl4 administration elicited a significant decrease in the levels of reduced glutathione as well as an increase in thiobarbituric acid reactive substances (TBARS) and H2O2 concentrations. Pre-treatment of rats with XN resulted in a significant (p<0.05) increase in reduced glutathione (GSH) content and a reduction in TBARS and H2O2 concentrations to their normal values. XN pre-treatment also prevented the significant reductions of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase activities observed in CCl4-treated rats compared to control animals. Our results suggest that the hepatoprotective effect of XN is based on its antioxidant properties as well as it being an efficient inhibitor of lipid peroxidation and a protector against the degradation of antioxidant enzymes induced by CCl4 intoxication.

  17. Hepatoprotective effect of commercial herbal extracts on carbon tetrachloride-induced liver damage in Wistar rats

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    Paula Cordero-Pérez

    2013-01-01

    Full Text Available Background : Various hepatoprotective herbal products from plants are available in Mexico, where up to 85% of patients with liver disease use some form of complementary and alternative medicine. However, only few studies have reported on the biological evaluation of these products. Objective : Using a model of carbon tetrachloride (CCl4 -induced hepatotoxicity in rats, we evaluated the effects of commercial herbal extracts used most commonly in the metropolitan area of Monterrey, Mexico. Materials and Methods : The commercial products were identified through surveys in public areas. The effect of these products given with or without CCl4 in rats was evaluated by measuring the serum concentrations of aspartate amino transferase (AST and alanine amino transferase (ALT, and histopathological analysis. Legalon® was used as the standard drug. Results : The most commonly used herbal products were Hepatisan® capsules, Boldo capsules, Hepavida® capsules, Boldo infusion, and milk thistle herbal supplement (80% silymarin. None of the products tested was hepatotoxic according to transaminase and histological analyses. AST and ALT activities were significantly lower in the Hepavida+CCl4 -treated group as compared with the CCl4 -only group. AST and ALT activities in the silymarin, Hepatisan, and Boldo tea groups were similar to those in the CCl4 group. The CCl4 group displayed submassive confluent necrosis and mixed inflammatory infiltration. Both the Hepatisan+CCl4 and Boldo tea+CCl4 groups exhibited ballooning degeneration, inflammatory infiltration, and lytic necrosis. The silymarin+CCl4 group exhibited microvesicular steatosis. The Hepavida+CCl4 - and Legalon+CCL4 -treated groups had lower percentages of necrotic cells as compared with the CCl4 -treated group; this treatment was hepatoprotective against necrosis. Conclusion : Only Hepavida had a hepatoprotective effect.

  18. Hepatoprotective activity of Haridradi ghrita on carbon tetrachloride-induced liver damage in rats.

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    Satturwar, P M; Fulzele, S V; Joshi, S B; Dorle, A K

    2003-12-01

    Haridradi ghrita, a ghee based polyherbal formulation, (50, 100, 200 and 300 mg/kg) significantly lowered marker enzymes (SGPT, SGOT, ALP) and bilirubin in serum and liver peroxide, superoxide dismutase and catalase in liver homogenate following CCl4 (0.7 ml/kg, ip) toxicity. The protective effect was further supported by reversal of CCl4 induced histological changes. The results demonstrate significant hepatoprotective action of H. ghrita in CCl4 damaged rats.

  19. In vitro and in vivo protective effects of proteoglycan isolated from mycelia of Ganoderma lucidum on carbon tetrachloride-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Xiao-Jun Yang; Jing Liu; Lin-Bai Ye; Fan Yang; Li Ye; Jin-Rong Gao; Zheng-Hui Wu

    2006-01-01

    AIM: To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan (GLPG) isolated from Ganoderma lucidum mycelia, against carbon tetrachloride-induced liver injury.METHODS: A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTT assay.The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase (SOD) and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Liver sections were stained with hematoxylin and eosin (H&E) for histological evaluation and examined under light microscope.RESULTS: We found that GLPG can alleviate the L-02liver cells injury induced by carbon tetrachloride (CCl4)through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCl4 with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCl4 in mice liver. We also found that GLPG reduced TNF-α level induced by CCl4 in the plasma of mice, whereas increased SOD activity in the rat serum.CONCLUSION: GLPG has hepatic protective activity against CCl4-induced injury both in vitro and in vivo. The possible anti-hepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.

  20. High-fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by betaine treatment in rats.

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    Bingül, İlknur; Aydın, A Fatih; Başaran-Küçükgergin, Canan; Doğan-Ekici, Işın; Çoban, Jale; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-10-01

    Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine (BET) has antioxidant, antiinflammatory and hepatoprotective effects. However, the effects of BET on liver fibrosis development are unknown. Rats were treated with high-fat diet (60% of total calories from fat) for 14weeks. Carbon tetrachloride (0.2mL/kg; two times per week; i.p.) was administered to rats in the last 6weeks with/without commercial food containing BET (2%; w/w). Serum liver function tests and tumor necrosis factor-α, insulin resistance, hepatic triglyceride (TG) and hydroxyproline (HYP) levels and oxidative stress parameters were determined along with histopathologic observations. Alpha-smooth muscle-actin (α-SMA), transforming growth factor-β1 (TGF-β1) and type I collagen (COL1A1) protein expressions and mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were evaluated. BET decreased TG and HYP levels, prooxidant status and fibrotic changes in the liver. α-SMA, COL1A1 and TGF-β1 protein expressions, MMP-2, TIMP-1, and TIMP-2 mRNA expressions diminished due to BET treatment. BET has an antifibrotic effect and this effect may be related to its antioxidant and antiinflammatory actions together with suppression on HSC activation.

  1. Electroporative interleukin-10 gene transfer ameliorates carbon tetrachloride-induced murine liver fibrosis by MMP and TIMP modulation

    Institute of Scientific and Technical Information of China (English)

    Wen-ying CHOU; Cheng-nan LU; Tsung-hsing LEE; Chia-ling WU; Kung-sheng HUNG; Allan M CONCEJERO; Bruno JAWAN; Cheng-haung WANG

    2006-01-01

    Aim:Liver fibrosis represents a process of healing and scarring in response to chronic liver injury.Effective therapies for liver fibrosis are lacking.Interleukin-10 (IL-10) is a cytokine that downregulates pro-inflammatory responses and has a modulatory effect on hepatic fibrogenesis.The aim of this study was to investigate whether electroporative IL-10 gene therapy has an hepatic fibrolytic effect on mice.Methods:Hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) for 10 weeks in mice.The human IL-10 expression plasmid was delivered via electroporation after hepatic fibrosis was established.Histopathology,reverse transcription polymerase chain reaction (RT-PCR) ,immunoblotting,and gelatin zymography were used to investigate the possible mechanisms of action of IL-10.Results:Human IL-10 gene therapy reversed CCl4-induced liver fibrosis in mice.RT-PCR revealed that IL-10 gene therapy attenuated liver TGF-β1,collagen αl,fibronectin,and cell adhesion molecule mRNA upregulation.Following gene transfer,both the activation of α-smooth muscle actin and cyclooxygenase-2 were significantly attenuated.Furthermore.IL-10 significantly inhibited matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase (TIMP) activation after CCl4 intoxication.Conclusions:We demonstrated that IL-10 gene therapy attenuated CCl4-induced liver fibrosis in mice.IL-10 prevented upregulated fibrogenic and pro-inflammatory gene responses.Its collagenolytic effect may be attributed to MMP and TIMP modulation.IL-10 gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use.

  2. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  3. Antioxidant and Protective Effect of Ethyl Acetate Extract of Podophyllum hexandrum Rhizome on Carbon Tetrachloride Induced Rat Liver Injury

    Directory of Open Access Journals (Sweden)

    Showkat Ahmad Ganie

    2011-01-01

    Full Text Available The antioxidant and hepatoprotective activities of ethyl acetate extract was carefully investigated by the methods of DPPH radical scavenging activity, Hydroxyl radical scavenging activity, superoxide radical scavenging activity, hydrogen peroxide radical scavenging activity, and its reducing power ability. All these in vitro antioxidant activities were concentration dependent, which were compared with standard antioxidants such as BHT, α-tocopherol. The hepatoprotective potential of Podophyllum hexandrum extract was also evaluated in male Wistar rats against carbon tetrachloride- (CCl4- induced liver damage. Pretreated rats were given ethyl acetate extract at 20, 30, and 50 mg/kg dose prior to CCl4 administration (1 mL/kg, 1:1 in olive oil. Rats pretreated with P. hexandrum extract remarkably prevented the elevation of serum AST, ALT, LDH, and liver lipid peroxides in CCl4-treated rats. Hepatic glutathione levels were significantly increased by the treatment with the extract in all the experimental groups. The extract at the tested doses also restored the levels of liver homogenate enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase, and glutathione-S-transferase significantly. This study suggests that ethyl acetate extract of P. hexandrum has a liver-protective effect against CCl4-induced hepatotoxicity and possess in vitro antioxidant activities.

  4. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    Energy Technology Data Exchange (ETDEWEB)

    Hamdy, Nadia [Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-06-15

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  5. ABHRAK BHASMA MEDIATED ALTERATIONS IN LIVER AND KIDNEY FUNCTIONS IN MALE ALBINO RATS DURING CARBON TETRACHLORIDE INDUCED TOXICITY

    Directory of Open Access Journals (Sweden)

    Teli Parashuram

    2013-10-01

    Full Text Available Abhrak bhasma, an Ayurvedic drug used against many diseases including hepatitis. In present study various doses of abhrak bhasma (10, 20, 30 and 40 mg/kg body wt were tested for hepatoprotective efficacy against carbon tetrachloride (CCl4 intoxicated liver and kidney functions in male albino rat. Administration of CCl4 to the normal rat increased serum levels of AST, ALT, ALP and bilirubin indicated acute damage. Abhrak bhasma treatment counteracted the action of CCl4 on liver and kidney functions. With the administration of increasing doses of abhrak bhasma all activities were dropped progressively and significantly at 40 mg dose as compared with silicate control. Conjugation metabolism and excretion of bilirubin were improved with increasing doses of abhrak bhasma suggesting dose dependent protection of all metabolic steps in bilirubin metabolism. Also CCl4 induced acute toxicity increased serum urea and creatinine content, which was progressively controlled by increasing abhrak bhasma doses. The findings of this study indicated that abhrak bhasma exert dose dependent protective effects in liver and kidneys functions against CCl4 induced toxicity in albino rat.

  6. Management of carbon tetrachloride-induced acute liver injury in rats by syngeneic hepatocyte transplantation in spleen and peritoneal cavity

    Institute of Scientific and Technical Information of China (English)

    Charalampos Pilichos; Despina Perrea; Maria Demonakou; Athena Preza; Ismini Donta

    2004-01-01

    AIM: Acute hepatitis may seldom have a fulminant course.In the treatment of this medical emergency, potential liver support measure must provide immediate and sufficient assistance to the hepatic function. The goal of our study was to study the adequacy of hepatocyte transplantation (HCTx) in two different anatomical sites, splenic parenchyma and peritoneal cavity, in a rat model of reversible acute hepatitis induced by carbon tetrachloride (CCl4).METHODS: After CCl4 intoxication, 84 male Wistar rats used as recipients were divided in to four experimental groups accordingly to their treatment: Group A (n=24): intrasplenic transplantation of 10x106 isolated hepatocytes, Group B (n=24):intraperitoneal transplantation of 20xL06 isolated hepatocytes attached on plastic microcarriers, Group C (n= 18): i ntrasplenic injection of 1 mL normal saline (sham-operated controls),Group D (n=18): intraperitoneal injection of 2.5 mL normal saline (sham-operated controls). Survival, liver function tests (LFT) and histology were studied in all four groups, on d 2,5 and 10 post-HCTx.RESULTS: The ten-day survival (and mean survival) in the 4 groups was 72.2% (8.1±3.1), 33.3% (5.4±3.4), 0%(3.1±1.3) and 33.3% (5.4±3.6) in groups A, B, C, D,respectively (PAB<0.05, PAC<0.05, PBD=NS). In the final survivors, LFT (except alkaline phosphatase) and hepatic histology returned to normal, independently of their previous therapy. Viable hepatocytes were identified within splenic parenchyma (in group A on d 2) and both in the native liver and the fatty tissue of abdominal wall (in group B on d 5).CONCLUSION: A significantly better survival of the intrasplenically transplanted animals has been demonstrated.Intraperitoneal hepatocytes failed to promptly engraft. A different timing between liver injury and intraperitoneal HCTx may give better results and merits further investigation.

  7. Hepatoprotective activity of Chhit-Chan-Than extract powder against carbon tetrachloride-induced liver injury in rats

    Directory of Open Access Journals (Sweden)

    Yi-Chun Lin

    2014-06-01

    Full Text Available The capability of Chhit-Chan-Than extract powder (CCTEP, 10% aqueous Ocimum gratissimum L. extract to protect against carbon tetrachloride (CCl4-induced oxidative stress and hepatotoxicity in vivo was investigated. Wistar rats were divided into five groups. Group A was a normal control group given only vehicle; Group B, the hepatotoxic group, was injected intraperitoneally twice a week with repeated 8% CCl4/olive oil (0.1 mL/100 g of body weight; Groups C–E, extract-treated groups received CCl4 and different doses of CCTEP (100 mg/kg and 200 mg/kg or silymarin (200 mg/kg of body weight daily by gavage for 8 weeks, respectively. The results showed that the CCl4-induced histopathogical changes may be prevented by CCTEP through reducing the intercellular collogen stack, dropping blood serum alanine aminotransferase and aspartate aminotransferase levels, and restoring the catalase activity and glutathione content. The hepatoprotective properties were further confirmed by the marked improvement in histopathological examination and by quantitative steatosis-fibrosis scoring. The above results suggest that CCTEP is able to prevent the liver inflammation and fibrosis induced by repeated CCl4 administration, and the hepatoprotective effects might be correlated partly with its antioxidant and free radical scavenging effects.

  8. Hepatoprotective effect ofAverrhoea carambolafruit extract on carbon tetrachloride induced hepatotoxicity in mice

    Institute of Scientific and Technical Information of China (English)

    AK Azeem; Molly Mathew; Chandramohan Nair DilipC

    2010-01-01

    Objective:To investigate the hepatoprotective activity ofAverroha carambola fruit extract against carbon tetrachloride induced hepatic injury.Methods:Hepatotoxicity was induced on albino mice by intraperitoneal administration ofCCl4, half an hour after the administration of the last dose of the extract ofAverroha carambola fruit. Aqueous extract of the fruit ofAverroha carambola was administered at a dose of 0.9 g/kg body weight once daily for seven days. The hepatic injury and its prevention was assessed by the estimation of serum activities of alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphates(ALP), glutathione level and histopathological studies of liver.Results: Pre-treatment of mice with the fruit extract ofAverrhoea carambola significantly reduced serum levels ofALT, AST andALP enzyme and significantly increased the liver reduced glutathione levels24 h after the administration of carbon tetrachloride. A marked improvement in the enzyme activities and the liver reduced glutathione level was observed in the pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analysis. Conclusions:The aqueous extract of the fruit ofAverrhoea carambola has hepatoprotective effect against carbon tetrachloride induced liver damage in mice.

  9. Attenuation of Carbon Tetrachloride-Induced Hepatotoxicity by Cow Urine Distillate in Rats

    Institute of Scientific and Technical Information of China (English)

    M PGURURAJA; A B JOSHI; HIMANSHU JOSHI; D SATHYANARAYANA; E V S SUBRAHMANYAM; K S CHANDRASHEKHAR

    2009-01-01

    Objectives To study the carbon tetrachloride-induced hepatoprotective activity in cow urine. Methods Effect of cow urine distillate on liver function was studied in vivo in rats intoxicated with carbon tetrachloride (CCl4). Hepatotoxicity was induced by a 1:1 (v/v) mixture of CCl4 in olive oil (5 mL/kg i.p). Protective effect of cow urine distillate (in three dose levels) and standard drug Silymarin (100 mg/kg, p.o) on liver function were studied in intoxicated rats. Parameters in the study included liver function tests and histological observations. Results The cow urine distillate decreased the levels of SGOT, SGPT, ALP, GGT, and total bilirubin in a dose-dependent manner (P<0.05) as sylimarin. Conclusion The observed protective effects of cow urine distillate on liver function might be due to the presence of antioxidants in cow urine.

  10. HEPATOPROTECTIVE ACTIVITY OF ETHANOLIC EXTRACT OF ALTHAEA OFFICINALIS LINN AGAINST CARBON TETRACHLORIDE INDUCED HEPATOTOXICITY ON ALBINO WISTAR RATS

    OpenAIRE

    Jabbar Zoobi; Ali Mohd.

    2011-01-01

    In Indian traditional system of medicine, herbal remedies are prescribed for the treatment of various diseases including liver diseases. The present study was aimed to investigate the hepatoprotective activity of the ethanolic extract of Althaea officinalis against Carbon tetrachloride induced hepatotoxicity in rats. Liver function were assessed by the determination of SGPT and SGOT studies. The serum biochemical analysis results suggested that the use of ethanolic extract of Althaea officina...

  11. Schisandra Lignan Extract Protects against Carbon Tetrachloride-Induced Liver Injury in Mice by Inhibiting Oxidative Stress and Regulating the NF-κB and JNK Signaling Pathways

    Science.gov (United States)

    Chen, Qingshan; Zhan, Qi; Li, Ying; Sun, Sen; Zhao, Liang

    2017-01-01

    Schisandra chinensis (S. chinensis) is a traditional Chinese herbal medicine widely used for the treatment of liver disease, whose main active components are lignans. However, the action mechanisms of the lignans in S. chinensis remain unclear. This study aimed to investigate the protective effect and related molecular mechanism of Schisandra lignan extract (SLE) against carbon tetrachloride- (CCl4-) induced acute liver injury in mice. Different doses of SLE at 50, 100, and 200 mg/kg were administered daily by gavage for 5 days before CCl4 treatment. The results showed that SLE significantly decreased the activities of serum ALT/AST and reduced liver pathologic changes induced by CCl4. Pretreatment with SLE not only decreased the content of MDA but increased SOD, GSH, and GSH-Px activities in the liver, suggesting that SLE attenuated CCl4-induced oxidative stress. The expression levels of inflammatory cytokines TNF-a, IL-1β, and IL-6 were decreased after oral administration of SLE, probably because lignans inhibited the NF-κB activity. Additionally, SLE also inhibited hepatocyte apoptosis by suppressing JNK activation and regulating Bcl-2/Bax signaling pathways. In conclusion, these results suggested that SLE prevented CCl4-induced liver injury through a combination of antioxidative stress, anti-inflammation, and antihepatocyte apoptosis and alleviated inflammation and apoptosis by regulating the NF-κB, JNK, and Bcl-2/Bax signaling pathways.

  12. (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione protects rats from carbon tetrachloride-induced liver injury and fibrogenesis

    Institute of Scientific and Technical Information of China (English)

    Zhi-Zhi Chen; Li-Juan Chen; Yu-Quan Wei; Zheng-Lin Wang; Chong-Yang Deng; Hao Zheng; Xian-Huo Wang; Liang Ma; Xia Ye; Ying-Hua Ma; Cai-Feng Xie

    2012-01-01

    AIM:To evaluate the hepatoprotective roles of (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (SKLB010) against carbon tetrachloride (CCl4)-induced acute and chronic liver injury and its underlying mechanisms of action.METHODS:In the first experiment,rats were weighed and randomly divided into 5 groups (five rats in each group) to assess the protective effect of SKLB010on acute liver injury.For induction of acute injury,rats were administered a single intraperitoneal injection of 2 mL/kg of 50% (v/v) CCl4 dissolved in olive oil (1∶1).Group 1 was untreated and served as the control group; group 2 received CCl4 for induction of liver injury and served as the model group.In groups 3,4 and 5,rats receiving CCl4 were also treated with SKLB010 at doses of 25,50 and 100 mg/kg,respectively.Blood samples were collected at 6,12 and 24 h after CCl4 intoxication to determine the serum activity of alanine amino transferase.Tumour necrosis factor-α (TNF-α),interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay.At 24 h after CCl4 injection,liver fibrogenesis was evaluated by hematoxylin-eosin (HE) staining and immunohistochemical analyses.Cytokine transcript levels of TNF-α,IL-1β and inducible nitric oxide synthase in the liver tissues of rats were measured using a reverse transcriptase reverse transcription-polymerase chain reaction technique.In the second experiment,rats were randomly divided into 2 groups (15 rats in each group),and liver injury in the CCl4-administered groups was induced by a single intraperitoneal injection of 2 mL/kg of 50% (v/v) CCl4 dissolved in olive oil (1∶1).The SKLB010-treated groups received oral 100 mg/kg SKLB010 before CCl4 administration.Five rats in each group were sacrificed at 2 h,6 h,12 h after CCl4 intoxication and small fortions of livers were rapidly frozen for extraction of total RNA,hepatic proteins and glutathione (GSH) assays.In the hepatic fibrosis model group,rats were randomly divided into 2

  13. Puerarin attenuates carbon tetrachloride-induced liver oxidative stress and hyperlipidaemia in mouse by JNK/c-Jun/CYP7A1 pathway.

    Science.gov (United States)

    Ma, Jie-Qiong; Ding, Jie; Zhao, Hai; Liu, Chan-Min

    2014-11-01

    Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to investigate the effects of puerarin on hepatic oxidative stress and hyperlipidaemia in mice exposed to carbon tetrachloride (CCl4). Male ICR mice were injected with CCl4 with or without puerarin co-administration (200 and 400 mg/kg intragastrically once-daily) for 8 weeks. Our data showed that puerarin significantly prevented CCl4-induced hepatotoxicity, indicated by both diagnostic indicators of the liver damage (serum aminotransferase levels) and histopathological analysis. Puerarin decreased the thiobarbituric acid reactive substances (TBARS) and the protein carbonyl content (PCO) in the liver of CCl4-treated mice. Puerarin also restored the levels of reduced glutathione (GSH) and total antioxidant capacity (TAC) in the liver. Furthermore, the increase in serum cholesterol, triglycerides and low-density lipoproteins (LDL) induced by CCl4 was effectively suppressed by puerarin. The high-density lipoprotein (HDL) level in the CCl4 treatment mice was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidaemia by regulating the expression of phosphorylated Jun N-terminal kinases (JNK), phosphorylated c-Jun protein and cholesterol 7a-hydroxylase (CYP7A1) in the liver of CCl4-treated mice. Altogether, these results suggest that puerarin could protect the CCl4-induced liver injury and hyperlipidaemia by reducing reactive oxygen species S production, renewing the total antioxidant capacity and influencing expression of hepatic lipid biosynthesis and metabolism genes.

  14. The molecular mechanisms of the hepatoprotective effect of gomisin A against oxidative stress and inflammatory response in rats with carbon tetrachloride-induced acute liver injury.

    Science.gov (United States)

    Teraoka, Ryutaro; Shimada, Tsutomu; Aburada, Masaki

    2012-01-01

    Oxidative damage and inflammation are implicated in the pathogenesis of liver injury and fibrosis. In the present study, we investigated the molecular mechanism by which gomisin A conferred a hepatoprotective effect, focusing on its antioxidant and anti-inflammatory effects using rats with carbon tetrachloride (CCl(4))-induced acute liver injury. Pretreatment with gomisin A prior to the administration of CCl(4) markedly prevented an increase in alanine aminotransferase, aspartate aminotransferase, and histological hepatic lesions. Gomisin A was also associated with a decrease in hepatic lipid peroxidation, and increased superoxide dismutase activity, suggesting that gomisin A has an antioxidant effect. In addition gomisin A treatment ameliorated mRNA levels of CCl(4)-induced inflammatory mediators, including tumor necrosis factor-α, interleukin-1β and inducible nitric oxide (NO) synthase, and the protein levels of transcriptional upregulator nuclear factor kappa B (NF-κB) and phospho-inhibitor of NF-κB (IκB). Furthermore, α-smooth muscle actin (α-SMA), a myofibroblast marker, was also inhibited by gomisin A treatment. These results suggest that gomisin A inhibits the oxidative stress and activation of NF-κB, leading to down-regulation of pro-inflammatory mediators and amelioration of fibrogenesis.

  15. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Haw-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Li, Chien-Chun [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Ai-Hsuan; Huang, Yu-Ju [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Tsu-Shing [Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan (China); Yao, Hsien-Tsung, E-mail: htyao@mail.cmu.edu.tw [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei, E-mail: cklii@mail.cmu.edu.tw [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

    2014-10-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense

  16. Establishment of carbon tetrachloride-induced acute liver injury model in mice%四氯化碳致小鼠急性肝损伤动物模型建立方法的研究

    Institute of Scientific and Technical Information of China (English)

    周琼; 刘芳萍; 刘颖姝; 赵玉林; 李昌文; 李睿; 张秀英

    2012-01-01

    通过对染毒途径、剂量和时间的研究,建立四氯化碳(CCl4)致小鼠急性肝损伤模型.采取腹腔注射和灌胃两种途径给予小鼠1% CCl4,染毒后24h检测血清转氨酶含量,并观察肝脏病变.结果显示,灌胃组比腹腔注射组小鼠血清转氨酶变化个体差异小,肝脏病变明显,病灶分布均匀,且与实际中毒途径一致,故采用灌胃方法进行确定染毒剂量及时间试验.分别以0.125%、0.25%、0.35%、0.5%的CCl4给小鼠灌胃,染毒24h后检测血清转氨酶含量,确定最佳染毒剂量.以该浓度给小鼠灌胃,分别于染毒后2、6、12、16、20、24、28、32、48h检测小鼠血清转氨酶含量.结果表明,灌胃0.35% CCl4,小鼠血清转氨酶升高与对照组相比差异极显著(P<0.01),此浓度灌胃后,20h血清转氨酶含量显著升高(P<0.01),24h达到最高值,与对照组相比差异极显著(P<0.01).因此,以0.35%四氯化碳,按0.1mL·10g-1体重灌胃,染毒24h,可建立较理想的小鼠急性肝损伤模型.%Established the model of carbon tetrachloride-induced acute liver injury in mice by investigating the optimal exposure pathway, dose and time. Mice were prepared with 1% CCU by intraperitoneal injection and gavage respectively. Serum transaminase levels were detected and liver lesions were examined after 24 h. The results showed that individual difference of serum transaminase level in gavage group was smaller than intraperitoneal injection group, liver lesions were more uniform. Optimal dose and time was investigated by gavage because it has the same poisoning way with reality. Mice were given carbon tetrachloride in oil solution by gavage, with concentration of 0.125%, 0.25%, 0.35% and 0.5%. Detected serum transaminase levels after 24 h to measure optimal exposure dose. Serum transaminase levels was detected at 2,6,12,16, 20, 24, 28, 32, 48 h after mice were expoed to optimal dose of CCU. The results showed that mice received 0.35% CCU

  17. Telmisartan ameliorates carbon tetrachloride-induced acute hepatotoxicity in rats.

    Science.gov (United States)

    Atawia, Reem T; Esmat, Ahmed; Elsherbiny, Doaa A; El-Demerdash, Ebtehal

    2017-02-01

    This study assessed the potential hepatoprotective effect of telmisartan (TLM), a selective angiotensin II type 1 (AT1 ) receptor blocker, on carbon tetrachloride (CCl4 )-induced acute hepatotoxity in rats. Intraperitoneal injection of male Wistar rats with CCl4 1 mL kg(-1) , 1:1 mixture with corn oil for 3 days increased serum alanine transaminase, aspartate transaminase, and alkaline phosphatase activities as well as total bilirubin, triglycerides and total cholesterol levels. This is in addition to the disrupted histological architecture in the CCl4 group. Rats receiving CCl4 and co-treated with TLM (3 and 10 mg kg(-1) , orally) showed ameliorated serum biochemical and histological changes almost to the control level. Nevertheless, rats treated with TLM (1 mg kg(-1) ) didn't show any significant changes compared to CCl4 intoxicated group. In addition, TLM rectified oxidative status disrupted by CCl4 intoxication. Interestingly, TLM protected against CCl4 -induced expressions of nuclear factor-κB, inducible nitric oxide synthase and cyclooxygenase-II, in a dose related manner. Moreover, TLM (3 and 10 mg kg(-1) ) significantly modified CCl4 -induced elevation in tumor necrosis factor-α and nitric oxide levels. Furthermore, TLM showed a marked decline in CD68+ cells stained areas and reduced activity of myeloperoxidase enzyme compared to CCl4 -intoxicated group. In conclusion, both doses of TLM (3 and 10 mg kg(-1) ) showed significant hepato-protective effects. However, TLM at a dose of 10 mg kg(-1) didn't show significant efficacy above 3 mg kg(-1) which is nearly equivalent to the human anti-hypertensive dose of 40 mg. Thus, may be effective in guarding against several hepatic complications due to its antioxidant and anti-inflammatory activities. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 359-370, 2017.

  18. Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats.

    Science.gov (United States)

    Mochizuki, Masahiro; Shimizu, Satomi; Urasoko, Yoshinaka; Umeshita, Kazuhiko; Kamata, Takashi; Kitazawa, Takahiro; Nakamura, Daichi; Nishihata, Yoshito; Ohishi, Takumi; Edamoto, Hiroshi

    2009-04-01

    Carbon tetrachloride (CCl4) is well known to induce hepatotoxicity after being metabolized to trichloromethyl free radical ((.)CCl3) by CYP2E1. In the present study, the hepatotoxicity induced by a single oral dose (2,000 mg/kg) of CCl4 was compared between pregnant (gestation days (GD) 13 and 19) or postpartum (postpartum days (PPD) 1, 13 and 27) and non-pregnant rats. Hepatotoxicity in CCl4-treated pregnant rats evaluated by blood chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities) and histopathological finding (area of damaged hepatocytes) was minimal on GD19, being weaker than that in non-pregnant rats. CYP2E1 expression in non-treated pregnant rats decreased as pregnancy progressed and reached minimum level on GD19. Thus, the degree of CCl4-induced hepatotoxicity roughly corresponded to CYP2E1 levels during pregnancy. After delivery, hepatotoxicity in CCl4-treated lactating rats was maximal on PPD13, being stronger than that in non-pregnant rats, and then it decreased slightly on PPD27. The CYP2E1 level in the non-treated lactating rats tended to increase but remained at lower levels until PPD13 compared with that in non-pregnant rats. Thus, the degree of CCl4-induced hepatotoxicity did not correspond to CYP2E1 levels during lactation. This suggests that during lactation, there may be certain factors other than CYP2E1 expression responsible for the degree of CCl4-induced hepatotoxicity.

  19. Effect of Apitherapy Formulations against Carbon Tetrachloride-Induced Toxicity in Wistar Rats after Three Weeks of Treatment

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    Calin Vasile Andritoiu

    2014-08-01

    Full Text Available The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the influence of the apitherapy diet in Wistar rats with carbon tetrachloride-induced hepatotoxicity, by analyzing the biochemical determinations (enzymatic, lipid and protein profiles, coagulation parameters, minerals, blood count parameters, bilirubin levels and histopathological changes at the level of liver, spleen and pancreas. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution. Two mL per 100 g were administered, every 2 days, for 2 weeks. Hepatoprotection was achieved with two apitherapy diet formulations containing honey, pollen, propolis, Apilarnil, with/without royal jelly. Biochemical results reveal that the two apitherapy diet formulations have a positive effect on improving the enzymatic, lipid, and protein profiles, coagulation, mineral and blood count parameters and bilirubin levels. The histopathological results demonstrate the benefits of the two apitherapy diet formulations on reducing toxicity at the level of liver, spleen and pancreas in laboratory animals.

  20. Synthesis of platelet-activating factor and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Yin-Ying Lu; Chun-Ping Wang; Lin Zhou; Yan Chen; Shu-Hui Su; Yong-Yi Feng; Yong-Ping Yang

    2008-01-01

    AIM:To determine the platelet-activating factor (PAF)synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induce dcirrhosis.METHODS:Kupffer cells,isolated from the livers of control and CCl4-induced cirrhotic rats,were placed in serum-free medium overnight.PAF saturation binding,ET-1 saturation and competition binding were assayed.ET-1 induced PAF synthesis,mRNA expression of PAF,preproendothelin-1,endothelin A (ETA) and endothelin B (ETB) receptors were also determined.RESULTS:A two-fold increase of PAF synthesis (1.42±0.14 vs 0.66±0.04 pg/μg DNA) and a 1.48-fold increase of membrane-bound PAF (1.02±0.06 vs 0.69±0.07 Pg/μg DNA) were observed in activated Kupffer cells of cirrhotic rats.The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor,but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells.In activated Kupffer cells,PAF receptor expression and PAF binding capacity were markedly enhanced.Activated Kupffer cells raised the [125I]-ET-1 binding capacity,but changed neither the affinity of the receptors,nor the expression of ETA receptor.CONCLUSION:Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF.ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine.ETA receptor did not appear in activated Kupffer cells,which may exacerbate the hepatic and extrahepatic complications of cirrhosis.

  1. Hepatoprotective activity of Ficus carica Linn leaf extract against carbon tetrachloride-induced hepatotoxicity in rats

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    Mohan G.K.

    2007-06-01

    Full Text Available The methanol extract of the leaves of Ficus carica Linn. (Moraceae was evaluated for hepatoprotective activity in rats with liver damage induced by carbon tetrachloride. The extract at an oral dose of 500 mg/kg exhibited a significant protective effect by lowering the serum levels of aspartate aminotransferase, alanine aminotransferase, total serum bilirubin, and malondialdehyde equivalent, an index of lipid peroxidation of the liver. These biochemical observations were supplemented by histopathological examination of liver sections. The activity of extract was also comparable to that of silymarin, a known hepatoprotective. 

  2. Carbon tetrachloride-induced hepatotoxicity: Protective effect of 'Rocket' Eruca sativa L. in rats.

    Science.gov (United States)

    Alqasoumi, Saleh

    2010-01-01

    The hepatoprotective and antioxidant effect of an ethanolic extract of 'Rocket' Eruca sativa L. (EER), on liver injury induced by carbon tetrachloride (CCl(4)) was investigated. Wistar albino rats were administered 250 and 500 mg/kg body weight extract orally for 10 consecutive days. Marker enzymes GOT, GPT, ALP, GGT and bilirubin were estimated in serum. Whereas, non-protein sulfhydryl (NP-SH), total protein (TP) and malondialdehyde (MDA) were estimated in liver tissue as markers for oxidative stress. Histopathological assessment was also done on liver tissue. CCl(4) induced liver poisoning in all treated animals was evident by elevated serum GOT, GPT, ALP, GGT and bilirubin levels. Induction of oxidative stress in the liver tissue by CCl(4) was evidenced by a fall in the levels of NP-SH and TP; and an increased level of MDA concentration. EER administration for 10 days prevented the CCl(4) induced hepatic injury and oxidative stress. Furthermore, the extract also reduced the pentobarbital-induced prolongation of sleeping time in mice. The ability of rocket extract to protect the liver toxicity in rats was further confirmed by histological findings in the liver tissue. In conclusion, it was observed that Eruca sativa L. extract protects the liver against CCl(4) induced hepatic injury through its potent antioxidant activity in rats.

  3. HEPATOPROTECTIVE ACTIVITY OF ALSTONIA SCHOLARIS FRUITS AGAINST CARBON TETRACHLORIDE-INDUCED HEPATOTOXICITY IN RATS

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    K. RAVI SHANKAR, A. LAKSHMANA RAO, L. KALYANI

    2013-09-01

    Full Text Available The hepatoprotective activity of ethanolic extract of fruits of Alstonia scholaris was evaluated by carbon tetrachloride (CCL4-induced hepatotoxicity in rats. The toxicant CCL4 was used to induce hepatotoxicity at a dose of 2 ml/kg as 1:1 mixture with olive oil. The ethanolic extract of fruits of Alstonia scholaris was administered in the dose of 150 and 300 mg/kg/day orally for 5 days. Silymarin (50 mg/kg was used as standard drug. The hepatoprotective effect of the ethanolic extract was evaluated by the assessment of biochemical parameters such as SGOT, SGPT, SALKP, total bilirubin and histopathological studies of the liver. Treatment of animals with the ethanolic extract significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver as indicated by lower levels of serum bilirubin as compared with the normal and silymarin treated groups.

  4. Hepatoprotective effect of Origanum vulgare in Wistar rats against carbon tetrachloride-induced hepatotoxicity.

    Science.gov (United States)

    Sikander, Mohammad; Malik, Shabnam; Parveen, Kehkashan; Ahmad, Maqsood; Yadav, Deepak; Hafeez, Zubair Bin; Bansal, Manish

    2013-04-01

    The effect of an aqueous extract of Origanum vulgare (OV) leaves extract on CCl4-induced hepatotoxicity was investigated in normal and hepatotoxic rats. To evaluate the hepatoprotective activity of OV, rats were divided into six groups: control group, O. vulgare group, carbon tetrachloride (CCl4; 2 ml/kg body weight) group, and three treatment groups that received CCl4 and OV at doses of 50, 100, 150 mg/kg body weight orally for 15 days. Alanine amino transferase (ALT), alkaline phosphatase (ALP), and aspartate amino transferase (AST) in serum, lipid peroxide (LPO), GST, CAT, SOD, GPx, GR, and GSH in liver tissue were estimated to assess liver function. CCl4 administration led to pathological and biochemical evidence of liver injury as compared to controls. OV administration led to significant protection against CCl4-induced hepatotoxicity in dose-dependent manner, maximum activity was found in CCl4 + OV3 (150 mg/kg body weight) groups and changes in the hepatocytes were confirmed through histopathological analysis of liver tissues. It was also associated with significantly lower serum ALT, ALP, and AST levels, higher GST, CAT, SOD, GPx, GR, and GSH level in liver tissue. The level of LPO also decreases significantly after the administration of OV leaves extract. The biochemical observations were supplemented with histopathological examination of rat liver sections. Thus, the study suggests O. vulgare showed protective activity against CCl4-induced hepatotoxicity in Wistar rats and might be beneficial for the liver toxicity.

  5. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin.

    Science.gov (United States)

    Al-Harbi, Naif O; Imam, Faisal; Nadeem, Ahmed; Al-Harbi, Mohammed M; Iqbal, Muzaffar; Ahmad, Sheikh Fayaz

    2014-08-01

    Liver is a vital organ for the detoxification of toxic substances present in the body and hepatic injury is associated with excessive exposure to toxicants. The present study was designed to evaluate the possible hepatoprotective effects of riboflavin against carbon tetrachloride (CCl4) induced hepatic injury in rats. Rats were divided into six groups. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl4 in experimental rats. Riboflavin was administered at 30 and 100mg/kg by oral gavage to test its protective effect on hepatic injury biochemically and histopathologically in the blood/liver and liver respectively. The administration of CCl4 resulted in marked alteration in serum hepatic enzymes (like AST, ALT and ALP), oxidant parameters (like GSH and MDA) and pro-inflammatory cytokine TNF-α release from blood leukocytes indicative of hepatic injury. Changes in serum hepatic enzymes, oxidant parameters and TNF-α production induced by CCl4 were reversed by riboflavin treatment in a dose dependent manner. Treatment with standard drug, silymarin also reversed CCl4 induced changes in biomarkers of liver function, oxidant parameters and inflammation. The biochemical observations were paralleled by histopathological findings in rat liver both in the case of CCl4 and treatment groups. In conclusion, riboflavin produced a protective effect against CCl4-induced liver damage. Our study suggests that riboflavin may be used as a hepato-protective agent against toxic effects caused by CCl4 and other chemical agents in the liver.

  6. Protective effects of sodium molybdate on carbon tetrachloride-induced hepatotoxicity in rats.

    Science.gov (United States)

    Eidi, Akram; Eidi, Maryam; Al-Ebrahim, Mahsa; Rohani, Ali Haeri; Mortazavi, Pejman

    2011-01-01

    Molybdenum is an essential trace micronutrient element that plays an important role in animal and plant physiology. Molybdenum is a constituent of at least three mammalian metalloflavoproteins: xanthine oxidase, aldehyde oxidase and sulphite oxidase. In the present study, the hepatoprotective potential of sodium molybdate was investigated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Administration of CCl(4) increased the serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in rats and reduced levels of the antioxidant enzymes superoxide dismutase and catalase in the liver. Treatment with sodium molybdate significantly attenuated these changes to nearly undetectable levels. The histopathological changes induced by CCl(4) were also significantly attenuated by sodium molybdate treatment. Therefore, the results of this study suggest that sodium molybdate can protect the liver against CCl(4)-induced oxidative damage in rats, and this hepatoprotective effect might be attributable to its modulation of detoxification enzymes and/or its antioxidant and free radical scavenger effects.

  7. Hepatoprotective and antioxidant activity of pentagamavunon-0 against carbon tetrachloride-induced hepatic injury in rats

    Institute of Scientific and Technical Information of China (English)

    Arief Nurrochmad; Supardjan Amir Margono; Sardjiman; Arief Rahman Hakim; Ernawati; Erna Kurniawati; Erva Fatmawati

    2013-01-01

    Objective: To investigate the hepatoprotective and antioxidant activity of pentagamavunon-0(PGV-0) against CCl4-induced hepatic injury in rats. Methods: The groups of animals were administered with PGV-0 at the doses 2.5, 5, 10, and 20 mg/kg b.w., p.o. once in a day for 6 days and at day 7 the animals were administrated with carbon tetrachloride (CCl4) (20%, 2 mL/kg b.w. in liquid paraffin (i.p.). The effect of PGV-0 on serum transaminase (SGPT), alkaline phosphates (ALP) and total bilirubin were determined in CCl4-induced hepatotoxicity in rats. Further, the effects of PGV-0 on glutathione (GSH) content, catalase (CAT) and NO free radical scavenging activity also were investigated. Results: The results demonstrated that PGV-0 significantly reduced the activity of SGPT, serum ALP and total bilirubin in CCl4 induced rat hepatotoxicity. PGV-0 has effect on the antioxidant and free radical defense system. It prevented the depletion level of GSH and decrease activity of CAT in CCl4-induced liver injury in rats. PGV-0 also demonstrated the free radical scavenger effects on NO free radical scavenging activity with ES value of 32.32 μM. Conculsion: All of our findings suggests that PGV-0 could protect the liver cells from CCl4-induced liver damages and the mechanism may through the antioxidative effect of PGV-0 to prevent the accumulation of free radicals and protect the liver damage.

  8. Hepatoprotective mechanism of lycorine against carbon tetrachloride induced toxicity in swiss albino mice - A proteomic approach

    Institute of Scientific and Technical Information of China (English)

    Soundarrajan Ilavenil; Dhanaraj Karthik; Mariadhas Valan Arasu; Mayakrishnan Vijayakumar; Srisesharam Srigopalram; Selvaraj Arokiyaraj; Sivanesan Ravikumar; Ki Choon Choi

    2015-01-01

    Objective: To investigate the differential of protein expression in CCl4 induced mice treated with lycorine. Methods: The present study was carried out to identify the differentially expressed protein in carbon tetrachloride (CCl4) induced oxidative stress mice treated with lycorine (5 mg/kg. bw) using 2D gel and MALDI-TOF. Results: We observed many kinds of differentially expressed protein in experimental liver. Among these, three are much differently expressed protein which is identified as ATP synthase, regucalcin and HSP60; these proteins are involved in the ATP synthesis, calcium regulation and rescue the integrity cellular proteins respectively. Conclusion: This investigation provided a molecular mechanism of the lycorine during CCl4 induced oxidative stress in mice liver.

  9. Effect of Ribavirin Alone or Combined with Silymarin on Carbon Tetrachloride Induced Hepatic Damage in Rats

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    Omar M.E. Abdel Salam

    2007-01-01

    Full Text Available The effect of the antiviral agent ribavirin given alone or in combination with silymarin on the development of liver injury induced in rats with carbon tetrachloride (CCl4; 2.8 ml/kg followed by 1.4 ml/kg after one week was studied. Ribavirin at three dose levels (30, 60 or 90 mg/kg, silymarin (25 mg/kg or combination of ribavirin (60 mg/kg and silymarin (25 mg/kg was administered once daily orally for 14 days, starting at time of administration of CCl4. The administration of ribavirin decreased the elevations in serum alanine aminotransferase (ALT by 78.5, 82.1, 75.1%, aspartate aminotransferase (AST 47.5, 37.4, 38.8%, and alkaline phosphatase (ALP by 23.4, 16, 21.6%, respectively and also prevented the development of hepatic necrosis caused by CCl4. In comparison, the elevated serum ALT, AST and ALP levels decreased to 43.3%, 46%, and 37.5% of controls, respectively by silymarin. When silymarin was combined with ribavirin, the serum activities of AST and ALP were further decreased, indicating a benefi cial additive effect. Morphometric analysis indicated signifi cant reduction in the area of necrosis and fi brosis on ribavirin treatment and this was further reduced after the addition of silymarin. Metabolic pertuberations caused by CCl4 as refl ected in a decrease in intracellular protein content in hepatocytes were improved by ribavirin monotherapy and to higher extent by combined silymarin and ribavirin therapy. Proliferating cell nuclear antigen was reduced in nuclei of hepatocytes by ribavirin montherapy or the combination of ribavirin and silymarin compared with CCl4-control group. The study demonstrates that ribavirin treatment in the model of CCl4- induced liver injury results in less liver damage. Results also indicate that the combined application of ribavirin and silymarin is likely to be a useful additive in reducing liver injury.

  10. Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis

    Science.gov (United States)

    2012-01-01

    The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E) staining and Masson Trichrome (MT) examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis. PMID:22559721

  11. Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Gao Hong-Ying

    2012-05-01

    Full Text Available Abstract The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, hexadecenoic acid (HA, laminin (LN, hydroxyproline (Hyp, and glutathione (GSH, malondialdehyde (MDA, superoxide dismutase (SOD in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E staining and Masson Trichrome (MT examination. The expression of transforming growth factor-β1 (TGF-β1 and α-smooth muscle actin (α-SMA was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis.

  12. Erythropoietin decreases carbon tetrachloride-induced hepatic fibrosis by inhibiting transforming growth factor-beta

    Institute of Scientific and Technical Information of China (English)

    Soo Young Park; Joo Young Lee; Won Young Tak; Young Oh Kweon; Mi Suk Lee

    2012-01-01

    Background In addition to hematopoietic effect,the erythropoietin is known as a multifunctional cytokine with anti-fibrosis and organ-protective activities.The purpose of this study was to evaluate the effect of recombinant human erythropoietin (rhEPO) on hepatic fibrosis and hepatic stellate cells (HSCs).Methods Carbon tetrachloride (CCl4) induced hepatic fibrosis mice models were used for in vivo study and HSCs line for in vitro study.CCl4 and rhEPO (0,200 or 1000 U/kg) was injected intraperitoneally in BALB/c mice three times a week for 4 weeks.Immunohistochemistry and immunoblotting were performed to evaluate expressions of transforming growth factor-β31 (TGF-β1),α-smooth muscle actin (α-SMA),and fibronectin in explanted liver.Immunoblotting of α-SMA,phophorylated Smad-2 and Smad-2/3 was performed in HSCs treated with TGF-β1 and/or rhEPO.Results Expressions of TGF-β1,α-SMA,and fibronectin were increased in CCl4 injected mice livers,but significantly attenuated by co-treatment with CCl4 and rhEPO.Co-treatment of rhEPO markedly suppressed fibrosis in Masson's trichrome compared with treatment of only CCl4.TGF-β1 increased phosphorylated α-SMA,Smad-2 expressions in HSCs,which were decreased by rhEPO co-treatment.Conclusions Treatment of rhEPO effectively suppressed fibrosis in CCl4-induced liver fibrosis mice models.Anti-fibrosis effect of rhEPO could be related to inhibition of TGF-β1 induced activation of HSCs.

  13. Antioxidant and hepatoprotective effects of flower extract of Millingtonia hortensis Linn. on carbon tetrachloride induced hepatotoxicity

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    S Babitha

    2012-01-01

    Full Text Available Objective: Millingtonia hortensis Linn is an abundant resource of flavonoids, which might be beneficial in protecting liver tissue from injury. The hepatoprotective and antioxidant potential of ethanolic extract of M. hortensis on carbon tetrachloride (CCl 4 induced hepatotoxicity and the possible mechanism involved therein were investigated in rats. Materials and Methods: Preliminary phytochemical studies were carried out to determine the total phenol and flavonoid contents. 30 adult Wistar rats were allocated into 5 groups. Control group received vehicle, group-2 received CCl 4 alone (1 ml/kg body weight, intraperitonially, groups 3 - 5 received the ethanolic flower extract in 2 dose levels (200 and 400 mg/kg and Curcumin (100 mg/kg as a standard for 8 days orally, followed by CCl 4 as a single dose on the 8 th day. 48 hours later, blood was withdrawn, serum was subjected to biochemical assessments, and liver homogenate was examined for lipid peroxides, glutathione, superoxide dismutase, catalase and total protein levels. Furthermore, hepatic tissues were subjected to histopatological studies. Results: CCl 4 treatment produced a profound increase in the levels of malondialdehyde, hepatic marker enzymes and bilirubin content compared with the control (P < 0.05. Pre-treatment with the flower extract of M. hortensis significantly enhanced the levels of endogenous antioxidants and reduced the levels of hepatic marker enzymes in relation to the CCl 4 treated group (P < 0.05. Balloning degeneration and fatty changes in hepatocytes was prevented by pre-treatment with the flower extract. Conclusion: The antioxidant nature of the flower extract of M. hortensis could be responsible for averting damage to the liver.

  14. Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects of cacao polyphenol.

    Science.gov (United States)

    Suzuki, Koichiro; Nakagawa, Kiyotaka; Yamamoto, Takayuki; Miyazawa, Taiki; Kimura, Fumiko; Kamei, Masanori; Miyazawa, Teruo

    2015-01-01

    Here, we investigated the protective effect of cacao polyphenol extract (CPE) on carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats were administered CPE for 7 days and then received intraperitoneal injection of CCl4. Two hours after injection, we found that CCl4 treatment significantly increased biochemical injury markers, lipid peroxides (phosphatidylcholine hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione peroxidase activity in kidney rather than liver, suggesting that kidney is more vulnerable to oxidative stress under the present experimental conditions. CPE supplementation significantly reduced these changes, indicating that this compound has antioxidant properties against CCl4-induced oxidative stress. An inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an explanation for CPE antioxidant property. Together, these results provide quantitative evidence of the in vivo antioxidant properties of CPE, especially in terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats.

  15. Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice.

    Science.gov (United States)

    Kim, Hyo-Yeon; Kim, Joon-Ki; Choi, Jun-Ho; Jung, Joo-Yeon; Oh, Woo-Yong; Kim, Dong Chun; Lee, Hee Sang; Kim, Yeong Shik; Kang, Sam Sik; Lee, Seung-Ho; Lee, Sun-Mee

    2010-01-01

    Forsythiae Fructus is known to have diuretic, anti-bacterial, and anti-inflammatory activities. This study examined the hepatoprotective effects of pinoresinol, a lignan isolated from Forsythiae Fructus, against carbon tetrachloride (CCl(4))-induced liver injury. Mice were treated intraperitoneally with vehicle or pinoresinol (25, 50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 microl/kg) injection. In the vehicle-treated CCl(4 )group, serum aminotransferase activities were significantly increased 24 h after CCl4 injection, and these increases were attenuated by pinoresinol at all doses. Hepatic glutathione contents were significantly decreased and lipid peroxidation was increased after CCl4 treatment. These changes were attenuated by 50 and 100 mg/kg of pinoresinol. The levels of protein and mRNA expression of inflammatory mediators, including tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2, were significantly increased after CCl4 injection; and these increases were attenuated by pinoresinol. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of c-Jun, one of the components of activating protein 1 (AP-1), were inhibited by pinoresinol. Our results suggest that pinoresinol ameliorates CCl4)-induced acute liver injury, and this protection is likely due to anti-oxidative activity and down-regulation of inflammatory mediators through inhibition of NF-kappaB and AP-1.

  16. The protective role of pomegranate juice against carbon tetrachloride-induced oxidative stress in rats.

    Science.gov (United States)

    Pirinççioğlu, Mihdiye; Kızıl, Göksel; Kızıl, Murat; Kanay, Zeki; Ketani, Aydın

    2014-11-01

    Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study was carried out to determine the phenolic and flavonoid contents of Derik pomegranate juice and determine its effect against carbon tetrachloride (CCl4)-induced toxicity in rats. Animals were divided into four groups (n = 6): group I: control, group II: CCl4 (1 ml/kg), group III: CCl4 + pomegranate juice and group IV: CCl4 + ursodeoxycholic acid (UDCA). Treatment duration was 4 weeks, and the dose of CCl4 was administered once a week to groups II, III and IV during the experimental period. CCl4-treated rats caused a significant increase in serum enzyme levels, such as aspartate aminotransferase, alanine aminotransferase and total bilirubin, and decrease in albumin, when compared with control. Administration of CCl4 along with pomegranate juice or UDCA significantly reduces these changes. Analysis of lipid peroxide (LPO) levels by thiobarbutiric acid reaction showed a significant increase in liver, kidney and brain tissues of CCl4-treated rats. However, both pomegranate juice and UDCA prevented the increase in LPO level. Histopathological reports also revealed that there is a regenerative activity in the liver and kidney cells. Derik pomegranate juice showed to be hepatoprotective against CCl4-induced hepatic injury. In conclusion, present study reveals a biological evidence that supports the use of pomegranate juice in the treatment of chemical-induced hepatotoxicity.

  17. Radon inhalation protects mice from carbon-tetrachloride-induced hepatic and renal damage.

    Science.gov (United States)

    Kataoka, Takahiro; Nishiyama, Yuichi; Toyota, Teruaki; Yoshimoto, Masaaki; Sakoda, Akihiro; Ishimori, Yuu; Aoyama, Yutaka; Taguchi, Takehito; Yamaoka, Kiyonori

    2011-12-01

    We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m3 radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl(4)-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.

  18. Phytochemical analysis, hepatoprotective and antioxidant activity of Alchornea cordifolia methanol leaf extract on carbon tetrachloride-induced hepatic damage in rats

    Institute of Scientific and Technical Information of China (English)

    Patience O Osadebe; Festus BC Okoye; Philip F Uzor; Nneka R Nnamani; Ijeoma E Adiele; Nkemakonam C Obiano

    2012-01-01

    ABSTRACT Objective:To investigate the hepatoprotective and antioxidant activities ofAlchornea cordifolia (A. cordifolia) leaf extract.Methods: Various solvent fractions of the methanol extract of the leaf of the plantA. cordifolia Mull. Arg (Fam: Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats. The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase(SGOT/AST), serum glutamate pyruvate transaminase(SGPT/ALT), alkaline phosphatase(ALP) and total bilirubin. Thein vitro antioxidant activity of the extract was also evaluated by the 1, 1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging assay. The extract was subjected to preliminary phytochemical screening.Results:The ethyl acetate and chloroform fractions, at a dose of 300mg/kg, produced significant(P<0.05) hepatoprotection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions. The effects were comparable to those of the standard drugs used for the respective experiments, silymarin and ascorbic acid. Alkaloids, flavonoids, saponins and tannins were detected in the phytochemical screening.Conclusion: From this study, it was concluded that the plant ofA. cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract.

  19. The Aqueous Seed Extract Of Carica papaya Linn. Prevents Carbon Tetrachloride Induced Hepatotoxicity In Rats

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    A A Adeneye

    2009-06-01

    Full Text Available Summary: Carica papaya Linn. is known to have a versatile application in African folkloric medicine. In the current study, the dose-dependent (100 – 400 mg/kg/day/oral route and time-course protective effects of the 400 mg/kg/oral route of the aqueous seed extract of unripe and mature Carica papaya fruit (CPE were investigated in carbon tetrachloride (CCl4 hepatotoxic rats for 72 hours. Results showed the extract to cause significant (p<0.05, p<0.001, dose related attenuation in the elevation of serum liver enzyme markers of acute hepatocellular injury (ALT, AST, serum lipids (TG, TC, HDL-c, LDL-c and VLDL-c and serum proteins (TP and ALB. Maximum hepatoprotection was offered at an oral dose of 400 mg/kg/day of the extract. The biochemical results obtained were corroborated by improvements in the CCl4-induced hepatic histological changes. In addition, maximum hepatoprotection was offered at the 400 mg/kg of CPE for up to 3 hours post-CCl4 induction. In conclusion, the results obtained in the current study justify the folkloric application of CPE in the treatment of drug-related hepatic injury. Industrial relevance: Results of the current study provide some scientific information to develop safe and effective products such as food supplements, dietary supplements, etc. that could be useful in the clinical management of patients with drug related hepatic disorders.

  20. Hepatoprotective effect of Rosa canina fruit extract against carbon tetrachloride induced hepatotoxicity in rat

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    Heibatollah Sadeghi

    2016-03-01

    Full Text Available Objective: The present study was conducted to investigate the hepatoprotective activity of hydro-ethanolic fruit extract of Rosa canina (R. canina against carbon tetrachloride (CCl4-induced hepatotoxicity in rats. Methods: Male Wistar albino rats were randomly divided into six groups of 8 animals of each, including control, toxic (CCl4, R. canina 250, 500, and 750 mg/kg + CCl4 and R. canina 750 mg/kg alone. R. canina (p.o., daily and CCl4 (1 ml/kg twice a week, 50% v/v in olive oil, i.p. were administered to animals for six weeks. Serum analysis was performed to assay the levels of aspartate aminotransferase (AST, alanine amino transaminase (ALT, alkaline phosphatase (ALP, albumin (ALB, total protein (TP and malondialdehyde (MDA. Biochemical observations were also supplemented with histopathological examination (haematoxylin and eosin staining of liver section.Results: Hepatotoxicity was evidenced by considerable increase in serum levels of AST, ALT, ALP, and lipid peroxidation (MDA and decrease in levels of ALB and TP. Injection of CCL4 also induced congestion in central vein, and lymphocyte infiltration. Treatment with hydro-alcoholic fruit extract of R. canina at doses of 500 and 750 mg/kg significantly reduced CCl4-elevated levels of ALT, AST, ALP and MDA (p

  1. Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats.

    Science.gov (United States)

    Achliya, Girish S; Wadodkar, Sudhir G; Dorle, Avinash K

    2004-02-01

    Amalkadi Ghrita (AG), a polyherbal formulation, was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl4)-induced hepatic damage in rats. The hepatoprotective activity of AG was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and acid phosphatase (ACP). The serum levels of total proteins and bilirubin were also estimated. The histological studies were also carried out to support the above parameters. Silymarin was used as standard drug. Administration of AG (100 and 300 mg/kg, p.o.) markedly prevented CCl4-induced elevation of levels of serum GPT, GOT, ACP, ALP, and bilirubin. The decreased level of total proteins due to hepatic damage induced by CCl4 was found to be increased in AG-treated group. The results are comparable to that of silymarin. A comparative histopathological study of liver exhibited almost normal architecture, as compared to CCl4-treated group. Hepatoprotective effect of AG is probably due to combined action of all ingredients.

  2. Protective Effect of Berberis integerrima Fruit Extract on Carbon-Tetrachloride Induced Hepatotoxicity in Rats

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    fereshteh rafiee

    2013-09-01

    Full Text Available Background & Objective: Hepatoprotective effect of antioxidants such as flavnoids has been demonstrated. The aim of the present study was to assess the hepatoprotective effect of the methanolic extract of Berberis integerrima fruit (MEBIF on carbon-tetrachloride (CCL4 induced hepatotoxicity in rats. Materials & Methods: Forty male rats were divided into 5 groups as follows: 1 normal, 2 toxicant control (CCL4 was injected intraperitoneally (1 mg/kg bw, 3&4 toxicant rats treated with MEBIF at dose 250 and 500 mg/kg bw, and 5 toxicant rats treated with silymarin. At the end of the study, all the rats were sacrificed and some biochemical parameters of serum such as Alanine Aminotransferase (ALT, aspartate aminotransferase (AST and Alk‌aline Phosphatase (ALP, total proptein, total bilirubin and albumin, and concentrations of malondialdehyde (MDA, superoxide dismutase (SOD, Catalase (CAT and FRAP (Ferric Reducing/Antioxidant Power in liver tissue hemogenate were estimated. The Data was analyzed by one way variance analysis and Tukey’s test using SPSS 21. Results: injection of CCl4 significantly (P≤001/0 increased levels of ALT, AST, ALP, total bilirubin and MDA and decreased levels of total protein, albumin CAT, SOD (P≤ (001/0and FRAP in toxicant rats. In groups toxicant + Berberis (250&500 and toxicant + silymarin restored these changes to normal levels. Histopathological findings are cosistent with biochemical findings. Conclusion: MEBIF have a hepatoprotective effect on CCL4- induced hepatic damage in rats and these effects might be contributed to modulation of detoxification enzymes and antioxidant and free radical scavenger effects.

  3. The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats.

    Science.gov (United States)

    Atasever, Ayhan; Yaman, Duygu

    2014-10-01

    This study aims to determine the effects of grape seed and colchicine on carbon tetrachloride (CCl4) induced hepatic damage and on some serum biochemical parameters. Sixty male Wistar albino rats (200-250 g) were randomly divided into six groups (ten rats/group) and included the control group the group were given isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group treated i.p. injection of CCl4 (1.0 mL/kg b.w) in corn oil twice in the first week, Groups 3 and 4 injected with CCl4 as described for group 2 and the rats were orally given (100 mg/kg b.w) GSE and i.p. injected (10 μg/rat) with colchicine for four weeks, respectively and groups 5 and 6 were the grape seed and colchicine control groups in which rats were orally given grape seed (100 mg/kg b.w) and i.p. injected with colchicine (10 μg/rat), respectively. Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration, changes ranging from degenerative to necrotic, increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2, treated with CCl4. Histological hepatic changes in the rats in group 3 and 4 were similar to those in group 2. The levels of serum total protein, albumin and globulin decreased in groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT) activities increased. The lowest alkaline phosphatase (ALP) activities were in groups 4 and 5. We concluded that GSE and colchicine have not sufficient ameliorative effects to CCl4 induced acute hepatic damage.

  4. Role of the sympathetic nervous system in carbon tetrachloride-induced hepatotoxicity and systemic inflammation.

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    Jung-Chun Lin

    Full Text Available Carbon tetrachloride (CCl4 is widely used as an animal model of hepatotoxicity and the mechanisms have been arduously studied, however, the contribution of the sympathetic nervous system (SNS in CCl4-induced acute hepatotoxicity remains controversial. It is also known that either CCl4 or SNS can affect systemic inflammatory responses. The aim of this study was to establish the effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA in a mouse model of CCl4-induced acute hepatotoxicity and systemic inflammatory response. Mice exposed to CCl4 or vehicle were pretreated with 6-OHDA or saline. The serum levels of aminotransferases and alkaline phosphatase in the CCl4-poisoning mice with sympathetic denervation were significantly lower than those without sympathetic denervation. With sympathetic denervation, hepatocellular necrosis and fat infiltration induced by CCl4 were greatly decreased. Sympathetic denervation significantly attenuated CCl4-induced lipid peroxidation in liver and serum. Acute CCl4 intoxication showed increased expression of inflammatory cytokines/chemokines [eotaxin-2/CCL24, Fas ligand, interleukin (IL-1α, IL-6, IL-12p40p70, monocyte chemoattractant protein-1 (MCP-1/CCL2, and tumor necrosis factor-α (TNF-α], as well as decreased expression of granulocyte colony-stimulating factor and keratinocyte-derived chemokine. The overexpressed levels of IL-1α, IL-6, IL-12p40p70, MCP-1/CCL2, and TNF-α were attenuated by sympathetic denervation. Pretreatment with dexamethasone significantly reduced CCl4-induced hepatic injury. Collectively, this study demonstrates that the SNS plays an important role in CCl4-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical- or drug-induced hepatotoxicity and circulating immune response.

  5. Restrictive model of compensated carbon tetrachloride-induced cirrhosis in rats

    Institute of Scientific and Technical Information of China (English)

    Jean-Marc Regimbeau; David Fuks; Niaz Kohneh-Shahri; Benoit Terris; Olivier Soubrane

    2008-01-01

    AIM: To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats.METHODS: In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride (CCI4) (dilution 50%) gavage to induce cirrhosis (frequency adjusted according to weight, but each subsequent dose was systematically administered) were tested, i.e. the rapid and slow protocols. Prothrombin time (PT) and total bilirubin (TB) were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy.RESULTS: Rapid protocol: This corresponded to 1 garage/4 d over 6 wk (mortality 30%). Mean PT was 35.2±2.8 s (normal: 14.5 s), and mean TB was 1.8±0.2mg/clL (normal: 0.1 mg/dL). Slow protocol: This corresponded to 1 gavage/6 d over 9 wk (mortality 10%).Mean PT was 11.8±0.2 s (normal: 14.5 s), and mean TB was 0.4 ± 0.04 mg/dL (normal: 0.1 mg/dL). Pathological analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid garage group who underwent 15% hepatectomy and in the slow garage group who underwent 70%hepatectomy was 50% and 70%, respectively.CONCLUSION: Our modified model is a simplified method to induce cirrhosis which is rapid (6 to 9 wk),efficient and stable up to 3 mo. Using this method, "Child Pugh A" or "Child Pugh BC" cirrhotic rats were obtained.Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.

  6. Hepatoprotective activity of Leptadenia reticulata stems against carbon tetrachloride-induced hepatotoxicity in rats

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    Amit Kumar Nema

    2011-01-01

    Conclusion: The ethanolic and aqueous extracts of stems of L. reticulata showed significant hepatoprotective activity. The ethanolic extract is more potent in hepatoprotection in CCl 4 -indiced liver injury model as compared with aqueous extract.

  7. Role of nuclear receptor CAR in carbon tetrachloride-induced hepatotoxicity

    Institute of Scientific and Technical Information of China (English)

    Yuichi Yamazaki; Satoru Kakizaki; Norio Horiguchi; Hitoshi Takagi; Masatomo Mori; Masahiko Negishi

    2005-01-01

    AIM: To investigate the precise roles of CAR in CCl4-induced acute hepatotoxicity.METHODS: To prepare an acute liver injury model, CCl4 was intraperitoneally injected in CAR+/+ and CAR-/- mice.RESULTS: Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR-/- mice compared to CAR+/+ mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR-/- mice compared with CAR+/+ mice. On the other hand,androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR+/+ but not in CAR-/- mice. Thus, CAR activation caused CCl4 hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity.There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR+/+ and CAR-/- mice. However, the expression of other CCl4-metabolizing enzymes, such as CYP2B10 and 3A11, was induced by PB in CAR+/+ but not in CAR-/- mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and 3A11 in the presence of activator or inhibitor.CONCLUSION: The nuclear receptor CAR modulates CCl4-induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drugdrug interaction even though such drugs themselves are not hepatotoxic.

  8. HEPATOPROTECTIVE ACTIVITY OF METHANOLIC EXTRACT OF ECBOLIUM VIRIDE (FORSSK. ALSTON ROOTS AGAINST CARBON TETRACHLORIDE INDUCED HEPATOTOXICITY

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    Ashoka Babu V.L

    2012-08-01

    Full Text Available In the present study, the methanolic extract of Ecbolium viride root was evaluated for its hepatoprotective effect against CCl4 induced hepatic injury in rats. Alteration in the levels of biochemical markers of hepatic damage like SGOT, SGPT, ALP, triglycerides, bilirubin, total proteins and liver weight were tested in both treated and untreated groups. CCl4 (1ml/kg enhanced the SGPT, SGOT, ALP, triglycerides, liver weight and reduced total proteins significantly. Treatment with methanolic extract of Ecbolium viride roots (200mg/kg and 400mg/kg has brought back the altered levels of altered levels of biochemical markers significantly to the near normal levels in the dose dependant manner.

  9. Protective effects of Coriandrum sativum extracts on carbon tetrachloride-induced hepatotoxicity in rats.

    Science.gov (United States)

    Sreelatha, S; Padma, P R; Umadevi, M

    2009-04-01

    Oxidative damage is implicated in the pathogenesis of various liver injuries. The study was aimed to investigate the antioxidant activity of Coriandrum sativum on CCl(4) treated oxidative stress in Wistar albino rats. CCl(4) injection induced oxidative stress by a significant rise in serum marker enzymes and thiobarbituric acid reactive substances (TBARS) along with the reduction of antioxidant enzymes. In serum, the activities of enzymes like ALP, ACP and protein and bilirubin were evaluated. Pretreatment of rats with different doses of plant extract (100 and 200mg/kg) significantly lowered SGOT, SGPT and TBARS levels against CCl(4) treated rats. Hepatic enzymes like SOD, CAT, GPx were significantly increased by treatment with plant extract, against CCl(4) treated rats. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation. Oral administration of the leaf extract at a dose of 200mg/kg body weight significantly reduced the toxic effects of CCl(4). The activity of leaf extract at the dose of 200mg/kg was comparable to the standard drug, silymarin. Based on these results, it was observed that C. sativum extract protects liver from oxidative stress induced by CCl(4) and thus helps in evaluation of traditional claim on this plant.

  10. Amelioration of carbon tetrachloride induced hepatotoxicity in rats by standardized Feronia limonia. Linn leaf extracts

    OpenAIRE

    Devkar, Ranjitsinh V; Jadeja, Ravirajsinh N.; Jain, Mahendra; Kapadia, Rakhee; Mishra, S. H.; Menaka C. Thounaojam

    2012-01-01

    The hepatoprotective potential of standardized Feronia limonia (Family, Rutaceae) methanolic extract (FL-7) and chloroform soluble fraction (FL-9) were assessed against carbon tetrachloride (CCl4) induced oxidative stress and hepatotoxicity in rats. Rats treated with CCl4 recorded significant elevation in plasma markers of hepatic injury, alteration in hepatic antioxidant status and histopathological damages. However, rats pretreated with FL-7 (200 or 400 mg/kg, p.o.) and FL-9 (100 or 200 mg/...

  11. Hepatoprotective effects of fermented Curcuma longa L. on carbon tetrachloride-induced oxidative stress in rats.

    Science.gov (United States)

    Kim, Yongjae; You, Yanghee; Yoon, Ho-Geun; Lee, Yoo-Hyun; Kim, Kyungmi; Lee, Jeongmin; Kim, Min Soo; Kim, Jong-Choon; Jun, Woojin

    2014-05-15

    The hepatoprotective effect of fermented Curcuma longa L. (FC) was investigated in rats under CCl4-induced oxidative stress. FC at a dose of 30 or 300 mg/kg body weight (b.w.) was orally administered for 14 days followed by a single dose of CCl4 (1.25 mL/kg b.w. in 20% corn oil) on day 14. Pretreatment with FC drastically prevented the elevated activities of serum AST, ALT, LDH, and ALP caused by CCl4-induced hepatotoxicity. Histopathologically evident hepatic necrosis was significantly ameliorated by FC pretreatment. When compared to the CCl4-alone treated group, rats pretreated with FC displayed the reduced level of malondialdehyde. Furthermore, FC enhanced antioxidant capacities with higher activities of catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase, and level of reduced glutathione. These results suggest that FC could be a candidate used for the prevention against various liver diseases induced by oxidative stress via elevating antioxidative potentials and decreasing lipid peroxidation.

  12. Hepatoprotective Activity of Cassia fistula root against Carbon tetrachloride-Induced Hepatic Injury in rats (Wistar

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    SAGAR DAWADA

    2012-04-01

    Full Text Available The protective effects of the alcoholic extract of Cassia fistula root; against CCl4 induced hepatic failure in male albino rats (wistar strain was investigated. For acute and massive invasion of hepatopathy, CCl4 (s.c injection of CCl4+Olive Oil in 1:1 ratio; 2ml/kg was used and the insidious intoxication was evidenced bysignificant turmoil of various biochemical parameters followed by significant (p<0.001 weight loss in toxic control group. The administration of alcoholic root extract (200mg/kg and 100mg/kg of body weight for 7 days, elicited protective action since the elevated levels of marker enzymes (SGOT, SGPT, ALP of liver functionswere found to be decreasing progressively in a dose dependent manner. The final body weight was also significantly (p<0.001 increased when compared with the toxic control group. The serum total protein and theserum albumin were also approaching normal values. The results found in alcoholic extract 200mg/kg treated rat were quite promising and were comparable with a standard drug Silymarin. In the alcoholic extract 200mg/kg treated rat group all the marker enzymes were analyzed to be decreasing significantly. The statistically processed results support the conclusion, that the alcoholic root extract of Cassia fistula root (200mg/kg and 100mg/kg possesses dose dependent, significant protective activity against CCl4 induced hepatotoxicity.

  13. Campomanesia adamantium (Myrtaceae fruits protect HEPG2 cells against carbon tetrachloride-induced toxicity

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    Thaís de Oliveira Fernandes

    2015-01-01

    Full Text Available Campomanesia adamantium (Myrtaceae is an antioxidant compounds-rich Brazilian fruit popularly known as gabiroba. In view of this, it was evaluated the hepatoprotective effects of pulp (GPE or peel/seed (GPSE hydroalcoholic extracts of gabiroba on injured liver-derived HepG2 cells by CCl4 (4 mM. The results showed the presence of total phenolic in GPSE was (60% higher when compared to GPE, associated with interesting antioxidant activity using DPPH·− assay. Additionally, HPLC chromatograms and thin layer chromatography of GPE and GPSE showed the presence of flavonoids. Pretreatment of HepG2 cells with GPE or GPSE (both at 800–1000 μg/mL significantly (p < 0.0001 protected against cytotoxicity induced by CCl4. Additionally, the cells treated with both extracts (both at 1000 μg/mL showed normal morphology (general and nuclear contrasting with apoptotic characteristics in the cells only exposed to CCl4. In these experiments, GPSE also was more effective than GPE. In addition, CCl4 induced a marked increase in AST (p < 0.05 and ALT (p < 0.0001 levels, while GPE or GPSE significantly (p < 0.0001 reduced these levels, reaching values found in the control group. In conclusion, the results suggest that gabiroba fruits exert hepatoprotective effects on HepG2 cells against the CCl4-induced toxicity, probably, at least in part, associated with the presence of antioxidant compounds, especially flavonoids.

  14. Hepatoprotective potential of Aloe barbadensis Mill. against carbon tetrachloride induced hepatotoxicity.

    Science.gov (United States)

    Chandan, B K; Saxena, A K; Shukla, Sangeeta; Sharma, Neelam; Gupta, D K; Suri, K A; Suri, Jyotsna; Bhadauria, M; Singh, B

    2007-05-22

    Aloe barbadensis Mill. Syn. Aloe vera Tourn. ex Linn.(Liliaceae) has been used in variety of diseases in traditional Indian system of medicine in India and its use for hepatic ailments is also documented. In the present study an attempt has been made to validate its hepatoprotective activity. The shade dried aerial parts of Aloe barbadensis were extracted with petroleum ether (AB-1), chloroform (AB-2) and methanol (AB-3). The plant marc was extracted with distilled water (AB-4). All the extracts were evaluated for hepatoprotective activity on limited test models as hexobarbitone sleep time, zoxazolamine paralysis time and marker biochemical parameters. AB-1 and AB-2 were observed to be devoid of any hepatoprotective activity. Out of two active extracts (AB-3 and AB-4), the most active AB-4 was studied in detail. AB-4 showed significant hepatoprotective activity against CCl4 induced hepatotoxicity as evident by restoration of serum transaminases, alkaline phosphatase, bilirubin and triglycerides. Hepatoprotective potential was confirmed by the restoration of lipid peroxidation, glutathione, glucose-6-phosphatase and microsomal aniline hydroxylase and amidopyrine N-demethylase towards near normal. Histopathology of the liver tissue further supports the biochemical findings confirming the hepatoprotective potential of AB-4. The present study shows that the aqueous extract of Aloe barbadensis is significantly capable of restoring integrity of hepatocytes indicated by improvement in physiological parameters, excretory capacity (BSP retention) of hepatocytes and also by stimulation of bile flow secretion. AB-4 did not show any sign of toxicity up to oral dose of 2 g/kg in mice.

  15. Curcuma longa attenuates carbon tetrachloride-induced oxidative stress in T-lymphocyte subpopulations.

    Science.gov (United States)

    Abu-Rizq, H A; Mansour, Mohamed H; Afzal, Mohammad

    2015-01-01

    A comparison of crude curcuminoid extract and purified curcumin was made to evaluate the immunoprotective effect of Curcuma longa (turmeric) Zingiberaceae. Carbon tetrachloride (CCl4) induced selective cytolytic effects among immature (PNA(+)) thymocytes and peripheral helper (CD4(+)) T lymphocytes in the spleen were paralleled by a significant reduction in CD25, CD71, and Con A receptor expression. Treatment with curcumanoid crude extract, at two different doses, showed a significant restoration of lymphocyte viability and CD25, CD71, and Con A receptor expression in both immature (PNA+) thymocytes and splenic helper (CD4(+)) T lymphocytes. Turmeric crude extract, at both low and high dose, was found to be more efficient as compared to purified curcumin, suggesting synergistic effect of curcumin with other components of the crude extract.

  16. Protective effects of Cornus mas fruit extract on carbon tetrachloride induced nephrotoxicity in rats.

    Science.gov (United States)

    Es Haghi, M; Dehghan, G; Banihabib, N; Zare, S; Mikaili, P; Panahi, F

    2014-09-01

    Oxidative damage is implicated in the pathogenesis of kidney injury. Cornus mas is used for in renal aliments traditionally in Iran. The present study was aimed to investigate the antioxidant activity of C. mas fruit extract (CMFE) on carbon tetrachloride (CCl4) treated oxidative stress in Wistar albino rats. Forty two male albino rats were divided into seven groups. Group I served as a sham; Group II served as a normal control; Group III served as a toxic control, with CCl4 (1 ml/kg body weight; 80% in olive oil); Groups IV and V received CMFE at doses of 300 and 700 mg/kg before CCl4 injection; Groups VI and VII received extract at same doses orally at 2, 6, 12, 24 and 48 h after CCl4 intoxication. CCl4 injection produced a significant rise in serum markers of oxidative stress and lipid peroxidation product malondialdehyde along with the reduction of antioxidant enzymes such as superoxide dismuta, catalase and glutathion peroxidase. Serum creatinine, urea and uric acid concentrations were increased whereas level of protein and albumin were reduced. Treatment of rats with different doses of fruit extract (300 and 700 mg/kg) significantly (P induced with CCl4 in lipid peroxidation, antioxidant defenses, biochemical and renal lesions. Based on these results, we conclude that CMFE protects kidney from oxidative stress induced by CCl4.

  17. D-Pinitol Protects Against Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Rengarajan, Thamaraiselvan; Rajendran, Peramaiyan; Nandakumar, Natarajan; Lokeshkumar, Boobathy; Balasubramanian, Maruthaiveeran Periyasamy

    2015-01-01

    The aim of the study was to evaluate the protective activity of D-Pinitol against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. The animals were divided into six groups, with each group consisting of six animals. Group I animals served as normal controls and received olive oil vehicle (1.0 ml/kg body weight intraperitoneally). Group II rats served as CCl4 controls, which received 30% CCl4 suspended in olive oil (3.0 ml/kg body weight intraperitoneally) twice a week for 4 weeks. Group III rats were treated with 30% CCl4 suspended in olive oil (3.0 ml/kg body weight intraperitoneally) twice a week for 4 weeks, followed by D-Pinitol (100 mg/kg body weight) given for 28 days intragastrically. Group IV rats received D-Pinitol alone at a concentration of 100 mg/kg body weight for 28 days intragastrically. At the end of the experimental period, serum marker enzymes and lipid peroxidation (LPO) levels were significantly increased in group II animals. On the other hand, D-Pinitol treatment significantly decreased marker enzymes and LPO levels and increased the antioxidant level. CYP expression was also investigated. Therefore, the present study revealed that D-Pinitol acts as a protective agent by decreasing metabolic activation of xenobiotics through its antioxidant nature.

  18. Phenylbutyric acid protects against carbon tetrachloride-induced hepatic fibrogenesis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian-Qing [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Second Affiliated Hospital, Anhui Medical University, Hefei 230601 (China); Chen, Xi [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Cheng [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Tao, Li [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Zhi-Hui; Liu, Xiao-Qian [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Xu, Yuan-Bao [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Wang, Hua [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Li, Jun, E-mail: lijun@ahmu.edu.cn [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Xu, De-Xiang, E-mail: xudex@126.com [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China)

    2013-01-15

    A recent report showed that the unfolded protein response (UPR) signaling was activated in the pathogenesis of carbon tetrachloride (CCl{sub 4})-induced hepatic fibrosis. Phenylbutyric acid (PBA) is a well-known chemical chaperone that inhibits endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling. In the present study, we investigated the effects of PBA on CCl{sub 4}-induced hepatic fibrosis in mice. All mice were intraperitoneally (i.p.) injected with CCl{sub 4} (0.15 ml/kg BW, twice per week) for 8 weeks. In CCl{sub 4} + PBA group, mice were i.p. injected with PBA (150 mg/kg, twice per day) from the beginning of CCl{sub 4} injection to the end. As expected, PBA significantly attenuated CCl{sub 4}-induced hepatic ER stress and UPR activation. Although PBA alleviated, only to a less extent, hepatic necrosis, it obviously inhibited CCl{sub 4}-induced tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β). Moreover, PBA inhibited CCl{sub 4}-induced hepatic nuclear factor kappa B (NF-κB) p65 translocation and extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK) phosphorylation. Interestingly, CCl{sub 4}-induced α-smooth muscle actin (α-SMA), a marker for the initiation phase of HSC activation, was significantly attenuated in mice pretreated with PBA. Correspondingly, CCl{sub 4}-induced hepatic collagen (Col)1α1 and Col1α2, markers for the perpetuation phase of HSC activation, were inhibited in PBA-treated mice. Importantly, CCl{sub 4}-induced hepatic fibrosis, as determined using Sirius red staining, was obviously attenuated by PBA. In conclusion, PBA prevents CCl{sub 4}-induced hepatic fibrosis through inhibiting hepatic inflammatory response and HSC activation. Highlights: ► CCl{sub 4} induces hepatic ER stress, inflammation, HSC activation and hepatic fibrosis. ► PBA alleviates CCl{sub 4}-induced hepatic ER stress and UPR signaling activation. ► PBA inhibits CCl{sub 4}-induced

  19. Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism%槲皮素对四氯化碳引起的小鼠急性肝损伤治疗作用及其机理

    Institute of Scientific and Technical Information of China (English)

    Jia-qi ZHANG; Liang SHI; Xi-ning XU; Si-chong HUANG; Bin LU; Li-li JI; Zheng-tao WANG

    2014-01-01

    This study observes the therapeutic detoxification of quercetin, a wel-known flavonoid, against carbon tetrachloride (CCl4) induced acute liver injuryin vivo and explores its mechanism. Quercetin decreased CCl4-increased serum activities of alanine and aspartate aminotransferases (ALT/AST) when orally taken 30 min after CCl4 intoxica-tion. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCl4-induced liver injury. Quercetin decreased the CCl4-increased malondialdehyde (MDA) and reduced the glutathione (GSH) amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal (4-HNE) in the liver induced by CCl4. Peroxiredoxin (Prx) 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 (TrxR1/2), thioredoxin 1 and 2 (Trx1/2), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) al play critical roles in maintaining celular redox homeostasis. Real-time polymerase chain reaction (PCR) results demonstrated that quercetin reversed the decreased mRNA expression of al those genes induced by CCl4. In conclusion, our results demonstrate that quercetin ameliorates CCl4-induced acute liver injuryin vivo via aleviating oxidative stress injuries when oraly taken after CCl4 intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin.

  20. Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats

    Directory of Open Access Journals (Sweden)

    Ebaid Hossam

    2013-02-01

    Full Text Available Abstract This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1, interferon gamma (IFN-γ, programmed cell death-receptor (Fas and Tumor necrosis factor-alpha (TNF-α mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA, cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

  1. Hepatoprotective effects of sesamol loaded solid lipid nanoparticles in carbon tetrachloride induced sub-chronic hepatotoxicity in rats.

    Science.gov (United States)

    Singh, Neha; Khullar, Neeraj; Kakkar, Vandita; Kaur, Indu Pal

    2016-05-01

    Sesamol is a phenolic component of sesame seed oil, which has been established as an antioxidant and also possesses potential for hepatoprotection. However, its protective role in carbon tetrachloride (CCl4 ) induced sub-chronic hepatotoxicity has not been studied. Limited oral bioavailability (BA) and rapid elimination (as conjugates) in rats is reported for sesamol. Considering its significant antioxidant potential and compromised BA, we packaged sesamol into solid lipid nanoparticles (S-SLNs) to enhance its hepatoprotective bioactivity. S-SLNs prepared by microemulsification method were nearly spherical in shape with an average particle size of 120.30 nm and their oral administration at 8 mg/kg body weight (BW) showed significantly (p induced sub-chronic liver injury in rats. Evaluations were done in terms of histological changes in the liver tissue, liver injury markers (serum alanine aminotransferase, serum aspartate aminotransferase, and serum lactate dehydrogenase); oxidative stress markers (lipid peroxidation, superoxide dismutase, and reduced glutathione) and proinflammatory response marker (tumor necrosis factor-alpha).

  2. Antihepatotoxic effect of marrubium vulgare and withania somnifera extracts on carbon tetrachloride-induced hepatotoxicity in rats.

    Science.gov (United States)

    Elberry, Ahmed A; Harraz, Fathalla M; Ghareib, Salah A; Nagy, Ayman A; Gabr, Salah A; Suliaman, Mansour I; Abdel-Sattar, Essam

    2010-09-01

    Marrubium vulgare and Withania somnifera are used in folk medicine of several countries. Many researches showed that they are used for the treatment of variety of diseases due to their antioxidant effects. The present aim of this study was to evaluate the antihepatotoxic and antioxidant activities of the both extracts against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Both extracts were given orally in a dose of 500 mg/kg/day for 4 weeks along with CCl4 started at the 7th week of induction of hepatotoxicity. The antihepatotoxic activity was assessed by measuring aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH), tissue content and malondialdehyde (MDA) as well as histopathological examination. Both extracts showed a significant antihepatotoxic effect by reducing significantly the levels of AST, ALT and LDH. However, ALP levels were decreased non-significantly. Regarding the antioxidant activity, they exhibited significant effects by increasing the GPx, GR and GST activities with increased GSH tissue contents and decreased production of MDA level. Furthermore, both extracts alleviated histopathological changes in rats' liver treated with CCl4. M. vulgare and W. somnifera protect the rats' liver against CCl4-induced hepatotoxicity. This effect may be attributed, at least in part, to the antioxidant activities of these extracts.

  3. Protective effects of neohesperidin dihydrochalcone against carbon tetrachloride-induced oxidative damage in vivo and in vitro.

    Science.gov (United States)

    Hu, Lihua; Li, Lingrui; Xu, Demei; Xia, Xiaomin; Pi, Ruxian; Xu, Duo; Wang, Wenchao; Du, Hong; Song, Erqun; Song, Yang

    2014-04-25

    The purpose of this study was to investigate the possible hepatoprotective effects of neohesperidin dihydrochalcone (NHDC) on carbon tetrachloride (CCl4)-induced acute oxidative injury in vivo and in vitro. In a mouse model, intraperitoneal injection of CCl4 resulted in a significant increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities. Histopathological examination revealed severe hepatocyte necrosis and destruction of architecture in liver lesions, and immunohistochemical staining illustrated a remarkable enhancement of COX-2 and iNOS expression. The levels of hepatic antioxidant, such as, catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GP-X) and glutathione (GSH) were decreased, compared to the control group. However, pretreatment of NHDC for six consecutive days significantly ameliorated these changes. Moreover, Western blotting assay indicated pretreatment with NHDC also down-regulated CCl4-induced protein expressions of NF-κB, IL-6, caspase 3 and caspase 8. In HepG2 cell model, CCl4-treatment caused significant decrease in cell viability, antioxidant activities and GSH level, increase in intracellular reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) level. Interestingly, pretreatment of NHDC effectively relieved CCl4-induced oxidative damage in a dose-dependent manner. In conclusion, NHDC appeared to possess promising anti-oxidative and anti-inflammatory capacities, it is possible to be used as a hepatoprotective agent.

  4. Toll-Like Receptor 3 Gene Deficiency Aggravates Carbon Tetrachloride-Induced Liver Fibrosis in Mice%Toll样受体3基因缺陷促进四氯化碳诱导的小鼠肝纤维化损伤

    Institute of Scientific and Technical Information of China (English)

    薛如意; 张丹瑛; 吴昊; 刘韬韬; 董玲; 沈锡中

    2016-01-01

    使肝组织中炎性因子 TNF‐α、IL‐6和 MCP‐1以及促纤维化分子TGF‐β、TIMP1和PDGFR表达升高。结论:TLR3基因缺陷可促进四氯化碳诱导的肝纤维化小鼠肝组织中的胶原沉积和肝星状细胞激活,促进肝组织炎性因子释放,使肝促纤维化分子上调。以上提示,T L R3是肝纤维化病理过程中的一个保护性基因。%Objective:To investigate the effect of Toll‐like receptor 3(TLR3) gene deficiency on the degree of liver fibrosis in mouse model of carbon tetrachloride(CCl4 )‐induced liver fibrosis .Methods :A total of 20 wild‐type male mice and 20 male mice with TLR3 gene deficiency (TLR3‐/‐) were divided into wild‐type control group and wild‐type model group ,TLR3‐/‐ control group and TLR3‐/‐ model group ,respectively ,with 10 mice in each group .The control group was injected with corn‐oil by intraperitoneal injection while the model group was injected with CCl4 by intraperitoneal injection .After 8 weeks ,blood sample wascollectedandserumlevelofalanineaminotransferase(ALT),aspartatetransaminase(AST),totalbilirubin(TBIL),and albumin(Alb) was analyzed by automatic biochemical analyzer .And the degree of collagen deposition in liver tissue was evaluated by Masson trichrome staining .And the activation of hepatic stellate cells was detected by immunohistochemistry staining of α‐smooth muscle actin(α‐SMA).And hydroxyproline content of liver tissue was detected with detection kit . Furthermore ,real‐time fluorescence polymerase chain reaction was used to detect the expression of liver fibrotic marker type I collagen ,and inflammatory cytokines including tumor necrosis factor‐alpha (TNF‐α) , interleukin‐6 (IL‐6 ) and monocyte chemotactic protein‐1(MCP‐1) ,as well as pro‐fibrotic molecule including transforming growth factor‐beta (TGF‐β) ,tissue inhibitor of metalloproteinase 1(TIMP1) and platelet‐derived growth factor receptor(PDGFR) .Results:TLR3 gene deficiency had no

  5. Protective effects of melatonin against carbon tetrachloride-induced hepatotoxicity in rats: a light microscopic and biochemical study.

    Science.gov (United States)

    Kus, Ilter; Ogeturk, Murat; Oner, Hakan; Sahin, Semsettin; Yekeler, Hayrettin; Sarsilmaz, Mustafa

    2005-01-01

    The aim of this study was to examine the protective effects of melatonin against CCl4-induced hepatotoxicity in the rat. Twenty-four male Wistar rats were divided into three groups. Group I was used as a control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and melatonin for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and conjugated bilirubin levels were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All serum biochemical parameters were significantly higher in animals treated with CCl4 than in the controls. When rats injected with CCl4 were treated with melatonin, significantly reduced elevations in serum biochemical parameters were found. In liver sections of the CCl4-injected group, necrosis, fibrosis, mononuclear cell infiltration, haemorrhage, fatty degeneration and formation of regenerative nodules were observed. Additionally, apoptotic figures, microvesicular steatosis and hydropic degeneration in hepatocytes were seen in this group. In contrast, the histopathological changes observed after administration of CCl4 were lost from rats treated with CCl4 and melatonin. Except for mild hydropic degeneration of the hepatocytes, a normal lobular appearance was seen in the livers of this group. The results of our study indicate that melatonin treatment prevents CCl4-induced liver damage in rats.

  6. Protective role of Cupressuflavone from Cupressus macrocarpa against carbon tetrachloride-induced hepato- and nephrotoxicity in mice.

    Science.gov (United States)

    Al-Sayed, Eman; Abdel-Daim, Mohamed M

    2014-12-01

    The hepatoprotective and nephroprotective activity of cupressuflavone isolated from Cupressus macrocarpa was investigated against CCl4-induced toxicity in mice. Cupressuflavone was administered (40, 80, and 160 mg/kg/day) for five days. CCl4 was administered (0.5 mL/kg intraperitoneally) at the end of the experiment. A substantial increase (p < 0.001) in the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, cholesterol, creatinine, uric acid, urea, and malondialdehyde was observed in the CCl4-treated group compared to the normal control group. In contrast, a significant reduction (p < 0.001) in glutathione and superoxide dismutase contents as well as the total protein level was evident in the CCl4-intoxicated mice. Cupressuflavone pretreatment markedly inhibited the CCl4-induced increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, cholesterol, creatinine, uric acid, urea, and malondialdehyde levels in a dose-dependent manner (p < 0.001 at all the tested doses). In addition, a significant (p < 0.001) and dose-dependent decrease in the total bilirubin levels was evident by cupressuflavone pretreatment (80 and 160 mg/kg/day) when compared to the CCl4-intoxicated group. Furthermore, cupressuflavone administration significantly increased the activity of antioxidant parameters glutathione and superoxide dismutase as well as the serum protein levels (p < 0.001 at all the tested doses) in a dose-dependent manner. Histological observations confirmed the strong hepato- and nephroprotective activity. These findings suggest that cupressuflavone could exert a beneficial effect against oxidative stress by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes induced by CCl4 in the liver and kidney tissues. The structure of cupressuflavone was identified by

  7. Protective Effects of Pleurotus tuber-regium on Carbon- Tetrachloride Induced Testicular Injury in Sprague Dawley Rats

    Science.gov (United States)

    Okolo, Kenneth O.; Siminialayi, Iyeopu M.; Orisakwe, Orish E.

    2016-01-01

    The high rate of male infertility and the meager resources to manage same in sub Saharan Africa have necessitated the search for cost effective and available alternatives. Mushrooms have been used traditionally in folk medicine and as nutraceuticals. This study has investigated the effect of the wild mushroom Pleurotus tuber-regium on carbon tetrachloride (CCl4) deleterious effects on the reproductive system of male rats. Thirty six rats were divided into six groups of six animals each. Group I (negative control) received 10 ml/kg olive oil intraperitoneal weekly in addition to feed and water ad libitum. Group II (positive control) received CCl4 10 ml/kg (30% in Olive oil) weekly. Group III, IV, and V received 100 mg, 20 0mg, and 500 mg P. tuber-regium (33.3% in feed) daily in addition to 10 ml/kg CCl4 weekly. Group VI received 500 mg P. tuber-regium (33.3% in feed) daily. After 4 weeks, sperm motility, epididymal count and vitality were determined. Serum malondialdehyde (MDA), testosterone, Luteinizing hormone (LH), Follicle stimulating hormone (FSH), prolactin and oestradiol were estimated using enzyme-linked immunosorbent assay (ELISA) kits. Histopathologic examinations of the testis were carried out. Carbon tetrachloride significantly reduced the sperm motility (54.33 ± 3.79%), epididymal count (28.73 ± 2.86 × 106/ml, vitality (4.96 ± 0.62), LH (0.88 ± 0.14), FSH (2.04 ± 0.33), and Testosterone (2.02 ± 0.24) when compared with control (89.33 ± 9.01), 91.91 ± 1.92 × 106/ml, 13.12 ± 0.19, 2.74 ± 0.32, 3.64 ± 0.62, and 4.16 ± 0.23, respectively, which were reversed by P. tuber-regium administration. Co-administration of P. tuber-regium plus CCl4 significantly reduced MDA level. P. tuber-regium showed dose dependent ameliorative activity against CCl4 deleterious action on the testis and may be beneficial in the management of male infertility. PMID:28018218

  8. Nigella sativa improves the carbon tetrachloride-induced lung damage in rats through repression of erk/akt pathway

    Directory of Open Access Journals (Sweden)

    Abdullah Aslan

    2015-08-01

    Full Text Available The objective of this study was to examine whether Nigella sativa plays a protective role against the damage in the lung by administering carbon tetra-chloride (CCl4 to rats. Male Wistar albino (n=28, 8 weeks old rats were divided into 4 groups: a negative control: Normal water consuming group to which no CCl4 and N. sativa was administered; b Positive control: Normal water consuming group to which no CCl4 was administered but N. sativa was administered; c CCl4 Group: Normal water consuming and group to which CCl4 was administered (1.5 mL/kg, ip; d N. sativa plus CCl4 group: CCl4 and N. sativa administered group (1.5 mL/kg, ip. Caspase-3, caspase -9, erk, akt protein syntheses were examined via Western blotting. Malondialdehyde determination in lung tissue was made using spectrophotometer. As a results, malondialdehyde amount was decreased in the CCl4 plus N. sativa group in comparison to CCl4 group whereas caspase-3, caspase-9 was increased and erk, akt had decreased. These results show that N. sativa protects the lung against oxidative damage.

  9. Protective effects of Chaenomeles thibetica extract against carbon tetrachloride-induced damage via the MAPK/Nrf2 pathway.

    Science.gov (United States)

    Ma, Bingxin; Wang, Jing; Tong, Jing; Zhou, Gao; Chen, Yuxin; He, Jingsheng; Wang, Youwei

    2016-03-01

    Chaenomeles thibetica, a type of fruit of the genus Chaenomeles, is commonly cultivated and used as Mugua in China and as liquor, candy, and functional food in Tibet. Total phenol, flavonoid, and proanthocyanidin contents were measured in C. thibetica extract (CTE). CTE had a positive effect on free radical scavenging and anti-lipid oxidation in vitro. The protective effects of CTE against carbon tetrachloride (CCl4)-induced oxidative damage in vivo were also measured. The results of antioxidative enzymes indicated that CTE can increase the activities of the catalase, superoxide dismutase, and glutathione contents and reduce the level of malondialdehyde in rats. The levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and total bilirubin were significantly reversed by CTE compared with the elevated levels in the CCl4 group. Besides, CTE could reverse the cell viability of HepG2 inoculated with CCl4via phosphorylation of mitogen-activated protein kinases (MAPKs), activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increasing the expression of phase II detoxification enzymes. These effects may expand the applications of C. thibetica and offer alternative food with antioxidant and hepatoprotective functions in the food industry.

  10. Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using (1)H NMR analysis.

    Science.gov (United States)

    Wu, Fang; Zheng, Hua; Yang, Zheng-Teng; Cheng, Bang; Wu, Jin-Xia; Liu, Xu-Wen; Tang, Chao-Ling; Lu, Shi-Yin; Chen, Zhao-Ni; Song, Fang-Ming; Ruan, Jun-Xiang; Zhang, Hong-Ye; Liang, Yong-Hong; Song, Hui; Su, Zhi-Heng

    2017-03-19

    Chronic liver injury has been shown to cause liver fibrosis due to the sustained pathophysiological wound healing response of the liver, and eventually progresses to cirrhosis. The total alkaloids of Corydalis saxicola Bunting (TACS), a collection of important bioactive ingredients derived from the traditional Chinese folk medicine Corydalis saxicola Bunting (CS), have been reported to have protective effects on the liver. However, the underlying molecular mechanisms need further elucidation. In this study, the urinary metabonomics and the biochemical changes in rats with carbon tetrachloride (CCl4)-induced chronic liver injury due to treatment TACS or administration of the positive control drug-bifendate were studied via proton nuclear magnetic resonance ((1)H NMR) analysis. Partial least squares-discriminate analysis (PLS-DA) suggested that metabolic perturbation caused by CCl4 damage was recovered with TACS and bifendate treatment. A total of seven metabolites including 2-oxoglutarate, citrate, dimethylamine, taurine, phenylacetylglycine, creatinine and hippurate were considered as potential biomarkers involved in the development of CCl4-induced chronic liver injury. According to pathway analysis using identified metabolites and correlation network construction, the tricarboxylic acid (TCA) cycle, gut microbiota metabolism and taurine and hypotaurine metabolism were recognized as the most affected metabolic pathways associated with CCl4 chronic hepatotoxicity. Notably, the changes in 2-oxoglutarate, citrate, taurine and hippurate during the process of CCl4-induced chronic liver injury were significantly restored by TACS treatment, which suggested that TACS synergistically mediated the regulation of multiple metabolic pathways including the TCA cycle, gut microbiota metabolism and taurine and hypotaurine metabolism. This study could bring valuable insight to evaluating the efficacy of TACS intervention therapy, help deepen the understanding of the

  11. Wu-Chia-Pi Solution Attenuates Carbon Tetrachloride-Induced Hepatic Injury through the Antioxidative Abilities of Its Components Acteoside and Quercetin

    Directory of Open Access Journals (Sweden)

    Ching-Chiung Wang

    2012-12-01

    Full Text Available Wu-Chia-Pi medicated wine, composed nine Chinese medicines soaked in 35% alcohol, is widely used in Asia for its health-promoting functions. However, long-term consumption of alcohol could result in liver dysfunction. In this study, Wu-Chia-Pi solution (WCPS and extract (WCPE were prepared by modification of the principals given by the Committee on Chinese Medicine and Pharmacy in Taiwan. The aim of this study was to explore the protective effect of WCPS against carbon tetrachloride (CCl4-induced liver injury and to clarify its active component(s. Antioxidative effects of the test samples were evaluated via MDA inhibition, catalase activity and DPPH-scavenging assays. HPLC was used to analysis the active components. Results showed that WCPS (1 and 5 mL/kg significantly prevented CCl4-induced liver injury without chronic liver toxicity. Referring to the antioxidative activities, WCPE displayed significant MDA inhibitory and DPPH-scavenging activities with IC50 values of 0.91 ± 0.03 and 0.60 ± 0.04 mg/mL, respectively. Catalase activity was also enhanced by treatment of WCPE, acteoside and quercetin. Therefore, we suggest that acteoside and quercetin are the major contributors to the antioxidative and hepatoprotective activities of WCPS, and a possible mechanism could be mediated through reduction of oxidative stress.

  12. Effects of Peppermint (Mentha piperita L. Alcoholic Extract on Carbon Tetrachloride-induced Hepatotoxicity in Broiler Chickens Under Heat Stress Condition

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    Khodadust MR

    2015-06-01

    Full Text Available In order to investigate the effects of peppermint (Mentha piperita L. alcoholic extract on liver injury caused by the oxidant carbon tetrachloride (CCl4, an experiment was performed as a completely randomized design in a factorial arrangement (2 × 2 with 4 replications of 10 broilers each. Factors included two levels of peppermint leaf alcoholic extract (0 and 2 mL/Kg body weight and CCl4 (0 and 1 mL/Kg body weight. Results showed significant (P interactions for body weight gain (BWG, feed intake (FI and feed conversion ratio (FCR on d 42 of the experiment. The alcoholic extract of peppermint leaf did not improve growth performance, whereas CCl4 worsened BWG and FCR (P. The interaction between peppermint extract and CCl4 indicated an ameliorative effect of peppermint extract on BWG and FCR (P. The interaction effects between peppermint extract and CCl4 significantly differed for blood serum concentrations of total protein, albumin, albumin:globulin ratio, glucose, triglyceride, total cholesterol, HDLC, LDLC, LDLC:HDLC ratio, and VLDLC as well as the amount of blood liver enzymes (P. Peppermint extract significantly increased blood serum concentrations of total protein, albumin, triglyceride and HDLC, whilst CCl4 decreased those concentrations (P. Blood serum concentrations of total cholesterol, LDLC, LDLC:HDLC ratio, VLDLC and glucose were decreased by peppermint extract, whereas those concentrations were increased by CCl4 (P. A significantly higher level of liver enzymes was found in blood serum of birds treated by CCl4 than those by peppermint extract (P. A moderate effect on blood serum liver enzymes was observed by the interaction between 2 mL of peppermint extract and 1 mL of CCl4 (P. Generally, this study indicated that in vivo administration of peppermint alcoholic extract ameliorated the adverse effects of CCl4 on growth performance and liver function, therefore it might be useful for the prevention of oxidative stress

  13. The Protective Properties of the Strawberry (Fragaria ananassa) against Carbon Tetrachloride-Induced Hepatotoxicity in Rats Mediated by Anti-Apoptotic and Upregulation of Antioxidant Genes Expression Effects.

    Science.gov (United States)

    Hamed, Sherifa S; Al-Yhya, Nouf A; El-Khadragy, Manal F; Al-Olayan, Ebtesam M; Alajmi, Reem A; Hassan, Zeinab K; Hassan, Salwa B; Abdel Moneim, Ahmed E

    2016-01-01

    The strawberry (Fragaria ananassa) has been extensively used to treat a wide range of ailments in many cultures. The present study was aimed at evaluating the hepatoprotective effect of strawberry juice on experimentally induced liver injury in rats. To this end, rats were introperitoneally injected with carbon tetrachloride (CCl4) with or without strawberry juice supplementation for 12 weeks and the hepatoprotective effect of strawberry was assessed by measuring serum liver enzyme markers, hepatic tissue redox status and apoptotic markers with various techniques including biochemistry, ELISA, quantitative PCR assays and histochemistry. The hepatoprotective effect of the strawberry was evident by preventing CCl4-induced increase in liver enzymes levels. Determination of oxidative balance showed that strawberry treatment significantly blunted CCl4-induced increase in oxidative stress markers and decrease in enzymatic and non-enzymatic molecules in hepatic tissue. Furthermore, strawberry supplementation enhanced the anti-apoptotic protein, Bcl-2, and restrained the pro-apoptotic proteins Bax and caspase-3 with a marked reduction in collagen areas in hepatic tissue. These findings demonstrated that strawberry (F. ananassa) juice possessed antioxidant, anti-apoptotic and anti-fibrotic properties, probably mediated by the presence of polyphenols and flavonoids compounds.

  14. Endogenous hydrogen sulfide is associated with angiotensin II type 1 receptor in a rat model of carbon tetrachloride-induced hepatic fibrosis

    Science.gov (United States)

    FAN, HUI-NING; CHEN, NI-WEI; SHEN, WEI-LIN; ZHAO, XIANG-YUN; ZHANG, JING

    2015-01-01

    The present study aimed to investigate the effects of endogenous hydrogen sulfide (H2S) on the expression levels of angiotensin II type 1 receptor (AGTR1) in a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis. A total of 56 Wistar rats were randomly divided into four groups: Normal control group, model group, sodium hydrosulfide (NaHS) group, and DL-propargylglycine (PAG) group. Hepatic fibrosis was induced by CCl4. The rats in the PAG group were intraperitoneally injected with PAG, an inhibitor of cystathionine-γ-lyase (CSE). The rats in the NaHS group were intraperitoneally injected with NaHS. An equal volume of saline solution was intraperitoneally injected into both the control and model groups. All rats were sacrificed at week three or four following treatment. The serum levels of hyaluronidase (HA), laminin protein (LN), procollagen III (PcIII), and collagen IV (cIV) were detected using ELISA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin (ALB) were detected using an automatic biochemical analyzer. The liver mRNA expression levels of CSE were detected by reverse transcription-quantitative polymerase chain reaction. The liver expression levels of AGTR1 and the plasma expression levels of H2S were detected using western blot analyses. The results indicated that the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly higher in the PAG group, as compared with the model group (P<0.05). Conversely, the expression levels of ALB were significantly lower in the PAG group, as compared with the model group. In addition, the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly lower in the NaHS group, as compared with

  15. Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats.

    Science.gov (United States)

    Zhang, Kexia; Zhang, Meiyu; Liu, Ziying; Zhang, Yuanyuan; Gu, Liqiang; Hu, Gaosheng; Chen, Xiaohui; Jia, Jingming

    2016-09-01

    Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0-∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level.

  16. Protective effects of the apigenin-O/C-diglucoside saponarin from Gypsophila trichotoma on carbone tetrachloride-induced hepatotoxicity in vitro/in vivo in rats.

    Science.gov (United States)

    Simeonova, Rumyana; Kondeva-Burdina, Magdalena; Vitcheva, Vessela; Krasteva, Ilina; Manov, Vassil; Mitcheva, Mitka

    2014-01-15

    This study investigated the hepatoprotective activity of saponarin, isolated from Gypsophila trichotoma Wend., using in vitro/in vivo hepatotoxicity model based on carbone tetrachloride (CCl₄)-induced liver damage in male Wistar rats. The effect of saponarin was compared with those of silymarin. In vitro experiments were carried out in primary isolated rat hepatocytes. Cell incubation with CCl₄ (86 μmol l⁻¹) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH and elevation in MDA quantity. Cell pre-incubation with saponarin (60-0.006 μg/ml) significantly ameliorated CCl₄-induced hepatic damage in a concentration-dependent manner. These results were supported by the following in vivo study. Along with decreased MDA quantity and increased level of cell protector GSH, seven day pre-treatment of rats with saponarin (80 mg/kg bw; p.o.) also prevented CCl₄ (10%, p.o.)-caused oxidative damage by increasing antioxidant enzyme activities (CAT, SOD, GST, GPx, GR). Biotransformation phase I enzymes were also assessed. Administered alone, saponarin decreased EMND and AH activities but not at the same extent as CCl₄ did. However, pre-treatment with saponarin significantly increased enzyme activities in comparison to CCl₄ only group. The observed biochemical changes were consistent with histopathological observations where the hepatoprotective effect of saponarin was comparative to the effects of the known hepatoprotecor silymarin. Our results suggest that saponarin, isolated from Gypsophila trichotoma Wend., showed in vitro and in vivo hepatoprotective and antioxidant activity against CCl₄-induced liver damage.

  17. Umbelliferone and daphnetin ameliorate carbon tetrachloride-induced hepatotoxicity in rats via nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1 expression.

    Science.gov (United States)

    Mohamed, Mohamed R; Emam, Manal A; Hassan, Nahla S; Mogadem, Abeer I

    2014-09-01

    Among various phytochemicals, coumarins comprise a very large class of plant phenolic compounds that have good nutritive value, in addition to their antioxidant effects. The purpose of the present study was to investigate the protective effects of two coumarin derivatives, umbelliferone and daphnetin, against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and elucidate the underlying mechanism. Treatment of rats with either umbelliferone or daphnetin significantly improved the CCl4-induced biochemical alterations. In addition, both compounds alleviated the induced-lipid peroxidation and boosted the antioxidant defense system. Moreover, the investigated compounds attenuated CCl4-induced histopathological alterations of the liver. Finally, umbelliferone and daphnetin induced the nuclear translocation of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective heme oxygenase-1 (HO-1). These results suggest that umbelliferone and daphnetin ameliorate oxidative stress-related hepatotoxicity via their ability to augment cellular antioxidant defenses by activating Nrf2-mediated HO-1 expression.

  18. Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride-induced hepatic injury in the Hanover Wistar rat.

    Science.gov (United States)

    Smyth, Rosemary; Munday, Michael R; York, Malcolm J; Clarke, Christopher J; Dare, Theo; Turton, John A

    2009-10-01

    Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD-1) is increased in the urine of rats with carbon tetrachloride (CCl(4))-induced hepatotoxicity. The present experiments aimed to investigate further the usefulness of urinary SOD-1 as a non-invasive biomarker of liver injury. Two investigations were carried out, a dose response study and a time course study. In the dose response study, rats were given a single dose of CCl(4) at 0 (control), 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 and 0.80 ml/kg and urine samples collected from 12 to 36 h postdosing. In the time course study, rats were dosed at 0.80 ml/kg CCl(4) and urine sampled at 4, 12, 24 and 36 h postdosing. In both studies, the presence of SOD-1 in the urine was confirmed by Western blotting with an SOD-1 antibody. In the dose response study, serum SOD activity was elevated in all CCl(4)-treated animals and urinary SOD-1 activity was increased 2.2 times at the lowest dose (0.10 ml/kg) and 60.4 times at the highest CCl(4) dose level (0.80 ml/kg). In the time course study, urinary SOD-1 was first detected in samples collected from 4 to 12 h postdosing. We conclude that urinary SOD-1 has potential as a sensitive non-invasive biomarker of CCl(4)-induced hepatocellular injury.

  19. Antioxidant and Prophylactic Effects of Delonix elata L., Stem Bark Extracts, and Flavonoid Isolated Quercetin against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Pradeepa Krishnappa

    2014-01-01

    Full Text Available Delonix elata L. (Ceasalpinaceae, is widely used by the traditional medical practitioners of Karnataka, India, to cure jaundice, and bronchial and rheumatic problems. The objective of this study was to screen the in vitro antioxidant and hepatoprotective activity of the stem bark extracts against CCl4-induced liver damage in rats. Among different stem bark extracts tested, the ethanol extract (DSE has shown significant in vitro antioxidant property in radicals scavenging, metal chelating, and lipid peroxidation inhibition assays. HPLC analysis of the DSE revealed the presence of known antioxidant molecules, namely, gallic acid, ellagic acid, coumaric acid, quercetin, and rutin. Bioassay-guided fractionation of DSE has resulted in the isolation and characterization of quercetin. DSE and quercetin have shown significant prophylactic effects by restoring the liver function markers (AST, ALT, ALP, serum bilirubin, and total protein and antioxidant enzymes (SOD, CAT, GPx, and GST. These results were proved to be hepatoprotective at par with silymarin and well supported by the histological observations of liver sections with distinct hepatic cells, and mild degree of fatty change and necrosis. The results indicated that the DSE and quercetin were significant for prophylactic activity against CCl4-induced liver damage in rats. This activity could be attributed to the antioxidant constituents in the DSE and hence justified the ethnomedicinal claims.

  20. Enrichment and purification of total flavonoids from Cortex Juglandis Mandshuricae extracts and their suppressive effect on carbon tetrachloride-induced hepatic injury in Mice.

    Science.gov (United States)

    Zhao, Pan; Qi, Chao; Wang, Gang; Dai, Xinpeng; Hou, Xiaohong

    2015-12-15

    In the present work, a simple and efficient chromatographic separation method was developed for preparative separation and enrichment of total flavonoids (TFs) from Cortex Juglandis Mandshuricae (CJM) extracts and then the protective effect of TFs against CCl4-induced acute liver injury in mice was investigated. Enrichment and purification of TFs from CJM extracts were studied using six macroporous resins and HPD-750 resin was selected as the best resin according to its adsorption and desorption properties. The operating parameters of resin column chromatography were optimized. Under the optimal conditions, TFs from CJM with purity larger than 50% were produced and their antioxidant activity was further evaluated in vitro. The mice were orally administrated with the purified TFs for seven days and then given CCl4 (0.3%, 10mL/kg i.p.). The results showed that TFs of CJM significantly attenuated the activities of serum aspartate transaminase (AST) and alanine transaminase (ALT) compared with model group, as well as the relative liver weight. Histopathological observation also revealed that TFs reduced the incidence of liver lesions and improved hepatocyte abnormality. Moreover, oral administration of TFs significantly enhanced antioxidant enzyme activities (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) and decreased the content of malondialdehyde (MDA). Histopathological and biochemical results elicited that TFs of CJM had significant hepatoprotective activity comparable to the standard silymarin. This is the first time to reveal the protective actions of the TFs from CJM against CCl4-induced liver damage in mice and this natural product should be developed as a new drug for treatment of live injury in future.

  1. Ameliorative and antidyslipidemic potentials of aqueous leaf extract of Gongronema latifolium in CCl4 carbon tetrachloride-induced oxidative stress rats

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    Asiat Na’Allah

    2016-10-01

    Full Text Available Objective: To investigate the effect of leaf aqueous extract from Gongronema latifolium (G. latifolium on CCl4 induced-oxidative stress in Wistar rat. This effect was assessed by measuring liver marker enzymes activity, analyzing the antioxidant parameters, lipid profile estimation and lipid peroxidation by-product following CCl4 induced-oxidative stress. Methods: Milled G. latifolium leaves were subjected to aqueous extraction and the filtrate was evaporated between 40–60 °C under reduced pressure and a calculated volume of the leaf extract was administered at a dose of 500 mg/kg body weight. Thirty-five rats were grouped into seven groups of 5 animals each namely; control and experimental groups. The experimental groups were treated with 2.0 mL/kg body weight CCl4, 25 mg/kg body weight/ day silymarin (a standard hepatoprotective antioxidant, 500 mg/kg body weight aqueous extract of G. latifolium leaves were administered to the CCl4 treated rats for 21 days. Results: Administration of the extract and silymarin increase significantly (P < 0.05 in liver marker enzyme (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase activities in serum, liver and kidney in the treated groups when compared with untreated groups. The antioxidant parameters (catalase, peroxidase and glutathione S-transferase were significantly elevated (P < 0.05 in animals treated with the extract and silymarin in comparison with untreated groups. CCl4 induced oxidative stress mediated variations in total cholesterol, triacylglycerides, high-density lipoprotein cholesterol, low density lipoprotein cholesterol and very low-density lipoprotein cholesterol were restored significantly (P < 0.05 by the extract. Conclusions: The result obtained from this study indicated the antioxidant and antidyslipidemic potentials of the aqueous extract of G. latifolium leaves.

  2. Ameliorative and antidyslipidemic potentials of aqueous leaf extract ofGongronema latifoliumin CCl4 carbon tetrachloride-induced oxidative stress rats

    Institute of Scientific and Technical Information of China (English)

    Asiat NaAllah; Aliu Babajide Sanusi; Hamdala AjokeOwoniyi; Abdulhakeem Olarewaju Sulyman; Jubril Olayinka Akolade

    2016-01-01

    Objective:To investigate the effect of leaf aqueous extract fromGongronema latifolium (G. latifolium) on CCl4 induced-oxidative stress in Wistar rat. This effect was assessed by measuring liver marker enzymes activity, analyzing the antioxidant parameters, lipid profile estimation and lipid peroxidation by-product following CCl4 induced-oxidative stress. Methods: MilledG. latifolium leaves were subjected to aqueous extraction and the filtrate was evaporated between 40–60°C under reduced pressure and a calculated volume of the leaf extract was administered at a dose of 500 mg/kg body weight. Thirty-five rats were grouped into seven groups of 5 animals each namely; control and experimental groups. The experimental groups were treated with 2.0 mL/kg body weight CCl4, 25 mg/kg body weight/day silymarin (a standard hepatoprotective antioxidant), 500 mg/kg body weight aqueous extract ofG. latifolium leaves were administered to the CCl4 treated rats for 21 days. Results: Administration of the extract and silymarin increase significantly (P < 0.05) in liver marker enzyme (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) activities in serum, liver and kidney in the treated groups when compared with untreated groups. The antioxidant parameters (catalase, peroxidase and glutathioneS-transferase) were significantly elevated (P < 0.05) in animals treated with the extract and silymarin in comparison with untreated groups. CCl4 induced oxidative stress mediated variations in total cholesterol, triacylglycerides, high-density lipoprotein cholesterol, low density lipoprotein cholesterol and very low-density lipoprotein cholesterol were restored significantly (P < 0.05) by the extract. Conclusions: The result obtained from this study indicated the antioxidant and antidyslipidemic potentials of the aqueous extract ofG. latifolium leaves.

  3. Tratamento homeopático da hepatotoxicose aguda induzida por tetracloreto de carbono em coelhos Homeopatic treatment of acute carbon tetrachloride induced hepatotoxicity in rabbits

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    Maria Cecília Ribeiro Moncorvo

    1998-09-01

    Full Text Available Quinze (15 coelhos (Oryctolagus cuniculus foram submetidos à intoxicação pelo tetracloreto de carbono na dosagem de 0,5 ml/kg de peso corporal, dose única, administrado por sonda gástrica. Foram realizadas as dosagens de alanina amino transferase (ALT, aspartato amino transferase (AST, fosfatase alcalina (FA e gama glutamil transferase (GGT antes e durante o experimento. Vinte e quatro (24 horas após a intoxicação, os coelhos foram divididos aleatoriamente em três grupos de 5 animais. Cada grupo recebeu um tratamento diferente durante 13 dias. O grupo I foi tratado com tetracloreto de carbono diluído na 30ª centesimal hahnemanniana (30 CH, uma vez ao dia. O grupo II recebeu Phosphorus 30 CH, também uma vez ao dia. O grupo III desempenhou o papel de controle, recebendo diariamente uma dose de placebo, pelo mesmo período de tempo que os grupos anteriores. Os resultados das concentrações séricas de ALT, AST, GGT e FA foram submetidos à análise estatística. A variação da concentração de todas as enzimas foi significativa entre os dias, mas nem todas variaram significativamente entre os grupos considerados. O tetracloreto de carbono 30 CH foi capaz de acelerar a recuperação do quadro de hepatite tóxica aguda determinada pela redução dos níveis de ALT. O tratamento com Phosphorus 30 CH mostrou-se incapaz seja de reverter o quadro de hepatite tóxica, seja de acelerar a regeneração hepática.Fithteen (15 New Zeland and Californian rabbits (Oryctolagus cuniculus were submitted to intoxication with carbon tethracloride in a dose 0/0.5 ml/kg, once a day, administred by orogastric sonde. Enzimatic parameters: alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase and gamma-glutamyltransferase of those rabbits were tested before and during the experiment. After the intoxication, the rabbits were divided in three groups of five animals. Each group received differents treatments during 13 days. The

  4. Effectiveness of cinnamon (Cinnamomum zeylanicum) bark oil in the prevention of carbon tetrachloride-induced damages on the male reproductive system.

    Science.gov (United States)

    Yüce, A; Türk, G; Çeribaşı, S; Güvenç, M; Çiftçi, M; Sönmez, M; Özer Kaya, Ş; Çay, M; Aksakal, M

    2014-04-01

    In this study, it was aimed to investigate the likelihood of detrimental effects of carbon tetrachloride (CCl4 ) on male reproductive system through oxidative stress mechanism and also protective effects of cinnamon bark oil (CBO). For this purpose, 28 healthy male Wistar rats were divided into four groups, seven rats in each. Group 1 received only olive oil daily; group 2 was treated with 100 mg kg(-1) CBO daily; group 3 was treated with only 0.25 ml kg(-1) CCl4 weekly; and group 4 received weekly CCl4 + daily CBO. All administrations were made by intragastric catheter and maintained for 10 weeks. Body and reproductive organ weights, sperm characteristics, testicular oxidative stress markers and testicular apoptosis were examined. CCl4 administration caused significant decreases in body and reproductive organ weights, testicular catalase (CAT) activity, sperm motility and concentration, and significant increases in lipid peroxidation (LPO) level, abnormal sperm rate and apoptotic index along with some histopathological damages compared with the control group. However, significant improvements were observed in absolute weights of testis and epididymis, all sperm quality parameters, LPO level, apoptotic index and testicular histopathological structure following the administration of CCl4 together with CBO when compared to group given CCl4 only. The findings of this study clearly suggest that CBO has protective effect against damages in male reproductive organs and cells induced by CCl4 .

  5. Sesamin ameliorates oxidative liver injury induced by carbon tetrachloride in rat

    OpenAIRE

    Lv, Dan; Zhu, Chang-Qing; Liu, Li

    2015-01-01

    Sesamin is naturally occurring lignan from sesame oil with putative antioxidant property. The present study was designed to investigate the protective role of sesamin against carbon tetrachloride induced oxidative liver injury. Male Wistar albino rats (180-200 g) were divided in to 5 groups (n=6). Hepatotoxicity was induced by the administration of CCl4 (0.1 ml/100 g bw., 50% v/v with olive oil) intraperitoneally. Sesamin was administered in two different dose (5 and 10 ml/kg bw) to evaluate ...

  6. Sesamin ameliorates oxidative liver injury induced by carbon tetrachloride in rat.

    Science.gov (United States)

    Lv, Dan; Zhu, Chang-Qing; Liu, Li

    2015-01-01

    Sesamin is naturally occurring lignan from sesame oil with putative antioxidant property. The present study was designed to investigate the protective role of sesamin against carbon tetrachloride induced oxidative liver injury. Male Wistar albino rats (180-200 g) were divided in to 5 groups (n=6). Hepatotoxicity was induced by the administration of CCl4 (0.1 ml/100 g bw., 50% v/v with olive oil) intraperitoneally. Sesamin was administered in two different dose (5 and 10 ml/kg bw) to evaluate the hepatoprotective activity. Sesamin significantly reduced the elevated serum liver marker enzymes (Psesamin treated groups shows the amelioration of oxidative stress induced by CCl4. Histopathological report also supported the hepatoprotection offered by sesamin. Sesamin effects in both the dose were in comparable to reference standard drug silymarin. From these above findings it has been concluded that sesamin ameliorate the oxidative liver injury in terms of reduction of lipid peroxidation and enhancement of liver antioxidant enzymes.

  7. Comprehensive characterization of serum clinical chemistry parameters and the identification of urinary superoxide dismutase in a carbon tetrachloride-induced model of hepatic fibrosis in the female Hanover Wistar rat.

    Science.gov (United States)

    Smyth, Rosemary; Munday, Michael R; York, Malcolm J; Clarke, Christopher J; Dare, Theo; Turton, John A

    2007-10-01

    Carbon tetrachloride (CCl(4)) was used to induce liver fibrosis in the rat. Using this model, we have identified changes in serum and urinary clinical chemistry parameters, and characterized histopathological lesions in the liver. Two experiments were conducted. In Experiment 1, rats were dosed at six levels of CCl(4) (0.06-0.36 ml/kg) twice weekly for 6 weeks, followed by a 6-week non-dosing recovery period (week 12). Livers were removed for histology at 6 and 12 weeks and serum parameters analysed. In Experiment 2, rats were given seven dose levels of CCl(4) (0.4-1.0 ml/kg) twice weekly for 6 weeks, followed by a 6-week recovery period (week 12); urine samples were analysed at 3, 6, 9 and 12 weeks using one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Liver fibrosis was evident at 6 weeks in Experiments 1 and 2, and the activity of serum enzymes (including alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase) was increased. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis (Experiment 2) revealed a protein band at 18.4 kDa in urine from rats treated with CCl(4), not present in control urine, which was identified as copper/zinc superoxide dismutase (Cu/Zn SOD). Western blotting revealed that SOD was increased in urine from rats treated with CCl(4) at 3 and 6 weeks, but not at 9 and 12 weeks. We conclude that Cu/Zn SOD is a urinary marker of hepatic necrosis, but not hepatic fibrosis.

  8. The potential protective effect of Physalis peruviana L. against carbon tetrachloride-induced hepatotoxicity in rats is mediated by suppression of oxidative stress and downregulation of MMP-9 expression.

    Science.gov (United States)

    Al-Olayan, Ebtisam M; El-Khadragy, Manal F; Aref, Ahmed M; Othman, Mohamed S; Kassab, Rami B; Abdel Moneim, Ahmed E

    2014-01-01

    The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice was determined by GC-MS. Quercetin and kaempferol were active components in the juice. In this study we have evaluated its potential protective effect on hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats divided into 4 groups: Group I served as control group, and Group II received weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were supplemented with Physalis juice via the drinking water. The animals of Group IV received Physalis juice as Group III and also were intraperitoneally injected weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated by improvement in liver enzymes serum levels, reduction in collagen areas, downregulation in expression of the fibrotic marker MMP-9, reduction in the peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and restoration of the activity of antioxidant enzymatic and nonenzymatic systems, namely, glutathione content, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities. The results show that the potential hepatoprotective effects of Physalis peruviana may be due to physalis acts by promotion of processes that restore hepatolobular architecture and through the inhibition of oxidative stress pathway.

  9. Comparison of cytoprotective effects of saponins isolated from leaves of Aralia elata Seem. (Araliaceae) with synthesized bisdesmosides of oleanoic acid and hederagenin on carbon tetrachloride-induced hepatic injury.

    Science.gov (United States)

    Saito, S; Ebashi, J; Sumita, S; Furumoto, T; Nagamura, Y; Nishida, K; Isiguro, I

    1993-08-01

    Glycosylations of 3-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl(1-->2)- 3,4-di-O-acetyl-alpha-L-arabinopyranosyl)-23-O-acetylhederageni n (15) with mono- (16), di- (17) and trisaccharide bromide (18) gave the bisdesmoside peracetates 19, 20 and 22, respectively, which were treated with 5% KOH in MeOH to give the bisdesmosides 25-27. Hydrolysis of the glycosides 6 and 9 having beta-D-glucopyranose as a terminal sugar component with beta-glucosidase in acetate buffer (pH 4.7) gave compounds 28 and 29, respectively. Cytoprotective effects of the synthesized triterpenoidal saponins against CCl4-induced hepatic injury were compared with those of saponins isolated from the leaves of Aralia elata Seem. (Araliaceae) using isolated hepatocytes from rat liver. Although the monodesmosides 1-4 having neutral sugar components only at the O-3 position on the aglycones showed no cytoprotective effect, bisdesmosides having sugar components at both the O-3 and O-28 positions on the aglycones had potent effects, even when the species of the sugar components were different. The bisdesmosides 10, 11, and 27 having five monosaccharides in the molecules exhibited the most potent cytoprotective effects.

  10. Prophylactic effect of four prescriptions of traditional Chinese medicine on α-naphthylisothiocyanate and carbon tetrachloride induced toxicity in rats%中医四方剂对异硫氰酸α-萘酯及四氯化碳诱发的大鼠肝损伤的预防作用

    Institute of Scientific and Technical Information of China (English)

    林国瑞; 陈荣洲; 曹伟; 林俊清; 林昭庚; 蔡金川

    2001-01-01

    目的:探讨四种中医方剂对实验性肝损伤的作用.方法:事先给予四磨饮(SMY)、桂枝茯苓丸(GFW)、泻青丸(XQW)及四逆散(SNS)的水提取物,对异硫氰酸α-萘酯(ANIT)、四氯化碳(CCl4)诱发的肝损伤,进行预防保肝评估,包括生化指标、肝组织脂质过氧化及组织病理.结果:大鼠给予ANIT后,总胆红素(TBI)、碱性磷酸酶(ALP)、谷草转氨酶(GOT)、谷丙转氨酶(GPT)皆有明显升高,组织病理显示胆道郁阻及局部坏死.四磨饮、泻青丸及四逆散在生化指标及病理观察上皆有显著的预防效果.在四氯化碳诱发的肝损伤实验中,四方剂对肝功能生化指标与肝组织脂质过氧化及病理变化等,皆显示出预防效果.结论:虽然异硫氰酸α-萘酯、四氯化碳的肝损伤机制不同,但此四方都有不同程度的保肝作用,且其作用是由多重机制来完成的.方剂处方均由君臣佐使的配合来设计,显示对不同毒物的多重保护作用.%AIM: To study the prophylactic effects of four Chinese traditional prescriptions against experimental liver injury. METHODS: Liver toxins, a-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl4) were used to induce acute liver injury. Simo Yin (SMY), Guizhi Fuling Wan (GFW), Xieqing Wan (XQW), and Sini San (SNS) were fed (500 mg/kg, in saline, po ) to the rats before toxin administration. All the animals were killed 48 h after toxin insulted. Serum index of liver function and hepatic lipid peroxidation (LPO) were estimated. Histopathological observation was conducted simultaneously. RESULTS: The rars treated with ANIT exhibited elevations of serum total bilirubin (TBI),alkaline phosphatase ( ALP ), glutamate-oxalatetransaminase ( GOT ), glutamate-pyruvate-transaminase (GPT), as well as cholestasis and parenchyma necrosis. In rats, challenged with ANIT, receiving the pretreatment of prescriptions of SMY, XQW, and SNS, the biochemical and morphological parameters of liver injury

  11. In vitro and in vivo hepatoprotective and antioxidant effects of sily-marin against carbon tetrachloride-induced hepatocyte damage in crucian carp Carassius auratus%水飞蓟素对四氯化碳致鲫肝(细胞)损伤的保护和抗氧化作用

    Institute of Scientific and Technical Information of China (English)

    贾睿; 曹丽萍; 杜金梁; 徐跑; 殷国俊

    2013-01-01

    We evaluated the hepatoprotective and antioxidant effects of silymarin (SM) against carbon tetrachlo-ride (CCl4)-induced hepatocyte and liver injury in crucian carp (carassius auratus) in vitro and in vivo. In vitro, 100, 300, and 600 μg/mL silymarin were added to carp primary hepatocytes before (pre-treatment), after (post-treatment), or both before and after(pre- and post-treatment) incubation of the hepatocytes with 8 mmol/L CCl4 in culture medium. We then measured lactate dehydrogenase (LDH), glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. In vivo, crucian carp were fed a diet containing one of three concentrations of silymarin [0.1, 0.5, or 1 g/kg (diet)] for 60 d. Each fish was then given a single intraperitoneal injection of CCl4 (30%in arachis oil), and 72 h after the injection, we collected blood and liver samples from each fish. We measured the serum biochemical indices and liver tissue indices described above. Silymarin improved cell viability and decreased GPT, GOT, LDH, MDA, and SOD activ-ity. Administration of silymarin at 0.5 and 1 g/kg diet for 60 d prior to CCl4 intoxication significantly decreased GPT, GOT, and LDH activity, increased levels of total protein and albumin in the serum, and increased SOD, glu-tathione peroxidase, catalase, glutathione, total antioxidant capacity, and MDA formation in liver tissue. However, these parameters, except for LDH, were not significantly altered in fish fed 0.1 g silymarin per kg diet. Our data suggest that silymarin exhibits a protective effect against CCl4-induced hepatotoxicity in fish, which is likely re-lated to its antioxidant activity. We suggest that silymarin may be used as a hepatoprotective agent against fish liver diseases.%  为了评价水飞蓟素(Silymarin, SM)对鲫(Cyprinus carpio)肝(细胞)的保护和抗氧化作用,分别从体外和体内两个方面探讨其作用效果。在体外,利用8

  12. Th2-Associated Alternative Kupffer Cell Activation Promotes Liver Fibrosis without Inducing Local Inflammation

    Science.gov (United States)

    López-Navarrete, Giuliana; Ramos-Martínez, Espiridión; Suárez-Álvarez, Karina; Aguirre-García, Jesús; Ledezma-Soto, Yadira; León-Cabrera, Sonia; Gudiño-Zayas, Marco; Guzmán, Carolina; Gutiérrez-Reyes, Gabriela; Hernández-Ruíz, Joselín; Camacho-Arroyo, Ignacio; Robles-Díaz, Guillermo; Kershenobich, David; Terrazas, Luis I.; Escobedo, Galileo

    2011-01-01

    Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis. PMID:22110380

  13. Th2-Associated Alternative Kupffer Cell Activation Promotes Liver Fibrosis without Inducing Local Inflammation

    Directory of Open Access Journals (Sweden)

    Giuliana López-Navarrete, Espiridión Ramos-Martínez, Karina Suárez-Álvarez, Jesús Aguirre-García, Yadira Ledezma-Soto, Sonia León-Cabrera, Marco Gudiño-Zayas, Carolina Guzmán, Gabriela Gutiérrez-Reyes

    2011-01-01

    Full Text Available Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.

  14. Expression of VDAC Regulated by Extracts of Limonium sinense Ktze root Against CCl4-induced Liver Damage

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    Xiaoning Zhao

    2007-03-01

    Full Text Available The expression of mitochondrial voltage-dependent anion channels (VDAC mayunderlie the protective effects of Limonium sinense (Girard Ktze root extracts (LSE againstcarbon tetrachloride-induced liver damage. Pretreatment of mice with 100 mg/kg, 200mg/kg or 400 mg/kg LSE significantly blocked the carbon tetrachloride-induced increase inboth serum aspartate aminotransferase (sAST and serum alanine aminotransferase (sALTlevels. Ultrastructural observations by electron microscope confirmed hepatoprotection,showing decreased nuclear condensation, ameliorated mitochondrial fragmentation of thecristae and less lipid deposition. Pretreatment with LSE prevented the decrease of thedisruption of mitochondrial membrane potential (15.3% observed in the liver of the carbontetrachloride-insulted mice, further demonstrating the mitochondrial protection. In addition,LSE treatment (100-400 mg/kg significantly increased both transcription and translation ofVDAC. The above data suggests that LSE mitigates the damage to liver mitochondriainduced by carbon tetrachloride, possibly through regulation of mitochondrial VDAC, one ofthe most important proteins in the mitochondrial outer membrane.

  15. Hepatoprotective activity of Eclipta alba against carbon tetrachloride-induced hepatotoxicity in albino rats

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    Ravindra S. Beedimani

    2015-06-01

    Conclusion: The results of the study confirmed the hepatoprotective activity of aqueous extracts of E. alba at doses of 250 mg/kg and 500 mg/kg against CCl4 induced hepatotoxicity in rats. However, the dose adjustments may be necessary to optimize the similar hepatoprotective efficacy in clinical settings. [Int J Basic Clin Pharmacol 2015; 4(3.000: 404-409

  16. Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney damage in rats.

    Science.gov (United States)

    Awodele, Olufunsho; Adeneye, Adejuwon Adewale; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

    2015-12-01

    There is little scientific evidence on the local use of Mangifera indica in kidney diseases. This study investigated the reno-modulatory roles of the aqueous stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.). Serum levels of electrolytes (Na+, K+, Cl(-), HCO3(-)), urea and creatinine were determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), superoxide (SOD) activities were also assessed. The histopathological changes in kidneys were determined using standard methods. In CCl4 treated rats the results showed significant (pMangifera indica may present a great prospect for drug development in the management of kidney disease with lipid peroxidation as its etiology.

  17. Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and scavenge free radicals in vitro.

    Science.gov (United States)

    Lapshina, Elena A; Zamaraeva, Maria; Cheshchevik, Vitali T; Olchowik-Grabarek, Ewa; Sekowski, Szymon; Zukowska, Izabela; Golovach, Nina G; Burd, Vasili N; Zavodnik, Ilya B

    2015-06-01

    The present study was undertaken for further elucidation of the mechanisms of flavonoid biological activity, focusing on the antioxidative and protective effects of cranberry flavonoids in free radical-generating systems and those on mitochondrial ultrastructure during carbon tetrachloride-induced rat intoxication. Treatment of rats with cranberry flavonoids (7 mg/kg) during chronic carbon tetrachloride-induced intoxication led to prevention of mitochondrial damage, including fragmentation, rupture and local loss of the outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids effectively scavenged nitric oxide (IC50  = 4.4 ± 0.4 µg/ml), superoxide anion radicals (IC50  = 2.8 ± 0.3 µg/ml) and hydroxyl radicals (IC50  = 53 ± 4 µg/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) was 2.2 ± 0.3 µg/ml. Flavonoids prevented to some extent lipid peroxidation in liposomal membranes and glutathione oxidation in erythrocytes treated with UV irradiation or organic hydroperoxides as well as decreased the rigidity of the outer leaflet of the liposomal membranes. The hepatoprotective potential of cranberry flavonoids could be due to specific prevention of rat liver mitochondrial damage. The mitochondria-addressed effects of flavonoids might be related both to radical-scavenging properties and modulation of various mitochondrial events.

  18. Observation of the hepatoprotective and antioxidant activities of Trianthema decandra Linn. (Vallai sharunnai roots on carbon tetrachloride-treated rats

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    G. Balamurugan

    2008-06-01

    Full Text Available The present study was carried out to observe the hepatoprotective effect and antioxidant activity of the ethanol extract of the roots of Trianthema decandra Linn. (200 and 400 mg/kg in rats treated with carbon tetrachloride for 8 weeks. Extract at the tested doses restored the levels of all serum (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and total protein and liver homogenate enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase significantly. Histology demonstrated profound steatosis degeneration and nodule formation were observed in the hepatic architecture of carbon tetrachloride treated rats which were found to acquire near-normalcy in extract plus carbon tetrachloride administrated rats, and supported the biochemical observations. This study suggests that ethanol extract of T. decandra has a liver protective effect against carbon tetrachloride- induced hepatotoxicity and possess antioxidant activities.

  19. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

    Science.gov (United States)

    Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau

    2015-01-01

    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis. PMID:26691857

  20. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Silvia Affò

    Full Text Available Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+ and mature dendritic (MHCII+CD11c+ cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

  1. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

    Science.gov (United States)

    Affò, Silvia; Rodrigo-Torres, Daniel; Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau

    2015-01-01

    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

  2. Cryopreserved hepatic progenitor cells derived from human embryonic stem cells can arrest progression of liver fibrosis in rats.

    Science.gov (United States)

    Mandal, Arundhati; Raju, Sheena; Viswanathan, Chandra

    2016-10-01

    Hepatocytes generated from human embryonic stem cells (hESCs) are considered to be an excellent candidate for restoring the liver function deficiencies. We have earlier standardized a three-step differentiation protocol to generate functional hepatocyte-like cells (HLCs) from hESCs, which expressed the major hepatic markers. We have also found that the HLCs remain stable and functional even after extended period of in vitro culture and cryopreservation. In the present study, we have aimed to investigate the therapeutic potential of cryopreserved-thawed hESC-derived hepatic progenitor cells following transplantation in carbon tetrachloride-induced fibrotic rat livers. Significant therapeutic effects, including improved hepatic histology and normal serum biochemistry of hepatic enzymes along with increased survival rate, were observed in the cell transplanted rats. This result is an encouraging indication to develop methods for clinical application of hESC-derived hepatic lineage cells.

  3. Endocannabinoid System Contributes to Liver Injury and Inflammation by Activation of Bone Marrow-Derived Monocytes/Macrophages in a CB1-Dependent Manner.

    Science.gov (United States)

    Mai, Ping; Yang, Le; Tian, Lei; Wang, Lin; Jia, Shuangshuang; Zhang, Yuanyuan; Liu, Xin; Yang, Lin; Li, Liying

    2015-10-01

    Hepatic injury undergoes significant increases in endocannabinoidsand infiltrations of macrophages, yet the concrete mechanisms of changes in endocannabinoids and the functions of macrophage-expressed cannabinoid receptors (CBs) are unclear. Biosynthetic and degradative enzymes of endocannabinoids revealed a significant change in human fibrotic liver. Meanwhile, we showed dynamic changes of these enzymes and CBs (CB1 and CB2) from 1 to 56 d in carbon tetrachloride-induced murine liver injury. Biosynthetic enzymes (N-acylphosphatidyl-ethanolamine selective phospholipase D and diacylglycerol lipase-α) and CBs were markedly increased, whereas degradative enzymes (fatty acid amidohydrolase and monoacylglycerol lipase) were downregulated. Moreover, these enzymes intimately correlated with the fibrosis parameter [procollagen α1(III)]. Bone marrow-derived monocytes/macrophages (BMM) expressed CBs. Interestingly, CB1 but not CB2 mediated BMM migration through a Boyden chambers assay, and the effect depended on the G(α)i/o/RhoA/ROCK signaling pathway. ICR mice were lethally irradiated and received BM transplants from enhanced GFP transgenic mice. Four weeks later, mice of BM reconstruction were subjected to carbon tetrachloride-induced liver injury. In the chimeric murine model, we found that blockade of CB1 by administration of a CB1 antagonist inhibited the recruitment of BMM into injured liver using immunofluorescence staining and FACS, but it did not have effects on migration of T cells and dendritic cells without CB1 expression. Furthermore, activation of CB1 enhanced cytokine expression of BMM. In vivo, inhibition of CB1 attenuated the inflammatory cytokine level through real-time RT-PCR and cytometric bead array, ameliorating hepatic inflammation and fibrosis. In this study, we identify inactivation of BMM-expressed CB1 as a therapeutic strategy for reducing hepatic inflammation and fibrosis.

  4. Corrections by melatonin of liver mitochondrial disorders under diabetes and acute intoxication in rats.

    Science.gov (United States)

    Cheshchevik, Vitali T; Dremza, Iosif K; Lapshina, Elena A; Zabrodskaya, Svetlana V; Kujawa, Jolanta; Zavodnik, Ilya B

    2011-08-01

    The aim of the present work was to investigate the mechanisms of oxidative damage of the liver mitochondria under diabetes and intoxication in rats as well as to evaluate the possibility of corrections of mitochondrial disorders by pharmacological doses of melatonin. The experimental (30 days) streptozotocin-induced diabetes mellitus caused a significant damage of the respiratory activity in rat liver mitochondria. In the case of succinate as a respiratory substrate, the ADP-stimulated respiration rate V₃ considerably decreased (by 25%, p diabetic liver damage. Acute rat carbon tetrachloride-induced intoxication resulted in considerable decrease of the phosphorylation coefficient because of uncoupling of the oxidation and phosphorylation processes in the liver mitochondria. The melatonin administration during diabetes (10 mg·kg⁻¹ body weight, 30 days, daily) showed a considerable protective effect on the liver mitochondrial function, reversing the decreased respiration rate V₃ and the diminished ACR to the control values both for succinate-dependent respiration and for glutamate-dependent respiration. The melatonin administration to intoxicated animals (10 mg·kg⁻¹ body weight, three times) partially increased the rate of succinate-dependent respiration coupled with phosphorylation. The impairment of mitochondrial respiratory plays a key role in the development of liver injury under diabetes and intoxication. Melatonin might be considered as an effector that regulates the mitochondrial function under diabetes.

  5. Carbon dioxide and liver blood flow.

    Science.gov (United States)

    Dutton, R; Levitzky, M; Berkman, R

    1976-01-01

    This study was designed to determine blood flow to the liver during hypercapnia and combined hypercapnia-hypoxia with the portal vein and hepatic artery intact except for placement of an electromagnetic flow probe around these vessels. Twenty mongrel dogs weighing 30-45 kg were anesthetized with pentobarbital and flow probes and occluders were surgically implanted. Ten of these dogs were subjected to hypercapnia alone. During inspiration of 6% CO2 in room air, portal vein flow increased from 588 +/- 73 ml/min to 731 +/- 113 ml/min (p less than .05), while hepatic artery flow did not change significantly from its control mean of 221 +/- 38 ml/min. In the remaining dogs, inhalation of 6% O2 resulted in a reduction of portal blood flow within 30 min from 527 +/- 55 ml/min to 381 +/- 41 ml/min (p less than .01). Again, mean hepatic artery flow did not increase significantly above its control of 273 +/- 43 ml/min. Subsequent inhalation of 6% CO2 plus 6% O2 (combined hypercapniahypoxia) for 30 min in these same animals resulted in a significant increase of portal vein blood flow from 514 +/- 46 ml/min to 716 +/- 116 ml/min (p less than .05). Thus, hypercapnia alone increases total liver blood flow, primarily by an increase in portal vein flow. Hypoxia results in a decrease in portal vein flow. The superimposition of hypercapnia on hypoxia restores blood flow to a level close to that found with hypercapnia alone. Hypercapnia in the range of 63 +/- 4 mmHg PCO2 overwhelms the tendency toward a reduction of portal vein blood flow induced by an arterial PO2 of 42 +/- 5 mmHg in the presence of mild hypocapnia (PCO2 : 30.2 +/- 1 mmHg).

  6. Proteinase activated receptor 1 mediated fibrosis in a mouse model of liver injury: a role for bone marrow derived macrophages.

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    Yiannis N Kallis

    Full Text Available Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1 is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment.

  7. Mechanism underlying carbon tetrachloride-inhibited protein synthesis in liver

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To study the mechanism underlying carbon tetrachloride (CCl4)-induced alterations of protein synthesis in liver. METHODS: Male Sprague-Dawley rats were given CCl4 (1 mL/100 g body weight) and 3H-leucine incorporation. Malondialdehyde (MDA) level in the liver, in vitro response of hepatocyte nuclei nucleotide triphosphatase (NTPase) to free radicals, and nuclear export of total mRNA with 3'-poly A+ were measured respectively. Survival response of HepG2 cells to CCl4 treatment was assessed by methyl thia...

  8. Effect of Rougan Huaqian granules combined with human mesenchymal stem cell transplantation on liver fibrosis in cirrhosis rats

    Institute of Scientific and Technical Information of China (English)

    Zhen-Chang Wang; Shan Yang; Jing-Jing Huang; Song-Lin Chen; Quan-Qiang Li; Yuan Li

    2014-01-01

    Objective:To observe the effect ofRouganHuaqian granules combined with human mesenchymal stem cell(hMSC) transplantation on the liver fibrosis in carbon tetrachloride-induced cirrhosis rats.Methods:SixtySD rats were randomly divided into five groups.The rats in control group received intraperitoneal injection of saline, while those in model control group, treatment groupA, groupB and groupC received intraperitoneal injection of carbon tetrachloride oily solution to induce liver cirrhosis within8 weeks.Then, the rats in the model control group, treatment groupA, treatment groupB, treatment groupC received vein tail injection of saline, RouganHuaqian granules, hMSC suspension andRouganHuaqian granules combined with hMSC suspension.Results:The treatment groups had significantly different liverfunction(AST levels), liver fibrosis index(laminin andHA), hepatic sinusoidal wallsα-smooth muscle actin,Ⅳ collagen and laminin protein expression andⅠ,Ⅲ collagen from the model group(P<0.05). The transplanted cells showed human hepatocyte-like cells differentiation trend in the liver. Conclusions:TheRouganHuaqian granules combined with hMSC transplantation can alleviate liver fibrosis in cirrhosis rats.

  9. Amelioration of carbon tetrachloride- and paracetamol-induced hepatotoxicity in rats by Ficus dalhousiae

    Directory of Open Access Journals (Sweden)

    Syed Safiullah Ghori

    2014-12-01

    Full Text Available The present study was undertaken to investigate hepatoprotective activity of Ficus dalhousiae leaves ethanolic extract based on its traditional claim. Paracetamol- and carbon tetrachloride-induced hepatotoxicity in albino Wistar rats, experimental models was used for the evaluation. Various biochemical parameters like SGPT, SGOT, serum albumin, alkaline phosphatase, total bilirubin, direct bilirubin and total protein were estimated. Oral treatment with the extract 250 and 500 mg/kg, significantly (p<0.01 altered all the serum marker levels to the normal in both the experimental models. The activity of the extract was comparable to that of standard drug, silymarin (25 mg/kg, p.o.. Histopathological observations also demonstrated protective effect of the test extract on liver anatomy. Overall results suggest that F. dalhousiae possesses in vivo hepatoprotective activity.

  10. In vitro and in vivo antioxidant activity of alfalfa (Medicago sativa L.) on carbon tetrachloride intoxicated rats.

    Science.gov (United States)

    Al-Dosari, Mohammed S

    2012-01-01

    The present study was conducted to determine whether lyophilized aqueous extract of alfalfa, or Medicago sativa L. could exert antioxidant activity against carbon tetrachloride-induced oxidative stress and liver injury in rats. The hepatoprotective activity of alfalfa extract was determined by assessing the levels of serum transaminases, ALP, bilirubin and lipid profile. Further, the effect of the test substance on malondialdehyde (MDA), an end product of lipid peroxidation; antioxidant liver enzyme non-protein sulfhydryl (NP-SH); and total protein (TP) were also studied. Serum transaminase, ALP, bilirubin level, lipid profile and liver MDA were significantly elevated and the antioxidant status in liver NP-SH and TP contents were declined in animals treated with CCl (4) alone. Pretreatment with alfalfa and silymarin for three weeks prior to the administration of CCl (4) significantly prevented the increase in the serum levels of hepatic marker, LDL, VLDL levels enzymes and reduced oxidative stress indicated by elevated NP-SH and TP concentration. The histopathological examination of the livers also showed that the alfalfa extract reduced the incidence of liver lesions induced by CCl (4). The in vitro antioxidant assessment of alfalfa extract on DPPH and carotene-linoleic assays demonstrated a moderate antioxidant potential. Results suggest that the alfalfa extract possesses hepatoprotective and antioxidative stress properties possibly through its antioxidant phytochemical constituents and substantiates its use in various liver disorders as a hepatoprotector.

  11. Gaseous persufflation with carbon monoxide during ischemia protects the isolated liver and enhances energetic recovery

    NARCIS (Netherlands)

    Koetting, Martina; Leuvenink, Henri; Dombrowski, Frank; Minor, Thomas

    2010-01-01

    Background: The benefit of carbon monoxide as applied by controlled, continuous gaseous persufflation during liver preservation on postischemic graft recovery was investigated in an isolated rat liver model. Methods: Livers from male Wistar rats were retrieved 30 min after cardiac arrest of the dono

  12. Ameliorative effect of alkaloid extract of Cyclea peltata (Poir.) Hook. f. & Thoms. roots (ACP) on APAP/CCl4 induced liver toxicity in Wistar rats and in vitro free radical scavenging property

    Institute of Scientific and Technical Information of China (English)

    Varghese Jancy Shine; Somasekharan Nair Rajam Suja; Gangadharan Indira Anuja; Gopan Raj; Sreedharan Nair Rajasekharan

    2014-01-01

    Objective: To evaluate the hepatoprotective and antioxidant properties of alkaloid extract of Cyclea peltata (C. peltata) against paracetamol/carbon tetra chloride induced liver damage in Wistar rats.Methods: In vivo paracetamol/carbon tetrachloride induced liver damage in Wistar rats, in vitro free radical scavenging studies, HPTLC estimation of tetrandrine and direct analysis in real time-mass spectrometry of alkaloid extract of C. peltata were used for the validation. Results: The results showed that pretreatment with alkaloid extract of C. peltata caused significant reduction of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, serum alkaline phosphatase, serum cholesterol, liver malondialdehyde levels. The reduced glutathione, catalase, superoxide dismutase levels in liver were increased with alkaloid extract of C. peltata treatment. These results were almost comparable to silymarin and normal control. Histopathological studies also substantiated the biochemical findings. The in vitro hydroxyl, superoxide and DPPH scavenging study of alkaloid extract of C. peltata showed significant free radical scavenging property.Conclusions:The hepatoprotective property of alkaloid extract of C. peltata against paracetamol/carbon tetrachloride may be due the synergistic action of alkaloids especially tetrandrine, fangchinoline through free radical scavenging and thus preventing oxidative stress.

  13. Spatio-temporal simulation of first pass drug perfusion in the liver.

    Directory of Open Access Journals (Sweden)

    Lars Ole Schwen

    2014-03-01

    Full Text Available The liver is the central organ for detoxification of xenobiotics in the body. In pharmacokinetic modeling, hepatic metabolization capacity is typically quantified as hepatic clearance computed as degradation in well-stirred compartments. This is an accurate mechanistic description once a quasi-equilibrium between blood and surrounding tissue is established. However, this model structure cannot be used to simulate spatio-temporal distribution during the first instants after drug injection. In this paper, we introduce a new spatially resolved model to simulate first pass perfusion of compounds within the naive liver. The model is based on vascular structures obtained from computed tomography as well as physiologically based mass transfer descriptions obtained from pharmacokinetic modeling. The physiological architecture of hepatic tissue in our model is governed by both vascular geometry and the composition of the connecting hepatic tissue. In particular, we here consider locally distributed mass flow in liver tissue instead of considering well-stirred compartments. Experimentally, the model structure corresponds to an isolated perfused liver and provides an ideal platform to address first pass effects and questions of hepatic heterogeneity. The model was evaluated for three exemplary compounds covering key aspects of perfusion, distribution and metabolization within the liver. As pathophysiological states we considered the influence of steatosis and carbon tetrachloride-induced liver necrosis on total hepatic distribution and metabolic capacity. Notably, we found that our computational predictions are in qualitative agreement with previously published experimental data. The simulation results provide an unprecedented level of detail in compound concentration profiles during first pass perfusion, both spatio-temporally in liver tissue itself and temporally in the outflowing blood. We expect our model to be the foundation of further spatially

  14. Amelioration of SD rats acute liver injury model induced by carbon tetrachloride%CCl4致SD大鼠急性肝损伤模型制作的改进

    Institute of Scientific and Technical Information of China (English)

    张旻; 唐晓鹏; 李代强; 童敏; 王文龙

    2004-01-01

    Objective: The purpose of this study was to optimize carbon tetrachloride-induced hepatotoxicity in the rat with respect to dose and time course. Method: Carbon tetrachloride with different dosage was given to SD rats by abdominal injection. Rat ALT and AST in serum were analyzed 48 h and rats liver were observed with routine pathology technique, to determine mice liyers' functional and morphological changes after administration. Results: The serum level of ALT and AST increased significantly in 3A~7A CCl4 groups compared with the control group (P<0.05 or P<0.01). The pathological changes in can be seen in every ccl4 group, the damnification degree of liver cells were remarkably aggravated with the control group. Deceased rats were seen in 6A and 7A group. Conclusion: Ameliorated acute liver injury model of mice was established, which has definite liver injury with lower mortality rate and less damnification to other organs, can be used for the mechanism and treatment research of acute liver injury.%目的本文筛选CCl4致SD大鼠急性肝损伤模型的最佳给药浓度和剂量,追踪观察模型大鼠肝损伤后修复过程.方法本文采用随机对照分组的研究方法,对不同的SD大鼠模型组给予不同剂量的CCl4一次性腹腔注射.给药后48h检测大鼠血清ALT,AST.各组随机处死一只SD大鼠,取肝组织制成病理切片镜下观察.追踪观察筛选后的CCl4模型大鼠肝组织病理变化恢复情况.结果本实验发现3A-7A组的ALT,AST较对照组明显升高(P<0.05或P<0.01),随着CCl4的剂量的增加,大鼠肝组织的病理损伤加重,6A和7A组可见自然死亡大鼠.结论本试验筛选了CCl4致SD大鼠急性肝损伤模型的较好CCl4的剂量.该模型肝损伤明显,死亡率低,对其他重要脏器影响小,可作为急性肝损伤研究的较好模型.

  15. Study on the Effect of Chinese Herbal Medicine in Regulating Peritoneal Lymphatic Stomata and Enhancing Drainage of Ascites in Mice with Liver Fibrosis

    Institute of Scientific and Technical Information of China (English)

    李继承; 袁淑慧; 赵坚培; 吕志连

    2001-01-01

    Objective: To observe the regulating effect of Chinese herbal medicine on peritoneal lymphatic stomata and its significance in treating ascites in liver fibrosis model mice. Methods: Two Chinese herbal compound prescriptions were used separately to treat the carbon tetrachloride induced mouse model of liver fibrosis, the histo-pathologic changes in mice were observed by using scanning electron microscope and processed by computer image processing. The changes of urinary volume and sodium ion concentration were measured, too.Results: In the treated group, the histo-pathologic changes were significantly less than those in the control group, the peritoneal lymphatic stomata enlarged with increased number of opening and higher density in distribution and the urinary volume and sodium ion excretion increased after treatment. Conclusion: Chinese herbal medicine has marked effect in alleviating liver fibrosis, regulating peritoneal lymphatic stomata, improving the drainage of ascites from peritoneal cavity, causing increase of urinary volume and sodium ion excretion to reduce water and sodium retention, and thus have favorable therapeutic effect in treating ascites.

  16. Deregulation of energy metabolism promotes antifibrotic effects in human hepatic stellate cells and prevents liver fibrosis in a mouse model.

    Science.gov (United States)

    Karthikeyan, Swathi; Potter, James J; Geschwind, Jean-Francois; Sur, Surojit; Hamilton, James P; Vogelstein, Bert; Kinzler, Kenneth W; Mezey, Esteban; Ganapathy-Kanniappan, Shanmugasundaram

    2016-01-15

    Liver fibrosis and cirrhosis result from uncontrolled secretion and accumulation of extracellular matrix (ECM) proteins by hepatic stellate cells (HSCs) that are activated by liver injury and inflammation. Despite the progress in understanding the biology liver fibrogenesis and the identification of potential targets for treating fibrosis, development of an effective therapy remains elusive. Since an uninterrupted supply of intracellular energy is critical for the activated-HSCs to maintain constant synthesis and secretion of ECM, we hypothesized that interfering with energy metabolism could affect ECM secretion. Here we report that a sublethal dose of the energy blocker, 3-bromopyruvate (3-BrPA) facilitates phenotypic alteration of activated LX-2 (a human hepatic stellate cell line), into a less-active form. This treatment-dependent reversal of activated-LX2 cells was evidenced by a reduction in α-smooth muscle actin (α-SMA) and collagen secretion, and an increase in activity of matrix metalloproteases. Mechanistically, 3-BrPA-dependent antifibrotic effects involved down-regulation of the mitochondrial metabolic enzyme, ATP5E, and up-regulation of glycolysis, as evident by elevated levels of lactate dehydrogenase, lactate production and its transporter, MCT4. Finally, the antifibrotic effects of 3-BrPA were validated in vivo in a mouse model of carbon tetrachloride-induced liver fibrosis. Results from histopathology & histochemical staining for collagen and α-SMA substantiated that 3-BrPA promotes antifibrotic effects in vivo. Taken together, our data indicate that sublethal, metronomic treatment with 3-BrPA blocks the progression of liver fibrosis suggesting its potential as a novel therapeutic for treating liver fibrosis.

  17. Mistletoe alkali inhibits peroxidation in rat liver and kidney

    Institute of Scientific and Technical Information of China (English)

    Zheng-Ming Shi; Ping Feng; Dong-Qiao Jiang; Xue-Jiang Wang

    2006-01-01

    AIM: To explore the antioxidant and free radical scavenger properties of mistletoe alkali (MA).METHODS: The antioxidant effect of mistletoe alkali on the oxidative stress induced by carbon tetrachloride (CCl4) in rats was investigated. The rats were divided into four groups (n = 8): CCl4-treated group (1 mL/kg body weight), MA -treated group (90 mg/kg), CCl4+MA-treated group and normal control group. After 4 wk of treatment,the level of malondialdehyde (MDA), a lipid peroxidation product (LPO) was measured in serum and homogenates of liver and kidney. Also, the level of glutathione (GSH),and activities of glutathione reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), and glutathione-S-transferase (GST) in liver and kidney were determined. Scavenging effects on hydroxyl free radicals produced in vitro by Fenton reaction were studied by ESR methods using 5,5-dimethyl-1-pyrroline-N-oxidesource. Urinary 8-hydroxydeoxyguanosine (8-OHdG) was determined by competitive ELISA.RESULTS: In CCl4-treated group, the level of LPO in serum of liver and kidney was significantly increased compared to controls. The levels of GSH and enzyme activities of SOD, GSPx and GR in liver and kidney were significantly decreased in comparison with controls. In CCl4+MA-treated group, the changes in the levels of LPO in serum of liver and kidney were not statistically significant compared to controls. The levels of SOD, GSPx and GR in liver and kidney were significantly increased in comparison with controls. There was a significant difference in urinary excretion of 8-OHdG between the CCl4-treated and MA-treated groups.CONCLUSION: Oxidative stress may be a major mechanism for the toxicity of CCl4. MA has a protective www.wjgnet.comeffect against CCl4 toxicity by inhibiting the oxidative damage and stimulating GST activities. Thus, clinical application of MA should be considered in cases with carbon tetrachloride-induced injury.

  18. Pharmacologic application of fourier transform IR spectroscopy: in vivo toxicity of carbon tetrachloride on rat liver.

    Science.gov (United States)

    Melin, A M; Perromat, A; Déléris, G

    2000-01-01

    Microsomal fractions from rat liver were examined by means of Fourier transform IR (FTIR) spectroscopy to study the in vivo toxic effect of carbon tetrachloride administered by intraperitoneal injection. Lipid content was significantly enhanced in the liver of treated rats compared with untreated ones. The level of saturated fatty acids largely increased while that of unsaturated acids slightly decreased as a consequence of lipid peroxidation induced by the xenobiotic compound. The conformational structure of membrane proteins was changed, which was shown by the large decrease in the alpha-helical configuration. In the polysaccharide region we observed an important loss in glucidic structures that could be related to the metabolic changes caused by carbon tetrachloride intoxication. Thus, FTIR spectroscopy appears to be a useful tool to rapidly investigate the chemical alterations induced by this drug in liver microsomes and to correlate them with biochemical and physiological data.

  19. Monitoring of liver glycogen synthesis in diabetic patients using carbon-13 MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tomiyasu, Moyoko [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan)], E-mail: moyo@fml.nirs.go.jp; Obata, Takayuki [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Nishi, Yukio; Nakamoto, Hiromitsu [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Pharmaceutical Division, Japan Tobacco Inc., Tokyo (Japan); Nonaka, Hiroi [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Takayama, Yukihisa [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan); Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Autio, Joonas; Ikehira, Hiroo; Kanno, Iwao [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba city, Chiba 263-8555 (Japan)

    2010-02-15

    To investigate the relationship between liver glucose, glycogen, and plasma glucose in diabetic patients, in vivo liver carbon-13 magnetic resonance spectroscopy ({sup 13}C MRS) with a clinical 3.0 T MR system was performed. Subjects were healthy male volunteers (n = 5) and male type-2 diabetic patients (n = 5). Pre- and during oral glucose tolerance tests (OGTT), {sup 13}C MR spectra without proton decoupling were acquired in a monitoring period of over 6 h, and in total seven spectra were obtained from each subject. For OGTT, 75 g of glucose, including 5 g of [1-{sup 13}C]glucose, was administered. The MR signals of liver [1-{sup 13}C]glucose and glycogen were detected and their time-course changes were assessed in comparison with the plasma data obtained at screening. The correlations between the fasting plasma glucose level and liver glycogen/glucose rate (Spearman: {rho} = -0.68, p < 0.05, n = 10) and the fasting plasma glucose level and liver glycogen peak/fasting rate (Spearman: {rho} = -0.67, p < 0.05, n = 10) indicated that {sup 13}C MRS can perform noninvasive measurement of glycogen storage/degradation ability in the liver individually and can assist in tailor-made therapy for diabetes. In conclusion, {sup 13}C MRS has a potential to become a powerful tool in diagnosing diabetes multilaterally.

  20. Proteomic Analysis of One-carbon Metabolism-related Marker in Liver of Rat Offspring.

    Science.gov (United States)

    You, Young-Ah; Lee, Ji Hye; Kwon, Eun Jin; Yoo, Jae Young; Kwon, Woo-Sung; Pang, Myung-Geol; Kim, Young Ju

    2015-11-01

    Maternal food intake has a significant effect on the fetal environment, and an inadequate maternal diet may result in intrauterine growth restriction. Intrauterine growth restriction newborn rat pups nursed by normal diet-fed dams exhibited rapid catch-up growth, which plays a critical role in the risk for metabolic and cardiovascular disease in later life. Specifically, one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. Data are available via ProteomeXchange with identifier PXD002578. We determined that betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p normal diet during lactation. However, in female offspring only expression levels of methylenetetrahydrofolate dehydrogenase 1 were negatively correlated with homocysteine concentration. This study shows that maternal food restriction during late gestation and normal diet during lactation lead to increased homocysteine concentration through disturbance of one-carbon metabolism in the livers of male offspring. This suggests that male offspring have an increased gender-specific susceptibility to disease in later life through fetal programming.

  1. Integrated plasma and urine metabolomics coupled with HPLC/QTOF-MS and chemometric analysis on potential biomarkers in liver injury and hepatoprotective effects of Er-Zhi-Wan.

    Science.gov (United States)

    Yao, Weifeng; Gu, Haiwei; Zhu, Jiangjiang; Barding, Gregory; Cheng, Haibo; Bao, Beihua; Zhang, Li; Ding, Anwei; Li, Wei

    2014-11-01

    Metabolomics techniques are the comprehensive assessment of endogenous metabolites in a biological system and may provide additional insight into the molecular mechanisms. Er-Zhi-Wan (EZW) is a traditional Chinese medicine formula, which contains Fructus Ligustri Lucidi (FLL) and Herba Ecliptae (HE). EZW is widely used to prevent and treat various liver injuries through the nourishment of the liver. However, the precise molecular mechanism of hepatoprotective effects has not been comprehensively explored. Here, an integrated metabolomics strategy was designed to assess the effects and possible mechanisms of EZW against carbon tetrachloride-induced liver injury, a commonly used model of both acute and chronic liver intoxication. High-performance chromatography/quadrupole time-of-flight mass spectrometry (HPLC/QTOF-MS) combined with chemometric approaches including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to discover differentiating metabolites in metabolomics data of rat plasma and urine. Results indicate six differentiating metabolites, tryptophan, sphinganine, tetrahydrocorticosterone, pipecolic acid, L-2-amino-3-oxobutanoic acid and phosphoribosyl pyrophosphate, in the positive mode. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan metabolism, sphingolipid metabolism, steroid hormone biosynthesis, lysine degradation, glycine, serine and threonine metabolism, and pentose phosphate pathway. Of note, EZW has a potential pharmacological effect, which might be through regulating multiple perturbed pathways to the normal state. Our findings also showed that the robust integrated metabolomics techniques are promising for identifying more biomarkers and pathways and helping to clarify the function mechanisms of traditional Chinese medicine.

  2. Pharmacological investigation of Polyherbal formulation on Carbon tetrachloride (CCl4-induced liver damage in wistar rats

    Directory of Open Access Journals (Sweden)

    Hardik Soni

    2014-09-01

    Full Text Available Objective: To investigate effect of Polyherbal formulation on Carbon tetrachloride (CCl4-induced liver damage in wistar rats. Methods: Wistar albino rats weighing 180-230 g either sex were used. The selected animals were divided in to four groups where each group consisted of six animals. Experimentally liver damage was produced by intra-peritoneal administration of CCl4 and olive oil mixture (1:1 v/v (1 mL/kg, once daily, i.p. for 7 days. Test Drug, Polyherbal formulation was administered orally for 7 consecutive days at 3 mL/kg, once daily. On 8th day, Blood samples were collected to evaluate different serum biochemical parameters like Aspartate aminotransferase (AST, Alanine aminotransferase (ALT, Alkaline phosphatase (ALP, Total bilirubin and Total protein. Liver from animals of each group was dissected out for histopathological examination. Statistical analysis: Statistical calculation were done by analysis of variance (ANOVA followed by post hoc Dunnett’s test, with significant level of p<0.05. Results and dDiscussion: Polyherbal formulation showed significant effect on activity levels of serum AST, ALT, ALP and total bilirubin level while comparing test group to disease control group. It also showed significant elevation in decreased level of serum total protein. Pre-treatment of Polyherbal formulation restored the hepatic architecture and protected the liver tissue from fatty degenerative changes by preventing the toxic chemical reaction induced by CCl4. Conclusion: Finding of this study concludes that Polyherbal formulation (Vasuliv Syrup has promising hepatoprotective activity against CCl4-induced liver damage. It can be employed as safe and effective treatment for hepato-toxicity or liver damage.

  3. Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing

    Directory of Open Access Journals (Sweden)

    Simon P. Robinson

    1999-12-01

    Full Text Available The effects of hyperoxia (induced by host carbogen 95% oxygen/5% carbon dioxide breathing. and hypoxia (induced by host carbon monoxide CO at 660 ppm. breathing were compared by using noninvasive magnetic resonance (MR methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb, which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen breathing, or carboxyhemoglobin with CO breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO breathing. There was no change in nucleoside triphosphates (NTP/PI in either tumor or liver after CO breathing, whereas NTP/Pl increased twofold in the hepatoma (but not in the liver after carbogen breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO breathing and more acid after carbogen breathing, respectively. This tumor type and the liver are unaffected by CO breathing at 660 ppm, which implies an adequate oxygen supply.

  4. Oxidation of carbon tetrachloride, bromotrichloromethane, and carbon tetrabromide by rat liver microsomes to electrophilic halogens

    Energy Technology Data Exchange (ETDEWEB)

    Mico, B.A. (National Inst. of General Medical Sciences, Bethesda, MD); Branchflower, R.V.; Pohl, L.R.; Pudzianowski, A.T.; Loew, G.H.

    1982-01-11

    In order to determine whether CCl/sub 4/, CBrCl/sub 3/, CBr/sub 4/ or CHCl/sub 3/ undergo oxidative metabolism to electrophilic halogens by liver microsomes, they were incubated with liver microsomes from phenobarbital pretreated rats in the presence of NADPH and 2,6-dimethylphenol. The analysis of the reaction mixtures by capillary gas chromatography mass spectrometry revealed that 4-chloro-2,6-dimethylphenol was a metabolite of CCl/sub 4/ and CBrCl/sub 3/ whereas 4-bromo-2,6-dimethylphenol was a metabolite of CBr/sub 4/. The formation of the metabolites was significantly decreased when the reactions were conducted with heat denatured microsomes, in the absence of NADPH or under an atmosphere of N/sub 2/. These results indicate that the chlorines of CBrCl/sub 3/ and CCl/sub 4/ and the bromines of CBr/sub 4/ are oxidatively metabolized by rat liver microsomes to electrophilic and potentially toxic metabolites.

  5. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism.

    Science.gov (United States)

    Deminice, Rafael; da Silva, Robin P; Lamarre, Simon G; Kelly, Karen B; Jacobs, René L; Brosnan, Margaret E; Brosnan, John T

    2015-04-01

    The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.

  6. Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage.

    Science.gov (United States)

    Lin, S C; Chung, T C; Lin, C C; Ueng, T H; Lin, Y H; Lin, S Y; Wang, L Y

    2000-01-01

    The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.

  7. Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver.

    Science.gov (United States)

    Suematsu, M; Goda, N; Sano, T; Kashiwagi, S; Egawa, T; Shinoda, Y; Ishimura, Y

    1995-11-01

    Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 microM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cell which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 microM) or a cGMP analogue 8-bromo-cGMP (1 microM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.

  8. Long Term Influence of Carbon Nanoparticles on Health and Liver Status in Rats.

    Directory of Open Access Journals (Sweden)

    Barbara Strojny

    Full Text Available Due to their excellent biocompatibility, carbon nanoparticles have been widely investigated for prospective biomedical applications. However, their impact on an organism with prolonged exposure is still not well understood. Here, we performed an experiment investigating diamond, graphene oxide and graphite nanoparticles, which were repeatedly administrated intraperitoneally into Wistar rats for four weeks. Some of the animals was sacrificed after the last injection, whereas the rest were sacrificed twelve weeks after the last exposure. We evaluated blood morphology and biochemistry, as well as the redox and inflammatory state of the liver. The results show the retention of nanoparticles within the peritoneal cavity in the form of prominent aggregates in proximity to the injection site, as well as the presence of some nanoparticles in the mesentery. Small aggregates were also visible in the liver serosa, suggesting possible transportation to the liver. However, none of the tested nanoparticles affected the health of animals. This lack of toxic effect may suggest the potential applicability of nanoparticles as drug carriers for local therapies, ensuring accumulation and slow release of drugs into a targeted tissue without harmful systemic side effects.

  9. A multiwall carbon nanotubes film-modified carbon fiber ultramicroelectrode for the determination of nitric oxide radical in liver mitochondria.

    Science.gov (United States)

    Wang, Yazhen; Li, Qing; Hu, Shengshui

    2005-02-01

    A novel chemically modified electrode based on the multiwall carbon nanotubes (MWNTs) film-coated carbon fiber ultramicroelectrode (CFUE) has been described for the determination of nitric oxide radical (.NO). The electrochemical behaviors of MWNTs-modified CFUE have been characterized in 0.2 mmol L(-1) K(4)Fe(CN)(6) and 0.1 mol L(-1) KCl solution. The Nafion film was used to avoid some electroactive interferences. The amount of Nafion was optimized, and some possible interferents [such as nitrite (NO(2)(-)), nitrate (NO(3)(-)), ascorbate, dopamine (DA), l-arginine (l-Arg), etc.] were tested and evaluated. The oxidation peak current of .NO increases significantly at the MWNT/Nafion-modified CFUE, in contrast to that at the bare and the Nafion-modified CFUE, and the oxidation peak potential is at 0.78 V (vs. SCE), which can be used for the detection of .NO. The oxidation peak current is linearly with the concentration of .NO from 2x10(-7) to 8.6x10(-5) mol L(-1), and the detection limit is 2x10(-8) mol L(-1). The liver mitochondria in Carassius auratus were isolated and .NO release from mitochondria was monitored by using this ultramicroelectrode system.

  10. Protective Effects of Garlic Oil against Liver Damage Induced by Combined Administration of Ethanol and Carbon Tetrachloride in Rats

    Directory of Open Access Journals (Sweden)

    Ashraf B. Abdel-Naim a, Amani E. Khalifaa, Sherif H. Ahmed b

    2002-03-01

    Full Text Available Herbs are known to play a vital role in the management of various liver diseases. Garlic oil (GO contains numerous organosulfur compounds with potential hepatoprotective effects. The present work was planned to evaluate the possible preventive role of GO on biochemical and histopathological alterations induced by combined administration of ethanol (EOH and carbon tetrachloride (CCl4 in rat liver. Two dose levels of GO (5 or 10 mg/kg/day were administered orally to rats for 7 consecutive days with EOH + CCl4-induced liver damage. Activity of GO against liver damage was compared with that of silymarin (25 mg/kg/day, p.o. for 7 consecutive days. Biochemical parameters including serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, gamma glutamyl transpeptidase (­GT, alkaline phophatase (ALP and bilirubin were estimated to assess the liver function. In addition, the level of total proteins, triglycerides, total cholesterol, glutathione (GSH, and thiobarbituric acid reactive substances (TBARS, in liver tissues were estimated. Liver damage was evidenced by an increase in the activity/level of AST, ALT, -GT, ALP and bilirubin in sera of rats after the combined administration of EOH and CCl4 compared to normal animals. Pretreatment of rats with GO reduced the EOH + CCl4-induced elevated levels of the above indices. Similarly, GO significantly prevented the decline in total proteins and the increase in triglycerides and total cholesterol resulted after EOH + CCl4 administration in rat liver homogenates. In addition, GO pretreatment restored liver GSH levels decreased due to EOH + CCl4 administration. The elevation in liver TBARS level due to EOH + CCl4 administration was also prevented by pretreatment with both low and high doses of GO. Histopathological examination indicated that GO exhibited an obvious preventive effect against the centrilobular necrosis and nodule formation induced by EOH + CCl4 administration. In conclusion, GO

  11. Inter-Strain Differences in Liver Injury and One-Carbon Metabolism in Alcohol-Fed Mice

    Science.gov (United States)

    Tsuchiya, Masato; Ji, Cheng; Kosyk, Oksana; Shymonyak, Svitlana; Melnyk, Stepan; Kono, Hiroshi; Tryndyak, Volodymyr; Muskhelishvili, Levan; Pogribny, Igor P.; Kaplowitz, Neil; Rusyn, Ivan

    2012-01-01

    Alcoholic liver injury is a major public health issue worldwide. Even though the major mechanisms of this disease have been established over the past decades, little is known about genetic susceptibility factors that may predispose individuals who abuse alcoholic beverages to liver damage and subsequent pathological conditions. We hypothesized that a panel of genetically diverse mouse strains may be used to examine the role of ER stress and one-carbon metabolism in the mechanism of inter-individual variability in alcoholic liver injury. We administered alcohol (up to 27 mg/kg/d) in high fat diet using intragastric intubation model for 28 days to male mice from 14 inbred strains (129S1/SvImJ, AKR/J, BALB/cJ, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, C57BL/10J, DBA/2J, FVB/NJ, KK/HIJ, MOLF/EiJ, NZW/LacJ, PWD/PhJ, and WSB/EiJ). Profound inter-strain differences (more than 3-fold) in alcohol-induced steatohepatitis were observed among the strains in spite of consistently high levels of urine alcohol that was monitored throughout the study. We found that endoplasmic reticulum stress genes were induced only in strains with the highest liver injury. Liver glutathione and methyl donor levels were affected in all strains, albeit to a different degree. Most pronounced effects that were closely associated with the degree of liver injury were hyperhomocysteinemia and strain-dependent differences in expression patterns of one-carbon metabolism-related genes. Conclusion Our data demonstrate that strain differences in alcohol-induced liver injury and steatosis are striking and independent of alcohol exposure and the most severely affected strains exhibit major differences in the expression of ER stress markers and genes of one-carbon metabolism. PMID:22307928

  12. Hepatoprotective effects of Quercus infectoria gall extract against carbon tetrachloride treated liver injury in rats

    Directory of Open Access Journals (Sweden)

    Gaurav Lodhi

    2012-08-01

    Full Text Available Summary. In the present study, galls of Quercus infectoria possessing potent antioxidant and antiinflammatory properties were evaluated for their hepatoprotective effect against carbon tetrachloride (CCl4 induced hepatotoxicity in rats. Subcutaneous injection of CCl4, administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase (AST, alanine transaminase (ALT and tumor necrosis factor alpha (TNF-α. Histological analysis of the liver of these rats revealed marked necro-inflammatory changes that were associated with increase in the levels of TBARS, PGE2 and catalase and decrease in the levels of glutathione (GSH, superoxide dismutase (SOD and glutathione peroxidase (GPx. Daily oral administration of aqueous ethanolic extract of Quercus infectoria galls at 200, 400 and 600 mg/kg doses produced a dose dependent reduction in the serum levels of liver enzymes and inflammatory mediators and attenuated the necroinflammatory changes in the liver. The QIE treatment also normalized various biochemical parameters of oxidative stress. Our study shows that the hepatoprotective effects of QIE and silymarin were comparable and suggests that QIE could be used as a hepatoprotective agent. Industrial relevance. Research in traditional medicine has lead to the development of many modern medicines. In recent times, focus on plants research has increased all over the world and a large body of evidence has been collected to show immense potential of medicinal plants used in various traditional systems. It is very interesting to note that there is no drug available in the modern system of medicine for treating hepatic disorders; only certain herbal preparations are available to treat this quite vulnerable disease. The situation/background thus explained above warrants for developing a safe, effective and scientifically validated hepatoprotective agent taking lead from traditional medicine, which is affordable for the rural poor

  13. Loss of Discoidin Domain Receptor 2 Promotes Hepatic Fibrosis after Chronic Carbon Tetrachloride through Altered Paracrine Interactions between Hepatic Stellate Cells and Liver-Associated Macrophages

    OpenAIRE

    Olaso, Elvira; ARTETA, BEATRIZ; BENEDICTO, AITOR; Crende, Olatz; Friedman, Scott L.

    2011-01-01

    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl4) to DDR2+/+ and DDR2−/− mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after...

  14. Protective Effect of the Persian Gulf brittle star Ophiocoma Erinaceus extract on carbon tetrachloride (CCl4 induced liver damage in adult male Wistar rats

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    Aida Soheili

    2015-12-01

    Full Text Available Background and Aim:  Brittle star possess  bioactive compounds which confer the wound healing capacity and regenerative potency of damaged  arms and organisms to this creature. The aim of the current study was to assess the   protective  effect  of  the  star extract on liver damages induced by carbon tetrachloride in adult male Wistar rats. Materials and Methods: In this experimental study, 32 adult male rats were randomly divided into 4 equal groups: control, Sham exposed, experimental 1 (treated with %25 extract and experimental 2 (treated with %50 extract of star Ophiocoma Erinaceus. The control group received no treatment. The sham exposed groups received carbon tetrachloride .(50% in olive oil .0.5 ml/kg for 7 days. The experimental groups firstly received carbon tetrachloride, then received %25, %50 brittle star extract as intragastric for 7 days. Finally, the animals were sacrificed, and their bodies and livers were weighed. Then, the livers sections were prepared and were examined by means of light microscope. Finally, the obtained  quantitative data was analyzed using SPSS (V; 20, Mini Tab software, ANOVA, and Tukey. at the significant level of P<0.001. Results: Carbon tetrachloride significantly decreased the rats’ body weight, but it increased their livers weight (P<0.001. Histopathological evaluations showed .extensive liver damage. On the other hand, treatment with brittle star extract .ncreased liver weight, reduced. body weight and significantly altered other induced changes by carbon tetrachloride on liver structure such as hepatocytes number, Kupffer cells, and arteritis, which indicated  the improvement of damaged liver tissue (P<0.001. Conclusion: It was found that brittle star extract can exert protective effects on  liver damages induced by carbon tetrachloride on male Wistar rat.

  15. Treatment with L-valine ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to carbon tetrachloride.

    Science.gov (United States)

    Nakanishi, Chikashi; Doi, Hideyuki; Katsura, Kazunori; Satomi, Susumu

    2010-06-01

    It has been reported that treatment with branched chain amino acids (BCAAs) increases the survival rates in cirrhotic patients. In this study, we investigated the effect of L-valine, one of BCAAs, on liver fibrosis in rat. To induce liver fibrosis, male Wistar rats were injected carbon tetrachloride (CCl(4)) intraperitoneally (2.0 mL/kg) twice a week for 12 weeks. The rats (seven to fifteen rats for each group) were then administered 1.688 g/kg/day of L-valine intravenously for 7 days or 10% amino acid preparation that provided the same amount of nitrogen. Seven days after the last administration, blood platelet counts and bone marrow megakaryocyte counts were significantly higher in the valine group than in the control group (131.2 +/- 38.3 vs. 106.3 +/- 14.5 x 10(4)/microL, p = 0.04; 18.0 +/- 2.1 vs. 13.5 +/- 2.2 per field, p valine group than the control group. Furthermore, hepatic fibrosis was significantly reduced in the valine group, and the mRNA levels of factors associated with liver fibrosis such as procollagen alpha1(III), transforming growth factor-beta1 and connective tissue growth factor were significantly lower in the liver of the valine group 10 days after the last administration. These results indicate that L-valine treatment ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to CCl(4). Therefore, L-valine supplementation may be helpful for patients with liver cirrhosis.

  16. Protective effect of aqueous extracts from Rhizopus oryzae on liver injury induced by carbon tetrachloride in rats.

    Science.gov (United States)

    Suzuki, Takehito; Fukuoka, Hideo; Ushikoshi, Setsuo; Sato, Reiichiro; Morita, Hidetoshi; Takizawa, Tatsuya

    2015-05-01

    Hepatoprotective effects of Rhizopus oryzae/ U-1 aqueous extract (RU) were demonstrated in carbon tetrachloride (CCl4 )-induced liver-injured rats. In order to investigate the RU effects, the rats were administered RU at a dose of 10 or 100 mg/kg of body weight for 10 days before induction of the liver injury by oral administration of CCl4 (125 mg/kg body weight). (i) Pretreatment with RU caused a significant decrease in serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities that were increased by the administration of CCl4 . (ii) RU pretreatment (100 mg/kg) increased 5-bromo-2'-deoxyuridine incorporation at 48 h after CCl4 treatment in hepatocytes. (iii) Histological hematoxylin and eosin staining of the liver showed that RU pretreatment reduced the damage induced by CCl4 administration. (iv) Reverse transcriptase PCR analysis showed RU retreatment caused a transient but significant increase in hepatocyte growth factor (HGF) and a sustained and significant increase in insulin-like growth factor-I (IGF-I) gene expression in hepatocytes injured by CCl4 treatment. From these results, we conclude that oral pre-administration of RU was effective to suppress liver injury induced by the subsequent oral CCl4 administration, and RU-induced increase in IGF-I and HGF gene expression may be, even in part, involved in biological actions of RU in rats.

  17. 骨髓间充质干细胞经尾静脉移植治疗肝纤维化%Bone marrow mesenchymal stem cell transplantationvia the tail vein for liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    王长武; 房新辉

    2016-01-01

    BACKGROUND:Liver fibrosis is the early stage of terminal liver diseases. Effective treatment for liver fibrosis can prevent the occurrence of terminal liver diseases. Bone marrow mesenchymal stem cel transplantation is a promising method to treat liver fibrosis. OBJECTIVE:To study the therapeutic effect of bone marrow mesenchymal stem cels on liver fibrosis in rats. METHODS: Eighteen Sprague-Dawely rats were randomized into three groups: control, model and cel transplantation groups. Animal models of carbon tetrachloride-induced liver fibrosis were made in the latter two groups. After modeling, 1 mL bone marrow mesenchymal stem cels (5×105) or the same volume of normal saline was injectedviathe tail vein into the rats in the cel transplantation and model groups, respectively. Rats in the control group were given no treatment. Degree of liver fibrosis, liver function, histological changes of the liver were detected and observed in the three groups at 4 weeks after treatment. RESULTS AND CONCLUSION:In the control group, the liver tissues had normal structure with no fibrosis; in the model group, proliferation of fibrous tissues in the portal area of the liver, inflammatory cel infiltration, vacuolar degeneration and irregular arrangement of liver cels, and tissue structure damage were observed; in the transplantation group, liver tissue damage was severer than the control group but milder than the model group. Levels of serum hyaluronidase, type IV colagen and procolagen III were significantly lower in the cel transplantation group than the model group (P< 0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation can aleviate liver fibrosis and improve liver function in rats with carbon tetrachloride-induced liver fibrosis.%背景:肝纤维化是终末肝病的早期阶段,对肝纤维化进行有效治疗可以防止终末肝病的发生,骨髓间充质干细胞是治疗肝纤维化的一种比较有前景的治疗方法。目的

  18. MR T1{rho} as an imaging biomarker for monitoring liver injury progression and regression: an experimental study in rats with carbon tetrachloride intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Feng; Wang, Yi-Xiang J.; Yuan, Jing; Deng, Min; Ahuja, Anil T. [Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR (China); Wong, Hing Lok [School of Public Health and Primary Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Jockey Club Centre for Osteoporosis Care and Control, Hong Kong SAR (China); Chu, Eagle S.H.; Go, Minnie Y.Y.; Yu, Jun [Chinese University of Hong Kong, Institute of Digestive Disease and Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Hong Kong SAR (China); Teng, Gao-Jun [Southeast University, Department of Radiology, Zhongda Hospital, Nanjing (China)

    2012-08-15

    Recently it was shown that the magnetic resonance imaging (MRI) T1{rho} value increased with the severity of liver fibrosis in rats with bile duct ligation. Using a rat carbon tetrachloride (CCl{sub 4}) liver injury model, this study further investigated the merit of T1{rho} relaxation for liver fibrosis evaluation. Male Sprague-Dawley rats received intraperitoneal injection of 2 ml/kg CCl{sub 4} twice weekly for up to 6 weeks. Then CCl{sub 4} was withdrawn and the animals were allowed to recover. Liver T1{rho} MRI and conventional T2-weighted images were acquired. Animals underwent MRI at baseline and at 2 days, 2 weeks, 4 weeks and 6 weeks post CCl{sub 4} injection, and they were also examined at 1 week and 4 weeks post CCl{sub 4} withdrawal. Liver histology was also sampled at these time points. Liver T1{rho} values increased slightly, though significantly, on day 2, and then increased further and were highest at week 6 post CCl{sub 4} insults. The relative liver signal intensity change on T2-weighted images followed a different time course compared with that of T1{rho}. Liver T1{rho} values decreased upon the withdrawal of the CCl{sub 4} insult. Histology confirmed the animals had typical CCl{sub 4} liver injury and fibrosis progression and regression processes. MR T1{rho} imaging can monitor CCl{sub 4}-induced liver injury and fibrosis. (orig.)

  19. Nutritional Quality and Physicochemical Characteristics of Defatted Bovine Liver Treated by Supercritical Carbon Dioxide and Organic Solvent

    Science.gov (United States)

    Kang, Sung-Won; Kim, Hye-Min; Rahman, M. Shafiur; Kim, Ah-Na; Yang, Han-Sul

    2017-01-01

    Defatted bovine liver (DBL) is a potential source of protein and minerals. Supercritical carbon dioxide (SC-CO2) and a traditional organic solvent method were used to remove lipid from bovine liver, and the quality characteristics of a control bovine liver (CBL), bovine liver defatted by SC-CO2 (DBLSC-CO2) at different pressures, and bovine liver defatted by organic solvent (DBL-OS) were compared. The DBLSC-CO2 samples had significantly higher (p<0.05) protein, amino acid, carbohydrate, and fiber contents than CBL and DBL-OS. There was a higher yield of lipid from CBL when using SC-CO2 than the organic solvent method. SDS-PAGE analysis demonstrated that the CBL and DBLSC-CO2 had protein bands of a similar intensity and area, whereas DBL-OS appeared extremely poor bands or no bands due to the degradation of proteins, particularly in the 50 to 75 kDa and 20 to 25 kDa molecular weight ranges. In addition, DBLSC-CO2 was shown to have superior functional properties in terms of total soluble content, water and oil absorption, and foaming and emulsification properties. Therefore, SC-CO2 treatment offers a nutritionally and environmentally friendly approach for the removal of lipid from high protein food sources. In addition, SC-CO2 may be a better substitute of traditional organic solvent extraction for producing more stable and high quality foods with high-protein, fat-free, and low calorie contents. PMID:28316468

  20. Effects of carbon tetrachloride and azathioprine on diethylnitrosamine and N-2-fluorenylacetamide-induced hyperplastic liver nodule and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Sakata,Tatsuro

    1984-12-01

    Full Text Available Effects of carbon tetrachloride (CCl4 and azathioprine (AZP on the evolution of hyperplastic liver nodules and foci and hepatocellular carcinoma (HCC were tested in short- and long-term in vivo experiments. In diethylnitrosamine (DEN-treated rats, which were fed a N-2-fluorenylacetamide (FAA-containing diet and additionally treated with repeated CCl4 injections, gamma-glutamyl transpeptidase (gamma-GTP-positive hyperplastic nodules were markedly developed in the 8th week of the experiment. However, their number and area in liver sections were remarkably small in DEN-treated rats fed a diet containing both FAA and AZP. Increased area of gamma-GTP-positive foci was also observed in the 12th week in DEN-injected rats fed a choline-devoid died alone or treated with repeated doses of CCl4 alone. Hepatocellular carcinoma in DEN-injected rats treated with both FAA and CCl4 was first detected in the 21st week, and the incidence up to the 36th week was very high. However, no hepatocellular carcinoma developed in DEN-injected rats treated with both FAA and AZP. The increased activity of liver aniline hydroxylase observed 12 h after the administration of FAA, AZP or DEN alone was not observed when AZP was administered simultaneously with FAA to DEN-injected rats. The mechanisms of the effects of CCl4 and AZP on hepatocarcinogenesis are discussed with special reference to drug interaction.

  1. Single nucleotide polymorphisms of one-carbon metabolism and cancers of the esophagus, stomach, and liver in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Shen-Chih Chang

    Full Text Available One-carbon metabolism (folate metabolism is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71 and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32. There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94. In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005 and stomach cancer (posterior homogeneity P = 0.004, and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021. Among non-alcohol drinkers, the variant allele (allele G of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of

  2. Effect of Pleurotus citrinopileatus Polysaccharides on Antioxidant Enzyme Activities and Isozyme Profiles in Liver,Heart and Kidney of Mice with CCl_4-induced Acute Liver Injury%金顶侧耳多糖对CCl_4所致急性肝损伤小鼠肝、心、肾抗氧化酶活性及同工酶影响

    Institute of Scientific and Technical Information of China (English)

    刘俊; 陶明煊; 程光宇; 周斌

    2011-01-01

    Objective:To investigate the effect of Pleurotus citrinopileatus polysaccharides(PCP) on antioxidant enzyme activities and isozyme profiles in the liver,heart and kidney of mice with carbon tetrachloride-induced acute liver injury.Methods:Mice were randomly divided into 6 groups:control group,model group,drug group(bifendate pills,150 mg/(kg·d)),low-dose PCP group(100 mg/(kg·d)),medium-dose PCP group(200 mg/(kg·d)) and high-dose PCP group(400 mg/(kg·d)).All mice were administered for 30 consecutive days,and were fasted for 16 h after the end of the administration period before oral administration of CCl4 dispersed in salad oil for creating CCl4-inducedacute liver injury model.At 24 h postadministration,all mice were sacrificed to assay the activities of ALT,AST and antioxidant enzymes in the blood,liver,heart and kidney and analyze the isozyme profiles of CAT and SOD by gradientpolyacrylamide gel electrophoresis.Results:Compared with the control group,the model group exhibited a significant increase in the activities of serum ALT and AST and a significant decrease in the activities of the investigated antioxidant enzymes in the liver,heart and kidney of mice(P 0.05 or 0.01).PCP administration resulted in a significant decrease in the activities of serum ALT and AST,and the medium-dose and high-dose PCP group exhibited significantly increased activities of CAT,GSH-Px and MnSOD in the liver,heart and kidney and could resume their normal levels.One CAT band was detected in the liver,heart and kidney and CCl4-induced acute liver injury resulted in a significant decrease in its staining intensity.In contrast,the staining intensity of the band was restored to the normal level after PCP administration.Similarly,One MnSOD and three CuZnSOD were detected in the liver and kidney,and PCP administration resulted in an increase in the staining intensity of total SOD and MnSOD,one MnSOD and two CuZnSOD were detected in the

  3. Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver

    DEFF Research Database (Denmark)

    Bourdon, Julie A; Saber, Anne T; Jacobsen, Nicklas R;

    2012-01-01

    Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo.......Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo....

  4. Loss of discoidin domain receptor 2 promotes hepatic fibrosis after chronic carbon tetrachloride through altered paracrine interactions between hepatic stellate cells and liver-associated macrophages.

    Science.gov (United States)

    Olaso, Elvira; Arteta, Beatriz; Benedicto, Aitor; Crende, Olatz; Friedman, Scott L

    2011-12-01

    Hepatic stellate cells (HSCs) interact with fibrillar collagen through the discoidin domain receptor 2 (DDR2) in acute hepatic injury, generating increased fibrosis. However, the contribution of DDR2 signaling to chronic liver fibrosis in vivo is unclear, despite its relevance to chronic human liver disease. We administered carbon tetrachloride (CCl(4)) to DDR2(+/+) and DDR2(-/-) mice twice weekly, and liver tissues and isolated HSCs were analyzed. In contrast to changes seen in acute injury, after chronic CCl(4) administration, DDR2(-/-) livers had increased collagen deposition, gelatinolytic activity, and HSC density. Increased basal gene expression of osteopontin, transforming growth factor-β1, monocyte chemoattractant protein-1, and IL-10 and reduced basal gene expression of matrix metalloproteinase-2, matrix metalloproteinase-13, and collagen type I in quiescent DDR2(-/-) HSCs were amplified further after chronic CCl(4). In concordance, DDR2(-/-) HSCs isolated from chronically injured livers had enhanced in vitro migration and proliferation, but less extracellular matrix degradative activity. Macrophages from chronic CCl(4)-treated DDR2(-/-) livers showed stronger chemoattractive activity toward DDR2(-/-) HSCs than DDR2(+/+) macrophages, increased extracellular matrix degradation, and higher cytokine mRNA expression. In conclusion, loss of DDR2 promotes chronic liver fibrosis after CCl(4) injury. The fibrogenic sinusoidal milieu generated in chronic DDR2(-/-) livers recruits more HSCs to injured regions, which enhances fibrosis. Together, these findings suggest that DDR2 normally orchestrates gene programs and paracrine interactions between HSCs and macrophages that together attenuate chronic hepatic fibrosis.

  5. Metabolomic Analysis of Liver Cells Exposed to Carbon Nanotubes and Graphene Oxide

    Science.gov (United States)

    Carbon nanotubes (CNTs) and other graphenic nanomaterials are being used extensively in industrial, consumer, and mechanical applications based in part on their unique structural, optical and electronic properties. Due to the widespread use of these nanoparticles (NPs), human and...

  6. Targeted therapy of SMMC-7721 liver cancer in vitro and in vivo with carbon nanotubes based drug delivery system.

    Science.gov (United States)

    Ji, Zongfei; Lin, Gaofeng; Lu, Qinghua; Meng, Lingjie; Shen, Xizhong; Dong, Ling; Fu, Chuanlong; Zhang, Xiaoke

    2012-01-01

    A new type of drug delivery system (DDS) involved chitosan (CHI) modified single walled carbon nanotubes (SWNTs) for controllable loading/release of anti-cancer doxorubicin (DOX) was constructed. CHI was non-covalently wrapped around SWNTs, imparting water-solubility and biocompatibility to the nanotubes. Folic acid (FA) was also bounded to the outer CHI layer to realize selective killing of tumor cells. The targeting DDS could effectively kill the HCC SMMC-7721 cell lines and depress the growth of liver cancer in nude mice, showing superior pharmaceutical efficiency to free DOX. The results of the blood routine and serum biochemical parameters, combined with the histological examinations of vital organs, demonstrating that the targeting DDS had negligible in vivo toxicity. Thus, this DDS is promising for high treatment efficacy and low side effects for future cancer therapy.

  7. Curative Effect of Bone Marrow Cells Transplantation and/or Low Dose Gamma Irradiation on Liver Injuries Induced by Carbon Tetrachloride

    Directory of Open Access Journals (Sweden)

    * Mohamed E.M. Zowail, ** Hanaa F. M. Waer, ** Noaman A. Eltahawy, * Eman H. S.

    2012-01-01

    Full Text Available Liver is the most common target for toxic injury. Toxic agents include chemicals such as carbon tetrachloride (CCl4 and trichloroethylene. This study aimed to evaluate the effect of bone marrow cells (BMC transplantation and/or fractionated low doses (0.5 Gy gamma radiation on established liver fibrosis induced by CCl4. BMCs of male albino rats were transplanted into 4-weeks carbon tetrachloride (CCl4­treated and/or fractionated low doses (0.5 Gy gamma irradiated rats through the tail vein, and the rats were treated for 4 more weeks with CCl4 (total 8 weeks. Histological and ultrastructural investigations revealed that both bone marrow cells transplantation and low dose (0.5 Gy gamma radiation exposure with continuous CCl4 injection had reduced liver fibrosis as compared with rats treated with CCl4 alone.

  8. Pulmonary exposure to carbon black by inhalation or instillation in pregnant mice: Effects on liver DNA strand breaks in dams and offspring

    DEFF Research Database (Denmark)

    Jackson, Petra; Hougaard, Karin Sørig; Boisen, Anne Mette Zenner

    2011-01-01

    Effects of maternal pulmonary exposure to carbon black (Printex 90) on gestation, lactation and DNA strand breaks were evaluated. Time-mated C57BL/6BomTac mice were exposed by inhalation to 42 mg/m3 Printex 90 for 1 h/day on gestation days (GD) 8–18, or by four intratracheal instillations on GD 7...... cells and liver, and in offspring liver. Persistent lung inflammation was observed in exposed mothers. Inhalation exposure induced more DNA strand breaks in the liver of mothers and their offspring, whereas intratracheal instillation did not. Neither inhalation nor instillation affected gestation...... and lactation. Maternal inhalation exposure to Printex 90-induced liver DNA damage in the mothers and the in utero exposed offspring....

  9. Epoxy composite dusts with and without carbon nanotubes cause similar pulmonary responses, but differences in liver histology in mice following pulmonary deposition

    DEFF Research Database (Denmark)

    Saber, Anne Thoustrup; Mortensen, Alicja; Szarek, Jozef;

    2016-01-01

    . Both CNT and epoxy dusts induced DNA damage in lung tissue up to 3 days after intratracheal instillation but not in liver tissue. There was no additive effect of adding CNT to epoxy resins for any of the pulmonary endpoints. In livers of mice instilled with CNT and epoxy dust with CNTs inflammatory......Background: The toxicity of dusts from mechanical abrasion of multi-walled carbon nanotube (CNT) epoxy nanocomposites is unknown. We compared the toxic effects of dusts generated by sanding of epoxy composites with and without CNT. The used CNT type was included for comparison.Methods: Mice...... received a single intratracheal instillation of 18, 54 and 162 mu g of CNT or 54, 162 and 486 mu g of the sanding dust from epoxy composite with and without CNT. DNA damage in lung and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Furthermore...

  10. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    Directory of Open Access Journals (Sweden)

    Williams Andrew

    2009-04-01

    Full Text Available Abstract Background Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP and serum amyloid A (SAA in humans. In this study we test the hypothesis that diesel exhaust particles (DEP – or carbon black (CB-induced lung inflammation initiates an acute phase response in the liver. Results Mice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005 177–182. As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap (the murine homologue of Crp and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3 responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT

  11. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  12. A Crucial Role of Bone Morphogenetic Protein Signaling in the Wound Healing Response in Acute Liver Injury Induced by Carbon Tetrachloride

    Directory of Open Access Journals (Sweden)

    Nao Oumi

    2012-01-01

    Full Text Available Background. Acute liver injury induced by administration of carbon tetrachloride (CCl4 has used a model of wound repair in the rat liver. Previously, we reported transient expression of bone morphogenetic protein (Bmp 2 or Bmp4 at 6–24 h after CCl4 treatment, suggesting a role of BMP signaling in the wound healing response in the injured liver. In the present study, we investigated the biological meaning of the transient Bmp expression in liver injury. Methods. Using conditional knockout mice carrying a floxed exon in the BMP receptor 1A gene, we determined the hepatic gene expressions and proliferative activity following CCl4-treated liver. Results. We observed retardation of the healing response in the knockout mice treated with CCl4, including aggravated histological feature and reduced expressions of the albumin and Tdo2 genes, and a particular decrease in the proliferative activity shown by Ki-67 immunohistochemistry. Conclusion. Our findings suggest a crucial role of BMP signaling in the amelioration of acute liver injury.

  13. Hydrodynamic Gene Delivery of Interleukin-22 Protects the Mouse Liver from Concanavalin A-, Carbon Tetrachloride-, and Fas Ligand-Induced Injury via Activation of STAT3

    Institute of Scientific and Technical Information of China (English)

    Hongna Pan; Feng Hong; Svetlana Radaeva; Bin Gao

    2004-01-01

    Interleukin-22 (IL-22) is a recently identified T cell-derived cytokine whose biological significance remains obscure. Previously, we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced by Concanavalin A (Con A), acting as a survival factor for hepatocytes. In the present paper, we demonstrate that hydrodynamic gene delivery of IL-22 cDNA driven either by a liver-specific albumin promoter or a human cytomegalovirus (CMV) promoter results in IL-22 protein expression, STAT3 activation, and expression of several anti-apoptotic proteins, including Bcl-xL, Bcl-2, and Mcl-1 in the liver. Immunohistochemical analysis reveals that IL-22 protein expression is mainly detected in the cytoplasm of hepatocytes. Overexpression of IL-22 by hydrodynamic gene delivery significantly protects against liver injury, necrosis, and apoptosis induced by administration of Con A, carbon tetrachloride (CCl4), or the Fas agonist Jo-2 mAb. Western blot analyses show that overexpression of IL-22 significantly enhances activation of STAT3 and expression of Bcl-xL, Bcl-2,and Mcl-1 proteins in liver injury induced by Con A. In conclusion, hydrodynamic gene delivery of IL-22 protects against liver injury induced by a variety of toxins, suggesting the therapeutic potential of IL-22 in treating human liver disease. Cellular & Molecular Immunology. 2004;1(1):43-49.

  14. Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride.

    Science.gov (United States)

    Lin, Song-Chow; Lin, Chia-Hsien; Lin, Chun-Ching; Lin, Yun-Ho; Chen, Chin-Fa; Chen, I-Cheng; Wang, Li-Ya

    2002-01-01

    Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s).

  15. The inhibitory effects in vitro of phenothiazines and other drugs on lipid-peroxidation systems in rat liver microsomes, and their relationship to the liver necrosis produced by carbon tetrachloride

    Science.gov (United States)

    Slater, T. F.

    1968-01-01

    1. The effects of several phenothiazine derivatives on lipid-peroxidation systems in rat liver microsomes were studied and the results are considered in relation to the hepatotoxic action of carbon tetrachloride. 2. The lipid-peroxidation system coupled to NADPH2 oxidation and stimulated by an ADP–Fe2+ mixture is strongly inhibited in vitro by promethazine (50% inhibition at 29μm). Chlorpromazine and Stelazine also inhibit the peroxidation system but are less effective than promethazine. 3. The effects of promethazine on three other systems involving oxygen uptake (sulphite oxidation, orcinol oxidation and mitochondrial succinate oxidation) were also studied. Promethazine does not inhibit these systems to the same extent as it does the NADPH2–ADP–Fe2+ lipid-peroxidation system. 4. Promethazine also produces an inhibition of the NADPH2–ADP–Fe2+ system in liver microsomes after administration in vivo. It is concluded that the inhibition involves the interaction of the drug (or a metabolite of it) with the microsomal electron-transport chain. 5. Several other compounds known to protect the rat against liver necrosis after the administration of carbon tetrachloride were tested for inhibitory action on the NADPH2–ADP–Fe2+ system. No clear correlation was observed between effectiveness in vivo as a protective agent and inhibitory effects on the NADPH2–ADP–Fe2+ system in vitro. 6. Promethazine was found to inhibit the stimulation of lipid peroxidation produced in rat liver microsomes by low concentrations of carbon tetrachloride. This effect occurs at a concentration similar to that observed in vivo after administration of a normal clinical dose. PMID:4388686

  16. Biomarker analysis of liver cells exposed to surfactant-wrapped and oxidized multi-walled carbon nanotubes (MWCNTs)

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, W. Matthew, E-mail: Henderson.Matt@epa.gov [U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, 960 College Station Road, Athens 30605, GA (United States); Bouchard, Dermont [U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, 960 College Station Road, Athens 30605, GA (United States); Chang, Xiaojun [Grantee to U.S. Environmental Protection Agency via National Research Council Cooperative Agreement, Athens 30605, GA (United States); Al-Abed, Souhail R. [U.S. Environmental Protection Agency, Office of Research and Development, National Risk Management Research Laboratory, 26 Martin Luther King Dr. W, Cincinnati, OH 45268 (United States); Teng, Quincy [U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, 960 College Station Road, Athens 30605, GA (United States)

    2016-09-15

    Carbon nanotubes (CNTs) have great potential in industrial, consumer, and mechanical applications, based partly on their unique structural, optical and electronic properties. CNTs are commonly oxidized or treated with surfactants to facilitate aqueous solution processing, and these CNT surface modifications also increase possible human and ecological exposures to nanoparticle-contaminated waters. To determine the exposure outcomes of oxidized and surfactant-wrapped multiwalled carbon nanotubes (MWCNTs) on biochemical processes, metabolomics-based profiling of human liver cells (C3A) was utilized. Cells were exposed to 0, 10, or 100 ng/mL of MWCNTs for 24 and 48 h; MWCNT particle size distribution, charge, and aggregation were monitored concurrently during exposures. Following MWCNT exposure, cellular metabolites were extracted, lyophilized, and buffered for {sup 1}H NMR analysis. Acquired spectra were subjected to both multivariate and univariate analysis to determine the consequences of nanotube exposure on the metabolite profile of C3A cells. Resulting scores plots illustrated temporal and dose-dependent metabolite responses to all MWCNTs tested. Loadings plots coupled with t-test filtered spectra identified metabolites of interest. XPS analysis revealed the presence of hydroxyl and carboxyl functionalities on both MWCNTs surfaces. Metal content analysis by ICP-AES indicated that the total mass concentration of the potentially toxic impurities in the exposure experiments were extremely low (i.e. [Ni] ≤ 2 × 10{sup −10} g/mL). Preliminary data suggested that MWCNT exposure causes perturbations in biochemical processes involved in cellular oxidation as well as fluxes in amino acid metabolism and fatty acid synthesis. Dose-response trajectories were apparent and spectral peaks related to both dose and MWCNT dispersion methodologies were determined. Correlations of the significant changes in metabolites will help to identify potential biomarkers associated with

  17. Diethylcarbamazine Reduces Chronic Inflammation and Fibrosis in Carbon Tetrachloride- (CCl4- Induced Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Sura Wanessa Santos Rocha

    2014-01-01

    Full Text Available This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl4 0.5 μL/g of body weight through two injections a week for 6 weeks. DEC (50 mg/kg was administered by gavage for 12 days before finishing the CCl4 induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1β, MDA, TGF-β, and αSMA immunopositivity, besides exhibiting decreased IL1β, COX-2, NFκB, IFNγ, and TGFβ expressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.

  18. Vanillin suppresses Kupffer cell-related colloidal carbon-induced respiratory burst activity in isolated perfused rat liver: anti-inflammatory implications.

    Science.gov (United States)

    Galgani, José E; Núñez, Bárbara; Videla, Luis A

    2012-12-01

    The inhibition of NADPH oxidase has become a potential therapeutic target for oxidative stress-related diseases. We investigated whether vanillin modifies hepatic O(2) consumption associated with Kupffer cell functioning. The influence of vanillin on Kupffer cell functioning was studied in isolated perfused rat liver by colloidal carbon (CC) infusion (0.5 mg ml(-1)), concomitantly with sinusoidal efflux of lactate dehydrogenase (LDH) as an organ viability parameter. CC infusion increased the rate of O(2) consumption of the liver above basal values, an effect that represents the respiratory burst activity of Kupffer cells. However, CC-dependent respiratory burst activity was suppressed by previous infusion of 2 mM vanillin. Vanillin did not affect the liver CC uptake rate and liver sinusoidal efflux of LDH efflux. These findings, elicited by vanillin, were reproduced by the well-established NADPH oxidase inhibitor apocynin. In conclusion, vanillin suppresses the respiratory burst activity of Kupffer cells as assessed in intact liver, which may be associated with the inhibition of macrophage NADPH oxidase activity. Such a finding may have relevance in conditions underlying Kupffer cell-dependent up-regulation of the expression and release of pro-inflammatory mediators by redox-dependent mechanisms.

  19. Studies of single-walled carbon nanotubes-induced hepatotoxicity by NMR-based metabonomics of rat blood plasma and liver extracts

    Science.gov (United States)

    Lin, Bencheng; Zhang, Huashan; Lin, Zhiqing; Fang, Yanjun; Tian, Lei; Yang, Honglian; Yan, Jun; Liu, Huanliang; Zhang, Wei; Xi, Zhuge

    2013-05-01

    The toxicological effects of single-walled carbon nanotubes (SWCNTs) were investigated after intratracheal instillation in male Wistar rats over a 15-day period using metabonomic analysis of 1H (nuclear magnetic resonance) NMR spectra of blood plasma and liver tissue extracts. Concurrent liver histopathology examinations and plasma clinical chemistry analyses were also performed. Significant changes were observed in clinical chemistry features, including alkaline phosphatase, total protein, and total cholesterol, and in liver pathology, suggesting that SWCNTs clearly have hepatotoxicity in the rat. 1H NMR spectra and pattern recognition analyses from nanomaterial-treated rats showed remarkable differences in the excretion of lactate, trimethylamine oxide, bilineurin, phosphocholine, amylaceum, and glycogen. Indications of amino acid metabolism impairment were supported by increased lactate concentrations and decreased alanine concentrations in plasma. The rise in plasma and liver tissue extract concentrations of choline and phosphocholine, together with decreased lipids and lipoproteins, after SWCNTs treatment indicated a disruption of membrane fluidity caused by lipid peroxidation. Energy, amino acid, and fat metabolism appeared to be affected by SWCNTs exposure. Clinical chemistry and metabonomic approaches clearly indicated liver injury, which might have been associated with an indirect mechanism involving nanomaterial-induced oxidative stress.

  20. 鬼针聚炔苷对CCl4诱导的小鼠急性肝损伤的保护作用%Protective effect of bipinnatpolyacetylenicloside on acute liVer injury induced by CCl4 in mice

    Institute of Scientific and Technical Information of China (English)

    刘建军; 陈飞虎; 许慧; 王晓宇; 林梅英; 汤文建; 张群林

    2012-01-01

    Objective To study the protective effect of bipinnatpolyacetylenicloside on acute liver injury induced by CCl4in mice. Methods Mice were divided into 6 groups including control group, model group, positive group Silymarin, and bipinnatpolyacetylenicloside treatment(12.5,25,50 mg · kg-1 ) group. Acute hepatic injury was induced by injecting 0. 1ml( 10g)-1 0.2% olive oil solution of carbon tetrachloride and mice in bipinnatpolyacetylenicloside treatment group were intragastric administered with bipinnatpolyacetylenicloside for 6 days before given carbon tetrachloride. Serum AST and ALT were detemined. The contents of SOD, GSH-Px , MDA, and NO in liver homogenate were determined. The index as well as the histopathological test of liver was observed and the expression of NF-ΚB p65 in liver was tested by immunohistochemistry. Results Compared with those in model group, the levels of AST, ALT in serum, the contents of MDA, NO in liver homogenate were reduced significantly while the levels of SOD, GSH-Px in liver homogenate were markedly increased. In bipinnatpolyacetylenicloside treatment (12. 5,25,50 mg ·kg-1) groups, histopathological study showed that the degenerative and necrotic liver cells could be evidently ameliorated , and, immunohistochemistry research demonstrated that the expression of NF-ΚB was dramatically decreased. Conclusion The bipinnatpolyacetylenicloside has a protective effect on the carbon tetrachloride induced acute liver injury in mice, the mechanism of which may be related to its antioxidant characteristic as well as the production of NO and the expression of NF-ΚB being inhibited.%目的 研究鬼针聚炔苷(BPC)对CCl4诱导的小鼠急性肝损伤的保护作用.方法 腹腔注射0.2%CCl4橄榄油溶液建立小鼠急性肝损伤模型,以水飞蓟素为阳性对照,鬼针聚炔苷(12.5、25、50 mg·kg-1)灌胃给药6 d,测定各组小鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的含量;检测肝组织

  1. The effects of carbon tetrachloride on rat liver microsomes during the first hour of poisoning in vivo, and the modifying actions of promethazine

    Science.gov (United States)

    Slater, T. F.; Sawyer, B. C.

    1969-01-01

    The effects of an oral administration of carbon tetrachloride on various liver microsomal and supernatant components were studied 1hr. and 2hr. after dosing. The modifications of such early changes resulting from a concomitant administration of promethazine together with the carbon tetrachloride were also investigated. The microsomal components studied were: cytochromes P-450 and b5; inorganic pyrophosphatase; NADH– and NADPH–cytochrome c reductases; NADH– and NADPH–neotetrazolium reductases; a lipid-peroxidation system associated with the oxidation of NADPH and stimulated by ADP and Fe2+. NAD– and NADP– DT-diaphorases were measured in the supernatant solution remaining after isolation of liver microsomes, and the distribution of RNA phosphorus between the microsomes and supernatant solution was also determined. Carbon tetrachloride produced a rapid fall in inorganic pyrophosphatase activity, a rather slower decrease in cytochrome P-450 content of the microsomes and small increases in the activities of NADH–cytochrome c reductase and neotetrazolium reductases. The activities of NADPH–cytochrome c reductase, the NADPH–ADP/Fe2+-linked lipid-peroxidation system, DT-diaphorases and the content of cytochrome b5 in the microsomes were unchanged. There was also a loss of RNA phosphorus from the microsomes into the supernatant solution. The RNA phosphorus redistribution, the decrease in inorganic pyrophosphatase and the increases in neotetrazolium reductase activities were at least partially prevented by a concomitant dosing with promethazine. However, the decrease in cytochrome P-450 was not affected by promethazine treatment. These early changes are discussed in terms of the liver necrosis produced by carbon tetrachloride and which is greatly retarded in its onset by the administration of promethazine. PMID:5767054

  2. Liver Transplant

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  3. Molecularly imprinted polymer solid-phase extraction coupled to square wave voltammetry at carbon fibre microelectrodes for the determination of fenbendazole in beef liver.

    Science.gov (United States)

    Guzmán-Vázquez de Prada, A; Loaiza, Oscar A; Serra, B; Morales, D; Martínez-Ruiz, P; Reviejo, A J; Pingarrón, J M

    2007-05-01

    A molecularly imprinted polymer was developed and used for solid-phase extraction (MISPE) of the antihelmintic fenbendazole in beef liver samples. Detection of the analyte was accomplished using square wave voltammetry (SWV) at a cylindrical carbon fibre microelectrode (CFME). A mixture of MeOH/HAc (9:1) was employed both as eluent in the MISPE system and as working medium for electrochemical detection of fenbendazole. The limit of detection was 1.9x10(-7) mol L-1 (57 microg L-1), which was appropriate for the determination of fenbendazole at the maximum residue level permitted by the European Commission (500 microg kg-1 in liver). Given that the SW voltammetric analysis could not be directly performed in the sample extract as a consequence of interference from some sample components, a sample clean-up with a MIP for selectively retaining fenbendazole was performed. The MIP was synthesized using a 1:8:22 template/methacrylic acid/ethylene glycol dimethacrylate ratio. A Britton-Robinson Buffer of pH 9.0 was selected for retaining fenbendazole in the MIP cartridges, and an eluent volume of 5.0 mL at a flow rate of 2.0 mL min-1 was chosen in the elution step. Cross-reactivity with the MIP was observed for other benzimidazoles. The synthesized MIP exhibited a good selectivity for benzimidazoles with respect to other veterinary drugs. The applicability of the MISPE-SWV method was tested with beef liver samples, spiked with fenbendazole at 5,000 and 500 microg kg-1. Results obtained for ten different liver samples yielded mean recoveries of (95+/-12)% and (96+/-11)% for the upper and lower concentration level, respectively.

  4. Biomarker analysis of liver cells exposed to surfactant-wrapped and oxidized multi-walled carbon nanotubes (MWCNTs)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Carbon nanotubes (CNTs) have great potential in industrial, consumer, and mechanical applications, based partly on their unique structural, optical and electronic...

  5. 四氯化碳法兔肝硬化模型的建立%Establishment of Liver Cirrhosis in Rabbit by subcutaneous injection of carbon tetrachloride

    Institute of Scientific and Technical Information of China (English)

    郭丽丽; 张铁成; 赵明; 杨雁萍; 张肇慧; 王阿樱; 付旷

    2011-01-01

    目的 探讨通过皮下注射四氯化碳(carbon tetrachloride,CCl4)-橄榄油溶液制备兔肝硬化模型的可行性.方法 体重在2.0-2.5 kg的新西兰大白兔42只,其中实验组36只,分成三组(Ⅰ、Ⅱ、Ⅲ),每组12只,前两周均每周两次皮下注射50%的CCl4-橄榄油溶液0.3 ml/kg,第三周起Ⅰ组每周两次皮下注射50%的CCl4-橄榄油溶液1.5 ml/kg; Ⅱ组每周两次皮下注射50%的CCl4-橄榄油溶液0.9 ml/kg;Ⅲ组每周两次皮下注射50%的CCl4-橄榄油溶液0.4 ml/kg,对照组6只,分成三组,每组2只,分别与实验组相对应注射等量的橄榄油,实验组与对照组均于第12周末处死并取肝组织做病理.结果 三个实验组均造成肝硬化模型,实验过程中兔子死亡率分别为67%、50%、8.3%.结论 皮下注射四氯化碳-橄榄油溶液制备兔肝硬化模型可行,且Ⅲ组造模成功率高,适用于临床研究.%Objective To evaluate the feasibility of rabbit model of liver cirrhosis established by subcutaneous injection of carbon tetrachloride-olive oil solution .Methods 42 body weight during 2.0-2.5 kg New Zealand white rabbits ,36 in experimental group were divided into three groups ( Ⅰ , Ⅱ ,Ⅲ ), 12 in each group, the first two weeks was injected subcutaneously by 0.3 ml/kg 50% carbon tetrachloride-olive oil solution twice-weekly, from the third week Ⅰ , Ⅱ, Ⅲ was injected subcutaneously by 1.5 ml/kg ,0.9 ml/kg ,0.4 ml/kg respectively 50% carbon tetrachloride-olive oil solution twice-weekly ;6 in control group were divided into three groups, 2 in each group corresponding to the experimental group ,was injected with te same amount of olive oil, all rabbits were sacrificed at 12 weeks and obtained liver tissues for pathology .Results Three experimental groups turned into liver cirrhosis models ,rabbit mortality rate during the experiment was 67% ,50% ,8.3% respectively .Conclusion The establishment of liver cirrhosis in rabbit by subcutaneous injection of

  6. Biomarker analysis of liver cells exposed to surfactant-wrapped and oxidized multi-walled carbon nanotubes (MWCNTs)

    Science.gov (United States)

    Carbon nanotubes (CNTs) have great potential in industrial, consumer, and mechanical applications, based partly on their unique structural, optical and electronic properties. CNTs are commonly oxidized or treated with surfactants to facilitate aqueous solution processing, and the...

  7. Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase exhibit enhanced liver fibrosis and delayed recovery from fibrosis in carbon tetrachloride-treated mice

    Directory of Open Access Journals (Sweden)

    Hiroko Habuchi

    2016-08-01

    Results and conclusion: On 2 days after cessation of CCl4 administration, higher fibrosis was observed in KO mice than in WT mice by Sirius Red staining. Serum alanine aminotransferase activity was higher in KO mice than in WT mice. Hydroxyproline contents and Sirius Red staining showed that repair of liver fibrosis in the recovery stages appeared to be delayed in KO mice. Expression of mRNA of matrix metalloproteinase (MMP-2, MMP-13 and versican peaked at 2 days after cessation of CCl4 administration and was higher in KO mice than in WT mice. Expression of MMP-9 in the recovery stage was lower in KO mice than in WT mice. Our findings demonstrate that defect in GalNAc4S-6ST, which resulted in disappearance of CS/DS containing GalNAc(4,6SO4, appear to contribute to progression of liver fibrosis, delayed recovery from fibrosis, and various changes in the expression of proteoglycans and MMPs in carbon tetrachloride–treated mice.

  8. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation

    DEFF Research Database (Denmark)

    Saber, Anne T; Halappanavar, Sabina; Folkmann, Janne K

    2009-01-01

    BACKGROUND: Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute...... analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E...

  9. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  10. [Evaluation of the action of a fat diet on the state of the liver poisoned by carbon tetrachloride].

    Science.gov (United States)

    Sadykh-zade, K S; Volgarev, M N; Piatnitskiĭ, N N; Zhminchenko, V M; Mal'tsev, G Iu

    1981-01-01

    The effects of the diet containing different amounts of fat on the liver with CCl4 poisoning were studied in two series of experiments on 150 male Wistar rats. In the first series th priming was given in the presence of the laboratory diet for 1 1/2 months. In the second series, the 1 1/2-month priming was given in the presence of the diets tested. The control animals given no priming were kept on the laboratory diet in which the fat (sunflower oil) amount constituted 23% as regards the caloricity. The experimental animals were distributed into 2 groups kept on the diets containing 27 and 43% of fat as regards the caloricity (creamery butter and sunflower oil at a ratio of 2 : 1). All three diets were isocaloric, having the identical content of protein. Change in the fat amount was compensated for the respective change in the carbohydrate content. It was found that application of the diet with the increased content of milk and vegetable fat (43% as regards the caloricity) led to a marked improvement of the liver, while early application of the test diets in the presence of CCl4 brought about a significant decrease in the lethality of the experimental animals.

  11. Protective Effects of Quercetin and Quercetin-5',8-Disulfonate against Carbon Tetrachloride-Caused Oxidative Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yanmang Cui

    2013-12-01

    Full Text Available Oxidative stress is one of the major factors in the pathogenesis of liver disease. Quercetin is a plant-based antioxidant traditionally used as a treatment for hepatic injury, but its poor solubility affects its bioavailability. We here report the regulative effects on hepatoprotection and absorption in mice of quercetin sulfation to form quercetin-5',8-disulfonate (QS, a novel synthetic compound. Oral administration of both QS and the parent quercetin at 100, 200 and 500 mg/kg·bw prior to acute CCl4 oxidative damage in mice, effectively attenuated serum alanine aminotransferase (ALT, aspartate aminotransferase (AST and lactate dehydrogenase (LDH activities and hepatic malondialdehyde (MDA levels (p < 0.05, and suppressed the CCl4-induced depletion of glutathione peroxidase (GSH-Px and total superoxide dismutase (T-SOD. Selective 5',8-sulfation of quercetin increased the hepatoprotective effect, and its relative absorption relative to quercetin (p < 0.05 as indicated by an improved 24-hour urinary excretion and a decreased fecal excretion determined by HPLC. These results and histopathological observations collectively demonstrate that quercetin sulfation increases its hepatoprotective effects and absorption in mice, and QS has potential as a chemopreventive and chemotherapeutic agent for liver diseases.

  12. Natural carbon isotope abundance of plasma metabolites and liver tissue differs between diabetic and non-diabetic Zucker diabetic fatty rats.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Godin

    Full Text Available BACKGROUND: 'You are what you eat' is an accurate summary for humans and animals when it comes to carbon isotope abundance. In biological material, natural(13C/(12C ratio is subject to minute variations due to diet composition (mainly from ingestion of C3 and C4 metabolism plants and to the discrimination between 'light' and 'heavy' isotopes during biochemical reactions (isotope effects and isotopic fractionation. METHODOLOGY/PRINCIPAL FINDINGS: Carbon isotopic abundance was measured in ZDF (fa/+ and ZDF (fa/fa, (lean and obese-diabetic rats respectively fed the same diet. By analysing plasma metabolites (glucose and non-esterified fatty acids, breath and liver tissue by high-precision isotope ratio mass spectrometry, we demonstrate for the first time statistically distinguishable metabolic carbon isotope abundance between ZDF (fa/+ and ZDF (fa/fa rats based on plasma glucose, palmitic, oleic, linoleic, arachidonic acids and bulk analysis of liver tissue (P<0.005 resulting into clear isotopic fingerprints using principal component analysis. We studied the variation of isotopic abundance between both groups for each metabolite and through the metabolic pathways using the precursor/product approach. We confirmed that lipids were depleted in (13C compared to glucose in both genotypes. We found that isotopic abundance of linoleic acid (C18: 2n-6, even though both groups had the same feed, differed significantly between both groups. The likely reason for these changes between ZDF (fa/+ and ZDF (fa/fa are metabolic dysregulation associated with various routing and fluxes of metabolites. CONCLUSION/SIGNIFICANCE: This work provides evidence that measurement of natural abundance isotope ratio of both bulk tissue and individual metabolites can provide meaningful information about metabolic changes either associated to phenotype or to genetic effects; irrespective of concentration. In the future measuring the natural abundance δ(13C of key metabolites

  13. Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin

    Directory of Open Access Journals (Sweden)

    Cornel Iancu

    2011-01-01

    Full Text Available Cornel Iancu1, Lucian Mocan1, Constantin Bele2, Anamaria Ioana Orza2, Flaviu A Tabaran3, Cornel Catoi3, Rares Stiufiuc4, Ariana Stir1, Cristian Matea2, Dana Iancu1, Lucia Agoston-Coldea1, Florin Zaharie1, Teodora Mocan11Department of Nanomedicine, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Third Surgery Clinic, Cluj-Napoca, Romania; 2Department of Biochemistry, 3Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; 4Department of Biophysics, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, RomaniaAbstract: The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC. We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line based on a simple multiwalled carbon nanotube (MWCNT carrier system, such as human serum albumin (HSA, and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA–MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA–MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA–MWCNTs ranged from 88.24% (for 50 mg/L at 60 sec to 92.34% (for 50 mg/L at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA–MWCNTs in a similar manner. Our results clearly show that HSA–MWCNTs selectively attach on the albondin (aka Gp60 receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis

  14. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  15. Negundoside, an irridiod glycoside from leaves of Vitex negundo, protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride

    Institute of Scientific and Technical Information of China (English)

    Sheikh A Tasduq; Peerzada J Kaiser; Bishan D Gupta; Vijay K Gupta; Rakesh K Johri

    2008-01-01

    AIM: To evaluate the protective effect of 2'-p-hydroxy benzoylmussaenosidic acid [negundoside (NG), against carbon tetrachloride (CCl4)-induced toxicity in HUH-7 cells.METHODS: CCl4 is a well characterized hepatotoxin, and inducer of cytochrome P4502E1 (CYP2E1)-mediated oxidative stress. In addition, lipid peroxidation and accumulation of intracellular calcium are important steps in the pathway involved in CCl4 toxicity. Liver cells (HUH-7) were treated with CCl4, and the mechanism of the cytoprotective effect of NG was assessed. Silymarin, a known hepatoprotective drug, was used as control.RESULTS: NG protected HUH-7 cells against CCl4 toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl4, toxicity was associated with a reduction in oxidative damage as reflected by decreased generation of reactive oxygen species (ROS), a decrease in lipid peroxidation and accumulation of intracellular Ca2+ levels and maintenance of intracellular glutathione homeostasis. Decreased mitochondrial membrane potential (MMP), induction of caspases mediated DNA fragmentation and cell cycle arrest, as a result of CCl4 treatment, were also blocked by NG. The protection afforded by NG seemed to be mediated by activation of cyclic adenosine monophosphate (cAMP) synthesis and inhibition of phospholipases (cPLA2).CONCLUSION: NG exerts a protective effect on CYP2El-dependent CCl4 toxicity via inhibition of lipid peroxidation, followed by an improved intracellular calcium homeostasis and inhibition of Ca2+-dependent proteases.

  16. Liver Disease

    Science.gov (United States)

    ... stay still. Liver disease has many causes. Infection Parasites and viruses can infect the liver, causing inflammation ... beyond. National Institute of Diabetes and Digestive and Kidney Diseases. http://digestive.niddk.nih.gov/ddiseases/pubs/ ...

  17. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  18. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  19. Kinetics of carbon monoxide binding to phenobarbital-induced cytochrome P-450 from rat liver microsomes: a simple bimolecular process.

    Science.gov (United States)

    Oertle, M; Richter, C; Winterhalter, K H; Di Iorio, E E

    1985-01-01

    The kinetics of carbon monoxide binding to phenobarbital-induced cytochrome P-450 (P-450PB) and to its enzymatically inactive form P-420PB have been investigated by both stopped-flow and flash-photolysis spectrophotometry. When the simultaneous presence of both forms of the enzyme is taken into account, the binding of CO to these two proteins can be described in terms of two bimolecular processes with rate constants of 4.5 X 10(6) M-1.S-1 and 4.7 X 10(5) M-1.S-1 for P-450PB and 1.7 X 10(7) M-1.S-1 and 1.5 X 10(6) M-1.S-1 for P-420PB. From kinetic studies of the binding of CO to P-450PB under different experimental conditions, investigations of the homogeneity of our P-450PB preparations, and comparative kinetic investigations of P-450s from different sources, we conclude that CO binding to reduced P-450PB is a simple bimolecular process and that the observed biphasic traces are due to heterogeneity of the proteins. This conclusion is in contrast with previous reports of complex reaction mechanisms for the binding of CO to P-450PB. Optical spectroscopy studies indicate the existence of an equilibrium between P-450PB and P-420PB, at least for the reduced carbonyl derivatives of the enzymes. The interconversion is strongly influenced by the aggregation state of the protein. Large differences between the CO binding properties of P-450PB and those of P-420PB are found. These are discussed in terms of possible effects of the proximal ligation state of the iron on heme reactivity. PMID:3860832

  20. Compound list: carbon tetrachloride [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available carbon tetrachloride CCL4 00003 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/carbon...ates/LATEST/Rat/in_vitro/carbon_tetrachloride.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open...-tggates/LATEST/Rat/in_vivo/Liver/Single/carbon_tetrachloride.Rat.in_vivo.Liver.S...ingle.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/carbon_tetrachloride.Rat.in_vivo.Liver.Repeat.zip ...

  1. What Is Liver Cancer?

    Science.gov (United States)

    ... Treatment? Liver Cancer About Liver Cancer What Is Liver Cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  2. Genetically graded activation of Nrf2 protects mice against carbon tetrachloride-induced hepatotoxicity%Nrf2抗氧化损伤通路在CCl4所致小鼠肝毒性中的保护作用

    Institute of Scientific and Technical Information of China (English)

    陆远富; Connie Wu; 刘杰; Curtis Dean Klaassen

    2015-01-01

    目的 观察核转录相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)抗氧化损伤通路对四氯化碳(CCl4)所致小鼠肝毒性的保护作用.方法 选取Nrt2-null、Wild-type、Keap1-KD、Keapl-HKO小鼠,按基因型分为4组,分别给予40 mg/kg CCl4腹腔注射,腹腔注射生理盐水(10 mL/kg)作对照,16 h后收集血浆和肝组织样本,检测血中谷丙转氨酶(alanine transaminase,ALT)和乳酸脱氢酶(lactic dehydrogenase,LDH)活性以及肝组织中丙二醛(malondialdehyde,MDA)含量;HE染色观察肝组织病理学变化,Real-time PCR和Western blot法检测相关基因表达.结果 CCl4增加Nrf2-null组和Wild-type组血中ALT、LDH活性及肝组织MDA含量,同时造成肝组织病理损伤,而在Keap1-KD组和Keap1-HKO组影响不明显;Nrf2因子靶基因(Nqo1和Gclc)在CCl4的诱导表达逐渐增高(顺序为Nrf2-null、Wild-type、Keapl-KD、Keap1-HKO),继而使炎症因子、内质网应激基因、细胞凋亡基因、细胞坏死基因的表达(mKC、MIP-2、IL-1β、TNFα、Gadd45、Chop10、Bax、Caspase3、Mcl、Noxa)按Nrf2-null、Wild-type、Keap1-KD、Keap1-HKO顺序逐渐下降.结论 Nrf2因子激活保护CCl4所致小鼠肝损伤反应.

  3. 四氯化碳诱导兔肝纤维化模型的改良%Modification of liver fibrosis model of rabbit induced by carbon tetrachloride

    Institute of Scientific and Technical Information of China (English)

    侯洪伟; 潘峥; 陈敏; 徐佳佳; 李卫民; 嵇振岭

    2015-01-01

    the traditional process of carbon tetrachloride ( CCl4 ) induced liver fibrosis of rabbit.Methods:50 healthy male new Zealand rabbits were included in this research and divided into 2 batches on average.Rabbits in first batch( traditional batch) were separated into 2 groups:modeling group(n=21) and control group(n=4).Rabbits in modeling group were injected with 50%CCl4 olive oil solution subcutaneously twice a week for 12 weeks in succession while control group were treated with the same amount of pure olive oil.Rabbits in modeling group received color Doppler ultrasound, spiral computed tomography and serum biochemical examination every 4 weeks from the beginning to 12 weeks, 7 rabbits ( remanent were divided equally when rabbits died unexpected ) were sacrificed after blood drawing every 4 weeks to measure portal venous pressure(PVP) and obtained liver tissues for biopsy and immunohistochemical(IHC) staining as well as staging according the ISHAK grading system; Control group were treated with the same way with modeling group and sacrificed at 12 weeks.Modify disadvantages exposed during experiment of first batch and apply revised scheme to the second batch( modified batch) .Results:Mortality of traditional patch was 42.9%and significantly higher than modified batch of 9.5%( P<0.05 ) and the success rate of traditional patch ( 57.1%) was obviously lower than that of modified batch ( 85.7%) , too.With progression of modeling process, ALT, AST, ALB, TP of modeling group underwent significant changes compare to control group ( P<0.05 ); color doppler flow imaging showed the speed of portal venous blood flow of modeling group was obviously slower and CT values were significantly reduced comparing to control group;HE, Masson and IHC staining showed explicit liver fibrosis and pseudolobule could be seen, ISHAK score rised over time(1.33 ±0.52,1.83 ±0.75,4.17 ±0.75 of modified modeling group at 4,8,12 week respectively).Conclusion:Continuous injection of CCl4 can induce

  4. Liver Transplant

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  5. Metal Concentrations in the Liver and Stable Isotope Ratios of Carbon and Nitrogen in the Muscle of Silvertip Shark (Carcharhinus albimarginatus) Culled off Ishigaki Island, Japan: Changes with Growth.

    Science.gov (United States)

    Endo, Tetsuya; Kimura, Osamu; Ohta, Chiho; Koga, Nobuyuki; Kato, Yoshihisa; Fujii, Yukiko; Haraguchi, Koichi

    2016-01-01

    We analyzed Hg, Cd, Zn, Cu and Fe concentrations in liver samples as well as the Hg concentration and stable isotope ratios of carbon and nitrogen (δ13C and δ15N) in muscle samples from silvertip sharks (Carcharhinus albimarginatus) in Japan. Muscular and hepatic Hg concentrations increased with increased body length. However, these increases were more prominent in the liver than in the muscle samples, and appeared to occur after maturation. Hepatic Zn and Cu concentrations decreased during the growth stage, and then increased concomitantly thereafter with increases in Cd burden. Hepatic Fe concentration from males increased proportionally with increases in body length, whereas no increase was observed in samples from females, probably due to the mother-to-embryo transfer of Fe. The δ13C values tended to decrease with increases in body length, whereas no decrease in the δ15N values was observed.

  6. Liver spots

    Science.gov (United States)

    Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ultraviolet light, or causes that are not known. Liver spots are very common after age 40. They occur ...

  7. Metabolism of nitrogenous compounds by ruminant liver.

    Science.gov (United States)

    Reynolds, C K

    1992-03-01

    Ruminants absorb substantial amounts of ammonia nitrogen and very little glucose. Ammonia absorbed is removed by the liver and converted to urea, which can be recycled to the digestive tract and add to the pool of ammonia absorbed. When ammonia absorption and liver urea production are increased by changes in nitrogen intake, an associated increase in liver alpha-amino nitrogen removal has been observed. Reasons for the increase in liver removal of amino acids with greater ureagenesis are uncertain, but the aspartate/glutamate requirement of ureagenesis and the complex relationships between ureagenesis and the tricarboxylic acid cycle, glucogenesis, liver energy metabolism and redox state all may be involved. Amino acids represent potential sources of carbon for liver glucogenesis and precise reckonings of the contributions of amino acid carbon to glucogenesis are needed for ruminants fed differing diets. There is evidence for the involvement of peptides in liver nitrogen exchanges and amino acids in peptides represent a potential source of carbon for glucogenesis and nitrogen for ureagenesis. A number of endocrine factors have an impact on liver nitrogen metabolism in ruminants. Growth hormone decreases liver urea release and increases liver glutamate release.

  8. Liver metastases

    Science.gov (United States)

    ... no symptoms. When symptoms occur, they may include: Decreased appetite Confusion Fever , sweating Jaundice (yellowing of the skin ... can include: Blockage of the flow of bile Decreased appetite Fever Liver failure (usually only in the late ...

  9. Enlarged Liver

    Science.gov (United States)

    ... A blood sample is tested to determine liver enzyme levels. This can give clues about the health ... prescription medications. Limit contact with chemicals. Use aerosol cleaners, insecticides and other toxic chemicals only in well- ...

  10. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  11. (13)Carbon and (15)nitrogen isotopes in autopsy liver tissue samples from Greenlandic Inuit and Danes: consumption of marine versus terrestrial food

    DEFF Research Database (Denmark)

    Milman, N.; Laursen, J.; Mulvad, G.

    2010-01-01

    Background/Objectives: The content of C-13 and N-15 isotopes is higher in marine than in terrestrial food. C-13 and N-15 in human tissue therefore reflects the relative proportions of marine and terrestrial food consumed by the individual. The objective of this study was to measure C-13 and N-15...... in liver tissue from Greenlandic Inuit and Danes. Subjects/Methods: Normal liver tissue was obtained at autopsy in 1992-1994 from 60 Inuit with a median age of 61 years (range 25-83) and in 1986 from 15 ethnic Danes with a median age of 84 years (range 66-93). By sieving, liver tissue was separated...

  12. Impact of abhrak bhasma and silicon dioxide on histological architecture of liver and kidney in single dose of carbon tetrachloride intoxicated male albino rat

    Directory of Open Access Journals (Sweden)

    Parashuram Teli

    2015-01-01

    Full Text Available Abhrak bhasma is a widely used Ayurvedic drug in various diseases including hepatotoxicity. In the present study, protective effect of graded doses (10, 20, 30 and 40mg/kg body wt of abhrak bhasma and its silica control, SiO2 was studied against CCl4 induced liver and kidney damage in male albino rats during single dose experimental schedule for 24 hrs. Administration of CCl4 (3.0ml/ kg body wt induced fatty necrosis in hepatic cells without affecting kidney histology. Treatment of abhrak bhasma showed dose dependent protection against CCl4 induced liver damage by free radical scavenging activity. Silica in SiO2 form also positively influences liver fatty degeneration induced by single dose of CCl4 but is associated with some hepatocytes hypertrophy.

  13. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats

    Institute of Scientific and Technical Information of China (English)

    Mehmet Kanter; Omer Coskun; Mustafa Budancamanak

    2005-01-01

    AIM: To investigate the effects of Nigella sativa L (NS)and Urtica dioica L (UD) on lipid peroxidation, antioxidant enzyme systems and liver enzymes in CCl4-treated rats.METHODS: Fifty-six healthy male Wistar albino rats were used in this study. The rats were randomly allotted into one of the four experimental groups: A (CCl4-only treated), B (CCl4+UD treated), C (CCl4+NS treated) and D (CCl4+UD+NS treated), each containing 14 animals.All groups received CCl4 (0.8 mL/kg of body weight, sc,twice a week for 60 d). Tn addition, B, C and D groups also received daily J.p. injections of 0.2 mL/kg NS or/and 2 mL/kg UD oils for 60 d. Group A, on the other hand,received only 2 mL/kg normal saline solution for 60 d.Blood samples for the biochemical analysis were taken by cardiac puncture from randomly chosen-seven rats in each treatment group at beginning and on the 60th d of the experiment.RESULTS: The CCl4 treatment for 60 d increased thelipid peroxidation and liver enzymes,and also decreasedthe antioxidant enzyme levels. NS or UD treatment (aloneor combination) for 60 d decreased the elevated lipidperoxidation and liver enzyme levels and also increasedthe reduced antioxidant enzyme levels.The weight ofrats decreased in group A,and increased in groups B, Cand D.CONCLUSION: NS and UD decrease the lipid peroxidation and liver enzymes, and increase the antioxidant defense system activity in the CCl4-treated rats.

  14. Application of hyperbaric oxygen in liver transplantation

    Directory of Open Access Journals (Sweden)

    Hu Lv

    2016-01-01

    Full Text Available In recent years, hyperbaric oxygen (HBO has been used in the treatment of a lot of diseases such as decompression sickness, arterial gas embolism, carbon dioxide poisoning, soft tissue infection, refractory osteomyelitis, and problematic wound, but little is known about its application in liver transplantation. Although several studies have been conducted to investigate the protective effects of HBO on liver transplantation and liver preservation, there are still some controversies on this issue, especially its immunomodulatory effect. In this short review, we briefly summarize the findings supporting the application of HBO during liver transplantation (including donors and recipients.

  15. 四氯化碳皮下注射诱导兔肝硬化模型的建立%Development of Rabbit Liver Cirrhosis by Carbon Tetrachloride Subcutaneous Injection

    Institute of Scientific and Technical Information of China (English)

    于晓红; 金博; 邱慧彬; 付山峰; 路平

    2011-01-01

    Objective To establish a liver cirrhosis animal model in rabbit through carbon tetrachloride subcutaneous injections. Methods Total 50 male rabbits were divided into 2 groups randomly. The experimental group (n =35 ) were injected 50% CCl4-olive oil subcutaneously with the dosage 0. 23ml/kg in the gluteal region,twice a week. The same dosage of olive oil was injected in the control group by a same way. The liver function test and the histopathology were investigated at the end of 4,8,12weeks. Results The hepatic fibrosis progressed gradually as continuous injection of the toxin. The ALT,AST,GGT increased obviously. At the end of 12 weeks,the albumin/globulin ratio was reversed. A typical pathology of liver cirrhosis was detected. In the control group the liver function and histology were normal. The mortality is 20% at the end of experiment and the achievement ratio of animal model is 83%. Conclusion The rabbit liver cirrhosis model can be established by subcutaneous injection of carbon tetrachloride. This animal model can be used in liver cirrhosis experiment.%目的 应用四氯化碳(CCI4)皮下注射方法,建立兔肝硬化动物模型.方法 50只雄性新西兰大白兔随机分为实验组(n=35)和对照组(n=15).实验组臀部皮下注射50%CCI4橄榄油0.23 mL/kg,每周2次,对照组注射等量橄榄油.分别于4 w、8 w和12 w末检测各组兔肝脏功能及组织病理学变化.结果 随时间延长,实验组兔肝脏纤维化程度逐渐加重,血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和γ-谷氨酰转肽酶(GGT)明显升高,12 w末出现白蛋白/球蛋白比例倒置,可观察到典型肝硬化病理表现,兔肝组织出现典型的假小叶结构,动物死亡率20%,造模成功率83%.对照组肝脏功能正常,肝脏组织学结构正常.结论 此方法可成功地建立兔肝硬化动物模型,该方法成功率高,可用于相关实验研究.

  16. Liver Function Tests

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  17. Benign Liver Tumors

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  18. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  19. Liver Transplant: Nutrition

    Science.gov (United States)

    ... ZIP code here Enter ZIP code here Liver Transplant: Nutrition for Veterans and the Public Nutrition Liver ... apply to transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver ...

  20. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  1. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008447 Identification of gene expression patterns in a rat model of nonalcoholic fatty liver disease. ZHANG Xuequn(张雪群), et al. Dept Gastroenterol, 1st Hosp, Med Coll, Zhejiang Univ, Hangzhou 310003. Chin J Dig 2008;28(5):323-327. Objective To compare and analyze gene expression patterns in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.

  2. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008310 Expression of αVβ3 integrin and platelet-endothelial cell adhesion molecule-1 in progressive liver fibrosis: experiment with rats. SONG Zhengji(宋正已), et al. Dept Gastroenterol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Natl Med J China 2008;88(16):1121-1125.Objective To investigate the expression ofαVβ3 integrin and platelet endothelial cell adhesion molecule-1(CD31)in progressive liver fibrosis of rats.Methods Sixty-four SD rats were randomly divided into 4 equal groups:TAA group,undergoing peritoneal injection of

  3. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  4. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970345 An experimental and clinical study on α1-adrenergic receptor of liver plasma membranes in cir-rhosis with portal hypertension. ZHANG Youcheng(张有成), et al. Dept Surg, People’s Hosp, Beijing MedUniv, Beijing, 100044 Chin J Dig 1996; 16(6): 332-335.

  5. The in vivo toxicity of carbon tetrachloride and carrageenan on heart microsomes: analysis by Fourier transform infrared spectroscopy.

    Science.gov (United States)

    Melin, A M; Perromat, A; Deleris, G

    2001-09-01

    We investigated the sensitivity of rat heart microsomes to free radical attack using Fourier transform infrared (FT-IR) spectroscopy. This physico-chemical method seemed a valuable technique: quite sensitive to changes in the vibrational spectra. The spectral variations observed between normal and treated rats were in great part due to reactive oxygen species that led to changes in protein conformation involving beta-sheets, aggregation of proteins, and modification of protein synthesis. Carrageenan-induced inflammation slightly enhanced the total lipid content; rearrangement of acyl chains and accumulation of cholesterol esters and phospholipids also occurred in the treated rats. Carbon tetrachloride induced a decrease in both lipid and protein contents. The level of glucidic substrates was diminished with carbon tetrachloride and enhanced with carrageenan; these changes were due to metabolic interactions between cell components and drugs. FT-IR spectroscopy provided an accurate means to monitor, in rat heart, the in vivo effects of inflammatory and peroxidative damages, to discriminate and classify the affected cells, and to correlate the findings with known physiological and biochemical data in close relationship with metabolic disruptions induced by the two xenobiotics.

  6. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930137 Effects of selective and non-selectiveβ-adrenoreceptor blockers on portal hemody-namics in patients with liver cirrhosis.HUANGTianwei(黄天卫),et al.1st Affili Hosp,DalianMed Coll.Chin J Digest 1992;12(3):145-147.Effects of selective(atenolol)and non-selec-tive(propranolol)β-adrenoreceptor blockerson portal hemodynamics in patients with livercirrhosis were measured by pulsed Doppler du-

  7. Liver in systemic disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

  8. Liver transplant for cholestatic liver diseases.

    Science.gov (United States)

    Carrion, Andres F; Bhamidimarri, Kalyan Ram

    2013-05-01

    Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT.

  9. Liver Disease and IBD

    Science.gov (United States)

    ... Home > Resources > Liver Disease and IBD Go Back Liver Disease and IBD Email Print + Share Several complications ... be necessary to make the definitive diagnosis. FATTY LIVER DISEASE (HEPATCI STEATOSIS) This is the most common ...

  10. Pyogenic liver abscess

    Science.gov (United States)

    Liver abscess; Bacterial liver abscess ... There are many possible causes of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

  11. Liver Function Tests

    Science.gov (United States)

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  12. Amebic liver abscess

    Science.gov (United States)

    Hepatic amebiasis; Extraintestinal amebiasis; Abscess - amebic liver ... Amebic liver abscess is caused by Entamoeba histolytica. This parasite causes amebiasis , an intestinal infection that is also called ...

  13. Liver regeneration in nonalcoholic fatty liver disease

    OpenAIRE

    Aldo Lagomarsino

    2012-01-01

    Steatosis is the accumulation of fat in hepatocytes, which may be the result of liver regeneration or pathological processes such as alcoholic and nonalcoholic fatty liver disease. Despite its importance, in both cases the exact mechanism that prevails in fatty liver regeneration is poorly understood. Previous studies have shown that patients with fatty liver express dispar regeneration, possibly due to the accumulation of reactive oxygen species generated by inflammatory processes caused by ...

  14. Getting a New Liver: Facts about Liver Transplants

    Science.gov (United States)

    ... 2002 December 2006 March 2012 Getting A New Liver Facts About Liver Transplants American Society of Transplantation 1120 Route 73, ... views of the Society. _________________________________________________________________ 1 Getting a New Liver Facts About Liver Transplants A liver transplant is ...

  15. Evaluation of hepatoprotective effect of Gentiana olivieri herbs on subacute administration and isolation of active principle.

    Science.gov (United States)

    Orhan, Didem Deliorman; Aslan, Mustafa; Aktay, Göknur; Ergun, Ender; Yesilada, Erdem; Ergun, Fatma

    2003-04-04

    Hepatoprotective effect of Gentiana olivieri Griseb. (Gentianaceae) flowering herbs on subacute administration were studied using in vivo models in rats. For the activity assessment on carbon tetrachloride-induced hepatic damage following biochemical parameters were evaluated; plasma and hepatic tissue malondialdehyde formation, and liver tissue glutathione level, as well as plasma transaminase enzyme levels (aspartate transferase and alanine transferase). Results of biochemical tests were also confirmed by histopathological examination. Through bioassay-guided fractionation procedures isoorientin, a known C-glycosylflavone, was isolated from the ethyl acetate fraction as the active antihepatotoxic constituent by silica gel column chromatography. Isoorientin exhibited significant hepatoprotective effect at 15 mg/kg b.w. dose.

  16. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930537 Preliminary report on portal hyperten-tion in liver cirrhosis treated by transjugular in-trahepatic portosystemic stent shunt(analysis of8 cases).XU Ke(徐克),et al.Dept Radiol,lst Hosp,China Med Univ,Shenyang,110001.Chin J Radiol 1993;25(5):294—297.Transjugular intrahepatic portosystemic stentshunt(TIPPS)was performed in 8 cases of livercirrhosis with portal hypertention.Moderate orsevere hemorrhage from gastroesophageal variceshad happened in all patients for 2~5 times beforTIPSS.The average pressure of portal veindropped from 3.80±0.50kPa to 2.58±0.26kPa.The diameter of the shunt established be-tween portal and hepatic veins was 10~12mm.Gastrointestinal bleeding and ascites were effec-

  17. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950330 Effect of tetrandrine on mitochondria of hep-atofibrosis rats.LI Dingguo(李定国),et al.XinhuaHosp,Shanghai 2nd Med Univ,200092 Chin J Digest1994;14(6):339-341Carbon tetrachloride was used to create the hep-atofibrotic rat model.Different doses of tetrandrine(Tet) were used to treat these rats in the early andlate hepatofibrotic stages.We observed that small dos-June 1995 Vol 12 No 2

  18. Role of Gut Microbiota in Liver Disease.

    Science.gov (United States)

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

  19. Immune mediated liver failure

    OpenAIRE

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  20. Appropriateness of Liver Biopsy

    OpenAIRE

    Thierry Poynard; Vlad Ratziu; Pierre Bedossa

    2000-01-01

    This review aims to discuss the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The medical literature, published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heter...

  1. Effect of matrine hydrochloride on liver injury

    Institute of Scientific and Technical Information of China (English)

    CHEN Li-bo; XU Feng; MA Wen-hui

    2008-01-01

    Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、 immunity liver injury of mice and chronic liver injury of rats. Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride (CCl4), thioacetamide(TAA), D-galactosamine(D-GalN), immunity hepatic injury model of mice induced by BCG and fat polysaccharide (LPS), chronic liver injury model of rats induced by CCI, were introduced in the experiment. The serum ALT and AST were measured in acute hepatic injury experiments. Serum ALT, AST, AKP, ALB, TP, BiL-T, ereatinine, triglyceride, sialie acid, larninin, hyaluronic acid, type Ⅲ proeollagen and type Ⅳ collagen, hepatic hydroxyproline (HyP) of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride. Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4, TAA and D-GaIN. The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment. Compared with the model group, the injection may obviously inhibited serum ALT, AST, TP, AKP, TRI, BiL-T, creatinine, triglyceride, sialic acid, laminin , hyaluronic acid , type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4, elevated ALB、A/G, reduced the liver HyP, decreased the index of the liver and the spleen. The liver visual observation, the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue, restrain the liver cell damage, reduce the pseudolobuli formation. Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and

  2. Biomarkers for liver fibrosis

    Science.gov (United States)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  3. Liver disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Noel M Lee; Carla W Brady

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

  4. Bioartificial liver: current status.

    Science.gov (United States)

    Pless, G; Sauer, I M

    2005-11-01

    Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

  5. Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats

    Directory of Open Access Journals (Sweden)

    M Anusha

    2011-01-01

    Full Text Available Objective : To investigate the hepatoprotective activity of the aqueous extract of the aerial parts of Portulaca oleracea (P. oleracea in combination with lycopene against carbon tetrachloride induced hepatotoxicity in rats. Materials and Methods : Hepatotoxicity was induced in male Wistar rats by intraperitoneal injection of carbon tetrachloride (0.1 ml/kg b.w for 14 days. The aqueous extract of P. oleracea in combination with lycopene (50 mg/kg b.w was administered to the experimental animals at two selected doses for 14 days. The hepatoprotective activity of the combination was evaluated by the liver function marker enzymes in the serum [aspartate transaminases (AST, alanine transaminases (ALT, alkaline phosphatase (Alk.P, total bilirubin (TB, total protein (TP and total cholesterol (TC], pentobarbitone induced sleeping time (PST and histopathological studies of liver. Results : Both the treatment groups showed hepatoprotective effect against carbon tetrachloride induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal which was comparable to that of silymarin group. Besides, the results obtained from PST and histopathological results also support the study. Conclusions : The oral administration of P. oleracea in combination with lycopene significantly ameliorates CCl 4 hepatotoxicity in rats.

  6. 碳酸盐碱度对青海湖裸鲤幼鱼肝和肾SOD、ACP和AKP酶活性的影响%Effects of carbonate alkalinity stress on SOD, ACP, and AKP activities in the liver and kidney of juvenile Gymnocypris przewalskii

    Institute of Scientific and Technical Information of China (English)

    王卓; 么宗利; 林听听; 史建全; 周凯; 王慧; 祁洪芳; 来琦芳

    2013-01-01

    青海湖裸鲤(Gymnocypris przewalskii,以下简称裸鲤)为耐盐碱鱼类。自青海湖裸鲤救护中心取裸鲤幼鱼,全长(4.42±0.02) cm,体质量(0.84±0.01) g。碳酸盐碱度暴露浓度设定为32 mmol/L(CA32)和64 mmol/L(CA64),通过测定青海湖裸鲤幼鱼肝和肾中超氧化物歧化酶(SOD)、酸性磷酸酶(ACP)和碱性磷酸酶(AKP)酶活性变化规律,探索裸鲤幼鱼肝和肾中 SOD、ACP 和 AKP 对碳酸盐碱度胁迫的生理响应。在本试验范围内,裸鲤在高碱环境中显示出较强的适应调节能力,在碳酸盐碱度胁迫下, SOD、ACP和AKP酶活性均能在发生显著变化后快速恢复到初始水平,但3种酶显示出不同的变化规律:(1)肝SOD在CA32和CA64胁迫3 d、肾SOD在CA32胁迫4 d、CA64胁迫3 d时,酶活性均显著升高。(2)肝和肾ACP活性出现不同的变化趋势,肝ACP活性仅在CA64胁迫组4 d出现显著上升,而肾ACP活性在CA32胁迫0.5 d、7 d和CA64胁迫1 d时分别出现了显著性波动。(3)肝AKP在CA32胁迫1 d、CA64胁迫3 d时,酶活性显著升高,而肾AKP仅在CA32胁迫0.5 d时,酶活性显著升高。在碳酸盐碱度胁迫下,3种酶活性均能发生显著变化,说明青海湖裸鲤幼鱼通过抗氧化及去磷酸化应激调节,来更好地应对高碱环境。%Saline-alkaline water is relatively prevalent throughout China. High alkalinity is thought to represent a significant stressor for aquatic organisms that occupy saline-alkaline waters. Gymnocypris przewalskii is a com-mercially important fish that is endemic to Qinghai Lake, a high saline-alkali environment. This species is ana-dromous and migrates up rivers to spawn between April to July. The abundance of G. przewalskii has decreased dramatically because of over-fishing and habitat degradation. As a result, it is now listed as an endangered fish. Thus, an understanding of the changes in stress-related enzymes in the liver and kidney of juvenile G. przewalskii exposed to carbonate

  7. Tests for Liver Cancer

    Science.gov (United States)

    ... has come back after treatment Alpha-fetoprotein blood (AFP) test AFP is normally present at high levels in the ... liver disease, liver cancer, or other cancers. If AFP levels are very high in someone with a ...

  8. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  9. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  10. Antioxidants in liver health

    Institute of Scientific and Technical Information of China (English)

    Sael; Casas-Grajales; Pablo; Muriel

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals(FR).However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leadsto deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases.

  11. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  12. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  13. Percutaneous liver biopsy.

    Science.gov (United States)

    Rustagi, Tarun; Newton, Eric; Kar, Premashish

    2010-01-01

    Percutaneous liver biopsy has been performed for more than 120 years, and remains an important diagnostic procedure for the management of hepatobiliary disorders. Modern biochemical, immunologic, and radiographic techniques have facilitated the diagnosis and management of liver diseases but have not made liver biopsy obsolete. This comprehensive review article will discuss the history of development of percutaneous liver biopsy, its indications, contraindications, complications and the various aspects of the biopsy procedure in detail.

  14. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna

    2009-01-01

    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  15. Research Areas: Liver Disease

    Science.gov (United States)

    ... and C, or by genetic mutations. Other liver diseases can be triggered by autoimmune reactions or drug toxicity. The rise in obesity in the United States has led to a rise in nonalcoholic fatty liver disease. Many liver diseases place individuals at higher risk ...

  16. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    11.1 Liver cirrhosis and fatty liver2003230 The relevance of fatty liver and insulin resistance. LIU Jun(刘军), et al. Dept Endocrinol, Zhong-shan Hosp, Fudan Univ, Shanghai 200032, Shanghai Med J 2003; 16(1): 14-17

  17. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    9.1 Liver Function2007108 Blood pressure changes post liver transplantation in 206 recipients. LIU Hai(刘海),et al. 1st People′s Hosp, Shanghai Jiaotong Univ, Shanghai 200080. Chin J Cardiol 2006;34(10):902-904. Objective To study the blood pressure (BP)changes in the liver transplant recipients.

  18. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... 1- to 2-Year-Old Blood Test: Hepatic (Liver) Function Panel KidsHealth > For Parents > Blood Test: Hepatic (Liver) Function Panel Print A A A What's in ... Is The hepatic function panel, also known as liver function tests, is a group of seven tests ...

  19. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    9.1 Liver cirrhosis and fatty liver2003335 The effects of weight reduction in reversing fatty liver changes in overweight and obese patients.ZHU Huijuan(朱惠娟), et al.Dept Endocrinol, PUMC Hosp,CAMS & PUMC, Beijing 100730. Chin J Intern Med 2003:42(2):98-102.Objective:To study the effects of weight loss on non-

  20. Imaging in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Settimo Caruso; Roberto Miraglia; Luigi Maruzzelli; Salvatore Gruttadauria; Angelo Luca; Bruno Gridelli

    2009-01-01

    The aim of this study was to illustrate the role of noninvasive imaging tools such as ultrasonography, multidetector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation.

  1. 乙胺嗪对四氯化碳致急性肝损伤大鼠的保护作用%Hepatoprotective effects of diethylcarbamazine in acute liver damage induced by carbon tetrachloride in rats

    Institute of Scientific and Technical Information of China (English)

    Gonzàlez R; Ancheta O; Màrquez M; Rodriguez S

    1994-01-01

    This research was carried out to determine a potential role of leukotrienes in the acute hepatotoxicity induced by CCl4 in rats. An inhibitor of leukotrienes biosynthesis,diethylcarbamazine (DEC, 25 and 50 mg creasing the activity of alanine aminotransferase in serum and the concentration of liver triglycerides. DEC reduced histological damage of liver evidenced by electron micr oscopy.The hepatoprotective effects of DEC were dose-dependent. The results favor the role of leukotrienes in CCl4 hepatotoxicity.

  2. [Liver and sport].

    Science.gov (United States)

    Watelet, J

    2008-11-01

    The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

  3. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

    2009-01-01

    Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 150...

  4. Endovascular management in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Kyu-Bo Sung

    2006-01-01

    @@ Liver transplantation was developed for the treatment of hepatic failure, and the first human liver transplantation was done in 1963. From the 1990 s,liver transplantation was generally accepted as a treatment modality for both end-stage liver disease and selected liver malignancies. Initially, liver transplantation was started with deceased donor whole-size liver transplantation (whole-size LT) as in other organ transplantation, but there is now a shortage of deceased liver donors has occurred. As a solution, deceased donor split liver transplantation (split LT) began in 1989 and living donor liver transplantation (LDLT) in the early 1990 s. Current liver transplantation techniques include whole-size LT, reduced-size liver transplantation (reduced-size LT), split LT and single or dual LDLT. Two donors give a part of their livers to one adult recipient simultaneously in dual LDLT.

  5. Transjugular liver biopsy.

    Science.gov (United States)

    Ble, Michel; Procopet, Bogdan; Miquel, Rosa; Hernandez-Gea, Virginia; García-Pagán, Juan Carlos

    2014-11-01

    Liver biopsy is still the gold standard for evaluation of acute and chronic liver diseases, despite achievements regarding noninvasive diagnosis and staging in liver diseases. Transjugular liver biopsy (TJLB) has proved a good option when ascites and/or significant coagulopathy precludes a percutaneous approach. Because diagnostic hemodynamic procedures can be performed during the same session, it is useful in many clinical settings, regardless of the absence of percuteaneous contraindications. TJLB is a safe technique able to provide good-quality specimens with a low rate of complications. This article presents an overview of TJLB that discusses the technique, applicability, indications, contraindications, complications, and diagnostic accuracy.

  6. Evaluation of Hepatoprotective Effect of Leaves of Cassia sophera Linn.

    Directory of Open Access Journals (Sweden)

    Arijit Mondal

    2012-01-01

    Full Text Available In the present study, the hepatoprotective activity of ethanolic extracts of Cassia sophera Linn. leaves was evaluated against carbon-tetrachloride- (CCl4- induced hepatic damage in rats. The extracts at doses of 200 and 400 mg/kg were administered orally once daily. The hepatoprotection was assessed in terms of reduction in histological damage, changes in serum enzymes, serum glutamate oxaloacetate transaminase (AST, serum glutamate pyruvate transaminase (ALT, serum alkaline phosphatase (ALP, total bilirubin, and total protein levels. The substantially elevated serum enzymatic levels of AST, ALT, ALP, and total bilirubin were restored towards the normalization significantly by the extracts. The decreased serum total protein level was significantly normalized. Silymarin was used as standard reference and exhibited significant hepatoprotective activity against carbon tetrachloride-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that Cassia sophera leaves have potent hepatoprotective action against carbon tetrachloride-induced hepatic damage in rats. This study suggests that possible activity may be due to the presence of flavonoids in the extracts.

  7. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...

  8. Bioartificial Liver Support

    Directory of Open Access Journals (Sweden)

    Vincent G Bain

    2001-01-01

    Full Text Available Bioartificial liver support has been increasingly the focus of both basic and clinical research in an attempt to replicate the multiplicity of normal liver function. The concept is attractive because, if it is effective, patients with acute liver failure may be supported until native liver regeneration occurs or, by optimizing their condition, until liver transplantation is possible. Current bioartificial liver support systems utilize primary porcine hepatocytes or transformed human hepatocytes, which are housed within a bioreactor, through which the patient's blood or plasma is pumped in an extracorporeal circuit. The optimal source for the hepatocytes is an area of debate; however, a genetically engineered cell line may provide optimal function. Novel three-dimensional matrices that anchor the hepatocytes are being designed to mimic architectural features of the normal liver. Large multicentre, randomized, controlled trials are ongoing following several pilot studies. Serious side effects such as hemodynamic instability and immune reactions have been infrequent. Much controversy, however, surrounds the issue of possible transmission of pig endogenous retrovirus to humans, and current trials are being carefully monitored. Bioartificial liver support is a promising technology, and the results of current and planned studies are awaited with great interest.

  9. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    9.1.Liver cirrhosis and fatty liver2005376 The role of ribosomal S6 kinase in thepathogenesis of rat hepatic fibrosis.YANG Miaofang(杨妙芳),et al.Dept Gastroenterol,Changzheng Hosp,2nd Milit Med Univ,Shanghai 200003.Chin J Dig 2005;25(2):98-100.

  10. Prolactin and liver disease

    NARCIS (Netherlands)

    A.G.C. Bauer (Alexander)

    1982-01-01

    textabstractCirrhosis of the liver is associated with profound endocrinological disturbances. Until recently it was thought that these disturbances were caused mainly by ineffective elimination of hormones by the diseased liver. It is now known that the pathogenesis of disturbed hormonal function in

  11. LIVER AND BILIARGY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    8.1 Liver cirrhosis and fatty liver2004100 The clinical feature and prognosis of Aero-monas septicaemia in hepatic cirrhosis: a report of 50 cases. QU Fen (曲芬), et al. Clin Centre, 302nd Hosp PLA, Beijing 100039. Chin J Intern Med 2003; 42 (12): 840 - 846Objective: Aeromonas septicaemia complicating cirrhosis

  12. Hypoxia and fatty liver.

    Science.gov (United States)

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-07

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

  13. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011220 Value of liver biopsy in diagnosis of chronic hepatitis B. YANG Fang(杨方) ,et al. 2nd Ward, Shenyang 6th People’s Hosp,Shenyang 110006. Chin J Infect Dis 2011; 29(2):99-103. Objective To explore the value of liver biopsy in diagnosis of the severity of chronic hepatitis

  14. Acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Lee, William M; Wendon, Julia;

    2015-01-01

    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...

  15. Multiple pyogenic liver abscess

    Institute of Scientific and Technical Information of China (English)

    Mabrouk Bahloul; Anis Chaari; Nadia Bouaziz-Khlaf; Hatem Kallel; Leila Herguefi; Hedi Chelly; Chokri Ben Hamida; Mounir Bouaziz

    2006-01-01

    Multiple pyogenic liver abscesses have been rarely described. We report a fatal case of multiple pyogenic liver abscesses affecting a 38-year-old woman requiring surgical drainage. Evolution was marked by occurrence of a septic shock with multi-organ system failure. The patient died 48 h after surgery. Causes, therapeutics and outcome of the disease are discussed.

  16. [Xenotransplantation of the liver].

    Science.gov (United States)

    Winkler, M; Schlitt, H J

    1999-01-01

    The development of pigs transgenic for human regulators of complement activation resulted in the nearly total elimination of episodes of hyperacute rejection following discordant solid organ xenotransplantation. Following discordant heart or kidney transplantation, in subhuman primates, graft survival rates of up to several months can be observed. In contrast to these organs, the xenotransplantation of the liver is associated with the inherent problem of the immunological and metabolic compatibility of the large variety of xenoproteins generated. Based on a review of data mainly derived from experimental ex-vivo xenoliver perfusions in patients with hepatic coma, whole organ orthotopic or heterotopic liver xenotransplantation currently is not likely to become a relevant option for the treatment of patients with endstage liver failure. In contrast, clinical studies utilizing different forms of bioartificial liver assist devices are currently underway. Based on preliminary data published, this form of liver support therapy might enter the clinic in the near future.

  17. Liver cancer oncogenomics

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B

    2015-01-01

    Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches....... Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer...... development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could...

  18. Disturbance of hepatic and intestinal microcirculation in experimental liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Sasa-Marcel Maksan; Eduard Ryschich; Zilfi (U)lger; Martha Maria Gebhard; Jan Schmidt

    2005-01-01

    AIM: To analyze hepatic, mesenteric and mucosal microcirculation and leukocyte-endothelium interaction (LEI) in a rat model with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in Wistar rats by gavage with carbon tetrachloride, and intravital videomicroscopy was performed in liver, mesentery and small intestine mucosa. Special emphasis is given on microcirculatory and morphometric changes during cirrhotic portal hypertension.RESULTS: LEI was influenced significantly in the cirrhotic liver but not in the gut. Blood flow measurement showed significant differences among liver, main mesenteric vessels and the mucosa. The results of our study indicate that liver cirrhosis leads to alterations in hepatic and mesenteric blood flow but not in mucosal blood flow.CONCLUSION: The enhanced inflammatory response in hepatic microvessels may be caused by a decrease of antithrombin Ⅲ levels and could be responsible for disturbances of organ pathology.

  19. Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines, Transforming Growth Factor-β1 and Angiogenic Markers in Carbon Tetrachloride-Intoxicated Rats

    Directory of Open Access Journals (Sweden)

    Nouf M. Al-Rasheed

    2015-01-01

    Full Text Available Previous data indicated the protective effect of date fruit extract on oxidative damage in rat liver. However, the hepatoprotective effects via other mechanisms have not been investigated. This study was performed to evaluate the antifibrotic effect of date flesh extract (DFE or date pits extract (DPE via inactivation of hepatic stellate cells (HSCs, reducing the levels of inflammatory, fibrotic and angiogenic markers. Coffee was used as reference hepatoprotective agent. Liver fibrosis was induced by injection of CCl4 (0.4 mL/kg three times weekly for 8 weeks. DFE, DPE (6 mL/kg, coffee (300 mg/kg, and combination of coffee + DFE and coffee + DPE were given to CCl4-intoxicated rats daily for 8 weeks. DFE, DPE, and their combination with coffee attenuated the elevated levels of inflammatory cytokines including tumor necrosis factor-α, interleukin-6, and interleukin-1β. The increased levels of transforming growth factor-β1 and collagen deposition in injured liver were alleviated by both extracts. CCl4-induced expression of α-smooth muscle actin was suppressed indicating HSCs inactivation. Increased angiogenesis was ameliorated as revealed by reduced levels and expression of vascular endothelial growth factor and CD31. We concluded that DFE or DPE could protect liver via different mechanisms. The combination of coffee with DFE or DPE may enhance its antifibrotic effects.

  20. Antioxidant supplements for liver diseases

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka

    2011-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  1. [Lipogenesis and gluconeogenesis in the liver of irradiated rats].

    Science.gov (United States)

    Sedlakova, A; Paulikova, E; Diatelinka, I

    1984-01-01

    The incorporation of 14C from [U-14C] glucose and 3H from 3H2O into the total lipids fatty acids and glycogen of the liver incorporation of 3H from 3H2O into blood glucose was studied in rats totally irradiated in a dose of 14.4 Gy. It is shown that in the liver of irradiated rats glucose is accumulated in considerable amounts as glycogen but it is slightly used as a source of carbon for lipid synthesis. The study of 3H incorporation shows that irradiation stimulates glucogenesis, glyconeogenesis and lipogenesis in the liver.

  2. Liver biopsy in liver patients with coagulopathy

    DEFF Research Database (Denmark)

    Ott, P.; Gronbaek, H.; Clausen, M.R.;

    2008-01-01

    The risk of severe bleeding after liver biopsy is estimated to be 1:12,000 in patients with near normal coagulation (INR 60 billion /l). Beyond these limits, the risk is higher, but still uncertain. The Danish guidelines require INR > 1.5, platelet count

  3. A proteomic approach in investigating the hepatoprotective mechanism of Schisandrin B: role of raf kinase inhibitor protein.

    Science.gov (United States)

    Chen, Yan; Ip, Siu-Po; Ko, Kam-Ming; Poon, Terence C W; Ng, Eddy W Y; Lai, Paul B S; Mao, Qing-Qiu; Xian, Yan-Fang; Che, Chun-Tao

    2011-01-01

    To identify key proteins involved in the hepatoprotection afforded by schisandrin B (Sch B), we used a proteomic approach to screen proteins that were specifically regulated by Sch B in mouse livers and to investigate the role of the proteins in hepatoprotection. Thirteen proteins were specifically activated or suppressed by Sch B treatment. Among the 13 proteins, Raf kinase inhibitor protein (RKIP) was postulated to be the key regulator involved in the development of hepatotoxin-induced cellular damage. The results indicated that the downregulation of RKIP by antisense RKIP vector transfection led to the activation of the Raf-1/MEK/ERK signaling pathway, as evidenced by increases in the level of MEK/ERK phosphorylation and the level of nuclear factor erythroid 2-related factor 2 in the nucleus. The signaling effect produced by RKIP downregulation resembled that triggered by Sch B, wherein both treatments resulted in a decrease in the extent of carbon tetrachloride-induced apoptotic cell death in AML12 hepatocytes. Overexpression of RKIP by the sense RKIP transfection vector or the inhibition of MEK kinase by PD98059 was able to abrogate the cytoprotective effect of Sch B in the hepatocytes. The results indicate that Sch B triggers the Raf/MEK/ERK signaling pathway, presumably by downregulating RKIP, thereby protecting against carbon tetrachloride-induced cytotoxicity.

  4. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  5. Proteoglycans in liver cancer

    Science.gov (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  6. Proteoglycans in liver cancer.

    Science.gov (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-07

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects.

  7. Elastin in the Liver

    Directory of Open Access Journals (Sweden)

    Jiri Kanta

    2016-10-01

    Full Text Available A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs, microfibrillar-associated proteins (MFAPs and fibulins. Lysyl oxidase (LOX and lysyl oxidase-like proteins (LOXLs are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibres are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the backgound of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

  8. Imaging of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ben Ariff; Claire R Lloyd; Sameer Khan; Mohamed Shariff; Andrew V Thillainayagam; Devinder S Bansi; Shahid A Khan; Simon D Taylor-Robinson; Adrian KP Lim

    2009-01-01

    Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identi-fication and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality.

  9. [Cysts of the liver

    DEFF Research Database (Denmark)

    Hillingso, J.G.; Kirkegaard, P.

    2008-01-01

    Cysts of the liver are discovered in connection with a scope of diseases ranging from simple, infectious, or parasitic to neoplastic cysts. Symptoms, paraclinical, radiological and diagnostic characteristics are described with emphasis on ruling out malignancy. The treatment options from ultrasound...... guided drainage to resections and liver transplantation are discussed. It is concluded that up to 25% of cysts must be treated surgically, because recurrence after percutaneous or laparoscopic treatment is between 5% and 71%, and only resection or liver transplantation are curative Udgivelsesdato: 2008/4/14...

  10. Mice with humanized liver endothelium

    NARCIS (Netherlands)

    el Filali, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical tri

  11. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  12. Pediatric liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Marco Spada; Silvia Riva; Giuseppe Maggiore; Davide Cintorino; Bruno Gridelli

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term followup, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation.

  13. [Wilson disease: liver form].

    Science.gov (United States)

    Guerra Montero, Luis; Ortega Álvarez, Félix; Sumire Umeres, Julia; Cok García, Jaime

    2015-01-01

    Wilson disease (WD) is a disorder of copper metabolism that is inherited as an autosomal recessive, which produces toxic copper accumulation mainly in the liver and brain, in general has two ways presentation, liver at early ages and neurological in later ages. We present the case of a female patient of 21 years diagnosed of WD in liver cirrhosis that started with an edematous ascites without any neurological symptoms despite the age. Their laboratory studies showed decrease in serum ceruloplasmin and high cupruria within 24 hours of the disease , characteristic data of WD. Although WD is not a common disease should be suspected in all chronic liver disease of unknown etiology with negative viral markers and autoimmunity with or without neurological manifestations as soon as posible and starting treatment with copper chelating mainly leads to a substantial improvement the prognosis of these patients.

  14. Liver Transplant: Nutrition

    Science.gov (United States)

    ... include poultry, eggs, fish, tofu, and soy protein. Low Sodium -- Symptoms of advanced liver disease include excess fluid ... it is very important to stick to a low sodium diet, especially when these symptoms start to develop. ...

  15. [Nutrition and liver failure].

    Science.gov (United States)

    Plauth, M

    2013-06-01

    In the critically ill liver patient, nutrition support is not very different from that given for other illnesses. In hyperacute liver failure, nutrition support is of less importance than in the other subtypes of acute liver failure that take a more protracted course. Nasoenteral tube feeding using a polymeric standard formula should be the first-line approach, while parenteral nutrition giving glucose, fat, amino acids, vitamins, and trace elements is initiated when enteral nutrition is insufficient or impracticable. In chronic liver disease, notably cirrhosis, there is frequently protein malnutrition indicating a poor prognosis and requiring immediate initiation of nutrition support. Enteral nutrition ensuring an adequate provision of energy and protein should be preferred. Particular care should be taken to avoid refeeding syndrome and to treat vitamin and trace element deficiency.

  16. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  17. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008546 Effects of gene-transfected bone marrow-derived liver stem cell transplantation on accumulation of extracellular matrix in rats with liver fibrosis.SUN Chao(孙超),et al.Dept Gastroenterol,Xinhua Hosp,Shanghai Jiaotong Univ,Shanghai 200092.Natl Med J China 2008;88(38):2685-2689. Objective To explore the effects of urokinase-type plasminogen activator(uPA)gene modified bone marrow-derived stem cell(BDLSC)

  18. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mogaddasi,; Hasani, Alka; Ghaffari, Shamsi

    2009-01-01

    Mandana Rafeey1, Fakhrossadat Mortazavi2, Nafiseh Mogaddasi2, Ghergherehchi Robabeh2, Shamsi Ghaffari2, Alka Hasani31Liver and gastrointestinal Research Center; 2Tabriz University (Medical Science) Tabriz, Iran; 3Research Center of Infectious Diseases and Tropical MedicineAims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran.Methods: In this cross-section...

  19. Liver disease and malnutrition.

    Science.gov (United States)

    Purnak, Tugrul; Yilmaz, Yusuf

    2013-08-01

    Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

  20. Split liver transplantation.

    Science.gov (United States)

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  1. Excellent survival after liver transplantation for isolated polycystic liver disease : an European Liver Transplant Registry study

    NARCIS (Netherlands)

    van Keimpema, Loes; Nevens, Frederik; Adam, Rene; Porte, Robert J.; Fikatas, Panagiotis; Becker, Thomas; Kirkegaard, Preben; Metselaar, Herold J.; Drenth, Joost P. H.

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR) d

  2. Excellent survival after liver transplantation for isolated polycystic liver disease: an European Liver Transplant Registry study

    DEFF Research Database (Denmark)

    van Keimpema, Loes; Nevens, Frederik; Adam, René

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR...

  3. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, E.; Oliveira, C. P.; Alvares-da-Silva, M. R.;

    2012-01-01

    -citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCl4-treated...

  4. Liver transplantation for polycystic liver and massive hepatomegaly

    Institute of Scientific and Technical Information of China (English)

    Salvatore; Gruttadauria; Fabrizio; di; Francesco; Bruno; Gridelli

    2010-01-01

    Liver tumor and other benign liver diseases such as polycystic liver disease can cause massive hepatomegaly and may represent an indication for liver transplantation(LT)in some instances.In this setting,LT can be extremely difficult and challenging due to its decreased mobility and access to vascular supply.Benefit from either a right or a left partial liver resection during the transplant procedure has been advocated to safely accomplish the hepatectomy of the native liver.Although we believe that partial ...

  5. Characterization of Polysaccharides with Antioxidant and Hepatoprotective Activities from the Edible Mushroom Oudemansiella radicata

    Directory of Open Access Journals (Sweden)

    Qin Liu

    2017-02-01

    Full Text Available The preliminary structure, in vitro antioxidant and in vivo hepatoprotective activities of water-soluble polysaccharides (ORWP and alkali-soluble polysaccharides (ORAP, prepared from the mushroom Oudemansiella radicata, were investigated. Both ORWP and ORAP were heteropolysaccharides with mannose, glucose and galactose being the main monosaccharide components. Regarding the antioxidant activities, ORWP and ORAP showed effective 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging activity, hydrogen peroxide scavenging activity and lipid peroxidation inhibitory effects, as well as moderate reducing power and Fe2+ chelating activity. For the hepatoprotective activity, administration of ORWP and ORAP prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities in a carbon tetrachloride-induced acute liver damage model, suppressed hepatic malondialdehyde formation and stimulated the activities of hepatic superoxide dismutase and glutathione peroxidase. Thus, we speculate that ORWP and ORAP may protect the liver from CCl4-induced hepatic damage via antioxidant mechanisms.

  6. Gut microbiota and liver diseases.

    Science.gov (United States)

    Minemura, Masami; Shimizu, Yukihiro

    2015-02-14

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases.

  7. In vivo magnetic resonance spectroscopy of liver tumors and metastases

    Institute of Scientific and Technical Information of China (English)

    EGW ter Voert; L Heijmen; HWM van Laarhoven; A Heerschap

    2011-01-01

    Primary liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. The liver is also the second most common site for metastatic spread of cancer. To assist in the diagnosis of these liver lesions non-invasive advanced imaging techniques are desirable. Magnetic resonance (MR) is commonly used to identify anatomical lesions, but it is a very versatile technique and also can provide specific information on tumor pathophysiology and metabolism,in particular with the application of MR spectroscopy (MRS). This may include data on the type, grade and stage of tumors, and thus assist in further management of the disease. The purpose of this review is to summarize and discuss the available literature on proton, phosphorus and carbon-13-MRS as performed on primary liver tumors and metastases, with human applications as the main perspective. Upcoming MRS approaches with potential applications to liver tumors are also included. Since knowledge of some technical background is indispensable to understand the results, a basic introduction of MRS and some technical issues of MRS as applied to tumors and metastases in the liver are described as well. In vivo MR spectroscopy of tumors in a metabolically active organ such as the liver has been demonstrated to provide important information on tumor metabolism, but it also is challenging as compared to applications on some other tissues, in particular in humans, mostly because of its abdominal location where movement may be a disturbing factor.

  8. Liver transplantation in Germany.

    Science.gov (United States)

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  9. [Alcoholic liver disease and liver transplantation].

    Science.gov (United States)

    Testino, Gianni; Patussi, Valentino; Scafato, Emanuele

    2013-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT) in Europe and in the United States. The outcome of patients transplanted for ALD is at least as good as that for most other diagnoses and better than that for hepatitis C virus. In case of severe acute alcoholic hepatitis (AAH) non-responders to medical therapy, the reason for denying LT is that it requires abstinence from alcohol for six months before consideration for a transplant. A strict application of a period of abstinence as a policy for transplant eligibility is unfair to non-responder patients, as most of them will have died prior to the end of the six-month sober period. In our opinion, in severe AAH subjects with a good social support, with the frequency of self-help groups (alcoholics anonymous or association of clubs of alcoholics in treatment), with the frequency of Alcohol Unit and without severe psychotic or personality disorders, the lack of pre-LT abstinence alone should not be a barrier against being listed.

  10. Alcoholic liver disease: The gut microbiome and liver crosstalk

    OpenAIRE

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing ...

  11. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  12. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Fede, Giuseppe; Germani, Giacomo; Gluud, Christian;

    2011-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  13. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    ... fats, produces several important com- pounds, stores certain vitamins, makes specific amino acids, converts glucose to glycogen, ... liver. This increased pres- sure causes blood to bypass the liver. As a result, the blood is ...

  14. 25 Ways to Love Your Liver

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  15. General Information about Childhood Liver Cancer

    Science.gov (United States)

    ... Liver Cancer Prevention Liver Cancer Screening Research Childhood Liver Cancer Treatment (PDQ®)–Patient Version General Information About Childhood Liver Cancer Go to Health Professional Version Key Points Childhood ...

  16. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2002-01-01

    Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease.......Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease....

  17. Radioembolization of liver tumors

    NARCIS (Netherlands)

    van den Hoven, AF

    2016-01-01

    Radioembolization is a therapy during which radioactive microspheres are administered through a microcatheter placed in the hepatic arterial vasculature in order to irradiate liver tumors from within. In the past decennium, this treatment has evolved as a safe and effective treatment option for pati

  18. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    12.1 Liver function2003091 Treatment of acute hepatic failure by transplantation of microencapsulated xenogenic hepatocyte.ZHANG Weijie(张伟杰), et al. Instit Organ Transplant, Tongji Hosp, Huazhong Univ Sci & Technol, Wuhan 430030. World Chin J Digestol 2002; 10 (12): 1396-1398.

  19. Coffee and liver health.

    Science.gov (United States)

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients.

  20. Cirrhosis of the liver

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Larsen, Fin Stolze; Ott, Peter;

    2014-01-01

    Cirrhosis of the liver is a frequent and dangerous disease that causes numerous clinical contacts due to its complications. Competent and fast clinical decisions are often necessary in the acute setting and a broad clinical approach for the long-term problems due to the co-morbidity. Danish...

  1. Angiogenesis and liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Gülsüm ?zlem Elpek

    2015-01-01

    Recent data indicate that hepatic angiogenesis,regardless of the etiology, takes place in chronic liverdiseases (CLDs) that are characterized by inflammationand progressive fibrosis. Because antiangiogenictherapy has been found to be efficient inthe prevention of fibrosis in experimental models ofCLDs, it is suggested that blocking angiogenesis couldbe a promising therapeutic option in patients withadvanced fibrosis. Consequently, efforts are beingdirected to revealing the mechanisms involved inangiogenesis during the progression of liver fibrosis.Literature evidences indicate that hepatic angiogenesisand fibrosis are closely related in both clinical andexperimental conditions. Hypoxia is a major inducer ofangiogenesis together with inflammation and hepaticstellate cells. These profibrogenic cells stand at theintersection between inflammation, angiogenesis andfibrosis and play also a pivotal role in angiogenesis.This review mainly focuses to give a clear view on therelevant features that communicate angiogenesis withprogression of fibrosis in CLDs towards the-end point ofcirrhosis that may be translated into future therapies.The pathogenesis of hepatic angiogenesis associatedwith portal hypertension, viral hepatitis, non-alcoholicfatty liver disease and alcoholic liver disease are alsodiscussed to emphasize the various mechanisms involvedin angiogenesis during liver fibrogenesis.

  2. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

  3. Systems level analysis and identification of pathways and networks associated with liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Mohamed Diwan M AbdulHameed

    Full Text Available Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways associated with liver fibrosis can provide insight into the underlying molecular mechanisms of the disease, as well as identify potential diagnostic or prognostic biomarkers. Towards this end, we analyzed rat gene expression data from a range of chemical exposures that produced observable periportal liver fibrosis as documented in DrugMatrix, a publicly available toxicogenomics database. We identified genes relevant to liver fibrosis using standard differential expression and co-expression analyses, and then used these genes in pathway enrichment and protein-protein interaction (PPI network analyses. We identified a PPI network module associated with liver fibrosis that includes known liver fibrosis-relevant genes, such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue growth factor, and lipocalin-2. We also identified several new genes, such as perilipin-3, legumain, and myocilin, which were associated with liver fibrosis. We further analyzed the expression pattern of the genes in the PPI network module across a wide range of 640 chemical exposure conditions in DrugMatrix and identified early indications of liver fibrosis for carbon tetrachloride and lipopolysaccharide exposures. Although it is well known that carbon tetrachloride and lipopolysaccharide can cause liver fibrosis, our network analysis was able to link these compounds to potential fibrotic damage before histopathological changes associated with liver fibrosis appeared. These results demonstrated that our approach is capable of identifying early-stage indicators of liver fibrosis and underscore its potential to aid in predictive toxicity, biomarker identification, and to

  4. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    Science.gov (United States)

    AbdulHameed, Mohamed Diwan M.; Tawa, Gregory J.; Kumar, Kamal; Ippolito, Danielle L.; Lewis, John A.; Stallings, Jonathan D.; Wallqvist, Anders

    2014-01-01

    Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways associated with liver fibrosis can provide insight into the underlying molecular mechanisms of the disease, as well as identify potential diagnostic or prognostic biomarkers. Towards this end, we analyzed rat gene expression data from a range of chemical exposures that produced observable periportal liver fibrosis as documented in DrugMatrix, a publicly available toxicogenomics database. We identified genes relevant to liver fibrosis using standard differential expression and co-expression analyses, and then used these genes in pathway enrichment and protein-protein interaction (PPI) network analyses. We identified a PPI network module associated with liver fibrosis that includes known liver fibrosis-relevant genes, such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue growth factor, and lipocalin-2. We also identified several new genes, such as perilipin-3, legumain, and myocilin, which were associated with liver fibrosis. We further analyzed the expression pattern of the genes in the PPI network module across a wide range of 640 chemical exposure conditions in DrugMatrix and identified early indications of liver fibrosis for carbon tetrachloride and lipopolysaccharide exposures. Although it is well known that carbon tetrachloride and lipopolysaccharide can cause liver fibrosis, our network analysis was able to link these compounds to potential fibrotic damage before histopathological changes associated with liver fibrosis appeared. These results demonstrated that our approach is capable of identifying early-stage indicators of liver fibrosis and underscore its potential to aid in predictive toxicity, biomarker identification, and to generally identify

  5. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within week

  6. Systemic abnormalities in liver disease

    Institute of Scientific and Technical Information of China (English)

    Masami Minemura; Kazuto Tajiri; Yukihiro Shimizu

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

  7. Acute fatty liver in pregnancy.

    NARCIS (Netherlands)

    Tan, A.; Krieken, J.H.J.M. van; Peters, W.H.M.; Steegers, E.A.P.

    2002-01-01

    When confronted with liver abnormalities during the third trimester of pregnancy, one should consider acute fatty liver of pregnancy. The differential diagnosis with (pre-)eclampsia and HELLP syndrome is sometimes difficult. In these cases a liver biopsy is helpful though rarely performed during pre

  8. [Local treatment of liver tumors

    DEFF Research Database (Denmark)

    Pless, T.K.; Skjoldbye, Bjørn Ole

    2008-01-01

    Local treatment of non-resectable liver tumors is common. This brief review describes the local treatment techniques used in Denmark. The techniques are evaluated according to the evidence in literature. The primary local treatment is Radiofrequency Ablation of both primary liver tumors and liver...

  9. Improved transvenous liver biopsy needle

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Matzen, P; Christoffersen, P;

    1979-01-01

    A modified type of the standard transvenous cholangiography biopsy needle is described. The modified tranvenous liver biopsy needle caused only minimal artefactual changes of the liver biopsy specimens. The new type of biopsy needle is a modified Menghini needle. The conventional Menghini needle...... should be avoided for transvenous catheter biopsies because of risk of leaving catheter fragments in the liver....

  10. Pediatric obesity and the liver

    NARCIS (Netherlands)

    Koot, B.G.P.

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of obesity. In some of those with NAFLD, the fat accumulation in the liver will cause inflammation and fibrosis and can ultimately cause liver failure. In addition, in adults it has been established that NAFLD increases the risk of

  11. Research Progress of Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    XU Lie-ming; JIA Ji-dong

    2005-01-01

    @@ Liver diseases are widespread in China.The disease mostly includes viral hepatitis,alcoholic or non alcoholic fatty degeneration or steatohepatitis, autoimmune liver disease,hepatic fibrosis/cirrhosis and hepatic cancer.The mechanism of most liver diseases was studied clearly in developed countries.

  12. Experimental study of bioartificial liver with cultured human liver cells

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF).METHODS The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs.RESULTS The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rd h and 5th h. In addition, a good viability of human liver cells was noted after 5 h experiment.CONCLUSION EBLSS playing a metabolic role of cultured human hepatocytes, is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF.

  13. Carbon Carbon Composites: An Overview .

    Directory of Open Access Journals (Sweden)

    G. Rohini Devi

    1993-10-01

    Full Text Available Carbon carbon composites are a new class of engineering materials that are ceramic in nature but exhibit brittle to pseudoplastic behaviour. Carbon-carbon is a unique all-carbon composite with carbon fibre embeded in carbon matrix and is known as an inverse composite. Due to their excellent thermo-structural properties, carbon-carbon composites are used in specialised application like re-entry nose-tips, leading edges, rocket nozzles, and aircraft brake discs apart from several industrial and biomedical applications. The multidirectional carbon-carbon product technology is versatile and offers design flexibility. This paper describes the multidirectional preform and carbon-carbon process technology and research and development activities within the country. Carbon-carbon product experience at DRDL has also been discussed. Development of carbon-carbon brake discs process technology using the liquid impregnation process is described. Further the test results on material characterisation, thermal, mechanical and tribological properties are presented.

  14. Role of liver functions on liver cell mitosis

    Directory of Open Access Journals (Sweden)

    Takata,Tameyuki

    1974-06-01

    Full Text Available The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized fed.partners by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

  15. Hemostasis and the diseased liver : a study on hemostatic disorders in liver disease and liver transplantation

    NARCIS (Netherlands)

    C.M. Bakker (Minke)

    1993-01-01

    textabstractIn this thesis studies on hemostatic disorders in liver cirrhosis and liver transplantation have been described. Aims of the work were to further investigate; 1. Whether (low-grade) DIC occurs in liver cirrhosis applying new quantitative tests, measuring thrombin-antithrombin Ill complex

  16. [Running through the liver transplantation].

    Science.gov (United States)

    Grecu, F

    2003-01-01

    An overview of the organization, timing and developing of the liver transplantation is difficult to be made in terms of multiple sequences and a great variety of activities during the developing of such activity. A well-trained transplant team must carry out the potential donor, the liver grafts manipulation and the graft receptor, in the condition of a competitive medical system. A summary presentation, showing the essentials of the proceedings in liver transplantation could be assimilated as a guide of multidisciplinary sequences that leads to the completion of the liver grafting. The common feature of all that means the liver transplantation and generally in organ transplantation is the performance and exactingness.

  17. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of

  18. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  19. [Effect of rapeseed from different distributors on the rat liver].

    Science.gov (United States)

    Alvizouri, M

    1993-01-01

    In previous papers it was reported that rapeseed could prevent the development of cirrhosis induced by carbon tetrachloride and at the same time can induce liver regeneration in the rat. In such experiments rapeseed was always obtained from the same distributor "Semillas Berentsen". When reseed of different distributors was used, neither cirrhosis prevention or liver regeneration was observed. The difference among the rapeseed used was that "Semillas Berentsen" utilizes a fungicide to preserve the seed and the other distributors do not use any preservative. This circumstance made think that the active principle responsible for the effects observed is probably the fungicide.

  20. Liver iron transport

    Institute of Scientific and Technical Information of China (English)

    Ross M Graham; Anita CG Chua; Carly E Herbison; John K Olynyk; Debbie Trinder

    2007-01-01

    The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors (TFR1 and 2), a ferrireductase (STEAP3), the transporters divalent metal transporter-1 (DMT1) and ferroportin (FPN) as well as the haemochromatosis protein, HFE and haemojuvelin (HJV),which are signalling molecules. Many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis.

  1. Polycystic Liver Disease

    Energy Technology Data Exchange (ETDEWEB)

    Linda, Nguyen, E-mail: nguyenli@einstein.edu [5501 Old York Road, Philadelphia, PA 19141 (United States)

    2016-03-25

    A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations. The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.

  2. Fatty liver in childhood

    Institute of Scientific and Technical Information of China (English)

    Yesim; Ozturk; Ozlem; Bekem; Soylu

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease(NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.

  3. Hypoxia and fatty liver

    OpenAIRE

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-01-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty li...

  4. Fatty liver in childhood

    OpenAIRE

    Ozturk,Yesim; Soylu, Ozlem Bekem

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is repor...

  5. Nonalcoholic Fatty Liver Disease

    OpenAIRE

    You, Jie; Huang, Sha; Huang, Gui-Qian; Zhu, Gui-Qi; Ma, Rui-Min; Liu, Wen-yue; Shi, Ke-Qing; Guo, Gui-Long; Chen, Yong-Ping; Braddock, Martin; Zheng, Ming-Hua

    2015-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) is known to be associated with an increased risk of colorectal cancer (CRC). However, the relationship between NAFLD and the prognosis of CRC remains unclear. The primary objective of this study was to evaluate the overall survival (OS) and disease-free survival (DFS) rates in patients with CRC and the secondary objective was to compare clinicopathologic variables which were stratified by NAFLD. We performed a large cohort study of 1314 patien...

  6. Voriconazole and the liver

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Voriconazole is an azole useful for the prophylaxis andthe treatment of aspergillosis and other fungal infectionsin immunosuppressed subjects, as those found in aplasiaafter aggressive polychemotherapy treatments, afterhematopoietic stem cell, liver or lung transplantation.Its administration in therapeutic doses lead to extremelyvaried serum levels from patient to patient and even tothe same patient. The explanations are varied nonlinearpharmacokinetics, certain patient-related factors,including genetic polymorphisms in the cytochrome P4502C19 gene, the kidney and liver function, simultaneousadministration with other drugs metabolised by the samecytochrome. It is recommended to maintain the serumconcentrations of voriconazole between 1.5 and 4 μg/mL.At lower values its efficacy decreases and at highervalues the risk of neurological toxicity increases. Evenat these concentrations it is not excluded the possibleappearance of a variety of toxic effects, including onthe liver, manifested by cholestasis, hepatocytolisis, ortheir combination. It is recommended to monitor theclinical and laboratory evolution of all patients treatedwith voriconazole, and of the serum levels of the drugof those who belong to risk groups, even if there is stillno consensus on this issue, given the lack of correlationbetween the serum level and the occurrence of adverseeffects in many patients.

  7. Management of liver trauma.

    LENUS (Irish Health Repository)

    Badger, S A

    2012-02-01

    BACKGROUND: Blunt and penetrating liver trauma is common and often presents major diagnostic and management problems. METHODS: A literature review was undertaken to determine the current consensus on investigation and management strategies. RESULTS: The liver is the most frequently injured organ following abdominal trauma. Immediate assessment with ultrasound has replaced diagnostic peritoneal lavage in the resuscitation room, but computerised tomography remains the gold standard investigation. Nonoperative management is preferred in stable patients but laparotomy is indicated in unstable patients. Damage control techniques such as perihepatic packing, hepatotomy plus direct suture, and resectional debridement are recommended. Major complex surgical procedures such as anatomical resection or atriocaval shunting are now thought to be redundant in the emergency setting. Packing is also recommended for the inexperienced surgeon to allow control and stabilisation prior to transfer to a tertiary centre. Interventional radiological techniques are becoming more widely used, particularly in patients who are being managed nonoperatively or have been stabilised by perihepatic packing. CONCLUSIONS: Management of liver injuries has evolved significantly throughout the last two decades. In the absence of other abdominal injuries, operative management can usually be avoided. Patients with more complex injuries or subsequent complications should be transferred to a specialist centre to optimise final outcome.

  8. Naproxen-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Sharif Ali; Jason D Pimentel; Chan Ma

    2011-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractablepruritusthatdevelopedshortlyaftertakingnaproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS:  Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

  9. [Liver damage caused by drugs].

    Science.gov (United States)

    Strohmeyer, G; Weik, C

    1999-05-01

    The liver has a central role in the metabolism of many drugs, since this organ is the main site of biotransformation of endo- and xenobiotics. Water-soluble drugs have a small volume of distribution and can be eliminated unchanged in the urine. By contrast, lipid-soluble drugs have a larger volume of distribution and require conversion to water-soluble metabolites for their elimination in urine or bile. The liver with its specific receptors, transporters and enzymes is responsible for the uptake, transformation and excretion of the lipophilic drugs. While most of the drugs are transformed into stable metabolites, other drugs form reactive, potentially toxic, metabolites producing liver cell damage. Liver injury caused by drugs may mimic almost any kind of liver disease. Clinical findings are gastrointestinal symptoms with nausea, vomiting and abdominal pain, cholestatic liver injury with jaundice and pruritus of severe inflammatory and cirrhotic liver damage with signs of liver failure, encephalopathy and cerebral edema. The morphological changes vary from hepatitis, cholestasis, fatty liver, granulomatous hepatitis, peri-/portal inflammation, to fibrosis with cirrhotic alterations and vascular lesions and tumors. The most commonly used drugs causing severe liver injury are discussed in detail. These are anabolics, oral contraceptives, antituberculous and antifungal agents, nonsteroidal anti-inflammatory drugs, ring substituted amphetamins ("designer drugs"), antiarrhythmics and antibiotics.

  10. massive excision of liver

    Directory of Open Access Journals (Sweden)

    Dong-liang LI

    2014-10-01

    Full Text Available Objective To observe the promotion effect of bone mesenchymal stem cells (BMSCs transplantation and mobilized bone marrow stem cells on the recovery of liver function and liver tissue regeneration after massive partial hepatectomy in rats. Methods The rats were randomly divided into four groups after massive partial hepatectomy (about 85%, namely massive hepatectomy group (control group, n=15, received massive hepatectomy only, G-CSF group [n=15, received rhG-CSF 150μg/(kg•d by intraperitoneal injection after the operation for 5 days], MSCs group [n=15, received 5ml suspension of MSCs (about 1.5×106 by tail vein injection after the operation], and G-CSF+MSCs group [n=14, received 1.5ml suspension of MSCs (about 1.5×106 by tail vein injection and rhG-CSF 150μg/(kg•d by intraperitoneal injection for 5 days after the operation]. The CD34+ cells in the peripheral blood of the rats were assessed by flow cytometry after G-CSF mobilization. Liver function tests including ALT, AST and ALB were performed on the 3rd and 9th day after surgery. All the rats were sacrificed and liver tissue was harvested for histopathological study. The expression of Ki-67 and BrdU positive cells in the liver were determined by immunohistochemistry. Results Flow cytometric results identified the isolated cells were MSCs. BMSCs in peripheral blood significantly increased in number after rhG-CSF mobilization, and reaching the maximum number on the 5th day. After mobilization for 3, 5 and 9 days, the positive CD34 cells in G-CSF group were 0.009%, 0.016%, 0.019% respectively, which were higher than those in control group. The level of albumin was significantly elevated in three treatment groups compared with control group on the 9th day after the hepatectomy (P<0.05 or P<0.01. The expression of Ki-67 (110.16±27.64, 103.57±33.90, 98.52±21.87 vs 72.39±27.04 cells and BrdU positive cells (17.96±5.57, 16.45±5.75, 16.66±5.11 vs 11.72±3.83 cells in three

  11. Liver transplant in HCC

    Directory of Open Access Journals (Sweden)

    Sergio I. Duque Duque

    2007-02-01

    Full Text Available

     

    Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide, and is the leading cause of death in cirrhotic individuals. 80% of HCC develops in cirrhotic patients. Unfortunately only 20 to 25% of patients can have a radical treatment, like resection, liver transplantation (LT, or percutaneous ablation. The other 75 to 80% of patients can only have supportive care.

    There is no evidence to establish the optimal first-line treatment for early HCC (one tumor of 5 cm or less, in patients with well preserved liver function, because of the lack of RCTs comparing these radical therapies. Resection and transplantation achieve a very good outcome (5-year survival of 60 to 70% but with very different recurrence rates (60-70% and 15-20% respectively. Due to the lack of liver donors, these two techniques compete as the first option for treatment in cirrhotic patients with well preserved liver function and only one tumor.

    There is no question in considering LT as the best option for patients with liver function impairment (Child-Pugh B-C patients and early tumors (less than three tumors of less than three centimeters. LT provides cure of both the neoplastic disease and the underlying liver disease. There are a few numbers of reports that shows a decrease in the overall survival, from an intention-to treat perspective as a result of the impact of dropouts from the waiting list because of death or progression. These numbers can be as high as 20%. Adjuvant therapies during the waiting period, although intuitively effective, have not had an impact on the outcome. Expansion of the accepted Milan criteria (single nodule <5 cm, two or three nodules <3 cm has been advocated by some groups

  12. THE DIAGNOSIS OF LIVER ALLOGRAFT ACUTE REJECTION IN LIVER BIOPSIES

    Directory of Open Access Journals (Sweden)

    L. V. Shkalova

    2011-01-01

    Full Text Available We performed histological examination of 80 liver allograft biopsies, the diagnosis of acute rejection was proved in 34 cases. Histological changes in liver biopsies in different grades of acute rejection were estimated according to Banff classification 1995, 1997 and were compared with current literature data. The article deals with the question of morphological value of grading acute rejection on early and late, also we analyze changes in treat- ment tactics after morphological verification of liver allograft acute rejection. 

  13. What's New in Liver Cancer Research and Treatment?

    Science.gov (United States)

    ... Liver Cancer About Liver Cancer What's New in Liver Cancer Research and Treatment? Because there are only a ... in Liver Cancer Research and Treatment? More In Liver Cancer About Liver Cancer Causes, Risk Factors, and Prevention ...

  14. Alcoholic liver disease and the gut-liver axis

    Institute of Scientific and Technical Information of China (English)

    Gyongyi; Szabo; Shashi; Bala

    2010-01-01

    Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4...

  15. Celecoxib-induced cholestatic liver failure requiring orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Ihab I El Hajj; Shahid M Malik; Hany R Alwakeel; Obaid S Shaikh; Eizaburo Sasatomi; Hossam M Kandil

    2009-01-01

    Selective cyclooxygenase-2 (COX-2) inhibitors are widely used due to their efficacy and good safety profile.However, recent case reports have described varying degrees of liver injuries associated with the use of COX-2 inhibitors. We report the case of a patient who developed acute cholestatic hepatitis progressing to hepatic failure requiring liver transplantation, following a 3-d course of celecoxib for treatment of generalized muscle aches and pains. The clinical presentation, the laboratory data, as well as the liver histopathology were supportive of the putative diagnosis of drug induced liver injury.

  16. Liver transplantation for Wilson's disease.

    Science.gov (United States)

    Schilsky, Michael L

    2014-05-01

    Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ∼5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors.

  17. Liver involvement in systemic infection

    Institute of Scientific and Technical Information of China (English)

    Masami; Minemura; Kazuto; Tajiri; Yukihiro; Shimizu

    2014-01-01

    The liver is often involved in systemic infections,resulting in various types of abnormal liver function test results.In particular,hyperbilirubinemia in the range of 2-10 mg/dL is often seen in patients with sepsis,and several mechanisms for this phenomenon have been proposed.In this review,we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic.In most patients with systemic infections,treatment for the invading microbes is enough to normalize the liver function tests.However,some patients may show severe liver injury or fulminant hepatic failure,requiring intensive treatment of the liver.

  18. Management strategies for liver fibrosis.

    Science.gov (United States)

    Altamirano-Barrera, Alejandra; Barranco-Fragoso, Beatriz; Méndez-Sánchez, Nahum

    2017-01-01

    Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.

  19. Obesity, inflammation, and liver cancer.

    Science.gov (United States)

    Sun, Beicheng; Karin, Michael

    2012-03-01

    Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.

  20. Neurological complications after liver retransplantation.

    Science.gov (United States)

    Lopez, O L; Estol, C; Colina, I; Quiroga, J; Imvertarza, O C; van Thiel, D H

    1992-07-01

    Postoperative neurological complications in 185 patients who underwent two or more orthotopic liver transplantations were reviewed. The most common neurological complications were alteration of mental status (84%), seizures (33%) and focal motor deficits (15%). The frequency of neurological complications after a second orthotopic liver transplantation was significantly greater than that after a single orthotopic liver transplantation. However, neurological complications were more frequent after a second orthotopic liver transplantation than after a third transplant. Significantly more neurological complications occurred in patients who did not survive a year than in those who did, regardless of the number of transplants they underwent. These findings indicate that the risk of neurological complications among patients with multiple orthotopic liver transplantations is greater in those who require a second transplant; this risk appears to diminish after a third transplant. Importantly, the presence of neurological complications is associated with increased post-orthotopic liver transplantation mortality rate.

  1. DNA Ploidy and Liver Cell Dysplasia in Liver Biopsies from Patients with Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Sayed S El-Sayed

    2004-01-01

    Full Text Available There is controversy among pathologists when assessing the presence or absence of liver cell dysplasia in liver biopsies taken from cirrhotic patients. The objective of the present study was to determine the DNA ploidy pattern of hepatocytes of patients with liver cirrhosis and its relationship to liver cell dysplasia. A total of 48 male patients diagnosed with liver cirrhosis based on clinical, laboratory and histopathological criteria were included in the study. A liver biopsy was taken from each patient; one part of the biopsy was subjected to histopathology, and the other to flow cytometry. The histopathological examination revealed liver cell dysplasia in 60% of patients with liver cirrhosis (62% of them had large cell dysplasia [LCD] and 38% had small cell dysplasia [SCD]. Abnormal DNA content (aneuploidy was found in 81.5% of positive liver cell dysplasia specimens and found only in 11.1% of negative liver cell dysplasia specimens, with a statistically significant difference (P0.05 in comparison with SCD. In conclusion, SCD (similar to LCD is also associated with aneuploidy and elevated DNA index, and may carry the same risk for progression to hepatocellular carcinoma.

  2. Serum markers of liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne Skovgård; Bay-Jensen, Anne-Christine; Tougas, Gervais

    2010-01-01

    BACKGROUND: Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable......-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo...

  3. Abacavir-induced liver toxicity

    Directory of Open Access Journals (Sweden)

    Maria Diletta Pezzani

    Full Text Available Abstract Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine.

  4. Abacavir-induced liver toxicity.

    Science.gov (United States)

    Pezzani, Maria Diletta; Resnati, Chiara; Di Cristo, Valentina; Riva, Agostino; Gervasoni, Cristina

    2016-01-01

    Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine.

  5. Liver morphology in morbid obesity

    DEFF Research Database (Denmark)

    Andersen, T; Gluud, C

    1984-01-01

    methods including a computerized survey. Forty-one original articles were included, comprising information on liver morphology in 1515 morbidly obese patients. Liver biopsy was considered normal in 12 per cent of the cases. The most frequent abnormality reported was fatty change, present in 80 per cent...... of obesity, age, sex, alcohol consumption, diabetes mellitus) does not point towards a single causal factor. Co-influence of additional pathogenetic factors are likely in the development of liver changes in morbid obesity....

  6. The formation of sinusoidal capillarization in the process of liver fibrosis induced by carbon tetrachloride in rats%四氯化碳诱导的肝纤维化大鼠肝窦毛细血管化的形成

    Institute of Scientific and Technical Information of China (English)

    郭杞兰; 黄月红; 陈治新; 王小众

    2014-01-01

    Objective To observe the formation of sinusoidal capillarization in the process of liver fibrosis induced by carbon tetrachloride (CCl4 )in rats,and to explore the relevance between sinusoidal capillarization and hepatic fibrosis. Methods Thirty-two SD rats were divided randomly into control group (group N)and fibrosis model group (group M). Rats in group N were treated with 2 ml/kg normal sodium twice a week for eight weeks via intraperitoneal injection,while rats in group M were treated with 2 ml/kg a mixture of 50% CCl4 and castor oil twice a week for eight weeks. Rats were executed at the end of 2th wk,4th wk,6th wk,8th wk to collect samples of liver tissue and serum. Grading and staging of hepatic fibrosis were measured by HE staining and masson staining. Changes of HA from serum were measured by radioimmunoassay. Structure of sinus wall in liver sinusoids was observed by TEM. Expressions of CD3 1 ,LN and Col-IV in liver tissue were measured by S-P immunohistochemistry. Results Liver pathohistology analysis confirmed that hepatic fibrosis rat model induced by CCl4 was established successfully. Fibrous septum could be observed at the end of 6th wk. TEM showed that fenestrae of some liver sinusoidal endothelial cells (LSECs)diminished after treated with CCl4 for two weeks with observing no basement membrane (BM). Fenestrae of LSECs diminished along with the development of hepatic fibrosis,even disappeared. Consecutive BM formed at the end of 6th wk~8th wk in local sinusoidal endothelium. Concentration of HA from serum,and expressions of CD31 ,Col-IV and LN in hepatic sinusoids increased gradually along with development of hepatic fibrosis. Conclusion Formation of sinusoidal capillarization was occurred gradually along with development of hepatic fibrosis. Fibrous septa formed later than fenestrae losing in LSECs,but earlier than formation of sinusoidal endothelial basement membrane.%目的:观察四氯化碳(CCl4)诱导的大鼠肝纤维化过程中肝窦

  7. Heavy smoking and liver

    Institute of Scientific and Technical Information of China (English)

    Abdel-Rahman El-Zayadi

    2006-01-01

    Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. It induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects and oncogenic effects. Smoking yields chemical substances with cytotoxic potential which increase necroinflammation and fibrosis. In addition, smoking increases the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α) that would be involved in liver cell injury. It contributes to the development of secondary polycythemia and in turn to increased red cell mass and turnover which might be a contributing factor to secondary iron overload disease promoting oxidative stress of hepatocytes. Increased red cell mass and turnover are associated with increased purine catabolism which promotes excessive production of uric acid. Smoking affects both cell-mediated and humoral immune responses by blocking lymphocyte proliferation and inducing apoptosis of lymphocytes.Smoking also increases serum and hepatic iron which induce oxidative stress and lipid peroxidation that lead to activation of stellate cells and development of fibrosis.Smoking yields chemicals with oncogenic potential that increase the risk of hepatocellular carcinoma (HCC)in patients with viral hepatitis and are independent of viral infection as well. Tobacco smoking has been associated with supression of p53 (tumour suppressor gene). In addition, smoking causes suppression of T-cell responses and is associated with decreased surveillance for tumour cells. Moreover, it has been reported that heavy smoking affects the sustained virological response to interferon (IFN) therapy in hepatitis C patients which can be improved by repeated phlebotomy. Smoker's syndrome is a clinico-pathological condition where patients complain of episodes of facial flushing, warmth of the palms and soles of feet, throbbing headache,fullness in the head, dizziness, lethargy, prickling sensation

  8. Fast 4D Ultrasound Registration for Image Guided Liver Interventions

    NARCIS (Netherlands)

    J. Banerjee (Jyotirmoy)

    2016-01-01

    markdownabstractLiver problems are a serious health issue. The common liver problems are hepatitis, fatty liver, liver cancer and liver damage caused by alcohol abuse. Continuous, long term disease may cause a condition of the liver known as the Liver Cirrhosis. Liver cirrhosis makes the liver scarr

  9. Liver transplantation in the UK

    Institute of Scientific and Technical Information of China (English)

    SR Bramhall; E Minford; B Gunson; JAC Buckels

    2001-01-01

    Introduction: This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.``Referral and Assessment: This section reviews the process of referral and assessment of patients with liver disease with reference to UK practice.``Donor Organs: The practice of brainstem death and cadaveric organ donation is peculiar to individual countries and rates of donation and potential areas of improvement are addressed.``Operative Technique: The technical innovations that have led to liver transplantation becoming a semi-elective procedure are reviewed. Specific emphasis is made to the role of liver reduction and splitting and living related liver transplantation and how this impacts on UK practice are reviewed. The complications of liver transplantation are also reviewed with reference to our own unit.``Imrnunosuppression: The evolution of immunosuppression and its impact on liver transplantation are reviewed with some reference to future protocols.Retransplantation: The role of retransplantation is reviewed.``Outcome and Survival: The results of liver transplantation are reviewed with specific emphasis on our own experience.``Future: The future of liver transplantation is addressed.``

  10. Parenteral Nutrition in Liver Resection

    Directory of Open Access Journals (Sweden)

    Carlo Chiarla

    2012-01-01

    Full Text Available Albeit a very large number of experiments have assessed the impact of various substrates on liver regeneration after partial hepatectomy, a limited number of clinical studies have evaluated artificial nutrition in liver resection patients. This is a peculiar topic because many patients do not need artificial nutrition, while several patients need it because of malnutrition and/or prolonged inability to feeding caused by complications. The optimal nutritional regimen to support liver regeneration, within other postoperative problems or complications, is not yet exactly defined. This short review addresses relevant aspects and potential developments in the issue of postoperative parenteral nutrition after liver resection.

  11. Fibropolycystic liver disease in children

    Energy Technology Data Exchange (ETDEWEB)

    Veigel, Myka Call [Kansas City University of Medicine and Biosciences, Kansas City, MO (United States); University of Missouri-Kansas City, St. Luke' s Hospital, Department of Radiology, Kansas City, MO (United States); Prescott-Focht, Julia; Zinati, Reza [University of Missouri-Kansas City, St. Luke' s Hospital, Department of Radiology, Kansas City, MO (United States); Rodriguez, Michael G. [University of Missouri-Kansas City School of Medicine, Kansas City, MO (United States); Shao, Lei [Children' s Mercy Hospitals and Clinics, Department of Pathology, Kansas City, MO (United States); Moore, Charlotte A.W.; Lowe, Lisa H. [University of Missouri-Kansas City, Department of Radiology, Kansas City, MO (United States); Children' s Mercy Hospitals and Clinics, Department of Radiology, Kansas City, MO (United States)

    2009-04-15

    Fibropolycystic liver diseases are a group of associated congenital disorders that present most often in childhood. These disorders include congenital hepatic fibrosis, biliary hamartomas, autosomal dominant polycystic liver disease, choledochal cysts and Caroli disease. We present a discussion and illustrations of the embryology, genetics, anatomy, pathology, imaging approach and key imaging features that distinguish fibropolycystic liver disease in children. The pathogenesis of these disorders is believed to be abnormal development of the embryonic ductal plates, which ultimately form the liver and biliary systems. An understanding of the abnormal embryogenesis helps to explain the characteristic imaging features of these disorders. (orig.)

  12. Fatty Liver Disease (Nonalcoholic Steatohepatitis)

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  13. Split-liver transplantation : An underused resource in liver transplantation

    NARCIS (Netherlands)

    Rogiers, Xavier; Sieders, Egbert

    2008-01-01

    Split-liver transplantation is an efficient tool to increase the number of liver grafts available for transplantation. More than 15 years after its introduction only the classical splitting technique has reached broad application. Consequently children are benefiting most from this possibility. Full

  14. Antifibrinolytics in liver surgery

    Directory of Open Access Journals (Sweden)

    Jalpa Makwana

    2010-01-01

    Full Text Available Hyperfibrinolysis, a known complication of liver surgery and orthotopic liver transplantation (OLT, plays a significant role in blood loss. This fact justifies the use of antifibrinolytic drugs during these procedures. Two groups of drug namely lysine analogues [epsilon aminocaproic acid (EACA and tranexamic acid (TA] and serine-protease-inhibitors (aprotinin are frequently used for this purpose. But uniform data or guidelines on the type of antifibrinolytic drugs to be used, their indications and correct dose, is still insufficient. Antifibrinolytics behave like a double-edged sword. On one hand, there are benefits of less transfusion requirements but on the other hand there is potential complication like thromboembolism, which has been reported in several studies. We performed a systematic search in PubMed and Cochrane Library, and we included studies wherein antifibrinolytic drugs (EACA, TA, or aprotinin were compared with each other or with controls/placebo. We analysed factors like intraoperative red blood cell and fresh frozen plasma requirements, the perioperative incidence of hepatic artery thrombosis, venous thromboembolic events and mortality. Among the three drugs, EACA is least studied. Use of extensively studied drug like aprotinin has been restricted because of its side effects. Haemostatic effect of aprotinin and tranexamic acid has been comparable. However, proper patient selection and individualized treatment for each of them is required. Purpose of this review is to study various clinical trials on antifibrinolytic drugs and address the related issues like benefits claimed and associated potential complications.

  15. Deficiency of DJ-1 Ameliorates Liver Fibrosis through Inhibition of Hepatic ROS Production and Inflammation

    Science.gov (United States)

    Yu, Yingxue; Sun, Xuehua; Gu, Jinyang; Yu, Chang; Wen, Yankai; Gao, Yueqiu; Xia, Qiang; Kong, Xiaoni

    2016-01-01

    Liver fibrosis is a global health problem and previous studies have demonstrated that reactive oxygen species (ROS) play important roles in fibrogenesis. Parkinson disease (autosomal recessive, early onset) 7 (Park7) also called DJ-1 has an essential role in modulating cellular ROS levels. DJ-1 therefore may play functions in liver fibrogenesis and modulation of DJ-1 may be a promising therapeutic approach. Here, wild-type (WT) and DJ-1 knockout (DJ-1 KO) mice were administrated with carbon tetrachloride (CCl4) to induce liver fibrosis or acute liver injury. Results showed that DJ-1 depletion significantly blunted liver fibrosis, accompanied by marked reductions in liver injury and ROS production. In the acute CCl4 model, deficiency of DJ-1 showed hepatic protective functions as evidenced by decreased hepatic damage, reduced ROS levels, diminished hepatic inflammation and hepatocyte proliferation compared to WT mice. In vitro hepatic stellate cells (HSCs) activation assays indicated that DJ-1 has no direct effect on the activation of HSCs in the context of with or without TGFβ treatment. Thus our present study demonstrates that in CCl4-induced liver fibrosis, DJ-1 deficiency attenuates mice fibrosis by inhibiting ROS production and liver injury, and further indirectly affecting the activation of HSCs. These results are in line with previous studies that ROS promote HSC activation and fibrosis development, and suggest the therapeutic value of DJ-1 in treatment of liver fibrosis.

  16. Critical appraisal of 13C breath tests for microsomal liver function: aminopyrine revisited.

    Science.gov (United States)

    Pijls, Kirsten E; de Vries, Hanne; Nikkessen, Suzan; Bast, Aalt; Wodzig, Will K W H; Koek, Ger H

    2014-04-01

    As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the (13) C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the (13) C(2) -aminopyrine and the (13) C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the (13) C(2) -aminopyrine breath test in clinical practice.

  17. What Happens After Treatment for Liver Cancer?

    Science.gov (United States)

    ... Support Liver Cancer After Treatment Living as a Liver Cancer Survivor Completing treatment can be both stressful and ... and treatment. Can I lower my risk of liver cancer progressing or coming back? If you have (or ...

  18. Antifibrotic effect of heparin on liver fibrosis model in rats

    Institute of Scientific and Technical Information of China (English)

    Binita; Shah; Gaurang; Shah

    2012-01-01

    AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl 4 ) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl 4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl 4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups.CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.

  19. Liver fibrogenesis and genetic factors.

    Science.gov (United States)

    Boursier, Jérôme; Louvet, Alexandre

    2011-06-01

    Chronic liver diseases lead to the accumulation of fibrosis in the liver with eventual progression to cirrhosis and its complications. However, there is a wide range of inter-individual variation in the liver fibrogenesis process, thus posing a challenge to physicians to identify patients with poor prognosis. As demographic and environmental factors only account for a small portion of fibrogenesis variability, host genetic factors have been suggested as playing an important role. Due to technical limitations, the first genetic studies were restricted to the evaluation of candidate genes having a known or supposed function in liver fibrogenesis. Recently, technological improvements have made it possible to study the whole human genome in a single scan. Genome-wide association studies have considerably heightened the interest in genetics as part of the study of liver fibrogenesis through their identification of previously unsuspected genes that are statistically associated with liver fibrosis. It is thus possible to determine new diagnostic or prognostic genetic markers for the management of patients with chronic liver diseases. Moreover, functional analyses of these genes may provide new insights into the pathophysiology of liver fibrogenesis.

  20. 13.LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    13.2.Liver cirrhosis and fatty liver930691 Experimental observation of high portal ve-nous resistance in dogs.WANG Weimin,etal.Dept Surg,1st Teach Hosp,Beijing Med Univ,Beijing,100034 Natl Med J China 1993;73(6):349—351.To study the relationship between portal resistanceand formation of portal hypertension,we designed a

  1. Cystic echinococcosis of the liver

    DEFF Research Database (Denmark)

    Branci, Sonia; Ewertsen, Caroline; Thybo, Søren;

    2012-01-01

    Cystic echinococcosis (CE) of the liver can be treated with ultrasound-guided puncture, aspiration, injection, and re-aspiration (PAIR), with surgery and with benzimidazole derivatives. The aim of this study was to review available data concerning treatment modality and outcome for patients treated...... for CE of the liver in a Danish tertiary reference center....

  2. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, Efstathios; Oliveira, Claudia P; Alvares-da-Silva, Mario R;

    2012-01-01

    -citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. RESULTS: In CCl(4.......75, PNAFLD cohort, VICM levels were 20.6% higher in F0 (339...... ±12 ng/mL, PNAFLD patients. These data...

  3. Protective effect of xanthohumol on toxin-induced liver inflammation and fibrosis

    OpenAIRE

    Dorn, Christoph; Heilmann, Jörg; Hellerbrand, Claus

    2012-01-01

    Xanthohumol, the major prenylated chalcone found in hops, is known for its anti-inflammatory properties. We have recently shown that xanthohumol inhibits hepatic inflammation and fibrosis in a murine model of nonalcoholic steatohepatitis. The aim of this study was to investigate the effect of xanthohumol in an acute model of liver injury. Carbon tetrachloride (CCl4), an industrial solvent, is a hepatotoxic agent and its administration is widely used as an animal model of toxin-induced liver i...

  4. Drug-induced liver injury

    DEFF Research Database (Denmark)

    Nielsen, Mille Bækdal; Ytting, Henriette; Skalshøi Kjær, Mette

    2017-01-01

    biochemical findings included bilirubin elevated to above 3.2 × ULN, ALT elevated to above 9 × ULN in 86%, INR above 1.4 in 70%. Twenty two patients needed treatment in the liver intensive care unit. Fifteen patients developed acute liver failure with a severe outcome. Six patients were liver transplanted......OBJECTIVE: The idiosyncratic subtype of drug-induced liver injury (DILI) is a rare reaction to medical treatment that in severe cases can lead to acute liver failure and death. The aim of this study was to describe the presentation and outcome of DILI and to identify potential predictive factors...... and outcome. RESULTS: Of 43 patients, 25 (58%) were female with a mean age of 54 years. The two most frequent causes of DILI were Disulfiram (30%) and antibiotics (19%). The most common symptoms were jaundice, nausea, fatigue and gastrointestinal discomfort. At the time of admission, the most frequent...

  5. The heart and the liver

    DEFF Research Database (Denmark)

    Møller, Søren; Dümcke, Christine Winkler; Krag, Aleksander

    2009-01-01

    Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek...... against the heart failure. Transjugular intrahepatic portosystemic shunt insertion and liver transplantation affect cardiac function in portal hypertensive patients and cause stress to the cirrhotic heart, with a risk of perioperative heart failure. The risk and prevalence of coronary artery disease...... are increasing in cirrhotic patients and since perioperative mortality is high, careful evaluation of such patients with dobutamine stress echocardiography, coronary angiography and myocardial perfusion imaging is required prior to liver transplantation. Future research should focus on beneficial effects...

  6. Liver allograft pathology in healthy pediatric liver transplant recipients.

    Science.gov (United States)

    Briem-Richter, Andrea; Ganschow, Rainer; Sornsakrin, Marijke; Brinkert, Florian; Schirmer, Jan; Schaefer, Hansjörg; Grabhorn, Enke

    2013-09-01

    Liver transplantation offers excellent results for children with end-stage liver disease, and efforts should be directed toward maintaining long-term graft health. We evaluate graft pathology in healthy pediatric transplant recipients with low-maintenance immunosuppressive medications to assess whether protocol biopsies are helpful for adapting immunosuppression and protecting long-term graft function. Liver biopsies were performed on 60 healthy pediatric liver transplant recipients, and histological findings were correlated with laboratory, serological, and radiological results. Fourteen patients (23%) were diagnosed with acute or early chronic rejection, and immunosuppressive medications were increased in these children. Liver function tests did not correlate with histological findings. The incidence of fibrosis was 36% in transplant recipients five or more years after liver transplantation. We observed an unexpectedly high prevalence of rejection and fibrosis in children with no laboratory abnormalities, which led to changes in their immunosuppressive medications. Scheduled biopsies appear to be useful in pediatric transplant recipients with low immunosuppressive medications for early detection of morphological changes in liver transplants. Further studies are needed to evaluate whether adaption of immunosuppression helps to reduce tissue damage and the incidence of allograft dysfunction in the long term.

  7. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2004-01-01

    to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin......Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic...... hemodynamics in cirrhosis. The most characteristic findings in cirrhotic patients are vasodilatation with low systemic vascular resistance, increased cardiac output, high arterial compliance, secondary activation of counterregulatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system...

  8. [Liver transplantation and pregnancy].

    Science.gov (United States)

    Goarin, A-C; Homer, L

    2010-11-01

    Management during their sexual life of patients with a liver transplantation is a more or less common situation depending centers. Based on literature review, a focus on management of recipient women was conducted, from contraception to pregnancy, describing the complications related to the status of transplant recipient, but also those that may be related to immunosuppressive agents. If fertility and access to contraception are only slightly modified by graft, complications related to graft or immunosuppressive drugs can affect the pregnancy. On the maternal side, hypertension and preeclampsia are more common, as well as renal dysfunction, iatrogenic diabetes and bacterial or viral infections, acute rejection and graft loss do not appear to be influenced by pregnancy. The fetus is also exposed to risks such as induced prematurity and IUGR. Pregnancy in recipients of hepatic grafts therefore requires joint follow-up by transplant specialist and perinatologist, which leads in most cases to successful outcome for mother and child.

  9. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens H; Møller, Søren

    2004-01-01

    Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic......, neuropituitary release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through nitric oxide, calcitonin gene-related peptide, adrenomedullin, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance...... to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin...

  10. Liver involvement in Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Adelaine; Ortiz-Neira, Clara L.; Abou Reslan, Walid; Kaura, Deepak [Alberta Children' s Hospital, Department of Diagnostic Imaging, Calgary, Alberta (Canada); Sharon, Raphael; Anderson, Ronald [Alberta Children' s Hospital, Department of Oncology, Calgary, AB (Canada); Pinto-Rojas, Alfredo [Alberta Children' s Hospital, Department of Pathology, Calgary, AB (Canada)

    2006-10-15

    Liver involvement in Langerhans cell histiocytosis (LCH) typically presents with hepatomegaly and other signs of liver dysfunction. We present an 11-month-old child having only minimally elevated liver enzymes as an indication of liver involvement. Using sonography as the initial diagnostic tool followed by MRI, LCH of the liver was revealed. A review of sonographic, CT, MRI and MR cholangiopancreatography findings in liver LCH is presented. We recommend that physicians consider sonography and MRI screening for liver involvement in patients with newly diagnosed LCH, as periportal involvement may be present with little or no liver function abnormality present, as in this patient. (orig.)

  11. Screening in liver disease

    Institute of Scientific and Technical Information of China (English)

    Paolo Del Poggio; Marzio Mazzoleni

    2006-01-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines,although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors,such as transfusion before 1992 and drug addiction,is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation.

  12. Uncommon liver tumors

    Science.gov (United States)

    Wu, Chia-Hung; Chiu, Nai-Chi; Yeh, Yi-Chen; Kuo, Yu; Yu, Sz-Shian; Weng, Ching-Yao; Liu, Chien-An; Chou, Yi-Hong; Chiou, Yi-You

    2016-01-01

    Abstract Background: Beside hepatocellular carcinoma, metastasis, and cholangiocarcinoma, the imaging findings of other relatively uncommon hepatic lesions are less discussed in the literature. Imaging diagnosis of these lesions is a daily challenge. In this article, we review the imaging characteristics of these neoplasms. Methods: From January 2003 to December 2014, 4746 patients underwent liver biopsy or hepatic surgical resection in our hospital. We reviewed the pathological database retrospectively. Imaging of these lesions was reviewed. Results: Imaging findings of uncommon hepatic lesions vary. We discuss the typical imaging characteristics with literature review. Clinical and pathological correlations are also described. Primary hepatic lymphoma consists only of 1% of the extranodal non-Hodgkin lymphoma, and is defined as the one involving only the liver and perihepatic lymph nodes within 6 months after diagnosis. Combined hepatocellular and cholangiocarcinoma (cHCC-CC) shares some overlapping imaging characteristics with both HCC and cholangiocarcinoma because of being an admixture of them. Angiosarcoma is the most common hepatic mesenchymal tumor and is hypervascular in nature. Inflammatory pseudotumor is often heterogeneous on ultrasonography and with enhanced septations and rims in the portovenous phase after contrast medium. Angiomyolipoma (AML) typically presents with macroscopic fat components with low signal on fat-saturated magnetic resonance imaging (MRI) and presence of drainage vessels. Intraductal papillary neoplasm of the bile duct (IPNB) is thought of as a counterpart to the pancreatic intraductal papillary mucinous neoplasm. Most of the IPNBs secrete mucin and cause disproportional dilatation of the bile ducts. Mucinous cystic neoplasm (MCN) contains proteinaceous and colloidal components without ductal communication and characterizes with hyperintensity on T1-weighted imaging. Other extremely rare lesions, including epithelioid

  13. Rat liver metabolism of dicarboxylic acids.

    Science.gov (United States)

    Vamecq, J; Draye, J P; Brison, J

    1989-04-01

    Recently, we demonstrated in rat liver that dicarboxylic acids containing more than five carbons can be activated by a microsomal dicarboxylyl-CoA synthetase (J. Vamecq, E. de Hoffmann, and F. Van Hoof. Biochem. J. 230: 683-693, 1985). The products of this reaction, dicarboxylyl-CoA esters, were found to be substrates for an H2O2-generating dicarboxylyl-CoA oxidase. In the present work we report that 1) the catalytic center or the essential domains of dicarboxylyl-CoA synthetase are located at the cytosolic aspect of the endoplasmic reticulum membrane; 2) dicarboxylyl-CoA oxidase is optimally active on dodecanedioyl-CoA and is a peroxisomal enzyme; 3) cyanide-insensitive dodecanedioyl-CoA oxidation (NADH production) is catalyzed by rat liver homogenates. Cell fractionation studies disclose that, similar to dodecanedioyl-CoA oxidase (H2O2 production), the cyanide-insensitive dodecanedioyl-CoA oxidizing activity also belongs to peroxisomes; 4) a dodecanedioyl-CoA oxidoreductase reaction can be assayed by the dichlorphenolindophenol procedure in rat liver homogenates, and the activity is abundant in peroxisomal, mitochondrial, and soluble fractions; 5) by contrast with monocarboxylyl-CoA esters, the dicarboxylyl-CoAs are apparently not substrates for mitochondrial fatty acid oxidation; however, the use of dicarboxylylcarnitine esters as direct substrate for mitochondria suggests the existence of an active beta-oxidation of dicarboxylates in these organelles, which is further confirmed by experiments in which mitochondria are permeabilized with digitonin; 6) the in vivo oxidation of infused dodecanedioic acid results in a rapid appearance in urine of medium-chain dicarboxylic acids, with only 30-50% of the infused dose recovered in urine.

  14. Propylthiouracil-induced acute liver failure: role of liver transplantation.

    Science.gov (United States)

    Carrion, Andres F; Czul, Frank; Arosemena, Leopoldo R; Selvaggi, Gennaro; Garcia, Monica T; Tekin, Akin; Tzakis, Andreas G; Martin, Paul; Ghanta, Ravi K

    2010-01-01

    Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.

  15. Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Andres F. Carrion

    2010-01-01

    Full Text Available Propylthiouracil- (PTU- induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.

  16. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yalamanchili, Kanthi; Saadeh, Sherif; Klintmalm, Göran B; Jennings, Linda W; Davis, Gary L

    2010-04-01

    Nonalcoholic steatohepatitis (NASH) may account for many cases of cryptogenic cirrhosis. If so, then steatosis might recur after liver transplantation. Two thousand fifty-two patients underwent primary liver transplantation for chronic liver disease between 1986 and 2004. Serial liver biopsy samples were assessed for steatosis and fibrosis. Two hundred fifty-seven patients (12%) had a pretransplant diagnosis of cryptogenic cirrhosis (239) or NASH (18). Fatty liver developed in 31% and was more common when the pretransplant diagnosis was NASH (45% at 5 years versus 23% for cryptogenic cirrhosis, P = 0.007). NASH developed in only 4% and occurred exclusively when steatosis had already occurred. Steatosis after liver transplantation was associated with the baseline body weight and body mass index by univariate analyses, but no pretransplant or posttransplant characteristic independently predicted steatosis after liver transplantation because obesity was so common in all groups. Five percent and 10% developed bridging fibrosis or cirrhosis after 5 and 10 years, respectively, and this was more common after NASH (31%) than in those who developed steatosis alone (6%) or had no fat (3%, P = 0.002). One-, 5-, and 10-year survival was the same in patients who underwent transplantation for cryptogenic cirrhosis or NASH (86%, 71%, and 56%) and in patients who underwent transplantation for other indications (86%, 71%, and 53%; not significant), but death was more often due to cardiovascular disease and less likely from recurrent liver disease. In conclusion, fatty liver is common after liver transplantation for cryptogenic cirrhosis or NASH but is twice as common in the latter group; this suggests that some cryptogenic cirrhosis, but perhaps not all, is caused by NASH. Posttransplant NASH is unusual, and steatosis appears to be a prerequisite. Advanced fibrosis is uncommon, and survival is the same as that of patients who undergo transplantation for other causes.

  17. Arrhythmia risk in liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ioana Mozos

    2015-01-01

    Interactions between the functioning of the heart andthe liver have been described, with heart diseasesaffecting the liver, liver diseases affecting the heart,and conditions that simultaneously affect both. Theheart is one of the most adversely affected organs inpatients with liver cirrhosis. For example, arrhythmiasand electrocardiographic changes are observed inpatients with liver cirrhosis. The risk for arrhythmia isinfluenced by factors such as cirrhotic cardiomyopathy,cardiac ion channel remodeling, electrolyte imbalances,impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT intervalprolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions.

  18. Liver Development, Regeneration, and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Janet W. C. Kung

    2010-01-01

    Full Text Available The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

  19. Correlation between liver morphology and haemodynamics in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, J H;

    1985-01-01

    was found with haemodynamic variables. The present data substantiate the concept that established portal hypertension in alcoholic liver disease is mainly accomplished by a derangement in hepatic architecture, whereas parenchymal changes, including hepatocyte size, are of less importance....

  20. Autoantibodies in autoimmune liver diseases.

    Science.gov (United States)

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  1. Hyperaldosteronism associated with liver metastases.

    Science.gov (United States)

    Pandya, K J; Whitehead, R; Crowley, J; Citrin, D L

    1980-07-11

    Plasma aldosterone levels were measured in 50 patients with confirmed liver metastases from various histologically proved primary tumors. None of these patients had electrolyte abnormalities or history of benign liver disease, congestive heart failure, hypertension, or renal disease. Patients with edema, ascites, or both had significantly greater elevation of plasma aldosterone levels compared to nonedematous patients; these patients also demonstrated a substantial degree of hepatic dysfunction as evidenced by lower serum albumin levels and higher bilirubin and alkaline phosphatase levels. This study provides a rational basis for the use of the specific aldosterone inhibitor spironolactone in the treatment of patients with advanced metastatic liver disease and edematous states.

  2. Ventilatory strategy during liver transplantation

    DEFF Research Database (Denmark)

    Sørensen, Henrik; Grocott, Hilary P; Niemann, Mads;

    2014-01-01

    BACKGROUND: As measured by near infrared spectroscopy (NIRS), cerebral oxygenation (ScO2) may be reduced by hyperventilation in the anhepatic phase of liver transplantation surgery (LTx). Conversely, the brain may be subjected to hyperperfusion during reperfusion of the grafted liver. We...... liver, ScO2 increased by 5.5% (3.8-7.3%), EtCO2 by 0.7 kPa (0.5-0.8 kPa), and VE by 0.6 L/min (0.3-0.9 L/min; all P

  3. Cyst and tumor of liver

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950340 Radioimmunoassay of acid isoferritin in pa-tients with primary liver cancer.LI Liren(李立人),etal.Dept Nucl Med,Guangdong Prov People’s Hosp,Guangzhou,Chin J Clin Oncol 1995;22(1):24-26.In order to measure the levels of serum acid isofer-ritin(AIF) in healthy subjects and patients with pri-mary liver caner (PLC).AIF were titrated with ra-dioimmunoassay technic in 128 cases of PLC,37 casesof liver cirrhosis (LC),as well as 60 healthy subjects.The AIF values in serum of healthy subjects were 112

  4. Muscle cramps in liver disease.

    Science.gov (United States)

    Mehta, Shivang S; Fallon, Michael B

    2013-11-01

    Muscle cramps are common in patients with liver disease and adversely influence quality of life. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes. Treatments have focused on these particular areas with varied results. This review will focus on the clinical features of muscle cramps in patients with liver disease and review potential mechanisms and current therapies.

  5. Association of nonalcoholic fatty liver disease and liver cancer

    Science.gov (United States)

    Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

    2015-01-01

    AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

  6. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    Science.gov (United States)

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  7. Recurrence of cholestatic liver disease after living donor liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Sumihito Tamura; Masatoshi Hakuuchi; Yasuhiko Sugawara; Junichi Kaneko; Junichi Togashi; Yuichi Matsui; Noriyo Yamashiki; Norihiro Kokudo

    2008-01-01

    End-stage liver disease,due to cholestatic liver diseases with an autoimmune background such as primary biliary cirrhosis(PBC)and primary sclerosing cholangitis(PSC),is considered a good indication for liver transplantation.Excellent overall patient and graft outcomes,based mostly on the experience from deceased donor liver ransplantation(DDLT),have been reported.Due to the limited number of oraan donations from deceased donors in most Asian countries,living donor liver transplantation(LDLT)is the mainstream treatment for end-stage liver disease,including that resulting from PBC and PSC.Although the initial experiences with LDLT for PBC and PSC seem satisfactory or comparable to that with DLT,some aspects,including the timing of transplantation,the risk of recurrent disease,and its long-term clinical implications,require further evaluation.Whether or not the long-term outcomes of LDLT from a biologically related donor are equivalent to that of DDLT requires further observations.The clinical course following LDLT may be affected by he genetic background shared between the recipient and the living related donor.(C)2008 The WJG Press.All rights reserved.

  8. Role of liver biopsy in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Nalbantoglu, I L Ke; Brunt, Elizabeth M

    2014-07-21

    Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the "gold standard" for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

  9. Impact of asialoglycoprotein receptor deficiency on the development of liver injury

    Institute of Scientific and Technical Information of China (English)

    Serene ML Lee; Carol A Casey; Benita L McVicker

    2009-01-01

    The asialoglycoprotein (ASGP) receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis (RME). The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously,we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease (ALD). The studies revealed profound ethanolmediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations,studies were performed utilizing knockout mice (lacking a functional ASGP receptor) to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti-Fas (CD95) antibody, carbon tetrachloride (CCl4) and lipopolysaccharide (LPS)/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels,histopathological scores, as well as hepatocellular death.Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.

  10. Laminin and Fibronectin in Cell Adhesion: Enhanced Adhesion of Cells from Regenerating Liver to Laminin

    Science.gov (United States)

    Carlsson, Roland; Engvall, Eva; Freeman, Aaron; Ruoslahti, Erkki

    1981-04-01

    Laminin, a basement membrane glycoprotein isolated from cultures of mouse endodermal cells and rat yolk sac carcinoma cells, promoted the attachment of liver cells obtained from regenerating mouse liver. Cells from normal mouse liver attached readily to dishes coated with fibronectin but attached poorly to surfaces coated with laminin. Both proteins efficiently promoted the attachment of cells from livers undergoing regeneration. After regeneration, the attachment to laminin returned to the low levels found in animals not subjected to partial hepatectomy but attachment to fibronectin remained high. Immunofluorescent staining of sections of normal liver with antilaminin revealed the presence of laminin in or adjacent to the walls of the bile ducts and blood vessels. After induction of regeneration by partial hepatectomy, increased amounts of laminin appeared in the sinusoidal areas. After carbon tetrachloride poisoning, staining for laminin was especially pronounced in the necrotic and postnecrotic areas around the central veins. This additional expression of laminin was transient. It reached a maximum around 5-6 days after the injury and then gradually disappeared. These findings show that laminin is an adhesive protein. The increase of laminin in regenerating liver and the adhesiveness of cells from such livers to laminin suggest a role for laminin in the maintenance of a proper tissue organization during liver regeneration.

  11. Prevention of liver fibrosis by intrasplenic injection of high-density cultured bone marrow cells in a rat chronic liver injury model.

    Directory of Open Access Journals (Sweden)

    Jie Lian

    Full Text Available Endothelial progenitor cells (EPCs from bone marrow have proven to be functional for the prevention of liver fibrosis in chronic liver injury. However, expansion of EPCs in culture is complicated and expansive. Previously, we have established a simple method that could enrich and expand EPCs by simple seeding bone marrow cells in high density dots. The purpose of this study is to evaluate whether cells derived from high-density (HD culture of rat bone marrow cells could prevent the liver fibrosis in a chronic liver injury rat model, induced by carbon tetrachloride (CCl4. Flow cytometric analysis showed that cells from HD culture were enriched for EPCs, expressing high levels of EPC markers. Intrasplenic injection of HD cultured bone marrow cells in the CCl4-induced liver injury rat showed an enhanced antifibrogenic effect compared with animals treated with cells from regular-density culture. The antifibrogenic effect was demonstrated by biochemical and histological analysis 4 weeks post-transplantation. Furthermore, cells from HD culture likely worked through increasing neovascularization, stimulating liver cell proliferation, and suppressing pro-fibrogenic factor expression. HD culture, which is a simple and cost-effective procedure, could potentially be used to expand bone marrow cells for the treatment of liver fibrosis.

  12. Role of liver stem cells in hepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Lei-Bo; Xu; Chao; Liu

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the "cancer stem cell hypothesis", which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells(liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future.

  13. Bioartificial liver: Its pros and cons

    NARCIS (Netherlands)

    R.A.F.M. Chamuleau; P.P.C. Poyck; M.P. van de Kerkhove

    2006-01-01

    Both the large variety of liver functions for maintaining body homeostasis and the proven effectivity of whole liver transplantation in the therapy of acute liver failure (ALF), are important reasons to presume that cell-free liver support systems will not be able to adequately support the failing l

  14. Drugs Approved for Liver Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  15. Epigenetic biomarkers in liver cancer.

    Science.gov (United States)

    Banaudha, Krishna K; Verma, Mukesh

    2015-01-01

    Liver cancer (hepatocellular carcinoma or HCC) is a major cancer worldwide. Research in this field is needed to identify biomarkers that can be used for early detection of the disease as well as new approaches to its treatment. Epigenetic biomarkers provide an opportunity to understand liver cancer etiology and evaluate novel epigenetic inhibitors for treatment. Traditionally, liver cirrhosis, proteomic biomarkers, and the presence of hepatitis viruses have been used for the detection and diagnosis of liver cancer. Promising results from microRNA (miRNA) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers. Some of these epigenetic biomarkers may be useful in risk assessment and for screening populations to identify who is likely to develop cancer. Challenges and opportunities in the field are discussed in this chapter.

  16. Pleural effusion in liver disease.

    Science.gov (United States)

    Alonso, José Castellote

    2010-12-01

    Hepatic hydrothorax is the paradigmatic pleural effusion in liver cirrhosis. It is defined as a pleural effusion in a patient with portal hypertension and no cardiopulmonary disease. The estimated prevalence of this complication in patients with liver cirrhosis is 5 to 6%. Its pathophysiology involves movement of ascitic fluid from the peritoneal cavity into the pleural space through diaphragmatic defects. Thoracentesis and pleural fluid analysis are necessary for diagnosis. Initial management consists of sodium restriction, diuretics, and therapeutic thoracentesis. A transjugular intrahepatic portosystemic shunt may provide a bridge prior to liver transplantation. Spontaneous bacterial empyema is the infection of a preexisting hydrothorax. The more frequent bacteria involved are ENTEROBACTERIACEAE and gram-positive cocci. Antibiotic therapy is the cornerstone of therapy. This article reviews etiology, clinical manifestations, and therapy of these two complications of liver cirrhosis and portal hypertension.

  17. Immunological treatment of liver tumors

    Institute of Scientific and Technical Information of China (English)

    Maurizio Chiriva-Internati; Fabio Grizzi; Cynthia A Jumper; Everardo Cobos; Paul L Hermonat; Eldo E Frezza

    2005-01-01

    Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resection and the use of chemotherapy, the potential of immunotherapy and gene manipulation is still largely unexplored.Immunological therapy by gene manipulation is based on the interaction between virus-based gene delivery systems and dendritic cells. Using viruses as vectors, it is possible to transduce dendritic cells with genes encoding tumor-associated antigens, thus inducing strong humoral and cellular immunity against the antigens themselves.Both chemotherapy and radiation therapy have the disadvantage of destroying healthy cells, thus causing severe side-effects. We need more precisely targeted therapies capable of killing cancer cells while sparing healthy cells. Our goal is to establish a new treatment for solid liver tumors based on the concept of cytoreduction,and propose an innovative algorithm.

  18. Liver Cancer and Hepatitis B

    Science.gov (United States)

    ... Our Accomplishments Annual Reports Our Videos What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  19. Liver Disease and Adult Vaccination

    Science.gov (United States)

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  20. MicroRNA Expression Profiling in CCl4-Induced Liver Fibrosis of Mus musculus

    Directory of Open Access Journals (Sweden)

    Jeongeun Hyun

    2016-06-01

    Full Text Available Liver fibrosis is a major pathological feature of chronic liver diseases, including liver cancer. MicroRNAs (miRNAs, small noncoding RNAs, regulate gene expression posttranscriptionally and play important roles in various kinds of diseases; however, miRNA-associated hepatic fibrogenesis and its acting mechanisms are poorly investigated. Therefore, we performed an miRNA microarray in the fibrotic livers of Mus musculus treated with carbon-tetrachloride (CCl4 and analyzed the biological functions engaged by the target genes of differentially-expressed miRNAs through gene ontology (GO and in-depth pathway enrichment analysis. Herein, we found that four miRNAs were upregulated and four miRNAs were downregulated more than two-fold in CCl4-treated livers compared to a control liver. Eight miRNAs were predicted to target a total of 4079 genes. GO analysis revealed that those target genes were located in various cellular compartments, including cytoplasm, nucleolus and cell surface, and they were involved in protein-protein or protein-DNA bindings, which influence the signal transductions and gene transcription. Furthermore, pathway enrichment analysis demonstrated that the 72 subspecialized signaling pathways were associated with CCl4-induced liver fibrosis and were mostly classified into metabolic function-related pathways. These results suggest that CCl4 induces liver fibrosis by disrupting the metabolic pathways. In conclusion, we presented several miRNAs and their biological processes that might be important in the progression of liver fibrosis; these findings help increase the understanding of liver fibrogenesis and provide novel ideas for further studies of the role of miRNAs in liver fibrosis.

  1. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    Science.gov (United States)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  2. Patient selection for liver transplantation.

    Science.gov (United States)

    Carrion, Andres F; Aye, Lydia; Martin, Paul

    2013-08-01

    Improved outcomes in liver transplant recipients reflect advances in surgical technique, post-operative care, immunosuppression as well as better selection of potential candidates. The pre-transplant evaluation is a multidisciplinary process intended to recognize and treat important comorbid conditions that may impair outcomes during the peri- and post-transplant periods. Important psychosocial issues should also be ascertained and tackled early during the pre-transplant evaluation with an overarching intention to improve the success of liver transplantation.

  3. Morbidity after percutaneous liver biopsy.

    OpenAIRE

    Lichtman, S; Guzman, C; Moore, D.; Weber, J L; Roberts, E.A.

    1987-01-01

    The safety of percutaneous liver biopsy with a 1.2 mm Menghini needle in infants aged one year or less was investigated. One hundred and eighty four procedures performed from 1975 to 1985 were reviewed. There were no deaths or major complications within 48 hours associated with the procedure. In five instances specific complications occurred: a drop in haemoglobin concentration (three), transient hypotension (one), and haematoma at the biopsy site (one). The result of liver biopsy was diagnos...

  4. [Non-invasive assessment of liver fibrosis].

    Science.gov (United States)

    Cohen-Ezra, Oranit; Ben-Ari, Ziv

    2015-03-01

    Chronic liver diseases represent a major public health problem, accounting for significant morbidity and mortality worldwide. Prognosis and management of chronic liver diseases depend on the amount of liver fibrosis. Liver biopsy has long remained the gold standard for assessment of liver fibrosis. Liver biopsy is an invasive procedure with associated morbidity, it is rarely the cause for mortality, and has a few limitations. During the past two decades, in an attempt to overcome the limitations of liver biopsy, non-invasive methods for the evaluation of liver fibrosis have been developed, mainly in the field of viral hepatitis. This review will focus on different methods available for non-invasive evaluation of liver fibrosis including a biological approach which quantifies serum levels of biomarkers of fibrosis and physical techniques which measure liver stiffness by transient elastography, ultrasound or magnetic resonance based elastography, their accuracy, advantages and disadvantages.

  5. [Liver resection by water jet].

    Science.gov (United States)

    Horie, T

    1989-01-01

    Major problem in resecting liver parenchyma is how to control the bleeding. Recently, resection of the liver by water jet has been reported. So, experimental and clinical studies were performed to investigate the usefulness of the water jet equipment. Ten pigs weighing around 17kg were used. The optimal pressure to resect the porcine liver was 7 to 15kg/cm2. By 4 weeks the cut surface was covered with fibrous capsule. Portal angiography showed no abnormality in the resected area. The water jet was also used in 30 human operations. The optimal pressure was 12 to 18kg/cm2 for non cirrhotic liver and 15 to 20kg/cm2 for cirrhotic liver. The surface immediately after jet cutting was more smooth than that of CUSA and histologically there was slight bleeding and necrosis. The volume of blood loss during dissection was not different between water jet group and CUSA group. No significant changes were found in the laboratory data. These results suggest that water jet is as useful as CUSA for cutting the liver parenchyma.

  6. HEMOSTATIC DISORDERS IN LIVER DISEASES

    Directory of Open Access Journals (Sweden)

    A. F. Minov

    2010-01-01

    Full Text Available The liver is an essential player in the pathway of coagulation in both primary and secondary hemostasis as it is the site of synthesis of all coagulation factors and their inhibitors. Liver diseases are associated with complex changes in coagulation and the delicate balance between pro and antithrombotic factors is preserved but reset to a lower level. There is growing evidence that portal and hepatic vein thrombosis is cause of disease progression in cirrhotic patients and worsens hemostatic abnormalities. These hemostatic abnormalities do not always lead to spontaneous bleeding, which may be triggered only by additional factors, such as infections. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. In patients with end stage liver disease liver transplantation is the only treatment available, which can restore normal hemostasis, and correct genetic clotting defects. During liver transplantation hemorrhage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis. 

  7. Doctors Look for Liver Transplant Alternatives

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ Robert Pennington, a 19 - year - old boy, suffers from liver disease. His name was put on a transplant waiting list, but no livers were available. Then Dr. Marlon Levy, a transplant surgeon at Baylor University Medical Center, offered an alternative: a procedure2 using a dead pig's liver. But not a liver from an ordinary pig, "They're genetically modified3 to try to prevent a reaction between the human blood and the pig liver" , Levy said.

  8. Carbonized asphaltene-based carbon-carbon fiber composites

    Energy Technology Data Exchange (ETDEWEB)

    Bohnert, George; Lula, James; Bowen, III, Daniel E.

    2016-12-27

    A method of making a carbon binder-reinforced carbon fiber composite is provided using carbonized asphaltenes as the carbon binder. Combinations of carbon fiber and asphaltenes are also provided, along with the resulting composites and articles of manufacture.

  9. Acute toxicity of CCl4 but not of paracetamol induces a transcriptomic signature of fibrosis in precision-cut liver slices

    NARCIS (Netherlands)

    Vatakuti, Suresh; Schoonen, Willem G E J; Elferink, Maria; Groothuis, Geny M M; Olinga, Peter

    2015-01-01

    In rat in vivo, both paracetamol (APAP) and carbon tetrachloride (CCl4) induce liver necrosis, but long-term treatment with CCl4, in contrast to paracetamol, causes liver fibrosis. The aim of this study was to perform transcriptomic analysis to compare the early changes in mRNA expression profiles i

  10. Toward surface quantification of liver fibrosis progression

    Science.gov (United States)

    He, Yuting; Kang, Chiang Huen; Xu, Shuoyu; Tuo, Xiaoye; Trasti, Scott; Tai, Dean C. S.; Raja, Anju Mythreyi; Peng, Qiwen; So, Peter T. C.; Rajapakse, Jagath C.; Welsch, Roy; Yu, Hanry

    2010-09-01

    Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver with minimally invasive optical methods. This would be possible only if the information contained on or near liver surfaces accurately reflects the liver fibrosis progression in the liver interior. In our study, we acquired the second-harmonic generation and two-photon excitation fluorescence microscopy images of liver tissues from bile duct-ligated rat model of liver fibrosis. We extracted morphology-based features, such as total collagen, collagen in bile duct areas, bile duct proliferation, and areas occupied by remnant hepatocytes, and defined the capsule and subcapsular regions on the liver surface based on image analysis of features. We discovered a strong correlation between the liver fibrosis progression on the anterior surface and interior in both liver lobes, where biopsy is typically obtained. The posterior surface exhibits less correlation with the rest of the liver. Therefore, scanning the anterior liver surface would obtain similar information to that obtained from biopsy for monitoring liver fibrosis progression.

  11. Segmentation of liver and liver tumor for the Liver-Workbench

    Science.gov (United States)

    Zhou, Jiayin; Ding, Feng; Xiong, Wei; Huang, Weimin; Tian, Qi; Wang, Zhimin; Venkatesh, Sudhakar K.; Leow, Wee Kheng

    2011-03-01

    Robust and efficient segmentation tools are important for the quantification of 3D liver and liver tumor volumes which can greatly help clinicians in clinical decision-making and treatment planning. A two-module image analysis procedure which integrates two novel semi-automatic algorithms has been developed to segment 3D liver and liver tumors from multi-detector computed tomography (MDCT) images. The first module is to segment the liver volume using a flippingfree mesh deformation model. In each iteration, before mesh deformation, the algorithm detects and avoids possible flippings which will cause the self-intersection of the mesh and then the undesired segmentation results. After flipping avoidance, Laplacian mesh deformation is performed with various constraints in geometry and shape smoothness. In the second module, the segmented liver volume is used as the ROI and liver tumors are segmented by using support vector machines (SVMs)-based voxel classification and propagational learning. First a SVM classifier was trained to extract tumor region from one single 2D slice in the intermediate part of a tumor by voxel classification. Then the extracted tumor contour, after some morphological operations, was projected to its neighboring slices for automated sampling, learning and further voxel classification in neighboring slices. This propagation procedure continued till all tumorcontaining slices were processed. The performance of the whole procedure was tested using 20 MDCT data sets and the results were promising: Nineteen liver volumes were successfully segmented out, with the mean relative absolute volume difference (RAVD), volume overlap error (VOE) and average symmetric surface distance (ASSD) to reference segmentation of 7.1%, 12.3% and 2.5 mm, respectively. For live tumors segmentation, the median RAVD, VOE and ASSD were 7.3%, 18.4%, 1.7 mm, respectively.

  12. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Renata Salatti Ferrari

    2012-01-01

    Full Text Available The use of carbon tetrachloride (CCl4 in rats is an experimental model of hepatic tissue damage; which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is the consequence of progressive continued liver damage, it may be reversible when the damaging noxae have been withdrawn. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCI4 administration. We used 18 male Wistar rats divided into three groups: control (CO and two groups divided by the time of cirrhosis induction by CCI4: G1 (11 weeks, G2 (16 weeks. We found significant increase of transaminase levels and lipid peroxidation (TBARS in liver and lung tissue and also increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-α and IL-1β in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces a model of liver cirrhosis, which causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

  13. Nitrofurantoin-induced immune-mediated lung and liver disease

    Directory of Open Access Journals (Sweden)

    Milić Rade

    2012-01-01

    Full Text Available Introduction. Nitrofurantoin, a furan derivative, introduced in the fifties has widely been used as an effective agent for the treatment and prevention of urinary tract infections (UTI. Spectrum of adverse reactions to nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease, acute hepatitis and granulomatous reaction, to the chronic active hepatitis, a very rare adverse effect, that can lead to cirrhosis and death. Case report. We presented a 55-year-old female patient with eosinophilic interstitial lung disease, severe chronic active hepatitis and several other immune- mediated multisystemic manifestations of prolonged exposure to nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We estimated typical radiographic and laboratory disturbances, also restrictive ventilatory changes, severe reduction of carbon monoxide diffusion capacity and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was consistent with druginduced reaction. Hepatitis was confirmed by liver biopsy. After withdrawal of nitrofurantoin and application of high dose of glicocorticosteroids, prompt clinical and laboratory recovery was achieved. Conclusion. Adverse drug reactions should be considered in patients with concomitant lung and liver disease. The mainstay of treatment is drug withdrawal and the use of immunosuppressive drugs in severe cases. Consideration should be given to monitor lung and liver function tests during long term nitrofurantoin therapy.

  14. Accuracy of Hepatobiliary Scintigraphy after Liver Transplantation and Liver Resection

    Directory of Open Access Journals (Sweden)

    Manuel Eckenschwiller

    2016-01-01

    Full Text Available Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX (n=13 or hepatic resection (n=26 were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14. Overall diagnostic accuracy was 76% (19/25 in this group and 54% (7/13 in the LTX group. False negative (FN diagnoses occurred more often among LTX patients (p=0.011. Hyperbilirubinemia (>5 mg/dL significantly influenced the excretion function of the liver, prolonging HBS’s time-activity-curve (p=0.001. Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX.

  15. Assessment of liver fibrosis by Fibroscan as compared to liver biopsy in biliary atresia

    OpenAIRE

    Shen, Qiu-Long; Chen, Ya-Jun; Wang, Zeng-Meng; Zhang, Ting-Chong; Pang, Wen-Bo; Shu, Jun; Peng, Chun-Hui

    2015-01-01

    AIM: To evaluate liver stiffness measurement (LSM) using non-invasive transient elastography (Fibroscan) in comparison with liver biopsy for assessment of liver fibrosis in children with biliary atresia (BA).

  16. CCl4诱导大鼠纤维化肝组织 microRNA 差异表达及其初步分析%Differentially expressed and preliminary analysis of microRNA profiles in liver tissue of rat induced by carbon tetrachloride

    Institute of Scientific and Technical Information of China (English)

    刘业方; 张传涛; 李白雪; 郭尹玲; 王宝家; 唐洪屈; 王政; 张凤; 杨宇

    2015-01-01

    Objective To explore the differences of expression profiles and significance of the microRNA in liver tissue of rat induced by carbon tetrachloride(CCl4 ).Methods The microRNA differential expression analysis between normal group(n = 10) and model group(n=10)was conducted on high-throughput methods.Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes pathway analysis of the targets of miRNA were carried out in this study.Results Some differentally expressed microRNA with 29 up-regulated and 8 down-regulated were identified in our study.Through evaluaing the value of microRNA in the network,we find that the key microRNA of rising are miR-184,miR-10b-5p,miR-1 99a-3p,and the key microRNA of cutting are miR-200b-3p,miR-1 99a-5p,miR-125b-5p and so on.Conclusion The microRNA expression level in the model group has a signifi-cant change.Therefore,the courses of liver fibrosis is related to some process which microRNA control the regulation of cell prolif-eration,cell apoptosis,cell cycle,and so on.%目的:探索 microRNA 在四氯化碳(CCl4)诱导的大鼠纤维化肝组织中的差异表达及其意义。方法采用 microR-NA 高通量测序分析技术检测对照组(n=10)与模型组(n=10)肝脏组织 microRNA 表达,对差异 microRNA 进行靶基因预测,对靶基因进行基因本(GO)分析、pathway 分析。结果对照组与模型组间筛选出37个差异 microRNA,上调29个,下调8个;从microRNA-基因网络图中发现关键上调为 miR-184、miR-10b-5p、miR-199a-3p 等;关键下调为 miR-200b-3p、miR-199a-5p、miR-125b-5p 等。结论模型组 microRNA 表达谱变化明显,肝纤维化的形成与 microRNA 调控细胞增殖、凋亡、细胞周期等有关。

  17. Alleviating liver failure conditions using an integrated hybrid cryogel based cellular bioreactor as a bioartificial liver support

    Science.gov (United States)

    Damania, Apeksha; Hassan, Mohsin; Shirakigawa, Nana; Mizumoto, Hiroshi; Kumar, Anupam; Sarin, Shiv K.; Ijima, Hiroyuki; Kamihira, Masamichi; Kumar, Ashok

    2017-01-01

    Conventionally, some bioartificial liver devices are used with separate plasmapheresis unit to separate out plasma from whole blood and adsorbent column to detoxify plasma before it passes through a hepatocytes-laden bioreactor. We aim to develop a hybrid bioreactor that integrates the separate modules in one compact design improving the efficacy of the cryogel based bioreactor as a bioartificial liver support. A plasma separation membrane and an activated carbon cloth are placed over a HepG2-loaded cryogel scaffold in a three-chambered bioreactor design. This bioreactor is consequently connected extracorporeally to a rat model of acute liver failure for 3 h and major biochemical parameters studied. Bilirubin and aspartate transaminase showed a percentage decrease of 20–60% in the integrated bioreactor as opposed to 5–15% in the conventional setup. Urea and ammonia levels which showed negligible change in the conventional setup increase (40%) and decrease (18%), respectively in the integrated system. Also, an overall increase of 5% in human albumin in rat plasma indicated bioreactor functionality in terms of synthetic functions. These results were corroborated by offline evaluation of patient plasma. Hence, integrating the plasmapheresis and adsorbent units with the bioreactor module in one compact design improves the efficacy of the bioartificial liver device. PMID:28079174

  18. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

    OpenAIRE

    Ibarra, R.; Dazard, J-E.; Y. Sandlers; Rehman, F; Abbas, R.; Kombu, R.; Zhang, G-F; Brunengraber, H; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+...

  19. Alcoholic liver disease: the gut microbiome and liver cross talk.

    Science.gov (United States)

    Hartmann, Phillipp; Seebauer, Caroline T; Schnabl, Bernd

    2015-05-01

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with ALD have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses to microbial products protect from experimental ALD. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship, and consequences for ALD. We also discuss how the liver affects the intestinal microbiota.

  20. The International Liver Transplant Society Guideline on Living Liver Donation.

    Science.gov (United States)

    Miller, Charles M; Durand, Francois; Heimbach, Julie K; Kim-Schluger, Leona; Lee, Sung-Gyu; Lerut, Jan; Lo, Chung-Mau; Quintini, Cristiano; Pomfret, Elizabeth Anne

    2016-06-01

    The following guideline represents the position of the International Liver Transplantation Society (ILTS) on key preoperative, operative, and postoperative aspects surrounding living liver donation. These recommendations were developed from experts in the field from around the world. The authors conducted an analysis of the National Library of Medicine indexed literature on "living donor liver transplantation" [Medline search] using Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). ILTS members, and many more nonmembers, were invited to comment. Recommendations have been based on information available at the time of final submission (March 2016). The lack of randomized controlled trials in this field to date is acknowledged and is reflected in the grading of evidence. Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care.

  1. Protective effect of glycine on liver injury during liver transplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Yao-sheng; YAN Ye-hong; ZOU Xun-feng

    2010-01-01

    @@ Multiple procedures of liver transplantation bring conditions producing cold ischemia-reperfusion (I/R) injury. During cold storage, the graft organ is subjected to cold ischemia, also known as hypoxia injury. After reperfusion, although hypoxic condition has been ameliorated, reoxygenation of the graft liver can produce not only reperfusion injury including generation of oxygen free radical, lipoperoxidation and calcium overload, but also aggravate the hypoxia damage, involving endothelial cell (EC) damage, Kupffer cell (KC) activation, and adherence of neutrophils and platelets to Ecs. Clinically, I/R injury is one of the major problems complicating liver transplantation, and can ultimately result in serious complications such as primary nonfunction and delayed graft function, which may lead to the need of urgent retransplantation. Therefore, the therapeutic strategies of attenuating graft I/R injury are clinically significant and might improve overall graft function and survival.

  2. Targeting collagen expression in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Kyle J Thompson; Iain H McKillop; Laura W Schrum

    2011-01-01

    Alcoholic liver disease (ALD) is a leading cause of liver disease and liver-related deaths globally, particularly in developed nations. Liver fibrosis is a consequence of ALD and other chronic liver insults, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Liver fibrosis is characterized by accumulation of excess extracellular matrix components, including type Ⅰ collagen, which disrupts liver microcirculation and leads to injury. To date, there is no therapy for the treatment of liver fibrosis; thus treatments that either prevent the accumulation of type Ⅰ collagen or hasten its degradation are desirable. The focus of this review is to examine the regulation of type Ⅰ collagen in fibrogenic cells of the liver and to discuss current advances in therapeutics to eliminate excessive collagen deposition.

  3. INTRATHYMIC INOCULATION OF LIVER SPECIFIC ANTIGEN ALLEVIATES LIVER TRANSPLANT REJECTION

    Institute of Scientific and Technical Information of China (English)

    贾长库; 郑树森; 朱有法

    2004-01-01

    Objective To study the effects of liver specific antigen (LSA) on liver allotransplantation rejection. Methods Orthotopic liver transplantation was performed in this study. Group Ⅰ: syngeneic control (Wistar-to-Wistar); Group Ⅱ: acute rejection (SD-to-Wistar). Group Ⅲ: thymic inoculation of SD rat LSA day 7 before transplantation. The observation of general condition and survival time, rejection grades and the NF-κB activity of splenocytes were used to analyze severity of acute rejection and immune state of animals in different groups. Results The general condition of group Ⅰ was fair post transplantation with no sign of rejection. All recipients of group Ⅱ died within days 9 to 13 post transplantation with median survival time of 10.7 ±1.37 days. As for group Ⅲ, 5 out of 6 recipients survived for a long period with remarkably better general condition than that of group Ⅱ. Its rejection grades were significantly lower than group Ⅱ (P< 0.05).NF-κB activity was only detected in group Ⅰ between days 5 and 7 after transplantation, whereas high activity of NF-κB was detected at all points in group Ⅱ and low NF-κB activity was detected in group Ⅲ which was significantly lower than that of group Ⅱ (P < 0.05). Conclusions LSA is an important transplantation antigen directly involved in the immunorejection of liver transplantation. Intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation,grafts survive for a period of time thereby, allowing a novel way to liver transplantation immunotolerance.

  4. Advancesincellsourcesofhepatocytesfor bioartiifcial liver

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Pan; Lan-Juan Li

    2012-01-01

    BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartiifcial liver (BAL) shows great potential as an alternative therapy for liver failure. In recent years, progress has been made in BAL regarding genetically  engineered  cell  lines,  immortalized  human hepatocytes, methods for preserving the phenotype of primary human hepatocytes, and other functional hepatocytes derived from stem cells. DATA SOURCES: A systematic search of PubMed and ISI Web of Science was performed to identify relevant studies in English language literature using the key words such as liver failure, bioartiifcial liver, hepatocyte, stem cells, differentiation, and immortalization. More than 200 articles related to the cell sources of hepatocyte in BAL were systematically reviewed. RESULTS: Methods for preserving the phenotype of primary human hepatocytes have been successfully developed. Many genetically  engineered  cell  lines  and  immortalized  human hepatocytes have also been established. Among these cell lines, the incorporation of BAL with GS-HepG2 cells or alginate-encapsulated HepG2 cells could prolong the survival time and improve pathophysiological parameters in an animal model of liver failure. The cBAL111 cells were evaluated using the AMC-BAL bioreactor, which could eliminate ammonia and lidocaine, and produce albumin. Importantly, BAL loading with  HepLi-4  cells  could  signiifcantly  improve  the  blood biochemical parameters, and prolong

  5. Learning to program the liver.

    Science.gov (United States)

    Klaassen, Curtis D

    2014-01-01

    Half a century ago, people were learning to program computers. Similarly, we have been trying to learn how to program the liver to protect us from chemicals. We have given various chemicals that activate transcription factors such as the nuclear receptors: These ligand-activated nuclear receptors enter the nucleus of liver cells (hepatocytes) and bind to their specific motifs in DNA to increase the transcription of various genes that protect against chemical-induced injury. Several examples from our laboratory are given to demonstrate this detoxification process: (a) a steroid chemical that increases the expression of a hepatic transporter to enhance the elimination of other chemicals and thus decrease their toxicity, (b) a metal that decreases its own toxicity by increasing the production of a protein to which it binds, and (c) an herbal chemical that activates a transcription factor that serves as a sensor of oxidative stress and electrophiles to protect against cytotoxicity by increasing the expression of numerous antioxidant proteins. In addition, at the present time, we are investigating which bile acids that are synthesized in the liver and altered by bacteria in the intestine may be used to alter the programming of the liver, as well as how the liver reprograms itself after birth in the transition from a hematopoietic organ to one that decreases the toxicity of chemicals.

  6. Focal liver lesions found incidentally

    Institute of Scientific and Technical Information of China (English)

    Abdullah; A; Algarni; Abdullah; H; Alshuhri; Majed; M; Alonazi; Moustafa; Mabrouk; Mourad; Simon; R; Bramhal

    2016-01-01

    Incidentally found focal liver lesions are a commonfinding and a reason for referral to hepatobiliary service.They are often discovered in patients with history of liver cirrhosis,colorectal cancer,incidentally during work up for abdominal pain or in a trauma setting.Specific points should considered during history taking such as risk factors of liver cirrhosis;hepatitis,alcohol consumption,substance exposure or use of oral con-traceptive pills and metabolic syndromes.Full blood count,liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease.Imaging should start with B-mode ultrasound.If available,contrast enhanced ultrasound is a feasible,safe,cost effective option and increases the ability to reach a diagnosis.Contrast enhanced computed tomography should be considered next.It is more accurate in diagnosis and better to study anatomy for possible operation.Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity.If doubt still remains,the options are biopsy or surgical excision.

  7. Current advances in liver surgery

    Directory of Open Access Journals (Sweden)

    Shannon Melissa Chan

    2015-01-01

    Full Text Available Hepatobiliary surgery has taken a big step forward in recent decades especially in the minimally invasive approach for hepatectomy. From being sceptical at the beginning of the 1990s when laparoscopic surgery had become prevalent, to now, where laparoscopic hepatectomy has been well-established, especially in minor hepatectomies; this new technique has evolved rapidly over the past 20-years demonstrating better short-term outcomes and equivalent oncological outcomes in selected patients and in expert hands. Laparoscopic hepatectomy is indeed, more difficult to master than the open procedure with restrictions in working space, difficulty in haemostasis and the potential risk of gas embolism. However, with better visibility of the operative field around the liver, especially beneath the costal margin, the magnified view and theoretical advantage of pneumoperitoneum acting as haemostatic pressure have made laparoscopic hepatectomy increasingly popular. Another important advancement is the new surgical technique of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS. This procedure induces more rapid liver hypertrophy within a median period of 9-days, allowing resection to be performed in candidates with borderline functional liver remnant and at an earlier date. However, studies have shown that ALPPS is associated with a relatively higher rate of morbidity and mortality. Therefore, it remains a highly controversial treatment option and more studies have to be performed to establish its usefulness and define its role in liver surgery.

  8. Malnutrition, liver damage, and cancer.

    Science.gov (United States)

    Grasso, P

    1981-01-01

    There is no clear indication that malnutrition, per se, is a principal cause of cancer in man, but the prevalence of liver cancer in areas where malnutrition exists supports this hypothesis. Liver damage and liver cancer have been induced in laboratory rats by diets consisting of peanut meal and proteins deficient in some essential amino acids. However, liver damage, but not cancer, was produced when the diets contained no peanut meal but consisted of a mixture of amino acids deficient in methionine and cysteine, so that it is possible that aflatoxin, a contaminant of peanut meal, may have been responsible for the malignancies seen in the earlier experiments. Liver cancer developes in a high proportion of mice allowed to feed ad libitum or given a diet containing a high proportion of fat (groundnut oil) or protein (casein). Dietary restriction reduced the incidences of this cancer. This findings lends some support to current thinking that diet may be a factor in the development of cancer in man.

  9. Hemostatic abnormalities in liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Kendal YALÇIN

    2009-06-01

    Full Text Available In this study, 44 patients with liver cirrhosis were investigated for hemostatic parameters. Patients with spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome and cholestatic liver diseases were excluded. Patients were classified by Child-Pugh criterion and according to this 4 patients were in Class A, 20 in Class B and 20 in C. Regarding to these results, it was aimed to investigate the haematological disturbances in liver cirrhotic patients.In the result there was a correlation between activated partial thromboplastin time, serum iron, ferritin, transferrin, haptoglobin and Child-Pugh classification. Besides there was no correlation between prothrombin time, factor 8 and 9, protein C and S, anti-thrombin 3, fibrinogen, fibrin degradation products, serum iron binding capacity, hemoglobin, leukocyte, mean corpuscular volume and Child-Pugh classification.There were significant difference, in terms of AST, ferritin, haptoglobulin, sex and presence of ascites between groups (p0.05. In the summary, we have found correlation between hemostatic abnormalities and disease activity and clinical prognosis in patients with liver cirrhosis which is important in the management of these patients. This is also important for identification of liver transplant candidiates earlier.

  10. 13.2.Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930313 Clinical research of portal hyperten-sion and relatives in liver cirrhosis.QIU Rihuo(仇日火),et al.175th Hosp,PLA,Chin J Digest1992;12 (4):220—222.Potral vein pressure (PVP) of portal vein hy-pertension (PVH) was studied in 40 patients ofcirrhosis guided by ultrasound with thin needlepereutaneous transhepatic measurement.The re-sults indicated that PVP were negatively corre-lated with liver volume,and correlated withspleen volume,degree of classification child’s

  11. Decorin prevents the development of CCl4-induced liver fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    Ma Rui; He Shilin; Liang Xiao; Yu Hong; Liang Yuelong; Cai Xiujun

    2014-01-01

    Background Liver fibrosis normally progresses to cirrhosis and destroys the normal architecture of the liver,resulting in liver dysfunction and irreversible cirrhosis.The aim of this study was to investigate the anti-fibrosis effect and the possible underlying mechanisms of decorin.Methods The mice model of liver fibrosis was induced by intraperitoneal injection of 50% (v/v) of carbon tetrachloride (CCl4) diluted in olive oil (1 ml/kg body weight) once every 2 days for 5 weeks.Three weeks after injecting CCl4 intraperitoneally,mice were randomly divided into normal control with vehicles only (olive oil),mouse model given CCl4 only,and CCl4 plus decorin (DCN,250 μg/kg).Two weeks later,all the mice were sacrificed and their liver tissues were analyzed for the expressions of genes related to liver fibrosis and under hematoxylin-eosin staining,Masson staining,and immunohistochemical staining of all groups.Aspartate transaminase,alanine transaminase,and total bilirubin of the serum were determined for evaluation of the liver function.Results Exogenous protein decorin could reduce liver fibrosis induced by CCl4 in mice.The degree of fibrosis in the experimental group was alleviated,and the contents of collagen fibers were lower in the experimental group than those of the control group.In addition,expressions of transforming growth factor β1 and α-smooth muscle actin decreased in the experimental group.Conclusions Taking liver fibrosis model of mouse as the experimental target and by injecting exogenous protein decorin into the model,we confirmed that decorin could inhibit the expression of proteins related to fibrosis and reduce the formation of liver fibrosis in mice.

  12. 不同碳链长度n-3脂肪酸及脂肪水平对罗非鱼生长、肝功能和餐后血液指标的影响%Effects of n-3 Fatty Acids with Different Carbon Chain Lengths and Lipid Levels on Growth, Liver Function and Postprandial Blood Indices of Tilapia (Oreochromis niloticus)

    Institute of Scientific and Technical Information of China (English)

    林鑫; 李法见; 林仕梅; 彭祥和; 朱旺明

    2015-01-01

    An 8-week feeding trial was conducted to evaluate the effects of n-3 fatty acids with different carbon chain lengths and lipid levels on growth, liver function and postprandial blood indices of tilapia ( Oreochromis niloticus) . Four experimental diets were formulated containing either 5% fish oil ( low level of fish oil) , 10%fish oil ( high level of fish oil) , 5% linseed oil ( low level of linseed oil) or 10% linseed oil ( high level of lin-seed oil ) on the basis of practical diet formulation. A total of 360 tilapia with the initial body weight of (43.70±1.06) g were randomly distributed into 4 groups with 3 replicates per group and 30 fish per replicate, and the fish in each group were randomly fed one of four experimental diets. The results showed that no signifi-cant differences were found in finial body weight ( FBW) , specific growth rate ( SGR) , feed conversion ratio (FCR) and protein efficiency ratio (PER) of fish among all groups (P>0.05), but the feed intake (FI) in low level of linseed oil group was significantly lower than that in high level of linseed oil group ( P0.05) . Hepatopancreas malondialdehyde ( MDA) content showed a trend of high level of fish oil group>high level of linseed oil group>low level of fish oil group>low level of linseed oil group, and the difference among all groups was significant (P0.05), but the hepatopancreas SOD activity in low level of fish oil group was significantly higher than that in high level of fish oil group ( P0.05),但高水平亚麻籽油组的摄食量显著低于低水平亚麻籽油组( P0.05)。肝胰脏丙二醛( MDA)含量表现为高水平鱼油组>高水平亚麻籽油组>低水平鱼油组>低水平亚麻籽油组,且组间差异极显著( P0.05),而低水平鱼油组肝胰脏SOD活性显著高于高水平鱼油组( P<0.05)。由此可见,不同碳链长度n-3脂肪酸及脂肪水平不会影响罗非鱼的生长,但会影响其肝功能以及餐后血液指标。

  13. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    ) and an increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

  14. The Complement System in Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Xuebin Qin; Bin Gao

    2006-01-01

    The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors.Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases.

  15. Liver toxicity of rosuvastatin therapy

    Institute of Scientific and Technical Information of China (English)

    Giuseppe Famularo; Luca Miele; Giovanni Minisola; Antonio Grieco

    2007-01-01

    We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.

  16. Multicystic Hepatocarcinoma Mimicking Liver Abscess

    Directory of Open Access Journals (Sweden)

    Evangelos Falidas

    2013-01-01

    Full Text Available The diagnosis of hepatocellular carcinoma (HCC became easier in relation to the improved radiological examinations; however, the neoplasm may occur under atypical presentations mimicking other benign or malignant processes. Multicystic HCC mimicking a liver abscess associated with septic-type fever and leukocytosis is rare, has a poor prognosis, and poses diagnostic and therapeutic dilemmas. We present the case of an 80-year-old patient, who presented with fever, leukocytosis, and large cystic masses involving right and left lobes of the liver initially considered abscesses and finally diagnosed as HCC after open drainage and liver biopsy. Although the patient died on the tenth postoperative day due to pulmonary oedema, the authors emphasize the high index of suspicion needed in the diagnosis of this unusual presentation of HCC.

  17. Hepatoprotective Activity of Herbal Composition SAL, a Standardize Blend Comprised of Schisandra chinensis, Artemisia capillaris, and Aloe barbadensis

    Science.gov (United States)

    Yimam, Mesfin; Jiao, Ping; Moore, Breanna; Hong, Mei; Cleveland, Sabrina; Chu, Min; Jia, Qi; Lee, Young-Chul; Kim, Hyun-Jin; Nam, Jeong-Bum; Kim, Mi-Ran; Hyun, Eu-Jin; Jung, Gayoung; Do, Seon Gil

    2016-01-01

    Some botanicals have been reported to possess antioxidative activities acting as scavengers of free radicals rendering their usage in herbal medicine. Here we describe the potential use of “SAL,” a standardized blend comprised of three extracts from Schisandra chinensis, Artemisia capillaris, and Aloe barbadensis, in mitigating chemically induced acute liver toxicities. Acetaminophen and carbon tetrachloride induced acute liver toxicity models in mice were utilized. Hepatic functional tests from serum collected at T24 and hepatic glutathione and superoxide dismutases from liver homogenates were evaluated. Histopathology analysis and merit of blending 3 standardized extracts were also confirmed. Statistically significant and dose-correlated inhibitions in serum ALT ranging from 52.5% (p = 0.004) to 34.6% (p = 0.05) in the APAP and 46.3% (p < 0.001) to 29.9% (p = 0.02) in the CCl4 models were observed for SAL administered at doses of 400–250 mg/kg. Moreover, SAL resulted in up to 60.6% and 80.2% reductions in serums AST and bile acid, respectively. The composition replenished depleted hepatic glutathione in association with an increase of hepatic superoxide dismutase. Unexpected synergistic protection from liver damage was also observed. Therefore, the composition SAL could be potentially utilized as an effective hepatic-detoxification agent for the protection from liver damage. PMID:27066270

  18. Hepatoprotective Activity of Herbal Composition SAL, a Standardize Blend Comprised of Schisandra chinensis, Artemisia capillaris, and Aloe barbadensis

    Directory of Open Access Journals (Sweden)

    Mesfin Yimam

    2016-01-01

    Full Text Available Some botanicals have been reported to possess antioxidative activities acting as scavengers of free radicals rendering their usage in herbal medicine. Here we describe the potential use of “SAL,” a standardized blend comprised of three extracts from Schisandra chinensis, Artemisia capillaris, and Aloe barbadensis, in mitigating chemically induced acute liver toxicities. Acetaminophen and carbon tetrachloride induced acute liver toxicity models in mice were utilized. Hepatic functional tests from serum collected at T24 and hepatic glutathione and superoxide dismutases from liver homogenates were evaluated. Histopathology analysis and merit of blending 3 standardized extracts were also confirmed. Statistically significant and dose-correlated inhibitions in serum ALT ranging from 52.5% (p=0.004 to 34.6% (p=0.05 in the APAP and 46.3% (p<0.001 to 29.9% (p=0.02 in the CCl4 models were observed for SAL administered at doses of 400–250 mg/kg. Moreover, SAL resulted in up to 60.6% and 80.2% reductions in serums AST and bile acid, respectively. The composition replenished depleted hepatic glutathione in association with an increase of hepatic superoxide dismutase. Unexpected synergistic protection from liver damage was also observed. Therefore, the composition SAL could be potentially utilized as an effective hepatic-detoxification agent for the protection from liver damage.

  19. Successful transplantation of human hepatic stem cells with restricted localization to liver using hyaluronan grafts.

    Science.gov (United States)

    Turner, Rachael A; Wauthier, Eliane; Lozoya, Oswaldo; McClelland, Randall; Bowsher, James E; Barbier, Claire; Prestwich, Glenn; Hsu, Edward; Gerber, David A; Reid, Lola M

    2013-02-01

    Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.

  20. Pediatric Liver Transplantation: Our Experiences

    Science.gov (United States)

    Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha

    2016-01-01

    Objective: The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Materials and Methods: Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. Results: In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months–17 years). The 4 most common reasons for liver transplantation were: Wilson’s disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. Conclusion: The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature. PMID:28149148

  1. Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage

    Science.gov (United States)

    Schreiter, Thomas; Sowa, Jan-Peter; Schlattjan, Martin; Treckmann, Jürgen; Paul, Andreas; Strucksberg, Karl-Heinz; Baba, Hideo A.; Odenthal, Margarete; Gieseler, Robert K.; Gerken, Guido; Arteel, Gavin E.; Canbay, Ali

    2016-01-01

    Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period. Three liver sections incubated with low-dose acetaminophen revealed strong damage, with ICG half-lives significantly higher than in non-treated livers. In addition, the release of microRNA-122 was significantly higher in acetaminophen-treated than in non-treated livers. Thus, this model allows for investigation of hepatotoxicity in human liver tissue upon applying drug concentrations relevant in patients. PMID:27550092

  2. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  3. Gene expression profiles in liver cancer and normal liver tissues

    Institute of Scientific and Technical Information of China (English)

    Lian Xin Liu; Hong Chi Jiang; An Long Zhu; Jin Zhou; Xiu Qin Wang; Min Wu

    2000-01-01

    AIM To describe a liver cancer = specific gene expression profile and to identify genes that showed alteredexpression between liver cancer tissues and their adjacent nearly normal tissues.METHODS The cDNA probes which were labeled with a-32P dATP were synthesized from total RNA ofliver cancer and adjacent normal tissues and hybridized separately to two identical Atlas human cancer eDNAexpression array membranes containing 588 known genes.RESULTS Autoradiographic results were analyzed by specific Atlas ImageTM (version 1. 0) software.Among the 588 genes analyzed, 18 genes were found up-regulated in cancer, including TFDP2, Aktl, E2F-3etc, and 25 genes were down-regulated in cancer, including TDGF1, BAK, LAR, etc. Expression levels ofgenes that associated with the regulation of cell proliferation, apoptosis, differentiation, cell-cellinteraction, invasion regulators and eytokines altered mostly.CONCLUSION The result obtained from Atlas microarray provides a comprehensive liver cancer-specificexpression profile. The results can lead to the identification of liver cancer-specific biomarkers and may behelpful in early diagnosis and dentifiction of target genes for designing rational therapeutic strategies.

  4. LIVER MORPHOLOGICAL CHANGES IN SHEEP INFESTED FROM LIVER FLUKE

    Directory of Open Access Journals (Sweden)

    N. Papaioannou

    2012-06-01

    Full Text Available Fascioliasis and dicroceliosis are pathologies very often found in animals, and mostly in small ruminants. They can be found in many places around the world. We get reports quite often about their presence on herds, mostly on those of grazing arrangement in Albania. Infestations from Fasciola hepatica and Dicrocelium dentricum in sheep cause not only health damage but considerable economical losses because of affection on blegtoral products. This study’s goal is the presence of these parasites and the macroscopical and microscopical interpretation of lesions in liver, as well as. We have randomly sampled 224 sheep livers in different Tirana slaughterhouses. The animals were of the different origin. The examination showed that 39 (17.4% livers were infested with Dicrocelium dentricum and 29.9 % of animals were infested with Fasciola hepatica. In 22.2% of samples with presence of these parasites, Fasciola hepatica and Dicrocelium dentricum accompany each-other. From macroscopic examination resulted livers with hemorrhage, fibrosis, hyperplasia of bile ducts etc. From microscopic examination, portal inflammation, hyperplasia, fibrosis, presence of parasites and their eggs in the lumen of bile ducts may be distinguished.

  5. Autophagy and Liver Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Raffaele Cursio

    2015-01-01

    Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

  6. Dichlorvos Exposure Results in Large Scale Disruption of Energy Metabolism in the Liver of the Zebra Fish, Danio Rerio

    Science.gov (United States)

    2015-10-24

    proteins involved in glucose metabolism was profoundly affected, suggesting that carbon flux might be diverted toward the pentose phosphate pathway to...To obtain a broader understanding of the effects of dichlorvos on liver metabolism , we per- formed a genome-wide analysis of gene expression in the...liver dysfunction [8, 25]. Our functional analysis revealed enrichment for processes in- volved in glutathione metabolism , suggesting that DDVP

  7. Carbonate aquifers

    Science.gov (United States)

    Cunningham, Kevin J.; Sukop, Michael; Curran, H. Allen

    2012-01-01

    Only limited hydrogeological research has been conducted using ichnology in carbonate aquifer characterization. Regardless, important applications of ichnology to carbonate aquifer characterization include its use to distinguish and delineate depositional cycles, correlate mappable biogenically altered surfaces, identify zones of preferential groundwater flow and paleogroundwater flow, and better understand the origin of ichnofabric-related karst features. Three case studies, which include Pleistocene carbonate rocks of the Biscayne aquifer in southern Florida and Cretaceous carbonate strata of the Edwards–Trinity aquifer system in central Texas, demonstrate that (1) there can be a strong relation between ichnofabrics and groundwater flow in carbonate aquifers and (2) ichnology can offer a useful methodology for carbonate aquifer characterization. In these examples, zones of extremely permeable, ichnofabric-related macroporosity are mappable stratiform geobodies and as such can be represented in groundwater flow and transport simulations.

  8. Primary sclerosing cholangitis and liver transplantation

    NARCIS (Netherlands)

    Klompmaker, IJ; Haagsma, EB; Jansen, PLM; Slooff, MJH

    1996-01-01

    Primary sclerosing cholangitis is a chronic disease, strongly associated with ulcerative colitis and cholangiocarcinoma. Ulcerative colitis itself does not influence the liver transplant results. However; intensified screening after liver transplantation for carcinoma of the colon may be necessary.

  9. More Evidence Linking Obesity to Liver Cancer

    Science.gov (United States)

    ... fullstory_161494.html More Evidence Linking Obesity to Liver Cancer And type 2 diabetes more than doubles the ... type 2 diabetes, may raise your risk for liver cancer, a new study suggests. "We found that each ...

  10. Pathophysiology of Non Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Petta, Salvatore; Gastaldelli, Amalia; Rebelos, Eleni; Bugianesi, Elisabetta; Messa, Piergiorgio; Miele, Luca; Svegliati-Baroni, Gianluca; Valenti, Luca; Bonino, Ferruccio

    2016-01-01

    The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation. PMID:27973438

  11. Perfusion magnetic resonance imaging of the liver

    Institute of Scientific and Technical Information of China (English)

    Choon; Hua; Thng; Tong; San; Koh; David; J; Collins; Dow; Mu; Koh

    2010-01-01

    Perfusion magnetic resonance imaging (MRI) studies quantify the microcirculatory status of liver parenchyma and liver lesions, and can be used for the detection of liver metastases, assessing the effectiveness of antiangiogenic therapy, evaluating tumor viability after anticancer therapy or ablation, and diagnosis of liver cirrhosis and its severity. In this review, we discuss the basic concepts of perfusion MRI using tracer kinetic modeling, the common kinetic models applied for analyses, the MR scanning t...

  12. Does breast feeding influence liver biochemistry?

    DEFF Research Database (Denmark)

    Jørgensen, Marianne Hørby; Ott, Peter; Juul, Anders

    2003-01-01

    It is assumed that early feeding can affect liver biochemistry because breast-fed infants have a higher risk of hyperbilirubinemia than formula-fed infants. The authors sought to determine how feeding mode affected liver biochemistry in healthy term infants.......It is assumed that early feeding can affect liver biochemistry because breast-fed infants have a higher risk of hyperbilirubinemia than formula-fed infants. The authors sought to determine how feeding mode affected liver biochemistry in healthy term infants....

  13. Mechanisms of platelet-mediated liver regeneration.

    Science.gov (United States)

    Lisman, Ton; Porte, Robert J

    2016-08-04

    Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.

  14. Erythropoietin stimulates hepatocyte regeneration after liver resection

    OpenAIRE

    Schön, Michael R.; Hogrebe, Esther; Hengstler, Jan Georg; Donaubauer, Bernd; Faber, Sonya C.; Bauer, Alexander; Pietsch, Uta-Carolin; Jelkmann, Wolfgang; Thiery, Joachim; Hauss, Johann Peter; Tannapfel, Andrea

    2008-01-01

    The increased relevance of liver surgery and transplantation as a therapeutic modality over the last two decades mandates the development of novel strategies to improve liver regeneration. Here we studied whether erythropoietin (EPO) improves liver regeneration after hepatectomy in pigs. Eighteen female pigs underwent laparoscopic left lateral liver resection and were allocated randomly into three groups. No EPO was administered to the control group (group 1, n=6). Group 2 (...

  15. Multidisciplinary imaging of liver hydatidosis

    Institute of Scientific and Technical Information of China (English)

    Gianluca Marrone; Francesca Crino'; Settimo Caruso; Giuseppe Mamone; Vincenzo Carollo; Mariapina Milazzo; Salvatore Gruttadauria

    2012-01-01

    Liver hydatidosis is a parasitic endemic disease affecting extensive areas in our planet,a significant stigma within medicine to manage because of its incidence,possible complications,and diagnostic involvements.The diagnosis of liver hydatidosis should be as fast as possible because of the relevant complications that may arise with disease progression,involving multiple organs and neighboring structures causing disruption,migration,contamination.The aim of this essay is to illustrate the role of imaging as ultrasonography (US),multi detector row computed tomography,and magnetic resonance imaging (MRI) in the evaluation of liver hydatidosis:the diagnosis,the assessment of extension,the identification of possible complications and the monitoring the response to therapy.US is the screening method of choice.Computed tomography (CT) is indicated in cases in which US is inadequate and has high sensitivity and specificity for calcified hydatid cysts.Magnetic resonance is the best imaging procedure to demonstrate a cystic component and to show a biliary tree involvement.Diagnostic tests such as CT and MRI are mandatory in liver hydatidosis because they allow thorough knowledge regarding lesion size,location,and relations to intrahepatic vascular and biliary structures,providing useful information for effective treatment and decrease in post-operative morbidity.Hydatid disease is classified into four types on the basis of their radiologic appearance.

  16. Transplantation in autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marcus Mottershead; James Neuberger

    2008-01-01

    Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A variety of approaches to selection and allocation have been developed and vary from country to country.The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs;these include splitting grafts,use of extended criteria livers,livers from nonheart-beating donors and from living donors.Post transplantation, most patients will need life-long immunosuppression,although a small proportion can have immunosuppression successfully withdrawn.Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in sideeffects and so improve the patient and graft survival.For autoimmune diseases, transplantation is associated with significant improvement in the quality and length of life.Disease may recur after transplantation and may affect patient and graft survival.

  17. Treatment of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Colorectal cancer (CRC is the third most common cancer in the word. Liver metastasis is the most common site of colorectal metastases. The prognosis of resectable colorectal liver metastases (CRLM was improved in the recent years with the consideration of chemotherapy and surgical resection as part of the multidisciplinary management of the disease; the current 5-year survival rates after resection of liver metastases are 25% to 40%. Resectable synchronous or metachronous liver metastases should be treated with perioperative chemotherapy based on three months of FOLFOX4 (5-fluorouracil [5FU], folinic acid [LV], and oxaliplatin chemotherapy before surgery and three months after surgery. In the case of primary surgery, pseudo-adjuvant chemotherapy for 6 months, based on 5FU/LV, FOLFOX4, XELOX (capecitabine and oxaliplatin or FOLFIRI (5FU/LV and irinotecan, should be indicated. In potentially resectable disease, primary chemotherapy based on more intensive regimens such as FOLFIRINOX (5FU/LV, irinotecan and oxaliplatin should be considered to enhance the chance of cure. The palliative chemotherapy based on FOLFIRI, or FOLFOX4/XELOX with or without targeted therapies, is the mainstay treatment of unresectable disease. This review would provide additional insight into the problem of optimal integration of chemotherapy and surgery in the management of CRLM.

  18. Liver Flukes: the Malady Neglected

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Hoon [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected.

  19. Investigations on Collectin Liver 1

    DEFF Research Database (Denmark)

    Axelgaard, Esben; Jensen, Lisbeth; Dyrlund, Thomas Franck;

    2013-01-01

    Collectins are pattern recognition molecules of the innate immune system showing binding to carbohydrate structures on microorganisms in a calcium-dependent manner. Recently, three novel collectins, collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1 and CL-11), and collectin placenta 1 (CL-P1...

  20. Liver Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  1. Kidney transplantation after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Li-Yang Wu; Hang Liu; Wei Liu; Han Li; Xiao-Dong Zhang

    2016-01-01

    Kidney transplantation after liver transplanta-tion (KALT) offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efifcacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplanta-tion because of calcineurin inhibitor (CNI)-induced neph-rotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses, maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them. Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival.

  2. The "liver-first approach" for patients with locally advanced rectal cancer and synchronous liver metastases.

    NARCIS (Netherlands)

    Verhoef, C.; Pool, A.E. van der; Nuyttens, J.J.; Planting, A.S.; Eggermont, A.M.M.; Wilt, J.H.W. de

    2009-01-01

    PURPOSE: This study was designed to investigate the outcome of "the liver-first" approach in patients with locally advanced rectal cancer and synchronous liver metastases. METHODS: Patients with locally advanced rectal cancer and synchronous liver metastases were primarily treated for their liver me

  3. Assessment of liver volume with spiral computerized tomography scanning: predicting liver volume by age and height

    Directory of Open Access Journals (Sweden)

    Madhu Sharma

    2016-07-01

    Conclusions: Liver volume is a reliable index of liver size and measurement of liver volume with spiral CT is useful method. Spiral CT can be utilized for measurement of liver volume for such purpose. [Int J Res Med Sci 2016; 4(7.000: 3020-3023

  4. Liver protein expression in dairy cows with high liver triglycerides in early lactation

    DEFF Research Database (Denmark)

    Sejersen, Henrik; Sørensen, Martin Tang; Larsen, Torben;

    2012-01-01

    in the liver proteome between early lactation dairy cows with a low or high liver TG content. The liver proteome analysis indicated that a high liver TG content in early lactation dairy cows is associated with increased oxidation of saturated fatty acids, oxidative stress, and urea synthesis...

  5. Factors influencing liver and spleen volume changes after donor hepatectomy for living donor liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Ji Hee; Ryeom, Hunku; Song, Jung Hup [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2013-11-15

    To define the changes in liver and spleen volumes in the early postoperative period after partial liver donation for living-donor liver transplantation (LDLT) and to determine factors that influence liver and spleen volume changes. 27 donors who underwent partial hepatectomy for LDLT were included in this study. The rates of liver and spleen volume change, measured with CT volumetry, were correlated with several factors. The analyzed factors included the indocyanine green (ICG) retention rate at 15 minutes after ICG administration, preoperative platelet count, preoperative liver and splenic volumes, resected liver volume, resected-to-whole liver volume ratio (LV{sub R}/LV{sub W}), resected liver volume to the sum of whole liver and spleen volume ratio [LV{sub R}/(LV{sub W} + SV{sub 0})], and pre and post hepatectomy portal venous pressures. In all hepatectomy donors, the volumes of the remnant liver and spleen were increased (increased rates, 59.5 ± 50.5%, 47.9 ± 22.6%). The increment rate of the remnant liver volume revealed a positive correlation with LV{sub R}/LV{sub W} (r = 0.759, p < 0.01). The other analyzed factors showed no correlation with changes in liver and spleen volumes. The spleen and remnant liver volumes were increased at CT volumetry performed 2 weeks after partial liver donation. Among the various analyzed factors, LV{sub R}/LV{sub W} influences the increment rate of the remnant liver volume.

  6. Ochrobactrum intermedium infection after liver transplantation

    NARCIS (Netherlands)

    Moller, LVM; Arends, JP; Harmsen, HJM; Talens, A; Terpstra, P; Slooff, MJH

    1999-01-01

    A case of bacteremia due to Ochrobactrum intermedium, with concomitant liver abscesses, in an orthotopic liver transplant recipient is presented. Identical microorganisms were isolated from fecal specimens and from an aspirate of a liver abscess that was indicative of invasion of the graft by gastro

  7. Liver diseases and aging : friends or foes?

    NARCIS (Netherlands)

    Sheedfar, Fareeba; Di Biase, Stefano; Koonen, Debby; Vinciguerra, Manlio

    2013-01-01

    The liver is the only internal human organ capable of natural regeneration of lost tissue, as little as 25% of a liver can regenerate into a whole liver. The process of aging predisposes to hepatic functional and structural impairment and metabolic risk. Therefore, understanding how aging could affe

  8. Liver surgery: Imaging and image guided therapies

    NARCIS (Netherlands)

    M.G. van Vledder (Mark)

    2012-01-01

    textabstractThe liver is the most common site of malignant tumors in patients worldwide, including both primary (hepatocellular carcinoma) and metastatic liver cancer (eg colorectal liver metastases). Complete resection or thermal ablation of all tumor deposits currently offers the only potentially

  9. Aspects of the regulation of liver lipase

    NARCIS (Netherlands)

    G.C. Schoonderwoerd (Kees)

    1986-01-01

    textabstractIt is evident that factors that influence the activity of liver lipase could be important because of the role of liver lipase in HDL-cholesterol metabolism. At the start of this study not much was known about the regulation of liver lipase. The activity had been found to be decreased aft

  10. Primary pleomorphic sarcoma of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Mani, S.; Naik, L.; Shet, S.; Vora, I.M.; Rananavare, R. [BYL Nail Hospital, Bombay (India). Departments of Radiology and Pathology

    1998-02-01

    A 35-year-old woman presented with abdominal distension and a palpable liver mass. Ultrasonography and computed tomography revealed a large well-delineated liver mass with bilobar involvement. Based on autopsy and immunohistochemical findings, a final diagnosis of primary pleomorphic liver sarcoma with myogenic differentiation W established. Copyright (1998) Blackwell Science Pty Ltd 8 refs., 5 figs.

  11. Plasma Glutamine Concentrations in Liver Failure.

    Directory of Open Access Journals (Sweden)

    Gunnel Helling

    Full Text Available Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations.Four different groups of patients were studies; chronic liver failure (n = 40, acute on chronic liver failure (n = 20, acute fulminant liver failure (n = 20, and post-hepatectomy liver failure (n = 20. Child-Pugh and Model for End-stage Liver Disease (MELD scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion.All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100, severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong.Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure.

  12. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

    Liu, Jianping; Kjaergard, Lise Lotte; Als-Nielsen, Bodil;

    2002-01-01

    Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure.......Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure....

  13. Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells.

    Science.gov (United States)

    Kim, Kang Ho; Lee, Jae Man; Zhou, Ying; Harpavat, Sanjiv; Moore, David D

    2016-08-01

    Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis. In the carbon tetrachloride hepatotoxin-induced fibrosis model, both steroidal and nonsteroidal GR ligands suppressed expression of fibrotic genes and decreased extracellular matrix deposition but also inhibited immune cell infiltration and exacerbated liver injury. These counteracting effects of GR ligands were dissociated in mice with conditional GR knockout in immune cells (GR(LysM)) or HSC (GR(hGFAP)): the impacts of dexamethasone on immune cell infiltration and liver injury were totally blunted in GR(LysM) mice, whereas the suppression of fibrotic gene expression was diminished in GR(hGFAP) mice. The effect of GR activation in HSC was further confirmed in the LX-2 HSC cell line, in which antifibrotic effects were mediated by GR ligand inhibition of Sma and mad-related protein 3 (SMAD3) expression. We conclude that GR has differential roles in immune cells and HSCs to modulate liver injury and liver fibrosis. Specific activation of HSC-GR without alteration of GR activity in immune cells provides a potential therapeutic approach to treatment of hepatic fibrosis.

  14. Glutathione metabolism and glucose 6-phosphate dehydrogenase activity in experimental liver injury.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-12-01

    Full Text Available Increased activities of liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44 in the pentose phosphate cycle were accompanied with a depletion of reduced glutathione (GSH following an intragastric administration of carbon tetrachloride (CCl4 to rats. Oxidized glutathione (GSSG also decreased remarkably, keeping the GSSG: GSH ratio constant. No significant alteration of glutathione reductase (EC 1.6.4.2., glutathione peroxidase (EC 1.11.1.9 and malic enzyme (EC 1.1.1.40 activities in the supernatant and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2 activity in the homogenate of the injured liver were observed. Furthermore, no marked difference in the GSH-synthesizing activity was found between control and CCl4-intoxicated liver. An intraperitoneal injection of GSH produced a significant increase in liver GSH content in control rats but not in CCl4-treated rats; G6PD activity was not affected. Intraperitoneal injections of diethylmaleate resulted in continuously diminished levels of liver GSH without any alteration of liver G6PD activity. In vitro disappearance of GSH added to the liver homogenate from CCl4-treated rats occurred enzymatically and could not be prevented by the addition of a NADPH-generating system. The results suggest that increased G6PD activity in CCl4-injured liver does not play an important role in the maintenance of glutathione in the reduced form and that the decreased GSH content in the injured liver might be caused by enhanced GSH catabolism not due to gamma-GTP.

  15. Carbon classified?

    DEFF Research Database (Denmark)

    Lippert, Ingmar

    2012-01-01

    How does a corporation know it emits carbon? Acquiring such knowledge starts with the classification of environmentally relevant consumption information. This paper visits the corporate location at which this underlying element for their knowledge is assembled to give rise to carbon emissions. Us...

  16. Porous carbons

    Indian Academy of Sciences (India)

    Satish M Manocha

    2003-02-01

    Carbon in dense as well as porous solid form is used in a variety of applications. Activated porous carbons are made through pyrolysis and activation of carbonaceous natural as well as synthetic precursors. Pyrolysed woods replicate the structure of original wood but as such possess very low surface areas and poor adsorption capacities. On activation, these exhibit increased adsorption volumes of 0.5–0.8 cm3 /gm and surface areas of 700–1800 m2 /gm depending on activation conditions, whether physical or chemical. Former carbons possess mixed pore size distribution while chemically activated carbons predominantly possess micropores. Thus, these carbons can be used for adsorption of wide distributions of molecules from gas to liquid. The molecular adsorption within the pores is due to single layer or multilayer molecule deposition at the pore walls and hence results in different types of adsorption isotherm. On the other hand, activated carbon fibres with controlled microporous structure and surface area in the range of 2500 m2 /gm can be developed by controlled pyrolysis and physical activation of amorphous carbon fibres. Active carbon fibres with unmatchable pore structure and surface characteristics are present and futuristic porous materials for a number of applications from pollution control to energy storage.

  17. Carbon photonics

    Energy Technology Data Exchange (ETDEWEB)

    Konov, V I [A M Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow (Russian Federation)

    2015-11-30

    The properties of new carbon materials (single-crystal and polycrystalline CVD diamond films and wafers, single-wall carbon nanotubes and graphene) and the prospects of their use as optical elements and devices are discussed. (optical elements of laser devices)

  18. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

    Liu, J P; Gluud, L L; Als-Nielsen, B;

    2004-01-01

    Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery.......Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery....

  19. EVALUATION OF CIRRHOTIC LIVER WITH PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING: A PRELIMINARY EXPERIMENTAL STUDY IN ANIMAL MODELS WITH HALF-LIVER CIRRHOSIS

    Institute of Scientific and Technical Information of China (English)

    Zheng-han Yang; Xiao-hua Ye; Ye Tan; Min Zhang; Ming-zhu Zhou; Jing-xia Xie; Min Chen; Cheng Zhou

    2006-01-01

    Objective To investigate the role of perfusion-weighted magnetic resonance imaging (MRI) in evaluation of cirrhotic liver.Methods With a 4F catheter,1% diluted carbon tetrachloride (1 ml/kg) was selectively injected into right or left hepatic artery of 12 dogs fortnightly.The half liver into which carbon tetrachloride was injected was called as study side (SS),while the other half liver without carbon tetrachloride injection was called as study control side (SCS).Conventional and perfusion-weighted MRI were performed in every 4 weeks.Via a 4F catheter,5ml gadolinium diethylentriamine pentaaceti acid (Gd-DTPA) dilution was injected into superior mesenteric artery at the 5th scan.The signal intensity-time curves of SS,SCS,and portal vein were completed in MR workstation.The maximal relative signal increase (MRSI),peak time (tp),and slope of the curves were measured.Results On conventional MR images,no abnormalities of externality and signal intensity were observed in both SS and SCS of liver at each stage.The mean tp,MRSI,and slope of intensity-time curves in normal liver were 10.56 seconds,1.01,and 10.23 arbitrary unit (au)/s,respectively.Three parameters of curves didn't show obvious change in SCS of liver at every stage.Abnormal perfusion curves occurred in SS of liver at the 12th week after the 1st injection.The abnormality of perfusion curve in SS was more and more serious as the times of injection increased.The mean tp,MRSI,and slope intensity-time curves in SS of liver were 19.45 seconds,0.43,and 3.60 au/s respectively at the 24th week.Conclusion Perfusion-weighted imaging can potentially provide information about portal perfusion of hepatic parenchyma,and to some degree,reflect the severity of cirrhosis.

  20. Carbon-Carbon Piston Architectures

    Science.gov (United States)

    Rivers, H. Kevin (Inventor); Ransone, Philip O. (Inventor); Northam, G. Burton (Inventor); Schwind, Francis A. (Inventor)

    2000-01-01

    An improved structure for carbon-carbon composite piston architectures is disclosed. The improvement consists of replacing the knitted fiber, three-dimensional piston preform architecture described in U.S. Pat.No. 4,909,133 (Taylor et al.) with a two-dimensional lay-up or molding of carbon fiber fabric or tape. Initially, the carbon fabric of tape layers are prepregged with carbonaceous organic resins and/or pitches and are laid up or molded about a mandrel, to form a carbon-fiber reinforced organic-matrix composite part shaped like a "U" channel, a "T"-bar, or a combination of the two. The molded carbon-fiber reinforced organic-matrix composite part is then pyrolized in an inert atmosphere, to convert the organic matrix materials to carbon. At this point, cylindrical piston blanks are cored from the "U"-channel, "T"-bar, or combination part. These blanks are then densified by reimpregnation with resins or pitches which are subsequently carbonized. Densification is also accomplished by direct infiltration with carbon by vapor deposition processes. Once the desired density has been achieved, the piston billets are machined to final piston dimensions; coated with oxidation sealants; and/or coated with a catalyst. When compared to conventional steel or aluminum alloy pistons, the use of carbon-carbon composite pistons reduces the overall weight of the engine; allows for operation at higher temperatures without a loss of strength; allows for quieter operation; reduces the heat loss; and reduces the level of hydrocarbon emissions.