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Sample records for cirrhotic rat liver

  1. Activity of glycogen synthase and glycogen phosphorylase in normal and cirrhotic rat liver during glycogen synthesis from glucose or fructose.

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    Bezborodkina, Natalia N; Chestnova, Anna Yu; Okovity, Sergey V; Kudryavtsev, Boris N

    2014-03-01

    Cirrhotic patients often demonstrate glucose intolerance, one of the possible causes being a decreased glycogen-synthesizing capacity of the liver. At the same time, information about the rates of glycogen synthesis in the cirrhotic liver is scanty and contradictory. We studied the dynamics of glycogen accumulation and the activity of glycogen synthase (GS) and glycogen phosphorylase (GP) in the course of 120min after per os administration of glucose or fructose to fasted rats with CCl4-cirrhosis or fasted normal rats. Blood serum and liver pieces were sampled for examinations. In the normal rat liver administration of glucose/fructose initiated a fast accumulation of glycogen, while in the cirrhotic liver glycogen was accumulated with a 20min delay and at a lower rate. In the normal liver GS activity rose sharply and GPa activity dropped in the beginning of glycogen synthesis, but 60min later a high synthesis rate was sustained at the background of a high GS and GPa activity. Contrariwise, in the cirrhotic liver glycogen was accumulated at the background of a decreased GS activity and a low GPa activity. Refeeding with fructose resulted in a faster increase in the GS activity in both the normal and the cirrhotic liver than refeeding with glucose. To conclude, the rate of glycogen synthesis in the cirrhotic liver is lower than in the normal one, the difference being probably associated with a low GS activity.

  2. Safe upper limit of intermittent hepatic inflow occlusion for liver resection in cirrhotic rats

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    Dao-Xiong Lei; Cheng-Hong Peng; Shu-You Peng; Xian-Chuan Jiang; Yu-Lian Wu; Hong-Wei Shen

    2001-01-01

    AIM To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion.``METHODS Hepatic ischemia in cirrhotic rats was induced by clamping the common pedicle of left and median lobes after non-ischemic lobes resection. The cirrhotic rats were divided into six groups according to the duration and form of vascular clamping: sham occlusion (SO),intermittent occlusion for 10 (IO-10), 15(IO-15). 20(IO-20)and 30(IO-30) minutes with 5 minutes of refiow andcontinuous occlusion for 60 minutes (CO-60). All animals received a total duration of 60 minutes of hepatic inflow occlusion. Liver viability was investigated in relation of hepatic adenylate energy charge ( EC ).Triphenyltetrazollum chloride (TTC) reduction activities were assayed to qualitatively evaluate the degree of irreversible hepatocellular injury. The biochemical and morphological changes were also assessed and a 7-day mortality was observed.``RESULTS At 60 minutes after reperfusion following atotal of 60 minutes of hepatic inflow occlusion, EC values in lO-L0 (0.749±:0.012) and IO-15 (0.699 ±0.002) groups were rapidly restored to that in SO group (0. 748± 0.016).TTC reduction activities remained in high levels (0. 144 ±0.002 mg/mg protein, 0. 139 + 0.003 mg/mg protein and 0.121 ± 0.003 mg/mg protein in SO, IO-10 and IO-15groups, respectively). But in IO-20 and IO-30 groups, EC levels were partly restored (0.457 ± 0.023 and 0.534 ±0.027) accompanying with a significantly decreased TTCreduction activities (0.070 ± 0.005 mg/mg protein and 0.061 ±0.003 rng/mg protein). No recovery in EC values , i).228 ± 0.004) and a progressive decrease in TTC reduction activities ( 0.03.3 ± 0.002 mg/mg protein) were shown in CO-60 group. Although not significantly different, the activities of the serum aspartate aminotransferase (AST) on the third postoperative day (POD3 ) and POD7 and of the serum alanineaminotransferase

  3. Changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate early changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation (OLT) in normal and cirrhotic rats. Methods Male Sprague-Dawley rats were divided into 4 groups:normal controls (NL,n=10),intrahepatic portal hypertension (IHPH, n=10) induced by injection of CCl4, normal rats with OLT (NL-OLT,n=9) and IHPH rats with OLT (IHPH-OLT,n=16). IHPH-OLT rots were divided into 2 subgroups: 3 days (Group A, n=9) and 7 days (Group B, n=7) after OLT. OLT was pedormed in rats using cuffs for the anastomosis of the suprahepatic inferior vena cava,infrahepatic vena cava and portal vein. Two weeks after production of IHPH rots, 7 days after NL-OLT rats, 3 days and 7 days after IHPH-OLT rats, radicective microspheres were used in a hemodynamic study. Results There were no significant differences in hemodynamic changes between NL-OLT and NL rets, except mean arterial blood pressure (MAP).The characteristies of systemic and splanchnic hyperdynamic circulatory slate,including increased cardiac output and splanchnic blood flow, decreased mean acterial blood pressure, total peripheral vascular resistance and splanchnic vascular resistance were ibserved in IHPH, IHPH-OLT A, and IHPH-OLT B rats,The magnitude of hyperhemodynamics was in the order of IHPH>IHPH-OLT A>IHPH-OLT B rats. Moreover, the derangement of splanchnic hyper hemodynamice was more significant than that of systemic hyperhemodynamics. Conclusioos The present study demonstrates that the persistence of early systemic and splanchnic hyperkinetic circulation after OLT may be the consequence of factors which maintain hyperhemo dynamics in liver cirrhosis, where portal hypertension is not completely eliminated. Hyperhemodynamics is not induced by OLT per se.

  4. [Enzyme levels and morphological picture of normal and cirrhotic rat livers following portal vein ligation and subcutaneous transposition of the spleen].

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    Zelder, O; Dorn, R; Bürcklein, H H; Bode, Ch; Bode, J C; Jerusalem, C R

    1975-01-01

    The effect of portal vein ligation after subcutaneous transposition of the spleen is investigated on enzyme-activities. and morphological pattern of the normal and cirrhotic rat-liver. The increase of glycolytic enzyme-activities and the decrease of enzyme-activities of oxidative metabolic pathways can be explained by adaptation on throttled blood supply of the liver. Significant decrease of arginase-activity (urea-cycle) can not be explained by reduced protein content of food (pair-fed-animals). Diminished substrate (ammonia)-level (NH3/t/hepatocytes) may be an explanation. Histological pattern of normal and cirrhotic rat liver is nearly unchanged after portal vein ligation.

  5. Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

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    Tripathi, Dinesh M; Erice, Eva; Lafoz, Erica; García-Calderó, Héctor; Sarin, Shiv K; Bosch, Jaime; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2015-09-01

    Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (α-smooth muscle actin, platelet-derived growth factor receptor β polypeptide, transforming growth factor-βR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation.

  6. VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Francois Labrousse; Yves Denizot

    2006-01-01

    @@ TO THE EDITOR We read with a great interest the recent work of Deli and colleagues.[1] in the World Journal of Gastroenterology reporting vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and cirrhotic liver tissues.

  7. Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

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    Fatemeh Sarhadi Kholari

    2016-11-01

    Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

  8. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

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    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  9. Effects of lactulose on intestinal endotoxin and bacterial translocation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    张顺财; 王唯; 任卫英; 戴茜; 贺伯明; 周康

    2003-01-01

    Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats. Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of 51 Cr in the intestine. Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT was closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which was closely associated with increased intestinal transit and improved intestinal permeability by lactulose. Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

  10. CONCENTRATION AND HEMODYNAMICS PATTERN CHANGES IN CIRRHOTIC RATS

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    黄颖秋; 萧树东; 莫剑忠; 张德中

    2000-01-01

    Objective To investigate the effects of hemoglobin (Hb) on serum nitric oxide (NO) concentration and hemodynamics pattern changes in rats with cirrhosis. Methods Cirrhosis model was induced in male SD rats by injection of 60% CCl4 oily solution subcutaneously. Cirrhotic rats were treated with erythropoietin (l00U/kg) injected subcutaneously for 2 weeks. Mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR), splanchnic blood flow (SBF) and serum NO concentration were determined in erythropoietin - treated, erythropoietin - untreated cirrhotic rats and controls by using 57Co- labelled microsphere technique and a fluorometric assay, respectively. In addition, blood Hb levels were also measured in the 3 groups. Results Untreated cirrhotic rats had significantly lower MAP, SVR, Hb and higher CO, CI, SBF and NO concentration than those of the controls (P<0.01). In treated cirrhotic rats, erythropoietin significantly attenuated the increase of CO, CI, SBF, NO concentration and the decrease of MAP and SVR. In cirrhotic rats,epoetin beta in subcutaneous dose of 100U· kg-1· d-1 induced a markedly increment of blood Hb levels and decrement of NO concentration in comparison with untreated cirrhotic rats (181±11g/L vs 120±15g/L;1.14±0.62μmol/L vs 4.20±1.25μmol/L). Conclusion The endogenous NO may play an important role in the changes of hemodynamics pattern in cirrhosis, and hyperdynamic circulatory status in rats with cirrhosis might be ameliorated by inactivation of overproduced NO by increasing hemoglobin with erythropoietin.

  11. Hepatocellular carcinoma (HCC) in non-cirrhotic liver: clinical, radiological and pathological findings

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    Di Martino, Michele; Di Miscio, Rossella; Lombardo, Concetta Valentina; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Department of Radiological Sciences, Oncology and Anatomical Pathology, Rome (Italy); Saba, Luca; Piga, Mario [Department of Radiology Azienda Ospedaliera Universitaria (A.O.U.), Monserrato (Italy); Bosco, Sandro [University of Rome ' ' Sapienza' ' , Department of Molecular Medicine, Rome (Italy); Rossi, Massimo [University of Rome ' ' Sapienza' ' , Department of General Surgery, Division of Organ Transplantation, Rome (Italy); Miles, Kirchin A. [Worldwide Medical and Regulatory Affairs, Milan (Italy); Tamponi, Elisabetta [Azienda Ospedaliera Universitaria (A.O.U.), Department of Anatomical Pathology, Monserrato (Italy)

    2014-07-15

    Our aim was to evaluate the clinical and pathological findings, mutidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) appearances, treatment and 1-year survival of patients with HCC in non-cirrhotic liver. Histopathological and laboratory findings of 30 non-cirrhotic patients with 32 HCCs were reviewed retrospectively. MDCT and gadobenate dimeglumine-enhanced MR images were evaluated in consensus by two radiologists in terms of HCC size, presence of tumour capsule, necrosis, haemorrhage, fat and calcification, and vascular involvement. Imaging patterns were compared directly with HCC findings in a matched group of cirrhotic patients. No differences between non-cirrhotic and cirrhotic patients were noted in terms of serum α-fetoprotein levels (elevated in 11 [36.7 %] and 21 [35 %] patients, respectively). The imaging appearance at CT and contrast-enhanced MRI was typical in 27 (84.3 %) and 28 (87.5 %) cases respectively. Most lesions presented as a well-differentiated large solitary mass, with well-defined margins, areas of necrosis and peripheral capsule. No significant differences in HCC pattern were observed between cirrhotic and non-cirrhotic liver. In non-cirrhotic patients, HCC is more likely to manifest as an asymptomatic mass with elevation of serum tumour markers similar to that seen in cirrhotic patients. HCC in cirrhotic and non-cirrhotic livers show similar enhancement patterns. (orig.)

  12. Prevalence of simple liver cysts and hemangiomas in cirrhotic and non-cirrhotic patients submitted to magnetic resonance imaging

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    Breno Victor Tomaz Galvao

    2013-07-01

    Full Text Available Objective To determine the prevalence of liver cysts and hemangiomas in the general population and in cirrhotic patients. Materials and Methods Retrospective, observational, and cross-sectional study selecting consecutive magnetic resonance imaging studies performed in the period from February to July 2011. A total of 303 patients (187 women and 116 men with mean age of 53.3 years were included in the present study. Patients with previously known liver lesions were excluded. The images were consensually analyzed by two observers in the search for simple liver cysts and typical liver hemangiomas, according to universally accepted imaging criteria. Lesions prevalence, diameters and location were determined in both cirrhotic and non-cirrhotic individuals. Results The authors observed prevalence of 8.6% for hemangiomas and 14.5% for simple cysts. No statistically significant difference was observed in relation to prevalence of hemangiomas and cysts among cirrhotic and non-cirrhotic patients (p = 0.954; p = 0.472. Conclusion In the present study, the prevalence of cysts and hemangiomas was higher than the prevalence reported by autopsy series. No influence of cirrhosis was observed on the prevalence and appearance of such incidental lesions.

  13. Melatonin protects the liver and erythrocytes against oxidative stress in cirrhotic rats Melatonina protege o fígado e eritrócitos do estresse oxidativo em ratos cirróticos

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    Darlan Pase da Rosa

    2010-03-01

    Full Text Available CONTEXT: Cirrhosis is a progressive chronic hepatopathy which constitutes an irreversible stage of liver dysfunction. OBJECTIVES: To evaluate the oxidative stress in the blood of cirrhotic rats treated with the antioxidant melatonin. METHODS: Cirrhosis was induced through inhalation of carbon tetrachloride. Liver integrity was evaluated by measuring serum enzymes, oxidative damage measured by lipoperoxidation, and antioxidant enzyme activity in erythrocytes. Lipoperoxidation, total nitrates, collagen, and histology by picrosirius staining were evaluated in the livers of these animals (n = 15, which were divided in three groups: control, carbon tetrachloride, and carbon tetrachloride + melatonin. Melatonin (20 mg/kg was administered intraperitoneal from week 10 of carbon tetrachloride inhalation. In order to shorten the cirrhosis induction time, phenobarbital (0.3 g/L was added to the animals' drinking water. RESULTS: A significant impairment in the liver integrity of melatonin-treated animals as compared to cirrhotic animals was observed. In rat erythrocytes and liver, lipoperoxidation was significantly increased in the cirrhotic rats as compared to controls, as measured through thiobarbituric acid reactive substances, and significantly decreased in melatonin-treated animals as compared to cirrhotic ones. In blood, a decrease in superoxide dismutase and glutathione peroxidase enzymes was detected in the cirrhotic group as compared to the control group, with increased superoxide dismutase activity when melatonin was administered. A reduction in the levels of total nitrates was detected in the hepatic tissue of the animals in the carbon tetrachloride group as compared to the control group and an increase of these levels in the carbon tetrachloride + melatonin group. As for hepatic collagen, we found a significant increase in the carbon tetrachloride group as compared to the controls and a regression of these values in the treated group. In

  14. Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats

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    Hao Xu; Bao-Min Shi; Xiao-Fei Lu; Feng Liang; Xing Jin; Tai-Huang Wu; Jian Xu

    2008-01-01

    AIM: To investigate the effect of vascular endothelial growth factor (VEGF) transfection on hepatic sinusoidal capillarization.MEthODS: Enhanced green fluorescent protein (EGFP)/VEGF transfection was confirmed by immunofluorescencemicroscopy and immunohistoche-mistry both in primaryhepatocytes and in normal liven Cirrhotic rats weregenerated by thioacetamide (TAA) administration andthen divided into a treatment group, which receivedinjections of 400 μg of plasmid DNA encoding an EGFP-VEGF fusion protein, and a blank group, which receivedan equal amount of normal saline through the portalvein. The portal vein pressure was measured in the normal and cirrhotic state, in treated and blank groups.The average number of fenestrae per hepatic sinusoidwas determined using transmission electron microscopy(TEM), while the relative abundance of VEGF transcriptswas examined by Gene array.RESULTS: Green fluorescent protein was observed in the cytoplasms of liver cells under immunofluorescence microscopy 24 h after transfection with EGFP/VEGFplasmid in vitro. Staining with polyclonal antibodies against VEGF illustrated that hepatocytes expressed immunodetectable VEGF both in vitro and in vitro. There were significant differences in the number of fenestrae and portal vein pressures between normal and cirrhotic rats (7.40±1.71 vs 2.30± 2.26 and 9.32± 0.85 cmH2Ovs 27.92± 0.90 cmH2O1, P < 0.02), between cirrhotic and treated rats (2.30 + 1.16 cmH2O vs 4.60± 1.65 and 17.92± 0.90 cmH2O vs 15.52±0.93 cmH20, P < 0.05)and between the treatment group and the blank group (4.60±1.65 cmH20 vs 2.10 ± 1.10 cmH20 and 25.52 +0.93 cmH20 vs 17.26 ± 1.80 cmH20, P < 0.05). Gene-array analysis revealed that the relative abundance oftranscripts of VEGF family members decreased in the cirrhotic state and increased after transfection. CONCLUSION: Injection of a plasmid encoding VEGFthrough the portal vein is an effective method toinduce the formation of fenestrae and decrease portalvein

  15. Effects of raloxifene on portal hypertension and hepatic encephalopathy in cirrhotic rats.

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    Chang, Ching-Chih; Lee, Wen-Shin; Chuang, Chiao-Lin; Hsin, I-Fang; Hsu, Shao-Jung; Chang, Ting; Huang, Hui-Chun; Lee, Fa-Yauh; Lee, Shou-Dong

    2017-05-05

    Raloxifene, a selective estrogen receptor modulator, has been used extensively for osteoporosis. In addition to the effect of osteoporosis treatment, emerging evidences show that raloxifene affects the vascular function in different tissues. Cirrhosis is characterized with portal hypertension and complicated with hepatic encephalopathy. Portal hypertension affects portal-systemic shunt which leads to hepatic encephalopathy that the vascular modulation might influence severity of hepatic encephalopathy. Herein, we evaluated the impact of raloxifene on bile duct ligation (BDL)-induced cirrhotic rats. The female Sprague-Dawley rats received BDL plus ovariectomy or sham-operation. Four weeks later, rats were divided into 2 subgroups respectively to receive of raloxifene (10mg/kg/day) or saline (vehicle) for 14 days. On the 43th day, motor activities and hemodynamic parameters were measured. Hepatic and vascular mRNA and protein expressions were determined. The histopathological change of liver was examined. We found that the liver biochemistry, ammonia level and motor activity were similar between cirrhotic rats with or without raloxifene administration. The hemodynamic parameters were not significantly different except that raloxifene reduced portal venous inflow. Raloxifene exacerbated hepatic fibrosis and up-regulated hepatic endothelin-1 and cyclooxygenase 2 protein expressions. In addition, raloxifene modulated the mRNA expressions of endothelial nitric oxide synthase, cyclooxygenase and endothelin-1 in the superior mesenteric artery and collateral vessel. In conclusion, raloxifene aggravates hepatic fibrosis and decreases portal venous inflow in cirrhotic rats without adversely affecting portal hypertension and hepatic encephalopathy. The modulation of hepatic and vascular endothelin-1, endothelial nitric oxide synthase and cyclooxygenase expressions may play a role in the mechanism.

  16. Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

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    Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka

    2016-01-01

    BACKGROUND: Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics......, and compared it to human NCIPH. METHODS: Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one...... in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. DISCUSSION: This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies....

  17. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

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    Seo, J.M. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, S.J., E-mail: lucia@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, S.H. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, C.K.; Ha, S.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-04-15

    Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

  18. Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

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    Gemma (ò)dena; Mireia Miquel; Anna Serafín; Amparo Galan; Rosa Morillas; Ramon Planas; Ramon Bartolí

    2012-01-01

    AIM:To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis; Cirrhosis + IGF-1;Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters (bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.

  19. Hepatic venous oxygen content in alcoholic cirrhosis and non-cirrhotic alcoholic liver disease

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    Bendtsen, F; Henriksen, Jens Henrik Sahl; Widding, A

    1987-01-01

    Blood gas analyses and hepatic blood flow were determined during hepatic vein catheterization in order to establish a possible hypoxic component in alcoholic liver disease. Fifty-six patients (9 non-cirrhotic liver disease, 14 cirrhosis Child-Turcotte class A, 23 class B, 10 class C) and 10 control...

  20. Increase of Serum gamma-Glutamyltransferase Associated With Development of Cirrhotic Cystic Fibrosis Liver Disease

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    Bodewes, Frank A. J. A.; van der Doef, Hubert P. J.; Houwen, Roderick H. J.; Verkade, Henkjan J.

    2015-01-01

    Background:Identification of patients at risk for developing cirrhotic cystic fibrosis liver disease (CCFLD) is essential for targeting potentially preventive treatment. We studied the evolution of serum liver enzymes and thrombocyte counts as predictors of CCFLD development.Methods:For this study,

  1. Effect of early propranolol administration on portal hypertensive gastropathy in cirrhotic rats

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    Savas Rafailidis; Charalampos Demertzidis; Konstantinos Ballas; Michail Alatsakis; Nikolaos Symeonidis; Theodoros Pavlidis; Kyriakos Psarras; Valentini Tzioufa-Asimakopoulou; Athanassios Sakadamis

    2009-01-01

    AIM: To investigate any protective effect of early propranolol administration in the development of portal hypertensive gastropathy in cirrhotic rats. METHODS: For the development of liver cirrhosis and portal hypertensive gastropathy, 60 rats underwent ligation of the left adrenal vein and complete devascularization of the left renal vein, followed by phenobarbital and carbon tetrachloride (CCl4) administration. After two weeks of CCl4 administration, the rats were randomly separated into two groups. In group A, propranolol was continuously administered intragastrically throughout the study, whereas in group B normal saline (placebo) was administered instead. Hemodynamic studies and vascular morphometric analysis of gastric sections were performed after complete induction of cirrhosis. RESULTS: Vascular morphometric studies showed higher numbers of vessels in all mucosal layers in the control group. Statistical analysis revealed a significantly higher total vascular surface in the control group compared to the propranolol group, but with no statistically significant difference between the mean vascular surfaces between the groups. Our study clearly shows that the increased mucosal blood flow is manifested by a marked increase of vessel count. CONCLUSION: Early propranolol's administration in portal hypertensive cirrhotic rats seems to prevent intense gastric vascular congestion that characterizes portal hypertensive gastropathy.

  2. HGF, MET, and matrix-related proteases in hepatocellular carcinoma, fibrolamellar variant, cirrhotic and normal liver.

    Science.gov (United States)

    Schoedel, Karen E; Tyner, Valerie Zajac; Kim, Tae-Hyoung; Michalopoulos, George K; Mars, Wendy M

    2003-01-01

    Fibrolamellar variant is an uncommon subcategory of hepatocellular carcinoma with a better prognostic outcome. Proteinases and growth factors that are involved in the remodeling of extracellular matrix may influence the behavior of cancers. To determine whether these factors contribute to the distinct etiologies of fibrolamellar hepatocellular carcinoma and traditional hepatocellular carcinoma, we assayed hepatocyte growth factor, the hepatocyte growth factor receptor, and two hepatocyte growth factor activators, hepatocyte growth factor activator and urokinase-type plasminogen activator, in hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, cirrhotic liver and normal liver. In addition, we examined the urokinase-type plasminogen activator receptor, the type 1 plasminogen activator inhibitor, plasmin, fibrinogen, and the type IV matrix metalloproteinases. Eighteen hepatocellular carcinomas and 11 fibrolamellar hepatocellular carcinomas were obtained as paraffin embedded sections from the University of Pittsburgh Department of Pathology. Frozen tissues from a subset of cases (9 hepatocellular carcinomas, 4 fibrolamellar hepatocellular carcinomas, 12 cirrhotic livers and 2 normal livers) were also available for analysis. Antibodies against urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, hepatocyte growth factor and hepatocyte growth factor receptor were used to analyze immunoperoxidase stained slides from the paraffin blocks. Western blot analyses using antibodies against hepatocyte growth factor, hepatocyte growth factor receptor, phosphotyrosine, hepatocyte growth factor activator, urokinase-type plasminogen activator receptor, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, fibrinogen and plasmin were performed on membrane-enriched fractions from the frozen tissue, as was collagen zymography for matrix metalloproteinase-2 and matrix metalloproteinase-9. The most notable findings are as

  3. Discoidin domain receptor 1: isoform expression and potential functions in cirrhotic human liver.

    Science.gov (United States)

    Song, Sunmi; Shackel, Nicholas A; Wang, Xin M; Ajami, Katerina; McCaughan, Geoffrey W; Gorrell, Mark D

    2011-03-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell-collagen interactions in chronic liver injury.

  4. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

    Institute of Scientific and Technical Information of China (English)

    Jin-Ping Li; De-Li Zhao; Hui-Jie Jiang; Ya-Hua Huang; Da-Qing Li; Yong Wan; Xin-Ding Liu; Jin-E Wang

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhoticliverdiseasebythisfastimagingmethod. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The

  5. Evaluation of the protective effects of quercetin in biliary cirrhotic rats

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    Derakhshanian H

    2013-04-01

    Full Text Available Background: Biliary cirrhosis is a chronic disease marked by the progressive destruct-tion of liver. There is no known cure for this disease; however, medications may slow its progression. The present study was designed to investigate the effect of quercetin as a plant derived flavonoid on the hepatic injury reduction of biliary cirrhotic rats.Methods: Thirty male Sprague-Dawley rats aged 6-7 months were randomized into three groups of ten each. One group served as control (sham operated, while the other two groups underwent a complete bile-duct ligation (BDL. Four weeks after the opera-tion, serum bilirubin, alkaline phosphatase (ALP, alanine amino-transferase (ALT, and aspartate amino-transferase (AST were measured in two BDL groups to confirm the occurrence of cirrhosis. Then one of the BDL groups received placebo and the other one injected intraperitoneally with 50mg/kg of quercetin once a day for a period of four weeks. At the end of the study, hepatic enzymes and serum bilirubin were measured again. Liver species were tested for histological characteristics.Results: Quercetin could decrease serum level of bilirubin (7.4±0.9 vs. 8.9±1.6 mg/dL; P<0.05, ALP (1387±76.9 vs. 2273±65.3 IU/L; P<0.001 and ALT (601.9±38.1 vs. 644.8±37.4 IU/L; P<0.05 compared to cirrhotic group. AST was higher in cirrhotic groups compared to control both in the 4th and 8th week. However, the difference between BDL and BDL+Q groups was not statistically significant. Quercetin decreased ALT/AST ratio, as an indicator of liver damage. No significant histological changes were observed in quercetin group.Conclusion: These data suggest that although quercetin did not change histological characteristics of liver, it could significantly decrease bilirubin, alkaline phosphatase and alanine amino-transferase, indicating less liver injury.

  6. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients

    Science.gov (United States)

    Araújo, Oscar C.; Rosa, Agatha S.; Fernandes, Arlete; Niel, Christian; Villela-Nogueira, Cristiane A.; Pannain, Vera; Araujo, Natalia M.

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer mortality worldwide. Most cases of HCC are associated with cirrhosis related to chronic hepatitis B virus or hepatitis C virus infections. Hypermethylation of promoter regions is the main epigenetic mechanism of gene silencing and has been involved in HCC development. The aim of this study was to determine whether aberrant methylation of RASSF1A and DOK1 gene promoters is associated with the progression of liver disease in Brazilian patients. Methylation levels were measured by pyrosequencing in 41 (20 HCC, 9 cirrhotic, and 12 non-cirrhotic) liver tissue samples. Mean rates of methylation in RASSF1A and DOK1 were 16.2% and 12.0% in non-cirrhotic, 26.1% and 19.6% in cirrhotic, and 59.1% and 56.0% in HCC tissues, respectively, showing a gradual increase according to the progression of the disease, with significantly higher levels in tumor tissues. In addition, hypermethylation of RASSF1A and DOK1 was found in the vast majority (88%) of the HCC cases. Interestingly, DOK1 methylation levels in HCC samples were significantly higher in the group of younger (<40 years) patients, and higher in moderately differentiated than in poorly differentiated tumors (p < 0.05). Our results reinforce the hypothesis that hypermethylation of RASSF1A and DOK1 contributes to hepatocarcinogenesis and is associated to clinicopathological characteristics. RASSF1A and DOK1 promoter hypermethylation may be a valuable biomarker for early diagnosis of HCC and a potential molecular target for epigenetic-based therapy. PMID:27078152

  7. EXHALED AND PLASMA NITRITE: a comparative study among healthy, cirrhotic and liver transplant patients

    Directory of Open Access Journals (Sweden)

    Viviane S AUGUSTO

    2014-03-01

    Full Text Available Context There is a relative lack of studies about exhaled nitrite (NO2- concentrations in cirrhotic and transplanted patients. Objective Verify possible differences and correlations between the levels of NO2-, measured in plasma and exhaled breath condensate collected from patients with cirrhosis and liver transplant. Method Sixty adult male patients, aged between 27 and 67 years, were subdivided into three groups: a control group comprised of 15 healthy volunteers, a cirrhosis group composed of 15 volunteers, and a transplant group comprised of 30 volunteers. The NO2- concentrations were measured by chemiluminescence. Results 1 The analysis of plasma NO2- held among the three groups showed no statistical significance. 2 The comparison between cirrhotic and control groups, control and transplanted and cirrhotic and transplanted was not statistically significant. 3 The measurements performed on of NO2- exhaled breath condensate among the three groups showed no statistical difference. 4 When comparing the control group samples and cirrhotic, control and transplanted and cirrhotic and transplanted, there was no significant changes in the concentrations of NO2-. Conclusion No correlations were found between plasma and exhaled NO2-, suggesting that the exhaled NO2- is more reflective of local respiratory NO release than the systemic circulation.

  8. Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease:Potential mechanistic pathways

    Institute of Scientific and Technical Information of China (English)

    Ryan; B; Perumpail; Andy; Liu; Robert; J; Wong; Aijaz; Ahmed; Stephen; A; Harrison

    2015-01-01

    Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.

  9. Doppler study of hepatic vein in cirrhotic patients: Correlation with liver dysfunction and hepatic hemodynamics

    Institute of Scientific and Technical Information of China (English)

    KC Sudhamshu; Shoiichi Matsutani; Hitoshi Maruyama; Taro Akiike; Hiromitsu Saisho

    2006-01-01

    AIM: To elucidate the significance of Doppler measurements of hepatic vein in cirrhotic patients and to correlate with liver dysfunction and hepatic hemodynamics.METHODS: One hundred patients with liver cirrhosis and 60 non-cirrhotic controls were studied. Doppler waveforms were obtained from right hepatic vein and flow velocity measured during quiet respiration. Doppler measurements were also obtained from portal trunk,right portal vein and proper hepatic artery.RESULTS: Hepatic vein waveforms were classified into three classical patterns. Flat waveform was uncommon.Mean hepatic vein velocity was significantly higher in cirrhotic patients (12.7 ± 6.4 vs 5.1 ± 2.1 and 6.2 ± 3.2 cm/s; P < 0.0001). The poorer the grade of cirrhosis,the higher was the mean velocity. Maximum forward velocity was never greater than 40 cm/s in controls.Degree of ascites was found to be highly correlated with mean velocity. "Very high" group (≥ 20 cm/s) presented clinically with moderate to massive ascites. Correlations between right portal flow and mean velocity was significant (P < 0.0001, r = 0.687).CONCLUSION: Doppler waveforms of hepatic vein,which is independent of liver dysfunction, should be obtained during normal respiration. Mean hepatic vein velocity reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of liver cirrhosis.

  10. [Guidelines for diagnosis and management of cirrhotic ascites and its complications. The Israeli Association for the Study of the Liver].

    Science.gov (United States)

    Sikuler, Emanuel; Ackerman, Zvi; Braun, Marius; Baruch, Yaakov; Bruck, Refael; Safadi, Rifaat; Shlomai, Amir; Ben-Ari, Ziv

    2012-12-01

    Ascites is the most common manifestation of decompensated liver cirrhosis. The life expectancy of cirrhotic patients developing uncomplicated ascites is 50% for 3 years. Refractory ascites, electrolyte imbalance, hepato-renal syndrome and spontaneous bacterial peritonitis may develop. Successful treatment can improve symptoms and outcomes. This article summarizes the Israeli Association for the Study of the Liver guidelines for diagnosis and management of cirrhotic ascites and its complications.

  11. Local regulator adrenomedullin contributes to the circulatory disturbance in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Shinya Sakurai; Hideyuki Kojima; Masahito Uemura; Hiroyasu Satoh; Hiroshi Fukui

    2006-01-01

    AIM: To investigate whether adrenomedullin, a potent vasodilator peptide, plays a role in the circulatory disturbance in cirrhosis.METHODS: Cirrhosis was induced in rats by weekly gavage of carbon tetrachloride. Hemodynamic studies were performed in vivo using radioactive microspheres andin vitro using isolated aortic rings.The adrenomedullin concentrations were measured by radioimmunoassay.RESULTS: Acute administration of adrenomedullin to the control rats reduced the systemic arterial pressure along with an increase of serum levels of the stable metabolite of nitric oxide (NOx), in a dose-dependent manner. Chronic infusion of adrenomedullin reduced the vascular resistance and increased the blood flow in the systemic and splanchnic circulation. Intravenous administration of anti-adrenomedullin antibody did not affect any hemodynamic parameters in the cirrhotic rats, whereas this antibody ameliorated the blunted contractile response to phenylephrine, a-adrenergic receptor agonist, in the aortic rings of the cirrhotic rats.The adrenomedullin concentrations in the aorta were higher in the cirrhotic rats than in the controls, and correlated with the mean arterial pressure in the cirrhotic rats. Moreover, adrenomedullin blunted the contractile response to phenylephrine in both of the control aorta and cirrhotic aorta, but not in the presence of NG-nitroL-arginine methyl ester, an NO synthase inhibitor.CONCLUSION: Adrenomedullin overproduced in the vascular wall may contribute to the circulatory disturbance in cirrhosis as a local regulator of the vascular tonus rather than a circulating hormone.

  12. Novel approaches to assessing renal function in cirrhotic liver disease.

    Science.gov (United States)

    Portal, Andrew J; Austin, Mark; Heneghan, Michael A

    2007-09-01

    Renal dysfunction is common in patients with end-stage liver disease. Etiological factors include conditions as diverse as acute tubular necrosis, immunoglobulin A nephropathy and hepatorenal syndrome. Current standard tests of renal function, such as measurement of serum urea and creatinine levels, are inaccurate as the synthesis of these markers is affected by the native liver pathology. This article reviews novel markers of renal function and their potential use in patients with liver disease.

  13. Omega-3 polyunsaturated fatty acids prevent progression of liver fibrosis and promote liver regeneration after partial hepatectomy in cirrhotic rats%ω-3多不饱和脂肪酸对肝硬化大鼠肝切除术后肝细胞再生及肝纤维化程度的影响

    Institute of Scientific and Technical Information of China (English)

    杨跃; 段飞; 蔡浩; 陈靓; 林建宇; 仇毓东

    2013-01-01

    Objective:To evaluate the effect of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on liver regeneration after hepatectomy and antifibrosis under the condition of liver cirrhosis in rats. Methods:Seventy precent hepatectomy was carried out in rats,which were subsequently divided into 4 groups: ①normal and hepatectomy group(PH) ,②liver cirrhosis and hepatectomy group(LC + PH) , ③liver cirrhosis,n-3 PUFA (1 ml/kg) and hepatectomy group (LC +n-3 PUFA[S] +PH) ,④liver cirrhosis , n-3 PUFA (2 ml/kg) and hepatectomy group (LC + n-3PUFA[ L] + PH). Body/liver weight ratios , Serum parameters, histopathological examination, immunostaining and quantification of mRNA expression were also investigated. Results:Liver regeneration in LC + PH group was significantly delayed compared with PH group 7 days after hepatectomy. On the other hand,liver regeneration in LC + n-3 PUFA[L] +PH group increased significantly. The liver fibrosis was significantly lower in the groups with use of n-3 PUFA. Conclusion: The n-3 PUFA can reduce liver fibrosis and promote liver regeneration, even under cirrhotic conditions.%目的:观察ω-3多不饱和脂肪酸(ω-3PUFA)对肝硬化大鼠70%肝切除术后肝细胞再生及肝纤维化程度的影响. 方法:将96只大鼠随机分为四组,即正常对照组(仅行70%肝切除);肝硬化对照组(肝硬化大鼠行70%肝切除);肝硬化小剂量组(肝硬化大鼠行70%肝切除后静脉注射ω-3PUFA 1 ml/kg);肝硬化大剂量组(肝硬化大鼠行70%肝切除后静脉注射ω-3PUFA 2 ml/kg).观察大鼠术后第1、3、5和7天肝细胞再生的情况,肝功能指标,残肝肝纤维化程度的变化等. 结果:与肝硬化对照组比,肝硬化大剂量组大鼠术后肝有明显的再生(P<0.05);术后第1和第3天ALT和AST有明显降低(P<0.05).术后第7天,肝硬化小剂量组和肝硬化大剂量组肝纤维化程度有明显减轻(P<0.05). 结论:ω-3PUFA不仅能促进肝硬化大鼠术后肝细胞再

  14. Hepatocyte differentiation of human fibroblasts from cirrhotic liver in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Yu-Ling Sun; Sheng-Yong Yin; Lin Zhou; Hai-Yang Xie; Feng Zhang; Li-Ming Wu; Shu-Sen Zheng

    2011-01-01

    BACKGROUND: Mesenchymal stem cells (MSCs) and fibro-blasts have intimate relationships, and the phenotypic homology between fibroblasts and MSCs has been recently described. The aim of this study was to investigate the hepatic differentiating potentialofhumanfibroblastsincirrhoticliver. METHODS: The phenotypes of fibroblasts in cirrhotic liver were labeled by biological methods. After that, the differentiation potential of these fibroblasts in vitro was characterized in terms of liver-specific gene and protein expression. Finally, an animal model of hepatocyte regeneration in severe combined immunodeficient (SCID) mice was created by retrorsine injection and partial hepatectomy, and the expression of human hepatocyte proteins in SCID mouse livers was checked by immunohistochemicalanalysisafterfibroblastadministration. RESULTS: Surface immunophenotyping revealed that a minority of fibroblasts expressed markers of MSCs and hepatic epithelial cytokeratins as well as alpha-smooth muscle actin, but homogeneously expressed vimentin, desmin, prolyl 4-hydroxylase and fibronectin. These fibroblasts presented the characteristics of hepatocytes in vitro and differentiated directly into functional hepatocytes in the liver of hepatecto-mized SCID mice. CONCLUSIONS: This study demonstrated that fibroblasts in cirrhotic liver have the potential to differentiate into hepatocyte-like cells in vitro and in vivo. Our findings infer that hepatic differentiation of fibroblasts may serve as a new target for reversion of liver fibrosis and a cell source for tissue engineering.

  15. Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Q. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China); Wang, L.X. [Department of Pharmacology, School of Medicine, Shandong University, Jinan (China); Zeng, J.P. [Department of Biochemistry, School of Medicine, Shandong University, Jinan (China); Liu, X.J.; Liang, X.M.; Zhou, Y.B. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China)

    2013-09-06

    Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.

  16. New concepts in liver cirrhosis: clinical significance of sarcopenia in cirrhotic patients.

    Science.gov (United States)

    Montano-Loza, A J

    2013-06-01

    The natural history of cirrhotic patients is highly variable due to several factors including hepatic synthetic function, presence and degree of portal hypertension, the cause of cirrhosis, the possibility of resolution of the underlying damaging process, and the occurrence of liver cancer. Currently, D'Amico stage classification and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of evaluation of the nutritional and functional status. Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, sarcopenia or severe muscle wasting is one of the most common and frequently hidden complications which negatively impact survival, quality of life, and response to stressor, such as infection and surgery. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis, and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduced morbidity related to cirrhosis. Finally, we propose that future studies including sarcopenia with the MELD score may allow better prediction of mortality among cirrhotic patients waiting for liver transplantation; however, due to the worldwide shortage of organs for transplants, one of the vital clinical questions is the feasibility to treat sarcopenia in cirrhosis without the need of liver transplant.

  17. Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic ischemia/reperfusion injury Efeito do pré-condicionamento isquêmico hepático submetidos a lesão de isquemia/reperfusão do fígado

    Directory of Open Access Journals (Sweden)

    Eduardo Garcia Pacheco

    2006-01-01

    Full Text Available PURPOSE: The main aim of this study was to determine the influence of ischemic preconditioning (IPC on rat liver cirrhosis. METHODS: Cirrhosis was induced in Wistar rats by occlusion of the hepatic duct. The animals were divided into four groups of six animals each: non-cirrhotic group (simulated operation only, cirrhotic control group (simulated operation in cirrhotic rats, I/R group (40-minute ischemia without IPC, and IPC group (cirrhotic rats with ischemia, previously submitted to IPC. The IPC procedure consisted of partial hepatic ischemia for five minutes, followed by 10 minutes of reperfusion. In the case of the IPC group, the animals were submitted to liver ischemia for 40 minutes after the preconditioning procedure, followed by 2 hours of reperfusion. Blood samples were collected for measurement of serum aminotransferases (ALT and AST. The respiratory control ratio (RCR, the mitochondrial membrane potential (MMP, and malondialdehyde (MDA values in the hepatic tissue were analyzed. Nonparametric statistical analysis was used and a value of pOBJETIVO: O objetivo deste estudo foi determinar a influência do pré-condicionamento isquêmico (IPC em fígados de ratos cirróticos. MÉTODOS: A cirrose hepática foi induzida em ratos Wistar machos (250 a 300g por oclusão, durante 30 dias, do ducto hepático comum.A seguir, os animais cirróticos foram divididos em três grupos de seis; Grupo controle cirrótico (operação simulada para isquemia/reperfusão/pré-condicionamento, Grupo I/R, isquemia de 40 minutos sem pré-condicionamento (IPC e grupo IPC com isquemia precedida por IPC. O IPC consistiu de uma isquemia parcial por cinco minutos, seguida por 10 minutos de reperfusão. No grupo IPC, após o pré-condicionamento, os animais foram submetidos à isquemia hepática de 40 minutos seguida de 2 horas de reperfusão. Foram colhidas amostras de sangue para dosagem sérica de aminotransferases (ALT e AST. Razão de controle respiratório (RCR

  18. Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats: role of cannabinoid and vanilloid receptors

    Science.gov (United States)

    Domenicali, M; Ros, J; Fernández-Varo, G; Cejudo-Martín, P; Crespo, M; Morales-Ruiz, M; Briones, A M; Campistol, J-M; Arroyo, V; Vila, E; Rodés, J; Jiménez, W

    2005-01-01

    Background and aims: Anandamide is an endocannabinoid that evokes hypotension by interaction with peripheral cannabinoid CB1 receptors and with the perivascular transient receptor potential vanilloid type 1 protein (TRPV1). As anandamide has been implicated in the vasodilated state in advanced cirrhosis, the study investigated whether the mesenteric bed from cirrhotic rats has an altered and selective vasodilator response to anandamide. Methods: We assessed vascular sensitivity to anandamide, mRNA and protein expression of cannabinoid CB1 receptor and TRPV1 receptor, and the topographical distribution of cannabinoid CB1 receptors in resistance mesenteric arteries of cirrhotic and control rats. Results: Mesenteric vessels of cirrhotic animals displayed greater sensitivity to anandamide than control vessels. This vasodilator response was reverted by CB1 or TRPV1 receptor blockade, but not after endothelium denudation or nitric oxide inhibition. Anandamide had no effect on distal femoral arteries. CB1 and TRPV1 receptor protein was higher in cirrhotic than in control vessels. Neither CB1 mRNA nor protein was detected in femoral arteries. Immunochemistry showed that CB1 receptors were mainly in the adventitia and in the endothelial monolayer, with higher expression observed in vessels of cirrhotic rats than in controls. Conclusions: These results indicate that anandamide is a selective splanchnic vasodilator in cirrhosis which predominantly acts via interaction with two different types of receptors, CB1 and TRPV1 receptors, which are mainly located in perivascular sensory nerve terminals of the mesenteric resistance arteries of these animals. PMID:15753538

  19. Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Dan-Hong Yang; Zai-Yuan Ye; Yuan-Jun Xie; Xu-Jun He; Wen-Juan Xu; Wei-Ming Zhou

    2012-01-01

    AIM:To study the effect of salvianolate on tight junctions (TJs) and zonula occludens protein 1 (ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate (12 mg/kg) treatment group,medium-dose salvianolate (24 mg/kg) treatment group,and high-dose salvianolate (48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group (P < 0.01).The number of microvilli decreased and showed

  20. Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Xin Wang; Jie Ding; Kai-Cun Wu; Bo-Rong Pan; Dai-Ming Fan; Yue-Xia Zhong; Zong-You Zhang; Ju Lu; Mei Lan; Ji-Yan Miao; Xue-Gang Guo; Yong-Quan Shi; Yan-Qiu Zhao

    2002-01-01

    AIM: To invsstigare the effect of L-NAME on nitric oxide andgastriubtestubal motility alterations in cirrhotic ratsMETHODS: Rats with cirrhosis induced by carbontetrachloride were randomly divided into two groups, one( n= 13) receiving 0. 5 mg@ kg-1 per clay of NG-nitro-L-argininemethyl ester (L-NAME), a nitric oxide synthase inhibitor,for 10 days, whereas the other group ( n = 13) and control( n = 10) rats were administrated the same volume of 9 g@ L-1saline.Half gastric emptying time and 2 h residual rate weremeasured by SPECT, using 99m Tc-DTPA-labeled bariumsuifate as test meal. Gastrointestinal transition time wasrecorded simultaneously. Serum concentration of nitrcoxide (NO) was determined by the kinetic cadmiunreduction and colorimetric methods. ImmunohistochemicalSABC method was used to observe the expression anddistribution of three types of nitric oxide synthase (NOS)isoforms in the mt gastrointestinal tract. Western blot wasused to detect expression of gastrointestinal NOS isoforms.RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged( 124.0 ± 26.4min; 33.7± 8.9min;72.1 ± 15.3 min; P<0.01), (12.4±0.5h; 9.5±0.3 h; 8.2±0.8 h; P<0.01), 2h residual rate wasraised in cirrhotic rots than in controls and cirrhotic ratstreated with L-NAME(54.9± 7.6 % ,13.7 ± 3.2 %, 34.9± 10.3%, P< 0.01). Serum concentration of NO was significantlyincreased in cirrhotic rots than in the other groups (8.20 ± 2.48)μmol@L-1, (5.94± 1.07) μmol@L-1 ,and control (5.66± 1.60) tμmol@L-1, P< 0.01. NOS staining intensities which weremainly located in the gastrointestinal tissues were markedlylower in cirrhotic rats than in the controls and cirrhotic ratsafter treated with L- NAME.CONCLUSION: Gastrointestinal motility was remarkablyinhibited in cirrhotic rats, which could he alleviated by L-NAME. Nitric oxide may play an important role in theinhibition of gastrointestinal motility in cirrhotic rats.

  1. Suppression of angiotensin II stimulated responses in aortic vascular smooth muscle cells of experimental cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Functional responses to angiotensin II(AT-II) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats.Our data showed that AT-II-stimulated extracellular acidification rate (ECAR),which was measured by Cytosesor microphysiometry,was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals.The ability of AT-II to promote formation of inositol phosphates,the second messenger produced by the activation of Gq-coupled receptors,was also considerably suppressed in the cirrhotic VSMCs.Furthermore,the maximal p42/44 MAPK phosphorylation stimulated by AT-II was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs.Taken together,our data clearly demonstrated that the functional responses to AT-II was severely suppressed in aortic VSMCs in cirrhosis,indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.

  2. Effect of sorafenib on liver regeneration after partial hepatoectomy in liver cirrhotic rats%索拉菲尼对肝硬化大鼠部分肝切除术后肝脏再生的影响

    Institute of Scientific and Technical Information of China (English)

    周小虎; 张红卫; 万云乐

    2012-01-01

    AIM:To sludy lhe effecl of sorafenib on lhe liver regeneration afler parlial hepaleclomy (PH) in cirrholic rals. METHODS: Thirly Wislar rals wilh liver cirrhosis induced successfully wilh dielhylnilrosamine (DEN) un-derwenl 30% PH and lhen were randomly divided inlo 2 groups ( n = 15 ). The rals in experimental group were fed wilh sorafenib al dose of 30 mg ? Kg-1·d-1 from lhe lsl day lo lhe l0th day afler PH, while ihose in conlrol group were fed wilh vehicle by gavage. The blood and liver lissues of lhe rals were collected afler PH and al lhe end of lhe experimenl. Liver regeneralion rale (LRR) and proliferating cell nuclear anligen (PCNA) expression were assessed for determining lhe hepatocyle proliferation. The conlent of alanine Iransaminase (ALT) , albumin (ALB) , tolal bilirubin (TBIL) , direct bili-rubin (DBIL) , angiogenesis relaled factors including vascular endolhelial growth faclor ( VEGF) , vascular endothelial growlh factor receplor 2 ( VEGFR - 2) , platelel - derived growth faclor receptor (3 ( PDGFR - (3 ) and micro - vessel densily ( MVD) were measured in both groups. RESULTS: LRRs on day 10 afler PH were 45.43% ±3.36% and 44.21% ±2.77% in experimental group and conlrol group, respectively (P>0. 05) , and lhe expression of PCNA in hepatic lissues of the rals was not found by lhe method of immunohislochemistry in bolh groups. Liver function index had no significant difference between lhe 2 groups (P >0. 05) . However, other lhan VEGF, sorafenib resulted in inhibilion of VEGFR -2 and PDGFR - (3 expression and reduction of MVD in experimenl group, and significant difference belween the 2 groups was observed (P0.05);(2)免疫组织化学(IHC)没有检测到PCNA;(3)2组的生化指标无显著差异(P>0.05);(4)实验组VEGFR-2和PDGFR-β的表达受到抑制,MVD降低,并且实验组与对照组差异有统计学意义(P<0.01).结论:索拉菲尼虽然对肝硬化血管再生相关因子有抑制作用,但是对肝细胞再生和肝功能没有明显影响.

  3. Pulmonary Complications in Cirrhotic Candidates for Liver Transplantation

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    Seiyed Mohammad Ali Ghayumi

    2010-04-01

    Full Text Available Background and Aims: The determination of the prevalence of cardiopulmonary complications at a liver transplant center in Iran.Methods: Ninety-nine patients (61 male and 38 female with a mean age of 36.5 (15-66 years with proven cirrhosis were enrolled in this study. Patients with primary cardiac disease, current smokers, those with sepsis, hepatocellular carcinoma, recently ruptured esophageal varices and chronic pulmonary or renal diseases were excluded from the study. Sixty-nine patients had ascites. Forty-four patients had grade C Child-Pugh classification. All patients were evaluated for respiratory function by chest X-ray (CXR, room air arterial blood gas, simultaneous pulse oximetry, cardiac echocardiography and spirometry. Results: Sixty-one patients (66.1% had a widened alveolar-arterial O2 difference ( > 20 mmHg; 14 (14.1% had hy- poxemia; 6 (6.1% had mean pulmonary arterial pressure (MPAP = 25-40 mmHg; 12 (12.1% had tricuspid regurgita- tion; pleural effusion and lung restriction were detected in 4 (4% and 50 (50.5%, respectively. P(A-aO2 was nega- tively associated with pulmonary hypertension (P < 0.03 and tricuspid regurgitation (P < 0.005. Portal hypertension and portal vein thrombosis were detected in 91 and 8 patients, respectively. Conclusions: A widened alveolar-arterial oxygen difference was common in our patients, but hypoxemia occurred in 14% of patients. Portopulmonary hypertension was preponderant in those patients of male gender.

  4. Hepatocellular adenoma with malignant transformation in male patients with non-cirrhotic livers

    Institute of Scientific and Technical Information of China (English)

    Song-Lin An; Jian-Xiong Wu; Li-Ming Wang; Wei-Qi Rong; Fan Wu; Wei Sun; Wei-Bo Yu; Li Feng; Fa-Qiang Liu; Fei Tian

    2015-01-01

    Introduction:Hepatocellular adenomas (HCAs), with a risk of malignant transformation into hepatocellular carcinoma (HCC), classically develop in young women who are taking oral contraceptives. It is now clear that HCAs may also occur in men. However, it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers. This study aimed to characterize the malignancy of HCAs occurring in male patients. Methods:Al patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical Col ege between January 1, 1999 and December 31, 2011 were enrolled in the study. The clinical characteristics as well as radiologic and pathologic data were reviewed. Results:HCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers, but not in female patients. The alpha-fetoprotein (AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation. The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases. The 5 patients were all alive without recurrence by the end of the study period. The disease-free survival times of the 5 patients were 26, 48, 69, 69, and 92 months. Conclusion:Our results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter, especially in male patients.

  5. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Wiese, Signe; Hove, Jens Dahlgaard; Bendtsen, Flemming;

    2014-01-01

    causes of cardiac disease. This condition is primarily revealed by inducing physical or pharmacological stress, but echocardiography is excellent at revealing diastolic dysfunction and might also be used to detect systolic dysfunction at rest. Furthermore, measurement of circulating levels of cardiac...... in relation to invasive procedures such as shunt insertion and liver transplantation. Current pharmacological treatment is nonspecific and directed towards left ventricular failure, and liver transplantation is currently the only proven treatment with specific effect on cirrhotic cardiomyopathy....

  6. The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

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    Hamed Shafaroodi

    2017-02-01

    Full Text Available  Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA, and the activities of catalase (CAT, glutathione peroxidase (GSHPx and superoxide dismutase (SOD have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with L-NAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats.

  7. PDEs1-5 activity and expression in tissues of cirrhotic rats reveal a role for aortic PDE3 in NO desensitization.

    Science.gov (United States)

    Tahseldar-Roumieh, Rima; Keravis, Thérèse; Maarouf, Suha; Justiniano, Hélène; Sabra, Ramzi; Lugnier, Claire

    2009-12-01

    Liver cirrhosis is associated with increased nitric oxide (NO) production in the vasculature. We have previously demonstrated that aorta from rats with liver cirrhosis have a reduced relaxant response to NO donors that is corrected by DMPPO, a PDE5-specific inhibitor. Vasodilator responses to DMPPO itself were also reduced in rings from cirrhotic rats. These results supported previous suggestions that upregulation of PDE5 in liver cirrhosis might contribute to renal sodium retention, and consequently modulate vascular reactivity in the context of increased NO production (Tahseldar-Roumieh et al. in Am. J. Physiol. Heart Circ. Physiol. 290, H481-H488, 2006). Here, we investigated the possible alteration in activity and expression of cyclic nucleotide phosphodiesterase PDE1-PDE5 in kidney and vascular tissues in rats 4 weeks after bile duct ligation. The kidney of rats with cirrhosis had increased activity of PDE1 and PDE4 but not PDE5, and increased expression of PDE1A. Unexpectedly and interestingly, there was no change in cirrhotic aorta PDE5, but an increase in PDE3 and PDE4 activity associated with increased expression of PDE3A and PDE3B. Cilostamide, a specific PDE3 inhibitor, corrected the decreased response to an NO donor in isolated aorta from cirrhotic rats, suggesting that the difference in response to NO donors was due to differences in PDE3-induced hydrolysis of cGMP or to cGMP-induced inhibition of PDE3, rather than to differences in PDE5 contribution. In conclusion, these changes in PDE isozymes could greatly contribute to NO desensitization and to the regulation of vascular and renal function in liver cirrhosis.

  8. Magnetic resonance imaging of the cirrhotic liver: diagnosis of hepatocellular carcinoma and evaluation of response to treatment - Part 1

    Science.gov (United States)

    Ramalho, Miguel; Matos, António P.; AlObaidy, Mamdoh; Velloni, Fernanda; Altun, Ersan; Semelka, Richard C.

    2017-01-01

    Magnetic resonance imaging (MRI) is the modern gold standard for the noninvasive evaluation of the cirrhotic liver. The combination of arterial phase hyperenhancement and delayed wash-out allows a definitive diagnosis of hepatocellular carcinoma (HCC) in patients with liver cirrhosis or chronic liver disease, without the requirement for confirmatory biopsy. That pattern is highly specific and has been endorsed in Western and Asian diagnostic guidelines. However, the sensitivity of the combination is relatively low for small HCCs. In this two-part review paper, we will address MRI of the cirrhotic liver. In this first part, we provide a brief background on liver cirrhosis and HCC, followed by descriptions of imaging surveillance of liver cirrhosis and the diagnostic performance of the different imaging modalities used in clinical settings. We then describe some of the requirements for the basic MRI technique, as well as the standard MRI protocol, and provide a detailed description of the appearance of various types of hepatocellular nodules encountered in the setting of the carcinogenic pathway in the cirrhotic liver, ranging from regenerative nodules to HCC. PMID:28298731

  9. Rapamycin ameliorates inflammation and fibrosis in the early phase of cirrhotic portal hypertension in rats through inhibition of mTORC1 but not mTORC2.

    Directory of Open Access Journals (Sweden)

    Weijie Wang

    Full Text Available OBJECTIVE: Hepatic stellate cells (HSCs transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR pathway as a potential modulator in the early phase of cirrhotic portal hypertension. METHODS: Early cirrhotic portal hypertension was induced by bile duct ligation (BDL for three weeks. One week after operation, sham-operated (SHAM and BDL rats received rapamycin (2 mg/kg/day by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2, p-ERK1/2, and interleukin-1 beta (IL-1β were assessed by western blot. RESULTS: The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K and phosphorylated ribosomal protein S6 (p-S6 but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1 rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. CONCLUSIONS: The AKT/mTOR signaling pathway played an important

  10. Systemic chemotherapy for hepatocellular carcinoma in non-cirrhotic liver: A retrospective study

    Institute of Scientific and Technical Information of China (English)

    Julien Edeline; Jean-Luc Raoul; Elodie Vauleon; Anne Guillygomac'h; Karim Boudjema; Eveline Boucher

    2009-01-01

    AIM: To investigate the efficacy and toxicity of systemic chemotherapy in a retrospective study of patients with hepatocellular carcinoma (HCC) occurring in normal or fibrotic liver without cirrhosis. METHODS: Twenty-four patients with metastatic or locally advanced HCC in a normal or a fibrotic liver were given systemic chemotherapy (epirubicin, cisplatin and 5-fluorouracil or epirubicin, cisplatin and capecitabine regimens). Tumor response, time to progression, survival, and toxicity were evaluated. RESULTS: There were 7 women and 17 men, mean 6 had a fibrotic liver (F1/F2 on biopsy). Mean tumor size was 14 cm, 5 patients had portal vein thrombosis and 7 had metastasis. Patients received a median of 4 chemotherapy sessions. Overall tolerance was good. There were 5 partial responses (objective response rate = 22%), and tumor control rate was 52%. Second line surgical resection was possible in two patients. Median survival was 11 mo, and 1- and 2-year overall survival rates were 50% ± 10% and 32% ± 11%, respectively. ``CONCLUSION: In patients with HCC in a non-cirrhotic liver, chemotherapy was well tolerated and associated with an objective response rate of 22%, including two patients who underwent secondary surgical resection.

  11. Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Jean-Louis Frossard; Rafael Quadri; Antoine Hadengue; Philippe Morel; Catherine M Pastor

    2006-01-01

    AIM: To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase(eNOS) expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 (Hsp90),as well as by the modifications of calmodulin binding to eNOS.METHODS: Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats.RESULTS: Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length (and the severity) of the disease. Because coimmunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast,cirrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity.CONCLUSION: In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide (NO) production is significantly decreased by two mechanisms: a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.

  12. Hepatocellular carcinoma in cirrhotic patients with portal hypertension: Is liver resection always contraindicated?

    Institute of Scientific and Technical Information of China (English)

    Andrea Ruzzenente; Alessandro Valdegamberi; Tommaso Campagnaro; Simone Conci; Silvia Pachera; Calogero Iacono,; Alfredo Guglielmi

    2011-01-01

    AIM: To analyze the outcome of hepatocellular carcinoma (HCC) resection in cirrhosis patients, related to presence of portal hypertension (PH) and extent of hepatectomy. METHODS: A retrospective analysis of 135 patients with HCC on a background of cirrhosis was submitted to curative liver resection. RESULTS: PH was present in 44 (32.5%) patients. Overall mortality and morbidity were 2.2% and 33.7%, respectively. Median survival time in patients with or without PH was 31.6 and 65.1 mo, respectively (P = 0.047); in the subgroup with Child-Pugh class A cirrhosis, median survival was 65.1 mo and 60.5 mo, respectively (P = 0.257). Survival for patients submitted to limited liver resection was not significantly different in presence or absence of PH. Conversely, median survival for patients after resection of 2 or more segments with or without PH was 64.4 mo and 163.9 mo, respectively (P = 0.035). CONCLUSION: PH is not an absolute contraindication to liver resection in Child-Pugh class A cirrhotic patients, but resection of 2 or more segments should not be recommended in patients with PH.

  13. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens H

    2010-01-01

    , nitric oxide overproduction, and cannabinoid receptor activation. Systolic incompetence in patients can be revealed by pharmacological or physical strain and during stressful procedures, such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. Systolic dysfunction has...... and electrophysiological abnormalities. This syndrome is termed cirrhotic cardiomyopathy. Results of experimental studies indicate the involvement of several mechanisms in the pathophysiology, such as reduced beta-adrenergic receptor signal transduction, altered transmembrane currents and electromechanical coupling...

  14. Impact of future remnant liver volume on post-hepatectomy regeneration in non-cirrhotic livers

    Directory of Open Access Journals (Sweden)

    Duilio ePagano

    2014-04-01

    Full Text Available Objective: The purpose of the study is to detect if some parameters can be considered as predictors of liver regeneration in two different patient populations composed of in living donors for adult to adult living donor liver transplant and patients with hepatic malignancies within a single institution.Summary Background Data: Preoperative multi-detector computed tomography volumetry is an essential tool to assess the volume of the remnant liver. Methods: a retrospective analysis from an ongoing clinical study on 100 liver resections, between 2004 and 2010. 70 patients were right lobe living donors for liver transplantation and 30 patients were resected for treatment of tumors. Pre-surgical factors such as age, weight, height, body mass index (BMI, original liver volume, future remnant liver volume (FRLV, spleen volume, liver function tests, creatinine, platelet count, steatosis, portal vein embolization (PVE and number of resected segments were analyzed to evidence potential markers for liver regeneration. Results: Follow-up period did not influence the amount of liver regenerated: the linear regression evidenced that there is no correlation between percentage of liver regeneration and time of follow-up (p=0.88. The pre-surgical variables that resulted markers of liver regeneration include higher preoperative values of BMI (p=0.01, bilirubin(p=0.04, glucose (p=0.05 and GGT (p=0.014; the most important association was revealed regarding the lower FRLV (pConclusions: Liver regeneration follows similar pathway in living donor and in patients resected for cancer. Small FRLV tends to regenerate more and faster, confirming that a larger resections may lead to a greater promotion of liver regeneration in patients with optimal conditions in terms of body habitus, preoperative liver function tests and glucose level.

  15. Classification tool for the systematic histological assessment of hepatocellular carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver

    Institute of Scientific and Technical Information of China (English)

    A Quaglia; MA Jutand; A Dhillon; A Godfrey; R Togni; P Bioulac-Sage; C Balabaud; M Winnock; AP Dhillon

    2005-01-01

    AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver.METHODS: Two hundred and twelve hepatocellular nodules (106 HCC;74 MRN;32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA).RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale".Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss,capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool dassified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepandes were present for DN and MRN between the routine histological assignment and the classification tool. Of 25 HCC assigned by routine assessment in the validation set, 8were assigned to the DN category by the classification tool.CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.

  16. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Directory of Open Access Journals (Sweden)

    Yoshimura Kazunori

    2010-11-01

    Full Text Available Abstract Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs. This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control and from cirrhotic livers (LC (Child A-LC and Child C-LC. Immunohistochemical (IHC, Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.

  17. Prevalence of hepatitis A and B markers and vaccine indication in cirrhotic patients evaluated for liver transplantation in Spain.

    Science.gov (United States)

    Aoufi, S; Pascasio, J M; Sousa, J M; Sayago, M; Ferrer, M T; Gómez-Delgado, E; De la Cruz, M D; Alamo, J M; Gómez-Bravo, M A; Bernardos, A; Márquez, J L

    2008-11-01

    Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (-), 11.5%; anti-HBc (-)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients vaccine among cirrhotic patients evaluated for liver transplantation, as is time for HAV vaccine, especially among patients younger than 45 years of age.

  18. Liver angiogenesis as a risk factor for hepatocellular carcinoma development in hepatitis C virus cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma (HCC) in hepatitis C virus(HCV) cirrhotic patients.METHODS: One hundred-five patients (69 males,36 females; age range, 51-90 year; median 66 year)with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 mo. Angiogenesis was assessed by using microvessel density (MVD), hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies.RESULTS: Forty six patients (43.8%) developed HCC after a median time of 55 (6-120) mo while 59 (56.2%)did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low (median MVD = 3; range 0-20) and high (median MVD = 7; range 1-24) MVD was statistically significant (χ2 = 22.06; P < 0.0001) which was not the case for MIB1 or PCNA (MIB-1: χ2 = 1.41;P = 0.2351; PCNA: χ2 = 1.27; P = 0.2589). The median MVD was higher in patients who developed HCC than in those who did not. HCC-free interval was significantly longer in patients with the MVD ≤ 4 (P = 0.0006).No relationship was found between MIB1 or PCNA and MVD (MIB-1 r2 = 0.00007116, P = 0.9281; PCNA: r2 =0.001950; P = 0.6692). MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk.CONCLUSION: Liver angiogenesis has a role for in HCVrelated liver carcinogenesis and for defining patients at higher risk.

  19. Expression of glyoxalase-I is reduced in cirrhotic livers: A possible mechanism in the development of cirrhosis

    Science.gov (United States)

    Hollenbach, Marcus; Thonig, Antje; Pohl, Sabine; Ripoll, Cristina; Michel, Maurice; Zipprich, Alexander

    2017-01-01

    Background High concentrations of methylglyoxal (MGO) cause cytotoxiticy via formation of advanced glycation endproducts (AGEs) and inflammation. MGO is detoxificated enzymatically by glyoxalase-I (Glo-I). The aim of this study was to analyze the role of Glo-I during the development of cirrhosis. Methods In primary hepatocytes, hepatic stellate cells (pHSC) and sinusoidal endothelial cells (pLSEC) from rats with early (CCl4 8wk) and advanced cirrhosis (CCl4 12wk) expression and activity of Glo-I were determined and compared to control. LPS stimulation (24h; 100ng/ml) of HSC was conducted in absence or presence of the partial Glo-I inhibitor ethyl pyruvate (EP) and the specific Glo-I inhibitor BrBzGSHCp2. MGO, inflammatory and fibrotic markers were measured by ELISA and Western blot. Additional rats were treated with CCl4 ± EP 40mg/kg b.w. i.p. from wk 8–12 and analyzed with sirius red staining and Western blot. Results Expression of Glo-I was significantly reduced in cirrhosis in whole liver and primary liver cells accompanied by elevated levels of MGO. Activity of Glo-I was reduced in cirrhotic pHSC and pLSEC. LPS induced increases of TNF-α, Nrf2, collagen-I, α-SMA, NF-kB and pERK of HSC were blunted by EP and BrBzGSHCp2. Treatment with EP during development of cirrhosis significantly decreased the amount of fibrosis (12wk CCl4: 33.3±7.3%; EP wk 8–12: 20.7±6.2%; p<0.001) as well as levels of α-SMA, TGF-β and NF-κB in vivo. Conclusions Our results show the importance of Glo-I as major detoxifying enzyme for MGO in cirrhosis. The reduced expression of Glo-I in cirrhosis demonstrates a possible explanation for increased inflammatory injury and suggests a “vicious circle” in liver disease. Blunting of the Glo-I activity decrease the amount of fibrosis in established cirrhosis and constitutes a novel target for antifibrotic therapy. PMID:28231326

  20. Protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats

    Institute of Scientific and Technical Information of China (English)

    Wei Gao; Hai-Ying Li; Li-Xin Wang; Li-Jun Hao; Jian-Li Gao; Rong-Juan Zheng; Chun-Jiang Cai; Yan-Ling Si

    2014-01-01

    Objective:To observe the protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats.Methods:All rats were randomly divided into normal control group, cirrhosis and treatment group.Thioacetamide was used to establish rat model of cirrhotic portal hypertension.The necrotic tissue of gastric mucosa ulcer focus, degree of neutrophils infiltration at the ulcer margin, portal pressure, portal venous flow, abdominal aortic pressure, abdominal aortic blood flow at front end, gastric mucosal blood flow(GMBF), glycoprotein(GP) of gastric mucosa,basal acid secretion,H+ back -diffusion, gastric mucosal damage index,NO, prostaglandinE2(PGE2) and tumor necrosis factor-α(TNF-α) were determined respectively, and the pathological changes of gastric mucosa were also observed by microscope.Results:Compared with cirrhosis group and the control group, the ulcer bottom necrotic material, gastric neutrophil infiltration andUI of the treatment group were all decreased significantly(P<0.01), GMBF value,GP values, serumNO,PGE2,TNF-α were all significantly increased.Conclusions:Omeprazole has an important protective effect on gastric mucosal and it can increase gastric mucosal blood flow and related to many factors.

  1. 支链氨基酸强化的肠内肠外营养对肝硬化大鼠术后肝功能及血浆氨基酸谱的影响%Effects of branched-chain amino acids-enriched early parenteral and enteral nutrition on the liver function and serum aminograms in cirrhotic rats after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    赖佳明; 胡文杰; 王恕同; 华赟鹏; 郝元涛; 罗时敏; 赖英荣; 梁力建

    2010-01-01

    -chain amino acids-enriched early parenteral and enteral nutrition on the liver function and serum aminograms in cirrhotic rats after partial hepatectomy. Methods In this prospective randomized controlled study, 24 cirrhotic rats, induced by thioacetamide, were randomized into three groups: enteral nutrition (EN) group, EN + branched-chain amino acid (BCAA) group, and parenteral nutrition (PN) + BCAA group. After receiving partial hepatectomy, rats in all three groups were nutritionally supported with equal amount of calorie and nitrogen contents from the 1st postoperative day ( PO day 1 ) to PO day 5. On PO day 6, parameters including body weight, liver functions, prealbumin, transferring, and serum aminograms were measured or determined, and the level of liver albumin mRNA was detected by reversal transcription-polymerase chain reaction and morphological examinations such as HE staining and immunohistochemical staining, which were assessed by index of Ki67 protein index. Results Body weight was significantly decreased in all three groups on PO day 6 (P <0.05 ). Compared with EN + BCAA group, serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase after partial hepatectomy were significantly higher in PN + BCAA group (P <0.05 ). Serum alkaline phosphatase level was significantly higher in PN + BCAA group than in EN group ( P <0. 05). The level of prealbumin was significantly lower in PN + BCAA group when compared with EN group or EN +BCAA group ( both P < 0. 05 ), although no such significant difference was noted in terms of transferrin ( P >0. 05 ). The levels of leucine and isoleucine elevated while those of tyrosine, phenylalanine, arginine and tryptophan declined in PN + BCAA group or EN + BCAA group when compared with EN group ( P < 0. 05 ). Aminograms were not significantly different between EN + BCAA group and PN + BCAA group ( P > 0. 05 ). Levels of total amino acid and aromatic amino acid (AAA) were significantly lower while

  2. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

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    Jin-Hang Gao

    Full Text Available BACKGROUND: Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2 in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVE: To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODS: Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA. 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF, VEGF receptor-2 (VEGFR-2 and related signal molecules were quantitated. RESULTS: Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2, phosphorylated extracellular signal-regulated kinase (p-ERK, hypoxia-inducible factor-1α (HIF-1α, and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONS: Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its

  3. Tetrandrine Ameliorates Cirrhosis and Portal Hypertension by Inhibiting Nitric Oxide in Cirrhotic Rats

    Institute of Scientific and Technical Information of China (English)

    王海; 陈孝平

    2004-01-01

    To examine the role and effect of nitric oxide synthase type Ⅱ (NOSⅡ) in cirrhotic rats,expression of NOSⅡ mRNA was detected by real time RT-PCR. The enzymatic activity of nitric oxide synthase and the circulating levels of NO, systemic and portal hemodynamics and quantification of cirrhosis were measured. Chinese traditional medicine was used to treat cirrhotic rats and the effect of NO was evaluated. Double-blind method was used in experiment. Our results showed the concentration of NO and the enzymatic activity of NOS increased markedly at all stages of cirrhosis and iNOSmRNA was strongly expressed. Meanwhile, the portal-venous-pressure (PVP) and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the degree of hepatic fibrosis. Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA. Our results suggested that increased hepatic expression of NOS Ⅱ is one of the important factors causing cirrhosis and portal hypertension. Tetrandrine can significantly ameliorate cirrhosis and portal hypertension.

  4. Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation (LDLT), and to clarify how systemic hemodynamics impact on local graft circulation after LDLT.METHODS: Systemic hemodynamics, indocyanine green (ICG) elimination rate (KICG) and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry (PDD) and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output (CO) to blood volume (BV) and mean transit time (MTT), defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative qraft function.RESULTS: Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance (TPR) were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and MTT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased KICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow.CONCLUSION: We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.

  5. Nitric oxide mediates effects of acute, not chronic, naltrexone on LPS-induced hepatic encephalopathy in cirrhotic rats.

    Science.gov (United States)

    Ghiassy, Bentolhoda; Rahimi, Nastaran; Javadi-Paydar, Mehrak; Gharedaghi, Mohammad Hadi; Norouzi-Javidan, Abbas; Dehpour, Ahmad R

    2017-01-01

    Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.

  6. Predictive Value of the Model of End-Stage Liver Disease in Cirrhotic Patients with and without Spontaneous Bacterial Peritonitis

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    Bledar Kraja

    2012-01-01

    Full Text Available Objective. We aimed to assess the predictive value of the model of end-stage liver disease (MELD in hospitalized cirrhotic patients with and without spontaneous bacterial peritonitis (SBP and fatal outcome. Methods. A cross-sectional study included 256 consecutive patients (199 men and 57 women diagnosed with cirrhosis and ascites who were hospitalized at the University Hospital Center in Tirana from January 2008 to December 2009. SBP was defined as a neutrophil count of ≥250 cells/mm3 in ascitic fluid. MELD score was based on laboratory parameters determined by UNOS Internet site MELD calculator. Results. In multivariable-adjusted logistic regression models controlling for age, sex, diabetes, and etiology, there was evidence of a positive association of SBP with MELD score: the odds ratio (OR for SBP for one unit increment of MELD score was 1.06 (95% Cl = 1.02–1.09. MELD score was significantly higher in fatal cases than nonfatal patients (mean age-adjusted score was 32.7 versus 18.4 overall; 34.8 versus 18.0 in SBP patients, and 32.0 versus 18.5 in non-SBP patients; all P<0.001. Conclusions. In this Albanian sample of hospitalized cirrhotic patients, MELD score was confirmed as a significant predictor of both SBP and fatal outcome.

  7. Management of cirrhotic ascites

    DEFF Research Database (Denmark)

    Pedersen, Julie Steen; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the na......The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark...... in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic...

  8. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension.

    Science.gov (United States)

    Uschner, Frank E; Ranabhat, Ganesh; Choi, Steve S; Granzow, Michaela; Klein, Sabine; Schierwagen, Robert; Raskopf, Esther; Gautsch, Sebastian; van der Ven, Peter F M; Fürst, Dieter O; Strassburg, Christian P; Sauerbruch, Tilman; Diehl, Anna Mae; Trebicka, Jonel

    2015-09-28

    Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical (Shh/RhoA) hedgehog pathway. Cirrhotic (bile duct ligation/BDL; CCl4 intoxication) and non-cirrhotic (partial portal vein ligation/PPVL) rats received either atorvastatin (15 mg/kg; 7d) or control chow before sacrifice. Invasive hemodynamic measurement and Matrigel implantation assessed angiogenesis in vivo. Angiogenesis in vitro was analysed using migration and tube formation assay. In liver and vessel samples from animals and humans, transcript expression was analyzed using RT-PCR and protein expression using Western blot. Atorvastatin decreased portal pressure, shunt flow and angiogenesis in cirrhosis, whereas atorvastatin increased these parameters in PPVL rats. Non-canonical Hh was upregulated in experimental and human liver cirrhosis and was blunted by atorvastatin. Moreover, atorvastatin blocked the non-canonical Hh-pathway RhoA dependently in activated hepatic steallate cells (HSCs). Interestingly, hepatic and extrahepatic Hh-pathway was enhanced in PPVL rats, which resulted in increased angiogenesis. In summary, statins caused contrary effects in cirrhotic and non-cirrhotic portal hypertension. Atorvastatin inhibited the non-canonical Hh-pathway and angiogenesis in cirrhosis. In portal vein obstruction, statins enhanced the canonical Hh-pathway and aggravated PHT and angiogenesis.

  9. Biopsychosocial functioning among cirrhotic patients in various stages of transplant process in comparison to liver transplant recipients

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    Agustín Martín-Rodríguez

    2014-01-01

    Full Text Available Background: Although assessment of pre and posttransplant quality of life is a current scientific target; it has not yet been carried out throughout the entire transplant process. Aims: 1 To analyze differences in mental health and quality of life at prewaiting list study, waiting list, and post transplant phases; 2 to analyze correlation between these quality of life and affective variables and Model for End Stage Liver Disease (MELD scores. Methods: Two liver patient groups were recruited: 51 cirrhotic patients, who were assessed at two different stages (at pre waiting list study and waiting list phases, and 51 cadaveric liver transplant recipients; groups were homogeneous in gender and age variables by matching. Anxiety depressive symptomatology and quality of life were assessed by HADS and SF-36 Health Survey, respectively. Results: Pre waiting list study patients self perceived their global health status much worse than transplant recipients. Waiting list patients displayed much higher anxiety, more role limitations due to physical problems, worse physical functioning, as well as perceiving their global health status much worse than transplant recipients. Statistically significant correlations were only found in waiting list patients between MELD-Anxiety and MELD-Social Functioning subscales. Conclusions: Waiting list patients displayed the worst biopsychosocial well being status; liver transplant recipients enjoyed the best status instead.

  10. Laparoscopic versus Open Liver Resection: Differences in Intraoperative and Early Postoperative Outcome among Cirrhotic Patients with Hepatocellular Carcinoma—A Retrospective Observational Study

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    Antonio Siniscalchi

    2014-01-01

    Full Text Available Introduction. Laparoscopic liver resection is considered risky in cirrhotic patients, even if minor surgical trauma of laparoscopy could be useful to prevent deterioration of a compromised liver function. This study aimed to identify the differences in terms of perioperative complications and early outcome in cirrhotic patients undergoing minor hepatic resection for hepatocellular carcinoma with open or laparoscopic technique. Methods. In this retrospective study, 156 cirrhotic patients undergoing liver resection for hepatocellular carcinoma were divided into two groups according to type of surgical approach: laparoscopy (LS group: 23 patients or laparotomy (LT group: 133 patients. Perioperative data, mortality, and length of hospital stay were recorded. Results. Groups were matched for type of resection, median number of nodules, and median diameter of largest lesions. Groups were also homogeneous for preoperative liver and renal function tests. Intraoperative haemoglobin decrease and transfusions of red blood cells and fresh frozen plasma were significantly lower in LS group. MELD score lasted stable after laparoscopic resection, while it increased in laparotomic group. Postoperative liver and renal failure and mortality were all lower in LS group. Conclusions. Lower morbidity and mortality, maintenance of liver function, and shorter hospital stay suggest the safety and benefit of laparoscopic approach.

  11. Focal masses in a non-cirrhotic liver: The additional benefit of CEUS over baseline imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chiorean, L., E-mail: lilichiorean@yahoo.com [Sino-German Research Center of Ultrasound in Medicine, The First Affiliated Hospital of Zhengzhou University (China); Med. Klinik 2, Caritas Krankenhaus Bad Mergentheim, Uhlandstr. 7, D-97980 Bad Mergentheim (Germany); Département d’imagerie médicale, Clinique des Cévennes, 07100 Annonay (France); Cantisani, V., E-mail: vito.cantisani@uniroma1.it [Dipartimento di Scienze Radiologiche, Oncologiche, Anatomo-patologiche, Policlinico Umberto I, Univ. Sapienza, Roma (Italy); Jenssen, C., E-mail: C.Jenssen@khmol.de [Innere Medizin, Krankenhaus Märkisch Oderland, Prötzeler Chaussee 5, 15433 Strausberg (Germany); Sidhu, P.S., E-mail: paulsidhu@nhs.net [Department of Radiology, King' s College Hospital, Denmark Hill, London SE5 9RS, England (United Kingdom); Baum, U., E-mail: Ulrich.Baum@ckbm.de [Department of Radiology, Caritas Krankenhaus Bad Mergentheim, Uhlandstr. 7, D-97980 Bad Mergentheim (Germany); Dietrich, C.F., E-mail: christoph.dietrich@ckbm.de [Sino-German Research Center of Ultrasound in Medicine, The First Affiliated Hospital of Zhengzhou University (China); Med. Klinik 2, Caritas Krankenhaus Bad Mergentheim, Uhlandstr. 7, D-97980 Bad Mergentheim (Germany)

    2015-09-15

    Highlights: • Contrast-enhanced ultrasound in detection of focal liver lesions. • Contrast-enhanced ultrasound in characterization of focal liver lesions. • Contrast-enhanced ultrasound in differential diagnosis of focal liver lesions. • Contrast-enhanced ultrasound in final diagnosis of focal liver lesions. • Contrast-enhanced ultrasound in liver metastases screening. • Roles of cross-sectional imaging techniques for focal liver lesions assessment. • Advantages of contrast-enhanced ultrasound over other imaging procedures. - Abstract: Incidentally detected focal liver lesions are commonly encountered in clinical practice presenting a challenge in the daily department work flow. Guidelines for the management of incidental focal liver lesions have been published but comments, illustrations and recommendations regarding practical issues are crucial. The unique features of contrast-enhanced ultrasound in non-invasive assessment of focal liver lesion enhancement throughout the vascular phases in real-time has allowed an impressive improvement in the diagnostic accuracy of ultrasound. We highlight the additional benefit of contrast-enhanced ultrasound over conventional B-mode ultrasound imaging in detection, characterization, differential and final diagnosis of focal liver lesions, as well as for liver metastases screening. The current roles of cross-sectional imaging are explained in detail, with indications and limitations for each procedure. The advantages of CEUS, such as non-ionizing radiation exposure, cost benefits, non-iodinate contrast agents, and repeatability are also described ultimately improving patient management.

  12. Prevalence of hepatitis B and A virus markers and vaccination indication in cirrhotic patients evaluated for liver transplantation in Spain.

    Science.gov (United States)

    Gutiérrez Domingo, I; Pascasio Acevedo, J M; Alcalde Vargas, A; Ramos Cuadra, A; Ferrer Ríos, M T; Sousa Martín, J M; Sayago Mota, M; Giráldez Gallego, A; Suárez Artacho, G

    2012-01-01

    In the absence of immunity, vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic liver disease and those evaluated for liver transplantation (OLT) HAV and HBV infections after OLT which are frequent in this setting, are associated with a worse prognosis. The aim of this study was to estimate the need for vaccination against HBV and HAV among cirrhotic patients who were candidates for OLT and associations with gender, age, and etiologic factors. HBV and HAV serological markers HBsAg, anti-HBc, antiHBs, immunoglobulin G (IgG)-anti-HAV were investigated among 568 patients, including 75% men. The overall mean age was 53.6 ± 8.9 years range 17-69, and 20% were diabetic. This etiologies were alcohol (68%), hepatitis C virus (35%) or other causes (10.4%). Child-Pugh classes were: A (26%), B (44%), and C (30%). In contrast with 359 patients (63.2%) who had negative HBV markers, 209 (36.8%) were positive: HBsAg (+), 43 (7.6%), isolated anti-HBc (+), 57 (10%), isolated anti-HBs (+), 19 (3.3%), anti-HBc (+)/anti-HBs (+), 90 (15.8%). HBV vaccine indication was performed in 416 patients (73.2%) who either had negative HBV markers or isolated anti-HBc (+). It was more frequently performed in women (82.3% versus 70.3%, P = .005), albeit with no differences according to age or etiology. There were only 8.2% (44/538) IgG-anti-HAV-negative, an indication for vaccination against HAV, which was more frequent affecting patients who were younger [≤ 45 years (27.6%), 46-55 (7.2%), >55 (2.6%); P < .0001)]; nondiabetic (9.5% versus 2.8%, P = .023); nonalcoholic (11.4% versus 6.6%, P = .056); and displayed negative HBV markers (10.2% versus 4.6%, P = .023). Only three patients with IgG-anti- HAV (-) were over 60 years. In conclusion, there is a frequent indication for HBV vaccination among cirrhotic and especially HAV vaccine for under 45 year old patients undergoing evaluation for OLT.

  13. Diffusion weighted MRI in intrahepatic bile duct adenoma arising from the cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    An, Chansik [Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Sumi; Choi, Yoon Jung [National Health Insurance Corporation Ilsan Hospital, Goyang (Korea, Republic of)

    2013-10-15

    A 64-year-old male patient with liver cirrhosis underwent a CT study for hepatocellular carcinoma surveillance, which demonstrated a 1.4-cm hypervascular subcapsular tumor in the liver. On gadoxetic acid-enhanced MRI, the tumor showed brisk arterial enhancement and persistent hyperenhancement in the portal phase, but hypointensity in the hepatobiliary phase. On diffusion-weighted MRI, the tumor showed an apparent diffusion coefficient twofold greater than that of the background liver parenchyma, which suggested that the lesion was benign. The histologic diagnosis was intrahepatic bile duct adenoma with alcoholic liver cirrhosis.

  14. Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lee

    Full Text Available Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL-induced cirrhosis received vehicle (citrate buffer or streptozotocin (diabetic, BDL/STZ. The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist and overcome by NaF (a G protein activator. The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

  15. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

    2011-01-01

    Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged treatment...

  16. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

    2011-01-01

    Abstract Objective. Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged...

  17. 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.

  18. Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats.

    Directory of Open Access Journals (Sweden)

    Jian-Bo Wen

    Full Text Available Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg, and non-treatment group, which received the same dose of 5% glucose solution (vehicle. The blank group (n = 10 healthy rats received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-α (TNF-α and interleukin 6 (IL-6 in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA, respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-κB p65, TNF-α, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in

  19. Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats

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    Santiago Marfà

    2016-06-01

    Full Text Available At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1 were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis.

  20. Alteration in membrane protein, antioxidant status and hexokinase activity in erythrocytes of CCl4- induced cirrhotic rats.

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    Amir Hossein Doustimotlagh

    2014-11-01

    Full Text Available Several studies have shown that hepatocyte membrane composition changes in patients with cholestasis and cirrhosis. These alterations that are because of intracellular oxidative stress are supposed to be reflected in erythrocyte membrane. The aim of this study was to investigate the modification of erythrocyte membrane along with hexokinase and antioxidant enzymes during development of cirrhosis. Cirrhosis was induced by intraperitoneal injection of CCl4 in male Wistar rats. The test groups were: baseline, cholestatic, early cirrhotic and advanced cirrhotic along with an equal number of sham-control animals. The erythrocyte membrane modifications (protein sulfhydryl, protein carbonyl, and lipid peroxidation, as well as NO metabolites, were assessed. Activities of GPX, CAT, SOD and HK were also measured. Protein sulfhydryl content of the erythrocyte membrane (after 2, 6 and 10 weeks of injection had significant progressive decrease. In contrast, protein carbonyls were remarkably increased 2 weeks after injection but significantly decreased after 6 weeks and returned to normal levels after 10 weeks. No significant difference in erythrocyte HK activity or MDA content was observed. Test groups showed significantly lower erythrocyte GPx activity after six weeks and CAT and SOD activities along with NO metabolites content after two weeks (P<0.05. This study indicates that the progression of cirrhosis is accompanied by alterations in antioxidant enzyme and decreased NO metabolites. Protein carbonyl alteration occurs in the early stages of cirrhosis while protein sulfhydryl alterations have a progressive decrease in advanced cirrhosis.

  1. Large ({>=}2 cm) non-hypervascular nodules depicted on MRI in the cirrhotic liver: fate and implications

    Energy Technology Data Exchange (ETDEWEB)

    Yu, J.S. [Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, YongDong Severance Hospital, Seoul (Korea, Republic of)], E-mail: yjsrad97@yuhs.ac; Chung, J.J.; Kim, J.H.; Kim, K.W. [Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, YongDong Severance Hospital, Seoul (Korea, Republic of)

    2008-10-15

    Aim: To determine the fate and clinical implication of large ({>=}2 cm), non-hypervascular nodules depicted on magnetic resonance imaging (MRI) in the cirrhotic liver. Materials and methods: In 21 patients with cirrhosis (14 hepatitis B, two ethanol abuse, four cryptogenic, one Wilson's disease), 25 large ({>=}2 cm in the longest dimension) non-hypervascular nodules were identified on dynamic MRI. The implications for diagnosis of the initial size, contour, and signal characteristics on MRI in addition to patients' age and cause of cirrhosis were assessed in our analysis. Results: Twelve (75%) out of 16 lesions were malignant or potentially-malignant from 14 hepatitis B patients, while seven (78%) of the nine lesions from other patients were benign (p = 0.016). The mean age of the patients who had malignant or potentially malignant lesions (57 years) was older than that for the other patients (47 years; p = 0.039). The ratio of the short-to-long diameter was higher in malignant or potentially malignant lesions (mean 0.86) than in benign lesions (mean 0.69; p = 0.008). There was no discriminative signal intensity characteristic (p > 0.2 for all factors) that indicated the malignant potential for each non-hypervascular nodule. For all 10 lesions in the hepatitis B patients who were older than 52 years with a short-to-long diameter ratio of more than 0.75, the positive predictive value for malignant potential based on these three combined factors was 100%. Conclusion: In older patients with cirrhosis from hepatitits B, large ({>=}2 cm), non-hypervascular nodules with a spherical contour have a high malignant potential.

  2. Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

    Directory of Open Access Journals (Sweden)

    R.R. Guerra

    2009-11-01

    Full Text Available Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF. Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg by intraperitoneal injections of thioacetamide (200 mg/kg. Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1 and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a reduced the relative mRNA expression of the genes: Col-α1 (-53%, TIMP-1 (-31.7%, TGF-β1 (-57.7%, and MMP-2 (-41.6%, whereas Plau mRNA remained unchanged; b reduced GGT (-43.1%, ALT (-17.6%, and AST (-12.2% serum levels; c increased liver weight (11.3%, and reduced liver collagen (-37.1%, regenerative nodules size (-22.1%, and fibrous septum thickness. Progranulin protein (immunohistochemistry and mRNA (in situ hybridization were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.

  3. Spontaneous bacterial peritonitis: The clinical challenge ofa leaky gut and a cirrhotic liver

    Institute of Scientific and Technical Information of China (English)

    Philipp Lutz; Hans Dieter Nischalke; Christian P Strassburg; Ulrich Spengler

    2015-01-01

    Spontaneous bacterial peritonitis (SBP) is a frequent,life-threatening bacterial infection in patients withliver cirrhosis and ascites. Portal hypertension leadsto increased bacterial translocation from the intestine.Failure to eliminate invading pathogens due to immunedefects associated with advanced liver disease on thebackground of genetic predisposition may result in SBP.The efficacy of antibiotic treatment and prophylaxis hasdeclined due to the spread of multi-resistant bacteria.Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infectionwith resistant bacteria. Therefore, it is important toadapt empirical treatment to these risk factors and tothe local resistance profile. Rifaximin, an oral, nonabsorbableantibiotic, has been proposed to preventSBP, but may be useful only in a subset of patients.Since novel antibiotic classes are lacking, we have todevelop prophylactic strategies which do not inducebacterial resistance. Farnesoid X receptor agonistsmay be a candidate, but so far, clinical studies are notavailable. New diagnostic tests which can be carriedout quickly at the patient's site and provide additionalprognostic information would be helpful. Furthermore,we need tools to predict antibiotic resistance in orderto tailor first-line antibiotic treatment of spontaneousbacterial peritonitis to the individual patient and toreduce mortality.

  4. Effects of a high protein diet on cognition and brain metabolism in cirrhotic rats.

    Science.gov (United States)

    Méndez-López, M; Méndez, M; Arias, J; Arias, J L

    2015-10-01

    Hepatic encephalopathy (HE) is a neurological complication observed in patients with liver disease. Patients who suffer from HE present neuropsychiatric, neuromuscular and behavioral symptoms. Animal models proposed to study HE resulting from cirrhosis mimic the clinical characteristics of cirrhosis and portal hypertension, and require the administration of hepatotoxins such as thioacetamide (TAA). The aim of this study was to assess the effects of a high protein diet on motor function, anxiety and memory processes in a model of cirrhosis induced by TAA administration. In addition, we used cytochrome c-oxidase (COx) histochemistry to assess the metabolic activity of the limbic system regions. Male rats were distributed into groups: control, animals with cirrhosis, Control rats receiving a high protein diet, and animals with cirrhosis receiving a high protein diet. Results showed preserved motor function and normal anxiety levels in all the groups. The animals with cirrhosis showed an impairment in active avoidance behavior and spatial memory, regardless of the diet they received. However, the animals with cirrhosis and a high protein diet showed longer escape latencies on the spatial memory task. The model of cirrhosis presented an under-activation of the dentate gyrus and CA3 hippocampal subfields and the medial part of the medial mammillary nucleus. The results suggest that a high protein intake worsens spatial memory deficits shown by the TAA-induced model of cirrhosis. However, high protein ingestion has no influence on the COx hypoactivity associated with the model.

  5. Generic and disease-specific health related quality of life in non-cirrhotic, cirrhotic and transplanted liver patients: a cross-sectional study.

    NARCIS (Netherlands)

    S.M. van der Plas (Simone); B.E. Hansen (Bettina); J.B. de Boer (Josien); Th. Stijnen (Theo); J. Passchier (Jan); R.A. de Man (Robert); S.W. Schalm (Solko)

    2003-01-01

    textabstractBACKGROUND: Studies on Health Related Quality of Life (HRQoL) of chronic liver patients were performed in clinical populations. These studies included various disease stages but small variations in aetiology and no transplanted patients. We performed a large HRQoL study

  6. Antioxidant effects of insulin-like growth factor-I (IGF-I in rats with advanced liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Puche Juan

    2005-03-01

    Full Text Available Abstract Background The exogenous administration of Insulin-like Growth Factor-I (IGF-I induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 μg. 100 g-1. day-1. Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO and nitric oxide (NO are known sources of free radicals and induce reduction of ferritin-Fe3+ into free Fe2+, contributing to oxidative damage. Methods Liver cirrhosis was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10. Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry. Results Liver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p Conclusion the hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage.

  7. A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats

    OpenAIRE

    Sarai Rodríguez; Imma Raurell; Manuel Torres-Arauz; Teresa García-Lezana; Joan Genescà; María Martell

    2017-01-01

    Statins present many beneficial effects in chronic liver disease, but concerns about safety exist. We evaluated the hepatic effects of a nitric oxide-releasing atorvastatin (NCX 6560) compared to conventional statins. Simvastatin, atorvastatin and NCX 6560 were evaluated in four-week bile duct-ligated rats (BDL) simulating decompensated cirrhosis and in thirteen-week carbon tetrachloride (CCl4) intoxicated rats, a model of early cirrhosis. In the BDL model, simvastatin treated rats showed hig...

  8. Pressure profile in liver sinusoids. A model of localization of sinusoidal resistance in the normal and cirrhotic liver

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Lassen, N A

    1988-01-01

    profiles along the sinusoids indicate a steep downstream pressure fall in cirrhosis, implying that the spatial average of sinusoidal pressure is close to that of the inlet, i.e. portal pressure. Another prediction is an increased blood flow rate (flow rate per vessel) in the region near the outlet......A model of pressure profile along the sinusoids in the liver is presented. The major prerequisite is a converging sinusoidal flow pattern through a network of tubes with almost equal diameter. In this case the main hemodynamic resistance is located downstream at the outlet. Different geometric...... configurations (sphere, cylinder, and sections of these) are considered, and it is concluded that the precise shape of the microcirculatory unit is not crucial. The applicability in cirrhosis is considered in relation to a decreased diameter and number of the sinusoids in this condition. Estimated pressure...

  9. Role of diffusion-weighted imaging, apparent diffusion coefficient and correlation with hepatobiliary phase findings in the differentiation of hepatocellular carcinoma from dysplastic nodules in cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    Inchingolo, Riccardo; De Gaetano, Anna Maria; Curione, Davide; Ciresa, Marzia; Bonomo, Lorenzo [Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Institute of Radiology, ' ' Agostino Gemelli' ' Hospital, Rome (Italy); Miele, Luca; Pompili, Maurizio [Catholic University of the Sacred Heart, Department of Internal Medicine, ' ' Agostino Gemelli' ' Hospital, Rome (Italy); Vecchio, Fabio Maria [Catholic University of the Sacred Heart, Department of Anatomo-Pathology, ' ' Agostino Gemelli' ' Hospital, Rome (Italy); Giuliante, Felice [Catholic University of the Sacred Heart, Department of Surgery, ' ' Agostino Gemelli' ' Hospital, Rome (Italy)

    2015-04-01

    To investigate the utility of diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and the correlation with hepatobiliary phase (delayed phase imaging, DPI) findings in the differentiation of cirrhotic hepatocellular nodules. Forty-three patients with 53 pathology-proven nodules (29 hepatocellular carcinomas (HCCs), 13 high-grade (HGDNs) and 11 low-grade dysplastic nodules (LGDNs); mean size 2.17 cm, range 1-4 cm), who underwent liver MRI with DWI and DPI sequences, were retrospectively reviewed. Lesions were classified as hypointense, isointense, or hyperintense relative to the adjacent liver parenchyma. ADC of each nodule, of the surrounding parenchyma, and lesion-to-liver ratio were calculated. Hyperintensity versus iso/hypointensity on DWI, hypointensity versus iso/hyperintensity on DPI, and the mean lesion-to-liver ratio showed a statistically significant difference both between HCCs versus DNs and between ''HCCs + HGDNs'' versus LGDNs (p < 0.05); sensitivity, specificity, and accuracy for the diagnosis of ''HCCs + HGDNs'' were 96.8 %, 100 %, 97.4 % respectively when combining hyperintensity on DWI and hypointensity on DPI, and 90.9 %, 81.0 %, 83.6 % respectively when lesion-to-liver ratio was <0.95. Hyperintensity on DWI, especially in association with hypointensity on DPI, and low lesion-to-liver ratios should raise the suspicion of HCC, or at least of HGDN, thus helping the characterization of atypically enhancing lesions. (orig.)

  10. MRI for characterization of primary tumors in the non-cirrhotic liver: Added value of Gd-EOB-DTPA enhanced hepatospecific phase

    Energy Technology Data Exchange (ETDEWEB)

    Donati, Olivio F.; Hunziker, Roger; Fischer, Michael A. [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich (Switzerland); Raptis, Dimitri A.; Breitenstein, Stefan [Department of Visceral and Transplant Surgery, Swiss Hepato-Pancreato-Biliary (HPB) Center, University Hospital Zurich, Zurich (Switzerland); Patak, Michael A., E-mail: Michael.Patak@hirslanden.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich (Switzerland); Clinic Hirslanden, Hirslanden Hospital Group, Zurich (Switzerland)

    2014-07-15

    Purpose: To evaluate the added value of hepatospecific phase in Gd-EOB-DTPA enhanced magnetic resonance imaging (MRI) in patients with primary tumors in non-cirrhotic liver. Methods: Twenty-nine patients (median, 39 years; range, 18–81 years; 11 male) underwent preoperative Gd-EOB-DTPA enhanced MRI including hepatospecific phase after 10 and 20 min of contrast injection at four institutions in Europe, North America and New Zealand. Images were evaluated by three different readers (R1–R3) who characterized liver tumors with and without consultation of the hepatospecific phase images. Confidence in diagnosis was scored on a visual analog scale from 1 to 10. Histopathology (adenoma, n = 5; focal nodular hyperplasia, n = 11 and hepatocellular carcinoma, n = 13) in all patients served as the standard of reference. Differences were evaluated using the McNemar and Wilcoxon signed rank test. Results: Without hepatospecific phase images available, 22 (76%), 19 (66%) and 19 (66%) of 29 tumors were characterized correctly by the three readers respectively. Mean confidence in diagnosis was 6.1, 5.7 and 5.8. With the hepatospecific phase included, characterization of liver tumors did not change significantly with 21 (72%), 23 (79%) and 19 (66%) of 29 tumors diagnosed correctly (p > 0.05). According confidence ratings increased to 6.3, 6.5 and 7.7, respectively. Increase in diagnostic confidence was significant for R2 and R3 (p < 0.05) and independent of reader's experience. Conclusion: The additional hepatospecific phase in Gd-EOB-DTPA enhanced MRI did not significantly increase diagnostic accuracy in characterization of primary tumors in the non-cirrhotic liver. However, 2/3 readers showed a significant increase in diagnostic confidence after consultation of the hepatospecific phase.

  11. Effect of oral testosterone treatment on serum concentrations of sex steroids gonadotrophins and prolactin in alcoholic cirrhotic men. Copenhagen Study Group for Liver Diseases

    DEFF Research Database (Denmark)

    Gluud, C; Bennett, Patrick; Svenstrup, Bo

    1988-01-01

    The aim of this study was to examine the serum concentrations of sex steroids and pituitary hormones in a randomly selected group of alcoholic cirrhotic men participating in a randomized, placebo-controlled study on the efficacy of oral testosterone treatment on the liver. Before treatment......, patients (n = 25) had median serum concentrations of testosterone, oestradiol, non-protein bound oestradiol, non-sex hormone binding globulin (SHBG) bound oestradiol and oestrone sulphate which did not differ significantly from those of healthy controls (n = 16), but the patients had significantly (P less...... than 0.01) higher median serum concentrations of oestrone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. The patients were randomized to treatment with either oral micronized testosterone (200 mg t.d.s.) or placebo for a median duration of 1 year. In the placebo group (n...

  12. Novel bioimaging techniques of metals by laser ablation inductively coupled plasma mass spectrometry for diagnosis of fibrotic and cirrhotic liver disorders.

    Directory of Open Access Journals (Sweden)

    Pornwilard M-M

    Full Text Available BACKGROUND AND AIMS: Hereditary disorders associated with metal overload or unwanted toxic accumulation of heavy metals can lead to morbidity and mortality. Patients with hereditary hemochromatosis or Wilson disease for example may develop severe hepatic pathology including fibrosis, cirrhosis or hepatocellular carcinoma. While relevant disease genes are identified and genetic testing is applicable, liver biopsy in combination with metal detecting techniques such as energy-dispersive X-ray spectroscopy (EDX is still applied for accurate diagnosis of metals. Vice versa, several metals are needed in trace amounts for carrying out vital functions and their deficiency due to rapid growth, pregnancy, excessive blood loss, and insufficient nutritional or digestive uptake results in organic and systemic shortcomings. Established in situ techniques, such as EDX-ray spectroscopy, are not sensitive enough to analyze trace metal distribution and the quantification of metal images is difficult. METHODS: In this study, we developed a quantitative biometal imaging technique of human liver tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS in order to compare the distribution of selected metals in cryo-sections of healthy and fibrotic/cirrhotic livers. RESULTS: Most of the metals are homogeneous distributed within the normal tissue, while they are redirected within fibrotic livers resulting in significant metal deposits. Moreover, total iron and copper concentrations in diseased liver were found about 3-5 times higher than in normal liver samples. CONCLUSIONS: Biometal imaging via LA-ICP-MS is a sensitive innovative diagnostic tool that will impact clinical practice in identification and evaluation of hepatic metal disorders and to detect subtle metal variations during ongoing hepatic fibrogenesis.

  13. Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

    Directory of Open Access Journals (Sweden)

    Campos de Carvalho Antonio

    2010-01-01

    Full Text Available Abstract Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%. One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease

  14. The Proper Scan Delay of the Hepatobiliary Phase of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging to Evaluate Small-Sized ({<=} 3 cm) Hepatocellular Carcinoma in Cirrhotic Liver

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yong Yeon; Heo, Sook Hee; Kim, Jin Woong; Kang, Heoung Keun [Dept. of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun (Korea, Republic of); Lee, Ji Hyun; Shin, Sang Soo [Dept. of Radiology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2013-04-15

    To assess the optimal scan delay of hepatobiliary phase of gadoxetic acid (GA)-enhanced magnetic resonance (MR) imaging for small-sized ({<=} 3 cm) hepatocellular carcinomas (HCCs) in cirrhotic liver. There were 71 HCCs included in this study, derived from 53 patients with liver cirrhosis. Hepatobiliary phase MR imaging was obtained at 10, 15 and 20 mins after GA injection. For quantitative analysis, 2 radiologists calculated signal to noise ratio (SNR), enhancement ratio (ER) of the tumor and liver parenchyma and contrast-to-noise ratio (CNR) at 10 min, 15 min, and 20 min images, respectively. For qualitative analysis, 3 radiologists independently reviewed the 3 different phase about HCC possibilities using a 5-point scale. For each observer, the diagnostic accuracy of different hepatobiliary phases was compared using the area under the alternative free-response receiver operating characteristic curve (Az). In addition, sensitivity and specificity were compared. No significant differences in SNR, ER and CNR at 10 min, 15 min, and 20 min were found. The Az values for HCC possibility were not significantly different. Sensitivity and specificity were also not significantly different. Hepatobiliary phase MR imaging were obtained at 10 min, 15 min and 20 min yield comparable diagnostic information, so that the choice of scan delay can be adapted according to the clinical routine needs.

  15. Chronic nitric oxide synthase inhibition ecacerbates renal dysfunction in cirrhotic rats

    DEFF Research Database (Denmark)

    Græbe, Martin; Miller, Lone Brønd; Christensen, Sten;

    2004-01-01

    (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were...... performed, followed by Western blotting of the electroneutral type 3 sodium/proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments...

  16. Renal effects of the novel selective adenosine A1 receptor blocker SLV329 in experimental liver cirrhosis in rats.

    Directory of Open Access Journals (Sweden)

    Berthold Hocher

    Full Text Available Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A(1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A(1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold and natriuretic (up to 13.5-fold effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p<0.05, especially in those receiving furosemide (-41.9%, p<0.01. SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05. SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A(1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis.

  17. A STUDY OF CORRELATION OF ESOPHAGEAL VARICES IN CIRRHOTIC PATIENTS WITH PORTAL HAEMODYNAMICS WITH SPECIAL REFERENCE TO PORTAL VEIN DIAMETER, PORTAL VEIN VELOCITY, CONGESTION INDEX, LIVER VASCULAR INDEX

    Directory of Open Access Journals (Sweden)

    Arvind

    2014-12-01

    Full Text Available OBJECTIVE : Approximately two thirds of patients with decompensated cirrhosis and one third of those with compensated cirrhosis have varices at the time of diagnosis. Therefore , it is essential to identify and treat those patients at highest risk because each episode of variceal hemorrhage carries a 20% to 30% risk of death , and 70% of patients not receiving treatment will die within 1 year of the initial bleeding episode . (1 METH OD S: For this study , patients with cirrhosis with or without the evidence of any upper Gastrointestinal bleed , admitted in the department of medicine , JA Group of Hospitals , GR Medical College were taken. The study was conducted between September 2011 and November 2012 and cases were evaluated on the basis of clinical , haematological , ultrasonographic and endoscopic findings. Total number of cases were 100. RESULT : The prevalence of esophageal varices was 75% in cirrhotic patients out of which 28% had bleeding. The prevalence of gastric varices was 1.33%. The portal vein diameter correlated with the presence of varices while portal vein velocity , congestion index and liver vascular index had no significant correlation with esophageal varices. The Portal vein diameter more than 1.4 cm can predict varices with sensitivity 76 % (p<0.05 and Portal vein diameter more than 1.5 cm can detect bleeding varices in cirrhotic patients with sensitivity 55.56% and specificity 80.70% . CONCLUSION : This study showed tha t duration of illness , spleen size and tense ascitis on ultrasonography and portal vein diameter correlated with the presence of esophageal varices. The duration of illness and portal vein diameter are also correlated with bleeding manifestation

  18. Hemodynamic and morphologic changes of peripheral hepatic vasculature in cirrhotic liver disease: A preliminary study using contrast-enhanced coded phase inversion harmonic ultrasonography

    Institute of Scientific and Technical Information of China (English)

    Rong-Qin Zheng; Bo Zhang; Masatoshi Kudo; Yasuhiro Sakaguchi

    2005-01-01

    AIM: To provide the useful information for the diagnosis of liver cirrhosis by observing the morphology of peripheral hepatic vessels and the hemodynamics of microbubble arrival time in these vessels.METHODS: Twenty-one subjects including 5 normal volunteers and 16 patients (liver cirrhosis, n=10;chronic hepatitis, n=6) were studied by contrast-enhanced coded phase inversion harmonic sonography (GE LOGIQ9 series) using a 6-8 MHz convex-arrayed wide-band transducer. The images of peripheral hepatic artery,portal and hepatic vein were observed in real-time for about 2 min after intravenous injection of Levovist. The time when microbubbles appeared in the peripheral vessels (microbubble arrival time) was also recorded. The morphologic changes of peripheral hepatic vasculature were classified as marked, slight, and no changes based on the regularity in caliber, course, ramification, and the delineation of vessels compared to normal subjects.RESULTS: The microbubble arrival time at peripheral artery, portal, and hepatic vein was shorter in cirrhotic patients than in chronic hepatitis patients and normal subjects. The marked, slight and no morphologic changes of peripheral hepatic vasculature found in 5 (5/6,83.3%), 1 (1/6, 16.7% ), and 0 (0/6, 0%) liver cirrhosis patients, respectively, and in 1 (1/10, 10%), 6 (6/10,60%), and 3 (3/10, 30%) chronic hepatitis patients,respectively. There was a significant difference between the two groups (P<0.001).CONCLUSION: Evaluation of the hemodynamics and morphology of peripheral hepatic vasculature by contrast-enhanced coded pulse inversion harmonic sonography can provide useful information for the diagnosis of liver cirrhosis.

  19. Changes of nitric oxide and endothelin, thromboxane A2 and prostaglandin in cirrhotic patients undergoing liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Zi-Qing Hei; He-Qing Huang; Chen-Fang Luo; Shang-Rong Li; Gang-Jian Luo

    2006-01-01

    AIM: To investigate the perioperative changes of nitric oxide (NO) and endothelin (ET), thromboxane A2 (TXA2) and prostaglandin (PGI2) during liver transplantation in end-stage liver disease patients.METHODS: Twenty-seven patients with end-stage cirrhosis undergoing liver transplantation were enrolled in this prospective study. Blood samples were obtained from superior vena at five different surgical stages.Plasma concentrations of nitrate and nitrite were determined to reflect plasma NO levels. Plasma levels of ET-1,6-keto-PGF1 alpha and thromboxane B2 (TXB2),the latter two being stable metabolites of PGI2 and TXA2 respectively, were measured.RESULTS: The NO level decreased significantly after vascular cross-clamping and increased significantly at 30 min after reperfusion. While the ET levels at 30 min after clamping and after reperfusion were significantly elevated. The ratio of NO/ET decreased significantly at 30 min after vascular cross-clamping and at the end of surgery. The PGI2 level and the TXA2 during liver transplantation were significantly higher than the baseline level, but the ratio of TXA2/PGI2 decreased significantly at 30 min after clamping.CONCLUSION: NO/ET and TXA2/PGI2 change during liver transplantation. Although the precise mechanism remains unknown, they may play a role in the pathobiology of a variety of liver transplant-relevant processes.

  20. The association between content of the elements S, Cl, K, Fe, Cu, Zn and Br in normal and cirrhotic liver tissue from Danes and Greenlandic Inuit examined by dual hierarchical clustering analysis

    DEFF Research Database (Denmark)

    Laursen, Jens; Milman, Nils; Pind, N.;

    2014-01-01

    contents according to calculated similarities, one clustering elements according to correlation coefficients between the element contents, both using Euclidian distance and Ward Procedure. RESULTS: One dendrogram separated subjects in 7 clusters showing no differences in ethnicity, gender or age....... The analysis discriminated between elements in normal and cirrhotic livers. The other dendrogram clustered elements in four clusters: sulphur and chlorine; copper and bromine; potassium and zinc; iron. There were significant correlations between the elements in normal liver samples: S was associated with Cl, K...

  1. Iron, copper, zinc and bromine mapping in cirrhotic liver slices from patients with hemochromatosis studied by microscopic synchrotron radiation X-ray fluorescence analysis in continuous scanning mode

    Energy Technology Data Exchange (ETDEWEB)

    Osterode, W. [Medizinische Universitaet Wien, Univ. Klinik fuer Innere Medizin IV, Klinische Abteilung fuer Arbeitsmedizin, Waehringer Guertel 18-20, A-1090 Wien (Austria)], E-mail: wolf.osterode@meduniwien.ac.at; Falkenberg, G. [Hamburger Synchrotronstrahlungslabor HASYLAB, Deutsches Elektronen-Synchrotron DESY (Germany); Hoeftberger, R. [Medizinische Universitaet Wien, Klinisches Institut fuer Neurologie (Austria); Wrba, F. [Medizinische Universitaet Wien, Klinisches Institut fuer Klinische Pathologie (Austria)

    2007-07-15

    Iron (Fe) and copper (Cu) are essential metals in physiological cell metabolism. While Fe is easy to determine biochemically in histological slices, Cu and zinc (Zn) distribution is frequently critical in confirming the presence of an overload in disturbed Fe/Cu metabolism. To analyze Fe, Cu and Zn in a near histological resolution, energy dispersive microscopic synchrotron radiation X-ray fluorescence was applied. In normal liver tissue, after fixation and imbedding in paraffin, mean Fe, Cu and Zn concentrations were 152 {+-} 54, 20.1 {+-} 4.3 and 88.919.5 {mu}g/g sample weight, respectively. No substantial, characteristic differences in their distribution were found in the two-dimensional scans. In slices from patients with hemochromatosis mean Fe, Cu and Zn concentrations were 1102 {+-} 539, 35.9 {+-} 14.6 and 27.2 {+-} 6.7 {mu}g/g sample weight, respectively. Additionally, a significant decrease in phosphorus and sulphur concentrations existed. An increased Cu around cirrhotic regenerations nodules is mostly associated with a lymphocytic infiltration in this region. Analyzing concentrations of Fe in different regions of the samples show a clear negative dependency between Fe and Cu, Cu and Zn, but a positive one between Fe and Zn. Conclusion: With a focal beam size of 15 {mu}m in diameter a resolution of the elemental distribution was achieved which is widely comparable with stained histological slices (20x light microscope). The analysis of simultaneous determined elements reveals metabolic differences between Fe, Cu and Zn in liver tissue from patients with hemochromatosis.

  2. Iron, copper, zinc and bromine mapping in cirrhotic liver slices from patients with hemochromatosis studied by microscopic synchrotron radiation X-ray fluorescence analysis in continuous scanning mode

    Science.gov (United States)

    Osterode, W.; Falkenberg, G.; Höftberger, R.; Wrba, F.

    2007-07-01

    Iron (Fe) and copper (Cu) are essential metals in physiological cell metabolism. While Fe is easy to determine biochemically in histological slices, Cu and zinc (Zn) distribution is frequently critical in confirming the presence of an overload in disturbed Fe/Cu metabolism. To analyze Fe, Cu and Zn in a near histological resolution, energy dispersive microscopic synchrotron radiation X-ray fluorescence was applied. In normal liver tissue, after fixation and imbedding in paraffin, mean Fe, Cu and Zn concentrations were 152 ± 54, 20.1 ± 4.3 and 88.919.5 μg/g sample weight, respectively. No substantial, characteristic differences in their distribution were found in the two-dimensional scans. In slices from patients with hemochromatosis mean Fe, Cu and Zn concentrations were 1102 ± 539, 35.9 ± 14.6 and 27.2 ± 6.7 μg/g sample weight, respectively. Additionally, a significant decrease in phosphorus and sulphur concentrations existed. An increased Cu around cirrhotic regenerations nodules is mostly associated with a lymphocytic infiltration in this region. Analyzing concentrations of Fe in different regions of the samples show a clear negative dependency between Fe and Cu, Cu and Zn, but a positive one between Fe and Zn. Conclusion: With a focal beam size of 15 μm in diameter a resolution of the elemental distribution was achieved which is widely comparable with stained histological slices (20× light microscope). The analysis of simultaneous determined elements reveals metabolic differences between Fe, Cu and Zn in liver tissue from patients with hemochromatosis.

  3. Single-Lobe Living Donor Liver Transplant in a Morbidly Obese Cirrhotic Patient Preceded by Laparoscopic Sleeve Gastrectomy

    Science.gov (United States)

    Gupta, Subash; Wadhawan, Manav; Goyal, Neerav

    2013-01-01

    Nonalcoholic steatohepatitis (NASH) is a stage of nonalcoholic fatty liver disease (NAFLD), and, in most patients, it is associated with obesity and metabolic syndrome with progression to end-stage liver disease in about 20% of patients (McCullough (2004); Matteoni et al. (1999); Liou and Kowdley (2006)). It has been estimated that between 20 and 30% of patients with end-stage cirrhosis referred for liver transplantation (LT) evaluation and 30 to 70% of LT recipients exhibit some degree of obesity (Muñoz and ElGenaidi (2005)). Management of obesity in chronic liver disease patients is not only difficult but also preludes them from undergoing major bariatric surgery due to associated high morbidity and mortality. Here, we present a case report of a morbidly obese patient who underwent laparoscopic sleeve gastrectomy followed by single-lobe living donor liver transplantation (LDLT) with a successful outcome. We believe that this is the first report of successful LDLT following planned weight loss to facilitate LDLT. PMID:24386588

  4. A Single Center Study Comparing the Stainable Iron Depositions in 1000 Explanted Cirrhotic Livers of Different Causes

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    Geramizadeh

    2015-12-01

    Full Text Available Background There have been very few studies evaluating the close association between excess iron and cirrhosis; however, cirrhosis could be regarded as an iron-loading disorder. Objectives In this study, the goal was to show the levels of the iron content in the liver tissue in certain types of cirrhosis. Patients and Methods In this 7 year study (2008 - 2014, in 1000 explanted livers, the amount of iron was scored and compared according to the cause of the cirrhosis. The amount of iron in the liver was determined via the histochemical staining of the liver tissue, using Prussian-blue staining. Additionally, in each patient, the serum iron was determined and compared according to the cause of cirrhosis. Results The highest content of iron has been found in cirrhosis caused by chronic hepatitis (i.e. hepatitis B, C, and autoimmune hepatitis, as well as in alcoholic cirrhosis. The least amount of stainable iron has been shown in biliary cirrhosis. Conclusions The presence of high stainable iron in patients with cirrhosis, secondary to chronic viral hepatitis, autoimmune hepatitis, and alcoholic hepatitis, should not be considered indicative of the presence of hereditary hemochromatosis; however, in those patients with biliary cirrhosis, a high iron content is rare, and can be a sign of the presence of the high iron Fe (HFE gene mutation, or another type of hereditary hemochromatosis.

  5. Liver uptake of biguanides in rats.

    Science.gov (United States)

    Sogame, Yoshihisa; Kitamura, Atsushi; Yabuki, Masashi; Komuro, Setsuko

    2011-09-01

    Metformin is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus. The liver is the primary target, metformin being taken up into human and rat hepatocytes via an active transport mechanism. The present study was designed to compare hepatic uptake of two biguanides, metformin and phenformin, in vitro and in vivo. In in vitro experiments, performed using rat cryopreserved hepatocytes, phenformin exhibited a much higher affinity and transport than metformin, with marked differences in kinetics. The K(m) values for metformin and phenformin were 404 and 5.17μM, respectively, with CLint (V(max)/K(m)) values 1.58μl/min per 10(6) cells and 34.7μl/min per 10(6) cells. In in vivo experiments, when (14)C-metformin and (14)C-phenformin were given orally to male rats at a dose of 50mg/kg, the liver concentrations of radioactivity at 0.5 hour after dosing were 21.5μg eq./g with metformin but 147.1μg eq./g for phenformin, ratios of liver to plasma concentrations being 4.2 and 61.3, respectively. In conclusion, the results suggest that uptake of biguanides by rat hepatocytes is in line with the liver distribution found in vivo, phenformin being more efficiently taken up by liver than metformin after oral administration.

  6. Hemoperitoneum in cirrhotic patients without abdominal trauma or tumor

    Institute of Scientific and Technical Information of China (English)

    Yuan-Ji Ma; En-Qiang Chen; Jia-Jie Lu; Ming-Zhen Tan; Hong Tang

    2011-01-01

    BACKGROUND: Hemoperitoneum is associated with several emergency conditions and is especially evident when it occurs in patients with liver cirrhosis. This study aimed to assess the clinical characteristics of cirrhotic patients who did not have abdominal trauma or tumor but who developed hemoperitoneum. METHODS: Wereviewedtheclinicalrecordsof1276consecutive cirrhotic patients with hemoperitoneum at our center between January 2007 and December 2009. Hemoperitoneum was confirmed by abdominal paracentesis. RESULTS: Of the 1276 cirrhotic patients, 19 were found to have hemoperitoneum, but only 6 did not have abdominal trauma or tumor. The occurrence of spontaneous hemoperitoneum in the cirrhotic patients was therefore 0.5%. Hemoperitoneum can occur spontaneously in severely decompensated cirrhotic patients with intra-abdominal collateral vessels and high scores on the model for end-stage liver disease and Child-Pugh-Turcotte test. Most patients presented with abdominal distension, abdominal pain, increased abdominal girth and hemodynamic instability with a significant drop in the hemoglobin level. Three patients died of hemorrhagic shock within 24 hours, and the other 3 died of hepatic encephalopathy or spontaneous bacterial peritonitis after 5 to 10 days because of further decompensation of the liver. CONCLUSIONS: Hemoperitoneum can occur in cirrhotic patients who do not have abdominal trauma or tumor. It mainly occurs in severely decompensated end-stage cirrhotic patients. Cirrhotic patients with hemoperitoneum have a poor prognosis.

  7. Intraoperative pulmonary hypertension occurred in an asymptomatic patient with pre-existent liver cirrhotic and portal hypertension

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Portopulmonary hypertension (PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension, with or without advanced hepatic disease. Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state. Similar signs of advanced liver disease can be observed in severe PPH, with ascites and lower extremity edema. Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation (LT). We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis. Since this patient had no preoperation laboratory data supporting the diagnosises of pulmonary hypertension and was asymptomatic for a number of years, it was necessary to send him to the intensive care unit after operation. Further study should be focued on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality.

  8. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

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    Motoh Iwasa

    Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

  9. Grey scale enhancement by a new self-made contrast agent in early cirrhotic stage of rabbit liver

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    Zhang Yong

    2007-08-01

    Full Text Available Abstract Background The development of new ultrasound contrast agents (UCAs has become one of the most promising fields in ultrasound medicine. This paper evaluates a new self-made contrast agent enhancement effect developed to study the fibrotic stages of the liver in perfusion models in vivo. Methods We constructed experimental models of hepatic fibrosis involving five stages from F0 to F4 via administration of CCL4 (0.01 ml/kg BW every 3 days for 3 months. The intrahepatic circulatory time of the contrast agent was analyzed via an image and Cine-loop display. Calculations of the perfusion-related parameters including the peak signal intensity (PSI and peak signal intensity time (PIT of the portal vein and parenchyma were obtained from an analysis of the time-acoustic intensity curve. Results Hepatic artery to vein transmit time (HA-HVTT was significantly shorter at F4 stage (mean 5.1 seconds compared with those in other stages (mean 8.3 s, 7.5 s, 6.9 s, 6.6 s, P Conclusion These results indicate that the new self-made contrast agent is capable of indicating intrahepatic hemodynamic changes. HA-HVTT and the PSI difference of the microbubble perfusion in liver parenchyma and PV were considered to differentiate the degree of hepatic fibrosis between F4 and other early stages.

  10. Intravenous patient-controlled fentanyl with and without transversus abdominis plane block in cirrhotic patients post liver resection

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    Serag Eldin M

    2014-05-01

    Full Text Available Manar Serag Eldin,1 Fatma Mahmoud,1 Rabab El Hassan,2 Mohamed Abdel Raouf,1 Mohamed H Afifi,2 Khaled Yassen,1 Wesam Morad31Department of Anaesthesia, Liver Institute, 2Department of Anaesthesia, Faculty of Medicine, 3Department of Community Medicine and Public Health, Liver Institute, Menoufiya University, Shebin El-Kom, EgyptBackground: Coagulation changes can complicate liver resection, particularly in patients with cirrhosis. The aim of this prospective hospital-based comparative study was to compare the postoperative analgesic efficacy of intravenous fentanyl patient-controlled analgesia (IVPCA with and without transversus abdominis plane (TAP block.Methods: Fifty patients with Child’s A cirrhosis undergoing liver resection were randomly divided into two groups for postoperative analgesia, ie, an IVPCA group receiving a 10 µg/mL fentanyl bolus of 15 µg with a 10-minute lockout and a maximum hourly dose of 90 µg, and an IVPCA + TAP group that additionally received TAP block (15 mL of 0.375% bupivacaine on both sides via a posterior approach with ultrasound guidance before skin incision. Postoperatively, bolus injections of bupivacaine 0.375% were given every 8 hours through a TAP catheter inserted by the surgeon in the open space during closure of the inverted L-shaped right subcostal with midline extension (subcostal approach guided by the visual analog scale score (<3, 5 mL; 3 to <6, 10 mL; 6–10, 15–20 mL according to weight (maximum 2 mg/kg. The top-up dosage of local anesthetic could be omitted if the patient was not in pain. Coagulation was monitored using standard coagulation tests.Results: Age, weight, and sex were comparable between the groups (P<0.05. The visual analog scale score was significantly lower at 12, 18, 24, 48, and 72 hours (P<0.01 in IVPCA + TAP group. The Ramsay sedation score was lower only after 72 hours in the IVPCA + TAP group when compared with the IVPCA group (1.57±0.74 versus 2.2±0.41, respectively, P

  11. Preparation of rough microsomes from rat liver.

    Science.gov (United States)

    Sabatini, David D

    2014-08-01

    This protocol describes how to prepare rat liver rough microsomes that contain undegraded membrane-bound polysomes and can function very well in an in vitro translation system. It uses endogenous ribonuclease inhibitor in all steps, avoiding pelleting rough microsomes in all steps and sacrificing good recovery.

  12. Ozone inhalation modifies the rat liver proteome

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    Whitney S. Theis

    2014-01-01

    Full Text Available Ozone (O3 is a serious public health concern. Recent findings indicate that the damaging health effects of O3 extend to multiple systemic organ systems. Herein, we hypothesize that O3 inhalation will cause downstream alterations to the liver. To test this, male Sprague-Dawley rats were exposed to 0.5 ppm O3 for 8 h/day for 5 days. Plasma liver enzyme measurements showed that 5 day O3 exposure did not cause liver cell death. Proteomic and mass spectrometry analysis identified 10 proteins in the liver that were significantly altered in abundance following short-term O3 exposure and these included several stress responsive proteins. Glucose-regulated protein 78 and protein disulfide isomerase increased, whereas glutathione S-transferase M1 was significantly decreased by O3 inhalation. In contrast, no significant changes were detected for the stress response protein heme oxygenase-1 or cytochrome P450 2E1 and 2B in liver of O3 exposed rats compared to controls. In summary, these results show that an environmentally-relevant exposure to inhaled O3 can alter the expression of select proteins in the liver. We propose that O3 inhalation may represent an important unrecognized factor that can modulate hepatic metabolic functions.

  13. Chronological protein synthesis in regenerating rat liver.

    Science.gov (United States)

    He, Jinjun; Hao, Shuai; Zhang, Hao; Guo, Fuzheng; Huang, Lingyun; Xiao, Xueyuan; He, Dacheng

    2015-07-01

    Liver regeneration has been studied for decades; however, its regulation remains unclear. In this study, we report a dynamic tracing of protein synthesis in rat regenerating liver with a new proteomic technique, (35) S in vivo labeling analysis for dynamic proteomics (SiLAD). Conventional proteomic techniques typically measure protein alteration in accumulated amounts. The SiLAD technique specifically detects protein synthesis velocity instead of accumulated amounts of protein through (35) S pulse labeling of newly synthesized proteins, providing a direct way for analyzing protein synthesis variations. Consequently, protein synthesis within short as 30 min was visualized and protein regulations in the first 8 h of regenerating liver were dynamically traced. Further, the 3.5-5 h post partial hepatectomy (PHx) was shown to be an important regulatory turning point by acute regulation of many proteins in the initiation of liver regeneration.

  14. Electrochemotherapy for rat implanted liver tumour

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The most common interventional therapies for liver cancer at present include transcatheter hepatic arterial chemoembolization (TACE),1 percutaneous ethanol injection2 and radiofrequency ablation,3 but all these therapies have some intrinsic disadvantages. Since the advent of electrochemo- therapy (EChT), it has been accepted as a safe and effective therapy for malignant tumors4,5 There are only a few experimental studies reporting the use of EChT in the treatment of liver cancer in the foreign medical literature.6-8 However, there have been some clinical studies, and even fewer reports of experimental studies on EChT for liver cancer in China. We used a rat implanted liver cancer animal model to monitor changes in tumour size, tumour necrosis, cellular apoptosis, expression of peripheral immunological markers (IL-2, sIL-2R, IL-6 and TNF-α) and survival.

  15. Ayurvedic management of cirrhotic ascites

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    G Aswathy

    2016-01-01

    Full Text Available Cirrhosis is the final stage of most of the chronic liver diseases and is most invariably complicated by portal hypertension resulting in ascites. A case of chronic liver disease with portal hypertension (cryptogenic cirrhosis, managed at Amrita School of Ayurveda is discussed in this paper. The clinical picture was that of an uncomplicated cirrhotic ascites. Snehapāna (therapeutic oral administration of lipids followed by virecana (purgation was done after an initial course of nityavirecana (daily purgation. Later Vardhamāna pippalī rasāyana [administration of single drug - pippalī (piper longum in a structured dose pattern] was administered with an intention of rejuvenating liver cells. Ascites and lower limb oedema were completely resolved after the therapy. No recurrence of ascites has been reported after a follow up period of one year.

  16. SOME THEORETICAL ASPECTS OF COMPLEX CLINICAL-PSYCHOLOGICAL INVESTIGATION OF PATIENTS WITH AUTOIMMUNE LIVER DISEASES IN CIRRHOTIC STAGE BEFORE LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    O. A. Gerasimova

    2010-01-01

    Full Text Available This article presents preliminary results of complex clinical-psychological investigation of patients with autoim- mune liver diseases with cirrhosis waiting for liver transplant. The data discussed defense role of anxiety com- bined with other emotional affective disorders, psychological mechanisms in combination with coping strategies of stress-overcoming behavior in the state of disease and their involvement in formation of the clinical picture of the disease. It considers the need for differential diagnosis of the pathology using modern experimental- psychological methods in connection with further building of psychological aid to patients with autoimmune liver diseases. 

  17. 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

  18. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure.

    Science.gov (United States)

    Kuijk, Ewart W; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M; Cuppen, Edwin

    2016-02-26

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah(-/-) Il2rg(-/-) rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat.

  19. Uso de quercetina a longo prazo em ratos cirróticos The long term use of quercetin in cirrhotic rats

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    Aline Miltersteiner

    2003-06-01

    Full Text Available OBJETIVO: Avaliar o uso a longo prazo do flavonóide quercetina em ratos cirróticos por ligadura de ducto biliar comum (LDB. MÉTODOS: Foram utilizados 32 ratos machos Wistar, sendo submetidos à LDB ou simulação, e distribuídos em 4 grupos: 1 controle, 2 cirróticos, 3 cirróticos tratados com quercetina 50mg/kg, intraperitonealmente, desde o segundo dia após o procedimento cirúrgico; e 4 cirróticos tratados após o décimo quarto dia do procedimento cirúrgico. Analisou-se a função hepática por meio de testes bioquímicos (BT e BD e atividade enzimática (ALT, AST, FA e GGT. Na análise anatomopatológica, utilizou-se a coloração de Hematoxilina & Eosina (H&E e de Picrosírius para fibrose. A análise estatística para avaliação de sobrevivência foi realizada pelo teste Kaplan-Meier. RESULTADOS: Os resultados de sobrevivência dos oito animais de cada grupo foram: Grupo 1 = 200 dias de sobrevivência; Grupo 2 = 46 dias; Grupo 3 = 71 dias; e o Grupo 4 = 90 dias. Nos animais com ligadura de ducto biliar comum houve aumento das provas de função hepática e enzimáticas que se reduziu hipoteticamente com o tratamento com quercetina. Foram identificadas cirrose, congestão vascular porta e centrolobular na análise histopatológica por H&E e Picrosírius. CONCLUSÃO: O uso da quercetina diminuiu de maneira significante as alterações bioquímicas provocadas pela cirrose, aumentando o tempo de sobrevivência dos animais com cirrose biliar secundária à LDB, como verificado pelo teste de análise de sobrevivência.PURPOSE: The long term use of quercetin flavonoid was evaluated in cirrhotic rats by common biliary duct bondage (LDB. METHODS: 32 male Wistar rats were submitted to LDB or simulation, and distributed in 4 groups: 1 control, 2 cirrhotic, 3 cirrhotic treated with quercetin the second day after the surgical procedure; and 4 cirrhotic treated with quercetin after the fourteenth day of the surgical procedure. The hepatic

  20. Impact of different levels of protein supply on the cytokines in cirrhotic rats%不同蛋白质供给水平对肝硬化大鼠血清细胞因子的影响

    Institute of Scientific and Technical Information of China (English)

    王真真; 齐玉梅; 郝春满; 陈亚军; 肖慧娟; 徐常杰

    2012-01-01

    目的 探讨不同蛋白质供给水平对肝硬化大鼠血清细胞因子的影响.方法 将清洁级健康雄性Wistar 大鼠60只随机分为4组,即正常对照组(N组)、低蛋白组(L组)、标准蛋白组(S组)、高蛋白组(H组).采用CCl4和酒精复合法复制肝硬化大鼠模型.成模后采用含不同蛋白质水平的饲料进行干预,干预周期为6周.在干预前后取血检测各组大鼠血清TNF-α、IL-10、IGF-1水平.结果 与干预前比较,干预后各模型组大鼠的TNF-α和IGF-1均升高(P<0.05);干预后,L组TNF-α低于H组(P<0.05),S组IL-10高于H组(P<0.05),S组IGF-1高于L组(P<0.05).结论 不同蛋白质供给水平对肝硬化大鼠血清细胞因子均有所改善;正常水平的蛋白质供给即可改善免疫功能,而高蛋白的摄入并不能增强这种作用.%Objective To explore the effect of different levels of protein on the cytokines in rats with liver cirrhosis. Methods A total of 60 healthy male Wistar rats were randomly divided into four groups: normal control group (N) , low-protein group (L) , the standard protein group (S) , high-protein group (H). Cirrhotic rat model was established by CC14 and alcohol. After modeling, supply different levels of protein to relevant groups, the intervention period was six weeks. Before and after the intervention, the serum levels of TNF-a, IL-10 and IGF-1 of rats in each group were detected. Results After intervention, the TNF-a and IGF-1 of model rats were significantly increased (P <0.05) ; but TNF-a of L group was lower than that in H group ( P < 0. 05 ) . The level of IL-10 in S group was higher than that in H group (P < 0. 05 ) , and IGF-1 of S group was higher than that in L group (P < 0.05 ). Conclusion After the supply of different levels of protein to cirrhotic rats, the levels of cytokines had improved; normal protein supply could improve immune function, but high protein intake didn't enhance this effect.

  1. Coenzyme metabolism in rat liver transketolase

    Energy Technology Data Exchange (ETDEWEB)

    Gorbach, Z.V.; Kubyshin, V.L.; Maglysh, S.S.; Zabrodskaya, S.V.

    1987-01-10

    On the basis of the results of kinetic investigations, two binding sites for hydroxythiamine diphosphate were determined in apotransketolase, with sharply differing values of K/sub i/: (7-22) x 10/sup -9/ and (13.0-19.7) x 10/sup -8/ M. A study was made of the turnover rate of thiamine diphosphate in holotransketolase in rat liver tissue by a radioisotope method, using (/sup 14/C) thiamine as the labeled precursor. The half-substitution time and rate constant of degradation of the coenzyme in transketolase are close in absolute values to the analogous indices for the protein portion of the enzyme and constitute 153 h and 0.108 day/sup -1/, respectively. Rat liver transketolase exists in vivo in the form of a substituted ..cap alpha..-carbanion. Replacement of thiamine diphosphate by hydroxythiamine diphosphate in the holoenzyme has no effect on the formation of the intermediate ..cap alpha..-carbanion form of the enzyme.

  2. Effects of Jianpi Huoxue Qushi recipe on the hepatic mitochondrial of cirrhotic rats complicated with ascites%健脾活血袪湿方对肝硬化腹水大鼠肝线粒体的影响

    Institute of Scientific and Technical Information of China (English)

    李嘉; 刘友章; 陈美仁; 吴海斌

    2014-01-01

    Objective: The study aims at observing whether Jianpi Huoxue Qushi recipe can improve the expression of the cytochrome C oxidase activity, ATP content, ATPase activity of liver to cirrhotic rats complicated with ascites treated by TCM. Methods:The animals experiment consists of ninety healthy Wistar rats which were specific pathogen free (SPF). The rats were divided randomly into the blank group, the model group and the group treating with Jianpi Huoxue Qushi recipe with high, medium and low dosages and the group treating with colchicines. Make the model group with an improved CCL4 combined with alcohol method. Then check their livers cytochrome C oxidase activity, ATP content, ATPase activity. Results: The expression of cytochrome C oxidase activity, ATP content, ATPase activity of blank group has remarkable difference with the model group (P0.05). Conclusions: Jianpi Huoxue Qushi recipe can increase the expression of cytochrome C oxidase activity, ATP content and ATPase activity. It can increase the energy synthesis of mitochondria and improve the disorder of energy metabolism of mitochondria.%目的:观察健脾活血祛湿方对肝硬化腹水大鼠肝线粒体细胞色素C氧化酶活性、ATP含量、ATP酶活性表达的影响。方法:将健康SPF级雄性Wistar大鼠90只,随机分为空白组、模型组、健脾活血祛湿方高、中、低剂量组及秋水仙碱组,运用改良CCL4-酒精综合法造肝硬化腹水大鼠模型。提取肝线粒体进行细胞色素C氧化酶活性、ATP含量、ATP酶活性测定。结果:模型组肝线粒体细胞色素 C 氧化酶活性、ATP 含量、ATP 酶活性均明显低于空白组,与空白组相比有显著差异(P0.05袪)。结论:健脾活血湿方能引起肝线粒体细胞色素 C 氧化酶活性、ATP含量、ATP酶活性的表达升高,缓解肝线粒体损伤,改善肝线粒体能量代谢作用,维持肝细胞功能。

  3. 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.

  4. Multi-organ perfusion CT in the abdomen using a 320-detector row CT scanner: Preliminary results of perfusion changes in the liver, spleen, and pancreas of cirrhotic patients

    Energy Technology Data Exchange (ETDEWEB)

    Motosugi, Utaroh, E-mail: utaroh-motosugi@nifty.com [Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi (Japan); Ichikawa, Tomoaki, E-mail: ichikawa@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi (Japan); Sou, Hironobu, E-mail: fffun0300@yahoo.ac.jp [Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi (Japan); Morisaka, Hiroyuki, E-mail: morisakahiroyuki@hotmail.co.jp [Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi (Japan); Sano, Katsuhiro, E-mail: snkthr@yahoo.co.jp [Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi (Japan); Araki, Tsutomu, E-mail: arakit@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi (Japan)

    2012-10-15

    Purpose: To utilize 320-detector row CT in perfusion CT of multiple abdominal organs and to compare the tissue perfusion between patients with and without liver cirrhosis. Materials and methods: This study included 21 patients with cirrhosis and 20 without cirrhosis. The 320-detector row CT scanner enabled multi-organ perfusion CT without requiring the scanner table to be moved. Perfusion was calculated using the maximum slope model for the aorta, the portal vein, the right and left lobes of the liver, the head and body of the pancreas, the spleen, and the corpus and antrum of the stomach. Perfusion in each organ of patients with and without cirrhosis was compared. Results: Portal venous perfusion of the right and left lobes of the liver in patients with cirrhosis (117 and 100 mL min{sup −1} 100 mL{sup −1}, respectively) was significantly less than that in patients without cirrhosis (213 and 174 mL min{sup −1} 100 mL{sup −1}, respectively; p = 0.0081 and 0.0294, respectively). Arterial perfusion of the spleen (111 mL min{sup −1} 100 mL{sup −1}) and the body of the pancreas (112 mL min{sup −1} 100 mL{sup −1}) in patients with cirrhosis was also significantly decreased compared with that in patients without cirrhosis (spleen, 162 mL min{sup −1} 100 mL{sup −1}, p = 0.0020; body of pancreas, 133 mL min{sup −1} 100 mL{sup −1}, p = 0.0405). Conclusion: The results of the perfusion CT suggest that arterial perfusion of the spleen and the body of the pancreas, as well as portal perfusion of the liver, in cirrhotic patients was decreased compared with that in non-cirrhotic patients.

  5. 正常肝脏和肝硬化门静脉高压患者CT增强扫描参数研究%Study on protocol in spiral CT scanning:comparison between normal liver and cirrhotic liver

    Institute of Scientific and Technical Information of China (English)

    程明; 陈文军; 赵新宇; 王恩峰

    2015-01-01

    Objective:To study the effect of scanning protocol on image quality when the normal and cirrhotic livers were examined by contrast-enhanced MSCT. Methods:Sixty healthy volunteers were divided into group A and B,which had the conventional and high dose respectively. And ninty patients were divided into group C,D and E,which had the conventional dose,high dose and high dose and delay time respectively. The CT values of hepatic artery,portal vein,liver parenchyma,hepatic vein and the density difference values between portal vein and liver parenchyma were measured. The image quality was scored with double-blind method. Results:The CT values of hepatic artery,portal vein,hepatic vein and the density difference values between portal vein and liver parenchyma had obvious statistical differences between group A and B (P<0.05),and liver parenchyma had no statistical difference. The image quality score had no statistical difference between group A and B. The CT values of hepatic artery,portal vein,liver parenchyma,hepatic vein and the density difference values between portal vein and liver parenchyma had obvious statistical differences between group C and D (P<0.05). The CT values of hepatic artery and portal vein in group E were lower than those in group D,but had no statistical difference (P>0.05),while the CT values of hepatic vein and liver parenchyma in group E increased and the density difference values between portal vein and liver parenchyma decreased ,and they had significant differences to those in group D (P<0.05). The image quality scores had statistical differences in group C, D and E (P<0.05). Conclusions:When the livers are examined by contrast-enhanced MSCT with the injection rate of 3 mL/s, the optimal protocol for normal livers: contrast agent dose is 1.5 mL/kg,start time of hepatic arterial phase is 28 s,start time of portal vein phase is 60 s. The optimal protocol for cirrhotic livers: contrast agent dose is 2.0 mL/kg ,start time of hepatic

  6. Toxicogenomics of resveratrol in rat liver.

    Science.gov (United States)

    Hebbar, Vidya; Shen, Guoxiang; Hu, Rong; Kim, Bok-Ryang; Chen, Chi; Korytko, Peter J; Crowell, James A; Levine, Barry S; Kong, A-N Tony

    2005-04-01

    Resveratrol, a polyphenolic compound found in grape skin and peanuts has been shown to prevent many diseases including cardiovascular diseases and cancer. To better understand resveratrol's potential in vivo toxicity, we studied the dose response using cDNA stress arrays coupled with drug metabolizing enzymatic (DME) assays to investigate the expression of stress-responsive genes and Phase I and II detoxifying enzymes in rat livers. Male and female CD rats were treated with high doses of resveratrol (0.3, 1.0 and 3.0 gm/kg/day) for a period of 28 days. Total RNA from rat liver was reverse-transcribed using gene-specific primers and hybridized to stress-related cDNA arrays. Among female rats, Phase I DME genes were repressed at 0.3 and 1.0 gm/kg/day doses, while genes such as manganese superoxide dismutase, cytochrome P450 reductase, quinone oxidoreductase and thiosulfate sulfurtransferase demonstrated a dose-dependent increase in gene expression. The modulation of these liver genes may implicate the potential toxicity as observed among the rats at the highest dose level of resveratrol. Real-Time PCR was conducted on some of the Phase II DME genes and anti-oxidant genes to validate the cDNA array data. The gene expression from real-time PCR demonstrated good correlation with the cDNA array data. UGT1A genes were amongst the most robustly induced especially at the high doses of resveratrol. We next performed Phase I and Phase II enzymatic assays on cytochrome P450 2E1 (CYP2E1), cytochrome P450 1A1 (CYP1A1), NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferase (GST) and UDP-glucuronosyl transferase (UGT). Induction of Phase II detoxifying enzymes was most pronounced at the highest dose of resveratrol. CYP1A1 activity demonstrated a decreasing trend among the 3 dose groups and CYP2E1 activity increased marginally among female rats over controls. In summary, at lower doses of resveratrol there are few significant changes in gene expression whereas the

  7. Comparison of homocysteine level between pre- and post- liver transplantation in cirrhotic patients%肝硬化患者肝移植术前后同型半胱氨酸水平对比分析

    Institute of Scientific and Technical Information of China (English)

    林建华; 周杰

    2011-01-01

    Objection To analyze the change of plasma homocysteine (Hey) of pre- and post-liver transplantation in cirrhotic patients. Methods The plasma concentrations of Hey were measured in 36 cases of cirrhotic patients before and three months after liver transplantation, and 40 healthy subjects (control group). Results were compared each other. Results The Hcy level was significantly decreased in patients post-operation compared with before operation (P <0.05), and also significantly decreased at three months post-operation. There was significant difference between pre- and three months post-operation (P <0.05). Conclusions It is demonstrated that the liver is the major site for the metabolism of Hcy.%目的 探讨肝硬化患者肝移植术前及术后血浆同型半胱氨酸(Hcy)水平变化的意义.方法 36例肝硬化行肝移植的患者于术前、术后3个月及40名健康人群进行血浆Hcy定量测定,比较各组之间的差别.结果 肝硬化肝移植患者术前Hcy水平较健康人群增高(P<0.05),术后3个月血浆Hcy水平明显下降,术前、术后相比较差异显著(P<0.05).结论 肝硬化肝移植患者术后血浆Hcy水平明显下降,提示肝脏是一个重要的Hcy代谢器官.

  8. 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.

  9. Donor liver natural killer cells alleviate liver allograft acute rejection in rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Dong Yu; Tian-Zhu Long; Guo-Lin Li; Li-Hong Lv; Hao-Ming Lin; Yong-Heng Huang; Ya-Jin Chen; Yun-Le Wan

    2011-01-01

    BACKGROUND: Liver enriched natural killer (NK) cells are of high immune activity. However, the function of donor liver NK cells in allogeneic liver transplantation (LTx) remains unclear. METHODS: Ten Gy of whole body gamma-irradiation (WBI) from a 60Co source at 0.6 Gy/min was used for depleting donor-derived leukocytes, and transfusion of purified liver NK cells isolated from the same type rat as donor (donor type liver NK cells, dtlNKs) through portal vein was performed immediately after grafting the irradiated liver. Post-transplant survival observation on recipients and histopathological detection of liver grafts were adoptive to evaluate the biological impact of donor liver NK cells on recipients' survival in rat LTx. RESULTS: Transfusion of dtlNKs did not shorten the survival time among the recipients of spontaneous tolerance model (BN to LEW rat) after rat LTx, but prolonged the liver graft survival among the recipients depleted of donor-derived leukocytes in the acute rejection model (LEW to BN rat). Compared to the recipients in the groups which received the graft depleted of donor-derived leukocytes, better survival and less damage in the allografts were also found among the recipients in the two different strain combinations of liver allograft due to transfusion of dtlNKs. CONCLUSIONS: Donor liver NK cells alone do not exacerbate liver allograft acute rejection. Conversely, they can alleviate it, and improve the recipients' survival.

  10. Using ultrasound Nakagami imaging to assess liver fibrosis in rats.

    Science.gov (United States)

    Ho, Ming-Chih; Lin, Jen-Jen; Shu, Yu-Chen; Chen, Chiung-Nien; Chang, King-Jen; Chang, Chien-Cheng; Tsui, Po-Hsiang

    2012-02-01

    This study explored the feasibility of using the ultrasound Nakagami image to assess the degree of liver fibrosis in rats. The rat has been widely used as a model in investigations of liver fibrosis. Ultrasound grayscale imaging makes it possible to observe fibrotic rat livers in real time. Statistical analysis of the envelopes of signals backscattered from rat livers may provide useful clues about the degree of liver fibrosis. The Nakagami-model-based image has been shown to be useful for characterizing scatterers in tissues by reflecting the echo statistics, and hence the Nakagami image may serve as a functional imaging tool for quantifying rat liver fibrosis. To validate this idea, fibrosis was induced in each rat liver (n=21) by an intraperitoneal injection of 0.5% dimethylnitrosamine. Livers were excised from rats for in vitro ultrasound scanning using a single-element transducer. The backscattered-signal envelopes of the acquired raw ultrasound signals were used for Nakagami imaging. The Metavir score determined by a pathologist was used to histologically quantify the degree of liver fibrosis. It was found that the Nakagami image could be used to distinguish different degrees of liver fibrosis in rats, since the average Nakagami parameter increased from 0.55 to 0.83 as the fibrosis score increased from 0 (i.e., normal) to 4. This correlation may be due to liver fibrosis in rats involving an increase in the concentration of local scatterers and the appearance of the periodic structures or clustering of scatterers that would change the backscattering statistics. The current findings indicate that the ultrasound Nakagami image has great potential as a functional imaging tool to complement the use of the conventional B-scan in animal studies of liver fibrosis.

  11. Dinucleosidasetetraphosphatase in rat liver and Artemia salina.

    Science.gov (United States)

    Vallejo, C G; Lobaton, C D; Quintanilla, M; Sillero, A; Sillero, M A

    1976-06-07

    A comparative study of an enzymatic activity present in Artemia salina and rat liver which specifically splits dinucleoside tetraphosphates is presented. All the purine and pyrimidine dinucleoside tetraphosphates tested, i.e. diadenosine, diguanosine, dixanthosine and diuridine tetraphosphates, were substrates of both enzymes with similar maximum velocities and Km values, (around 10 muM). The inhibition by nucleotides of the enzyme from the two sources is also similar. Particularly relevant is the strong inhibition caused by nucleoside tetraphosphates which have Ki values in the nanomolar range. The Artemia enzyme has a slightly lower molecular weight (17 500) than the liver enzyme (21 000) and is more resistant to acidic pH. Based on previous findings, the enzyme from Artemia salina was named diguanosinetetraphosphatase (EC 3.6.1.17) by the Enzyme Commission. The results presented in this paper show that the liver and Artemia enzymes are similar, and we propose to name this enzyme as dinucleosidetetraphosphatase or dinucleoside-tetraphosphate nucleotidehydrolase.

  12. 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.

  13. Importance Rat Liver Morphology and Vasculature in Surgical Research.

    Science.gov (United States)

    Vdoviaková, Katarína; Vdoviaková, Katarína; Petrovová, Eva; Krešáková, Lenka; Maloveská, Marcela; Teleky, Jana; Jenčová, Janka; Živčák, Jozef; Jenča, Andrej

    2016-12-02

    BACKGROUND The laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals. MATERIAL AND METHODS Forty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria. RESULTS We found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors. CONCLUSIONS Our results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations.

  14. Evaluation of Echocardiographic Findings in Cirrhotic Patients

    Directory of Open Access Journals (Sweden)

    M Seidian

    2005-10-01

    Full Text Available Introduction: Cardiovascular abnormalities have been reported in liver cirrhosis (LC. In these patients, cardiac symptoms and physical signs occur as the liver functions worsen. Cirrhosis is associated with hyper dynamic circulation and beta-adrenergic system changes responsible for the cardiovascular abnormalities. The purpose of the present study was to explore the echocardiographic findings in cirrhotic patients. Methods: A total of 90 patients (63 men, 27 women with imaging or biopsy-proven cirrhosis of various etiologies without any known cardiac dysfunction were included in the study. Ninety healthy persons of the same age and sex were enrolled as the control group. Cirrhotic patients and controls were investigated by echocardiography. Left ventricle diastolic function (E/A ratio, systolic function (ejection fraction, and wall thickness (left ventricle posterior wall thickness + interventricular septum thickness along with left and right ventricular dimensions were evaluated. Results: Right & left atrium and ventricle diameters were enlarged in 3 cirrhotic patients and the E/A ratio was decreased in class C patients (0.9 ± 0.2 as compared to class B and A (1.3 ± 0.4 and controls (1.3± 1 (P value < 0.05. The left ventricular end diastolic volumes were increased in 3 cirrhotic patients(5.9+/- 0.3(normal 3.5-4.7 cm. The estimated ejection fraction was decreased in39 cirrhotic patients; 28 patients with ascites (35 -47% as compared to 11 patients without ascites (40-48% and controls (50-75% (P < 0.05. Conclusion: Liver cirrhosis is associated with enlarged left cardiac chambers, but wall thickness and right ventricle functions and diameters are normal. LV Diastolic dysfunction and decreased ejection fraction are evident in cirrhotic patients with ascites in class C children. This demonstration of diastolic dysfunction together with the dilated left cardiac chambers suggests that the patients indeed have cardiac abnormalities. Cardiovascular

  15. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity

    DEFF Research Database (Denmark)

    Thiesson, Helle; Jensen, Boye L; Bistrup, Claus;

    2007-01-01

    rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining......, and reduced ascites formation to the same degree as direct inhibition of MR with K-canrenoate. Total potassium balance was negative in the BDL rats, whereas renal potassium excretion was unchanged. In the distal colon, expression of ENaC was increased in BDL rats. Fecal potassium excretion was increased...... by endogenous glucocorticoids. In addition, the overall potassium loss in the BDL model is due to increased fecal potassium excretion, which is associated with upregulation of ENaC in distal colon....

  16. Effects of heme oxygenase-1 on pulmonary function and structure in rats with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    GUO Shi-bin; DUAN Zhi-jun; LI Qing; SUN Xiao-yu

    2011-01-01

    Background The hepatopulmonary syndrome (HPS) is a severe vascular complication in lungs resulting in systemic hypoxemia in patients with cirrhosis and portal hypertension. The underlying structural change in HPS is intrapulmonary vasodilation, which can lead to impaired oxygenation of pulmonary venous blood. It has been demonstrated that the heme oxygenase-1/carbon monoxide (HO-1/CO) system plays an important role in the control of vascular tone. The aim of this study was to further investigate the role of HO-1 in the pathogenesis of HPS in animal model.Methods Totally 35 rats were divided into liver cirrhosis, zinc protoporphyrin Ⅸ (ZnPP), cobalt protoporphyrin (CoPP)and sham groups. Biliary cirrhosis was established in the first three groups by bile duct ligation. Rats in the ZnPP and CoPP groups received once intraperitoneal injection of ZnPP and CoPP, respectively, 24 hours before sample collection.Expression of HO-1 mRNA in lung was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohistochemical analysis. Hematoxylin and eosin staining was performed to confirm the presence of liver cirrhosis and intrapulmonary vasodilation. Arterial blood gases, mean arterial pressure and portal vein pressure were also measured. Analysis of variance or Wilcoxon statistical methods were used to determine statistical significance.Results Compared with the sham group, the cirrhotic group demonstrated increased expression of pulmonary HO-1 mRNA and protein (P<0.01). The level of arterial carboxyhemoglobin (COHb), alveolar-arterial oxygen gradient (A-aPO2),mean arterial pressure, portal vein pressure (P<0.05, respectively), and intrapulmonary vasodilation were also significantly increased. Compared with the cirrhotic group, CoPP treatment increased pulmonary HO-1 mRNA and protein expression, the level of A-aPO2 (P <0.05 respectively), COHb (P <0.01), and intrapulmonary vasodilation, while ZnPP treatment

  17. Potential neoplastic effects of parathion-methyl on rat liver

    Institute of Scientific and Technical Information of China (English)

    M. Nisa UNALDI CORAL; Sonay UCMAN; Hasan YILDIZ; Haydar OZTAS; Semih DALKILIC

    2009-01-01

    The mutagenic and carcinogenic effects of parathion-methyl were examined by bacterial reverse assay and a long term experiment with Wistar rats. The potential mutagenic effect of parathion-methyl in Salmonella typhimurium TA100 bacterial cells was observed without rat liver S9 metabolic activation. Parathion-methyl was further investigated for pathological changes in rat pancreas and liver. The long-term rat experiments showed that parathion-methyl exposure for 3 months can cause pathological changes in rat pancreases acinar cells and pancreatic hepatocytes. Atypical acinar cell focuses (AACF) were determined in the liver and pancreas of the rats. The results from short-term Ames test and long-term rat experiments suggest that parathion-methyl would be potential carcinogenic.

  18. Coagulation abnormalities in the cirrhotic patient.

    Science.gov (United States)

    Muciño-Bermejo, Jimena; Carrillo-Esper, Raúl; Uribe, Misael; Méndez-Sánchez, Nahum

    2013-01-01

    The clotting process is a dynamic array of multiple processes which can be described in four phases: platelet plug initiation and formation, clotting process propagation by the coagulation cascade, clotting termination by antithrombotic mechanisms and clot removal by fibrinolysis. The liver plays a central role in each of these phases of clotting process, as it synthesizes the majority of coagulation factors and proteins involved in fibrinolysis as well as thrombopoeitin, which is responsible for platelet production from megakaryocytes. Many pathological processes associated with cirrhosis, such as portal hypertension and endothelial dysfunction, as well as co-morbid conditions, may also alter the coagulation process. Consequently, patients with liver disease have a disturbed balance of procoagulant and anti-coagulant factors which deviates from the normal coagulation cascade. This situation poses an additional problem in the diagnostic and therapeutic approach to this group of patients, since traditional coagulation test may not be reliable for assessing bleeding or thrombotic risk and traditional transfusional strategies may not be applicable in cirrhotic patients. In this article, we review the pathophysiological bases of coagulation abnormalities, in cirrhotic patients, the diagnostic therapeutic strategies to be followed and its impact on the clinical outcome in the cirrhotic patient.

  19. Magnetic resonance diffusion-weighted imaging in the diagnosis of diffuse liver diseases in rats

    Institute of Scientific and Technical Information of China (English)

    GUAN Sheng; ZHOU Kang-rong; ZHAO Wei-dong; PENG Wei-jun; TANG Feng; MAO Jian

    2005-01-01

    Background The diagnosis of diffuse hepatic lesions in early stage is a tough task at any time for clinical conventional imaging Magnetic resonance diffusion-weighted imaging (MR DWI) can detect the changes of tissue structure at molecular level This study was designed to determine the value of DWI in the diagnosis of diffuse liver lesions in early stage.Methods Diffuse liver lesions were induced by diethylnitrosamine in 42 rats of test group. Fourteen rats in control group were fed with pure water. Dynamic changes of MR DWI were observed every week in both groups during the early stage of diffuse liver lesions (1 to 12 weeks after drug administration in the test group). Apparent diffusion coefficient (ADC) values of liver parenchyma in different stages and pathologic changes were analyzed.Results The process of diffuse hepatic lesions in the test group was classified into three stages according to pathological changes, namely hepatitis, hepatic fibrosis and cirrhosis. No obvious morphological changes were shown by conventional imaging in both groups during this stage. But MR DWI demonstrated heterogeneous signal changes in early stage of hepatic cirrhosis in the test group. No significant change of ADC values was found in the control group between different weeks (P>0.05). The ADC values of the test group declined from the fifth week, and after the tenth week the ADC values were significantly different between the test and control groups at gradient factor (b) value 300 sec/mm2 (P<0.05). At b value 600 and 1000 sec/mm2, significant difference was seen between the two groups from the sixth week onward. The range of ADC value of the groups was (1.7-0.9)±(0.40-0.04) mm2/sec (b=600) and (1.38-0.75)±(0.07-0.35) mm2/sec (b=1000), respectively. Dominant pathological changes included swelled hepatocytes within 1 to 4 weeks after the administration of diethylnitrosamine in the test group, hyperplasia of fibrous tissues in 5-8 weeks and formation of cirrhotic nodules in 9

  20. The role of endotoxin in the pathogenesis of gastric mucosal damage in cirrhotic rats with portal hypertensive gastropathy

    Institute of Scientific and Technical Information of China (English)

    ChengLan; XiaoningSun; LiweiDong; BailiHuang; SuYuan; KeliWu

    2011-01-01

    Objective:To study the role and the mechanism of endotoxin in the pathogenesis of gastric mucosa during portal vein hypertension gastrography (PHG) in the rats with cirrhosis. Methods:Rat model for PHG was established by injection of tetrachloride. The animals were injected with endotoxin i.p. at 3 mg/kg and endotoxin antagonist BPI21 i.v. at 2.0 mg/kg. The plasma level of endotoxin as well as the gastric mucosal level of tumor necrosis factor alpha (TNF-α) was measured with azobenzene and ELISA respectively. Furthermore, the pathological changes of the gastric mucosa were studied with HE stainning. Results:In rats with PHG, increased endotoxin and TNF-αas well as the gastric pathological lesion were observed. Injection of endotoxin remarkably increased plasma level of endotoxin as well as the gastric mucosal level of tumor necrosis TNF-αand induced more serious gastric lesion. Animals injected with endotoxin antagonist BPI21 showed improved gastric mucosal lesion, accompanied by the declining TNF-αlevel. Conclusions:Our results suggestes that endotoxin may play a pathogenetic role in PHG by inducing the expression of TNF-α.

  1. Kavalactone metabolism in rat liver microsomes.

    Science.gov (United States)

    Fu, Shuang; Rowe, Anthony; Ramzan, Iqbal

    2012-07-01

    The specific CYP enzymes involved in kavalactone (KLT) metabolism and their kinetics have not been fully examined. This study used rat liver microsomes (RLM) to determine kavain (KA), methysticin (MTS) and desmethoxyyangonin (DMY) enzyme kinetic parameters, to elucidate the major CYP450 isoforms involved in KLT metabolism and to examine gender differences in KLT metabolism. Formation of the major KLT metabolites was first-order, consistent with classic enzyme kinetics. In both male and female RLM, clotrimazole (CLO) was the most potent inhibitor of KA and MTS metabolism. This suggests CYP3A1/3A23 (females) and CYP3A2 (males) are the main isoenzymes involved in the metabolism of these KLTs in rats, while the roles of CYP1A2, -2 C6, -2 C9, -2E1 and -3A4 are limited. Desmethoxyyangonin metabolism was equally inhibited by cimetidine (CIM) and CLO in females, and CIM and nortriptyline in males. This implies that DMY metabolism involves CYP2C6 and CYP2C11 in males, and CPY2C12 in females. CYP3A1/3A23 may also be involved in females.

  2. Hydroxylation of pentamidine by rat liver microsomes.

    Science.gov (United States)

    Berger, B J; Reddy, V V; Le, S T; Lombardy, R J; Hall, J E; Tidwell, R R

    1991-03-01

    The antiprotozoal/antifungal drug pentamidine [1,5-bis(4-amidinophenoxy)pentane] has been recently shown to be metabolized by rat liver fractions to at least six putative metabolites as detected by high-performance liquid chromatography. Two minor metabolites have been previously identified as N-hydroxypentamidine and N,N'-dihydroxypentamidine. In this study, the two major microsomal metabolites have been identified as the 2-pentanol and 3-pentanol analogs of pentamidine [1,5-di(4-amidinophenoxy)-2-pentanol; and 1,5-bis(4-amidinophenoxy)-3-pentanol]. As well, a seventh putative metabolite has been discovered and identified as para-hydroxybenzamidine, a fragment of the original drug. Whereas the cytochromes P-450 have been demonstrated as the enzyme system responsible for pentamidine metabolism, hydroxylation of the drug was not inducible by phenobarbital, beta-naphthoflavone, clofibrate, isosafrole, pregnenolone-16 alpha-carbonitrile, ethanol or pentamidine pretreatment of rats. The kinetics of the production of the two major microsomal metabolites has been determined as Km = 56 +/- 19 microM and Vmax = 126 +/- 21 pmol/min/mg microsomal protein for the 2-pentanol analog, and Km = 28 +/- 0.28 microM and Vmax = 195 +/- 2.4 pmol/min/mg microsomal protein for the 3-pentanol analog. Therefore, the mixed-function oxidases readily convert pentamidine to hydroxylated metabolites, but exactly which isozyme(s) of cytochrome P-450 is responsible is not clear.

  3. Kinetics of lactate transport into rat liver in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lupo, M.A.; Cefalu, W.T.; Pardridge, W.M.

    1990-04-01

    Lactate clearance by liver plays an important role in lactate homeostasis and in the development of lactic acidosis. The role of lactate delivery to liver as a limiting factor in hepatic uptake of lactate is unclear. Lactate delivery of mechanisms could be important if rates of lactate transport approximate rates of lactate metabolism by liver. The rates of lactate transport into liver have been determined in vitro with isolated liver cells and the results have been conflicting. Therefore, the present studies measure the rate of transport of (14C)-L-lactate, and its poorly metabolizeable stereoisomer, (14C)-D-lactate, into rat liver in vivo using a portal vein injection technique. The transport of (3H)-water and of (14C)-sucrose, an extracellular reference compound, were also studied. Portal blood flow was determined from the kinetics of (3H)-water efflux in liver and was 1.93 +/- 0.22 mL/min/g. The volumes of distribution of (14C)-L-lactate, and (14C)-sucrose were 1.31 +/- 0.22, 0.71 +/- 0.07, and 0.22 +/- 0.07 mL/g, respectively. The extraction of unidirectional influx of (14C)-L-lactate and (14C)-D-lactate by rat liver was 93% +/- 10% and 91% +/- 9%, respectively. The rate of lactate transport into rat liver in vivo, 1.8 mumols.min-1.g-1, is approximately twofold greater than the rate of lactate metabolism by rat liver reported in the literature. Therefore, lactate uptake by liver may not be limited by transport under normal conditions. However, conditions such as decreased portal blood flow, which slow lactate delivery to liver by 50% or more, could cause lactate uptake by liver to be limited by transport of circulating lactate.

  4. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

    Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove;

    2015-01-01

    a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

  5. Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

    Science.gov (United States)

    Zhang, Lili; Zhang, Huiying; Lv, Minli; Jia, Jiantao; Fan, Yimin; Tian, Xiaoxia; Li, Xujiong; Li, Baohong; Ji, Jingquan; Wang, Limin; Zhao, Zhongfu; Han, Dewu; Ji, Cheng

    2015-01-01

    Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy. PMID:26464674

  6. Enantioselective Metabolism of Flufiprole in Rat and Human Liver Microsomes.

    Science.gov (United States)

    Lin, Chunmian; Miao, Yelong; Qian, Mingrong; Wang, Qiang; Zhang, Hu

    2016-03-23

    The enantioselective metabolism of flufiprole in rat and human liver microsomes in vitro was investigated in this study. The separation and determination were performed using a liquid chromatography system equipped with a triple-quadrupole mass spectrometer and a Lux Cellulose-2 chiral column. The enantioselective metabolism of rac-flufiprole was dramatically different in rat and human liver microsomes in the presence of the β-nicotinamide adenine dinucleotide phosphate regenerating system. The half-lives (t1/2) of flufiprole in rat and human liver microsomes were 7.22 and 21.00 min, respectively, for R-(+)-flufiprole, whereas the values were 11.75 and 17.75 min, respectively, for S-(-)-flufiprole. In addition, the Vmax of R-(+)-flufiprole was about 3-fold that of S-(-)-flufiprole in rat liver microsomes, whereas its value in the case of S-(-)-flufiprole was about 2-fold that of R-(+)-flufiprole in human liver microsomes. The CLint of rac-flufiprole also showed opposite enantioselectivy in rat and human liver microsomes. The different compositions and contents of metabolizing enzyme in the two liver microsomes might be the reasons for the difference in the metabolic behavior of the two enantiomers.

  7. Interaction of low density lipoproteins with rat liver cells

    NARCIS (Netherlands)

    L. Harkes (Leendert)

    1985-01-01

    textabstractThe most marked conclusion is the establishment of the important role of non-parenchymal cells in the catabolism of the low density lipoproteins by the rat liver. Because the liver is responsible for 70-80% of the removal of LDL from blood this conclusion can be extended to total LDL tur

  8. EFFECT OF ETHANOL ON HEPATOBILIARY TRANSPORT OF CATIONIC DRUGS - A STUDY IN THE ISOLATED-PERFUSED RAT-LIVER, RAT HEPATOCYTES AND RAT MITOCHONDRIA

    NARCIS (Netherlands)

    STEEN, H; MEIJER, DKF; Merema, M.T.

    1994-01-01

    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation tri-n-butylmethylam

  9. [Orthotopic liver transplant in rats. Surgical technique, complications and treatment].

    Science.gov (United States)

    Lausada, Natalia R; Gondolesi, G E; Ortiz, E; Dreizzen, E; Raimondi, J C

    2002-01-01

    The orthotopic rat liver transplant model is a widely used technique in transplantation research. It has many advantages over other animal transplant models because of its availability and low cost. However, it must be emphasized that success with the rat model requires thorough training. The aim of this paper is to describe the microsurgical technique involved in 60 rat liver transplants and to discuss the complications and their treatments. Forty-nine liver transplants were performed at the Experimental Laboratory of the University Hospital, Ontario, Canada (ELUH) and 11 were performed at the Laboratorio de Trasplante de Organos de la Facultad de Ciencias Médicas de La Plata, Buenos Aires. Argentina (LTO). Among the transplants performed at the ELUH, the observed complications were haemorrhage (n = 4), pneumothorax (n = 1), anastomotic failure (n = 15), bile leak (n = 3), and bile duct necrosis (n = 9). The remaining 17 rats at the ELUH were healthy at day 7 after surgery. Animal survival immediately postop, at 24 hours postop and at 7 days postop was achieved with the 9th, 20th and 21st transplants respectively. At the LTO, 3 rats died as a result of anaesthetic complications. Seven-day animal survival was achieved with the 11th transplant. We beleive that the description of the orthotopic rat liver transplantation technique, as well as the discussion regarding complications and their management, can be useful for researchers interested in performing liver transplantation in rats.

  10. TUMORICIDAL RESPONSE OF LIVER MACROPHAGES ISOLATED FROM RATS BEARING LIVER METASTASES OF COLON ADENOCARCINOMA

    NARCIS (Netherlands)

    THOMAS, C; NIJENHUIS, AM; DONTJE, B; DAEMEN, T; SCHERPHOF, GL

    1995-01-01

    Intraportal inoculation of CC531 adenocarcinoma cells into syngeneic rats causes an increase of liver macrophage cell number but not of major histocompatibility complex class II antigen expression. On day I after inoculation of 10(5) CC531 cells, a fixed number of isolated liver macrophages lysed si

  11. [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.

  12. Intestinal microflora in rats with ischemia/reperfusion liver injury

    Institute of Scientific and Technical Information of China (English)

    XING Hui-chun; LI Lan-juan; XU Kai-jin; SHEN Tian; CHEN Yun-bo; SHENG Ji-fang; YU Yun-song; CHEN Ya-gang

    2005-01-01

    Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.

  13. In Vitro transformation of LW13 Rat liver epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    SHICAN; KARLFETNANSKY; 等

    1992-01-01

    A rat liver epithelial cell line designated LW 13 was established using a sequential sedimentation method.The cell line retained many normal proerties of liver epithelial cells and showed some structural and functional features resembling those of liver parenchymal cells,LW13 cells became malignant after the intrduction of exogenous transforming EJ Ha ras gene,Tumors produced by inoculation of the transformed cells into baby rats contained areas of poorly differentialted hepatocellular carcinoma,In situ hybridization analysis confirmed the random rather than specific integration of exogenous ras gene into host chromosomes.Furthermore,an at least tenfold increase in the expression of the endogenous c mys gene was detected among transformed cell lines,suggesting the involvement of the c myc proto oncogene in the in vitro transformation of rat liver epithelial cells by EJ Ha ras oncogene.

  14. Protection effect of trigonelline on liver of rats with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    Dong-Fang Zhang; Fan Zhang; Jin Zhang; Rui-Ming Zhang; Ran Li

    2015-01-01

    Objective:To study the effect of trigonelline on the change of indicators of serum transaminase, lipoprotein and liver lipid of model rats with non-alcoholic fatty liver diseases and on the expression level of Bcl-2 and Bax proteins.Methods:A total of 45 SD rats were randomly divided into Fthe control group, model group and trigonelline intervention group. Rats in the control group were fed with the common diet, while rats in the model group and intervention group were fed with the high fat diet. 8 weeks later, the intervention group received the intragastric administration of trigonellin e (with the dosage of 40 mg/kg/d) for 8 weeks; while control group and model group received the intragastric administration of saline with the equal dosage. Blood was taken from the abdominal aorta of rats 8 weeks later, detecting the level of a series of indicators of ALT, AST, TG, TC, HDL-C and LDL-C in the serum. After the rats were sacrificed, detect the indicators of TG, TC, SOD and MDA in the liver tissue of rats, as well as the expression of Bcl-2 and Bax in the liver tissue.Results: Results of histopathologic examination showed that the damage degree of liver for rats in the trigonellineintervention group was smaller than the one in the model group, with significantly reduced hepatic steatosis and the partially visible hepatic lobule. The levels of ALT, AST, TC and LDL-C in the serum of rats in the trigonelline group were significantly reduced, while the change in the levels of TG and HDL-C was not significantly different. The levels of TG, TC and MDA in the liver tissues were significantly decreased, while the level of SOD significantly increased; the expression of Bcl-2 protein in the liver tissues of rats in the trigonelline intervention group was significantly increased, while the expression of Bax protein significantly decreased.Conclusions: The trigonelline contributes to the therapeutic effect of non-alcoholic fatty liver diseases. It can also increase the

  15. The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients

    Directory of Open Access Journals (Sweden)

    Alqahtani Saad

    2011-01-01

    Full Text Available Abstract Background Cirrhotic patients are characterized by a decreased synthesis of coagulation and anticoagulation factors. The coagulopathy of cirrhotic patients is considered to be auto-anticoagulation. Our aim was to determine the incidence and predictors of venous thromboembolism (VTE and examine the practice of deep venous thrombosis (DVT prophylaxis among hospitalized cirrhotic patients. Methods A retrospective cohort study was performed in a tertiary teaching hospital. We included all adult patients admitted to the hospital with a diagnosis of liver cirrhosis from January 1, 2009 to December 31, 2009. We grouped our cohort patients in two groups, cirrhotic patients without VTE and cirrhotic with VTE. Results Over one year, we included 226 cirrhotic patients, and the characteristics of both groups were similar regarding their clinical and laboratory parameters and their outcomes. Six patients (2.7% developed VTE, and all of the VTEs were DVT. Hepatitis C was the most common (51% underlying cause of liver cirrhosis, followed by hepatitis B (22%; 76% of the cirrhotic patients received neither pharmacological nor mechanical DVT prophylaxis. Conclusion Cirrhotic patients are at risk for developing VTE. The utilization of DVT prophylaxis was suboptimal.

  16. Clinical Significance of a Myeloperoxidase Gene Polymorphism and Inducible Nitric Oxide Synthase Expression in Cirrhotic Patients with Hepatopulmonary Syndrome

    Institute of Scientific and Technical Information of China (English)

    王燕颖; 王文多; 张艳霞; 赵欣; 杨东亮

    2010-01-01

    The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO-463 G/A geno...

  17. Transcriptome atlas of eight liver cell types uncovers effects of histidine catabolites on rat liver regeneration

    Indian Academy of Sciences (India)

    C. F. Chang; J. Y. Fan; F. C. Zhang; J. Ma; C. S. Xu

    2010-12-01

    Eight liver cell types were isolated using the methods of Percoll density gradient centrifugation and immunomagnetic beads to explore effects of histidine catabolites on rat liver regeneration. Rat Genome 230 2.0 Array was used to detect the expression profiles of genes associated with metabolism of histidine and its catabolites for the above-mentioned eight liver cell types, and bioinformatic and systems biology approaches were employed to analyse the relationship between above genes and rat liver regeneration. The results showed that the urocanic acid (UA) was degraded from histidine in Kupffer cells, acts on Kupffer cells itself and dendritic cells to generate immune suppression by autocrine and paracrine modes. Hepatocytes, biliary epithelia cells, oval cells and dendritic cells can convert histidine to histamine, which can promote sinusoidal endothelial cells proliferation by GsM pathway, and promote the proliferation of hepatocytes and biliary epithelia cells by GqM pathway.

  18. Hepatocellular Carcinoma Mimicking Liver Abscesses in a Cirrhotic Patient with Severe Septic Shock as a Result of Salmonella O9 HG Infection

    Directory of Open Access Journals (Sweden)

    Shuichi Hagiwara

    2009-04-01

    Full Text Available We describe a case of severe Salmonella O9 HG sepsis with a mass in the liver, which was diagnosed as hepatocellular carcinoma (HCC by autopsy of the liver. The patient was a 67-year-old man with chronic high blood pressure. In addition, he was an alcoholic and had been drinking every day for many years. He had had a dinner of ‘sukiyaki’ with a raw egg two days before admission. The next morning, he had developed vomiting, diarrhea, and abdominal pain. Salmonella O9 HG was found in the blood and stool cultures. In the computed tomography (CT finding of the liver, there was a 2 cm early-enhanced mass with a multilocular structure, with ringed enhancement and daughter nodes. Since we thought that the mass was a liver abscess, we performed needle aspiration from the liver mass and were able to withdraw blood. Despite adequate antibiotic treatment, the patient died as a result of complications on the 55th day after admission. After the patient’s death, we conducted an autopsy. There were two HCC masses, a moderately-differentiated and a well-differentiated mass, as a result of alcoholic cirrhosis of the liver. As the HCC had multilocular cyst-like structures, which were fiber- and necrosis-rich, CT images of the liver masses resembled abscesses.

  19. Establishment of animal model of dual liver transplantation in rat.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

  20. Postoperative day one serum alanine amino-transferase does not predict patient morbidity and mortality after elective liver resection in non-cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    RickY Harminder Bhogal; Amit Nair; Davide Papis; Zaed Hamady; Jawad Ahmad; For Tai Lam; Saboor Khan; Gabriele Marangoni

    2016-01-01

    Serum aminotransferases have been used as sur-rogate markers for liver ischemia-reperfusion injury that fol-lows liver surgery. Some studies have suggested that rises in serum alanine aminotransferase (ALT) correlate with patient outcome after liver resection. We assessed whether postopera-tive day 1 (POD 1) ALT could be used to predict patient mor-bidity and mortality following liver resection. We reviewed our prospectively held database and included consecutive adult patients undergoing elective liver resection in our in-stitution between January 2013 and December 2014. Primary outcome assessed was correlation of POD 1 ALT with patient’s morbidity and mortality. We also assessed whether concurrent radiofrequency ablation, neoadjuvant chemotherapy and use of the Pringle maneuver signiifcantly affected the level of POD 1 ALT. A total of 110 liver resections were included in the study. The overall in-hospital patient morbidity and mortality were 31.8% and 0.9%, respectively. The median level of POD 1 ALT was 275 IU/L. No correlation was found between POD 1 serum ALT levels and patient morbidity after elective liver resection, whilst correlation with mortality was not possible because of the low number of mortalities. Patients undergoing concur-rent radiofrequency ablation were noted to have an increased level of POD 1 serum ALT but not those given neoadjuvant chemotherapy and those in whom the Pringle maneuver was used. Our study demonstrates POD 1 serum ALT does not cor-relate with patient morbidity after elective liver resection.

  1. Estrogen reduces CCL4- induced liver fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Jun-Wang Xu; Jun Gong; Xin-Ming Chang; Jin-Yan Luo; Lei Dong; Zhi-Ming Hao; Ai Jia; Gui-Ping Xu

    2002-01-01

    AIM: Chronic liver diseases, such as fibrosis or cirrhosis,are more common in men than in women. This genderdifference may be related to the effects of sex hormones onthe liver. The aim of the present work was to investigatethe effects of estrogen on CCL4-induced fibrosis of the liverin rats.METHODS: Liver fibrosis was induced in male, female andovariectomized rats by CCL4 administration. All the groupswere treated with estradiol(1 mg/kg) twice weekly. Andtamoxifen wasgiven to male fibrosis model. At the end of 8weeks, all therats were killed to study serum indicators andthe livers.RESULTS: Estradiol treatment reduced aspartateaminotransferase(AST), alanine aminotransferase (ALT),hyaluronic acid(HA) and type IV collagen(CIV) in sera,suppressed hepatic collagen content, decreased the areas ofhepatic stellate cells (HSC) positive for α-smooth muscle actin(α-SMA), and lowered the synthesis of hepatic type I collagensignificantly in both sexes and ovariectomy fibrotic rats inducedby CCL4 administration. Whereas, tamoxifen had the oppositeeffect. The fibrotic response of the female liver to CCL4treatment was significantly weaker than that of male liver.CONCLUSION: Estradiol reduces CCL4-induced hepaticfibrosis in rats. The antifibrogenic role of estrogen in theliver may be one reason for the sex associated differencesin the progression from hepatic fibrosis to cirrhosis.

  2. Therapeutic effect of osthole on hyperlipidemic fatty liver in rats

    Institute of Scientific and Technical Information of China (English)

    Yan ZHANG; Mei-lin XIE; Lu-jia ZHU; Zhen-lun GU

    2007-01-01

    Aim: To study the effects of osthole on hyperlipidemic fatty liver and investigate the possible mechanisms. Methods: A rat model with hyperlipidemic fatty liver was successfully established by feeding fatty milk for 6 weeks. The experimental rats were then treated with 5-20 mg/kg osthole for 6 weeks. The mouse hypedipi-demic model was induced by feeding fatty milk when they were treated with 10-20 mg/kg osthole for 3 weeks. Results: After treatment with osthole, the levels of rat serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein-choles-terol significantly decreased as compared with the fatty liver model group (P<0.05 or P<0.01). Hepatic weight and its coefficient, the hepatic tissue contents of TC,TG, and malondialdehyde, also significantly decreased (P<0.05 or P<0.01). In fatty milk-induced hyperlipidemic mice, the post-heparin plasma activities of lipo-protein lipase (LPL), hepatic lipase (HL), and total lipase (TL) significantly increased after treatment with 10-20 mg/kg osthole for 3 weeks (P<0.05 or P<0.01).Importantly, the histological evaluation of rat liver demonstrated that osthole dramatically decreased lipid accumulation (P<0.01). Conclusion: Osthole was found to have therapeutic effects on fatty milk-induced rat fatty liver; the mecha-nisms might be associated with its anti-oxidation and the elevation of the activi-ties of LPL and HL.

  3. In vitro identification of metabolitesof verapamil in rat liver microsomes

    Institute of Scientific and Technical Information of China (English)

    LuSUN; Shu-qiuZHANG; Da-fangZHONG

    2004-01-01

    AIM: To investigate the metabolism of verapamil at low concentrations in rat liver microsomes. METHODS: Liver microsomes of Wistar rats were prepared using ultracentrifuge method. The in vitro metabolism of verapamil was studied with the rat liver microsomal incubation at concentration of 1.0 μmol/L and 5.0 μmol/L. The metabolites were separated and assayed by liquid chromatography-ion trap mass spectrometry (LC/MSn), and further identified by comparison of their mass spectra and chromatographic behaviors with reference substances. RESULTS: Eightmetabolites, including two novel metabolites (M4 and MS), were found in rat liver microsomal incubates. They were identified as O-demethyl-verapamil isomers (M1 - M4), N-dealkylated derivatives of verapamil (MS-MT), and N, O-didemethyl-verapamil (MS). CONCLUSION: O-Demethylation and N-dealkylation were the main metabolic pathways of verapamil at low concentrations in rat liver microsomes, and the relative proportion of them in verapamil metabolism changed with different substrate concentrations.

  4. Effects of Samarium on Liver and Kidney of Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Spraque-Dawley(SD)big rats with weaning weight of (195±15) g were randomly divided into 4 groups with 8 males and 8 females each group. One group drank de-ionized water served as control and also used for analysis with the background. The other three groups were cultured for five months by drinking de-ionized water with 3.0, 4.5 and 6.0 mg·L-1 Sm (NO3)3, respectively. Compared with the rats in control, it is found that the organs of the treated rats are apparently pathologically changed, such as liver swell, lung intumescence, peritoneum conglutination and hardness. Especially, in the high Sm group, the pathological percentage in liver and lung is up to 30%. The pathological changes in liver and lung show that rare earth Sm does hazard biological effects to animals. With increasing Sm concentration, the weight rate of organ/body has a tendency of increasing; the activity of superoxide dismutase (SOD) in liver and kidney decreases, but the maglonydiadehyde (MDA) concentration increases, indicating the abilities of anti-oxidation and the lipid per-oxidation inhibition degenerate, which leads to hard pathological changes in organs. Moreover, the relative weight rate of organ/body, the activity of SOD and the MDA concentration are remarkably lager in liver than in kidney and other organs, suggesting that the biological effect of Sm on liver is the greatest and Sm has a high affinity for liver.

  5. The effect of Sachalin rhodiola rhizome extract on liver starch and liver cell morphous of sports fatigue rat

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; LI Rui; JI Chen-feng

    2008-01-01

    Objective To inspect the effect of Sachalin rhodiola rhizome extract to the swimming time and content of liver starch and liver cells morphous of sports fatigue rat. Methods Using weight loading swimming to determine swimming time, using kits to determine liver starch, using transmission electron microscope to observe the diversify of rat liver ceils morphous and construction. Results To compare with negative control group, the Sachalin rhodiola rhizome extract can obviously extend survival time of swimming rat, increase the content of liver starch. Conclusions Sachalin rhodiola rhizome extract can raise the staying power of sports fatigue rat, strengthen sport ability and play a part in antifatigue by increasing the content of liver starch and protecting liver cells of sports fatigue rat.

  6. The Disposition of Oxymatrine in the Vascularly Perfused Rat Intestine-Liver Preparation and Its Metabolism in Rat Liver Microsomes.

    Science.gov (United States)

    Huang, Li Hua; Zhong, Yun Ming; Xiong, Xiao Hong; Cen, Mei Feng; Cheng, Xuan Ge; Wang, Gui Xiang; Chen, Ji Sheng; Wang, Su Jun

    2016-02-01

    The study was aimed to investigate the absorption and metabolism of oxymatrine (OMT) which contributed to its poor bioavailability. Determinations of OMT absorption and metabolism in rats were evaluated using techniques of the in situ perfused rat intestine-liver preparation and recirculated intestine preparation. Furthermore, chemical inhibition experiments in rat liver microsomes were used to determine the principal cytochrome P450 (CYP) isoforms involved in OMT metabolism. In the intestine-liver preparation, the steady state liver extraction ratio (0.753 ± 0.054) of OMT was 33 times higher than that for the intestine (0.023 ± 0.002). The portal vein mainly consisted of OMT, and was devoid of the metabolite matrine, whereas both OMT and matrine were detected in hepatic vein. With the intestine preparation, the extent of OMT absorption at the end of 120 min of perfusion was 4.79 ± 0.352%. The first-order rate constant for OMT absorption was 0.05 ± 0.003 min(-1). The inhibitor of CYP3A2 had strong inhibitory effect on OMT metabolism in a concentration-dependent manner, and value was reduced to 29.73% of control. The 2 perfusion techniques indicated that poor bioavailability of OMT in rats is due mostly to poor absorption and higher hepatic elimination and CYP3A2 appears to contribute to OMT metabolism in rat liver.

  7. New insights into cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Hove, Jens D; Dixen, Ulrik

    2013-01-01

    Cirrhotic cardiomyopathy designates a cardiac dysfunction, which includes reduced cardiac contractility with systolic and diastolic dysfunction, and presence of electrophysiological abnormalities in particular prolongation of the QT interval. Several pathophysiological mechanisms including reduce...

  8. Selective bioreduction of nitroxides by rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, G.M.; Rauckman, E.J.; Hanck, K.W.

    1977-09-01

    Presented are possible explanations for the inability of rat liver microsomes to reduce 2-ethyl-2,4,4-trimethyl-3-oxazolidinyloxy (OXAN) even though the reduction potential for OXAN is identical to that for 2,2,6,6-tetramethylpiperidinoxyl (TEMPO) and di-tert-butyl nitroxide (DTBN), both of which are reduced by these microsomes. It is suggested that the conformation of OXAN prevents these enzymes from reducing the compound. Administration of phenobarbital was found to induce the synthesis of a form of cytochrome P-450, which enabled the rat liver microsomes to reduce the OXAN. (2 diagrams, 9 references)

  9. Biotransformation of myrislignan by rat liver microsomes in vitro.

    Science.gov (United States)

    Li, Fei; Yang, Xiu-Wei

    2008-02-01

    Myrislignan (1), erythro-(1R,2S)-2-(4-allyl-2,6-dimethoxyphenoxyl)-1-(4-hydroxy-3-methoxyphenyl) propan-1-ol, is a major acyclic neolignan in seeds of Myristica fragrans. Studies have suggested that myrislignan may deter feeding activity, but little is known about its metabolism. We investigated the biotransformation of myrislignan by rat liver microsomes in vitro. Seven metabolites were produced by liver microsomes from rats pre-treated with sodium phenobarbital. These were identified, using spectroscopic methods, as myrislignanometins A-G (2-8), respectively.

  10. [A case of hepatic sarcoidosis presenting with cirrhotic symptoms].

    Science.gov (United States)

    Kaji, Kiichiro; Ogino, Hidero; Hirai, Satoshi; Shimatani, Akiyoshi; Horita, Yosuke; Matsuda, Kouichiro; Hiramatsu, Katsushi; Matsuda, Mitsuru; Shimizu, Koichi; Nakanishi, Yuko; Noda, Yatsugi

    2014-03-01

    A man in 40s with skin sarcoidosis presented with signs and symptoms of liver injury and thrombocytopenia. Enhanced computed tomography and magnetic resonance imaging revealed cholecystolithiasis, hepatic deformation, and giant splenomegaly. Gastrointestinal endoscopy showed esophageal varices. Cholecystectomy, splenectomy, and wedge biopsy of the liver were performed. Histopathology of the liver revealed many granulomas and severe periportal fibrosis without lobular reconstruction. These findings were compatible with hepatic sarcoidosis, but not liver cirrhosis. Here we report a rare case of hepatic sarcoidosis presenting with cirrhotic symptoms.

  11. The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat.

    Science.gov (United States)

    Chooi, Kum Fai; Kuppan Rajendran, Dinesh Babu; Phang, Siew Siang Gary; Toh, Han Hui Alden

    2016-06-17

    Four to six week old, male Wistar rats were used to produce animal models of liver fibrosis. The process requires four weeks of administration of 10 mg/kg dimethylnitrosamine (DMN), given intraperitoneally for three consecutive days per week. Intraperitoneal injections were performed in the fume hood as DMN is a known hepatoxin and carcinogen. The model has several advantages. Firstly, liver changes can be studied sequentially or at particular stages of interest. Secondly, the stage of liver disease can be monitored by measurement of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. Thirdly, the severity of liver damage at different stages can be confirmed by sacrifice of animals at designated time points, followed by histological examination of Masson's Trichome stained liver tissues. After four weeks of DMN dosing, the typical fibrosis score is 5 to 6 on the Ishak scale. The model can be reproduced consistently and has been widely used to assess the efficacy of potential anti-fibrotic agents.

  12. Nutritional assessment in cirrhotic patients with hepaticencephalopathy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatic encephalopathy (HE) is one of the worstcomplications of liver disease and can be greatly influencedby nutritional status. Ammonia metabolism, inflammationand muscle wasting are relevant processes inHE pathophysiology. Malnutrition worsens the prognosisin HE, requiring early assessment of nutritional statusof these patients. Body composition changes inducedby liver disease and limitations superimposed by HEhamper the proper accomplishment of exams in thispopulation, but evidence is growing that assessmentof muscle mass and muscle function is mandatory dueto the role of skeletal muscles in ammonia metabolism.In this review, we present the pathophysiologicalaspects involved in HE to support further discussionabout advantages and drawbacks of some methods forevaluating the nutritional status of cirrhotic patients withHE, focusing on body composition.

  13. Compliance with the clinical practice guidelines for the management of hepatitis B and C virus-related chronic liver disease: a survey based on hospitalized cirrhotic patients

    Directory of Open Access Journals (Sweden)

    Emanuele La Spada

    2013-04-01

    Full Text Available In recent years, significant progress has been made in furthering our knowledge of chronic liver disease (CLD and evaluating the therapeutic approaches. These have been updated in the form of recommendations by international scientific societies. Through a retrospective analysis, this study aimed to verify whether these recommendations have been applied in real practice. The study design included data gathered from all patients consecutively hospitalized for decompensated liver cirrhosis during one year. A pre-made master form was used to record data on the patients’ past knowledge of the etiology and management of their liver disease. As expected, hepatitis C virus (HCV was the most frequent cause of CLD, while 41 cases were cryptogenic. In 69 of 263 patients with HCV infection, viral genotyping had been performed, although only 39 of these cases had been treated. Only 3 of 44 patients suffering from hepatitis B virus (HBV-related liver cirrhosis had been treated in the past, while 11 patients were still being treated. Among the remaining patients, 15 were not aware that they had CLD and 15 had never been considered for antiviral treatment. In 81 cases, the disease had progressed to hepatocellular carcinoma, but only 19 patients had discovered the tumor following regular ultrasound screening. Thirty-seven patients were receiving specific treatment consistent with the stage of their disease. The management of HBV- and HCV-related CLD in Sicily is far from optimal, and although the natural history and management practices of these diseases are well known, this knowledge is a long way from being applied in our daily practice.

  14. Caffeine induction of sulfotransferases in rat liver and intestine.

    Science.gov (United States)

    Zhou, Tianyan; Chen, Yue; Huang, Chaoqun; Chen, Guangping

    2012-10-01

    Sulfotransferases (SULTs) are important phase II drug-metabolizing enzymes. Regulation of SULTs by hormones and other endogenous molecules is relatively well understood, while xenobiotic induction of SULTs is not well studied. Caffeine is one of the most widely consumed psychoactive substances. However, SULT regulation by caffeine has not been reported. In this report, male and female rats were treated with different oral doses of caffeine (2, 10, 50 mg kg⁻¹ per day) for 7 days. Western blot and real-time RT-PCR were used to investigate the changes in SULT protein and mRNA expression following the caffeine treatment. Caffeine induced both rat aryl sulfotransferase (rSULT1A1, AST-IV) and rat hydroxysteroid sulfotransferase (rSULT2A1, STa) in the liver and intestine of female rats in a dose-dependent manner. Caffeine induction of rSULT1A1 and rSULT2A1 in the female rat intestine was much stronger than that in the liver. Although caffeine induced rSULT1A1 significantly in the male rat liver, it did not significantly induce rSULT2A1. In male rat intestine, caffeine significantly induced rSULT2A1. The different SULTs induction patterns in male and female rats suggest that the regulation of rat SULTs by caffeine may be affected by different hormone secretion patterns and levels. Our results suggest that consumption of caffeine can induce drug metabolizing SULTs in drug detoxification tissues.

  15. 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.

  16. Research of combined liver-kidney transplantation model in rats

    Institute of Scientific and Technical Information of China (English)

    Jiageng Zhu; Jun Li; Ruipeng Jia; Jianghao Su; Mingshun Shen; Zhigang Cao

    2007-01-01

    Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.

  17. Two New Lactones Metabolized from Isoline by Rat Liver Microsomes

    Institute of Scientific and Technical Information of China (English)

    Jun TANG; Zheng Tao WANG; Teruaki AKAO; Norio NAKAMURA; Masao HATTORI

    2003-01-01

    Two new metabolites, namely bisline lactone and isolinecic acid lactone, were isolated from the resultant incubates after a scale-up incubation of isoline with rat liver microsomes. Their structures were determined by spectroscopic data, especially those from 1D and 2D NMR experiments.

  18. Phosphatidylcholine mobility in bile salt depleted rat liver microsomes

    NARCIS (Netherlands)

    Oliveira Filgueiras, O.M. de; Defize, B.; Echteld, C.J.A. van; Bosch, H. van den

    1980-01-01

    Rat liver microsomes prepared by differential centrifugation are known to contain measurable levels of bile salts. More than 90% of these can be removed by passing the microsomal preparation through a Bio-Gel A-150m column. Bile salt depleted microsomes show a high level (> 95%) of mannose-6-phospha

  19. Chemical structure and biochemical significance of lysolecithins from rat liver

    NARCIS (Netherlands)

    Bosch, H. van den; Deenen, L.L.M. van

    1965-01-01

    1. 1. Synthetic lecithins containing in 2-position a [14C]fatty acid constituent were found to be hydrolysed by rat-liver homogenates so as to form both 1-acyl-glycero-3-phosphorylcholine and 2-acyl-glycero-3-phosphorylcholine. 2. 2. A comparison of the fatty acid pattern of lysolecithin obtained f

  20. Melatonin protects liver from intestine ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Yi Li; Hong-Zhuan Yin; Xi Gu; Yong Zhou; Wen-Hai Zhang; Yi-Min Qin

    2008-01-01

    AIM:To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats.METHODS:One hundred and fifty male Wistar rats,weighing 190-210 g,aged 7 wk,were randomly divided into melatonin exposure group,alcohol solvent control group and normal saline control group.Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20 mg/kg) 30 min before intestinal ischemia-reperfusion (IR),rats in the alcohol solvent control group received the same concentration and volume of alcohol,and rats in the normal saline control group received the same volume of normal saline.Serum samples were collected from each group 0.5,1,6,12,and 24 h after intestinal IR.Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with an auto-biochemical analyzer.Serum TNF-a was tested by enzyme-linked immunosorbent assay (ELISA).Malondialdehyde (MDA) in liver was detected by colorimetric assay.Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope.RESULTS:The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups (P<0.05).The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels (%) 6,12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups (P<0.05).CONCLUSION:Exotic melatonin can inhibit the activity of ALT,AST and TNF-a decrease the accumulation of MDA,and depress the expression of ICAM-1 in liver after intestinal IR injury,thus improving the liver function.

  1. The effects of Helicobacter pylori infection on hyperammonaemia and hepatic encephalopathy in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    王良静

    2006-01-01

    Objective To evaluate the relationship among Helicobacter pylori (Hp) infection, blood ammonia concentrations , and hepatic encephalopathy (HE) status, and to investigate the effect of Hp eradication on blood ammonia levels and hepatic encephalopathy status in cirrhotic patients. Methods From July 2003 to Jan 2005, cirrhotic patients in 5 regions of Zhejiang Province were enrolled. Patients were evaluated for the demographic checklists, number connection test, Hp infection, liver impairment level, blood ammonia concentrations and he-

  2. No effect of oral testosterone treatment on sexual dysfunction in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Gluud, C; Wantzin, P; Eriksen, J

    1988-01-01

    The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind, placebo-controlled study on the effect of oral testosterone treatment on liver disease. At entry, 67% (95% confidence limits, 61%-74%) complained of sexual dysfunction....... In conclusion, oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men. However, sexual function improved after reduction of ethanol consumption in these patients....

  3. Protective effect of liver ischemic preconditioning on rat hepatocytes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Ischemic preconditioning (IPC) protects liver graft function following ischemia in liver transplantation and liver resection. The aim of this study was to assess the advantages and any potential disadvantages of liver IPC prior to isolation for rat hepatocytes during isolation and cryopreservation. After isolating and thawing the cryopreserved hepatocytes after 14 and 28 d,cell viability,efficiency,and lactate dehydrogenase (LDH) levels in preserve solution were examined for every group. Groups treated with IPC had better cell viability determination,assessment of plating efficiency and lactate dehydrogenase (LDH) assay than Group without IPC,suggesting that IPC prior to isolation may have a significant protective effect on hepatocytes subjected to isolation and short period cryopreservation.

  4. Quercetin protection against ciprofloxacin induced liver damage in rats.

    Science.gov (United States)

    Taslidere, E; Dogan, Z; Elbe, H; Vardi, N; Cetin, A; Turkoz, Y

    2016-01-01

    Ciprofloxacin is a common, broad spectrum antibacterial agent; however, evidence is accumulating that ciprofloxacin may cause liver damage. Quercetin is a free radical scavenger and antioxidant. We investigated histological changes in hepatic tissue of rats caused by ciprofloxacin and the effects of quercetin on these changes using histochemical and biochemical methods. We divided 28 adult female Wistar albino rats into four equal groups: control, quercetin treated, ciprofloxacin treated, and ciprofloxacin + quercetin treated. At the end of the experiment, liver samples were processed for light microscopic examination and biochemical measurements. Sections were prepared and stained with hematoxylin and eosin, and a histopathologic damage score was calculated. The sections from the control group appeared normal. Hemorrhage, inflammatory cell infiltration and intracellular vacuolization were observed in the ciprofloxacin group. The histopathological findings were reduced in the group treated with quercetin. Significant differences were found between the control and ciprofloxacin groups, and between the ciprofloxacin and ciprofloxacin + quercetin groups. Quercetin administration reduced liver injury caused by ciprofloxacin in rats. We suggest that quercetin may be useful for preventing ciprofloxacin induced liver damage.

  5. Primary culture of adult rat liver cells. I. Preparation of isolated cells from trypsin-perfused liver of adult rat

    Directory of Open Access Journals (Sweden)

    Miyazaki,Masahiro

    1977-12-01

    Full Text Available Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.

  6. [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.

  7. Role of Chymase in the Development of Liver Cirrhosis and Its Complications: Experimental and Human Data

    Science.gov (United States)

    Sansoè, Giovanni; Aragno, Manuela; Mastrocola, Raffaella; Mengozzi, Giulio; Novo, Erica; Parola, Maurizio

    2016-01-01

    Background Tissue Angiotensin II (Ang-II), produced through local non ACE-dependent pathways, stimulates liver fibrogenesis, renal vasoconstriction and sodium retention. Aim To highlight chymase-dependent pathway of Ang-II production in liver and kidney during cirrhosis development. Methods Liver histology, portal pressure, liver and kidney function, and hormonal status were investigated in rat liver cirrhosis induced through 13 weeks of CCl4, with or without chymase inhibitor SF2809E, administered between 4th and 13th CCl4 weeks; liver and kidney chymase immunolocation and Ang-II content were assessed. Chymase immunohistochemistry was also assessed in normal and cirrhotic human liver, and chymase mRNA transcripts were measured in human HepG2 cells and activated hepatic stellate cells (HSC/MFs) in vitro. Results Rats receiving both CCl4 and SF2809E showed liver fibrotic septa focally linking portal tracts but no cirrhosis, as compared to ascitic cirrhotic rats receiving CCl4. SF2809E reduced portal pressure, plasma bilirubin, tissue content of Ang-II, plasma renin activity, norepinephrine and vasopressin, and increased glomerular filtration rate, water clearance, urinary sodium excretion. Chymase tissue content was increased and detected in α-SMA-positive liver myofibroblasts and in kidney tubular cells of cirrhotic rats. In human cirrhosis, chymase was located in hepatocytes of regenerative nodules. Human HepG2 cells and HSC/MFs responded to TGF-β1 by up-regulating chymase mRNA transcription. Conclusions Chymase, through synthesis of Ang-II and other mediators, plays a role in the derangement of liver and kidney function in chronic liver diseases. In human cirrhosis, chymase is well-represented and apt to become a future target of pharmacological treatment. PMID:27637026

  8. Expressed genes in regenerating rat liver after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Cun-Shuan Xu; Salman Rahrnan; Jing-Bo Zhang; Cui-Fang Chang; Jin-Yun Yuan; Wen-Qiang Li; Hong-Peng Han; Ke-Jin Yang; Li-Feng Zhao; Yu-Chang Li; Hui-Yong Zhang

    2005-01-01

    AIM: To reveal the liver regeneration (LR) and its controlas well as the occurrence of liver disease and to study the gene expression profiles of 551 genes after partial hepatectomy (PH) in regenerating rat livers.METHODS: Five hundred and fifty-one expressed sequence tags screened by suppression subtractive hybridization were made into an in-house cDNA microarray, and the expressive genes and their expressive profiles in regenerating rat livers were analyzed by microarray and bioinformatics. RESULTS: Three hundred of the analyzed 551 genes were up- or downregulated more than twofolds at one or more time points during LR. Most of the genes were up- or downregulated 2-5 folds, but the highest reached 90 folds of the control. One hundred and thirty-nine of themshowed upregulation, 135 displayed downregulation, and up or down expression of 26 genes revealed a dependence on regenerating livers. The genes expressedin 24-h regenerating livers were much more than those in the others. Cluster analysis and generalization analysis showed that there were at least six distinct temporal patterns of gene expression in the regenerating livers, that is, genes were expressed in the immediate early phase, early phase, intermediate phase, early-late phase, late phase, terminal phase. CONCLUSION: In LR, the number of down-regulated genes was almost similar to that of the upregulated genes; the successively altered genes were more than the rapidly transient genes. The temporal patterns of gene expression were similar 2 and 4 h, 12 and 16 h, 48 and 96 h, 72 and 144 h after PH. Microarray combined with suppressive subtractive hybridization can effectively identify the genes related to LR.

  9. The effect of oral testosterone on serum TBG levels in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Bennett, Patrick

    1988-01-01

    , it is demonstrated that testosterone treatment significantly reduced TBG concentrations in cirrhotic men with preserved liver function, like normal men, but not in patients with moderate liver dysfunction. The lack of effect of testosterone in patients with more advanced cirrhosis may be due to a decreased function...

  10. Inhibitory effects of beryllium chloride on rat liver microsomal enzymes.

    Science.gov (United States)

    Teixeira, C F; Yasaka, W J; Silva, L F; Oshiro, T T; Oga, S

    1990-04-30

    A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

  11. In vitro biotransformation of flavonoids by rat liver microsomes

    DEFF Research Database (Denmark)

    Nielsen, S. E.; Breinholt, V.; Justesen, U.

    1998-01-01

    1. Sixteen naturally occurring flavonoids were investigated as substrates for cytochrome P450 in uninduced and Aroclor 1254-induced rat liver microsomes. Naringenin, hesperetin, chrysin, apigenin, tangeretin, kaempferol, galangin and tamarixetin were all metabolized extensively by induced rat liver...... pathway leading to the corresponding 3',4'-dihydroxylated flavonoids either by hydroxylation or demethylation. Structural requirements for microsomal hydroxylation appeared to be a single or no hydroxy group on the B-ring of the flavan nucleus. The presence of two or more hydroxy groups on the B......-ring seemed to prevent further hydroxylation. The results indicate that demethylation only occurs in the B-ring when the methoxy group is positioned at C-4'-, and not at the C-3'-position. 3. The CYP1A isozymes were found to be the main enzymes involved in flavonoid hydroxylation, whereas other cytochrome P...

  12. Characterization of cationic acid phosphatase isozyme from rat liver mitochondria.

    Science.gov (United States)

    Fujimoto, S; Murakami, K; Hosoda, T; Yamamoto, Y; Watanabe, K; Morinaka, Y; Ohara, A

    1992-05-01

    Acid phosphatase isozyme was highly purified from rat liver mitochondrial fraction. The enzyme showed an isoelectric point value of above 9.5 on isoelectric focusing, and the apparent molecular weight was estimated to be 32000 by Sephadex G-100 gel filtration or 16000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme catalyzed the hydrolysis of adenosine 5'-triphosphate, adenosine 5'-diphosphate, thiamine pyrophosphate, inorganic pyrophosphate, and phosphoprotein such as casein and phosvitin, but not of several phosphomonoesters, except for p-nitrophenyl phosphate and o-phosphotyrosine. The enzyme was not inhibited by L-(+)-tartrate, and was significantly activated by Fe2+ and reducing agents such as ascorbic acid, L-cysteine,and dithiothreitol. The enzyme was found to be distributed in various rat tissues including liver, spleen, kidney, small intestine, lung, stomach, brain and heart, but not in skeletal muscle.

  13. Functional state of rat liver RNA polymerase IA and IB.

    Science.gov (United States)

    Zoncheddu, A; Accomando, R; Pertica, M; Orunesu, M

    1979-01-01

    Phosphocellulose chromatography has been employed to characterize RNA polymerase I present in two different functional states in rat liver cells. The actively transcribing enzyme solubilized from nuclei appears to belong both to the IA and IB classes, whereas the non-transcribing enzyme present in the cytoplasmic fraction has been found to belong only to the IA class. Indirect and direct evidence indicates, however, that in isolated nuclei only the IB form is to be regarded as the physiological form of the enzyme, the IA form arising as a procedural artefact during the extraction process. It may, therefore, be concluded that rat liver IA and IB RNA polymerase are to be strictly regarded as the non-transcribing and transcribing form of the enzyme, respectively.

  14. Low-dose ATRA Supplementation Abolishes PRM Formation in Rat Liver and Ameliorates Ethanol-induced Liver Injury

    Institute of Scientific and Technical Information of China (English)

    PAN Zhihong; DAN Zili; FU Yu; TANG Wangxian; LIN Jusheng

    2006-01-01

    The effects of all-trans-retinoic acid (ATRA) in low doses supplementation on concentrations of polar retinoid metabolites (PRM) and retinoids in the ethanol-fed rat liver, and on hepatocyte injury were investigated. The rat model of alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol, and then the rats were administrated with ATRA in two different doses (150 μg/kg body weight and 1.5 mg/kg body weight) for 4 weeks. Concentrations of retinoids in rat liver and plasma were determined by using HPLC. Liver tissues pathologic changes were observed under the light microscopy and electron microscopy. The serum transaminases concentrations were measured. The results showed that the HPLC analysis of retinoids revealed that retinoids (vitamin A,RA, retinyl palmitate) concentrations in ethanol-fed rat liver and RA concentration in ethanol-fed rat plasma were markedly diminished (P<0.01) after ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRM were formed in livers of ethanol-fed rats. ATRA 150 μg/kg supplementation in ethanol-fed rats for 4 weeks raised RA concentration in both liver and plasma, and also raised vitamin A concentration in liver to control levels, partially restored retinyl palmitate concentration (P<0.05) in liver. ATRA 1.5 mg/kg supplementation raised not only RA concentrations in liver and plasma but also retinyl palmitate concentrations in liver. However, the vitamin A concentration in liver of ATRA-supplemented rats (1.5 mg/kg) was higher than that of controls (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling,steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER).ATRA treatment greatly decreased levels of serum transaminases as compared with the only ethanol-fed group (P<0.05). It was concluded that low-dose ATRA treatment could restore retinoids concentrations and abolish the PRM formation

  15. Bone disorders in experimentally induced liver disease in growing rats

    Institute of Scientific and Technical Information of China (English)

    Viktória Ferencz; Ferenc Szalay; Csaba Horváth; Béla Kári; János Gaál; Szilvia Mészáros; Zsuzsanna Wolf; Dalma Hegedüs; Andrea Horváth; Anikó Folhoffer

    2005-01-01

    AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats.METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride (CCl4), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (Fmax)of the femora were determined. The results in animals treated with DEN+PB+CCl4 (DPC, n = 21) were compared to those in untreated animals (UNT,n = 14) and in control group treated only with DEN+PB (DP, n = 20).RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8,but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and Fmax values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16.CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.

  16. 4-Nitrocatechol production from rho-nitrophenol by rat liver.

    Science.gov (United States)

    Chrastil, J; Wilson, J T

    1975-05-01

    Time course studies of rho-nitroanisole O-demethylation revealed formaldehyde production in excess of rho-nitrophenol (PNP) and 4-nitrocatechol (NTC) formation by rat liver microsomes. This indicated that these products (PNP, NTC) were metabolised further. The hydroxylation reaction PNP yields NTC showed substrate and product inhibition and a requirement for reduced nicotinamide adenine dinucleotide phosphate and O2 and was localized in liver microsomes. It was strongly activated by ascorbic acid, cysteine, adenosine triphosphate or hydroxylamine in vitro and enhanced by phenobarbital treatment in vivo. Mercapturic derivatives were metabolized to the corresponding hydroxy compounds with the same speed as their parent compounds. Both PNP and NTC were metabolized to the corresponding glucuronide and sulfate conjugates. On the other hand, the PNP or NTC glucuronides and sulfates were metabolized with liver microsomes to PNP and NTC.

  17. Stereoselective metabolism of tetrahydropalmatine enantiomers in rat liver microsomes.

    Science.gov (United States)

    Zhao, Ming; Li, Li-Ping; Sun, Dong-Li; Sun, Si-Yuan; Huang, Shan-Ding; Zeng, Su; Jiang, Hui-Di

    2012-05-01

    Tetrahydropalmatine (THP), with one chiral center, is an active alkaloid ingredient in Rhizoma Corydalis. The aim of the present paper is to study whether THP enantiomers are metabolized stereoselectively in rat, mouse, dog, and monkey liver microsomes, and then, to elucidate which Cytochrome P450 (CYP) isoforms are predominately responsible for the stereoselective metabolism of THP enantiomers in rat liver microsomes (RLM). The results demonstrated that (+)-THP was preferentially metabolized by liver microsomes from rats, mice, dogs, and monkeys, and the intrinsic clearance (Cl(int)) ratios of (+)-THP to (-)-THP were 2.66, 2.85, 4.24, and 1.67, respectively. Compared with the metabolism in untreated RLM, the metabolism of (-)-THP and (+)-THP was significantly increased in dexamethasone (Dex)-induced and β-naphthoflavone (β-NF)-induced RLM; meanwhile, the Cl(int) ratios of (+)-THP to (-)-THP in Dex-induced and β-NF-induced RLM were 5.74 and 0.81, respectively. Ketoconazole had stronger inhibitory effect on (+)-THP than (-)-THP, whereas fluvoxamine had stronger effect on (-)-THP in untreated and Dex-induced or β-NF-induced RLM. The results suggested that THP enantiomers were predominately metabolized by CYP3A1/2 and CYP1A2 in RLM, and CYP3A1/2 preferred to metabolize (+)-THP, whereas CYP1A2 preferred (-)-THP.

  18. Stereoselective degradation of chiral fungicide myclobutanil in rat liver microsomes.

    Science.gov (United States)

    Yan, Jin; Zhang, Ping; Wang, Xinru; Wang, Yao; Zhou, Zhiqiang; Zhu, Wentao

    2014-01-01

    Myclobutanil, (RS)-2-(4-chlorophenyl)-2-(1H-1, 2, 4-triazol-1-ylmethyl)hexanenitrile is a broad-spectrum systemic triazole fungicide which consists of a pair of enantiomers. The stereoselective degradation of myclobutanil was investigated in rat liver microsomes. The concentrations of myclobutanil enantiomers were determined by high-performance liquid chromatography (HPLC) with a cellulose-tris-(3,5-dimethyl-phenylcarbamate)-based chiral stationary phase (CDMPC-CSP) under reversed phase condition. The t(1/2) of (+)-myclobutanil is 8.49 min, while the t(1/2) of (-)-myclobutanil is 96.27 min. Such consequences clearly indicated that the degradation of myclobutanil in rat liver microsomes was stereoselective and the degradation rate of (+)-myclobutanil was much faster than (-)-myclobutanil. In addition, significant differences between two enantiomers were also observed in enzyme kinetic parameters. The V(max) of (+)-myclobutanil was about 4-fold of (-)-myclobutanil and the CL(int) of (+)-myclobutanil was three times as much as (-)-myclobutanil after incubation in rat liver microsomes. Corresponding consequences may shed light on the environmental and ecological risk assessment for myclobutanil and may improve human health.

  19. Heterotrimeric G protein subunits are located on rat liver endosomes

    Directory of Open Access Journals (Sweden)

    Van Dyke Rebecca W

    2004-01-01

    Full Text Available Abstract Background Rat liver endosomes contain activated insulin receptors and downstream signal transduction molecules. We undertook these studies to determine whether endosomes also contain heterotrimeric G proteins that may be involved in signal transduction from G protein-coupled receptors. Results By Western blotting Gsα, Giα1,2, Giα3 and Gβ were enriched in both canalicular (CM and basolateral (BLM membranes but also readily detectable on three types of purified rat liver endosomes in the order recycling receptor compartment (RRC > compartment for uncoupling of receptor and ligand (CURL > multivesicular bodies (MVB >> purified secondary lysosomes. Western blotting with antibodies to Na, K-ATPase and to other proteins associated with plasma membranes and intracellular organelles indicated this was not due to contamination of endosome preparations by CM or BLM. Adenylate cyclase (AC was also identified on purified CM, BLM, RRC, CURL and MVB. Percoll gradient fractionation of liver postnuclear supernatants demonstrated co-occurrence of endosomes and heterotrimeric G protein subunits in fractions with little plasma membrane markers. By confocal microscopy, punctate staining for Gsα, Giα3 and Gβ corresponded to punctate areas of endocytosed Texas red-dextran in hepatocytes from control and cholera toxin-treated livers. Conclusion We conclude that heterotrimeric G protein subunits as well as AC likely traffic into hepatocytes on endosome membranes, possibly generating downstream signals spatially separate from signalling generated at the plasma membrane, analogous to the role(s of internalized insulin receptors.

  20. Unusual cause of gastrointestinal bleeding in a cirrhotic patient:hepatocellular carcinoma with gastric invasion

    Institute of Scientific and Technical Information of China (English)

    Marcos Vinicius Perini; Paulo Herman; Rodrigo Pessoa; Willian Abraao Saad

    2009-01-01

    BACKGROUND: Upper gastrointestinal (GI) bleeding is a common complication of portal hypertension in cirrhotic patients, and hepatocellular carcinoma (HCC) is the most common tumor in cirrhotic livers. Bleeding from tumor erosion into the GI tract is very rare. A patient with HCC and gastric tumor invasion was described and the previously reported cases were reviewed. METHOD: A patient with upper GI bleeding was treated in a tertiary hospital. RESULTS: A cirrhotic patient with a HCC invading the stomach leading to upper GI bleeding was treated by left lateral segmentectomy and sub-total gastrectomy. The bleeding was controlled and a good surgical outcome was achieved. CONCLUSIONS: HCC with gastric invasion should be differentially diagnosed from upper GI bleeding in cirrhotic patients. Bleeding can be controlled and symptomatic relief marked in selected cases.

  1. EVALUATION AND COMPARISON OF HYPERTROPHY OF THENONEMBOLIZED LOBE OF THE LIVER AFTER DOUBLE AND SINGLEEMBOLIZATION

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To evaluate and compare the different result in hypertrophy of remained live lobe after double and single embolization. Methods Combined hepatic arterial embolization(HAE) with portal venous emboliza tion(PVE), HAE and sham operation were carried on the median and left lobes of the livers in normal and cirrhotic rats respectively. Three days later, the volume of the right lobe of the liver and its mitotic index and GPT content per gram protein were measured. Results In hormel rats, the indications mentioned increased significantly in experimen tal rats compared to control rats. The indications mentioned above also increased significantly in HAE+PVE group compared to HAE group. However, they increased more slightly in cirrhotic rats than in normal rats. Enlargement of the nonembolized part of the liver after double embolization is a result of hypertrophy, which enhanced the reserve function of the liver. Considering various degree of hypertrophy of liver cell and enhancement of reserve function, double embolization is more excellent than single embolization when the same volume liver is embolized.

  2. Expression of AFP and Rev-Erb A/Rev-Erb B and N-CoR in fetal rat liver, liver injury and liver regeneration

    OpenAIRE

    Meier, Volker; Tron, Kyrylo; Batusic, Danko; Elmaouhoub, Abderrahim; Ramadori, Giuliano

    2006-01-01

    Background Alpha-fetoprotein (AFP) expression can resume in the adult liver under pathophysiological conditions. Orphan nuclear receptors were supposed to regulate AFP gene expression, in vitro. We were interested to study the expression of AFP and orphan nuclear receptors, in vivo. Results The expression of AFP gene and orphan nuclear receptors in the liver was examined in different rat models: (a) fetal liver (b) liver regeneration [partial hepatectomy (PH) with and without 2-acetyl-aminofl...

  3. Hepato-biliary profile of potential candidate liver progenitor cells from healthy rat liver

    Institute of Scientific and Technical Information of China (English)

    Céric Maerckx; Isabelle Scheers; Tatiana Tondreau; David Campard; Omar Nyabi; Mustapha Najimi; Etienne Sokal

    2012-01-01

    AIM:To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent advanced hepatogenic profile as that obtained in humans.METHODS:Rat fibroblastic-like liver derived cells (rFLDC) were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry,immunocyto-chemistry,reverse transcription polymerase chain reaction and functional assays.RESULTS:rFLDC exhibit fibroblastoid morphology,express mesenchymal (CD73,CD90,vimentin,α-smooth muscle actin),hepatocyte (UGT1A1,CK8) and biliary (CK19) markers.Moreover,these cells are able to store glycogen,and have glucose 6 phosphatase activity,but not UGT1A1 activity.Under the hepatogenic differentiation protocol,rFLDC display an up-regulation of hepatocyte markers expression (albumin,tryptophan 2,3-dioxygenase,G6Pase) correlated to a down-regulation of the expression of the biliary marker CK19.CONCLUSION:Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC.However,we demonstrated the presence of an original rodent hepato-biliary cell type.

  4. Cirrhotic Multiorgan Syndrome

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming

    2015-01-01

    Patients with cirrhosis and portal hypertension are at an increased risk of the development of circulatory dysfunction that may potentially result in multiple organ failure. Apart from the liver, this may involve the heart, lungs, kidneys, the immune system, the adrenal glands, and other organ...... complications such as hepatorenal syndrome. In patients with chronic organ dysfunction, various precipitating events may induce an acute-on-chronic renal failure and acute-on-chronic liver failure that negatively affect the prognosis. Future research on the pathophysiologic mechanisms of the complications...... and the precipitating factors is essential to understand the basics of the treatment of these challenging conditions. The aim of the present review is to focus on the development and precipitating factors of various organ failures in patients with decompensated cirrhosis....

  5. PDGF-BB induces expression of LTBP-1 but not TGF-beta1 in a rat cirrhotic fat storing cell line.

    Science.gov (United States)

    Westhoff, Jens H; Sawitza, Iris; Keski-Oja, Jorma; Gressner, Axel M; Breitkopf, Katja

    2003-01-01

    TGF-beta, a profibrogenic cytokine is predominantly secreted as a latent molecule complexed with one of the latent TGF-beta binding proteins (LTBP). Due to the proposed functions of LTBP-1 and -3 in regulating TGF-beta-bioavailability and -activity, we investigated the effects of PDGF-BB and TGF-beta1 on their expression levels in Cirrhotic fat storing cells (CFSC). CFSC basally express LTBP-1 and -3 and TGF-beta1. LTBP-1 colocalizes with LAP and the cells secrete some active TGF-beta1. Promoter studies showed no strong induction of the LTBP-1 promoters after stimulation, although mRNA and protein levels were increased by PDGF-BB treatment without affecting TGF-beta1 expression. Vice versa, TGF-beta1 treatment did not alter LTBP-1 expression while an autocrine induction was found. Our data indicate that LTBP-1 but not TGF-beta1 is induced by PDGF-BB and that TGF-beta1 autoinduction does not affect the expression of LTBP-beta1. This divergent regulation may represent an important mechanism for modulation of TGF-beta bioavailability.

  6. Ebselen prevents early alcohol-induced liver injury in rats.

    Science.gov (United States)

    Kono, H; Arteel, G E; Rusyn, I; Sies, H; Thurman, R G

    2001-02-15

    Oxidants have been shown to be involved in alcohol-induced liver injury. Moreover, 2-phenyl-1,2-benzisoselenazole-3(2H)-one (ebselen), an organoselenium compound and glutathione peroxidase mimic, decreases oxidative stress and protects against stroke clinically. This study was designed to test the hypothesis that ebselen protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g/kg/d) continuously for up to 4 weeks using the intragastric enteral feeding protocol developed by Tsukamoto and French. Ebselen (50 mg/kg twice daily, intragastrically) or vehicle (1% tylose) was administered throughout the experiment. Mean urine ethanol concentrations were not significantly different between treatment groups, and ebselen did not affect body weight gains or cyclic patterns of ethanol concentrations in urine. After 4 weeks, serum ALT levels were increased significantly about 4-fold over control values (37 +/- 5 IU/l) by enteral ethanol (112 +/- 7 IU/l); ebselen blunted this increase significantly (61 +/- 8 IU/l). Enteral ethanol also caused severe fatty accumulation, mild inflammation, and necrosis in the liver (pathology score: 4.3 +/- 0.3). In contrast, these pathological changes were blunted significantly by ebselen (pathology score: 2.5 +/- 0.4). While there were no significant effects of either ethanol or ebselen on glutathione peroxidase activity in serum or liver tissue, ebselen blocked the increase in serum nitrate/nitrite caused by ethanol. Furthermore, ethanol increased the activity of NF-kappaB over 5-fold, the number of infiltrating neutrophils 4-fold, and the accumulation of 4-hydroxynonenal over 5-fold. Ebselen blunted all of these effects significantly. These results indicate that ebselen prevents early alcohol-induced liver injury, most likely by preventing oxidative stress, which decreases inflammation.

  7. Umbilical hernia in cirrhotic patients: outcome of elective repair.

    Science.gov (United States)

    Lasheen, Adel; Naser, Hatem M; Abohassan, Ahmed

    2013-12-01

    Cirrhotic patients with umbilical hernia have an increased likelihood of complications following repair. The aim of this study was to assess the outcomes of elective umbilical hernia repair in cirrhotic patients. Fifty patients having uncomplicated umbilical hernia with a cirrhotic liver were studied prospectively. These patients divided into three groups' according to Child-Turcotte-Pugh (CTP) classification. After management of coagulopathy, correction of hypoalbuminaemia and electrolytes imbalance, and control of ascites, all patients underwent elective hernia repair under regional anesthesia. A comparison was made between the three groups as regard the size of the defect in the linea Alba, operative time, postoperative morbidity and mortality, length of hospital stay, time of return to daily life and postoperative changes in liver function tests (LFTs) in relation to the regional anesthesia applied. hernioplasty was done under spinal anesthesia in 13 patients (26%), under epidural anesthesia in 10 patients (20%), under intercostal nerve block in 7 patients (14%), and under local anesthesia in 20 patients (40%). There was an increased safety (less changes in LFTs) in cases done under local anesthesia and intercostal nerve block. The overall complications rate was 30%. There was an increased complications rate towards the decompensated cases. The differences in the mean length of hospital stay and mean time of return to daily life are statistically significant between the three groups. Umbilical hernia recurrence rate was 2% and no mortality was reported in the study groups.

  8. Short-Term, Low-Dose Use of Tolvaptan as a Bridge Therapy to Expedite Liver Transplant for Severe Hyponatremic, Cirrhotic Patients With High Model for End-Stage Liver Disease Scores.

    Science.gov (United States)

    Lenci, Ilaria; Milana, Martina; Angelico, Mario; Baiocchi, Leonardo

    2015-11-17

    For patients on liver transplant waiting lists, hyponatremia is associated with increased mortality before transplant and complications during the early posttransplant period. Conventional therapies, such as fluid restriction or hypertonic saline infusion, are of limited value. We describe 2 patients with high Model for End-Stage Liver Disease scores (> 30) who were referred to our unit for expedited liver transplant. While on waiting lists, these patients developed severe hyponatremia (therapies. Low-dose, short-term tolvaptan therapy (15 mg/d for 5 d) was then administered, as a bridge therapy to transplant, resulting in prompt restoration of serum sodium levels without any major clinical event. One patient died a few days later as no suitable grafts were available. The other received a liver transplant, and the outcome was uneventful. In conclusion, our report demonstrates that a short-term, low-dose tolvaptan-based strategy promptly resolves hyponatremia in patients who are on expedited waiting lists for liver transplant, allowing surgery with improved sodium levels and possibly limiting peritransplant complications.

  9. Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China

    Institute of Scientific and Technical Information of China (English)

    Yu-Yuan Li; Yu-Qiang Nie; Wei-Hong Sha; Zheng Zeng; Fu-Ying Yang; Li Ping; Lin Jia

    2004-01-01

    AIM: Subclinical hepatic encephalopathy (SHE) is a common complication of liver diseases. The aim of this study was to find out the normal value of psychometric test and to investigate the prevalence of SHE in Chinese patients with stabilized hepatic cirrhosis.METHODS: Four hundred and nine consecutive cirrhotic patients without overt clinical encephalopathy were screened for SHE by using number connection test part A (NCT-A) and symbol digit test (SDT). SHE was defined as presence of at least one abnormal psychometric test. The age-corrected normal values were defined as the mean±2times standard deviation (2SD), and developed in 356 healthy persons as normal controls. Four hundred and sixteen patients with chronic viral hepatitis were tested as negative controls to assess the diagnostic validity of this test battery.RESULTS: There was no significant difference in NCT scores and SDT quotients between healthy controls and chronic hepatitis group (P>0.05). In all age subgroups,the NCT and SDT measurements of cirrhotic patients differed significantly from those of the controls (P<0.05).When mean±2SD of SDT and NCT measurements from healthy control group was set as the normal range, 119cirrhotic patients (29.1%) were found to have abnormal NCT-A and SDT tests, 53 (13.0%) were abnormal only in SDT and 36 (8.8%) only in NCT-A. Taken together, SHE was diagnosed in 208 (50.9%) cirrhotic patients by this test battery. The prevalence of SHE increased from 39.9%and 55.2% in Child-Pugh's grade A and B groups to 71.8%in Child-Pugh's grade C group (P<0.05). After the adjustment of age and residential areas required from the tests, no correlation was found in the rate of SHE and causes of cirrhosis, education level and smoking habit.CONCLUSION: Psychometric tests are simple and reliable indicators for screening SHE among Chinese cirrhotic patients. By using a NCT and SDT battery, SHE could be found in 50.9% of cirrhotic patients without overt clinical encephalopathy. The

  10. Melatonin and succinate reduce rat liver mitochondrial dysfunction in diabetes.

    Science.gov (United States)

    Zavodnik, I B; Lapshina, E A; Cheshchevik, V T; Dremza, I K; Kujawa, J; Zabrodskaya, S V; Reiter, R J

    2011-08-01

    Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, pdiabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V(3) and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

  11. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver

    DEFF Research Database (Denmark)

    Oertel, Michael; Menthena, Anuradha; Chen, Yuan-Qing

    2008-01-01

    BACKGROUND & AIMS: Previously, we showed high-level, long-term liver replacement after transplantation of unfractionated embryonic day (ED) 14 fetal liver stem/progenitor cells (FLSPC). However, for clinical applications, it will be essential to transplant highly enriched cells, while maintaining....... Rat ED14 FLSPC are alpha-fetoprotein(+)/cytokeratin-19(+) or alpha-fetoprotein(+)/cytokeratin-19(-) and contain all of the normal liver repopulation capacity found in fetal liver. Hematopoietic stem cells, a major component in crude fetal liver cell preparations that engraft in other organs......, such as bone marrow, spleen, and lung, are totally removed by Dlk-1 selection, and Dlk-1 purified FLSPC repopulate only the liver. CONCLUSIONS: This is the first study reporting purification of hepatic stem/progenitor cells from fetal liver that are fully capable of repopulating the normal adult liver...

  12. Resveratrol inhibits nonalcoholic fatty liver disease in rats

    Directory of Open Access Journals (Sweden)

    Irastorza Belen

    2008-09-01

    Full Text Available Abstract Background The prevalence of nonalcoholic fatty liver disease (NAFLD is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor α (TNF-α production, lipid peroxidation and oxidative stress. Methods Male Wistar CRL: Wi (Han (225 g rats were randomized into three groups. A control group (n = 12 was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12 and resveratrol (n = 12 groups were given free access to feed (a high carbohydrate-fat free modified diet and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-α in serum, hepatic malondialdehyde (MDA, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase and biochemical parameters were measured. Results Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P P P P Conclusion Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-α inhibition and antioxidant activities.

  13. Metabolism of Mequindox in Isolated Rat Liver Cells

    Institute of Scientific and Technical Information of China (English)

    LI Guang-hui; SHAN Qi; WANG Jing; LI Ya-fei; GAO Yan; ZENG Zhen-ling

    2014-01-01

    Mequindox (MEQ), 3-methyl-2-quinoxalinacetyl-1,4-dioxide, is widely used in Chinese veterinary medicine as an antimicrobial agent and feed additive. Its toxicity has been reported to be closely related to its metabolism. To understand the pathways underlying MEQ’s metabolism more clearly, we studied its metabolism in isolated rat liver cells by using liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap (LC-LTQ-Orbitrap) mass spectrometry. The structures of MEQ metabolites and their product ions were readily and reliably characterized on the basis of accurate MS2 spectra and known structure of MEQ. Eleven metabolites were detected in isolated rat liver cells, two of which were detected for the ifrst time in vitro. The major metabolic pathways reported previously for in vitro metabolism of MEQ in rat microsomes were conifrmed in this study, including N→O group reduction, carbonyl reduction, and methyl monohydroxylation. In addition, we found that acetyl hydroxylation was an important pathway of MEQ metabolism. The results also demonstrate that cellular systems more closely simulate in vivo conditions than do other in vitro systems such as microsomes. Taken together, these data contribute to our understanding of the in vivo metabolism of MEQ.

  14. Effects of Neurolytic Celiac Plexus Block on Liver Regeneration in Rats with Partial Hepatectomy

    OpenAIRE

    Jun Li; Hong-Tao Yan; Jian-Xiang Che; Shu-Rong Bai; Qing-Ming Qiu; Ling Ren; Fan Pan; Xiao-Qin Sun; Fu-Zhou Tian; Dong-Xuan Li; Li-Jun Tang

    2013-01-01

    Liver regeneration is the basic physiological process after partial hepatectomy (PH), and is important for the functional rehabilitation of the liver after acute hepatic injury. This study was designed to explore the effects of neurolytic celiac plexus block (NCPB) on liver regeneration after PH. We established a model of PH in rats, assessing hepatic blood flow, liver function, and serum CRP, TNF-α, IL-1β and IL-6 concentrations of the residuary liver after PH. Additionally, histopathologica...

  15. [Enzyme kinetics of ligustilide metabolism in rat liver microsomes].

    Science.gov (United States)

    Qian, Min; Shi, Li-fu; Hu, Jin-hong

    2009-04-01

    To study the enzyme kinetics of ligustilide metabolism and the effects of selective CYP450 inhibitors on the metabolism of ligustilide in liver microsomes of rat, a LC-MS method was established for quantitative analysis of ligustilide in liver microsomes incubation system with nitrendipine as internal standard. The determination m/z for ligustilide was 173, and for nitrendipine, 315. An optimum incubation system was found and various selective CYP inhibitors were used to investigate their inhibitory effects on the metabolism of ligustilide. The results showed that enzyme kinetics of ligustilide could be significantly inhibited by ketoconazole, trimethoprim and a-naphthoflavon but scarcely inhibited by omeprazole, 4-methylpyrazole and quinidine. Therefore, CYP3A4, CYP2C9 and CYP1A2 are the major isoenzyme participated in in vitro metabolism of ligustilide.

  16. Liver tumor promoting effects of fenbendazole in rats.

    Science.gov (United States)

    Shoda, T; Onodera, H; Takeda, M; Uneyama, C; Imazawa, T; Takegawa, K; Yasuhara, K; Watanabe, T; Hirose, M; Mitsumori, K

    1999-01-01

    In order to examine whether fenbendazole has tumor-promoting activity, a total of 70 male Fischer 344 rats were initiated with a single intraperitoneal injection of 100 mg/kg of diethylnitrosamine (DEN) or were given the saline vehicle alone; beginning 1 wk later, rats were given a diet containing 3,600; 1,800; 600; 200; 70; or 0 ppm of fenbendazole for 8 wk. Subgroups of 5 rats each from the DEN+ 1,800; DEN+0; 1,800; and 0 ppm groups were euthanatized after 1 wk of fenbendazole treatment, and the remaining animals were euthanatized at 8 wk. After 1 wk, relative liver weights (ratios to body weights) were significantly increased in the DEN+ 1,800 and 1,800 ppm groups, and based on light microscopy, periportal hepatocellular hypertrophy was evident in these groups. After 8 wk, relative liver weights were significantly increased in the groups given > or =600 ppm with or without DEN initiation. Periportal hepatocellular hypertrophy, characterized by a marked increase in smooth endoplasmic reticulum, was observed in the groups given > or =600 ppm with or without DEN initiation. Induction of cytochrome P-450 (CYP) 1A2, 2B1, or 4A1 was noted in the fenbendazole-treated groups with or without DEN initiation; that associated with CYP 1A2 was most marked. Positive immunostaining for anti-CYP 1A1/2 or CYP 2B1/2 was observed diffusely in the livers of animals in the DEN+1,800 and DEN+3,600 ppm groups. The numbers and areas of connexin 32 (Cx32)-positive spots per square centimeter in centrilobular hepatocytes were significantly decreased in an almost dose-dependent manner with fenbendazole treatment after DEN initiation. In situ hybridization for Cx32 mRNA revealed a remarkable decrease in its expression in the centrilobular hepatocytes in the DEN+70 ppm group. The numbers of glutathione S-transferase placental-form positive single cells (plus mini foci) were significantly increased in the DEN+ 1,800 and DEN+3,600 ppm groups. Since those agents that induce CYP 2B1/2 isozymes

  17. Interaction of sulfur mustard with rat liver salt fractionated chromatin.

    Science.gov (United States)

    Jafari, Mahvash; Nateghi, M; Rabbani, A

    2010-01-01

    In this study, the interaction of an alkylating agent, sulfur mustard (SM) with rat liver active (S1 and S2) and inactive (P2) chromatin was investigated employing UV/vis spectroscopy and gel electrophoreses. The results show that SM affects the chromatin structure in a dose-dependent manner. The binding of SM to fractions is different. At lower concentrations (<500 microM), SM seems to unfold the structure and at higher concentrations, it induces aggregation and condensation of chromatin possibly via forming cross-links between the chromatin components. The extent of condensation in S2 is higher when compared to the P2 fraction.

  18. Corticosteroids increase superoxide anion production by rat liver microsomes.

    Science.gov (United States)

    Nelson, D H; Ruhmann-Wennhold, A

    1975-01-01

    Superoxide anion production by liver microsomes from intact, adrenalectomized, and cortisoltreated adrenalectomized rats has been determined. The amount formed was roughly proportionate to the amount of cortisol given, and a similar response was seen in the activity of NADPH-cytochrome c reductase. The amount of measurable superoxide anion was markedly reduced by the addition of superoxide dismutase. The increased production of this potent free radical with cortisol therapy suggests that its formation may contribute to some of the harmful effects of corticosteroids given in more than physiologic amounts. PMID:239969

  19. Metabolism of 3-methylcholanthrene by rat liver microsomes: a reinvestigation

    Energy Technology Data Exchange (ETDEWEB)

    Stoming, T.A. (Medical Coll., Augusta, GA); Bornstein, W.; Bresnick, E.

    1977-01-01

    Metabolites of 3-methylcholanthrene (3-MC) formed by rat liver microsomes were analyzed by high pressure liquid chromatography. The metabolic profile is significantly different from previous studies using thin layer chromatography. The major metabolites include 1- and 2-hydroxy-3-MC. Use of the high pressure liquid chromatographic system allows for the separation of at least seven new metabolites. The amounts of three of these new metabolites are substantially decreased when the potent epoxide hydrase inhibitor 3,3,3-trichloropropene oxide is added to the incubation system. These results then suggest the formation of epoxides of 3-methylcholanthrene other than the K-region oxide.

  20. Loss and recovery of liver regeneration in rats with fulminant hepatic failure.

    Science.gov (United States)

    Eguchi, S; Lilja, H; Hewitt, W R; Middleton, Y; Demetriou, A A; Rozga, J

    1997-10-01

    We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased in weight four times reaching 30% of the original liver mass

  1. 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.

  2. Subchronic Toxicity of Lanthanum Nitrate on Liver in Rats

    Institute of Scientific and Technical Information of China (English)

    刘颖; 陈东; 陈爱军; 刘渤; 孙淑艳; 聂毓秀

    2002-01-01

    Young Wistar rats were divided into six groups,the experimental groups were given La(NO3)3 at dose of 20,10,2,0.2,0.1 mg*kg-1 and the control group was given physiological saline respectively for six months. The animalswere weighed and the ratios of the liver to body weight were counted. Pathological changes of liver were observed by light microscope and transmission electron microscope. Glutamic-oxalacetic transaminase(GOT), glutamic-pyruvic transaminase (GPT),gamma-glutamyl transferase(γ-GT) and alkline phosphatase(ALP) in the serum were measured. The results indicate that the body weight of animals gaines slowly in the group of 20 mg*kg-1 La(NO3)3, but it gained quickly in the rats fed with 0.1 mg*kg-1 La(NO3)3. Biochemical indexes have no abnormal changes. In the group of 20 mg*kg-1 La(NO3)3, there were lipid droplets and decrease of glycogen in the hepatocytes, denser matrix of the mitochondria, deformation of the nuclei of some hepatocytes to different degree and infiltration of inflammatory cells at portal area. The more the dose of La(NO3)3 were given to the rats, the more the number of bodies containing highly electronic dense gravel-like granules and the secondary lysosomes with dense bodies. The rats fed with 20 mg*kg-1 La(NO3)3 for six months shows injurious effects on the hepatocytes.

  3. Rat liver contains a limited number of binding sites for hepatic lipase

    NARCIS (Netherlands)

    G.C. Schoonderwoerd (Kees); A.J.M. Verhoeven (Adrie); H. Jansen (Hans)

    1994-01-01

    textabstractThe binding of hepatic lipase to rat liver was studied in an ex vivo perfusion model. The livers were perfused with media containing partially purified rat hepatic lipase or bovine milk lipoprotein lipase. The activity of the enzymes was determined in the pe

  4. Adrenomedullin in cirrhotic and non-cirrhotic portal hypertension

    Institute of Scientific and Technical Information of China (English)

    V Tahan; C Kalayci; A Okten; N Tozun; E Avsar; C Karaca; E Uslu; F Eren; S Aydin; H Uzun; HO Hamzaoglu; F Besisik

    2003-01-01

    AIM:Adrenomedullin (ADM) is a potent vasodilator peptide.ADM and nitric oxide (NO) are produced in vascular endothelial cells. Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH). The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown, plasma ADM levels were studied in patients with NCPH, compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups.METHODS: There were 4 groups of subjects. Group 1consisted of 27 patients (F/M: 12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age: 41±12years), group 2 consisted of 14 patients (F/M: 6/8) with compensated (Child-Pugh A) cirrhosis (mean age: 46±4),group 3 consisted of 16 patients (F/M: 6/10) with decompensated (Child-Pugh C) cirrhosis (mean age: 47±12).Fourteen healthy subjects (F/M: 6/8) (mean age: 44±8) were used as controls in Group 4. ADM level was measured by ELISA. NO was determined as nitrite/nitrate level by chemoluminescence.RESULTS: Adl level in Group 11 (236±61.4 pg/mL) was significantly higher than that in group 2 (108.4±28.3 pg/mL)and group 4 (84.1±31.5 pg/mL) (both P<0.0001) but was lower than that in Group3 (324±93.7 pg/mL) (P=0.002). NO level in group 1 (27±1.4 μmol/L) was significantly higher than that in group 2 (19.8±2.8 μmol/L) and group 4 (16.9±1.6μmol/L) but was lower than that in Group 3 (39±3.6 μmol/L)(for all three P<0.0001). A strong correlation was observed between ADM and NO levels (r=0.827, P<0.0001).CONCLUSION: Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated, Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis, and were significantly higher than those in patients with NCPH.Portal hypertension plays an important role in the increase of ADM and NO. Parenchymal damage in cirrhosis may

  5. Effects ofSalmonella infection on hepatic damage following acute liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    Yong-Tao Li; Cheng-Bo Yu; Dong Yan; Jian-Rong Huang; Lan-Juan Li

    2016-01-01

    BACKGROUND: Acute liver injury is a common clinical disor-der associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The pur-pose of this study was to address this unanswered question using a rat model. METHODS: Oral supplementation withSalmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the con-centrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury. RESULTS: The levels of liver damage and endotoxin were sig-niifcantly increased in theSalmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P CONCLUSIONS: OralS. enteritidis administration exacer-bates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inlfammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

  6. Evaluation of methylmercury biotransformation using rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, A. [Biochemistry Section, National Inst. for Minamata Disease, Minamata, Kumamoto (Japan); Hirayama, K. [Kumamoto University College of Medical Science, Kuhonji (Japan)

    2001-09-01

    To examine the demethylation reaction of methylmercury (MeHg) in rat liver, slices prepared from MeHg-treated rats were incubated in L-15 medium under 95% O{sub 2}/5% CO{sub 2} atmosphere. During the incubation, the amount of inorganic Hg in the slices markedly increased in a time-dependent manner, although the concentration of total Hg remained unchanged. Since the C-Hg bond in MeHg was demonstrated to be cleaved by the action of some reactive oxygen species, the effects on MeHg demethylation of several reagents that could modify reactive oxygen production were examined in the present system. Methylviologen was found to be an effective enhancer of the demethylation reaction with only a minor effect on lipid peroxidation. On the other hand, ferrous ion added to the medium showed no effect on demethylation in the presence or absence of methylviologen, although lipid peroxide levels were increased significantly by ferrous ion. Similarly, deferoxamine mesylate, which effectively suppressed the increase in lipid peroxide levels, also had no effect on demethylation. Furthermore, hydroxy radical scavengers, such as mannitol and dimethylsulfoxide, had no effect on inorganic Hg production. Rotenone, an inhibitor of complex I in the mitochondrial electron transport system, increased levels of both inorganic Hg and lipid peroxide. However, other inhibitors, such as antimycin A, myxothiazole and NaCN, significantly suppressed the demethylation reaction. Cell fractionation of the MeHg-treated rat liver revealed that the ratio of inorganic Hg to total Hg was highest in the mitochondrial fraction. Furthermore, superoxide anion could degrade MeHg in an organic solvent but not in water. These results suggested that the demethylation of MeHg by the liver slice would proceed with the aid of superoxide anion produced in the electron transfer system at the hydrophobic mitochondrial inner membrane. Furthermore, the involvement of hydroxy radicals, which have been demonstrated to be

  7. Effects of adenoviral-mediated hepatocyte growth factor on liver regeneration after massive hepatectomy in rats

    Directory of Open Access Journals (Sweden)

    Doihara,Hiroyoshi

    2007-04-01

    Full Text Available Resection is the only curative treatment for liver metastasis of colorectal cancers. Despite the supreme regenerative potential of the liver, major hepatectomy sometimes leads to liver failure, and the limitation of resectable liver volumes makes advanced tumors inoperable. This study was attempted to promote liver regeneration using hepatocyte growth factor (HGF gene transfection by venous-administered adenovirus and to improve the survival of rats after massive hepatectomy. The adenovirus that encodes HGF was administered to rats before 85%-hepatectomy. The administration of HGF gene improved the survival of rats after massive hepatectomy, while the administration of control adenovirus deteriorated their survival. Gene transfection of HGF showed up-regulation of serum HGF, stimulation of hepatocellular proliferation and rapid liver regeneration. Moreover, HGF administration reduced apoptosis of hepatocytes. The administration of HGF gene prevented liver dysfunction after major hepatectomy and may be a new assist for surgery.

  8. A Comparative Study of the Metabolism of 6-Methylbenzo [A] Pyrene and Benzo [A] Pyrene by Rat Liver Microsomes

    Science.gov (United States)

    1984-02-24

    Rat Liver Microsomes Name...pyrena by Rat Liver Microsomes Karen Lee Hamernik, Doctor of Philosophy, 1984 Dissertation directed by: Shan K. Yang, Ph.D., Professor, Department of...Microsomal Enzymes 85 Metabolism of 6-OHMBaP by Rat Liver Microsomes 94 Identification of 6-OHMBaP Metabolites 94 UV absorption spectral analysis

  9. Changes in serum ammonia concentration in cirrhotic patients with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study whether liver cirrhosis associated with Helicopacter pylori (H. pylori)infection will induce increased serum ammonia and whether the peripheral serum ammonia reflects the level of portal vein serum ammonia. Methods Blood was taken from the portal vein and the cubital vein in cirrhotic patients with and without H.pylori infection and non-cirrhotic patients (splenic rupiure) with and without H. pylori infection, and the serum ammonia was measured. Results The mean levels of serum ammonia in the group of cirrhotic patients with H. pylori infection were 167.82±8.97 μmol/L (pertal vein) and 142.2±13.35 μmol/L (cubital vein). They were increased significantly as compared with cirrhotic patients without H.pyiori infection(47.68±12.03 μmol/L portal vein and 37.23±7.04 μmol/L cubital vein),and also compared with the groups of splenic rupture patients with and without H. pylori infection (P<0.0t).There was no significant difference between the serum ammonia level of the cubital vein and pertal vein(P>0.05). Conclusions H.pylori intection can induce an increase in serum ammonia in patients with liver dysfunction,and the peripheral serum ammonia measurement may replace the portal vein serum ammania as a monitoring method. Eradication of H.pylori in cirrhotic patients may prevent hepatic encephalopathy(HE).

  10. Evaluación del estado nutricional de pacientes con cirrosis hepática alcohólica atendidos en la Clínica de Hígado del Hospital General de México Nutritional assessment of alcoholic liver cirrhotic patients treated in the liver Clinic of the Mexico's General Hospital

    Directory of Open Access Journals (Sweden)

    H. V. Landa-Galván

    2012-12-01

    Full Text Available La desnutrición en el paciente cirrótico se asocia a mayor morbi-mortalidad; sin embargo, su diagnóstico es complejo por lo que el objetivo del estudio fue evaluar el estado nutricional empleando distintos métodos. Se evaluaron pacientes adultos con cirrosis hepática de origen alcohólico que acudieron a la Clínica de Hígado del Hospital General de México. Se aplicó un recordatorio de 24 horas y antropometría, herramientas de tamizaje (Malnutrition Universal Screening Tool, Nutritional Risk Screening-2002 y de diagnóstico nutricional específica para pacientes con cirrosis hepática (Royal Free Hospital Global Assessment. Se incluyeron 62 pacientes y 51,6% fueron hombres. La desnutrición por área muscular de brazo fue de 31,3% en hombres y de 10% en mujeres, y por área grasa de brazo fue de 23,3% en mujeres y 3,1% en hombres (p Malnutrition in the cirrhotic patient is associated to a higher morbidity and mortality rate; however, the diagnosis is complex, so the study objective was to assess the nutritional status using different methods. Adult patients with alcoholic liver cirrhosis treated in the Liver Clinic of the Mexico's General Hospital were evaluated. Anthropometric measurements and a 24 hours recall were made; screening tools (Malnutrition Universal Screening Tool, Nutritional Risk Screening-2002 and a method for assessing nutritional status specifically in cirrhotic patients (Royal Free Hospital Global Assessment were used. We included 62 patients, 51.6% of them were men. Malnutrition by arm muscle area was 31.3% in men and 10% in women, and by arm fat area was 23.3% in women and 3.1% in men (p < 0.05. With the screening tools the percentages of malnutrition risk were 43.5% and 54.8% respectively, vs. 1.6% identified as "low weight" with the Body Mass Index. With the Royal Free Hospital Global Assessment tool the percentage of malnutrition was 45.2%. Patients with malnutrition had an energy and protein intake significantly

  11. Nesfatin-1 alleviates extrahepatic cholestatic damage of liver in rats

    Directory of Open Access Journals (Sweden)

    Ali Solmaz

    2016-11-01

    Full Text Available Obstructive jaundice (OJ can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8, control (n = 8, and nesfatin (n = 8. After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114. Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032. Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75. DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects.

  12. The histopathological effects of salvia officinalis on the kidney and liver of rats

    Directory of Open Access Journals (Sweden)

    D.A. Adekomi

    2013-03-01

    Full Text Available The aim of this investigation was to evaluate some of the effects of aqueous leaf extract of Salvia officinalis on the kidney and liver of male Sprague Dawley rats. Ten Sprague-Dawley rats (7-11 weeks old were randomly assigned into two groups; A and B. Aqueous extract of S. officinalis leaves (300 mg/kg body weight was administered orally to the rats in group B while the rats in group A received equal volume of normal saline for 14d. At termination of treatment, the histopathology of the kidney and liver were assessed. The kidney and the liver in the extract treated rat displayed organized and preserved histological profile. Our findings suggest that S. officinalis has no deleterious effects on the kidney and liver of the rats.  

  13. Signal profile on Gd-EOB-DTPA-enhanced MR imaging in non-alcoholic steatohepatitis and liver cirrhosis induced in rats: correlation with transporter expression

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, Natsuko [Diagnostic Imaging Medical Affairs, Medical Affairs, Bayer Yakuhin, Ltd., Osaka, Osaka (Japan); Matsui, Osamu [Kanazawa University Graduate School of Medical Science, Department of Radiology, Kanazawa, Ishikawa (Japan)

    2011-12-15

    To compare the transporter expression and signal profile on Gd-EOB-DTPA-enhanced MRI between non-alcoholic steatohepatitis (NASH) and cirrhotic liver induced in rats, and investigate the correlation of the transporter expression and fibrosis rate in both diseases. Forty-eight rats were divided into four groups of 12: TAA (cirrhosis), NASH 7- and 10-week, and control groups. Each group was divided into two subgroups: Group 1 for MRI and Group 2 for transporter examinations. The relative enhancement of the TAA group was significantly lower than those of other groups (p < 0.01). The T{sub max} and T{sub 1/2} of the NASH 10-week group was significantly prolonged in comparison with the TAA group (p < 0.01). There was no significant difference in the oatp1 expression, whereas the mrp2 expression of the TAA group was significantly higher than those of other groups (p < 0.01). There was no significant correlation between the fibrosis rate and oatp1 expression, whereas a paradoxical correlation was found between the fibrosis rate and mrp2 expression (NASH: negative correlation, r = 0.91, p < 0.01; TAA: positive correlation, r = 0.85, p < 0.01). Our findings showed that the mrp2 expression in cirrhosis increases in comparison with NASH, and there was a paradoxical correlation between the fibrosis rate and mrp2 expression. (orig.)

  14. Uptake of dodecanedioic acid by isolated rat liver.

    Science.gov (United States)

    Greco, A V; Mingrone, G; De Gaetano, A; Amigo, L; Puglielli, L; Castagneto, M; Nervi, F

    1997-02-17

    The uptake of dodecanedioic acid (C12); a dicarboxylic acid with 12 carbon atoms, was studied in the isolated perfused rat liver. Fifty mumol of C12 were injected as a bolus into the perfusing liver solution. The concentration of C12 in perfusate samples taken over 2 h from the beginning of the experiments were analyzed by high performance liquid chromatography. An in vitro experimental session was performed to determine the binding curve of C12 to defatted bovine serum albumin. These data were then used to compute the perfusate C12 free fraction. The number of binding sites on the albumin molecule was equal to 4.29 +/- 0.21 (S.E.), while the affinity constant was 6.33 +/- 0.87 x 10(3). M-1. Experimental values of perfusate C12 concentration versus time were individually plotted and fitted to a monoexponential decay for each liver perfused. The predicted C12 concentration at time zero averaged 0.354 +/- 0.0375 mumol/ml. Prom this value the apparent volume of distribution of C12 was obtained and corresponded to 153.02 +/- 14.56 ml. The disappearance rate constant from the perfusate was 0.0278 +/- 0.0030 min-1. The C12 half life was 26.6 +/- 2.3 min. The mean hepatic clearance from the perfusate was 4.08 +/- 0.38 ml/min. In conclusion, C12 is quickly taken up by the liver so that in about 100 min it was completely cleared from the perfusate.

  15. TRANSPLANTATION OF CRYOPRESERVED FETAL LIVER CELLS SEEDED INTO MACROPOROUS ALGINATE-GELATIN SCAFFOLDS IN RATS WITH LIVER FAILURE

    Directory of Open Access Journals (Sweden)

    D. V. Grizay

    2015-01-01

    Full Text Available Aim. To study the therapeutic potential of cryopreserved fetal liver cells seeded into macroporous alginategelatin scaffolds after implantation to omentum of rats with hepatic failure.Materials and methods.Hepatic failure was simulated by administration of 2-acetyl aminofl uorene followed partial hepatectomy. Macroporous alginate-gelatin scaffolds, seeded with allogenic cryopreserved fetal liver cells (FLCs were implanted into rat omentum. To prevent from colonization of host cells scaffolds were coated with alginate gel shell. Serum transaminase activity, levels of albumin and bilirubin as markers of hepatic function were determined during 4 weeks after failure model formation and scaffold implantation. Morphology of liver and scaffolds after implantation were examined histologically. Results. Macroporous alginate-gelatin scaffolds after implantation to healthy rats were colonized by host cells. Additional formation of alginate gel shell around scaffolds prevented the colonization. Implantation of macroporous scaffolds seeded with cryopreserved rat FLCs and additionally coated with alginate gel shell into omentum of rats with hepatic failure resulted in signifi cant improvement of hepatospecifi c parameters of the blood serum and positive changes of liver morphology. The presence of cells with their extracellular matrix within the scaffolds was confi rmed after 4 weeks post implantation.Conclusion. The data above indicate that macroporous alginate-gelatin scaffolds coated with alginate gel shell are promising cell carriers for the development of bioengineered liver equivalents.

  16. ON THE MECHANISM OF DRUG HYDROXYLATION IN RAT LIVER MICROSOMES

    Science.gov (United States)

    Orrenius, Sten

    1965-01-01

    The TPNH- and O2-dependent drug hydroxylation system of liver microsomes has been studied using normal rats and rats in which the drug-hydroxylating activity has been enhanced by repeated injections of phenobarbital. The oxidative demethylation of aminopyrine is employed as an assay. Optimal conditions for the assay with regard to the concentrations of TPNH and aminopyrine are established. TPN inhibits the reaction in a competitive manner, similarly to its effect on the microsomal TPNH-cytochrome c reductase. Drug hydroxylation, but not the "TPNH oxidase," TPNH-cytochrome c, -2,6-dichlorophenolindophenol, or -neotetrazolium reductase reaction, or the TPNH-dependent lipid peroxidation, is blocked by carbon monoxide. Microsomes from phenobarbital-treated rats exhibit increased activities of the various TPNH-linked reductase reactions, parallel to the increased drug hydroxylation activity, whereas the "TPNH oxidase" activity does not change appreciably. Measurements with microsomes from drug-treated animals reveal a 1:1:1 stoichiometry of aminopyrine-dependent oxygen uptake, TPNH oxidation, and formaldehyde formation. Attempts to solubilize the drug-hydroxylating enzyme system are also presented. It is concluded that the drug-hydroxylating enzyme system involves the microsomal TPNH-cytochrome c reductase and CO-binding pigment, and a hypothetic reaction scheme accounting for the data presented is proposed. PMID:19866674

  17. Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Yumin Xu

    Full Text Available BACKGROUND: Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF. METHODOLOGY: Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations. PRINCIPAL FINDINGS: Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats. CONCLUSIONS: sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

  18. Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    José Eymard Medeiros-Filho; Isabel Maria Vicente Guedes de Carvalho Mello; Jo(a)o Renato Rebello Pinho; Avidan U Neumann; Fernanda de Mello Malta; Luiz Caetano da Silva; Flair José Carrilho

    2006-01-01

    AIM: To evaluate the impact of hepatitis C virus (HCV)infection with genotype 1 or 3 and the presence or absence of liver cirrhosis (LC) in the early viral kinetics response to treatment.METHODS: Naive patients (n = 46) treated with interferon-α (IFN-α) and ribavirin and followed up with frequent early HCV-RNA determinations were analysed.Patients were infected with genotype 1 (n = 28, 7 with LC) or 3 (n = 18, 5 with LC).RESULTS: The first phase decline was larger in genotype 3 patients than in genotype 1 patients (1.72 vs 0.95log IU/mL, P < 0.001). The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients (0.87 vs 0.15 log/wk, P < 0.001). Differences were found in both cirrhotic and non-cirrhotic patients.Genotype 1 cirrhotic patients had a slower 2nd phase slope than non-cirrhotic patients (0.06 vs 0.18 log/wk, P< 0,02). None of genotype 1 cirrhotic patients had a 1stphase decline larger than 1 log (non-cirrhotic patients:55%, P < 0.02). A similar trend toward a slower 2ndphase slope was observed in genotype 3 cirrhotic patients but the 1st phase slope decline was not different.Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,(72% vs14%, P <0.001) and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients (19% vs 0%). A second phase decline slower than 0.3 log per week was predictive of non-response in all groups.CONCLUSION: Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1st phase slope decline in genotype 1 patients.

  19. Consecutive en-bloc liver (30%)-pancreas-duodenum-spleen-stomach transplant in Lewis rats.

    Science.gov (United States)

    Yoo, C H; Hong, I C; Lee, S; Nam, S; Bai, S; Kim, K; Pivetti, C D; Niewiadomski, S T; Wolf, P; Gittes, R F

    2003-01-01

    It is well-known that 30% of the remaining liver mass, following partial hepatectomy, regenerates to full original mass within 2 weeks in rats. In order to carry the transplanted rat liver to repeated transplantation, a technique of combining 30% of the liver with the pancreaticoduodenum and spleen transplantation is performed in this consecutive organ transplantation study. Our laboratory observed several 37-month-old transplanted rats by carrying through 2-3 generations, and histological disclosure were made. Because the partial liver transplants did not regenerate after the transplantation with other splanchnic organs, this technique is not so difficult though subsequent surgical maneuvers are needed and the liver histology proved entirely normal in every aspect when followed beyond the rat's life span of 24 months.

  20. Alcoholic fatty liver in rats: Role of fat and ethanol intake

    Energy Technology Data Exchange (ETDEWEB)

    Sankaran, H.; Deveney, C.W. (VA Medical Centers, Portland, OR (United States)); Larkin, E.C.; Rao, G.A. (VA Medical Centers, Martinez, CA (United States))

    1991-03-11

    The claim that high intake of both ethanol and fat is essential to induce fatty liver and high blood alcohol levels (BAL) was tested. Two groups of rats were fed liquid diets containing 26% and 36% of calories as ethanol respectively. After 4 weeks, all rats were bled for BAL and some were sacrificed to obtain liver morphology. Remaining rats in Group 1 (26% ethanol) were switched to 36% ethanol diet and Group 2 (36% ethanol) to 26% ethanol diet. All rats were sacrificed after 4 weeks to obtain blood for BAL and liver morphology. The results indicate that high ethanol intake and high fat ingestion is not the criterion for induction of fatty liver. Inadequate ingestion of macronutrients plays a major role in alcoholic fatty liver and BAL.

  1. The Epidermal Growth Factor Receptor (EGFR) Inhibitor Gefitinib Reduces but Does Not Prevent Tumorigenesis in Chemical and Hormonal Induced Hepatocarcinogenesis Rat Models

    OpenAIRE

    Silvia Ribback; Verena Sailer; Enrico Böhning; Julia Günther; Jaqueline Merz; Frauke Steinmüller; Kirsten Utpatel; Antonio Cigliano; Kristin Peters; Pilo, Maria G.; Matthias Evert; Calvisi, Diego F.; Frank Dombrowski

    2016-01-01

    Activation of the epidermal growth factor receptor (EGFR) signaling pathway promotes the development of hepatocellular adenoma (HCA) and carcinoma (HCC). The selective EGFR inhibitor Gefitinib was found to prevent hepatocarcinogenesis in rat cirrhotic livers. Thus, Gefitinib might reduce progression of pre-neoplastic liver lesions to HCC. In short- and long-term experiments, administration of N-Nitrosomorpholine (NNM) or intrahepatic transplantation of pancreatic islets in diabetic (PTx), thy...

  2. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    Science.gov (United States)

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).

  3. Dietary conjugated linoleic acid reciprocally modifies ketogenesis and lipid secretion by the rat liver.

    Science.gov (United States)

    Sakono, M; Miyanaga, F; Kawahara, S; Yamauchi, K; Fukuda, N; Watanabe, K; Iwata, T; Sugano, M

    1999-09-01

    The effects of dietary conjugated linoleic acid (CLA) and linoleic acid (LA) on ketone body production and lipid secretion were compared in isolated perfused rat liver. After feeding the 1% CLA diet for 2 wk, the concentration of post-perfused liver cholesterol was significantly reduced by CLA feeding, whereas that of triacylglycerol remained unchanged. Livers from CLA-fed rats produced significantly more ketone bodies; and the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to be consistently higher in the liver perfusate. Conversely, cumulative secretions of triacylglycerol and cholesterol were consistently lower in the livers of rats fed CLA, and the reduction in the latter was statistically significant. Thus dietary CLA appeared to exert its hypolipidemic effect at least in part through an enhanced beta-oxidation of fatty acids at the expense of esterification of fatty acid in the liver.

  4. Study on modified cold storage method of rat livers with self-made HYDsolution

    Institute of Scientific and Technical Information of China (English)

    Bei Sun; Hong Chi Jiang; Hai Quan Qiao; Jin Sheng Sun; Shi Jun Zhu; Xiao Ming Wang

    2000-01-01

    AIM To investigate the effect of cold preservation on rat livers by modified storage method with self-madeHYD solution.METHODS The modified method was that the vascular bed of rat livers was expended with an additional20 mL, 30 mL and 40 mL self-made HYD solution / 100 g liver. After resection of the liver, the extra HYDsolution expressed as % liver weight was entrapped via portal infusion by tying off the supra- and infrahepatic inferior vena cava. According to the amount of extra HYD solution, 40 rats were randomly dividedinto four groups: control group with conventional storage method, 20% group, 30% group and 40% group.The preservation effect of modified storage method was compared with that of conventional storage methodusing isolated perfused rat liver model.RESULTS Bile production and all the indices of hepatic microcirculation including portal perfused pressure, endothelin in the effluent, Trypan blue distribution time and histology in modified method groupswere significantly superior to those in control group (P< 0.05). The liver enzymes in 30% group weremarkedly lower than those in control group (P<0.05). The preservative efficiency of rat liver in 30% groupwas the best among the modified method groups.CONCLUSION The cold preservative efficiency with modified storage method is obviously superior to thatwith conventional storage method. It is suggested that the modified cold storage method is effective and mayhave potential for liver preservation

  5. Abnormal hepatic copper accumulation of spheroid composed of liver cells from LEC rats in vitro.

    Science.gov (United States)

    Ueno, K; Yoshizawa, M; Satoh, T; Yoneda, S; Ohmichi, M; Yamazaki, M; Mori, Y; Suzuki, K T

    1995-11-01

    The LEC rat is a mutant strain displaying hereditary hepatitis, and shows abnormal accumulation of copper (Cu) similar to that occurring in Wilson's disease. We prepared a multicellular spheroid composed of LEC rat liver cells to investigate the mechanism for abnormal accumulation of Cu. These multicellular spheroids were prepared by detaching the monolayer on the collagen-conjugated thermo-responsive polymer coated culture dish at a temperature below the critical solution temperature and culturing on the non-adhesive substratum. Long-term cultured spheroids of LEC rat liver cells as well as SD rat liver cells were attempted. Non-parenchymal cells obtained by collagenase perfusion from the LEC liver were fewer than those from the SD liver. Cells from the LEC rat, over 11 weeks of age, did not form a cell sheet; however, a mixture of parenchymal cells from LEC rats over aged 11 weeks and non-parenchymal cells from SD rats of any age yielded intact spheroids. We examined the toxicity, the accumulation and distribution of Cu in spheroids. The accumulation of Cu in LEC spheroids was higher than that in SD spheroids. Results suggest that spheroids consisting of LEC liver cells are useful as an alternative model to in vivo tests to investigate the mechanism for abnormal accumulation of Cu in liver.

  6. Antitumor activity of two gelsemine metabolites in rat liver microsomes.

    Science.gov (United States)

    Zhao, Qing-Chun; Hua, Wei; Zhang, Lin; Guo, Tao; Zhao, Ming-Hong; Yan, Ming; Shi, Guo-Bing; Wu, Li-Jun

    2010-09-01

    Gelsemine is one of the major alkaloids from Gelsemium elegans Benth., which has been used as an antitumor remedy in clinic. In this paper, metabolism of gelsemine has been investigated in vitro in phenobarbital-treated rat liver microsomes. The metabolites of gelsemine were separated and evaluated using the flash silica gel column, preparative HPLC, using NMR and MS methods. According to the spectral data, two metabolites, M1 and M2, were identified as 4-N-demethylgelsemine and 21-oxogelsemine, respectively. By the MTT method in vitro, the antitumor activities between gelsemine and its metabolites were compared in the HepG2 and HeLa cell lines. Moreover, the main metabolic pathway was further proposed.

  7. In vitro glucuronidation of ochratoxin a by rat liver microsomes.

    Science.gov (United States)

    Han, Zheng; Tangni, Emmanuel K; Di Mavungu, José Diana; Vanhaecke, Lynn; De Saeger, Sarah; Wu, Aibo; Callebaut, Alfons

    2013-12-18

    Ochratoxin A (OTA), one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), UHPLC-Orbitrap-high resolution mass spectrometry (HRMS) and liquid chromatography-multiple stage mass spectrometry (LC-MS(n)) were utilized to investigate the metabolic profile of OTA in rat liver microsomes. Three conjugated products of OTA corresponding to amino-, phenol- and acyl-glucuronides were identified, and the related structures were confirmed by hydrolysis with β-glucuronidase. Moreover, OTA methyl ester, OTα and OTα-glucuronide were also found in the reaction solution. Based on these results, an in vitro metabolic pathway of OTA has been proposed for the first time.

  8. In Vitro Glucuronidation of Ochratoxin A by Rat Liver Microsomes

    Directory of Open Access Journals (Sweden)

    Zheng Han

    2013-12-01

    Full Text Available Ochratoxin A (OTA, one of the most toxic mycotoxins, can contaminate a wide range of food and feedstuff. To date, the data on its conjugates via glucuronidation request clarification and consolidation. In the present study, the combined approaches of ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS, UHPLC-Orbitrap-high resolution mass spectrometry (HRMS and liquid chromatography-multiple stage mass spectrometry (LC-MSn were utilized to investigate the metabolic profile of OTA in rat liver microsomes. Three conjugated products of OTA corresponding to amino-, phenol- and acyl-glucuronides were identified, and the related structures were confirmed by hydrolysis with β-glucuronidase. Moreover, OTA methyl ester, OTα and OTα-glucuronide were also found in the reaction solution. Based on these results, an in vitro metabolic pathway of OTA has been proposed for the first time.

  9. Effect of the Aqueous Root Extract of Urena lobata (Linn on the Liver of Albino Rat

    Directory of Open Access Journals (Sweden)

    I.Y. Mshelia

    2013-01-01

    Full Text Available The effects of the aqueous root extract of urena lobata on the rat liver was investigated using a total of (25 adult Wister rats of both sexes that were randomly divided into five groups of five rats each. Group I served as the control, while rats in groups II-IV where administered 100, 200 and 300 mg/kg body weight of the extract, respectively for 28 days. Rats in group V were administered 300 mg/kg of the extract for 28 days and allowed to stay for 14 days post treatment to observe for reversibility, persistence or delayed occurrence of toxic effects. At the end of the experimental period the animals were sacrificed and liver weight taken and fixed for routine histological examinations. Administration of the extract to rats had no effects on liver and body weights but the extract caused a decrease in albumin level and increases in the levels of Aspartate Transaminases (AST, Alanine Transaminases (ALT and Alkaline Phosphatase (ALP. Histopathological assessment of the liver revealed mild to severe interstitial hemorrhage, mononuclear cell infiltration, necrosis, congestion and edema in the liver of the treated rats while withdrawal of the extract for 14 days showed a slight degree of recovery in the rats. This findings suggest that the biochemical and morphological organization of the liver can significantly be altered with continues and increase use of the extract, but further studies on the long term effect of the extract and a prolonged recovery period is recommended in further studies.

  10. Apoptosis of rat liver in cold preser vation with custom-designed K YL solution

    Institute of Scientific and Technical Information of China (English)

    Li Li; Chun-Man Li; Bing-Yan Zhang; Ming-Dao Hu; Xiao-Yan Li; Jiang-Hua Ran; Ming Huang

    2007-01-01

    BACKGROUND:A suitable perfusate is very important in reducing various problems in liver preservation, prolonging the time of organ preservation and enhancing the quality of donor tissue. University of Wisconsin (UW) solution is the most successful solution for preserving multiple organs at present, but it has many shortcomings. We set out to develop a new liver preservation solution (KYL solution) and study its effects on apoptosis in rat liver undergoing cold preservation. METHODS: Using non-circulated isolated perfused rat liver (IPRL), we randomly preserved Sprague-Dawley rat livers for 0, 4, 8, 16, 24, and 48 hours with KYL solution or UW solution. The effects were assessed by measuring the content of free radicals in Krebs-Henseleit solution and the intracellular calcium content of hepatocytes, assessing hepatocellular apoptosis and related-gene expression, and observing the morphological changes in liver. To evaluate the protection by KYL and UW solutions in rat liver perfusion and preservation, we chosed normal saline for negative comparison. RESULTS: The intracellular calcium content of the liver preserved in KYL solution was less than that preserved in UW solution. At every different period of preservation, the malonaldehyde and superoxide dismutase content in Krebs-Henseleit solution, the percentage of apoptotic cells and the expression patterns of apoptosis-related-genes were similar in livers preserved in KYL and UW solutions. Morphological changes in the two groups were almost the same. The variables in both groups were better than those of livers preserved in normal saline. Both KYL and UW solutions protected rat liver from ischemia-reperfusion injury. CONCLUSIONS:KYL solution is superior to UW solution in preventing calcium overload. More severe hepatocyte damage may appear in the KYL group than in the UW group and the effect of KYL solution on apoptosis in rat liver preservation is similar to that of UW solution.

  11. Vitamin A deficiency causes oxidative damage to liver mitochondria in rats.

    Science.gov (United States)

    Barber, T; Borrás, E; Torres, L; García, C; Cabezuelo, F; Lloret, A; Pallardó, F V; Viña, J R

    2000-07-01

    Mitochondrial damage in rat liver induced by chronic vitamin A-deficiency was studied using three different groups of rats: (i) control rats, (ii) rats fed a vitamin A-free diet until 50 d after birth and (iii) vitamin A-deficient rats re-fed a control diet for 30 d. No statistical difference in body weight and food intake was found between control and vitamin A-deficient rats. Liver GSH concentration was similar in both groups. However, in vitamin A-deficient rats, the mitochondrial GSH/GSSG ratio was significantly lower and the levels of malondialdehyde (MDA) and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (oxo8dG) were higher when compared to control rats. These values were partially restored in re-fed rats. The mitochondrial membrane potential of vitamin A-deficient rats was significantly lower than in control rats and returned to normal levels in restored vitamin A rats. Two populations of mitochondria were found in vitamin A-deficient rats according to the composition of membrane lipids. One population showed a similar pattern to the control mitochondria and the second population had a higher membrane lipid content. This report emphasizes the protective role of vitamin A in liver mitochondria under physiological circumstances.

  12. Isolation of hydroxy-Y base from rat liver tRNAPhe.

    Science.gov (United States)

    Kasai, H; Yamaizumi, Z; Kuchino, Y; Nishimura, S

    1979-03-01

    A Y-base derivative was isolated from rat liver tRNAPhe and its structure was assigned to be alpha-(carboxyamino)-beta-hydroxy-4,9-dihydro-4,6-dimethyl-9-oxo-1H-imidazol[1,2-a]purine-7-butyric acid dimethyl ester (hydroxy-Y), based on the results of mass spectrometry and chemical degradation. This modified base seems to be the major fluorescent component of rat liver tRNAPhe; the peroxy-Y base previously isolated from rat liver tRNAPhe and characterized by Nakanishi and his coworkers (1,2) was not present in our preparation.

  13. Oxidation of esterified arachidonate by rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Davis, H.W.; Suzuki, T.; Schenkman, J.B.

    1986-03-05

    The authors have previously demonstrated a relationship between phospholipid arachidonate in liver microsomes and malondialdehyde (MDA) formation during lipid peroxidation. In this study arachidonic acid (U-/sup 14/C) was incorporated into rat liver microsomes and NADPH-supported peroxidation was carried out at 37/sup 0/C for 15 minutes. The microsomes were pelleted by centrifugation and the labeled products in the supernatant were isolated by a solid phase method. Pellets were hydrolyzed with phospholipase A/sub 2/ and extracted with diethyl ether and the products from both fractions were separated by reverse phase HPLC. The results show that (1) oxidation occurs in all of the major phospholipids but that phosphatidylethanolamine is the most susceptible; (2) a linear correlation exists between MDA formation and supernatant radioactivity; (3) several different polar products are found in both the supernatant and the hydrolyzed pellet but that the ratios of product peaks in HPLC do not change during the peroxidation, indicating no secondary metabolism or propagation; and (4) cytochrome P-450 is not involved in the peroxidative reactions since no oxidation occurs in the absence of Fe/sup 3 +/ and since product formation is unaffected in the presence of carbon monoxide.

  14. Thin film voltammetry of metabolic enzymes in rat liver microsomes

    Science.gov (United States)

    Krishnan, Sadagopan; Rusling, James F.

    2007-01-01

    We report herein thin film voltammetry and kinetics of electron transfer for redox proteins in rat liver microsomes for the first time. Films were made layer-by-layer from liver microsomes and polycations on pyrolytic graphite electrodes. Cyclic voltammograms were chemically reversible with a midpoint potential of −0.48 V vs SCE at 0.1 V s−1 in pH 7.0 phosphate buffer. Reduction peak potentials shifted negative at higher scan rates, and oxidation-reduction peak current ratios were ∼1 consistent with non-ideal quasireversible thin film voltammetry. Analysis of oxidation-reduction peak separations gave an average apparent surface electron transfer rate constant of 30 s−1. Absence of significant electrocatalytic reduction of O2 or H2O2 and lack of shift in midpoint potential when CO is added that indicates lack of an iron heme cofactor suggest that peaks can be attributed to oxidoreductases present in the microsomes rather than cytochrome P450 enzymes. PMID:18037986

  15. Rat liver antioxidant response to iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Saporito-Magriñá, Christian; Semprine, Jimena; Torti, Horacio; Ferrarotti, Nidia; Castro-Parodi, Mauricio; Damiano, Alicia; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    The rat liver antioxidant response to Fe and Cu overloads (0-60mg/kg) was studied. Dose- and time-responses were determined and summarized by t1/2 and C50, the time and the liver metal content for half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58-66%) and Cu (79-81%) loads, with t1/2 of 4.0 and 2.0h. The C50 were in a similar range for all the indicators (110-124μgFe/g and 40-50μgCu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60-75%; t1/2: 4.5 and 4.0h). Lipophilic antioxidants were also decreased (30-92%; t1/2: 7.0 and 5.5h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t1/2: 8-8.5h and Mn-SOD: t1/2: 8.5-8.0h). Catalase activity was increased after Fe (65%; t1/2: 8.5h) and decreased after Cu (26%; t1/2: 8.0h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22-39% with a t1/2 of 4.5h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol (SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads.

  16. Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats.

    Directory of Open Access Journals (Sweden)

    Qinlong Liu

    Full Text Available Suppressed mitochondrial biogenesis (MB contributes to acute kidney injury (AKI after many insults. AKI occurs frequently after liver transplantation (LT and increases mortality. This study investigated whether disrupted mitochondrial homeostasis plays a role in AKI after LT.Livers were explanted from Lewis rats and implanted after 18 h cold storage. Kidney and blood were collected 18 h after LT.In the kidney, oxidative phosphorylation (OXPHOS proteins ATP synthase-β and NADH dehydrogenase-3 decreased 44% and 81%, respectively, with marked reduction in associated mRNAs. Renal PGC-1α, the major regulator of MB, decreased 57% with lower mRNA and increased acetylation, indicating inhibited synthesis and suppressed activation. Mitochondrial transcription factor-A, which controls mtDNA replication and transcription, protein and mRNA decreased 66% and 68%, respectively, which was associated with 64% decreases in mtDNA. Mitochondrial fission proteins Drp-1 and Fis-1 and mitochondrial fusion protein mitofusin-1 all decreased markedly. In contrast, PTEN-induced putative kinase 1 and microtubule-associated protein 1A/1B-light chain 3 increased markedly after LT, indicating enhanced mitophagy. Concurrently, 18- and 13-fold increases in neutrophil gelatinase-associated lipocalin and cleaved caspase-3 occurred in renal tissue. Both serum creatinine and blood urea nitrogen increased >2 fold. Mild to moderate histological changes were observed in the kidney, including loss of brush border, vacuolization of tubular cells in the cortex, cast formation and necrosis in some proximal tubular cells. Finally, myeloperoxidase and ED-1 also increased, indicating inflammation.Suppression of MB, inhibition of mitochondrial fission/fusion and enhancement of mitophagy occur in the kidneys of recipients of liver grafts after long cold storage, which may contribute to the occurrence of AKI and increased mortality after LT.

  17. A study of liver microsomal enzymes in rats following propoxur (Baygon) administration.

    Science.gov (United States)

    Nelson, D L; Lamb, D W; Mihail, F

    1984-08-01

    Groups of rats were given either propoxur, were left as untreated controls, or were given phenobarbital, DDT, chlordane or toxaphene which are known to induce liver microsomal detoxification enzymes. Microsomal enzyme activity was measured by testing the ability of liver homogenates to degrade EPN (O-ethyl O-(4-nitrophenyl) phenylphosphonothioate) to p-nitrophenol. The activity of aminopyrine-N-demethylase, cytochrome P-450 and p-nitroanisole-O-demethylase in liver homogenates of rats receiving propoxur was measured. Liver microsomal detoxification enzymes were not induced by propoxur exposure.

  18. Early changes of graft function, cytokines and superoxide dismutase serum levels after donor liver denervation and Kupffer cell depletion in a rat-to-rat liver transplantation model

    Institute of Scientific and Technical Information of China (English)

    Hong Zhu; Catena Marco; Ferla Gianfranco

    2009-01-01

    BACKGROUND:Hepatic reperfusion injury may cause acute inlfammatory damage, producing signiifcant organ dysfunction, and is an important problem in liver transplantation. This experiment aimed to study early changes of hepatic function after donor liver denervation and Kupffer cell depletion in rat-to-rat liver transplantation and to evaluate the effect of pre-treatment on liver reperfusion injury. METHODS:Donor rats were divided into four groups:control group; group G was pre-treated with gadolinium chloride (G), an inhibitor of Kupffer cells; group H with hexamethonium (H), a sympathetic ganglionic blocking agent; and group HG, with combined H and G pre-treatment. Under the same conditions, serum alanine aminotransferase (ALT), arterial ketone body ratio (AKBR), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and superoxide dismutase (SOD) of recipient rats were assessed at 4, 8, 16 and 24 hours after liver transplantation. Histological studies of the grafts were compared. RESULTS:HG pre-treatment signiifcantly decreased ALT, TNF-α, and IL-6 levels, increased AKBR and SOD levels, and demonstrated less pathological damage at 8, 16 and 24 hours compared with the control group. Similar trends were also found in the other groups (G and H). However, the differences among them were not signiifcant at 4 post-operative hours.CONCLUSIONS:Donor denervation and Kupffer cell depletion had preventive effect on liver reperfusion injury. HG pre-treatment is a feasible and reproducible method to protect grafts from reperfusion injury.

  19. Pituitary glycoprotein hormone a-subunit secretion by cirrhotic patients

    Directory of Open Access Journals (Sweden)

    Oliveira M.C.

    1999-01-01

    Full Text Available Secretion of the a-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the a-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6% presented hypogonadism (which was central in 45 cases and primary in 2, 7 were eugonadal, and 9 women were in normal menopause. The serum a-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively, with an intra-assay coefficient of variation (CV of less than 5% and an interassay CV of 5%, and sensitivity limit of 4 ng/l. The serum a-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the a-subunit and basal LH levels was significant both in the total sample (r = 0.48, P<0.01 and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02. Among men with central hypogonadism there was a negative correlation between a-subunit levels and total testosterone levels (r = 0.54, P<0.01 as well as free testosterone levels (r = -0.53, P<0.01. In conclusion, although the a-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver.

  20. Zinc finger protein A20 protects rats against chronic liver allograft dysfunction

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Ming-Qing Xu; Lu-Nan Yan; Xiao-Bo Chen; Jiao Liu

    2012-01-01

    AIM:To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats.METHODS:Allogeneic liver transplantation from DA rats to Lewis rats was performed.Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day (POD) 5.Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer administered intravenously every 10 d starting from POD 10.The recipient rats were injected with physiological saline,rAdEasy-A20 (1 x 109 pfu/30 g weight) or rAdEasy (1 x 109 pfu/30 g weight) every 10 d through the tail vein for 3 mo starting from POD 10.Liver tissue samples were harvested on POD 30 and POD 60.RESULTS:Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis.A20 overexpression ameliorated the effects on liver function,attenuated liver allograft fibrosis and prolonged the survival of the recipient rats.Treatment with A20 suppressed hepatic protein production of tumor growth factor (TGF)-β1,interleukin1β,caspase-8,CD40,CD40L,intercellular adhesion molecule-1,vascular cell adhesion molecule-1 and E-selectin.A20 treatment suppressed liver cell apoptosis and inhibited nuclear factor-κB activation of Kupffer cells (KCs),liver sinusoidal endothelial cells (LSECs)and hepatic stellate cells (HSCs),and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs.CONCLUSION:A20 might prevent chronic liver allograft dysfunction by re-establishing functional homeostasis of KCs,LSECs and HSCs.

  1. 苯巴比妥联合 CCl4法建立肝硬化腹水大鼠模型%To establish the model of cirrhotic rats with ascites phenobarbital combined with CCl4 method

    Institute of Scientific and Technical Information of China (English)

    方庆; 王成业; 姚瑶; 王满媛; 许钒

    2015-01-01

    Objective To establish a stable rat model of liver cirrhosis by using carbon tetrachloride combined with Phenobarbital Sodi-um.Methods 35%Phenobarbital Sodium was carried out in SD rats for 7 days to activate hepatic microsomal enzyme P450.From the second week,gradient carbon tetrachloride oil solution was offered by intraperitoneal injection (twice per week for 14 weeks).24 h u-rine of rats was collected and measured at the end time of the trial.HE staining of liver tissue was used to observe pathological process of liver.Results After induced with Phenobarbital Sodium for 7 days and then injected with carbon tetrachloride into abdominal cavity continuously for 13 weeks,a stable rat model of liver cirrhosis could be achieved.Conclusion The procedure is stable and reliable for building liver cirrhosis model,and the model has lower mortality and shorter cycle time than traditional one.%目的:采用苯巴比妥联合四氯化碳构建稳定的肝硬化腹水大鼠模型,为抗肝硬化腹水药物的研究提供有效可靠的动物模型。方法采用苯巴比妥联合CCl4法复制肝硬化腹水大鼠模型。35%苯巴比妥溶液诱导1周,激活肝脏肝药酶P450活性,第二周开始,按梯度腹腔注射CCl4油溶液,每周2次至第14周。实验进行至中后期,收集大鼠24 h尿液,测量尿量;检查腹腔积液量;肝组织HE染色观察肝脏病理进程。结果大鼠经苯巴比妥溶液诱导1周后,连续腹腔注射CCl4油溶液13周,可复制稳定的肝硬化腹水模型。结论该法可建立稳定、可靠的肝硬化腹水模型,比传统模型降低了死亡率,且造模时间缩短。

  2. In-hospital mortality among a cohort of cirrhotic patients admitted to a Tertiary Hospital

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    Mohammad A Alsultan

    2011-01-01

    Full Text Available Background/Aim : To determine the mortality rate in a cohort of hospitalized patients with cirrhosis and examine their resuscitation status at admission. Materials and Methods : A retrospective chart review was conducted of patients with cirrhosis who were admitted to a tertiary care hospital in Riyadh, Saudi Arabia, from January 1, 2009, to December 31, 2009. Results: We reviewed 226 cirrhotic patients during the study period. The hospital mortality rate was 35%. A univariate analysis revealed that worse outcomes were seen in patients with advanced age or who had worse child-turcotte-pugh (CPT scores, worse model for end-stage liver disease (MELD scores, low albumin and high serum creatinine. Using a multivariate analysis, we found that advanced age (P=0.004 and high MELD (P=0.001 scores were independent risk factors for the mortality of cirrhotic patients. The end-of-life decision were made in 34% of cirrhotic patients, and the majority of deceased patients were "no resuscitation" status (90% vs. 4%, P<0.001. Conclusions : The relatively high mortality in cirrhotic patients admitted for care in a tertiary hospital, Saudi Arabia was comparable to that reported in the literature. Furthermore, end-of-life discussions should be addressed early in the hospitalization of cirrhotic patients.

  3. The Role of Serum Cytokines in the Pathogenesis of Hepatic Osteodystrophy in Male Cirrhotic Patients

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    Ali Riza Soylu

    2012-01-01

    Full Text Available Objective. In this study, we aimed to investigate the possible role of serum cytokines in the development of hepatic osteodystrophy. Matherial and Methods. 44 consecutive male cirrhotic patients (17 alcoholic, 20 hepatitis B, 7 hepatitis C, 15 age- and sex-matched chronic alcoholics without liver disease, and 17 age- and sex-matched healthy controls were included in the study during one year period. Bone mineral density was measured by dual X-ray absorptiometry in the lumbar vertebrate and femoral neck. Serum interleukin levels were measured by ELISA method. Results. Although osteopenia frequency between our cirrhotic patients was 20%, there was no difference in T-scores among the controls and other groups. Serum interleukin-1, interleukin-8, and tumor necrosis factor-alpha levels were not different between all groups. Serum interleukin-2 and interleukin-6 levels were higher in the cirrhotics than controls (P<0.001. However, there were no significant difference between osteopenic and nonosteopenic cirrhotics. Conclusion. According to the results of the study in this small population of 44 male cirrhotic patients, frequency of hepatic osteopenia is small and serum interleukins 1, 2, 6, 8, and tumor necrosis factor-alpha may not play a role in the pathogenesis of hepatic osteodystrophy. Further studies in which large number of patients involved are necessary in this field.

  4. Reduced-size orthotopic liver transplantation with different grade steatotic grafts in rats

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    叶晟; 韩本立; 董家鸿

    2003-01-01

    Objective To explore the survival time, pathological change and liver regeneration in different kinds of reduced-size liver transplantation in rats using steatotic grafts. Methods Macrovesicular and microvesicular steatotic rat liver models were established by feeding rats with a diet consisting of 79% standard chow, 20% lard and 1% cholesterol for different time periods. With modified two cuff vascular anastomoses and end-to-end sutures on the bile duct, reduced-size orthotopic rat liver transplantations were performed in an attempt to explore the ratio of graft weight to recipient body weight, recipient original liver weight and histological and electron-microscopic findings in comparison with whole rat liver transplantations. Results A one-week survival rates for the rats undergoing whole liver transplantation, and those in the 70% reduced-size orthotopic liver transplantation (ROLT) group, the 60%ROLT group and the 50%ROLT group (grade Ⅰ macrosteatotic grafts) were 91.67%, 75%, 75% and 25%. A 2-week survival rate was 83.33%, 75%, 58.33% and 0 respectively. And their graft recipient body weight (GRBW) values SD were 3.56%±0.36%, 2.53%±0.15%, 2.28%±0.12% and 1.83%±0.16%, respectively. In grade Ⅱ macrosteatotic grafts, the one-week survival rate for those undergoiong whole liver transplantation and those in the 70% ROLT group was 83.33% and 25%. In the microsteatosis grafts for whole liver transplantation, 70% ROLT, 60% ROLT and 50% ROLT, the one-week survival rate was 83.33%, 75%, 75% and 33.33%; and the 2-week survival rate was 75%, 66.67%, 66.67% and 0, respectively. The survival rate of the 50% ROLT group using grade Ⅰ macrosteatotic grafts or grafts mainly with microsteatosis was significantly different from that of other groups. While using macrosteatotic grafts in grade Ⅱ, the 1-week survival rate of the 70% ROLT group was very poor. Pathological findings after operation included liver regeneration and portal space with mild lymphocyte

  5. Alloxan-Induced Diabetes Causes Morphological and Ultrastructural Changes in Rat Liver that Resemble the Natural History of Chronic Fatty Liver Disease in Humans

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    Amanda Natália Lucchesi

    2015-01-01

    Full Text Available Purpose. This study evaluated the long-term effects of alloxan-induced diabetes in rat liver. Methods. Thirty nondiabetic control rats (NC and 30 untreated diabetic (UD rats were divided into three subgroups sacrificed after 6, 14, or 26 weeks. Clinical and laboratory parameters were assessed. Fresh liver weight and its relationship with body weight were obtained, and liver tissue was analyzed. Results. UD rats showed sustained hyperglycemia, high glycosylated hemoglobin, and low plasma insulin. High serum levels of AST and ALT were observed in UD rats after 2 weeks, but only ALT remained elevated throughout the experiment. Fresh liver weight was equal between NC and UD rats, but the fresh liver weight/body weight ratio was significantly higher in UD rats after 14 and 26 weeks. UD rats showed liver morphological changes characterized by hepatic sinusoidal enlargement and micro- and macrovesicular hepatocyte fatty degeneration with progressive liver structure loss, steatohepatitis, and periportal fibrosis. Ultrastructural changes of hepatocytes, such as a decrease in the number of intracytoplasmic organelles and degeneration of mitochondria, rough endoplasmic reticulum, and nuclei, were also observed. Conclusion. Alloxan-induced diabetes triggered liver morphological and ultrastructural changes that closely resembled human disease, ranging from steatosis to steatohepatitis and liver fibrosis.

  6. Influence of zinc sulfate intake on acute ethanol-induced liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    Sema Bolkent; Pelin Arda-Pirincci; Sehnaz Bolkent; Refiye Yanardag; Sevim Tunali; Sukriye Yildirim

    2006-01-01

    AIM: To investigate the role of metallothionein and proliferating cell nuclear antigen (PCNA) on the morphological and biochemical effects of zinc sulfate in ethanol-induced liver injury.METHODS: Wistar albino rats were divided into four groups. Group I; intact rats, group Ⅱ; control rats given only zinc, group Ⅲ; animals given absolute ethanol, group Ⅳ; rats given zinc and absolute ethanol.Ethanol-induced injury was produced by the 1 mL of absolute ethanol, administrated by gavage technique to each rat. Animals received 100 mg/kg per day zinc sulfate for 3 d 2 h prior to the administration of absolute ethanol.RESULTS: Increases in metallothionein immunoreactivity in control rats given only zinc and rats given zinc and ethanol were observed. PCNA immunohistochemistry showed that the number of PCNA-positive hepatocytes was increased significantly in the livers of rats administered ethanol + zinc sulfate. Acute ethanol exposure caused degenerative morphological changes in the liver. Blood glutathione levels decreased, serum alkaline phosphatase and aspartate transaminase activities increased in the ethanol group when compared to the control group. Liver glutathione levels were reduced, but lipid peroxidation increased in the livers of the group administered ethanol as compared to the other groups. Administration of zinc sulfate in the ethanol group caused a significant decrease in degenerative changes, lipid peroxidation, and alkaline phosphatase and aspartate transaminase activities, but an increase in liver glutathione.CONCLUSION: Zinc sulfate has a protective effect on ethanol-induced liver injury. In addition, cell proliferation may be related to the increase in metallothionein immunoreactivity in the livers of rats administered ethanol + zinc sulfate.

  7. Peritoneal Dialysis is Associated With A Better Survival in Cirrhotic Patients With Chronic Kidney Disease.

    Science.gov (United States)

    Chou, Che-Yi; Wang, Shu-Ming; Liang, Chih-Chia; Chang, Chiz-Tzung; Liu, Jiung-Hsiun; Wang, I-Kuan; Hsiao, Lien-Cheng; Muo, Chih-Hsin; Chung, Chi-Jung; Huang, Chiu-Ching

    2016-01-01

    Peritoneal dialysis (PD) can be an ideal treatment in cirrhotic patients with ascites and chronic kidney disease stage 5 (CKD 5D) who require dialysis. The survival of cirrhotic patients with CKD 5D on PD, however, is not clear. We compared the survival of cirrhotic patients with CKD 5D on PD and the survival of those on HD. Two datasets including a cohort study of China Medical University Hospital (CMUH) from 2004 to 2013 and the Longitudinal National Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) of Taiwan from 1996 to 2011 were analyzed. The survival of cirrhotic patients on PD and the propensity score matched cirrhotic patients on HD were analyzed using Cox proportional hazards regression. In CMUH cohort of 85 PD and 340 HD patients, the all-cause mortality was lower in PD patients compared to it in HD patients (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.31-0.74, P model for end-stage liver disease (MELD) score, however, was not associated with all-cause mortality. In the LHID-CIP cohort of 285 PD and 1140 HD patients, the HR of all-cause mortality in PD patients was 0.61 (95% CI: 0.47 - 0.79, P < 0.01), as compared with HD patients. PD in cirrhotic patients who need dialysis is associated with lower all-cause mortality than HD is. This association is independent of patients' comorbidity, severity of liver cirrhosis, and serum albumin levels.

  8. Desensitization of G-protein-coupled receptors induces vascular hypocontractility in response to norepinephrine in the mesenteric arteries of cirrhotic patients and rats

    Institute of Scientific and Technical Information of China (English)

    Wei Chen; Jiang-Yong Sang; De-Jun Liu; Jun Qin; Yan-Miao Huo; Jia Xu and Zhi-Yong Wu

    2013-01-01

    BACKGROUND: The  increased  β-arrestin-2  and  its  combina-tion with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization.  The  latter  may  be  responsible  for  decreased contractile  reactivity  in  the  mesenteric  arteries  of  cirrhotic patients  and  rats.  The  present  study  is  to  investigate  the machinery  changes  of  α-adrenergic  receptors  and  G  proteins and  their  roles  in  the  contractility  of  mesenteric  arteries  of cirrhotic patients and animal models. METHODS: Patients  with  cirrhosis  due  to  hepatitis  B  and cirrhotic rats induced by CCl4 were studied. Mesenteric artery contractility  in  response  to  norepinephrine  was  determined by  a  vessel  perfusion  system.  The  contractile  effect  of  G protein-coupled  receptor  kinase-2  (GRK-2)  inhibitor  on  the mesenteric artery was evaluated. The protein expression of the α1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as  the  activity  of  Rho  associated  coiled-coil  forming  protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The  portal  vein  pressure  of  cirrhotic  patients  and rats  was  significantly  higher  than  that  of  controls.  The  dose-response curve to norepinephrine in mesenteric arteriole was shifted  to  the  right,  and  EC50  was  significantly  increased  in cirrhotic patients and rats. There were no significant differences in the expressions of the α1 adrenergic receptor and G

  9. Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

    Science.gov (United States)

    Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O

    2004-12-01

    Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats.

  10. MANAGEMENT OF PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS

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    Lucio Amitrano

    2009-11-01

    Full Text Available Portal vein thrombosis (PVT not associated with hepatocellular carcinoma is considered a frequent complication of liver cirrhosis but, unlike PVT occurring in non-cirrhotic patients, very few data are available on its natural history and management.  The reduced portal blood flow velocity is the main determinant of PVT but, as in other venous thromboses, multiple factors local and systemic, inherited or acquired often can concur with. PVT has a variety of clinical presentations ranging from asymptomatic to life-threatening diseases like gastroesophageal bleeding or acute intestinal ischemia. It is usually diagnosed by Doppler ultrasound but computed tomography and magnetic resonance imaging are useful to study the extent of thrombosis and the involvement of the abdominal organs. The risk of bleeding mainly determined by the presence of gastroesophageal varices and clotting alterations causes concern for the treatment of PVT in cirrhotic patients. To date, anticoagulant therapy seems to be indicated only in patients awaiting liver transplantation. This review focuses on the definition of the subgroups of patients with cirrhosis that might benefit from treatment of PVT and examines the pros and cons of the available treatments in terms of efficacy, monitoring and safety, providing also perspectives for future studies.

  11. MANAGEMENT OF PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS

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    Maria Anna Guardascione

    2009-11-01

    Full Text Available

    Portal vein thrombosis (PVT not associated with hepatocellular carcinoma is considered a frequent complication of liver cirrhosis but, unlike PVT occurring in non-cirrhotic patients, very few data are available on its natural history and management.  The reduced portal blood flow velocity is the main determinant of PVT but, as in other venous thromboses, multiple factors local and systemic, inherited or acquired often can concur with. PVT has a variety of clinical presentations ranging from asymptomatic to life-threatening diseases like gastroesophageal bleeding or acute intestinal ischemia. It is usually diagnosed by Doppler ultrasound but computed tomography and magnetic resonance imaging are useful to study the extent of thrombosis and the involvement of the abdominal organs. The risk of bleeding mainly determined by the presence of gastroesophageal varices and clotting alterations causes concern for the treatment of PVT in cirrhotic patients. To date, anticoagulant therapy seems to be indicated only in patients awaiting liver transplantation. This review focuses on the definition of the subgroups of patients with cirrhosis that might benefit from treatment of PVT and examines the pros and cons of the available treatments in terms of efficacy, monitoring and safety, providing also perspectives for future studies.

  12. Positional specificity of saturated and unsaturated fatty acids in phosphatidic acid from rat liver

    NARCIS (Netherlands)

    Possmayer, F.; Scherphof, G.L.; Dubbelman, T.M.A.R.; Golde, L.M.G. van; Deenen, L.L.M. van

    1969-01-01

    1. 1. The relative incorporation of a number of radioactive fatty acids into the different glycerolipids of rat liver microsomes has been investigated. 2. 2. Studies on the distribution of the radioactivity incorporated into phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid showed

  13. Anti-inflammatory liposomes have no impact on liver regeneration in rats

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    Betina Norman Jepsen

    2015-12-01

    Conclusion: Low dose dexamethasone targeted to Kupffer cells does not affect histological liver cell regeneration after 70% hepatectomy in rats, but reduces the inflammatory response judged by circulating markers of inflammation.

  14. Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Markus Neumeier; Jürgen Sch(o)lmerich; Christa Buechler; Claus Hellerbrand; Erwin G(a)bele; Roland Buettner; Cornelius Bollheimer; Johanna Weigert; Andreas Sch(a)ffler; Thomas S Weiss; Monika Lichtenauer

    2006-01-01

    AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level.METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA.RESULTS: Systemic adiponectin is reduced in fat fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice.CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.

  15. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been show...

  16. Uptake of phosphatidylserine-containing liposomes by liver sinusoidal endothelial cells in the serum-free perfused rat liver

    NARCIS (Netherlands)

    Rothkopf, C; Fahr, A; Fricker, G; Scherphof, GL; Kamps, JAAM

    2005-01-01

    We studied the kinetics of hepatic uptake of liposomes during serum-free recirculating perfusion of rat livers. Liposomes consisted of phosphatidylcholine, cholesterol and phosphatidylserine in a 6:4:0 or a 3:43 molar ratio and were radiolabelled with [H-3]cholesteryl oleyl ether. The negatively cha

  17. Participation of liver progenitor cells in liver regeneration: lack of evidence in the AAF/PH rat model.

    Science.gov (United States)

    Dusabineza, Ange-Clarisse; Van Hul, Noémi K; Abarca-Quinones, Jorge; Starkel, Peter; Najimi, Mustapha; Leclercq, Isabelle A

    2012-01-01

    When hepatocyte proliferation is impaired, liver progenitor cells (LPC) are activated to participate in liver regeneration. We used the 2-acetaminofluorene/partial hepatectomy (AAF/PH) model to evaluate the contribution of LPC to liver cell replacement and function restoration. Fischer rats subjected to AAF/PH (or PH alone) were investigated 7, 10 and 14 days post-hepatectomy. Liver mass recovery (LMR) was estimated, and the liver mass to body weight ratio calculated. We used serum albumin and bilirubin levels, and liver albumin mRNA levels to assess the liver function. LPC expansion was analyzed by cytokeratin 19 (CK19), glutathione S-transferase protein (GSTp) immunohistochemistry and by CK19, CD133, transforming growth factor-β1 and hepatocyte growth factor mRNA expression in livers. Cell proliferation was evaluated by Ki67 and BrdU immunostaining. Compared with PH alone where LMR was ∼100% 14 days post-PH, LMR was defective in AAF/PH rats (64.1±15.5%, P=0.0004). LPC expansion was scarce in PH livers (0.5±0.4% of CK19(+) area), but significant in AAF/PH livers (8.5±7.2% of CK19(+)), and inversely correlated to LMR (r(2)=0.63, PPH animals presented liver failure (low serum albumin and high serum bilirubin) 14 days post-PH. Compared with animals with preserved function, this was associated with a lower LMR (50±6.8 vs 74.6±9.4%, P=0.0005), a decreased liver to body weight ratio (2±0.3 vs 3.5±0.6%, P=0.001), and a larger LPC expansion such as proliferating Ki67(+) LPC covered 17.4±4.2% of the liver parenchyma vs 3.1±1.5%, (Plivers with preserved function. These observations suggest that, in this model, the efficient recovery of the liver function was ensured rather by the proliferation of mature hepatocytes than by the LPC expansion and differentiation into hepatocytes.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. In vitro characterization of borneol metabolites by GC-MS upon incubation with rat liver microsomes.

    Science.gov (United States)

    Zhang, Rong; Liu, Chang-hui; Huang, Tian-lai; Wang, Ning-sheng; Mi, Sui-qing

    2008-01-01

    The metabolism of borneol is studied by the analysis of incubations of in vitro-prepared rat liver microsomes. A sensitive gas chromatography (GC)-mass spectrometry (MS) method is developed for the identification of borneol and its metabolites. Four novel metabolites, which have not previously been reported, are isolated and confirmed by comparison of the GC-MS method. The biotransformation pathway of borneol in rat liver microsomes is proposed based on the in vitro results.

  20. Role of liver nerves and adrenal medulla in glucose turnover of running rats

    DEFF Research Database (Denmark)

    Sonne, B; Mikines, K J; Richter, Erik;

    1985-01-01

    Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had ident...... and duration, hepatic glycogenolysis and glucose production are not influenced by the autonomic liver nerves but are enhanced by circulating epinephrine....

  1. Ketogenesis and Malonyl Coenzyme. A Content of Liver from ’Streptococcus pneumoniae’-infected Rats.

    Science.gov (United States)

    1978-11-17

    Malonyl-CoA is a possible regulator of ketogenesis . Since infection partially inhibits starvation ketosis, studies were performed to determine if...malonyl-CoA content was the limiting factor in ketogenesis during an infection. Malonyl-CoA was increased in fed rat liver and decreased in fasted and...fasted-infected rat liver. This suggests that malonyl-CoA content does not regulate ketogenesis during an infection. (Author)

  2. Single liver lobe repopulation with wildtype hepatocytes using regional hepatic irradiation cures jaundice in Gunn rats.

    Directory of Open Access Journals (Sweden)

    Hongchao Zhou

    Full Text Available BACKGROUND AND AIMS: Preparative hepatic irradiation (HIR, together with mitotic stimulation of hepatocytes, permits extensive hepatic repopulation by transplanted hepatocytes in rats and mice. However, whole liver HIR is associated with radiation-induced liver disease (RILD, which limits its potential therapeutic application. In clinical experience, restricting HIR to a fraction of the liver reduces the susceptibility to RILD. Here we test the hypothesis that repopulation of selected liver lobes by regional HIR should be sufficient to correct some inherited metabolic disorders. METHODS: Hepatocytes (10(7 isolated from wildtype F344 rats or Wistar-RHA rats were engrafted into the livers of congeneic dipeptidylpeptidase IV deficient (DPPIV(- rats or uridinediphosphoglucuronateglucuronosyltransferase-1A1-deficient jaundiced Gunn rats respectively by intrasplenic injection 24 hr after HIR (50 Gy targeted to the median lobe, or median plus left liver lobes. An adenovector expressing hepatocyte growth factor (10(11 particles was injected intravenously 24 hr after transplantation. RESULTS: Three months after hepatocyte transplantation in DPPIV(- rats, 30-60% of the recipient hepatocytes were replaced by donor cells in the irradiated lobe, but not in the nonirradiated lobes. In Gunn rats receiving median lobe HIR, serum bilirubin declined from pretreatment levels of 5.17 ± 0.78 mg/dl to 0.96 ± 0.30 mg/dl in 8 weeks and remained at this level throughout the 16 week observation period. A similar effect was observed in the group, receiving median plus left lobe irradiation. CONCLUSIONS: As little as 20% repopulation of 30% of the liver volume was sufficient to correct hyperbilirubinemia in Gunn rats, highlighting the potential of regiospecific HIR in hepatocyte transplantation-based therapy of inherited metabolic liver diseases.

  3. 内源性硫化氢对肝硬化大鼠肝细胞凋亡的影响%Effect of endogenous hydrogen sulfide on apoptosis of cirrhosis rat liver cells

    Institute of Scientific and Technical Information of China (English)

    刘浩; 郑勇; 陈卫刚; 赵瑾; 李睿; 张宁; 刘芳; 阎继攀

    2012-01-01

    目的:探讨硫化氢(hydrogen sulfide,H2S)代谢酶抑制剂对肝硬化大鼠肝细胞凋亡的影响,进一步了解内源性H2S在大鼠肝硬化过程中发挥保护性作用的机制.方法:将40只♀SD大鼠分为4组,正常对照组(N组),正常对照组+炔丙基甘氨酸(PPG)组(P组),肝硬化组(H组),肝硬化+PPG组(PH组).H组、PH组利用CCL4复合因素法复制肝硬化大鼠模型,P组和PH组给予腹腔注射PPG(30 mg/kg·d)减少大鼠体内H2S含量;N组和H组腹腔注射同等剂量的生理盐水.免疫组织化学法检测大鼠肝组织中细胞胱硫醚γ裂解酶(CSE)的表达,Tunel法检测大鼠肝组织中肝细胞的凋亡,Western-blot法检测大鼠肝组织中凋亡相关蛋白Bax、Bcl-2的表达.结果:H组与N组相比,凋亡指数(AI)明显升高(P=0.000),凋亡促进蛋白Bax表达升高(P=0.001); PH组与H组相比,CSE表达降低(P=0.029),AI明显升高(P=0.000),Bax表达增高(P=0.021),差异均具有统计学意义.Bcl-2在各组间的表达无显著性差异(P=0.742).结论:H2S代谢酶抑制剂可促进肝硬化大鼠肝细胞的凋亡,其作用机制可能与其调节Bax的表达有关.%AIM:To explore the effect of a metabolic inhibitor of hydrogen sulfide on apoptosis of liver cells in rats with cirrhosis, and to explore the mechanism underlying the protective effect of hydrogen sulfide against cirrhosis.METHODS:Forty female SD rats were randomly divided into four groups: normal controls (group N), normal controls treated withpropargylglycine (PPG) (group P), cirrhotic rats (group H), and cirrhotic rats treated with PPG (group PH). Rats in groups H and PH were subjected to induction of cirrhosis by injecting carbon tetrachloride (CC14). Rats in groups P and PH were injected with PPG (30 mg/kgd) to decrease the content of hydrogen sulfide in the liver. Rats in groups N and H were injected with equal volume of normal saline. The distribution of cystathionine-γ-lyase (CSE) in the liver was examined by

  4. STUDY ON MODIFIED COLD STORAGE METHOD OF RAT LIVERS WITH SELF-MADE HYD SOLUTION

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. To investigate the cold preservation effect of rat livers by modified storage method with self-made HYD solution. Methods. The modified method was that the vascular bed of rat livers was expanded with an additional 20 to 40ml self-made HYD solution/100g liver. After removing the liver, the extra HYD solution expressed as % liver weight was entrapped via portal infusion by tying off the supra-and infra hepatic inferior vena cava. According to the amount of extra HYD solution, 40 rats were randomly divided into four groups including: control group with conventional storage method, 20% group, 30% group and 40% group. The preservation effect of modified storage method with that of conventional storage method by using isolated perfused rat liver model was compared. Results. Bile production and all the indices of hepatic microcirculation including portal perfusion pressure, en-dothelin-1 in the effluent, trypan blue distribution time and histology in modified method groups were significantly su-perior to those in control group ( P < 0.05). The liver enzymes in 30% group were markedly lower than those in con-trol group (P< 0.05). The preservation effect of rat hver in 30% group was the best among the modified methodgroups. Conclusion. The modified cold storage method is effective and may have potential for clinical apphcation for hverpreservation.

  5. Changing Interdigestive Migrating Motor Complex in Rats under Acute Liver Injury

    Directory of Open Access Journals (Sweden)

    Mei Liu

    2014-01-01

    Full Text Available Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by D-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.

  6. The ileum as a determinant organ of the functional liver cell mass in rats

    Directory of Open Access Journals (Sweden)

    Aldo Cunha Medeiros

    2013-03-01

    Full Text Available PURPOSE: To evaluate if the ileum resection changes the functioning liver cell mass, the hepatic metabolism and the biodistribution of radiopharmaceutical in rats. METHODS: Twelve Wistar rats weighing 285g±34g were randomly divided into the ileum resection group (n = 6 and sham group rats (n = 6. After 30 days, they were anesthetized and 0.1mL of 99m-Tc-phytate (0.66MBq was injected via femoral vein. After 30 minutes, blood samples were collected for red blood cells radioactive labeling and serum ALT, AST and gammaGT. Liver samples were used for 99m-Tc-phytate percentage of radioactivity/gram of tissue and histopathology. Student 's t test was used with significance 0.05. RESULTS: There was a higher uptake of 99m-Tc-phytate in the liver of sham rats, compared to the ileum resection group (p<0.05. GammaGT, ALT and AST were increased in ileum resection rats compared to sham (p<0.05. The he patocytes count was significantly lower in ileum resection group than in sham (p<0.05. Liver: body mass ratio was lower in experimental animals than in sham group (p<0.05. CONCLUSION: These data support that the ileum has important role in liver function and liver mass regulation, and they have potential clinical implications regarding the pathogenesis of liver injury following lower bowel resection.

  7. Hepcidin expression in the liver of rats fed a magnesium-deficient diet.

    Science.gov (United States)

    Ishizaki, Natsumi; Kotani, Megumi; Funaba, Masayuki; Matsui, Tohru

    2011-10-01

    Mg deficiency accelerates Fe accumulation in the liver, which may induce various metabolic disturbances. In the present study, we examined the gene expression of Hepcidin, a peptide hormone produced in the liver to regulate intestinal Fe absorption negatively, in Mg-deficient rats. Although liver Fe concentration was significantly higher in rats fed an Mg-deficient diet for 4 weeks than in rats fed a control diet, Hepcidin expression in the liver was comparable between the dietary groups. Previous studies revealed that Fe overload up-regulated Hepcidin expression through transcriptional activation by Fe-induced bone morphogenetic protein (Bmp) 6, a growth/differentiation factor belonging to the transforming growth factor-β family, in the liver. Mg deficiency up-regulated the expression of Bmp6 but did not affect the expression of inhibition of DNA binding 1, a sensitive Bmp-responsive gene. In addition, the expression of Bmp receptors such as activin receptor-like kinase 2 (Alk2), activin receptor type IIA (Actr2a), activin receptor type IIB (Actr2b) and Bmp type II receptor (Bmpr2) was lower in the liver of Mg-deficient rats than in that of control rats. The present study indicates that accumulation of hepatic Fe by Mg deficiency is a stimulant inducing Bmp6 expression but not Hepcidin expression by blunting Bmp signalling possibly resulting from down-regulation of the receptor expression. Unresponsive Hepcidin expression may have a role in Mg deficiency-induced changes related to increased liver Fe.

  8. High affinity binding of (/sup 3/H)cocaine to rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

    1988-01-01

    )/sup 3/H)cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in (/sup 3/H)cocaine binding. On the other hand, chronic administration of cocaine reduced (/sup 3/H)cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of (/sup 3/H)cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced (/sup 3/H)cocaine binding to liver with a different rank order of potency than their displacement of (/sup 3/H)cocaine binding to striatum. This high affinity (/sup 3/H)cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

  9. The permeability of polyethylene glycol oligomers in the isolated perfused rat liver

    NARCIS (Netherlands)

    Mengelers, M.J.B.

    1995-01-01

    Processes occuring in the liver are very important for the description of the kinetic behaviour of drugs and compounds present in food. Therefore this research was focussed on dispersion and distribution processes occuring in the rat liver. Polyethylene glycols were used as test compounds because th

  10. Pre-and postconditioning effects of metformin in rat donor livers

    NARCIS (Netherlands)

    Westerkamp, A.C.; De Jong, I.; Nijsten, M.W.; Leuvenink, H.G.D.; Touw, D.J.; Lisman, T.; Moshage, H.; Porte, R.J.

    2016-01-01

    Background: Pre- or reconditioning of donor livers can improve organ quality prior to transplantation. The aim of this study was to investigate whether metformin as pre- or reconditioning agent is able to reduce preservation injury in rat donor livers and improve hepatobiliary function during ex sit

  11. Liver and extrahepatic contributions to postheparin serum lipase activity of the rat

    NARCIS (Netherlands)

    H. Jansen (Hans); W.C. Hülsmann (William)

    1974-01-01

    textabstractThe influence of the amount of heparin injected on the contributions of liver and of extrahepatic tissues to the lipase activity of postheparin serum of the rat was studied. It was found that when high doses of heparin (20 I.U./100 g bodyweight) were injected, the liver contributes for 6

  12. Exposure of precision-cut rat liver slices to ethanol accelerates fibrogenesis

    NARCIS (Netherlands)

    Schaffert, Courtney S.; Duryee, Michael J.; Bennett, Robert G.; DeVeney, Amy L.; Tuma, Dean J.; Olinga, Peter; Easterling, Karen C.; Thiele, Geoffrey M.; Klassen, Lynell W.

    2010-01-01

    Schaffert CS, Duryee MJ, Bennett RG, DeVeney AL, Tuma DJ, Olinga P, Easterling KC, Thiele GM, Klassen LW. Exposure of precision-cut rat liver slices to ethanol accelerates fibrogenesis. Am J Physiol Gastrointest Liver Physiol 299: G661-G668, 2010. First published July 1, 2010; doi: 10.1152/ajpgi.002

  13. Magnetic resonance imaging of the cirrhotic liver: Anupdate

    Institute of Scientific and Technical Information of China (English)

    Agnes Watanabe; Miguel Ramalho; Mamdoh AlObaidy; Hye Jin Kim; Fernanda G Velloni; Richard C Semelka

    2015-01-01

    Noninvasive imaging has become the standard forhepatocellular carcinoma (HCC) diagnosis in cirrhoticlivers. In this review paper, we go over the basics ofMR imaging in cirrhotic livers and describe the imagingappearance of a spectrum of hepatic nodules markingthe progression from regenerative nodules to low- andhigh-grade dysplastic nodules, and ultimately to HCCs.We detail and illustrate the typical imaging appearancesof different types of HCC including focal, multifocal,massive, diffuse/infiltrative, and intra-hepaticmetastases; with emphasis on the diagnostic value ofMR in imaging these lesions. We also shed some lighton liver imaging reporting and data system, and therole of different magnetic resonance imaging (MRI)contrast agents and future MRI techniques includingthe use of advanced MR pulse sequences and utilizationof hepatocyte-specific MRI contrast agents, and howthey might contribute to improving the diagnosticperformance of MRI in early stage HCC diagnosis.

  14. Hepatoprotective Effects of Vitamin E Against Malathion-Induced Mitochondrial Dysfunction in Rat Liver

    Directory of Open Access Journals (Sweden)

    Ranjbar

    2014-09-01

    Full Text Available Background Malathion is an insecticide of the grouping of organophosphate pesticides (OPs, which shows strong insecticidal effects. In addition, vitamin E reacting to cell membrane site may prevent OP-induced oxidative injury. Objectives The aim of this study was to examine the protective function of vitamin E on toxicity of malathion, by measuring the activities of liver and liver mitochondrial superoxide dismutase (SOD, catalase (CAT,lipid peroxidation (LPO,and glutathione peroxidase (GPx in rats. Materials and Methods The mitochondrial viability was determined in liver. ‎Effective doses of malathion(200 mg/kg/day and vitamin E (alpha-tocopherylacetate [AT]; 15 mg/kg/day were administered alone or in combination for 14 days. At the end of the experiment, the liver tissue and liver mitochondria of the animals were harvested and examined. Results In liver tissue, the activity of LPO and CAT was higher in the malathion group in comparison to controls. AT reduced malathion-induced LPO, SOD, CAT, and GPx in rat liver. Coadministration of AT with malathion improved LPO, SOD, and CAT levels in liver as well as CAT and GPx in liver mitochondria. Malathion-induced mitochondria toxicity was recovered by AT. Conclusions In conclusion, AT measurement can be beneficial for the safety or recovery of malathion-induced toxic injury in liver tissue and liver mitochondria.

  15. Phenotypic changes of human cells in human-rat liver during partial hepatectomy-induced regeneration

    Institute of Scientific and Technical Information of China (English)

    Yan Sun; Dong Xiao; Hong-An Li; Jin-Fang Jiang; Qing Li; Ruo-Shuang Zhang; Xi-Gu Chen

    2009-01-01

    AIM: To examine the human hepatic parenchymal and stromal components in rat liver and the phenotypic changes of human cells in liver of human-rat chimera (HRC) generated by in utero transplantation of human cells during partial hepatectomy (PHx)-induced liver regeneration. METHODS: Human hepatic parenchymal and stromal components and phenotypic changes of human cells during liver regeneration were examined by flow cytometry, in situ hybridization and immunohistochemistry. RESULTS: ISH analysis demonstrated human Alupositive cells in hepatic parenchyma and stroma of recipient liver. Functional human hepatocytes generated in this model potentially constituted human hepatic functional units with the presence of donor-derived human endothelial and biliary duct cells in host liver. Alpha fetoprotein (AFP)+, CD34+ and CD45+ cells were observed in the chimeric liver on day 10 after PHxinduced liver regeneration and then disappeared in PHx group, but not in non-PHx group, suggesting that dynamic phenotypic changes of human cells expressing AFP, CD34 and CD45 cells may occur during the chimeric liver regeneration. Additionally, immunostaining for human proliferating cell nuclear antigen (PCNA) showed that the number of PCNA-positive cells in the chimeric liver of PHx group was markedly increased, as compared to that of control group, indicating that donor-derived human cells are actively proliferated during PHx-induced regeneration of HRC liver.

  16. Expression and significance of SOCS3 in liver tissue of rats with severe acute pancreatitis complicated by liver injury

    Directory of Open Access Journals (Sweden)

    Bin WANG

    2012-11-01

    Full Text Available Objective  To investigate the expression and mechanism of action of suppressor of cytokine signaling 3 (SOCS3 in liver tissue of rats with experimental severe acute pancreatitis (SAP concurring with liver injury. Methods  The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. Thirty-two male SD rats were randomly assigned into 4 groups (8 each: normal control group (NC, SAP 6h, 12h, and 18h groups. The levels of serum amylase (AMY, alanine aminotransferase (ALT and aspartate aminotransferase (AST were measured dynamically. The concentrations of IL -6 and IL -18 were determined by ELISA. The localization and expression of SOCS3 protein in liver were determined by immunohistochemical staining and Western blotting. Results  Compared with NC group, the serum levels of AMY, ALT and AST increased significantly in SAP groups (P < 0.05, and there was significant difference among SAP groups. The serum concentrations of IL-6 and IL-18 increased significantly in the SAP groups than in NC group (P < 0.05, and there was significant difference among SAP groups. Compared with NC group, the concentration of SOCS3 protein increased significantly in SAP groups, and increased gradually along with the increased duration of pancreatitis (P < 0.05. A minor expression of SOCS3 protein was found in NC group. The change in SOCS3 protein concentration was consistent with the severity of liver injury as well as the serum concentrations of IL-6 and IL-18. Conclusions  The inflammatory action induced by SAP concurring with liver injury may induce the expression of SOCS3 in liver tissue, and it may increase in intensity along with the severity of liver injury and inflammatory reaction. The mechanism may be attributed to a negative feedback regulation of the inflammatory action mediated by JAK/STAT pathway.

  17. Actions of juglone on energy metabolism in the rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Saling, Simoni Cristina; Comar, Jurandir Fernando; Mito, Marcio Shigueaki; Peralta, Rosane Marina; Bracht, Adelar, E-mail: adebracht@uol.com.br

    2011-12-15

    Juglone is a phenolic compound used in popular medicine as a phytotherapic to treat inflammatory and infectious diseases. However, it also acts as an uncoupler of oxidative phosphorylation in isolated liver mitochondria and, thus, may interfere with the hepatic energy metabolism. The purpose of this work was to evaluate the effect of juglone on several metabolic parameters in the isolated perfused rat liver. Juglone, in the concentration range of 5 to 50 {mu}M, stimulated glycogenolysis, glycolysis and oxygen uptake. Gluconeogenesis from both lactate and alanine was inhibited with half-maximal effects at the concentrations of 14.9 and 15.7 {mu}M, respectively. The overall alanine transformation was increased by juglone, as indicated by the stimulated release of ammonia, urea, L-glutamate, lactate and pyruvate. A great increase (9-fold) in the tissue content of {alpha}-ketoglutarate was found, without a similar change in the L-glutamate content. The tissue contents of ATP were decreased, but those of ADP and AMP were increased. Experiments with isolated mitochondria fully confirmed previous notions about the uncoupling action of juglone. It can be concluded that juglone is active on metabolism at relatively low concentrations. In this particular it resembles more closely the classical uncoupler 2,4-dinitrophenol. Ingestion of high doses of juglone, thus, presents the same risks as the ingestion of 2,4-dinitrophenol which comprise excessive compromising of ATP production, hyperthermia and even death. Low doses, i.e., moderate consumption of natural products containing juglone, however, could be beneficial to health if one considers recent reports about the consequences of chronic mild uncoupling. -- Highlights: Black-Right-Pointing-Pointer We investigated how juglone acts on liver metabolism. Black-Right-Pointing-Pointer The actions on hepatic gluconeogenesis, glycolysis and ureogenesis. Black-Right-Pointing-Pointer Juglone stimulates glycolysis and ureagenesis and

  18. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Hadi, Mackenzie; Laarakkers, Coby M. M.; Masereeuw, Rosalinde; Groothuis, Geny M. M.; Russel, Frans G. M.

    2014-01-01

    Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker ide

  19. 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.

  20. Early detection of liver fibrosis in rats using 3-D ultrasound Nakagami imaging: a feasibility evaluation.

    Science.gov (United States)

    Ho, Ming-Chih; Tsui, Po-Hsiang; Lee, Yu-Hsin; Chen, Yung-Sheng; Chen, Chiung-Nien; Lin, Jen-Jen; Chang, Chien-Cheng

    2014-09-01

    We investigated the feasibility of using 3-D ultrasound Nakagami imaging to detect the early stages of liver fibrosis in rats. Fibrosis was induced in livers of rats (n = 60) by intraperitoneal injection of 0.5% dimethylnitrosamine (DMN). Group 1 was the control group, and rats in groups 2-6 received DMN injections for 1-5 weeks, respectively. Each rat was sacrificed to perform 3-D ultrasound scanning of the liver in vitro using a single-element transducer of 6.5 MHz. The 3-D raw data acquired at a sampling rate of 50 MHz were used to construct 3-D Nakagami images. The liver specimen was further used for histologic analysis with hematoxylin and eosin and Masson staining to score the degree of liver fibrosis. The results indicate that the Metavir scores of the hematoxylin and eosin-stained sections in Groups 1-4 were 0 (defined as early liver fibrosis in this study), and those in groups 5 and 6 ranged from 1 to 2 and 2 to 3, respectively. To quantify the degree of early liver fibrosis, the histologic sections with Masson stain were analyzed to calculate the number of fiber-related blue pixels. The number of blue pixels increased from (2.36 ± 0.79) × 10(4) (group 1) to (7.68 ± 2.62) × 10(4) (group 4) after DMN injections for 3 weeks, indicating that early stages of liver fibrosis were successfully induced in rats. The Nakagami parameter increased from 0.36 ± 0.02 (group 1) to 0.55 ± 0.03 (group 4), with increasing numbers of blue pixels in the Masson-stained sections (p-value Nakagami imaging has potential in the early detection of liver fibrosis in rats and may serve as an image-based pathologic model to visually track fibrosis formation and growth.

  1. IMPACTS OF HIGH DIETARY FAT ON SERUM CHOLESTEROL AND DEVELOPMENT OF FATTY LIVER IN RATS

    Directory of Open Access Journals (Sweden)

    Rajesh Pandey et al

    2012-09-01

    Full Text Available The present study was designed to evaluate the impacts of high dietary fat on serum Total cholesterol and fatty liver syndrome in rats. Rats are fed on diets containing cholesterol; they develop fatty livers which are characterized by the presence in the liver of excessive amounts of cholesteryl esters, and glyceride. Increasement of glyceride content depend on a number of factors, such as the dietary contents of choline, While the nature of the "cholesterol" fatty liver and the effects on its composition of a number of dietary and other factors. In the present paper, we investigated the quantitative changes which occur in the "cholesterol" fatty liver, as a result of variations in the fat content of the diet, with particular reference to the deposition of cholesterol and of glyceride on diets of constant cholesterol content. Investigation was conducted on 90 day old Wister rats. It was observed that the serum TC values in rats of groups B and C were higher than control group. Furthermore, the serum TC and TG value was higher in rats of group C than group B. Grossly, the livers of rats of groups B and C were enlarged, pale in colour, soft in consistency and were having petechial haemorrhages with fat and fibrin deposits. Histopathologically, livers of groups B and C showed fatty infiltration, haemorrhages and mass of eosinophilic materials. The vacuoles coalesced to create clear space that displaced the nucleus to the periphery of the cell. The results suggested that addition of dietary fat from animal and vegetable sources in the diet of rats not only resulted in increase in serum TC and TG but also in marked macroscopic and microscopic changes in vital organ liver.

  2. Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib

    Institute of Scientific and Technical Information of China (English)

    Hai-yan XU; Zhi-yong XIE; Peng ZHANG; Jin SUN; Feng-ming CHU; Zong-ru GUO; Da-fang ZHONG

    2006-01-01

    Aim: To investigate the in vitro metabolism of imrecoxib in rat liver microsomes and to identify the cytochrome P450 (CYP) forms involved in its metabolism. Methods: Liver microsomes of Wistar rats were prepared using an ultracentrifuge. The in vitro metabolism of imrecoxib was studied by incubation with rat liver microsomes. To characterize the CYP forms involved in the 4'-methyl hydroxylation of imrecoxib, the effects of typical CYP inducers (such as dexamethasone, isoniazid and (3-naphthoflavone) and of CYP inhibitors (such as ketoconazole, quinine, a-naphthoflavone, methylpyrazole, and cimetidine) on the formation rate of 4'-hydroxymethyl imrecoxib were investigated. Results: Imrecoxib wasmetabolized to 3 metabolites by rat liver microsomes: 4'-hydroxymethyl imrecoxib (M4), 4'-hydroxymethyl-5-hydoxyl imrecoxib (M3), and 4'-hydroxymethyl-5-carbonyl imrecoxib (M5). Over the imrecoxib concentration range studied (5-600 umol/L), the rate of 4'-methyl hydroxylation conformed to monophasic Michaelis-Menten kinetics. Dexamethasone significantly induced the formation of M4. Ketoconazole markedly lowered the metabolic rate of imrecoxib in a concentration-dependent manner. Moreover, a significant inhibitory effect of quinine on the formation of M4 was observed in microsomes obtained from control rats, isoniazid-induced rats, and (3-naphthoflavone-induced rats. In contrast, α-naphthoflavone, cimetidine, and methylpyrazole had no inhibitory effects on this metabolic pathway. Conclusion: Imrecoxib is metabolized via 4'-methyl hydroxylation in rat liver microsomes. The reaction is mainly catalyzed by CYP 3A. CYP 2D also played a role in control rats, in isoniazid-induced rats and in β-naphthoflavone-induced rats.

  3. METABOLOMIC EVALUATION OF RAT LIVER AND TESTIS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES

    Science.gov (United States)

    The effects of two triazole fungicides, myclobutanil and triadimefon, on endogenous rat metabolite profiles in blood serum, liver, and testis was assessed using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Adult male Sprague-Dawley rats were dosed daily by gavage for...

  4. Endotoxin-induced liver damage in rats is minimized by β2- adrenoceptor stimulation

    NARCIS (Netherlands)

    Izeboud, C.A.; Hoebe, K.H.N.; Grootendorst, A.F.; Nijmeijer, S.M.; Miert, A.S. van; Witkamp, R.F.; Rodenburg, R.J.T.

    2004-01-01

    Objective and Design: To investigate the effects of β2- adrenoceptor (β2-AR) stimulation on endotoxin-induced liver damage and systemic cytokine levels in rats. Subjects: Standard male Wistar rats. Treatment: A disease-model of lipolysaccharide (LPS)-induced acute systemic inflammation was used. The

  5. Content of bioelements in the lungs and liver in rats with alimentary obesity.

    Science.gov (United States)

    Trunova, V A; Sidorina, A V; Zvereva, V V; Churin, B V; Starkova, E V; Sorokoletov, D S

    2016-01-01

    The synchrotron radiation X-ray fluorescence technique (SRXRF) was applied to the determination of K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb, and Sr concentrations in the liver and lungs in Wistar rats. The animals in the experiment included (1) healthy rats, (2) rats with alimentary obesity (AO), and (3) rats with alimentary obesity that were being given zinc sulphate with water for a long time (АО+Zn). Each group was divided into two subgroups. The experiment with the first subgroup was terminated with the animals in the state of physiological hunger and subsequent retrieval of liver and lung tissue, while the animals of the second subgroup were sacrificed two hours after ingestion of lard. The rats in physiological hunger manifested intergroup differences in the content of the bioelements (BEs) neither in the liver nor in the lungs. The rats with AO, as compared with the healthy animals, demonstrated in physiological hunger redistribution of inter-element correlations (IECs), which is an indirect reflection of sustained metabolic disorder. Additional zinc in the rats' ration did not affect their body weight and the concentration of the BEs (including zinc) in the liver and the lungs. However, the IECs in the tissues of these animals in physiological hunger also changed. This redistribution differed from that in the rats with AO. The IECs soon after ingestion of lard also changed, which also reflects sustained changes in the metabolism in the animals.

  6. Ribonucleases from rat and bovine liver : purification, specificity and structural characterization

    NARCIS (Netherlands)

    Zhao, W; Kote-Jarai, Z; van Santen, Y; Hofsteenge, J; Beintema, JJ

    1998-01-01

    The presence of four members of the pyrimidine-specific ribonuclease superfamily was demonstrated in rat liver. Three of them (RL1, RL2 and RL3) were purified and showed ribonuclease activity at pH 7.5 with yeast RNA as substrate. RL1 is identical to rat pancreatic ribonuclease (ribonuclease 1). N-t

  7. Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

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    A.L. Chagas

    2009-10-01

    Full Text Available Non-alcoholic steatohepatitis (NASH has been associated with hepatocellular carcinoma (HCC often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis. Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC criteria, we identified 7 cases (1.7% with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years were either overweight (4 or obese (3; 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1 based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

  8. Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

    Directory of Open Access Journals (Sweden)

    A.L. Chagas

    Full Text Available Non-alcoholic steatohepatitis (NASH has been associated with hepatocellular carcinoma (HCC often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis. Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC criteria, we identified 7 cases (1.7% with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years were either overweight (4 or obese (3; 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1 based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

  9. The expression of HIF-1 α in liver tissues in the rat model of paraquat poisoning

    Institute of Scientific and Technical Information of China (English)

    熊莺

    2014-01-01

    Objective To observe the levels of HIF-αand TGF-βin the liver tissue,change of serum transaminase in different phases after paraquat(PQ)toxicity and liver histopathology change in PQ-induced liver toxicity of rat models in order to analyze the relationship between HIF-αand hepatic toxicity induced by PQ.Methods A total of 48 healthy SD rats were randomly(random number)assigned into 2 groups:PQ poisoning group(n=42,

  10. Mono(ADP-ribosylation) in rat liver mitochondria.

    Science.gov (United States)

    Frei, B; Richter, C

    1988-01-26

    This paper investigates protein mono(ADP-ribosylation) in rat liver mitochondria. In isolated inner mitochondrial membranes, in the presence of both ADP-ribose and NAD+, a protein is mono-(ADP-ribosylated) with high specificity. The reaction apparently consists of enzymatic NAD+ glycohydrolysis and subsequent binding of free ADP-ribose to the acceptor protein. In terms of chemical stability, the resulting bond is unique among the ADP-ribose linkages thus far characterized. Formation of a Schiff base adduct between free ADP-ribose and the acceptor protein is excluded. In intact mitochondria at least three classes of proteins are ADP-ribosylated in vivo. One ADP-ribose-protein linkage is of the carboxylate ester type as indicated by its lability in neutral buffer. Another class of ADP-ribosylated proteins requires hydroxylamine for release of ADP-ribose. The third class is stable in hydroxylamine but labile to alkali, similar to the ADP-ribose-cysteine linkage in transducin formed by pertussis toxin.

  11. Four new koumine metabolites in rat liver microsomes.

    Science.gov (United States)

    Zhang, Lin; Du, Lan; Lv, Wen-Wen; Zhao, Qing-Chun; Hua, Wei; An, Ye; Guo, Tao; Wu, Li-Jun

    2013-01-01

    Four new metabolites M-1 [1,2,18,19-tetradehydro-4-demethyl-3,17-epoxy-7,20(2H,19H)-cyclovobasan], M-2 [1,2,4,21,18,19-hexadehydro-4-demethyl-3,17-epoxy-7,20(2H,19H)-cyclovobasan], M-3 [1,2,18,19-tetradehydro-4-demethyl-4-formaldehyde-3,17-epoxy-7,20(2H,19H)-cyclovobasan], and M-4 [1,2,4,21,18,19-hexadehydro-4-demethyl-4-oxy-3,17-epoxy-7,20(2H,19H)-cyclovobasan] were isolated from the chloroform extract of koumine incubated with phenobarbital-treated rat liver microsomes. The structures of M-1, M-2, M-3, and M-4 were elucidated by spectroscopic methods including ESI-TOF-MS, 1D, and 2D NMR experiments. The metabolic pathway of koumine was proposed. The cytotoxic activities between koumine and its metabolites were also compared in the A549 cell line.

  12. Stereoselective degradation of tebuconazole in rat liver microsomes.

    Science.gov (United States)

    Shen, Zhigang; Zhu, Wentao; Liu, Donghui; Xu, Xinyuan; Zhang, Ping; Zhou, Zhiqiang

    2012-01-01

    The aim of this study was to assess the stereoselectivity of two tebuconazole [(RS)-1-p-chlorophenyl-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol] enantiomers in in vitro system (rat liver microsomes). The analytes were extracted with acetic ether and concentrations were determined by high performance liquid chromatography (HPLC) with a cellulose tris(3,5-dimethylphenylcarbamate)-based chiral stationary phase. The degradation of rac-tebuconazole (15 μM) followed first-order kinetics, and the degradation of the S-tebuconazole (t(1/2) = 22.31 min) was faster than that of the R-tebuconazole (t(1/2) = 48.76 min), but no significant difference between the enantiomers was found in the respective incubation (7.5 μM for each). Kinetic assays showed that the K(m) was different between the two enantiomers (K(mR) = 14.83 ± 2.19, K(mS) = 12.23 ± 2.72). The interaction results revealed that there was competitive inhibition between S- and R-form, and there was a significant difference between the IC(50) of R- to S-tebuconazole and S- to R-tebuconazole (IC(50R/S)/IC(50S/R) = 4.98).

  13. A Biochemical and Morphological Study of Rat Liver Microsomes

    Science.gov (United States)

    Moulé, Y.; Rouiller, C.; Chauveau, J.

    1960-01-01

    Microsomes isolated by differential centrifugation from a rat liver homogenate in 0.88 M sucrose solution have been studied from the biochemical and morphological point of view. 1. Under these experimental conditions, the "total microsome" fraction was obtained by centrifuging the cytoplasmic extract free of nuclei and mitochondria, for 3 hours at 145,000 g. Morphologically, the total microsomes consist mainly of "rough-surfaced membranes" and "smooth" ones. 2. The total microsomes have been divided into 2 subfractions so that the 1st microsomal fraction contains the "rough" vesicles (2 hours centrifugation at 40,000 g) while the 2nd microsomal fraction consists essentially of smooth vesicles, free particles, and ferritin (centrifugation of the supernatant at 145,000 g for 3 hours). 3. By the action of 0.4 per cent sodium deoxycholate in 0.88 M sucrose, it was possible to obtain a pellet for each of the 2 fractions which consisted of dense particles, rich in RNA, poor in lipids, and which represented about 50 to 60 percent of the RNA and 10 to 15 per cent of the proteins. The results have been discussed taking into consideration the hypothesis of the presence of RNA in the membranes of microsomal vesicles. PMID:14424705

  14. The Effect of Zofenopril on Pancreas, Kidney and Liver of Diabetic Rats

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    Ayşe ÇARLIOĞLU

    2014-05-01

    Full Text Available OBJECTIVE: Oxidative stress is responsible for some important complications of diabetes mellitus. Zofenopril, which has an antioxidant effect, may decrease the oxidative stress of the diabetic microenvironment. The aim of our study was to evaluate the effect of zofenopril in the liver, pancreas and kidney of alloxan-induced diabetic rats. MATERIAL and METHODS: Rats were divided into five groups: control group (n=6, rats treated with zonenopril (50 mg/kg/day, orally four weeks; n=6, rats exposed to alloxane (120 mg/kg single dose intraperitoneal injection, n=6, rats administered alloxan+zofenopril (n=6 and rats administered insulin plus alloxan. RESULTS: After one month, we observed histological improvement in the kidneys but not in the pancreas and liver. CONCLUSION: In conclusion, zofenopril may be effective on the renal complications of diabetes mellitus.

  15. Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.

    Science.gov (United States)

    Zhang, Hongmei; Dong, Yan; Su, Qing

    2017-02-01

    In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

  16. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups often: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfu-sion for 45 min; (4) I-R/Resveratrol group: rats pretreat-ed with resveratrol (10 μmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratrol-treated livers.CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusion-related liver injury.

  17. Liver and plasma levels of descarboxyprothrombin (PIVKA II) in vitamin K deficiency in rats.

    Science.gov (United States)

    Harauchi, T; Takano, K; Matsuura, M; Yoshizaki, T

    1986-04-01

    Descarboxyprothrombin (PIVKA II) is a precursor of prothrombin without biological activity, and it increases with vitamin K deficiency. We studied the time course changes in liver and plasma levels of PIVKA II during the progress of vitamin K deficiency in rats. Good correlation was observed between liver PIVKA II and plasma PIVKA II and between liver or plasma PIVKA II and plasma prothrombin in experiments in which rats were fed a vitamin K-deficient diet. Feeding of a vitamin K-deficient diet or fasting caused marked increases in liver and plasma PIVKA II in male rats and a weaker response in female rats. Warfarin, a vitamin K antagonist, caused an abrupt increase in liver PIVKA II, but the increase in plasma PIVKA II was delayed about 3 hr. Plasma prothrombin decreased from about 30 min later. Factor VII decreased similarly to prothrombin, and changes in the prothrombin time and activated partial thromboplastin time were slower than the changes in these substances. Sex differences were not seen in these warfarin actions. These observations indicate that liver and plasma PIVKA II are sensitive markers of vitamin K deficiency in rats, and assay of PIVKA II can be useful for analyzing the action mechanism of drugs which influence blood coagulation.

  18. Pistacia Terebinthus Coffee Protects against Thioacetamide-Induced Liver Injury in Rats

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    Ibrahim Halil Bahcecioglu

    2015-08-01

    Full Text Available Aim/background: Pistacia terebinthus is used as a coffee substitute in the East and Southern Anatolia regions of Turkey. It contains unsaturated fatty acids, tocopherols, polyphenols and carotenoids. P. terebinthus has anti-inflammatory and potential antioxidant activity. In this study we evaluated the protective effects of P. terebinthus coffee (PTC on thioacetamide (TAA-induced liver injury in rats. Materials and methods: Twenty-eight male Sprague-Dawley rats were equally randomized into four groups. Chronic liver injury was induced with TAA (100 mg/kg i.p. three times weekly. The first group of rats served as control and received only tap water (G1, and the remaining groups of rats received PTC, p.o (G2; TAA (G3; TAA plus PTC, p.o (G4, respectively. Results: After 8 weeks, PTC intake significantly reduced fibrosis/ inflammation scores (p < 0.05 in the livers of TAA-treated group. Compared to control group, PTC intake reduced transforming growth factor beta (TGF-β concentrations in the liver (p < 0.05. Compared to the TAA group, TGF-β, nuclear factor kappa B (NF-κB (p < 0.05, tumor necrosis factor alpha (TNF-α concentrations in the liver tissue were reduced by PTC intake. Discussion and conclusion: PTC intake provided beneficial effects against TAA-induced liver injury in rats. PTC probably suppresses the proinflammatory cytokines through NF-κB signaling pathway.

  19. Protective effect of magnesium and selenium on cadmium toxicity in the isolated perfused rat liver system.

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    Ali Ghaffarian-Bahraman

    2014-12-01

    Full Text Available The isolated perfused rat liver (IPRL model has been used into toxicology study of rat liver. This model provides an opportunity at evaluation of liver function in an isolated setting. Studies showed that Cd, in a dose-dependent manner, induced toxic effects in IPRL models, and these effects were associated with aminotransferase activity and lipid peroxidation. The aim of this study was to investigate whether Mg  and/or Se could have protective effects against the Cd toxicity in the IPRL model. Male Wistar rats (9-10 weeks weighing 260-300 gr were used in this study. They were randomly divided into 8 groups of 4-6 rats per cage. In group 1, liver was perfused by Krebs-Henseleit buffer without MgSO4 (Control. Groups 2-8 were exposed to Mg, Se, Cd, Mg +Se, Cd + Mg, Cd + Se, Cd + Mg + Se respectively in Krebs-Henseleit buffer with no added MgSo4. Biochemical changes in the liver were examined within 90 minutes, and the result showed that the exposure to Cd, lowered glutathione level, while it increased malondialdehyde level and aminotransferase activities in IPRL model. Mg administration during exposure to Cd reduces the toxicity of Cd in the liver isolated while Se administration during exposure to Cd did not decrease Cd hepatotoxicity. Nevertheless, simultaneous treatment with Se and Mg on Cd toxicity have strengthened protective effects than the supplementation of Se alone in the liver.

  20. Inhibition of diethylnitrosamine-induced liver cancer in rats by Rhizoma paridis saponin.

    Science.gov (United States)

    Liu, Jing; Man, Shuli; Li, Jing; Zhang, Yang; Meng, Xin; Gao, Wenyuan

    2016-09-01

    Rhizoma Paridis saponin (RPS) had been regarded as the main active components responsible for the anti-tumor effects of the herb Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. In the present research, we set up a rat model of diethylnitrosamine (DEN) induced hepatoma to evaluate antitumor effect of RPS. After 20 weeks treatment, rats were sacrificed to perform histopathological examinations, liver function tests, oxidative stress assays and so forth. As a result, DEN-induced hepatoma formation. RPS alleviated levels of liver injury through inhibiting liver tissues of malondialdehyde (MDA) and nitric oxide (NO) formation, increasing superoxide dismutases (SOD) production, and up-regulating expression of GST-α/μ/π in DEN-induced rats. All in all, RPS would be a potent agent inhibiting chemically induced liver cancer in the prospective application.

  1. Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I

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    Castilla-Cortázar Inma

    2004-06-01

    Full Text Available Abstract Background Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I. The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine were studied in rats with ascitic cirrhosis. Methods Advanced cirrhosis was induced by CCl4 inhalation and Phenobarbital administration for 30 weeks. Cirrhotic animals were divided into two groups which received IGF-I or saline during two weeks. Control group was studied in parallel. Jejunal microvilli were studied by electron microscopy. Nutrient transport was assessed in brush border membrane vesicles using 14C or 35S-labelled subtracts in the three experimental groups. Results Intestinal active Na+-dependent transport was significantly reduced in untreated cirrhotic rats. Kinetic studies showed a decreased Vmax and a reduced affinity for sugar and four amino acids transporters (expressed as an increased Kt in the brush border membrane vesicles from untreated cirrhotic rats as compared with controls. Both parameters were normalised in the IGF-I-treated cirrhotic group. Electron microscopy showed elongation and fusion of microvilli with degenerative membrane lesions and/or notable atrophy. Conclusions The initial microvilli elongation reported in non ascitic cirrhosis develops into atrophy in rats with advanced cirrhosis and nutrient transports (monosaccharides and amino acids are progressively reduced. Both morphological and functional alterations improved significantly with low doses of IGF-I.

  2. The thalamus in cirrhotic patients with and without hepatic encephalopathy: A volumetric MRI study

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    Tao, Ran, E-mail: taoran1648@yahoo.cn [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Zhang, Jiuquan, E-mail: jiuquanzhang@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); You, Zhonglan, E-mail: you_zhonglan@163.com [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Wei, Luqing, E-mail: weiluqing@foxmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Fan, Yi, E-mail: fanyi1978@yahoo.cn [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Jinguo, E-mail: cuijinguo2005@163.com [Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Wang, Jian, E-mail: wangjian_811@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2013-11-01

    Background and aims: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. Methods: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. Results: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child–Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r = 0.659, P = 0.001; r = −0.577, P = 0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P = 0.001). Conclusions: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.

  3. Effects of cyclooxygenase-2 on sinusoidal capillarization in cirrhotic rats induced by carbon tetrachloride%环氧合酶-2在四氯化碳诱导肝硬化大鼠肝窦毛细血管化形成中的作用

    Institute of Scientific and Technical Information of China (English)

    涂传涛; 王吉耀; 郭津生

    2009-01-01

    目的 观察环氧合酶-2(COX-2)在实验性肝硬化大鼠肝窦毛细血管化形成中的作用.方法 腹腔注射CCl4每周2次共8周诱导雄性SD大鼠肝硬化模型.将SD大鼠分成3组:正常对照组(n=10)、模型对照组(n=15)和罗非昔布治疗组(10 mg·kg-1·d-1,n=15).光镜下观察肝组织标本,电镜观察肝窦超微结构改变.用Western印迹和免疫组化法检测基底膜蛋白主要成分层粘连蛋白(LN)和Ⅳ型胶原,同时通过Ⅷ因子相关抗原(vWF)免疫组化标记微血管牛成密度.结果 与模型对照组相比,罗非昔布干预治疗能减少肝纤维化面积(分别为30.7±8.9和23.5±6.5,P<0.05).光镜及电镜提示,在模型对照组可见肝窦内皮细胞窗孔减少、缩小,有完整的基底膜形成,Disse腔隙内有大量的胶原纤维沉积,罗非昔布组上述病变有所减轻.随着肝硬化的形成,肝组织微血管密度明显升高,罗非昔布组肝组织微血管密度(6.4±0.7)较模型对照组(11.3±1.6)明显降低(P<0.01).肝硬化时肝组织表达Ⅳ型胶原和LN蛋白明显增加(分别为3.8±0.4和3.7±0.5),罗非昔布能降低Ⅳ犁胶原和LN的表达(分别为3.0±0.5和3.0±0.5;与模型对照组相比两者均为Pliver cirrhotic rats. Methods The SD rats were intraperitoneally injected with carbon tetrachloride (CCl4) twice a week for 8 weeks to induce liver cirrhosis. The rats were randomly divided into three groups: normal control group (n= 10), model control group (n= 15) and rofecoxib treated group (received 10 mg/kg of rofecoxib daily, n = 15). Liver histopathology was examined by light microscopy, and sinusoidal ultrastructure was observed by transmission electron microscopy. Furthermore, the level of basement membrane proteins (collagen type

  4. A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation

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    Berendsen Tim A

    2012-05-01

    Full Text Available Abstract Background Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. Herein we present a simplified machine perfusion system without the need for oxygen carriers or temperature control, which we validated in a model of orthotopic liver transplantation. Methods Rat livers were procured and subnormothermically perfused with supplemented Williams E medium for 3 hours, then transplanted into healthy recipients (Fresh-SNMP group. Outcome was compared with static cold stored organs (UW-Control group. In addition, a rat liver model of donation after cardiac death was adapted using a 60-minute warm ischemic period, after which the grafts were either transplanted directly (WI group or subnormothermically perfused and transplanted (WI-SNMP group. Results One-month survival was 100% in the Fresh-SNMP and UW-Control groups, 83.3% in the WI-SNMP group and 0% in the WI group. Clinical parameters, postoperative blood work and histology did not differ significantly between survivors. Conclusion This work demonstrates for the first time in an orthotopic transplantation model that ischemically damaged livers can be regenerated effectively using practical subnormothermic machine perfusion without oxygen carriers.

  5. Metabolism and metabolic inhibition of gamboglc acid in rat liver microsomes

    Institute of Scientific and Technical Information of China (English)

    Yi-tong LIU; Kun HAO; Xiao-quan LIU; Guang-Ji WANG

    2006-01-01

    Aim: To study the metabolism of gambogic acid (GA) and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of GA in rat liver microsomes in vitro. Methods: Rat liver micrp,so,rn,e$ were used to perform metabolism studies. Various selective CYP450 inhibitors were used to investigate their effects on the metabolism of GA and the principal CYP450 isoform involved in the formation of major metabolite M1 in rat liver microsomes. Types of inhibition in an enzyme kinetics model were used to model the interaction. Results: GA was rapidly metabolized to two phase Ⅰ metabolites,, M1 and M2, in rat liver microsomes. M1 and M2 were tentatively presumed to be the hydration metabolite and epoxide metabolite of GA, respectively. α-Naphthoflavone uncompetitively inhibited the formation of M1 while ketoconazole, sulfophenazole, diethyl dithiocarbamate and quinidine had little or no inhibitory effects on the formation of M1. Conclusion: GA is rapidly metabolized in rat liver microsomes and M1 is crucial for the elimination of GA. Cytochrome P-450 1A2 is the major rat CYP involved in the metabolism of GA.

  6. Therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats.

    Science.gov (United States)

    Huang, J F; Zhan, T; Yu, X L; He, Q A; Huang, W J; Lin, L Z; Du, Y T; Pan, Y T

    2016-02-26

    The aim of this study was to explore the therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats. Rats were fed high-fat fodder to establish a rat fatty liver model, and were then fed different concentrations of Pleurotus eryngii cellulose for six weeks. Lipitor was used as a positive control. Measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and total triglyceride (TG); the activity of malondialdehyde (MDA), superoxide dismutase (SOD), hepatic lipase (HL), and lipoprotein lipase; and liver histopathological changes. Successfully established rat fatty liver model after feeding high-fat fodder for one week. A diet of P. eryngii cellulose for six weeks significantly reduced ALT, AST, TC, and TG levels in rat serum (P 0.05). SOD activity increased significantly, while MDA and HL activity decreased (P < 0.05); fatty degeneration and fat accumulation both decreased in hepatic tissue. Hepatic protection of P. eryngii cellulose showed dose-related effect. P. eryngii cellulose can affect lipid metabolism, having therapeutic effects on fatty liver in rats.

  7. Correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Guo; Ya-Min Li; Qing-Chun Li

    2015-01-01

    Objective:To study the correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model.Methods:Adult SD rats were selected and alcoholic fatty liver rat models were established by alcohol administration and high-fat diet feeding. Liver tissue was collected and contents of HIF-1α, PPARγ and lipid metabolism-related enzymes were detected; serum was collected and contents of lipid metabolism indexes and liver cell damage indexes were detected.Results:(1) one week, two weeks, three weeks and four weeks after models were established, HIF-1αα in livers of the model group showed an increasing trend and PPARγ showed a decreasing trend; HIF-1α content was higher than that of the control group and PPARγ content was lower than that of the control group; (2) contents of apoCII, apoCIII,α-GST and GLDH in serum as well as levels of FAT, FABP1, FAS, ACC and ACAT-2 in liver tissue of the model group all significantly increased, and were positively correlated with HIF-1α and negatively correlated with PPARγ.Conclusion:Transcription factor HIF-1α content abnormally increases and PPARγ content abnormally decreases in liver tissue of alcoholic fatty liver rat models; it results in abnormal lipid metabolism and liver cell damage through increasing the expression of lipid metabolism-related enzymes in the liver.

  8. Expression patterns and action analysis of genes associated with drug-induced liver diseases during rat liver regeneration

    Institute of Scientific and Technical Information of China (English)

    Qian-Ji Ning; Shao-Wei Qin; Cun-Shuan Xu

    2006-01-01

    AIM: To study the action of the genes associated with drug-induced liver diseases at the gene transcriptional level during liver regeneration (LR) in rats.METHODS: The genes associated with drug-induced liver diseases were obtained by collecting the data from databases and literature, and the gene expression changes in the regenerating liver were checked by the Rat Genome 230 2.0 array.RESULTS: The initial and total expression numbers of genes occurring in phases of 0.5-4 h after partial hepatectomy (PH), 4-6 h after PH (G0/G1 transition),6-66 h after PH (cell proliferation), 66-168 h after PH (cell differentiation and structure-function reconstruction) were 21, 3, 9, 2 and 21, 9, 19, 18, respectively. It is illustrated that the associated genes were mainly triggered at the initial stage of LR and worked at different phases. According to their expression similarity,these genes were classified into 5 types: only upregulated (12 genes), predominantly up-regulated (4genes), only down-regulated (11 genes), predominantly down-regulated (3 genes), and approximately up-/down-regulated (2 genes). The total times of their upand down-expression were 130 and 79, respectively,demonstrating that expression of most of the genes was increased during LR, while a few decreased. The cell physiological and biochemical activities during LR were staggered according to the time relevance and were diverse and complicated in gene expression patterns.CONCLUSION: Drug metabolic capacity in regenerating liver was enhanced. Thirty-two genes play important roles during liver regeneration in rats.

  9. Expression of liver-specific functions in rat hepatocytes following sublethal and lethal acetaminophen poisoning

    DEFF Research Database (Denmark)

    Tygstrup, N; Jensen, S A; Krog, B;

    1996-01-01

    AIM: In order to study the short-term effect of moderate and severe reduction of liver function by acetaminophen poisoning of different severity on gene expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg body weight acetaminophen intragastrically. The lower dose...... involved in metabolic liver functions, i.e. ureagenesis, gluconeogenesis, and drug metabolism, for acute phase proteins, "house-keeping" proteins, and for proteins related to liver regeneration. Results were expressed as per cent of the level in similarly fasted, untreated rats of the same stock RESULTS...... towards the end of the experiment. The greatest differences were seen for mRNA of arginase, beta-fibrinogen, alpha 1-acid glycoprotein, alpha-tubulin, histone 3, TGF beta, and cyclin d, i.e. proteins associated with acute phase response and liver cell replication and maintenance. CONCLUSIONS...

  10. Decellularization and Recellularization of Rat Livers With Hepatocytes and Endothelial Progenitor Cells.

    Science.gov (United States)

    Zhou, Pengcheng; Huang, Yan; Guo, Yibing; Wang, Lei; Ling, Changchun; Guo, Qingsong; Wang, Yao; Zhu, Shajun; Fan, Xiangjun; Zhu, Mingyan; Huang, Hua; Lu, Yuhua; Wang, Zhiwei

    2016-03-01

    Whole-organ decellularization has been identified as a promising choice for tissue engineering. The aim of the present study was to engineer intact whole rat liver scaffolds and repopulate them with hepatocytes and endothelial progenitor cells (EPCs) in a bioreactor. Decellularized liver scaffolds were obtained by perfusing Triton X-100 with ammonium hydroxide. The architecture and composition of the original extracellular matrix were preserved, as confirmed by morphologic, histological, and immunolabeling methods. To determine biocompatibility, the scaffold was embedded in the subcutaneous adipose layer of the back of a heterologous animal to observe the infiltration of inflammatory cells. Hepatocytes were reseeded using a parenchymal injection method and cultured by continuous perfusion. EPCs were reseeded using a portal vein infusion method. Morphologic and functional examination showed that the hepatocytes and EPCs grew well in the scaffold. The present study describes an effective method of decellularization and recellularization of rat livers, providing the foundation for liver engineering and the development of bioartificial livers.

  11. Anti-inflammatory liposomes have no impact on liver regeneration in rats

    DEFF Research Database (Denmark)

    Jepsen, Betina Norman; Andersen, Kasper Jarlhelt; Knudsen, Anders Riegels;

    2015-01-01

    ; liver tissue was sampled for analysis of regeneration rate and proliferation index. Results: The high dose dexamethasone group had significantly lower body and liver weight than the placebo and anti-CD163-dex groups. There were no differences in liver regeneration rates between groups. Hepatocyte......Introduction: Surgical resection is the gold standard in treatment of hepatic malignancies, giving the patient the best chance to be cured. The liver has a unique capacity to regenerate. However, an inflammatory response occurs during resection, in part mediated by Kupffer cells, that influences...... the speed of regeneration. The aim of this study was to investigate the effect of a Kupffer cell targeted anti-inflammatory treatment on liver regeneration in rats. Methods: Two sets of animals, each including four groups of eight rats, were included. Paired groups from each set received treatment...

  12. Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver.

    Science.gov (United States)

    Mahmoud, Y I; Hegazy, H G

    2016-01-01

    Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.

  13. In vitro covalent binding of /sup 14/C-mibolerone to rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Jaglan, P.S.

    1986-01-01

    Mibolerone (17-Hydroxy-7,17-dimethylestr-4-en-3-one; 7 alpha-17 alpha dimethyl-19-nortestosterone) is being marketed by The Upjohn Company for the inhibition of estrus in bitches. The aim of this study was to determine the extent of covalent binding of mibolerone to rat liver microsomes. Liver microsomes were obtained from Control and phenobarbitol-treated female Fisher rats, and were incubated with /sup 14/C-mibolerone at 37/sup 0/C for 10 minutes. No covalent binding to macromolecules was observed when /sup 14/C-mibolerone was incubated with rat liver microsomes. Under identical conditions, /sup 14/C-estradiol was covalently bound to macromolecules. Slightly higher covalent binding of estradiol was observed with microsomes from phenobarbitol-treated rats. Ascorbic acid and glutathione inhibited covalent binding of estradiol to macromolecules in the in vitro microsomal system.

  14. Convenient and efficient enrichment of the CD133+ liver cells from rat fetal liver as a source of liver stem/progenitor cells.

    Science.gov (United States)

    Liu, Weihui; You, Nan; Dou, Kefeng

    2012-01-01

    Although stem cells are commonly isolated by fluorescence-activated cell sorting or magnetic affinity cell sorting, they are very expensive, and they need known markers. However, there is no specific marker for liver stem/progenitor cells (LSPCs). Here, we describe a convenient and efficient method (three-step method) to enrich LSPCs. The fetal liver cells (FLCs) were firstly enriched by Percoll discontinuous gradient centrifugation from the rat fetal liver. Then the FLCs in culture were purified to be homogeneous in size by differential trypsinization and differential adherence. Finally, fetal liver stem/progenitor cells (FLSPCs) were enriched from purified FLCs by Percoll continuous gradient centrifugation. Flow cytometric analysis combining with marker CD133 was used to detect the purity of FLSPCs and evaluate the isolating effects of the three-step method.

  15. Paradoxical increase in liver ketogenesis during long-term insulin-induced hypoglycemia in diabetic rats.

    Science.gov (United States)

    Schiavon, Fabiana P M; Gazola, Vilma A F G; Furlan, Maria M D P; Barrena, Helenton C; Bazotte, Roberto B

    2011-02-01

    It is well established that insulin inhibits liver ketogenesis. However, during insulin-induced hypoglycemia (IIH) the release of counterregulatory hormones could overcome the insulin effect on ketogenesis. To clarify this question the ketogenic activity in livers from alloxan-diabetic rats submitted to long-term IIH was investigated. Moreover, liver glycogenolysis, gluconeogensis, ureagenesis and the production of L-lactate were measured, and its correlation with blood levels of ketone bodies (KB), L-lactate, glucose, urea and ammonia was investigated. For this purpose, overnight fasted alloxan-diabetic rats (DBT group) were compared with control non-diabetic rats (NDBT group). Long-term IIH was obtained with an intraperitoneal injection of Detemir insulin (1 U/kg), and KB, glucose, L-lactate, ammonia and urea were evaluated at 0, 2, 4, 6, 8 or 10 h after insulin injection. Because IIH was well established two hours after insulin injection this time was used for liver perfusion experiments. The administration of Detemir insulin decreased (P < 0.05) blood KB and glucose levels, but there was an increase in the blood L-lactate levels and a rebound increase in blood KB during the glucose recovery phase of IIH. In agreement with these results, the capacity to produce KB from octanoate was increased in the livers of DBT rats. Moreover, the elevated blood L-lactate levels in DBT rats could be attributed to the higher (P < 0.05) glycogenolysis when part of glucose from glycogenolysis enters glycolysis, producing L-lactate. In contrast, except glycerol, gluconeogenesis was negligible in the livers of DBT rats. Therefore, during long-term IIH the higher liver ketogenic capacity of DBT rats increased the risk of hyperketonemia. In addition, in spite of the fact that the insulin injection decreased blood KB, there was a risk of worsening lactic acidosis.

  16. What we should know about portal vein thrombosis in cirrhotic patients: A changing perspective

    Institute of Scientific and Technical Information of China (English)

    Francesca Romana Ponziani; Maria Assunta Zocco; Matteo Garcovich; Francesca D'Aversa; Davide Roccarina; Antonio Gasbarrini

    2012-01-01

    Portal vein thrombosis (PVT) is one of the most common complications occurring during the natural course of liver cirrhosis.Even though PVT is often asymptomatic,the worsening of liver function,an unexpected episode of gastrointestinal bleeding or ascitic decompensation may be landmarks of PVT development.Beyond these clinical manifestations,it is debated whether PVT really has an impact on liver cirrhosis natural history or rather represents only one of its consequences.Probably PVT development should not only be considered as a matter of impaired blood flow or pro-coagulation tendency.On one hand,PVT seems a consequence of the worsening in portal vein outflow due to the increased hepatic resistance in cirrhotic livers.On the other hand,vascular microthrombosis secondary to necroinflammation may cause liver ischemia and infarction,with loss of hepatic tissue (parenchymal extinction) which is replaced by fibrotic tissue.Therefore,PVT might also be considered as the overt manifestation of the liver fibrosing process evolution and anticoagulant therapy may thus have microscopic indirect effects also on the progression of liver disease.At present,a connection between PVT development and the progression of liver fibrosis/cirrhosis has not yet been demonstrated.Nevertheless,it is not clear if PVT development may worsen cirrhotic patients' outcome by itself.Some authors tried to assess liver transplant benefit in PVT cirrhotic patients but data are contrasting.In this review,we will try to answer these questions,providing a critical analysis of data reported in literature.

  17. Effects of Radix Puerariae flavones on liver lipid metabolism in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Ji-Feng Wang; Yan-Xia Guo; Jan-Zhao Niu; Juan Liu; Ling-Qiao Wang; Pei-Heng Li

    2004-01-01

    AIM: To study the effects of Radix Puerariae flavones (RPF)on liver lipid metabolism in ovariectomized (OVX) rats.METHODS: Forty adult female Wistar rats were randomly divided into four groups: OVX group; sham-OVX group;OVX+estrogen group and OVX+RPF group. One week after operation rats of the first two groups were treated with physiological saline, rats of OVX+estrogen group with estrogen (1 mg/kg.b.w.) and rats of OVX+RPF group with RPF (100 mg/kg.b.w.), respectively for 5 weeks. After the rats were killed, their body weight, the weight of the abdominal fat and uterus were measured, and the levels of total cholesterol (TC) and triglyceride (TG) in liver homogenate were determined.RESULTS: Compared with the sham-OVX group, the body mass of the rats in OVX group was found increased significantly;more abdominal fat in store; TC and TG in liver increased and uterine became further atrophy. As a result, the RPF was found to have an inhibitive action on those changes of various degrees.CONCLUSION: RPF has estrogen-like effect on lipid metabolism in liver and adipose tissue.

  18. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

    Science.gov (United States)

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2016-07-01

    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD.

  19. Mechanism of enhanced lipid peroxidation in the liver of Long-Evans cinnamon (LEC) rats.

    Science.gov (United States)

    Yamamoto, H; Hirose, K; Hayasaki, Y; Masuda, M; Kazusaka, A; Fujita, S

    1999-11-01

    The Long-Evans Cinnamon (LEC) rat is a mutant strain of rats that accumulate copper (Cu) in the liver in much the same way as individuals who suffer from Wilson's disease (WD) and has been suggested as a model for this disease. Lipid peroxidation (LPO) is considered to be involved in the toxic action of Cu in the livers of LEC rats. We investigated the mechanism of LPO in the livers of LEC rats showing apparent signs of hepatitis. Several-fold higher LPO levels were observed in post-mitochondrial supernatant (S-9) fraction of livers from hepatitic LEC rats than in those from Wistar rats. To mimic living cells, we introduced NADPH-generating system (NADPH-gs) into the S-9 incubation system. Thus was ensured a constant supply of NADPH to vital enzymes that may be directly or indirectly involved in the generation and/or elimination of reactive oxygen species (ROSs), such as glutathione reductase (GSSG-R), which require NADPH for their reactions. The levels of LPO in liver S-9 from hepatitic LEC rats were further increased by incubating liver S-9 at 37 degrees C in the presence of NADPH-gs. This increase was inhibited by EDTA, butylated hydroxytoluene (BHT), and catalase (CAT), suggesting that some metal, most likely the accumulated Cu, and ROSs derived from hydrogen peroxide (H2O2) are involved in the increased levels of LPO in the livers of hepatitic LEC rats. The requirement of NADPH-gs for enhanced LPO in the livers of hepatitic LEC rats indicates the consumption of NADPH during reactions leading to LPO. It is known that H2O2, and consequently hydroxyl radical are generated during Cu-catalyzed glutathione (GSH) oxidation. The cyclic regeneration of GSH from GSSG by NADPH-dependent GSSG-R in the presence of NADPH-gs may cause sustained generation of hydroxyl radical in the presence of excess free Cu. The generation of H2O2 in S-9 fraction of livers from hepatitic LEC rats was observed to be significantly higher than that in S-9 fraction of livers from non

  20. The mechanisms underlying the hypolipidaemic effects of Grifola frondosa in the liver of rats

    Directory of Open Access Journals (Sweden)

    Yinrun Ding

    2016-08-01

    Full Text Available The present study investigated the hypolipidaemic effects of Grifola frondosa and its regulation mechanism involved in lipid metabolism in liver of rats fed a high-cholesterol diet. The body weights and serum lipid levels of control rats, of hyperlipidaemic rats and of hyperlipidaemic rats treated with oral Grifola frondosa were determined. mRNA expression and concentration of key lipid metabolism enzymes were investigated. Serum cholesterol, triacylglycerol and low-density lipoprotein cholesterol levels were markedly decreased in hyperlipidaemic rats treated with Grifola frondosa compared with untreated hyperlipidaemic rats. mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR, acyl-coenzyme A: cholesterol acyltransferase (ACAT2, apolipoprotein B (ApoB, fatty acid synthase (FAS and acetyl-CoA carboxylase (ACC1 were significantly down-regulated, while expression of cholesterol 7-alpha-hydroxylase (CYP7A1 was significantly up-regulated in the livers of treated rats compared with untreated hyperlipidaemic rats. The concentrations of these enzymes also paralleled the observed changes in mRNA expression. Two-dimensional polyacrylamide gel electrophoresis (2-DE and Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS were used to identify twenty proteins differentially expressed in livers of rats treated with Grifola frondosa compared with untreated hyperlipidemic rats. Of these twenty proteins, seven proteins were down-regulated and thirteen proteins were up-regulated. These findings indicate that the hypolipidaemic effects of Grifola frondosa reflected its modulation of key enzymes involved in cholesterol and triacylglycerol biosynthesis, absorption and catabolic pathways. Grifola frondosa may exert anti-atherosclerotic effects by inhibiting LDL oxidation through down-regulation and up-regulating proteins expression in the liver of rats. Therefore, Grifola frondosa may produce both hypolipidaemic

  1. Pharmacokinetic Study of Frusemide in Healthy and Cirrhotic Indian Subjects

    Directory of Open Access Journals (Sweden)

    Dr. Yuvrajsing Dhunnoo

    2008-01-01

    Full Text Available Liver cirrhosis is associated with various complications such as ascites and fluid retention, progressing to development of hepatorenal syndrome, further compromising fluid elimination. Frusemide, a loop diuretic is normally administered to relieve fluid retentions. The kinetics of frusemide has not been conclusively reported in the three types of cirrhosis and among Indian subjects. The aim of the current study was to evaluate the kinetics of frusemide among healthy and Child’s A, B and C cirrhosis and compare with earlier data. 24 cirrhotic were selected and classified according to the Child’s-Pugh classification. 12 healthy male volunteers were screened and included in the study. 40 mg of frusemide was administered orally to both groups and blood samples were withdrawn at various intervals of time for a duration of 8 hrs. The amount of frusemide present in plasma was analyzed using HPLC. The volumes of distribution (Vd, area under curve (AUC, systemic clearance (CL, maximum concentration (Cmax, time for maximum concentration (tmax in healthy volunteers were respectively 4.56 ± 0.15 L, 2258 ± 530.7, 4.97 ± 1.67 L/h, 892 ± 49.4 ng/ml, 85.20± 7.49 mins. Corresponding values in Group A were 5.00 ± 0.31 L, 2471 ± 228.6, 6.60 ± 2.90L/h, 1021 ± 47.97 ng/ml and 88.25 V 2.12 mins; in Group B 7.73 ± 1.10 L, 4038 ± 154.7, 8.84 ± 0.45 L/h, 1448 ± 43.20 ng/ml and 120 ± 1.89 mins; In group C cirrhosis 9.69 ± 1.32 L, 4085 ± 131.75, 3.49 ± 1.40 L/h, 1551± 59.02 ng/ml and 185.7 ± 2.68 mins respectively. Significant differences at 1% and 5% were observed among the cirrhotic groups and between healthy v/s cirrhotic patients. Data from current study do not correlate with earlier reports, carried mainly in Western population, due to possibly differences in instrumentation, etc but a possible genetic interplay should not be ruled out. Data from cirrhotic patients could not be effectively compared with earlier studies as kinetics of frusemide

  2. Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.

    Science.gov (United States)

    Mazzucco, María Belén; Fornes, Daiana; Capobianco, Evangelina; Higa, Romina; Jawerbaum, Alicia; White, Verónica

    2016-01-01

    We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

  3. Effects of Kupffer cell inactivation on graft survival and liver regeneration after partial liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    Hang-Yu Luo; Shan-Fang Ma; Ji-Fu Qu; De-Hu Tian

    2015-01-01

    BACKGROUND: Gadolinium chloride (GdCl3) selectively in-activates Kupffer cells and protects against ischemia/reperfu-sion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplan-tation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process. METHODS: PLTx (30% partial liver transplantation) was per-formed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regen-eration by PCNA staining and BrdU uptake, apoptosis by TU-NEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting. RESULTS: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine amino-transferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overex-pression and STAT3 phosphorylation after PLTx in graft tissues. CONCLUSION: Kupffer cells may contribute to the liver re-generation after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.

  4. Metabolism of aildenafil in vivo in rats and in vitro in mouse, rat, dog, and human liver microsomes.

    Science.gov (United States)

    Li, Yan; Wu, Linan; Gu, Yuan; Si, Duanyun; Liu, Changxiao

    2014-06-01

    Aildenafil, 1-{[3-(6, 7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4, 3-d] primidin-5-yl)-4-ethoxyphenyl] sulfonyl}-cis-3, 5-dimethylpiperazine, a phosphodiesterase type V enzyme inhibitor (PDE5I), is under development for treatment of erectile dysfunction (ED). The purpose of this study was to elucidate metabolism of aildenafil in vivo in rats and in vitro in mouse, rat, dog, and human liver microsomes. Thirty-one phase I metabolites have been found by LTQ/Orbitrap hybrid mass spectrometry in rat urine, faeces, and bile after oral administration. Major biotransformation pathways of aildenafil included N-dealkylation of the piperazine ring, hydroxylation and dehydrogenation, aliphatic hydroxylation and loss of alkyl group of piperazine ring. Minor pathways involved hydroxylation on the phenyl ring, pyrazole N-demethylation, O-deethylation, loss of piperazine ring (cleavage of N-S bond) and dehydrogenation on the piperazine ring. Similar metabolic pathways of aildenafil were observed in the incubations of liver microsomes from mouse, rat, and dog as well as from human. The depletion rate of parent drug in mouse and rat liver microsomes was significantly different from that in human liver microsomes. The cytochrome P450 reaction phenotyping analysis was conducted using isozyme-specific inhibitors. The results indicated that CYP3A was the main isoenzyme involved in oxidative metabolism of aildenafil. Overall, these in vitro and in vivo findings should provide valuable information on possible metabolic behaviours of aildenafil in humans.

  5. Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

    Science.gov (United States)

    Sipahi, Mesut; Şahin, Sevinç; Arslan, Ergin; Börekci, Hasan; Metin, Bayram; Cantürk, Nuh Zafer

    2015-01-01

    Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations. PMID:26457000

  6. Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

    Directory of Open Access Journals (Sweden)

    Mesut Sipahi

    2015-01-01

    Full Text Available Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations.

  7. Evaluation of Zinc Plasma Level in Iranian Cirrhotic Patients due to Hepatitis B and Hepatitis C

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zali

    2010-01-01

    Full Text Available Background and Aims: Zinc (Zn has various significant roles in physiological functions of the liver. Furthermore, it has been reported that the administration of zinc has an important role in pharmacotherapy of viral hepatitis. Cirrhotic patients with decrease in plasma zinc level have been covered in previous studies. It is seemingly necessary to assess the zinc level, in Iranian cirrhotic patients, as a distinct population, Because of the large phytate amounts in Iranians diet. Regarding to etiology, disease progress, and treatment, there are some differences in the 2 most common causes of cirrhosis in the Iranian population (hepatitis B and hepatitis C and it is possible that the zinc level may be different between the two. This study was done to shadow some lights on the subject. Methods: Between April 2008 and November 2008, plasma zinc level was determined, by atomic absorption method, in 60 cirrhotic inpatients treated due to hepatitis B or hepatitis C in Talighani hospital (a referral center for gastrointestinal and liver diseases in Tehran, Iran. Results: Mean ± standard deviation (SD plasma zinc levels determined 0.34±0.22 mg/L and 0.37±0.22 mg/L in hepatitis B and hepatitis C patients respectively. Analysis of t-test showed there is no significant difference between 2 groups regarding to plasma zinc level (P = 0.745.Conclusions: It is concluded that zinc level of studied cirrhotic patients is less than half of the normal range. Moreover, there is no difference in plasma zinc level between cirrhotic patients due to hepatitis B or hepatitis C. Regarding to this result, supplementation with complementary zinc, may be recommended in both groups in order to optimize the nutritional support and probably better the treatment response.

  8. Effects of hepatotrophic factors on the liver after portacaval shunt in rats with portal hypertension

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-tao; JIANG Peng; WANG Yu; LI Jian-she; XUE Jian-guo; ZHOU Yan-zhong; YUAN Zhu

    2006-01-01

    Background Portacaval shunt (PCS) prevent hepatotrophic factors from flowing into the liver, but they enter directly the systemic circulation and worsen liver injury. This study was designed to investigate the effects of hepatotrophic factors through the portal vein on the liver in rats with portal hypertension after portacaval shunt.Methods Intrahepatic portal hypertension (IHPH) was induced by intragastric administration of carbon tetrachloride, and end-to-side PCS was performed. Eight normal rats served as controls, and eight rats with IHPH served as IHPH model (IHPH group). Another 32 rats with IHPH-PCS were randomly subdivided into 4 groups:normal saline (NS) given to 8 rats, hepatocyte growth factor (HGF) 8, insulin (INS) 8, hepatocyte growth factor and insulin (HGF+INS) 8. Hepatotrophic factors were infused into the portal vein through an intravenous catheter.Portal venous pressure (PVP) was measured. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested biochemically and those of hyaluronic acid (HA) and laminin (LN) were measured by radioimmunoassay. Hepatic fibrosis was assessed histologically and the expression of collagens type Ⅰ and Ⅲ were detected immunohistochemically. Ultrastructural change of hepatocytes and the number of mitochondria were observed under an electron microscope. The data were compared between groups and subgroups by Student-Newman-Keuls procedure with SPSS 10.0.Results PVP was significantly higher in the IHPH rats than in the control rats (P<0.05). The levels of serum ALT, AST, HA, and LN, hepatic fibrosis score, the amount of collagen deposition, collagens type Ⅰ and Ⅲ increased more significantly in the IHPH group than in the control rats (P<0.05). The number of mitochondria decreased more significantly in the IHPH rats than in the control rats (P<0.05). The levels of serum ALT, AST,HA and LN as well as hepatic fibrosis score, the amount of collagen deposition, and the

  9. [Regulation of autophagy on dendritic cells during rat liver regeneration by IPA].

    Science.gov (United States)

    Qiwen, Wang; Wei, Jin; Cuifang, Chang; Cunshuan, Xu

    2015-03-01

    To understand the mechanism underlying autophagy in regulating dendritic cells during rat liver regeneration, we used the method of percoll density gradient centrifugation combined with immunomagnetic bead to isolate dendritic cells, the Rat Genome 230 2.0 Array to determine the expression changes of autophagy-related genes, and Ingenuity Pathway Analysis 9.0 (IPA) to determine the autophagy activities. The results indicated that LC3, BECN1, ATG7 and SQSTM1 genes had significant expression changes during rat liver regeneration. There were 593 genes related to autophagy, among which 210 genes were identified as significant. We also showed that the activity of autophagy was enhanced in the priming phase and teminal phase of liver regeneration, weakened in the proliferative stage by comparative analysis method of IPA. The autophagy-related physiological activities mainly included RNA expression, RNA transcription, cell differentiation and proliferation, involving in PPARα/RXRα activation, acute phase response signaling, TREM1 signaling, IL-6 signaling, IL-8 signaling and IL-1 signaling, whose activities were increased or decreased in liver regeneration. Cluster analysis found that P53 and AMPK signaling participated in the regulation of dendritic cells autophagy, with AMPK signaling in the priming phase of liver regeneration, and both signaling pathways in the terminal phase. We conclude that dendritic cells autophagy played an important role in initiation of the immune response in priming phase and depletion of dendritic cells in late phase during rat liver regeneration.

  10. Iron deposition and fat accumulation in dimethylnitrosamine-induced liver fibrosis in rat

    Institute of Scientific and Technical Information of China (English)

    Jin-Yang He; Wen-Hua Ge; Yuan Chen

    2007-01-01

    AIM: To investigate if iron deposition and fat accumulation in the liver play a pathogenetic role in dimethylnitrosamine (DMN)-induced liver fibrosis in rat.METHODS: Thirty rats were treated with DMN at does consecutive days of 10 μL/kg daily, i.p., for 3 consecutive day each week for 4 wk. Rats (n = 30) were sacrificed on the first day (model group A) and 21st d (model group B) after cessation of DMN injection. The control group (n = 10) received an equivalent amount of saline. Liver tissues were stained with hematoxylin & eosin (HE) and Masson and Prussian blue assay and oberserved under electron microscopy. Serum alanine aminotransferase (ALT)and liver tissue hydroxyproline (Hyp) content were tested.RESULTS: The liver fibrosis did not automaticallyreverse, which was similar to previous reports, the perilobular deposition of iron accompanied with collagen showed marked characteristics at both the first and 21st d after cessation of DMN injection. However, fat accumulation in hepatocytes occurred only at the 21st d after cessation of DMN injection.CONCLUSION: Iron deposition and fat accumulation may play important roles in pathological changes in DMN-induced rat liver fibrosis. The detailed mechanisms of these characteristics need further research.

  11. Protective effect of black tea on integral membrane proteins in rat liver.

    Science.gov (United States)

    Szachowicz-Petelska, Barbara; Skrzydlewska, Elżbieta; Figaszewski, Zbigniew

    2013-01-01

    Ethanol intoxication is accompanied by oxidative stress formation. Consequently, it leads to disturbances in cellular metabolism that can alter the structure and function of cell membrane components. Black tea displays antioxidant properties, protects membrane phospholipids and may protect integral membrane proteins. In the present study, we examined whether black tea induces changes in the liver integral membrane proteins of 12-months old rats chronically intoxicated with ethanol. To estimate qualitatively and quantitatively the levels of the liver integral membrane proteins, the proteins were selectively hydrolyzed by trypsin, the obtained peptides were resolved by HPLC and the levels of specific amino acids within the individual peptides were determined. All of the obtained peptides contained phenylalanine (Phe), cysteine (Cys) and lysine (Lys). Compared to the control group, rats in the ethanol intoxication group showed decreased liver levels of integral membrane proteins as well as fewer trypsin-hydrolyzed peptides and amino acids in the hydrolyzed peptides. Administration of black tea to ethanol-intoxicated rats partially protected proteins against the structural changes caused by ethanol. Black tea prevented decreases in the levels of cysteine (in about 90% of cases), lysine (in about 60% of cases), phenylalanine (in about 70% of cases) and examined peptides (in about 60% of cases). The liver protein level was higher (by about 18%) in rats who received black tea and ethanol than in those who received ethanol alone. In conclusion, black tea partially protects the composition and level of rat liver cell integral membrane proteins against changes caused by ethanol intoxication.

  12. Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Masayoshi; Usuda, Koji; Hayashi, Seigo; Ogawa, Izumi; Furukawa, Satoshi [Nissan Chemical Industries Limited, Toxicology and Environmental Science Department, Biological Research Laboratories, Saitama (Japan); Igarashi, Maki [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Nakae, Dai [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Tokyo Metropolitan Institute of Public Health, Tokyo (Japan)

    2008-08-15

    Carcinogenic risk and molecular mechanisms underlying the liver tumor-promoting activity of copper gluconate, an additive of functional foods, were investigated using a rat medium-term liver carcinogenicity bioassay protocol (Ito test) and a 2-week short-term administration experiment. In the medium-term liver bioassay, Fischer 344 male rats were given a single i.p. injection of N-nitrosodiethylamine at a dose of 200 mg/kg b.w. as a carcinogenic initiator. Starting 2 weeks thereafter, rats received 0, 10, 300 or 6,000 ppm of copper gluconate in diet for 6 weeks. All rats underwent 2/3 partial hepatectomy at the end of week 3, and all surviving rats were killed at the end of week 8. In the short-term experiment, rats were given 0, 10, 300 or 6,000 ppm of copper gluconate for 2 weeks. Numbers of glutathione S-transferase placental form (GST-P) positive lesions, single GST-P-positive hepatocytes and 8-oxoguanine-positive hepatocytes, and levels of cell proliferation and apoptosis in the liver were significantly increased by 6,000 ppm of copper gluconate in the medium-term liver bioassay. Furthermore, hepatic mRNA expression of genes relating to the metal metabolism, inflammation and apoptosis were elevated by 6,000 ppm of copper gluconate both in the medium-term liver bioassay and the short-term experiments. These results indicate that copper gluconate possesses carcinogenic risk toward the liver at the high dose level, and that oxidative stress and inflammatory and pro-apoptotic signaling statuses may participate in its underlying mechanisms. (orig.)

  13. [Effect of pyruvate, threonine, and phosphoethanolamine on acetaldehyde metabolism in rats with toxic liver injury].

    Science.gov (United States)

    Pron'ko, P S; Satanovskaia, V I; Gorenshteĭn, B I; Kuz'mich, A B; Pyzhik, T N

    2002-01-01

    Pyruvate dehydrogenase, threonine aldolase and phosphoethanolamine lyase can produce acetaldehyde during normal metabolism. We studied the effect of loading with the substrates of these enzymes (pyruvate, 500 mg/kg, i.p., threonine 500 mg/kg, i.p., and phosphoethanolamine, 230 mg/kg, i.p.) on the blood concentrations of endogenous acetaldehyde and ethanol and the activities of enzymes producing and oxidizing acetaldehyde in the liver of normal rats and rats with liver injury provoked by chronic carbon tetrachloride (CCl4) treatment (0.2 ml i.p. per rat, 2 times a week during 4 weeks). Blood was collected before the treatment and then 30 min and 1 h following the administration of the substrates to intact and CCl4-treated rats. Endogenous acetaldehyde and ethanol were determined by headspace GC. The CCl4 treatment resulted in decreased liver alcohol dehydrogenase and aldehyde dehydrogenase activities and a significant elevation of liver endogenous ehtanol and a clear tendency to enhance blood acetaldehyde levels. Pyruvate increased blood endogenous acetaldehyde in CCl4-treated animals and endogenous ethanol--in the control group of animals. Threonine elevated endogenous acetaldehyde in normal rats. Phosphoethanolamine increased endogenous ethanol in the intact and CCl4 groups. At the same time, in CCl4-treated rats pyruvate administration increased the liver pyruvate dehydrogenase, threonine decreased threonine aldolase, whereas phosphoethanolamine decreased phosphoethanolamine lyase. Thus, the CCl4 effect on blood endogenous acetaldehyde and ethanol may be mediated through decreased liver ALDH and ADH activities. Liver injury promotes the accumulation of acetaldehyde, derived from physiological sources, including the degration of pyruvate and threonine by decreased acetaldehyde oxidation.

  14. Expression of tissue inhibitor of matrix metalloproteinases-1 during aging in rat liver

    Institute of Scientific and Technical Information of China (English)

    Yu-Mei Zhang; Xiang-Mei Chen; Di Wu; Suo-Zhu Shi; Zhong Yin; Rui Ding; Yang Lü

    2005-01-01

    AIM: To investigate the expression and role of tissueinhibitor of matrix metalloproteinases-1 (TIMP-1) during natural aging in rat liver and to detect the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9.METHODS: The rats were divided into 3-mo-old group (n = 5), 10-mo-old group (n = 5) and 24-mo-old group(n = 5). Histopathologic changes of liver were observed with HE and Masson stain. The location and protein expressions of TIMP-1 were determined by immunohistochemistry and Westem blot; message RNA (mRNA) levels were measured in livers from rats of various ages by semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR). In addition, the expression of MMP-2 and MMP-9was assessed by RT-PCR and Western blot.RESULTS: Histologic examination showed that the aging liver had excessive fatty degeneration and collagen deposition. Immunohistochemical staining showed that TIMP-1 related antigen in livers was located in cytoplasm. The proteinexpression of TIMP-1 was significantly higher in the oldestanimals and the mRNA expression was increased significantlyin the 24-mo-old rats (t= 4.61, P= 0.002<0.05, 24-vs 10-mo-old rats; t= 4.31, P= 0.003<0.05, 24- vs 3-mo-oldrats). The expression of MMP-2 and MMP-9 had no change during aging; the ratios TIMP-1/MMP-2 and TIMP-1/MMP-9 in aging liver were significantly higher than those in maturation and young livers.CONCLUSION: TIMP-1 may play an important role in the process of liver aging.

  15. Survey of serum procalcitonin in cirrhotic patients.

    Science.gov (United States)

    Rahimkhani, Monireh; Einollahi, Nahid; Khavari Daneshvar, Hossein; Dashti, Nasrin

    2013-04-06

    Procalcitonin (PCT) is a prohormone that has been used as a marker for the diagnosis of bacterial infections. The aim of this study was to survey PCT levels in patients with cirrhosis. Sixty-four patients with hepatic cirrhosis and 32 healthy blood donors were enrolled in this study. Serum PCT levels was detected using immunoluminometric assay. The rate of positive PCT was higher in patients with hepatitis C cirrhosis (92.8%) than the other groups. Among other cirrhotic patients, positive PCT levels were 77% for hepatitis B, 70% for cancer and 53.3% for unknown groups respectively. Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (2.65±1.11 ng/ml) than those without infection (0.59±0.16 ng/ml, P=0.0001). PCT assay in cirrhotic patients may help diagnosis of sepsis and reduce unnecessary antibiotic use.

  16. Survey of Serum Procalcitonin in Cirrhotic Patients

    Directory of Open Access Journals (Sweden)

    Monireh Rahimkhani

    2013-03-01

    Full Text Available Procalcitonin (PCT is a prohormone that has been used as a marker for the diagnosis of bacterial infections. The aim of this study was to survey PCT levels in patients with cirrhosis. Sixty-four patients with hepatic cirrhosis and 32 healthy blood donors were enrolled in this study. Serum PCT levels was detected using immunoluminometric assay. The rate of positive PCT was higher in patients with hepatitis C cirrhosis (92.8% than the other groups. Among other cirrhotic patients, positive PCT levels were 77% for hepatitis B, 70% for cancer and 53.3% for unknown groups respectively. Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (2.65±1.11 ng/ml than those without infection (0.59±0.16 ng/ml, P=0.0001. PCT assay in cirrhotic patients may help diagnosis of sepsis and reduce unnecessary antibiotic use

  17. Methanobactin reverses acute liver failure in a rat model of Wilson disease

    Science.gov (United States)

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K.; Schirmacher, Peter; DiSpirito, Alan A.; Bandow, Nathan; Baral, Bipin S.; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P.; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A.; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H.J.; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz

    2016-01-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration– and European Medicines Agency–approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  18. Butylbenzyl phthalate hydrolysis in liver microsomes of humans, monkeys, dogs, rats and mice.

    Science.gov (United States)

    Takahara, Yuka; Kinashi, Yu; Takahara, Yuusuke; Hichiya, Hiroyuki; Okada, Kenji; Murata, Mikio; Shigeyama, Masato; Hanioka, Nobumitsu

    2014-01-01

    Butylbenzyl phthalate (BBzP) is used as a plasticizer to import flexibility to polyvinylchloride plastics. In this study, hydrolysis of BBzP to monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP) in liver microsomes of humans, monkeys, dogs, rats and mice was examined. The kinetics for MBP formation by human, dog and mouse liver microsomes followed the Michaelis-Menten model, whereas the kinetics by monkey and rat liver microsomes fitted the Hill model. The kinetics for MBzP formation fitted the Hill model for all liver microsomes. The Vmax and in vitro clearance (CLint or CLmax) ratios of MBP/MBzP formation varied among animal species, although the Km for MBP and MBzP formation in each liver microsomes were generally comparable. The hydrolysis of BBzP to monoester phthalates in mammalian liver microsomes could be classified into two types: MBzP>MBP type for humans and dogs, and MBP>MBzP type for monkeys, rats and mice. These findings suggest that the formation profile of MBzP and MBP from BBzP by liver microsomes differs extensively among animal species.

  19. Dose-related effects of dexamethasone on liver damage due to bile duct ligation in rats

    Institute of Scientific and Technical Information of China (English)

    Halil Eken; Hayrettin Ozturk; Hulya Ozturk; Huseyin Buyukbayram

    2006-01-01

    AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats,weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10)were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10)received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa,n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the twoweek period, biochemical and histological evaluations were processed.RESULTS: The mean serum bilirubin and liver enzyme levels significantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group.CONCLUSION: Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not significantly lower in the high-dose corticosteroid group as compared to the lowdose group. Thus, low-dose corticosteroid provides a significant reduction of liver damage without increased side effects, while high dose is associated not with lower fibrosis but with increased side effects.

  20. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  1. Effect of Gadolinium Chloride on Liver Regeneration Following Thioacetamide-Induced Necrosis in Rats

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    María Isabel Sánchez-Reus

    2010-11-01

    Full Text Available Gadolinium chloride (GD attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. The effect of GD was studied in reference to postnecrotic liver regeneration induced in rats by thioacetamide (TA. Rats, intravenously pretreated with a single dose of GD (0.1 mmol/Kg, were intraperitoneally injected with TA (6.6 mmol/Kg. Hepatocytes were isolated from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication, and samples of blood and liver were obtained. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the time course of DNA distribution and ploidy were assayed in isolated hepatocytes. The levels of circulating cytokine TNFα was assayed in serum samples. TNFα was also determined by RT-PCR in liver extracts. The results showed that GD significantly reduced the extent of necrosis. The effect of GD induced noticeable changes in the post-necrotic regeneration, causing an increased percentage of hepatocytes in S phase of the cell cycle. Hepatocytes increased their proliferation as a result of these changes. TNFα expression and serum level were diminished in rats pretreated with GD. Thus, GD pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. No evidence of TNFα implication in this enhancement of hepatocyte proliferation and liver regeneration was found. These results demonstrate that Kupffer cells are involved in TA-induced liver damage, as well as and also in the postnecrotic proliferative liver states.

  2. Studies on responsiveness of hepatoma cells to catecholamines. II. Comparison of beta-adrenergic responsiveness of rat ascites hepatoma cells with cultured normal rat liver cells.

    Science.gov (United States)

    Miyamoto, K; Matsunaga, T; Takemoto, N; Sanae, F; Koshiura, R

    1985-05-01

    The pharmacological properties of beta-adrenoceptors in rat ascites hepatoma cells were compared with those in normal rat liver cells which were cultured for 24 hr after collagenase digestion. Adenylate cyclases in the homogenates of cultured normal rat liver cells and rat ascites hepatoma cells, AH44, AH66, AH109A, AH130 and AH7974, were all activated by isoproterenol or NaF to different degrees. The enzyme in rat liver cells was activated by several beta 2-agonists but those in all hepatoma cells hardly responded. Furthermore, salbutamol, a beta 2-partial agonist, antagonized the cyclase activation by isoproterenol in AH130 cells. The Kact value of isoproterenol for the activation of adenylate cyclase in AH130 cells was smaller than that in rat liver cells. A comparison of the Ki values of beta-antagonists for the inhibition of isoproterenol-stimulated cyclase activity shows that while the Ki values of propranolol and butoxamine in AH130 cells were similar to those in rat liver cells, a significant difference was observed in the values for beta 1-selective antagonists between AH130 cells and rat liver cells. The Ki values of metoprolol and atenolol for AH130 cells were 137- and 90-fold lower, respectively, than for normal rat liver cells. From these findings, it is strongly suggested that beta-adrenoceptors in rat ascites hepatoma cells including AH130 cells have similar properties to the mammalian beta 1-receptor.

  3. Evaluation of usefulness of [sup 99m]Tc-GSA liver scintigraphy on fatty liver in the rat

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    Kimoto, Mitsunori; Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo; Sakae, Katsuyoshi; Nagaya, Isao; Takeda, Yoshihiro; Hiraki, Yoshio (Okayama Univ. (Japan). School of Medicine)

    1994-10-01

    [sup 99m]Tc-GSA is a new liver-imaging radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes. We evaluated liver injury induced by fatty infiltration in the rats. Studies were performed in the Wistar rats under control conditions (6 cases), and with choline deficiency diet for 2, 4, 6, 10 and 12 weeks (6 cases respectively). [sup 99m]Tc-GSA was administered via the inferior vena cava. Immediately after injection, a dynamic imaging study was performed for 30 min. t[sub 90] (the time at which the liver time-activity curve reached 90% of its peak), K[sub u] and K[sub d] (calculated by 2 compartment model) were used as parameters which reflect on asialoglycoprotein receptors on the hepatocytes. t[sub 90] prolonged, and K[sub u] and K[sub d] decreased according to the severity of fatty infiltration. These results suggest that [sup 99m]Tc-GSA is useful for evaluating liver injury induced by fatty infiltration. (author).

  4. Nonalcoholic fatty liver disease progression in rats is accelerated by splenic regulation of liver PTEN/AKT

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    Ziming Wang

    2015-01-01

    Full Text Available Background/Aim: The spleen has been reported to participate in the development of nonalcoholic fatty liver disease (NAFLD, but the mechanism has not been fully characterized. This study aims to elucidate how the spleen affects the development of NAFLD in a rat model. Materials and Methods: Following either splenectomy or sham operation, male Sprague–Dawley (SD rats were fed a high-fat diet to drive the development of NAFLD; animals fed a normal diet were used as controls. Two months after surgery, livers and blood samples were collected. Serum lipids were measured; liver histology, phosphatase and tensin homologue deleted on chromosome 10 (PTEN gene expression, and the ratio of pAkt/Akt were determined. Results: Splenectomy increased serum lipids, except triglyceride (TG and high-density lipoprotein (HDL, in animals fed either a high-fat or normal diet. Furthermore, splenectomy significantly accelerated hepatic steatosis. Western blot analysis and real-time polymerase chain reaction showed splenectomy induced significant downregulation of PTEN expression and a high ratio of pAkt/Akt in the livers. Conclusions: The spleen appears to play a role in the development of NAFLD, via a mechanism involving downregulation of hepatic PTEN expression.

  5. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity.

  6. Transcription Profiles of Marker Genes Predict The Transdifferentiation Relationship between Eight Types of Liver Cell during Rat Liver Regeneration

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    Xiaguang Chen

    2015-07-01

    Full Text Available Objective: To investigate the transdifferentiation relationship between eight types of liver cell during rat liver regeneration (LR. Materials and Methods: 114 healthy Sprague-Dawley (SD rats were used in this experimental study. Eight types of liver cell were isolated and purified with percoll density gradient centrifugation and immunomagentic bead methods. Marker genes for eight types of cell were obtained by retrieving the relevant references and databases. Expression changes of markers for each cell of the eight cell types were measured using microarray. The relationships between the expression profiles of marker genes and transdifferentiation among liver cells were analyzed using bioinformatics. Liver cell transdifferentiation was predicted by comparing expression profiles of marker genes in different liver cells. Results: During LR hepatocytes (HCs not only express hepatic oval cells (HOC markers (including PROM1, KRT14 and LY6E, but also express biliary epithelial cell (BEC markers (including KRT7 and KRT19; BECs express both HOC markers (including GABRP, PCNA and THY1 and HC markers such as CPS1, TAT, KRT8 and KRT18; both HC markers (KRT18, KRT8 and WT1 and BEC markers (KRT7 and KRT19 were detected in HOCs. Additionally, some HC markers were also significantly upregulated in hepatic stellate cells ( HSCs, sinusoidal endothelial cells (SECs , Kupffer cells (KCs and dendritic cells (DCs, mainly at 6-72 hours post partial hepatectomy (PH. Conclusion: Our findings indicate that there is a mutual transdifferentiation relationship between HC, BEC and HOC during LR, and a tendency for HSCs, SECs, KCs and DCs to transdifferentiate into HCs.

  7. 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.

  8. Study on Biological Effects of La(3+) on Rat Liver Mitochondria by Microcalorimetric and Spectroscopic Methods.

    Science.gov (United States)

    Wu, Man; Gao, Jia-Ling; Feng, Zhi-Jiang; Liu, Wen; Zhang, Ye-Zhong; Liu, Yi; Dai, Jie

    2015-09-01

    The effects of lanthanum on heat production of mitochondria isolated from Wistar rat liver were investigated with microcalorimetry; simultaneously, the effects on mitochondrial swelling and membrane potential (Δψ) were determined by spectroscopic methods. La(3+) showed only inhibitory action on mitochondrial energy turnover with IC50 being 55.8 μmol L(-1). In the spectroscopic experiments, La(3+), like Ca(2+), induced rat liver mitochondrial swelling and decreased membrane potential (Δψ), which was inhibited by the specific permeability transition inhibitor, cyclosporine A (CsA). The induction ability of La(3+) was stronger than that of Ca(2+). These results demonstrated that La(3+) had some biotoxicity effect on mitochondria; the effects of La(3+) and Ca(2+) on rat liver mitochondrial membrane permeability transition (MPT) are different, and La represents toxic action rather than Ca analogy.

  9. [Cyclosporin, toxicity and efficacy in rejection of liver allografts in the rat].

    Science.gov (United States)

    Settaf, A; Gugenheim, J; Lahlou, M K; Gigou, M; Capron-Laudereau, M; Charpentier, B; Reynes, M; Lokiec, F; Bismuth, H

    1989-01-01

    52 orthotopic liver transplants were performed in DA to lewis rat strain combination, in order to appreciate cyclosporine toxicity, and efficacy at doses of 10 mg/kg day (G II) and 20 mg/kg/day (GIII) compared to liver allografts in DA/lewis rats. The first signs of cyclosporine hepatotoxicity are biological (increased plasma level of bilirubine and transaminase) that were noticed at the dose of 20 mg/kg/day. Histological signs (cells inclusion, hepatocytic necrosis) appeared late and were less constant as well as difficult to assert creatinine plasma level was the best reflect of cyclosporine nephrotoxicity. Renal toxicity was practically constant at the dose of 20 mg/kg/day. In spite of renal and hepatic toxicity, cyclosporin by itself, allows the abolition of the acute rejection of liver allografts in the rat.

  10. Molecular mechanism of null expression of aldehyde dehydrogenase-1 in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.; Yoshida, Akira [Institute of the City of Hope, Duarte, CA (United States); Yanagawa, Yuchio [Tokohu Univ., Sendai (Japan)

    1996-04-01

    In isozyme systems in general, the pattern of tissue-dependent expression of a given type of isozyme is uniform in various mammalian species. In contrast, a major cytosolic aldehyde dehydrogenase isozyme, termed ALDH1, which is strongly expressed in the livers of humans and other mammals, is hardly detectable in rat liver. Thirteen nucleotides existing in the 5{prime}-promoter region of human, marmoset, and mouse ALDH1 genes are absent in the four rat strains examined. When the 13 nucleotides were deleted from a chloramphenicol acetyltransferase expression construct, which contained the 5{prime} promoter region of the human ALDH1 gene and a low-background promoterless chloramphenicol acetyltransferase expression vector, the expression activity was severely diminished in human hepatic cells. Thus, deletion of the 13 nucleotides in the promoter region of the gene can account for the lack of ALDH1 expression in rat liver. 16 refs., 3 figs.

  11. High-performance liquid chromatographic assay detects pentamidine metabolism by Fisher rat liver microsomes.

    Science.gov (United States)

    Tuttle, R H; Hall, J E; Tidwell, R R

    1997-01-24

    Fisher rat liver microsomes metabolized the antimicrobial drug pentamidine to four new compounds detected by gradient elution reversed-phase high-performance liquid chromatography with variable wavelength detection. Coelution experiments with pentamidine metabolite standards determined the new peaks to be previously identified hydroxylated metabolites of pentamidine, with 1,5-bis(4'-amidinophenoxy)-3-pentanol and 1,5-di-(4'-amidinophenoxy)-2-pentanol formed in the greatest amount. The data contradict a previous report that Fisher rat liver homogenates do not metabolize pentamidine. Pentamidine and its known primary metabolites have almost identical absorption spectra; thus, pentamidine metabolism must be evaluated using gradient elution HPLC to resolve pentamidine from its metabolites. The current assay has now been used to demonstrate that Fisher and Sprague-Dawley rat, mouse, rabbit and human liver microsomes all metabolize pentamidine in vitro.

  12. Discovery of sphingosine 1-O-methyltransferase in rat kidney and liver homogenates

    Institute of Scientific and Technical Information of China (English)

    Santosh J SACKET; Dong-soon IM

    2008-01-01

    Aim:To characterize sphingosine methyltransferase in rat tissues.Methods:By using S-adenosyl-L-(methyl-3H) methionine,enzymatic activity was measured in the rat liver and kidney homogenates.Results:The optimum pH and reaction time for the enzyme assay were pH 7.8 and 1 h.ZnCl2 inhibited the activity,but not MgCl2,CaCl2,CoCl2,or NiCl2.In the kidney homogenate,enzymatic activity was detectable in the cytosol and all membrane fractions from the plasma membrane and other organelles; however,in the liver homogenate,enzymatic activity was detectable in all membrane fractions,but not in the cytosol.We also tested the enzymatic activity with structurally-modified sphingosine derivatives.Conclusion:We found sphingosine l-O-methyltransferase activity in the rat liver and kidney homogenates.

  13. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    Science.gov (United States)

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-01-09

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  14. Effect of Tridax procumbens (Linn.) on bile duct ligation-induced liver fibrosis in rats.

    Science.gov (United States)

    Joshi, P P; Patil, S D; Silawat, N; Deshmukh, P T

    2011-12-01

    The present study was undertaken to clarify whether methanolic extract of Tridax procumbens prevents liver fibrosis in rat. The hepatic fibrosis was induced by 28 days of bile duct ligation in rats. The 4-week treatment with Tridex procumbens reduced the serum aspartate aminotransferase (U L⁻¹), glutamate pyruvate transaminase (U L⁻¹), alkaline phosphatase (IU L⁻¹), lactate dehydrogenase (IU L⁻¹), total bilirubin (mg dL⁻¹), direct bilirubin (mg dL⁻¹) and hydroxyproline (mg gm⁻¹) content in liver and improved the histological appearance of liver section. The results of this study led us to conclude that T. procumbens can reduce the degree of hepatocellular damage and may become antifibrotic agent for liver fibrosis.

  15. Characterization of triptolide hydroxylation by cytochrome P450 in human and rat liver microsomes.

    Science.gov (United States)

    Li, W; Liu, Y; He, Y-Q; Zhang, J-W; Gao, Y; Ge, G-B; Liu, H-X; Huo, H; Liu, H-T; Wang, L-M; Sun, J; Wang, Q; Yang, L

    2008-12-01

    Triptolide, the primary active component of a traditional Chinese medicine Tripterygium wilfordii Hook F, has a wide range of pharmacological activities. In the present study, the metabolism of triptolide by cytochrome P450s was investigated in human and rat liver microsomes. Triptolide was converted to four metabolites (M-1, M-2, M-3, and M-4) in rat liver microsomes and three (M-2, M-3, and M-4) in human liver microsomes. All the products were identified as mono-hydroxylated triptolides by liquid chromatography-mass spectrometry (LC-MS). The studies with chemical selective inhibitors, complementary DNA-expressed human cytochrome P450s, correlation analysis, and enzyme kinetics were also conducted. The results demonstrate that CYP3A4 and CYP2C19 could be involved in the metabolism of triptolide in human liver, and that CYP3A4 was the primary isoform responsible for its hydroxylation.

  16. [Fatal pulmonary mycosis in a diabetic and cirrhotic patient].

    Science.gov (United States)

    Ayadi-Kaddour, Aïda; Braham, Emna; Marghli, Adel; Ismail, Olfa; Helal, Imen; Mlika, Mona; Kilani, Tarak; El Mezni, Faouzi

    2015-04-01

    Pulmonary mucormycosis is a rare, devastating, opportunistic fungal infection, caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. This infection occurs principally in some particular conditions, specially in diabetic patients and immunocompromised host, and rarely in cirrhotic patients. The diagnosis of mucormycosis can only be confirmed by pathological and mycological examination of biopsy specimens. We report a case of pulmonary mucormycosis in a 68-year-old woman with underlying liver cirrhosis and diabetes mellitus. Endoscopic and radiologic findings supported the diagnosis of hydatid cyst of the lung. The patient underwent surgical resection and was started on amphotericin B, after pathological examination. Unfortunately, she succumbed to the infection within one month of surgery.

  17. Copper Transporter 2 Content Is Lower in Liver and Heart of Copper-Deficient Rats

    Directory of Open Access Journals (Sweden)

    Jesse Bertinato

    2010-11-01

    Full Text Available Copper (Cu transporter 2 (Ctr2 is a transmembrane protein that transports Cu across cell membranes and increases cytosolic Cu levels. Experiments using cell lines have suggested that Ctr2 expression is regulated by Cu status. The importance of changes in Ctr2 expression is underscored by recent studies demonstrating that lower Ctr2 content in cells increases the cellular uptake of platinum-containing cancer drugs and toxicity to the drugs. In this study, we examined whether Ctr2 expression is altered by a nutritional Cu deficiency in vivo. Ctr2 mRNA and protein in liver and heart from rats fed a normal (Cu-N, moderately deficient (Cu-M or deficient (Cu-D Cu diet was measured. Rats fed the Cu-deficient diets showed a dose-dependent decrease in liver Ctr2 protein compared to Cu-N rats. Ctr2 protein was 42% and 85% lower in Cu-M and Cu-D rats, respectively. Liver Ctr2 mRNA was 50% lower in Cu-D rats and unaffected in Cu-M rats. In heart, Ctr2 protein was only lower in Cu-D rats (46% lower. These data show that Cu deficiency decreases Ctr2 content in vivo.

  18. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    Science.gov (United States)

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  19. The effect of avocado oils on some liver characteristics in growing rats.

    Science.gov (United States)

    Werman, M J; Mokady, S; Neeman, I; Auslaender, L; Zeidler, A

    1989-05-01

    The effects of various avocado oils on some liver characteristics were studied in growing rats. The rats were fed diets containing 10% (w/w) avocado oil for 4 wk. In comparison with rats fed refined oil obtained from cored fruit by centrifugal separation, rats fed unrefined avocado oil obtained by solvent extraction from the intact fruit, or refined avocado oil containing avocado-seed oil, showed significant growth inhibition, an increase in the amount of hepatic lipids (identified as steatosis by histopathological examination), and a decrease in levels of triglycerides in blood. Rats fed the refined oil containing unsaponifiable material prepared from unrefined oil from the intact fruit showed similar responses. Fatty livers were not induced by feeding rats unrefined avocado oil obtained from intact fruit by centrifugal separation, although a significant decrease in blood triglycerides was observed. There were no significant differences between groups in serum total protein, albumin or bilirubin content or in alanine aminotransferase activity. However, serum alkaline phosphatase activity was increased in rats fed the seed oil, the unrefined solvent-extracted oil from intact fruit, or the unsaponifiables, and aspartate aminotransferase activity was significantly increased in the group fed avocado-seed oil. These data suggest that consumption of avocado oil extracted from intact fruit may cause changes in liver metabolism.

  20. The Preventive Effect of Vitamin C on Styrene-Induced Toxicity in Rat Liver and Kidney

    Directory of Open Access Journals (Sweden)

    Ahmadizadeh

    2015-04-01

    Full Text Available Background Styrene (ST is widely used as an organic solvent in many industrial settings. Increasing evidence indicated that ST induced toxicity in human and animals. Occupational exposure to ST can result in multiple-organ toxicity. Objectives The aim of the present study was to investigate the preventive effect of vitamin C (Vit C on ST- induced toxicity in rat liver and kidney. Materials and Methods Adult male rats were pretreated with 300 mg/kg Vit C intraperitoneally. Control rats received vehicle only (distilled water, D H2O. Thirty minutes later, animals were given different doses (0, 200, 400, or 600 mg/kg of ST. Twenty-four hours later, animals were killed and their blood samples were processed for determination of biochemical parameters. Liver damage was estimated by measuring serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and alkaline phosphatase (ALP activity. nephrotoxicity was evaluated by measuring blood urea nitrogen (BUN and creatinine (CR concentrations. Liver and kidney tissues were removed, fixed and processed for light microscopy. Results Styrene induced a dose-dependent elevation in the AST, ALT, ALP, BUN, and CR levels when compared to those of the control animals. The liver and kidney tissues were intact in control rats. Moreover, ST provoked a dose-dependent injury in the liver and kidney tissues. Vitamin C significantly decreased all biochemical parameters and protected liver and kidney cells against ST-induced toxicity. Conclusions The results of this study showed that Vit C has potential to protect rat liver and kidney tissues against styrene toxicity.

  1. Effects of L-malate on mitochondrial oxidoreductases in liver of aged rats.

    Science.gov (United States)

    Wu, J-L; Wu, Q-P; Peng, Y-P; Zhang, J-M

    2011-01-01

    Accumulation of oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the aging process. The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-malate, a tricarboxylic acid cycle intermediate, plays an important role in transporting NADH from cytosol to mitochondria for energy production. Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. In the present study we focused on the effect of L-malate on the activities of electron transport chain in young and aged rats. We found that mitochondrial membrane potential (MMP) and the activities of succinate dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats were significantly decreased when compared to young control rats. Supplementation of L-malate to aged rats for 30 days slightly increased MMP and improved the activities of NADH-dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats when compared with aged control rats. In young rats, L-malate administration increased only the activity of NADH-dehydrogenase. Our result suggested that L-malate could improve the activities of electron transport chain enzymes in aged rats.

  2. Species and sex differences in propofol glucuronidation in liver microsomes of humans, monkeys, rats and mice.

    Science.gov (United States)

    Mukai, M; Isobe, T; Okada, K; Murata, M; Shigeyama, M; Hanioka, N

    2015-07-01

    Propofol (2,6-diisopropylphenol) is a short-acting anesthetic commonly used in clinical practice, and is rapidly metabolized into glucuronide by UDP-glucuronosyltransferase (UGT). In the present study, propofol glucuronidation was examined in the liver microsomes of male and female humans, monkeys, rats, and mice. The kinetics of propofol glucuronidation by liver microsomes fit the substrate inhibition model for humans and mice, the Hill model for monkeys, and the isoenzyme (biphasic) model for rats. The K(m), V(max), and CL(int) values of human liver microsomes were 50 μM, 5.6 nmol/min/mg protein, and 110 μL/min/mg protein, respectively, for males, and 46 μM, 6.0 nmol/min/mg protein, and 130 μL/min/mg protein, respectively, for females. The rank order of the CL(int) or CL(max) (in vitro clearance) values of liver microsomes was mice humans > monkeys > rats (high-affinity phase) rats (low-affinity phase) in both males and females. Although no significant sex differences were observed in the values of kinetic parameters in any animal species, the in vitro clearance values of liver microsomes were males females in monkeys, rats (high-affinity phase), and mice. These results demonstrated that the kinetic profile of propofol glucuronidation by liver microsomes markedly differed among humans, monkeys, rats, and mice, and suggest that species and sex differences exist in the roles of UGT isoform(s), including UGT1A9, involved in its metabolism.

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

    Science.gov (United States)

    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.

  4. Effect of x radiation on hydroperoxidase activity of rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Platonov, A.G.; Deev, L.I.

    1979-06-01

    The effect of single exposure to total-body x radiation on hydroperoxidase activity (HPA) of rat liver microsomes and levels of cytochromes P-450 and b/sub 5/ in them were studied. Cytochrome b/sub 5/ content was measured in view of data indicative of the possible involvement of this enzyme in breaking down hydroperoxides of the microsomal fraction of the liver.

  5. Protective Effect of Zizphus Vulgaris Extract, on Liver Toxicity in Laboratory Rats

    OpenAIRE

    S. Ebrahimi; Sadeghi, H.; A Pourmahmoudi; SH Askariyan; Askari, S

    2011-01-01

    Introduction & Objective: 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 Zizphus Vulgaris extracts on mice liver. Materials & Methods: This experimental study was conducted at Yasouj University of Medical Sciences in 2010 on 30 healthy adult male Wistar rats. Animals were randomly divided into five equal groups: the control group (receiving, olive oil), control group ...

  6. Can the rat donor liver tolerate prolonged warm ischemia ?

    Institute of Scientific and Technical Information of China (English)

    Ji Qi Yan; Hong Wei Li; Wei Yao Cai; Ming Jun Zhang; Wei Ping Yang

    2000-01-01

    The last two decades of the twentieth century have witnessed increasingly successful rates of liver transplantation. The number of liver transplantations has increased steadily while the number of organ donors has remained relatively constant. Thus a great disparity has developed between the demand and supply of donor organs and remains a major limiting factor for further expansion of liver transplantation. Although many procedures, such as split liver[1] , living-related transplantation[2] , and xenotransplantation[3], have been attempted clinically to overcome the shortage, it is hoped that livers harvested from non-heart-beating donors (NHBDs) would alleviatethe problem of organ shortage, which again becomes the focus of attention[4-9]. However, sensitivity of the liver to warm ischemia remains a major worry for use of theNHBDs. The aim of this animal study was to assess if murine liver could tolerate prolonged period of warm ischemia and to determine the optimum timing of intervention in the cadaver donor in order to preserve liver viability.

  7. Effect of matrine on Kupffer cell activation in cold ischemia reperfusion injury of rat liver

    Institute of Scientific and Technical Information of China (English)

    Xin-Hua Zhu; Yu-Dong Qiu; Hao Shen; Ming-Ke Shi; Yi-Tao Ding

    2002-01-01

    AIM: To study the effect of matrine on activation of Kupffer cell during cold ischemia and reperfusion injury in rat orthotopic liver transplantation (OLT).METHODS: 168 syngeneic SD rats were randomly divided into four groups: untreated group, small-dose treated group, large-dose treated group and sham operation group. After 5 hours of preservation in Ringer's (LR) solution, orthotopic implantation of the donor liver was performed. At 1 h, 2 h, 4 h and 24 h after reperfusion of the portal vein, 6 rats were killed in each group to collect the serum and the liver for assay and pathology.RESULTS: Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). TNF cytotoxicity level at 2 h decreased significantly by matrine treatment (7.94±0.42, 2.39±0.19 and 2.01±0.13 U/ml,respectively; P<0.01), so did the other three time points. The level of hylluronic acid (HA) and alanine transaminase (ALT) decreased significantly in both treated groups, and matrine treatment markedly ameliorated focal necrosis of hepatocytes, inflammatory cells aggregating, rounding and detachment of sinusoidal endothelial cells (SEC). And no significant difference was observed between the treated groups.CONCLUSION: Matrine can inhibit the activation of Kupffer cell and prevent the donor liver from cold preservation and reperfusion injury in rat orthotopic liver transplantation.

  8. THE EXCHANGE OF CONNECTIVE TISSUE BIOPOLYMERS IN THE LIVER OF ALLOXAN DIABETIC RATS

    Directory of Open Access Journals (Sweden)

    S. V. Lomaeva

    2013-01-01

    Full Text Available Aim. Study of the exchange of liver and blood plasma biopolymers of alloxan diabetic rats.Materials and Methods. Diabetes mellitus was modeled in rats by single subcutaneous injection of alloxan tetrahydrate (170 mg per100 gbody weight. Blood glucose, glycosylated hemoglobin were controlled and morphometric study of the pancreas was carried out for the verification of the model. A month later, concentration of glycosaminoglycans, free hydroxyproline and the level of hyaluronidase and collagenolytic activity in plasma were determined. The total concentration of collagen, glycosaminoglycans, and their fractions, the level of hyaluronidase and collagenolytic activity in rat liver homogenate were measured.Results. The level of all the parameters of interest in the liver and blood plasma increased on 30 day after alloxan injection, the accumulation of glycosaminoglycans in the liver occurred mainly due to unsulfonated fraction.Conclusion. The development of experimental diabetes in rats is accompanied by activation of both decay processes and synthesis of biopolymers studied. Accumulation of total collagen and glycosaminoglycans was observed in rats’ liver, which probably lead to the fibrosis changes in it.

  9. Protective effect of doxorubicin induced heat shock protein 72 on cold preservation injury of rat livers

    Institute of Scientific and Technical Information of China (English)

    Hao Chen; Ying-Yan Yu; Ming-Jun Zhang; Xia-Xing Deng; Wei-Ping Yang; Jun Ji; Cheng-Hong Peng; Hong-Wei Li

    2004-01-01

    AIM: To observe the protective effect of heat shock protein 72 (HSP 72) induced by pretreatment of doxorubicin (DXR)on long-term cold preservation injury of rat livers.METHODS: Sprague-Dawley rats were administered intravenously DXR at a dose of 1 mg/kg body mass in DXR group and saline in control group. After 48 h, the rat liver was perfused with cold Linger′s and University of Wisconsin (UW) solutions and then was preserved in UW solution at 4 ℃ for 24, 36 and 48 h. AST, ALT, LDH and hyaluronic acid in preservative solution were determined. Routine HE,immunohistochemical staining for HSP 72 and electron microscopic examination of hepatic tissues were performed.RESULTS: After 24, 36 and 48 h, the levels of AST, ALT and hyaluronic acid in preservative solution were significantly higher in control group than in DXR group (P<0.05), while LDH level was not significantly different between the 2 groups (P>0.05). Hepatic tissues in DXR group were morphologically normal and significantly injured in control group. HSP 72was expressed in hepatocytes and sinusoidal endothelial cells in DXR group but not in control group.CONCLUSION: Pretreatment of DXR may extend the time of rat liver cold preservation and keep liver alive. The expression of HSP 72 in liver can prevent hepatocytes and sinusoidal endothelial cells from long-term cold preservation injury.

  10. Adeno-associated viral vector serotype 5 poorly transduces liver in rat models.

    Directory of Open Access Journals (Sweden)

    Paula S Montenegro-Miranda

    Full Text Available Preclinical studies in mice and non-human primates showed that AAV serotype 5 provides efficient liver transduction and as such seems a promising vector for liver directed gene therapy. An advantage of AAV5 compared to serotype 8 already shown to provide efficient correction in a phase 1 trial in patients suffering from hemophilia B, is its lower seroprevalence in the general population. Our goal is liver directed gene therapy for Crigler-Najjar syndrome type I, inherited severe unconjugated hyperbilirubinemia caused by UGT1A1 deficiency. In a relevant animal model, the Gunn rat, we compared the efficacy of AAV 5 and 8 to that of AAV1 previously shown to be effective. Ferrying a construct driving hepatocyte specific expression of UGT1A1, both AAV8 and AAV1 provided an efficient correction of hyperbilirubinemia. In contrast to these two and to other animal models AAV5 failed to provide any correction. To clarify whether this unexpected finding was due to the rat model used or due to a problem with AAV5, the efficacy of this serotype was compared in a mouse and two additional rat strains. Administration of an AAV5 vector expressing luciferase under the control of a liver specific promoter confirmed that this serotype poorly performed in rat liver, rendering it not suitable for proof of concept studies in this species.

  11. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    Science.gov (United States)

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

  12. Methylene blue attenuates acute liver injury induced by paraquat in rats.

    Science.gov (United States)

    Chen, Jun-Liang; Dai, Li; Zhang, Peng; Chen, Wei; Cai, Gao-Shan; Qi, Xiao-Wei; Hu, Ming-Zhu; Du, Bin; Pang, Qing-Feng

    2015-09-01

    Paraquat (PQ) poisoning often leads to severe oxidative liver injury. Recent studies have reported that methylene blue (MB) can prevent oxidative stress-induced diseases. This study tested the hypothesis that MB treatment reduced acute liver injury induced by PQ in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: (1) normal group, (2) MB group (2mg/kg i.p.), (3) PQ group (35 mg/kg i.p.) and (4) PQ+MB group (MB 2mg/kg i.p. administrated 2h after PQ). We evaluated the changes of liver histopathology, serum liver enzymatic activities, oxidative stress, heme oxygenase-1 expression, and mitochondrial permeability transition. The rats were injected with PQ produced liver injury, evidenced by histological changes and elevated serum alkaline phosphatase and alanine transaminase levels; PQ also led to oxidative stress, an increase of malondialdehyde content and mitochondrial permeability transition pore opening. Pathological damage and all of the above mentioned markers were reversed in the animals treated with MB than in those who received PQ alone. Meanwhile, MB significantly increased the contents of superoxide dismutase, adenosine triphosphate and the expression of heme oxygenase-1. In conclusion, MB had a protective effect against PQ-induced hepatic damage in rats. The mechanisms of the protection seem to be the inhibition of mitochondrial permeability transition opening and the increase of heme oxygenase-1 expression.

  13. Changes in the fatty acid profile of lung, liver and serum of rats intratracheally given silica

    Energy Technology Data Exchange (ETDEWEB)

    Eskelson, C.D.; Stiffel, V.; Owen, J.A.; Chvapil, M.; Vickers, A.; Brendel, K.

    1988-01-01

    The esterified (E) and nonesterified (NE) fatty acid level and profile in the lung, serum, and liver of rats are significantly altered after intratracheal administration of silica. The changes include a silica-specific increase of the total long chain (C/sub 16/-C/sub 20:4/) fatty acid content in the lung, and a decrease in the serum and liver of both groups of rats intratracheally given silica and/or saline. In the silicotic lung, arachidonate and palmitate accumulated at the highest rate. A heat-labile, high-molecular weight component from lung homogenates increases lipogenesis in isolated hepatocytes in vitro. These findings, taken together with evidence indicating increased lipogenesis in the liver of rats treated with silica under identical conditions, suggest a lung-liver communication mechanism which coordinates lipid uptake by the lung and lipid synthesis and release by the liver. The stimulatory factor identified in lung homogenates might play an important regulatory role for hepatic lipogenesis in rats developing silicotic lungs.

  14. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    Energy Technology Data Exchange (ETDEWEB)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Hop Paul Brousse, INSERM, Hepatobiliary Ctr, U785, F-94800 Villejuif (France); Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Univ Paris Sud, Fac Med, F-94800 Villejuif (France); Boisgard, R.; Tavitian, B. [INSERM, U803, F-91400 Orsay (France); Boisgard, R.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Lab Imagerie Mol Expt, F-91400 Orsay (France); Roux, J.; Cales, P. [Univ Angers, UPRES EA 3859, Lab Hemodynam Interact Fibrose et Invas Tumorale H, Angers (France); Clerc, J. [Hop Cochin, AP HP, Dept Nucl Med, F-75014 Paris (France)

    2008-07-01

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III {alpha}, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of {sup 131}I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. {sup 131}I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  15. Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

    DEFF Research Database (Denmark)

    Olsen, Peter Skov; Boesby, S.; Kirkegaard, P.;

    2013-01-01

    growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner's glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner's glands decreased liver regeneration, whereas removal of the submandibular glands had......The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal...

  16. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes

    Science.gov (United States)

    Eagling, Victoria A; Tjia, John F; Back, David J

    1998-01-01

    Aims Chemical inhibitors of cytochrome P450 (CYP) are a useful tool in defining the role of individual CYPs involved in drug metabolism. The aim of the present study was to evaluate the selectivity and rank the order of potency of a range of isoform-selective CYP inhibitors and to compare directly the effects of these inhibitors in human and rat hepatic microsomes. Methods Four chemical inhibitors of human cytochrome P450 isoforms, furafylline (CYP1A2), sulphaphenazole (CYP2C9), diethyldithiocarbamate (CYP2E1), and ketoconazole (CYP3A4) were screened for their inhibitory specificity towards CYP-mediated reactions in both human and rat liver microsomal preparations. Phenacetin O-deethylation, tolbutamide 4-hydroxylation, chlorzoxazone 6-hydroxylation and testosterone 6β-hydroxylation were monitored for enzyme activity. Results Furafylline was a potent, selective inhibitor of phenacetin O-deethylation (CYP1A2-mediated) in human liver microsomes (IC50 = 0.48 μm), but inhibited both phenacetin O-deethylation and tolbutamide 4-hydroxylation (CYP2C9-mediated) at equimolar concentrations in rat liver microsomes (IC50 = 20.8 and 24.0 μm respectively). Sulphaphenazole demonstrated selective inhibition of tolbutamide hydroxylation in human liver microsomes but failed to inhibit this reaction in rat liver microsomes. DDC demonstrated a low level of selectivity as an inhibitory probe for chlorzoxazone 6-hydroxylation (CYP2E1-mediated). DDC also inhibited testosterone 6β-hydroxylation (CYP3A-mediated) in man and rat, and tolbutamide 4-hydroxylase activity in rat. Ketoconazole was a very potent, selective inhibitor of CYP3A4 activity in human liver (IC50 = 0.04 μm). Although inhibiting CYP3A in rat liver it also inhibited all other reactions at concentrations ≤5 μm. Conclusions It is evident that CYP inhibitors do not exhibit the same selectivity in human and rat liver microsomes. This is due to differential selectivity of the inhibitors and/or differences in the CYP

  17. Structures of nucleolus and transcription sites of rRNA genes in rat liver cells

    Institute of Scientific and Technical Information of China (English)

    陶伟; 焦明大; 赫杰; 何孟元; 郝水

    2000-01-01

    We observed the ultrastructure of nucleolus in rat liver cells by conventional electron microscopy, and employed cytochemistry NAMA-Ur DNA specific stain method to analyze the distribution and position of nucleolar DNA in situ. The results showed that nucleolar DNA of rat liver cells comes from nucleolus-associated chromatin, and continuously extends in the dense fibrillar component (DFC) of nucleolus, localizes at the periphery of fibrillar center (FC) and in DFC. Furthermore, by employing anti-DNA/RNA hybrid antibodies, we directly and selectively labeled transcription sites of rRNA genes and testified that localization of transcription sites not only to DFC but also to the periphery of FC.

  18. 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.

  19. Reciprocal effects of dietary sesamin on ketogenesis and triacylglycerol secretion by the rat liver.

    Science.gov (United States)

    Fukuda, N; Miyagi, C; Zhang, L; Jayasooriya, A P; Sakono, M; Yamamoto, K; Ide, T; Sugano, M

    1998-10-01

    The effects of dietary sesamin (a mixture of sesamin and episesamin, 1:1, w/w) on ketone body production and lipid secretion were studied in isolated perfused liver from rats given sesamin. Feeding sesamin at the dietary level of 0.2% from 14 to 16 d resulted in an enlargement of liver weight. Ketone body production was significantly elevated in the livers perfused with oleic acid in comparison with those perfused without an exogenous-free fatty acid, and sesamin feeding caused a stimulation of ketone body production, especially when exogenous oleic acid was provided. On the other hand, the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to increase in the livers perfused with oleic acid compared with those without fatty acid, thought it was consistently lowered by dietary sesamin. The cumulative secretion of triacylglycerol, but not of cholesterol, by the livers from sesamin-fed rats was decreased markedly, especially when exogenous oleic acid was provided, suggesting an inverse relationship between the rates of ketogenesis and triacylglycerol secretion. These results suggest that dietary sesamin exerts its hypotriglyceridemic effect at least in part through an enhanced metabolism of exogenous-free fatty acid to oxidation at the expense of esterification in rat liver.

  20. RNA interference against discoidin domain receptor 2 ameliorates alcoholic liver disease in rats.

    Directory of Open Access Journals (Sweden)

    Zheng Luo

    Full Text Available Discoidin domain receptor 2 (DDR2 is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.

  1. RNA interference against discoidin domain receptor 2 ameliorates alcoholic liver disease in rats.

    Science.gov (United States)

    Luo, Zheng; Liu, Huimin; Sun, Xiaomeng; Guo, Rong; Cui, Ruibing; Ma, Xiangxing; Yan, Ming

    2013-01-01

    Discoidin domain receptor 2 (DDR2) is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.

  2. Expression patterns and action analysis of genes associated with blood coagulation responses during rat liver regeneration

    Institute of Scientific and Technical Information of China (English)

    Li-Feng Zhao; Wei-Min Zhang; Cun-Shuan Xu

    2006-01-01

    AIM:To study the blood coagulation response after partial hepatectomy (PH) at transcriptional level.METHODS:After PH of rats, the associated genes with blood coagulation were obtained through reference to the databases, and the gene expression changes in rat regenerating liver were analyzed by the Rat Genome 230 2.0 array.RESULTS: It was found that 107 genes were associated with liver regeneration. The initially and totally expressing gene numbers occurring in initiation phase of liver regeneration (0.5-4 h after PH), G0/G1 transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) were 44, 11, 58, 7 and 44, 33,100, 71 respectively, showing that the associated genes were mainly triggered in the forepart and prophase, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups:only up-, predominantly up-, only down-, predominantly down-, up- and down-regulation, involving 44, 8, 36,13 and 6 genes, respectively, and the total times of their up- and down-regulation expression were 342 and 253, respectively, demonstrating that the number of the up-regulated genes was more than that of the downregulated genes. Their time relevance was classified into 15 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns,they were classified into 29 types, suggesting that their protein activities were diverse and complex during liver regeneration.CONCLUSION: The blood coagulation response is enhanced mainly in the forepart, prophase and anaphase of liver regeneration, in which the response in the forepart, prophase of liver regeneration can prevent the bleeding caused by partial hepatectomy, whereas that in the anaphase contributes to the structure-function reorganization of regenerating liver. In the process,107 genes associated with liver

  3. Effect of L-arginine supplement on liver regeneration after partial hepatectomy in rats

    Directory of Open Access Journals (Sweden)

    Kurokawa Tsuyoshi

    2012-05-01

    Full Text Available Abstract Background Nitric oxide (NO has been reported to be a key mediator in hepatocyte proliferation during liver regeneration. NO is the oxidative metabolite of L-arginine, and is produced by a family of enzymes, collective termed nitric oxide synthase (NOS. Thus, administration of L-arginine might enhance liver regeneration after a hepatectomy. Another amino acid, L-glutamine, which plays an important role in catabolic states and is a crucial factor in various cellular and organ functions, is widely known to enhance liver regeneration experimentally. Thus, the present study was undertaken to evaluate the effects of an L-arginine supplement on liver regeneration, and to compared this with supplementation with L-glutamine and L-alanine (the latter as a negative control, using a rat partial hepatectomy model. Methods Before and after a 70% hepatectomy, rats received one of three amino acid solutions (L-arginine, L-glutamine, or L-alanine. The effects on liver regeneration of the administered solutions were examined by assessment of restituted liver mass, staining for proliferating cell nuclear antigen (PCNA, and total RNA and DNA content 24 and 72 hours after the operation. Results At 72 hours after the hepatectomy, the restituted liver mass, the PCNA labeling index and the DNA quantity were all significantly higher in the L-arginine and L-glutamine groups than in the control. There were no significant differences in those parameters between the L-arginine and L-glutamine groups, nor were any significant differences found between the L-alanine group and the control. Conclusion Oral supplements of L-arginine and L-glutamine enhanced liver regeneration after hepatectomy in rats, suggesting that an oral arginine supplement can clinically improve recovery after a major liver resection.

  4. Protective effects of Centella asiatica leaf extract on dimethylnitrosamine-induced liver injury in rats

    Science.gov (United States)

    Choi, Myung-Joo; Zheng, Hong-Mei; Kim, Jae Min; Lee, Kye Wan; Park, Yu Hwa; Lee, Don Haeng

    2016-01-01

    Oxidative stress in liver injury is a major pathogenetic factor in the progression of liver damage. Centella asiatica (L.) Urban, known in the United States as Gotu kola, is widely used as a traditional herbal medicine in Chinese or Indian Pennywort. The efficacy of Centella asiatica is comprehensive and is used as an anti-inflammatory agent, for memory improvement, for its antitumor activity and for treatment of gastric ulcers. The present study investigated the protective effects of Centella asiatica on dimethylnitrosamine (DMN)-induced liver injury in rats. The rats in the treatment groups were treated with Centella asiatica at either 100 or 200 mg/kg in distilled water (D.W) or with silymarin (200 mg/kg in D.W) by oral administration for 5 days daily following intraperitoneal injections of 30 mg/kg DMN. Centella asiatica significantly decreased the relative liver weights in the DMN-induced liver injury group, compared with the control. The assessment of liver histology showed that Centella asiatica significantly alleviated mass periportal ± bridging necrosis, intralobular degeneration and focal necrosis, with fibrosis of liver tissues. Additionally, Centella asiatica significantly decreased the level of malondialdehyde, significantly increased the levels of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase and catalase, and may have provided protection against the deleterious effects of reactive oxygen species. In addition, Centella asiatica significantly decreased inflammatory mediators, including interleukin (IL)-1β, IL-2, IL-6, IL-10, IL-12, tumor necrosis factor-α, interferon-γ and granulocyte/macrophage colony-stimulating factor. These results suggested that Centella asiatica had hepatoprotective effects through increasing the levels of antioxidant enzymes and reducing the levels of inflammatory mediators in rats with DMN-induced liver injury. Therefore, Centella asiatica may be useful in preventing liver damage. PMID:27748812

  5. The role of cyclooxygenase-2/prostanoid pathway in visceral pain induced liver stress response in rats

    Institute of Scientific and Technical Information of China (English)

    PISTON Donald; WANG Shan; FENG Yi; YE Ying-jiang; ZHOU Jing; JIANG Ke-wei; XU Feng; ZHAO Yong; CUI Zhi-rong

    2007-01-01

    Background Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostanoids from arachidonic acid.COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway.Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/reperfusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.Methods Fifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase (GST) activity, COX-2 mRNA, prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-Ketone-prostaglandin F1α (6-K-PGF1α) contents were assessed.Results Thirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group (P<0.01 and P<0.05 respectively), accompanied by colonic inflammation. Liver GST activity levels significantly dropped (P<0.05). Liver COX-2 mRNA expression significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1α concentrations. NS398 and morphine both ameliorated post-stress liver GST activity (P<0.05 and P<0.01respectively), decreased stress

  6. PASS-Predicted Hepatoprotective Activity of Caesalpinia sappan in Thioacetamide-Induced Liver Fibrosis in Rats

    Directory of Open Access Journals (Sweden)

    Farkaad A. Kadir

    2014-01-01

    Full Text Available The antifibrotic effects of traditional medicinal herb Caesalpinia sappan (CS extract on liver fibrosis induced by thioacetamide (TAA and the expression of transforming growth factor β1 (TGF-β1, α-smooth muscle actin (αSMA, and proliferating cell nuclear antigen (PCNA in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY, and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson’s trichrome staining, immunohistochemical analysis, and western blotting. In vivo determination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1, and matrix metalloproteinases (MPPS was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1, αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.

  7. Glutamic oxaloacetic transaminase isozymes from rat liver. Purification and physicochemical characterization.

    Science.gov (United States)

    Huynh, Q K; Sakakibara, R; Watanabe, T; Wada, H

    1980-07-01

    Glutamic oxaloacetic transaminase isozymes were purified simultaneously to homogeneity from rat liver with high yields. Three subforms of mitochondrial isozyme and three subforms of cytosolic isozyme were separated by chromatography on CM-Sephadex and electrophoresis on polyacrylamide gel. The general enzymatic properties of the purified isozymes such as their kinetic parameters, isoelectric points, molecular weights, amino acid compositions, NH2-terminal amino acid sequences and COOH-terminal amino acids were determined. Most of these properties of the isozymes are similar to those of the corresponding isozymes from other sources, such as rat brain and pig and human heart. In amino acid compositions, cytosolic isozyme from rat liver has more proline and glycine and less arginine, threonine and leucine than pig heart cytosolic isozyme; the mitochondrial isozyme has more glutamic acid and glycine and less serine than the corresponding pig heart isozyme. The NH2-terminal amino acid sequences of GOT isozymes from rat liver were identical with those of the GOT isozymes from pig heart up to the 10th residues except for the 5th residues. The subforms of mitochondrial isozyme from rat liver were generated on storage at 4 degrees C for 4-8 weeks.

  8. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Dong-Chang Zhao; Jun-Xia Lei; Rui Chen; Wei-Hua Yu; Xiu-Ming Zhang; Shu-Nong Li; Peng Xiang

    2005-01-01

    AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing inflammation, collagen deposition, and remodeling. These results provide a clue to treatment of liver fibrosis. The aim of this study was to investigate the effect of infusion of bone marrow (BM)-derived MSCs on the experimental liver fibrosis in rats.METHODS: MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats induced with carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN).There were two random groups on the 42nd d of CCl4:CCl4/MSCs, to infuse a dose of MSCs alone; CCl4/saline,to infuse the same volume of saline as control. There were another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10; DMN20/MSCs, to infuse the same dose of MSCson d 20. The morphological and behavioral changes ofrats were monitored everyday. After 4-6 wk of MSCs administration, all rats were killed and fibrosis index were assessed by histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of liver were tested by immunohistochemistry and quantified by IBAS 2.5 software. Male rats sex determination region on the Y chromosome (sry) gene were explored by PCR.RESULTS: Compared to controls, infusion of MSCsreduced the mortality rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model (2040% vs 90%).The amount of collagen deposition and alpha-SMA staining was about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The similar results were observed in fibrosis index. And the effect of the inhibition of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was positive in the liver of rats with MSCs treatment by PCR.CONCLUSION: MSCs treatment can protect against

  9. Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats.

    Science.gov (United States)

    Kubota, Masatoshi; Watanabe, Reiko; Yamaguchi, Miki; Hosojima, Michihiro; Saito, Akihiko; Fujii, Mikio; Fujimura, Shinobu; Kadowaki, Motoni

    2016-10-01

    We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (Pdiabetes, fatty liver and diabetic nephropathy.

  10. Portal Vein Thrombosis in non cirrhotic patients

    NARCIS (Netherlands)

    M.C.W. Spaander (Manon)

    2010-01-01

    textabstractExtrahepatic portal vein thrombosis (EPVT) is the most common cause of portal hypertension in non- cirrhotic patients. EPVT has been defined as an obstruction of the extrahepatic portal vein with or without involvement of the intrahepatic portal veins. Although the portal vein accounts f

  11. The role of hydrogen peroxide on mesenteric artery RhoA/ROCK signal pathway in cirrhotic rats with portal hypertension%过氧化氢在肝硬化门静脉高压症大鼠肠系膜动脉RhoA/ROCK信号通路中的作用

    Institute of Scientific and Technical Information of China (English)

    段明; 刘德军; 秦骏; 吴志勇; 罗蒙; 陈炜

    2014-01-01

    目的 探讨过氧化氢(H2O2)对胆总管结扎诱导的肝硬化门静脉高压症(PHT)大鼠肠系膜动脉收缩反应性的影响及其在RhoA/Rho激酶(ROCK)信号通路中的作用机制.方法 结扎胆总管建立肝硬化门静脉高压症大鼠模型.每日1次腹腔内注射生理盐水或聚乙二醇-过氧化氢酶(PEG-catalase,10 000 U/kg)共8d,相应处理正常大鼠.测定肠系膜动脉H2O2含量,利用血管灌流系统测定肠系膜微动脉对去甲肾上腺素的反应.检测大鼠肠系膜动脉α1肾上腺素能受体和β-arrestin2蛋白表达及其相互作用的变化,以及肠系膜动脉内ROCK-1蛋白量和活性的变化.结果 肝硬化PHT大鼠的离体肠系膜微动脉对去甲肾上腺素剂量反应曲线右移,EC50升高,PEG-catalase降低动脉过氧化氢含量后能逆转上述表现.各组肠系膜动脉的α1肾上腺素能受体含量不变.但是,PEG-cat-alase处理后肝硬化PHT大鼠肠系膜动脉内β-arrestin-2蛋白量降低,与α1肾上腺素能受体结合程度也降低;PHT大鼠肠系膜动脉内ROCK-1蛋白含量及其活性明显升高.结论 肝硬化PHT肠系膜动脉H2O2含量升高,引起抑制蛋白β-arrestin-2水平上升,与α1肾上腺素能受体结合能力增强,使得ROCK蛋白含量和活性均明显下降,造成肠系膜动脉对缩血管物质的收缩低反应性.%Objective To explore the role of hydrogen peroxide in mesenteric artery contraction of cirrhotic rats with portal hypertension,which was induced by bile duct ligation.Possible mechanism in RhoA/ROCK signal pathway was also part of the focus.Methods The bile duct ligation-induced cirrhotic rats and normal rats (control group) were treated equally with PEG-catalase(10 000 U/kg-1 · d-1,ip.) or by its vehicle for 8 days.Then the level of H2O2 in mesenteric arteries was detected.The contractile response to norepinephrine of arterioles was analyzed by vascular perfusion system.The protein expressions of the α1 adrenergic receptor

  12. 不同病因肝硬化患者肝实时剪切波弹性成像测值范围比较%Comparison of the liver Young's modulus value range of cirrhotic patients with different etiologies by real-time ;shear wave elastography

    Institute of Scientific and Technical Information of China (English)

    汪惠鹏; 韩秀梅; 王学梅

    2015-01-01

    目的:分析不同病因的肝硬化患者肝杨氏模量值是否有差异。方法收集经临床确诊的肝硬化失代偿期患者199例,其中乙型肝炎后肝硬化患者139例,丙型肝炎后肝硬化患者26例,酒精性肝硬化患者34例。选择同期50名健康志愿者作为健康对照组。所有受试者均进行肝实时剪切波弹性成像检查,测量并记录肝组织的杨氏模量值,分析比较各组受试者肝组织的杨氏模量值差异。结果健康对照组的肝组织杨氏模量值最低,为(4.81±0.9)kPa。乙肝后肝硬化组、丙肝后肝硬化组、酒精性肝硬化组的肝组织杨氏模量值依次增高,分别为(16.3±8.9)kPa、(17.8±4.8)kPa、(30.6±12.3)kPa,组间差异有统计学意义(F =27.95,P <0.01)。结论实时剪切波弹性成像技术测量的不同病因肝硬化患者的肝组织杨氏模量值有一定的差异。%Objective To analyze the difference of Young's modulus between cirrhotic patients with different etiologies.Methods There were 1 99 patients with decompensated cirrhosis enrolled in this study, all of them had been diagnosed clinically.There were 139 cases of hepatitis B patients with cirrhosis,26 cases of hepatitis C patients with liver cirrhosis,34 cases of patients with alcoholic cirrhosis,and selected 50 healthy volunteers as control group in the same period.All subj ects underwent liver shear wave elastography examination,measured and recorded the Young's modulus,and compared the difference between each groups.Results The Young's modulus of liver in the healthy control group was (4.81±0.9)kPa,which was lowest in all groups.The Young's modulus of hepatitis B cirrhosis,hepatitis C cirrhosis,alcoholic cirrhosis increased successively,which was (16.3±8.9)kPa,(17.8±4.8)kPa,(30.6±12.3)kPa,respectively,and the difference between the groups was statistically significant(F =27.95,P <0.01).Conclusions There were some differences of the Young's modulus of cirrhotic patients with

  13. The influence of vitamin E supplementation on the oxidative status of rat liver

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    Đurašević S.F.

    2010-01-01

    Full Text Available We tested to see if the additional intake of vitamin E in the form of α-tocopheryl-succinate would improve liver antioxidative protection. Thus, we studied the tissue oxidative status in rats supplemented by two doses of the antioxidant over a four week period of time. Our results confirmed that the additional intake of vitamin E decreased the liver lipid peroxidation level and SOD activity level and preserved its vitamin C content. However, the hydrogen peroxide content and catalase activity remained unchanged, probably due to the mechanism of vitamin E liver metabolism. .

  14. Reciprocal Effects of Dietary Sesamin on Ketogenesis and Triacylglycerol Secretion by the Rat Liver

    OpenAIRE

    Fukuda, Nobuhiro; Miyagi, Chika; Zhang, Lei; Jayasooriya, Anura P.; Sakono, Masanobu; Yamamoto, Kyosuke; Ide, Takashi; Sugano, Michihiro

    1998-01-01

    The effects of dietary sesamin (a mixture of sesamin and episesamin, 1:1, w/w) on ketone body production and lipid secretion were studied in isolated perfused liver from rats given sesamin. Feeding sesamin at the dietary level of 0.2% from 14 to 16 d resulted in an enlargement of liver weight. Ketone body production was significantly elevated in the livers perfused with oleic acid in comparison with those perfused without an exogenous-free fatty acid, and sesamin feeding caused a stimulation ...

  15. Influência do grau de insuficiência hepática e do índice de congestão portal na recidiva hemorrágica de cirróticos submetidos a cirurgia de Teixeira-Warren Role of liver function and portal vein congestion index on rebleeding in cirrhotics after distal splenorenal shunt

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    Fabio Gonçalves Ferreira

    2007-06-01

    distal em relação aos Child-Pugh A.BACKGROUND: Bleeding from esophagogastric varices is the worst and most lethal complication of cirrhotic portal hypertension. Distal splenorenal shunt (Warren’s surgery is used in the therapeutic of this patients, Child A and B, with rebleeding after clinical endoscopic therapy. The portal vein congestion index is elevated in cirrhotic portal hypertension and could predict rebleeding after Warren’s surgery in these patients. AIM: To verify if the portal vein congestion index or liver function (Child-Pugh at preoperative are predictive factors of rebleeding after Warren’s surgery. METHODS: Sixty-two cirrhotic patients were submitted to Warren’s surgery at "Santa Casa" Medical School and Hospital - Liver and Portal Hypertension Unit, São Paulo, SP, Brazil. Fifty-eight were analyzed for Child-Pugh class and 36 for portal vein congestion index, divided in two groups: with or without rebleeding and statistical analysis was performed. RESULTS: In the rebleeding group, 69% were Child B, with portal vein congestion index = 0.09. The group without rebleeding show us 62% patients Child A with portal vein congestion index = 0.076. The difference was significant for Child-Pugh class but not to portal vein congestion index. CONCLUSION: Portal vein congestion index was not predictive of rebleeding after Warren’s surgery, but cirrhotics Child B have more chance to rebleed after this surgery than Child A.

  16. Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver.

    Science.gov (United States)

    Sahin, Mehmet; Cam, Hakan; Olgar, Seref; Tunc, Sevket Ercan; Arslan, Cagatay; Uz, Efkan; Yilmaz, H Ramazan

    2006-10-01

    Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.

  17. Liver regeneration with l-glutamine supplemented diet: experimental study in rats

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    Cibelle Ribeiro Magalhães

    2014-04-01

    Full Text Available OBJECTIVE: To assess liver regeneration in rats after 60% hepatectomy with and without supplementation of L-glutamine through liver weight changes, laboratory parameters and histological study. METHODS: 36 male rats were divided into two groups: glutamine group and control group. Each group was subdivided into three subgroups, with death in 24h, 72h and seven days. The glutamine group received water and standard diet supplemented with L-glutamine, and the control recieved 0.9% saline. In all subgroups analysis of liver regeneration was made by the Kwon formula, study of liver function (AST, ALT, GGT, total bilirubin, indirect and indirect bilirubin and albumin and analysis of cell mitosis by hematoxylin-eosin. RESULTS: In both groups there was liver regeneration by weight gain. Gamma-GT increased significantly in the control group (p < 0.05; albumin increased in the glutamine group. The other indicators of liver function showed no significant differences. Histological analysis at 72h showed a higher number of mitoses in the glutamine group, with no differences in other subgroups. CONCLUSION: Diet supplementation with L glutamine is beneficial for liver regeneration.

  18. Surface proteins in normal and transformed rat liver epithelial cells in culture.

    Science.gov (United States)

    Bannikov, G. A.; Saint Vincent, L.; Montesano, R.

    1980-01-01

    The pattern of surface proteins of different types of normal and transformed rat liver cells have been studied in culture by means of lactoperoxidase-catalysed iodination procedures, followed by SDS-gel electrophoresis. The cells examined were primary cultures of epithelial liver cells, long-term cultures of epithelial liver cells, in vitro transformed epithelial liver cell lines and liver tumour-cell lines; mesenchymal cells from liver and skin were also examined. The principal surface proteins of primary cultures of epithelial cells from adult or neonatal rats had components with mol. wts of 140,000-160,000, 100,000 and 40,000-70,000. A band that had the same position as fibronectin from mesenchymal cells was also present and this band, as well as other iodinated components, were less sensitive to trypsin than fibroblastic fibronectin. A similar pattern of iodinated proteins was seen in long-term cultures of epithelial liver cells, with a great reduction in the number and intensity of the bands in the mol. wt region below 100,000. Almost all the in vitro transformed and tumour epithelial cell lines contain a protein with a mol. wt 135,000 as one of the major iodinated bands, and in contrast to the observation in transformed fibroblasts, the fibronectin was retained by most of these transformed cell lines. Images Fig. 1 Fig. 2 Fig. 3 PMID:7053205

  19. Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats

    Science.gov (United States)

    Davidson, Alec J.; Stokkan, Karl-Arne; Yamazaki, Shin; Menaker, Michael

    2002-01-01

    The mammalian Per1 gene is an important component of the core cellular clock mechanism responsible for circadian rhythms. The rodent liver and other tissues rhythmically express Per1 in vitro but typically damp out within a few cycles. In the liver, the peak of this rhythm occurs in the late subjective night in an ad lib-fed rat, but will show a large phase advance in response to restricted availability of food during the day. The relationship between this shift in the liver clock and food-anticipatory activity (FAA), the circadian behavior entrained by daily feeding, is currently unknown. Insulin is released during feeding in mammals and could serve as an entraining signal to the liver. To test the role of insulin in the shift in liver Per1 expression and the generation of FAA, per-luciferase transgenic rats were made diabetic with a single injection of streptozotocine. Following 1 week of restricted feeding and locomotor activity monitoring, liver was collected for per-luc recording. In two separate experiments, FAA emerged and liver Per1 phase-shifted in response to daytime 8-h food restriction. The results rule out insulin as a necessary component of this system.

  20. Effects of quercetin on polychlorinated biphenyls-induced liver injury in rats

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    Cléia Rocha de Oliveira

    2014-05-01

    Full Text Available Introduction: Polychlorinated biphenyls (PCBs, used as pesticides in agriculture, can lead to irreversible injuries in living organisms, particularly in liver. Oxidative stress has been implicated in the liver pathogenesis induced by different molecules, including PCBs. It has been demonstrated that quercetin, an antioxidant flavonoid found in the diet, exhibits a potent antioxidant effect in different liver pathologies. Objective: To evaluate oxidative stress caused by PCBs in liver and the antioxidant activity of quercetin. Methodology: We used male Wistar rats (n = 36, divided in 4 groups: control, quercetin (50 mg/kg/day, PCBs (0.4 ml/kg/day, and rats treated with both PCBs and quercetin. On day 25 blood was collected to assess liver integrity (enzymes AST, ALT and ALP, and liver samples to measure oxidative stress (TBARS, activity of antioxidant enzymes (SOD, CAT, GPx and DNA damage (micronucleus assay, and histological damage. Results: TBARS concentration and SOD activity were significantly higher in PCBs animals as compared to the PCB group receiving quercetin. CAT and GPx decreased in PCBs and increased when quercetin was added. The histological analysis showed damage to hepatocytes in PCBs, but quercetin was able to afford protection against such damage. The micronucleus test showed there was an increase in the production of microclenucleus compared to control, and quercetin was able to reduce this effect. Conclusion: Contamination with PCBs led to increased lipid peroxidation and DNA damage, and the use of antioxidant quercetin was effective in reducing PCBs-induced liver injury.

  1. Distribution of nitric oxide synthase positive neurons in the substantia nigra of rats with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:Nitrogen monoxide plays an important role in the physiological activity and pathological process of striatum in substantia nigra, and the nitric oxide synthase in substantia nigra may have characteristic changes after liver cirrhosis.OBJECTIYE: To observe the distribution and forms of nitric oxide synthase (NOS) positive neurons and fibers in substantia nigra of rats with liver cirrhosis.DESIGN: A comparative observational experiment.SETTINGS: Beijing Friendship Hospital; Capital Medical University.MATERIALS: Twenty 4-month-old male Wistar rats (120 - 150 g) of clean grade, were maintained in a 12-hour light/dark cycle at a constant temperature with free access to standard diet and water. Cryostat microtome (LEICA, Germany); All the reagents were purchased from Sigma Company.METHODS: The experiment was carried out in the Department of Anatomy (key laboratory of Beijing city),Capital Medical University from July 2000 to March 2002. The rats were randomly divided into normal group (n=10) and liver fibrosis group (n=10). Rats in the liver fibrosis group were subcutaneously injected with 60% CCl4 oil at a dose of 5 mL/kg for the first time, and 3 mL/kg for the next 14 times, twice a week,totally 15 times. Liver fibrosis of grades 5 - 6 was taken as successful models. Whereas rats in the normal group were not given any treatment. Four months after CCl4 treatment, all the rats were anesthetized to remove brain, and frontal frozen serial sections were prepared. The expressions of nitric oxide synthase positive neurons in substantia nigra of rats were observed under inverted microscope. The number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra were detected with NADPH-diaphorase staining.MAIN OUTCOME MEASURES: ①Number and gray scale of cell body of nitric oxide synthase positive neurons in substantia nigra; ②Expressions of nitric oxide synthase positive neurons in substantia nigra.RESULTS: All the 20 rats were

  2. Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver

    Institute of Scientific and Technical Information of China (English)

    Samuel Wyllie; Neal R Barshes; Feng-Qin Gao; Saul J Karpen; John A Goss

    2008-01-01

    AIM: To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS: The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution.RESULTS: In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 min of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-κB was found between control and P-selectin antibody-treated livers.CONCLUSION: In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.

  3. Lipid composition of liver in rats fed diets supplemented with egg yolks of modified composition

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    Hodžić Aida

    2012-01-01

    Full Text Available The aim of this study was to examine the effects of diets supplemented with egg yolks of modified composition on the fatty-acid composition and lipid content in rat’s liver. During four weeks of the experiment 64 Wistar rats were divided into four groups of 16 individuals each (eight individuals of both sexes and fed a commercial feed mixture for rats (group C or diet containing 70% commercial mixture for rats and 30% freshly cooked egg yolks from laying hens fed diets with 3% fish oil (group F, 3% palm olein (group P or 3% lard (group L. Dietary supplementation with egg yolks significantly increased the hepatic cholesterol pool in rats, regardless of the type of fat in the diet of laying hens from which the eggs originated. The content of α-linolenic acid in the liver of male rats in group P was 4-6 times higher compared to males in the other groups. Liver lipids and their fatty-acid composition differ by both, sex and dietary modified egg yolk composition in rats.

  4. The Effect of Seaweed Eucheuma cottonii on Superoxide Dismutase (SOD Liver of Hypercholesterolemic Rats

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    TUTIK WRESDIYATI

    2008-09-01

    Full Text Available Intracellular antioxidant superoxide dismutase (SOD was reported decreased in the liver and kidney of hypercholesterolemic rats. This study was conducted to observe the effect of seaweed Eucheuma cottonii powder on the profile of blood cholesterol and the level of SOD in liver tissues of hypercholesterolemic rats by using immunohistochemical technique. Twenty male Wistar rats were used for this study. Those rats were divided into four groups; (i negative control group (A, (ii hypercholesterolemia group treated by 5% seaweed powder (B, (iii hypercholesterolemia group treated by 10% seaweed powder (C, and (iv Positive control group or hypercholesterolemia group (D. The experiment was carried out for 35 days. Hypercholesterolemia condition (> 130 mg/dl, except group A, was achieved by feeding the rats with commercial diet containing 1% cholesterol. Drinking water was given ad libitum for 40 days. The results showed that seaweed powder decreased the total cholesterol, low density lipoprotein (LDL, triglyceride, and increased the level of high density lipoprotein (HDL and SOD status in the liver tissues of hypercholesterolemic rats. The treatment of 10% seaweed powder gave better results than that of 5%. These results suggested that dietary fiber such in the seaweed powder has antioxidant activity.

  5. Convenient and efficient enrichment of the CD133+ liver cells from rat fetal liver cells as a source of liver stem/progenitor cells.

    Science.gov (United States)

    Liu, Wei-hui; Li, Ren; Dou, Ke-feng

    2011-03-01

    Although the stem cells are commonly isolated by FACS or MACS, they are very expensive and these is no specific marker for liver stem/progentior cells (LSPCs). This paper applied a convenient and efficient method to enrich LSPCs. The fetal liver cells (FLCs) were firstly enriched by Percoll discontinuous gradient centrifugation (PDGC) from the rat fetal liver. Then the FLCs in culture were purified to be homogeneous in size by differential trypsinization and differential adherence (DTDA). Flow cytometric analysis revealed more than half of the purified FLCs expressed alternative markers of LSPCs (CD117, c-Met, Sca-1, CD90, CD49f and CD133). In other words, the purified FLCs were heterogeneous. Therefore, they were sequentially layered into six fractions by Percoll continuous gradient centrifugation (PCGC). Both CD133 and CD49f expressed decreasingly from fraction 1 to 6. In fraction 1 and 2, about 85% FLCs expressed CD133, which were revealed to be LSPCs by high expressions of AFP and CK-19, low expressions of G-6-P and ALB. To conclude, the purity of CD133(+) LSPCs enriched by combination of PDGC, DTDA and PCGC is close to that obtained by MACS. This study will greatly contribute to two important biological aspects: liver stem cells isolation and liver cell therapy.

  6. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver

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    Azzouz I

    2013-12-01

    Full Text Available Inès Azzouz, Hamdi Trabelsi, Amel Hanini, Soumaya Ferchichi, Olfa Tebourbi, Mohsen Sakly, Hafedh AbdelmelekLaboratory of Integrative Physiology, Faculty of Sciences of Bizerte, Carthage University, TunisiaAbstract: The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip] in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip and selenium (0.20 mg/L, per os [by mouth] led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium to malondialdehyde level in rat liver.Keywords: nanocomplexes biosynthesis, antioxidative responses, X-ray diffraction, fluorescence microscopy, liver

  7. Effect of Oenanthe Javanica Extract on Antioxidant Enzyme in the Rat Liver

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    Choong-Hyun Lee

    2015-01-01

    Full Text Available Background: Oenanthe javanica (O. javanica has been known to have high antioxidant properties via scavenging reactive oxygen species. We examined the effect of O. javanica extract (OJE on antioxidant enzymes in the rat liver. Methods: We examined the effect of the OJE on copper, zinc-superoxide dismutase (SOD1, manganese superoxide dismutase (SOD2, catalase (CAT, and glutathione peroxidase (GPx in the rat liver using immunohistochemistry and western blot analysis. Sprague-Dawley rats were randomly assigned to three groups; (1 normal diet fed group (normal-group, (2 diet containing ascorbic acid (AA-fed group (AA-group as a positive control, (3 diet containing OJE-fed group (OJE-group. Results: In this study, no histopathological finding in the rat liver was found in all the experimental groups. Numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells and their protein levels were significantly increased in the AA-fed group compared with those in the normal-group. On the other hand, in the OJE-group, numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells in the liver were significantly increased by about 190%, 478%, 685%, and 346%, respectively, compared with those in the AA-group. In addition, protein levels of SOD1, SOD2, CAT, and GPx in the OJE-group were also significantly much higher than those in the AA-group. Conclusion: OJE significantly increased expressions of SOD1 and SOD2, CAT, and GPx in the liver cells of the rat, and these suggests that significant enhancements of endogenous enzymatic antioxidants by OJE might be a legitimate strategy for decreasing oxidative stresses in the liver.

  8. Effect of Oenanthe Javanica Extract on Antioxidant Enzyme in the Rat Liver

    Institute of Scientific and Technical Information of China (English)

    Choong-Hyun Lee; Joon-Ha Park; Jeong-Hwi Cho; In-Hye Kim; Ji-Hyeon Ahn; Jae-Chul Lee; Bai Hui Chen

    2015-01-01

    Background:Oenanthe javanica (O.javanica) has been known to have high antioxidant properties via scavenging reactive oxygen species.We examined the effect of O.javanica extract (OJE) on antioxidant enzymes in the rat liver.Methods:We examined the effect of the OJE on copper,zinc-superoxide dismutase (SOD1),manganese superoxide dismutase (SOD2),catalase (CAT),and glutathione peroxidase (GPx) in the rat liver using immunohistochemistry and western blot analysis.Sprague-Dawley rats were randomly assigned to three groups;(1) normal diet fed group (normal-group),(2) diet containing ascorbic acid (AA)-fed group (AA-group) as a positive control,(3) diet containing OJE-fed group (OJE-group).Results:In this study,no histopathological finding in the rat liver was found in all the experimental groups.Numbers of SOD1,SOD2,CAT,and GPx immunoreactive cells and their protein levels were significantly increased in the AA-fed group compared with those in the normal-group.On the other hand,in the OJE-group,numbers of SOD1,SOD2,CAT,and GPx immunoreactive cells in the liver were significantly increased by about 190%,478%,685%,and 346%,respectively,compared with those in the AA-group.In addition,protein levels of SOD 1,SOD2,CAT,and GPx in the OJE-group were also significantly much higher than those in the AA-group.Conclusion:OJE significantly increased expressions of SOD 1 and SOD2,CAT,and GPx in the liver cells of the rat,and these suggests that significant enhancements of endogenous enzymatic antioxidants by OJE might be a legitimate strategy for decreasing oxidative stresses in the liver.

  9. Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique

    Science.gov (United States)

    Lin, Jian; Lu, Fake; Zheng, Wei; Xu, Shuoyu; Tai, Dean; Yu, Hanry; Huang, Zhiwei

    2011-11-01

    We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for label-free monitoring of the progression of liver steatosis and fibrosis generated in a bile duct ligation (BDL) rat model. Among the 21 adult rats used in this study, 18 rats were performed with BDL surgery and sacrificed each week from weeks 1 to 6 (n = 3 per week), respectively; whereas 3 rats as control were sacrificed at week 0. Colocalized imaging of the aggregated hepatic fats, collagen fibrils, and hepatocyte morphologies in liver tissue is realized by using the integrated CARS, SHG, and TPEF technique. The results show that there are significant accumulations of hepatic lipid droplets and collagen fibrils associated with severe hepatocyte necrosis in BDL rat liver as compared to a normal liver tissue. The volume of normal hepatocytes keeps decreasing and the fiber collagen content in BDL rat liver follows a growing trend until week 6; whereas the hepatic fat content reaches a maximum in week 4 and then appears to stop growing in week 6, indicating that liver steatosis and fibrosis induced in a BDL rat liver model may develop at different rates. This work demonstrates that the integrated CARS and multiphoton microscopy imaging technique has the potential to provide an effective means for early diagnosis and detection of liver steatosis and fibrosis without labeling.

  10. Effects of pharmacological serum from normal and liver fibrotic rats on HSCs

    Institute of Scientific and Technical Information of China (English)

    Xi-Xian Yao; Tao Lv

    2005-01-01

    AIM: To make drug sera of Salvia miltiorrhiza and Yigankang, both of which are Chinese herbs that activate bleeding and eliminate stasis, in normal rats and those with liver fibrosis, respectively. To investigate and compare the effects of the two different drug sera on the proliferation and activation of hepatic stellate cells (HSCs).METHODS: Some rats were induced with liver fibrosis:40% carbon tetrachloride (CCl4) subcutaneous injection,twice a week for 9 wk. Salvia miltiorrhiza, Yigankang,colchicines and normal saline were administered into the stomachs of normal rats and those with liver fibrosis.Drug sera were extracted 5 d later. HSCs in vitro were cultivated in different drug sera for 24 h. The rates of proliferation and expression of α-smooth muscle actin (α-SMA) were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry stain, respectively.RESULTS: The drug sera from normal and liver fibrotic rats could be used to cultivate HSCs and to observe the effects of the corresponding components of herbs on HSCs. Salvia miltiorrhiza and Yigankang had better inhibitory effects on HSCs than colchicines (MTT: normal drug serum: Salvia miltiorrhiza 0.42±0.08, Yigankang 0.32±0.10 vs colchicines 0.45±0.12 pathological drug serum: Salvia miltiorrhiza 0.33±0.02, Yigankang 0.26±0.01vs colchicines 0.41±0.09. P<0.05). The drug sera of Salvia miltiorrhiza, Yigankang from liver fibrotic rats had a stronger inhibitory effect than the same ones from normal rats (MTT: Salvia miltiorrhiza: normal drug serum 0.42±0.08 vs pathological drug serum 0.33±0.02. Yigankang: normal drug serum 0.32±0.10 vs pathological drug serum 0.26±0.01.P<0.05).CONCLUSION: Salvia miltiorrhiza and Yigankang could inhibit the expression of α-SMA and the proliferation of HSCs. The drug sera from normal and liver fibrotic rats had different effects on HSCs, probably due to different metabolic processes, effective components and different

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

    OpenAIRE

    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...

  12. Formation of 4'-carboxyl acid metabolite of imrecoxib by rat liver microsomes

    Institute of Scientific and Technical Information of China (English)

    Hai-yan XU; Peng ZHANG; Ai-shen GONG; Yu-ming SUN; Feng-ming CHU; Zong-ru GUO; Da-fang ZHONG

    2006-01-01

    Aim:Imrecoxib is a novel and moderately selective COX-2 inhibitor.The aim of the present in vitro investigation was to study the formation of the major metabolite 4'-carboxylic acid imrecoxib (M2) and identify the enzyrne(s) involved in the reaction.Methods:The formation of M2 was studied in rat liver cytosol in the absence or presence of liver microsomes.The formed metabolite was identified and quantified by LC/MSn.In addition,to characterize the cytochrome P450 (CYP) isozymes involved in M2 formation,the effects of typical CYP inhibitors (such as ketoconazle,quinine,α-naphthoflavone, methylpyrazole,and cimetidine) on the formation rate of M2 were investigated.Results:The formation of M2 from 4'hydroxymethyl imrecoxib (M4) was completely dependent on rat liver microsomes and NADPH.Enzyme kinetic studies demonstrated that the formation rate of M2 conformed to monophasic Michaelis-Menten kinetics.Additional experiments showed that the formation of M2 was induced significantly by dexamethasone and lowered by ketoconazole strongly and concentration-dependently.By comparison.other CYP inhibitors.such as α-naphthoflavone,cimetidine,quinine,and methylpyrazole had no inhibitory effects on this metabolic pathway.Conclusion:These biotransformation studies of M4 and imrecoxib in rat liver at the subcellular level showed that the formation of M2 occurs in rat liver microsomes and is NADPH-dependent.The reaction was mainly catalyzed by CYP 3A in untreated rats and in dexamethasone-induced rats.Other CYP,such as CYP 1A,2C,2D,and 2E,seem unlikely to participate in this metabolic pathway.

  13. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Richardson, Jason R. [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States); Heck, Diane E. [Environmental Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  14. DECREASED BILIRUBIN TRANSPORT IN THE PERFUSED LIVER OF ENDOTOXEMIC RATS

    NARCIS (Netherlands)

    ROELOFSEN, H; VANDERVEERE, CN; OTTENHOFF, R; SCHOEMAKER, B; JANSEN, PLM; ELFERINK, RPJO

    1994-01-01

    Background/Aims: Hyperbilirubinemia associated with sepsis is frequently observed in humans. In this study, an experimental rat model was developed to study bilirubin metabolism and transport during endotoxemia. Methods: Rats were injected intravenously with a single bolus of lipopolysaccharide (1 m

  15. Effect of Oyster mushroom in Paracetamol Induced Toxicity of Liver in Wistar albino Rats

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    Afroza Khanam Sumy

    2014-09-01

    Full Text Available Backgroud: Liver is an important metabolic organ. It has wide range of functions including detoxification, storage of glycogen, vitamins A, D and B12, production of several coagulation factors, growth factors such as insulin-like growth factor-1 (IGF-1, angiotensinogen, and biochemicals necessary for digestion (bile. Its damage occurs due to its multidimensional functions, various xenobiotics and oxidative stress leading to distortion of all of its functions. Oyster mushroom which is excellently edible and nutritious has got free radical scavenging activity, and so may be considered as a hepatoprotective agent. Objective: To observe the hepatoprotective effect of Oyster mushroom (Pleurotus florida against paracetamol induced liver damage in Wistar albino rats. Materials and Methods: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC, Dhaka from 1st July 2009 to 30th June 2010. Thirty four Wistar albino rats, aged 90 to 120 days, weighing between 150 to 210 grams were used for the study. After acclimatization for 14 days, they were divided into two groups –– control group (Group A and experimental group (Group B, mushroom-pretreated and paracetamol-treated group. Control group was again subdivided into Group A1 (baseline control group and Group A2 (paracetamol-treated control group. Animals of all groups received basal diet for 30 consecutive days. In addition, Group A1 rats received propylene glycol (2 mL/kg body weight orally only on 30th day, Group A2 rats received single dose of paracetamol suspension (750 mg/kg body weight orally only on 30th day and Group B rats received mushroom extract (200 mg/kg body weight orally for 30 consecutive days and paracetamol suspension (750 mg/kg body weight orally only on 30th day. All the animals were sacrificed on 31st day. Then liver specimens were collected. Histology of liver was done by using standard laboratory procedure. Statistical

  16. Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats

    Institute of Scientific and Technical Information of China (English)

    Osamah Hussein; Masha Grosovski; Etti Lasri; Sergio Svalb; Uzi Ravid; Nimer Assy

    2007-01-01

    AIM: To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease (NAFLD).METHODS: A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group (n = 8) were on chow diet (Group 1), rats (n =6) on methionine choline-deficient diet (MCDD) (Group 2), rats (n = 6) on MCDD enriched with olive oil (Group 3), rats (n = 6) on MCDD with fish oil (Group 4) and rats (n = 6) on MCDD with butter fat (Group 5). After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters.RESULTS: The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups, but not in MCDD and MCDD + olive oil groups. The increase in hepatic triglycerides (TG) levels was blunted by 30% in MCDD+ olive oil group (0.59 ± 0.09) compared with MCDD group (0.85 ± 0.04, P < 0.004), by 37% compared with MCDD + fish oil group (0.95±0.07, P < 0.001), and by 33% compared with MCDD + butter group (0.09±0.1,P < 0.01). The increase in serum TG was lowered by10% in MCDD + olive oil group (0.9 ± 0.07) compared with MCDD group (1.05 ± 0.06). Hepatic cholesterol increased by 15-fold in MCDD group [(0.08 ± 0.02, this increment was blunted by 21% in MCDD + fish oil group(0.09 ± 0.02)]. In comparison with the control group,ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD + olive oil, MCDD + fish oil and MCDD + butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group(1.58±0.08), hepatic MDA contents in MCDD + olive oil(3.3±0.6), MCDD + fish oil (3.0±0.4), and MCDD +butter group (2.9±0.36) were increased by 108%, 91%and 87%, respectively (P < 0.004). Hepatic paraoxonase activity decreased significantly in all treatment groups

  17. HISTOPATHOLOGICAL STUDIES OF LIVER FUNCTION IN RATS FED ON GINGER LILLY CORM MEAL

    Directory of Open Access Journals (Sweden)

    UGWU OKECHUKWU P.C

    2013-01-01

    Full Text Available The effect of feeding Gladiolus unguiculata corm on a few liver function markers were evaluated in this study using albino Wistar rats. Twenty rats were randomly divided into four groups of five rats each. Various concentration of G. unguiculata formulations were fed to the test groups excluding the negative control which received normal feed for the 28 days of analysis. At the end of the feeding period the levels of the serum liver function markers of Aspartate aminotransferase (AST, Alanine aminotransferase (ALT, Alkaline phosphatase (ALP and Protein were determined. Mean serum liver function markers were all increased when compared with the control with only AST liver marker deviating. The ALT activity increased from 36.0 + 3.16 in the control to 38.0 + 3.16 in 20%. The AST significantly increased (p<0.05 from 66.0 + 3.16 in the 20% to 88.0 + 3.16 in the control group. ALP significantly increased from 47.0 +3.16 in the control group to 56.0 + 3.16 in 20%. Protein also increased from 7.0 +0.316 in the control group to 7.8 +0.316 in 20%. The results emanating from this study suggest that Gladiolus unguiculata corm formulations might have some deleterious effects on the liver function.

  18. Effect of zinc supplementation on type 2 diabetes parameters and liver metallothionein expressions in Wistar rats.

    Science.gov (United States)

    Wang, Xue; Li, Hongyan; Fan, Zhe; Liu, Ya

    2012-12-01

    Zinc is a trace metal and acts as an active component of various enzymes. Zinc deficiency has been suggested to be associated with the development of diabetes. The present study investigated the role of zinc supplementation on prevention of diabetic conditions. A double-disease model mimicking hyperlipidemia and type 2 diabetes was created by applying high-fat diet and streptozotocin (STZ) to Wistar rats. We demonstrated that zinc supplementation improved symptoms of diabetes such as polydipsia and increased serum level of high-density lipoprotein cholesterol, indicating that zinc supplementation has a potential beneficial effect on diabetic conditions. The level of maldondialdehyde (MDA), an oxidative stress marker, was reduced in liver by zinc supplementation in high fat-fed rats with or without STZ injection. Meanwhile, we observed an increase in the expression of metallothioneins (MTs) in liver of rats treated with zinc. This suggests that the induction of MTs in liver, which has been shown to be important in scavenging free radicals, could be one of the underlying mechanisms of zinc supplementation on reducing MDA levels in liver. Finally, we found that zinc levels in liver were increased while there was no change in serum zinc levels, indicating that local zinc level might be a critical factor for the induction of MTs. Also, the level of MTs could potentially be an index of zinc bioavailability. Taken together, these results suggest that both zinc and MT could play an important role in balancing nutrition and metabolism to prevent diabetic development.

  19. Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

    Science.gov (United States)

    El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

    2016-12-01

    Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

  20. Structural and ultrastructural study of rat liver influenced by electromagnetic radiation.

    Science.gov (United States)

    Holovská, K; Almášiová, V; Cigánková, V; Beňová, K; Račeková, E; Martončíková, M

    2015-01-01

    Mobile communication systems are undoubtedly an environmental source of electromagnetic radiation (EMR). There is an increasing concern regarding the interactions of EMR with the humans. The aim of this study was to examine the effects of EMR on Wistar rat liver. Mature rats were exposed to electromagnetic field of frequency 2.45 GHz and mean power density of 2.8 mW/cm2 for 3 h/d for 3 wk. Samples of the liver were obtained 3 h after the last irradiation and processed histologically for light and transmission electron microscopy. Data demonstrated the presence of moderate hyperemia, dilatation of liver sinusoids, and small inflammatory foci in the center of liver lobules. Structure of hepatocytes was not altered and all described changes were classified as moderate. Electron microscopy of hepatocytes revealed vesicles of different sizes and shapes, lipid droplets, and proliferation of smooth endoplasmic reticulum. Occasionally necrotizing hepatocytes were observed. Our observations demonstrate that EMR exposure produced adverse effects on rat liver.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Inhibition of classical complement activation attenuates liver ischaemia and reperfusion injury in a rat model

    NARCIS (Netherlands)

    B.H.M. Heijnen; I.H. Straatsburg; N.D. Padilla; G.J. Mierlo; C.E. Hack; T.M. van Gulik

    2006-01-01

    Activation of the complement system contributes to the pathogenesis of ischaemia/reperfusion (I/R) injury. We evaluated inhibition of the classical pathway of complement using C1-inhibitor (C1-inh) in a model of 70% partial liver I/R injury in male Wistar rats (n = 35). C1-inh was administered at 10

  3. [Biological function prediction of mir-210 in the liver of acute cold stress rat].

    Science.gov (United States)

    Guo, Wen-Jin; Lian, Shuai; Guo, Jing-Ru; Zhai, Jun-Fei; Zhang, Yu-Chen; Li, Yue; Zhen, Li; Ji, Hong; Yang, Huan-Min

    2016-04-25

    The study was aimed to observe mir-210 expression in liver tissue of acute cold stress rat and predict the function of mir-210 in cold stress. Thirty SPF Wistar male rats which were 12-week-old and weighed (340 ± 20) g were used. The rats were pre-fed in normal room temperature for one week, and then were randomly divided into acute cold stress group at (4 ± 0.1) °C and normal control group at (24 ± 0.1) °C. After the rats were treated with cold stress for 12 h, the liver tissue was extracted and the gene expression of mir-210 was assayed using qRT-PCR. The results demonstrated that the gene expression of mir-210 was significantly enhanced in acute cold stress group compared with that in normal control group (n = 3, P kinds of target genes such as E2F3, RAD52, ISCU and Ephrin-A3 are more relative with liver cold stress. ISCU regulates the cell respiratory metabolism and Ephrin-A3 is related with cell proliferation and apoptosis. On the other hand, up-regulated mir-210 affects the