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Sample records for cirrhotic rat liver

  1. Hepatic regeneration after sublethal partial liver irradiation in cirrhotic rats

    International Nuclear Information System (INIS)

    Our previous animal study had demonstrated that partial liver irradiation (IR) could stimulate regeneration in the protected liver, which supported the measurements adopted in radiotherapy planning for hepatocellular carcinoma. The purpose of this present study is to investigate whether cirrhotic liver repopulation could be triggered by partial liver IR. The cirrhosis was induced by thioacetamide (TAA) in rats. After cirrhosis establishment, TAA was withdrawn. In Experiment 1, only right-half liver was irradiated with single doses of 5 Gy, 10 Gy and 15 Gy, respectively. In Experiment 2, right-half liver was irradiated to 15 Gy, and the left-half to 2.5 Gy, 5 Gy and 7.5 Gy, respectively. The regeneration endpoints, including liver index (LI); mitotic index (MI); liver proliferation index (LPI); proliferating cell nuclear antigen-labeling index (PCNA-LI); serum hepatic growth factor (HGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-α and interleukin (IL)-6, were evaluated on 0 day, 30-day, 60-day, 90-day, 120-day and 150-day after IR. Serum and in situ TGF-β1 were also measured. In both experimental groups, the IR injuries were sublethal, inducing no more than 9% animal deaths. Upon TAA withdrawal, hepatic regeneration decelerated in the controls. In Experiment 1 except for LI, all other regeneration parameters were significantly higher than those in controls for both right-half and left-half livers. In Experiment 2 all regeneration parameters were also higher compared with those in controls for both half livers. Serum HGF and VEGF were increased compared with that of controls. Both unirradiated and low dose-irradiated cirrhotic liver were able to regenerate triggered by sublethal partial liver IR and higher doses and IR to both halves liver triggered a more enhanced regeneration. (author)

  2. Effect of portal vein ligation on tumor growth and liver regeneration in rat cirrhotic liver lobes

    OpenAIRE

    Xu, Rui; YUAN, YU-FENG; Ayav, Ahmet; JIANG, CHONG-QING; BRESLER, LAURENT; Liu, Zhi-Su; Tran, Nguyen

    2014-01-01

    The aim of the present study was to investigate the effect of portal vein ligation (PVL) on the tumor growth rate and liver regeneration in rat cirrhotic liver lobes. A total of 45 male Wistar rats were randomly divided into PVL, hepatic tumor (HT) and HT + PVL groups (n=15 per group). Liver regeneration and tumor growth in ligated and non-ligated lobes were evaluated prior to and following PVL. In addition, serum alanine transaminase, total bilirubin levels and liver tissue samples were eval...

  3. The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats

    OpenAIRE

    Min, Seon Ok; Kim, Sung Hoon; Lee, Sang Woo; Cho, Jin A.; Kim, Kyung Sik

    2011-01-01

    Background/Aims Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats. Methods To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (...

  4. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

    International Nuclear Information System (INIS)

    Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers. Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance

  5. The role of vasoactive substances in hyperhemodynamics after orthotopic liver transplantation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    曹晖; 吴志勇; 张效杰; 张海婴; 陈治平; 邝耀麟

    2003-01-01

    Objective To evaluate the role of endogenous vasoactive substances in hyperdynamic circulation after orthotopic liver transplantation (OLT) in cirrhotic rats.Methods Male SD rats were randomly divided into 4 groups: normal controls (NL, n=10), rats with intrahepatic portal hypertension (IHPH, n=10), normal rats with OLT (NL-OLT, n=9), and IHPH rats with OLT (IHPH-OLT, n=16). IHPH-OLT rats were divided into 2 subgroups: Group A (3 days after OLT, n=9) and Group B (7 days after OLT, n=7). IHPH was induced by injection of CCI4 and OLT was performed using cuffs for the anastomosis of suprahepatic inferior vena cava, infrahepatic vena cava and portal vein. Radioactive microsphere method was used for hemodynamic study. The concentrations of plasma glucagon (Glu), nitric oxide (NO), prostaglandin (PGI2), thromboxaneA2 (TXA2) and endothelin (ET) were measured by radioimmunoassay. Results No significant difference in hemodynamic changes was observed between NL-OLT and NL rats, except for mean arterial blood pressure. No significant changes in NO and PGI2 were seen between NL-OLT and NL rats. Glu, ET and TXA2 were significantly elevated in NL-OLT rats compared with NL rats (PIHPH-OLT A>IHPH-OLT B rats. The level of plasma PGI2 in IHPH rats was significantly elevated compared with NL rats, while PGI2 in IHPH-OLT A and B rats was found to be lower than in IHPH rats (P<0.05). There was no obvious difference in PGI2 between IHPH-OLT B and NL rats. Vasoconstrictors including ET and TXA2 were found elevated in IHPH-OLT rats. Conclusions OLT does not induce postoperative hyperhemodynamics per se. Vasodilators including NO and Glu, especially NO, play an important role in the hyperhemodynamics of IHPH and IHPH-OLT rats. The results of the present study demonstrate that the persistence of systemic and splanchnic hyperkinetic circulation in the early stages after OLT may result from those non-eliminated factors that caused hyperhemodynamics in liver cirrhosis patients with portal

  6. 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

    OpenAIRE

    Eduardo Garcia Pacheco; Maria Cecília Jordani Gomes; Gustavo Ribeiro Rodrigues; Walter Campos; Rafael Kemp; Orlando de Castro e Silva

    2006-01-01

    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...

  7. Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats.

    Science.gov (United States)

    Bingül, İlknur; Başaran-Küçükgergin, Canan; Aydın, A Fatih; Soluk-Tekkeşin, Merva; Olgaç, Vakur; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-09-01

    Diethylnitrosamine (DEN)-induced liver cancer normally develops in stages that progress from cirrhosis and carcinoma. Increased oxidative stress is suggested to play a role in DEN-induced carcinogenicity. Blueberries (BB) contain high antioxidant capacity. We investigated the effect of BB supplementation on development of DEN-induced cirrhosis and neoplastic lesions in the liver. Rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks and sacrificed 8 weeks after the last DEN injection. They were also fed on 8% BB (w/w) containing chow for 16 weeks. Hepatic damage markers in serum were determined together with hepatic histopathological examinations. Hydroxyproline (HYP), malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and their mRNA expressions were measured. Protein and mRNA expressions of glutathione transferase-pi (GST-pi) were evaluated as a marker of preneoplastic lesions. BB supplementation decreased hepatic damage markers in serum and hepatic MDA, DC, and PC levels, but SOD, CAT, and GSH-Px activities and their mRNA expressions remained unchanged in DEN-treated rats. BB attenuated cirrhotic changes and decreased hepatic HYP levels and GST-pi expressions. Our results indicate that BB is effective in decreasing development of DEN-induced hepatic cirrhosis and preneoplastic lesions by acting as an antioxidant (radical scavenger) itself without affecting activities and mRNA expressions of antioxidant enzymes. PMID:26684621

  8. Bacterial translocation in cirrhotic rats. Its role in the development of spontaneous bacterial peritonitis.

    OpenAIRE

    Llovet, J M; Bartolí, R; Planas, R; Cabré, E; Jimenez, M.; Urban, A; Ojanguren, I; Arnal, J; Gassull, M. A.

    1994-01-01

    Bacterial translocation occurs in ascitic cirrhotic rats, but its association with ascites infection is unknown. The aim of this study was to assess the relation between bacterial translocation and ascites infection in cirrhotic rats. Male Sprague-Dawley rats were induced to cirrhosis with intragastric CCl4. Ascitic fluid, portal and peripheral blood, mesenteric lymph nodes, liver and spleen samples were cultured before death in those cirrhotic rats with less (group A) or more (group B) than ...

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

    Science.gov (United States)

    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. PMID:26138461

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

    Institute of Scientific and Technical Information of China (English)

    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.

  11. In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats

    Science.gov (United States)

    Van de Casteele, M; Omasta, A; Janssens, S; Roskams, T; Desmet, V; Nevens, F; Fevery, J

    2002-01-01

    Background: Portal hypertension in cirrhosis results from enhanced intrahepatic resistance to an augmented inflow. The former is partly due to an imbalance between intrahepatic vasoconstriction and vasodilatation. Enhanced endothelin-1 and decreased activity of hepatic constitutive endothelial nitric oxide synthase (NOS 3) was reported in carbon tetrachloride (CCl4) cirrhotic rat liver. Aims: To study whether an increase in hepatic NOS 3 could be obtained in the CCl4 cirrhotic rat liver by in vivo cDNA transfer and to investigate a possible effect on portal pressure. Methods: Hepatic NOS 3 immunohistochemistry and western blotting were used to measure the amount of NOS 3 protein. Recombinant adenovirus, carrying cDNA encoding human NOS 3, was injected into the portal vein of CCl4 cirrhotic rats. Cirrhotic controls received carrier buffer, naked adenovirus, or adenovirus carrying the lac Z gene. Results: NOS 3 immunoreactivity and amount of protein (western blotting) were significantly decreased in CCl4 cirrhotic livers. Following cDNA transfer, NOS 3 expression and the amount of protein were partially restored. Portal pressure was 11.4 (1.6) mm Hg in untreated cirrhotic (n=9) and 11.8 (0.6) in lac Z transfected (n=4) cirrhotic rats but was reduced to 7.8 (1.0) mm Hg (n=9) five days after NOS 3 cDNA transfer. No changes were observed in systemic haemodynamics, in liver tests or urinary nitrates, or in NOS 3 expression in lung or kidney, indicating a highly selective transfer. Conclusions: NOS 3 cDNA transfer to cirrhotic rat liver is feasible and the increase in hepatic NOS 3 leads to a marked decrease in portal hypertension without systemic effects. These data indicate a major haemodynamic role of intrahepatic NOS 3 in the pathogenesis of portal hypertension in CCl4 cirrhosis. PMID:12171971

  12. Intrahepatic splenosis mimicking hepatocellular carcinoma in a cirrhotic liver

    International Nuclear Information System (INIS)

    We report a patient who has a cirrhotic liver secondary to hepatitis C virus infection with a liver lesion incidentally found on routine liver ultrasound. The patient had a history of splenectomy 30 years earlier. The magnetic resonance imaging (MRI) characteristics suggested the diagnosis of intrahepatic splenosis, which is confirmed by core needle biopsy. Knowledge of these imaging findings makes this entity important to be considered in the differential diagnosis of a hepatic tumor in the presence of a history of splenic trauma or surgery. (author)

  13. Hepatic cavernous hemangioma in cirrhotic liver: imaging findings

    International Nuclear Information System (INIS)

    To document the imaging findings of hepatic cavernous hemangioma detected in cirrhotic liver. The imaging findings of 14 hepatic cavernous hemangiomas in ten patients with liver cirrhosis were retrospectively analyzed. A diagnosis of hepatic cavernous hemangioma was based on the findings of two or more of the following imaging studies: MR, including contrast-enhanced dynamic imaging (n=10), dynamic CT (n=4), hepatic arteriography (n=9), and US (n=10). The mean size of the 14 hepatic hemangioma was 0.9 (range, 0.5-1.5) cm in the longest dimension. In 11 of these (79%), contrast-enhanced dynamic CT and MR imaging showed rapid contrast enhancement of the entire lesion during the early phase, and hepatic arteriography revealed globular enhancement and rapid filling-in. On contrast-enhanced MR images, three lesions (21%) showed partial enhancement until the 5-min delayed phases. US indicated that while three slowly enhancing lesions were homogeneously hyperechoic, 9 (82%) of 11 showing rapid enhancement were not delineated. The majority of hepatic cavernous hemangiomas detected in cirrhotic liver are small in size, and in many, hepatic arteriography and/or contrast-enhanced dynamic CT and MR imaging demonstrates rapid enhancement. US, however, fails to distinguish a lesion of this kind from its cirrhotic background. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

    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.)

  16. Intrarenal octreotide treatment prevents sodium retention in liver cirrhotic rats: evidence for direct effects within the thick ascending limb of Henle's loop

    DEFF Research Database (Denmark)

    Jonassen, Thomas; Christensen, Sten; Marcussen, Niels; Petersen, Jørgen Søberg

    2006-01-01

    We have previously shown that systemic treatment with the somatostatin analog octreotide has marked beneficial effects on renal function in rats with liver cirrhosis induced by common bile duct ligation (CBL; Jonassen TEN, Christensen S, Sørensen AM, Marcussen N, Flyvbjerg A, Andreasen F, and...... Petersen JS. Hepatology 29: 1387-1395, 1999). In the present study, we tested the hypothesis that octreotide has a direct effect on renal tubular function. Rats (CBL or Sham-CBL) were intrarenally treated with low-dose octreotide in a long-acting release formulation, which had no systemic actions (100...

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

    Directory of Open Access Journals (Sweden)

    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

  18. Cirrhotic cardiomyopathy: Implications for the perioperativemanagement of liver transplant patients

    Institute of Scientific and Technical Information of China (English)

    Suehana Rahman; Susan V Mallett

    2015-01-01

    Cirrhotic cardiomyopathy is a disease that has onlyrecently been recognised as a definitive clinical entity.In the setting of liver cirrhosis, it is characterizedby a blunted inotropic and chronotropic responseto stress, impaired diastolic relaxation of themyocardium and prolongation of the QT interval inthe absence of other known cardiac disease. A keypathological feature is the persistent over-activationof the sympathetic nervous system in cirrhosis, whichleads to down-regulation and dysfunction of theβ-adrenergic receptor. Diagnosis can be made using acombination of echocardiography (resting and stress),tissue Doppler imaging, cardiac magnetic resonanceimaging, 12-lead electrocardiogram and measurementof biomarkers. There are significant implications of cirrhoticcardiomyopathy in a number of clinical situations in whichthere is an increased physiological demand, whichcan lead to acute cardiac decompensation and heartfailure. Prior to transplantation there is an increasedrisk of hepatorenal syndrome, cardiac failure followingtransjugular intrahepatic portosystemic shunt insertionand increased risk of arrhythmias during acutegastrointestinal bleeding. Liver transplantation presentsthe greatest physiological challenge with a furtherrisk of acute cardiac decompensation. Peri-operativemanagement should involve appropriate choice of graftand minimization of large fluctuations in preload andafterload. The avoidance of cardiac failure during thisperiod has important prognostic implications, as thereis evidence to suggest a long-term resolution of theabnormalities in cirrhotic cardiomyopathy.

  19. Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis

    OpenAIRE

    Kim, Moon Young; Baik, Soon Koo; Won, Chan Sik; Park, Hong Jun; Jeon, Hyo Keun; Hong, Hyun Il; Kim, Jae Woo; Kim, Hyun Soo; Kwon, Sang Ok; Kim, Jang Young; Yoo, Byung Su; Lee, Seung Hwan

    2010-01-01

    Background/Aims The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the β-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). Methods Seventy-one cirrhotic patients with normal left...

  20. Differential distribution of age and HBV serological markers in liver cirrhosis and non-cirrhotic patients with primary liver cancer

    Directory of Open Access Journals (Sweden)

    XU Xiuhua

    2013-03-01

    Full Text Available ObjectiveTo compare the age distributions and presence of hepatitis B virus (HBV serological markers between primary hepatic cancer (PHC patients with and without liver cirrhosis. MethodsA total of 547 PHC cases were analyzed retrospectively. After dividing into two groups according to liver cirrhosis status, the between-group differences in age and HBV serological markers, such as hepatitis B e antigen (HBeAg status, were statistically compared using the Chi-squared test. ResultsThe number of cirrhotic and non-cirrhotic PHC patients was 265 and 282, respectively. HBV infection was present in 221 cirrhotic PHC patients and 256 non-cirrhotic PHC patients (834% vs. 90.8%. There was a substantial bias in the proportion of males to females in the cirrhotic PHC patients (7.83∶1. The number of PHC patients <60 years old was similar between the cirrhotic and non-cirrhotic groups, but the non-cirrhotic group had significantly more patients >60 years old (P<0.005. In cirrhotic PHC patients, the HBV infection rate was highest in the <40 years old age group (96.7% and the HBeAg serological conversion rate was highest in the 40-60 years old age group (89.5%. In non-cirrhotic PHC patients, the 40-60 years old age group showed the highest HBV infection rate (90.3% but the lowest HBeAg serological conversion rate (80.0%. ConclusionPHC with liver cirrhosis mainly occurred in males, with the HBV infection rate being higher in individuals <60 years old. Non-cirrhotic PHC patients were more often >60 years old. Many of the HBV-infected PHC patients with cirrhosis had high HBeAg serological conversion rate.

  1. Elements in normal and cirrhotic human liver. Potassium, iron, copper, zinc and bromine measured by X-ray fluorescence spectrometry

    DEFF Research Database (Denmark)

    Laursen, J.; Milman, N.; Leth, Peter Mygind;

    1990-01-01

    Various elements (K, Fe, Cu, Zn, Br) were measured by X-ray flourescence spectrometry in cellular and connective tissue fractions of normal and cirrhotic liver samples obtained at autopsy. Normal livers: 32 subjects (16 males, 16 females) median age 69 years. Cirrhotic livers: 14 subjects (13 males...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  3. The expression levels of prolyl oligopeptidase responds not only to neuroinflammation but also to systemic inflammation upon liver failure in rat models and cirrhotic patients

    OpenAIRE

    Tenorio-Laranga, Jofre; Montoliu, Carmina; Urios, Amparo; Hernandez-Rabaza, Vicente; Ahabrach, Hanan; García-Horsman, J. Arturo; Felipo, Vicente

    2015-01-01

    Background Liver failure in experimental animals or in human cirrhosis elicits neuroinflammation. Prolyl oligopeptidase (PREP) has been implicated in neuroinflammatory events in neurodegenerative diseases: PREP protein levels are increased in brain glial cells upon neuroinflammatory insults, but the circulating PREP activity levels are decreased in multiple sclerosis patients in a process probably mediated by bioactive peptides. In this work, we studied the variation of PREP levels upon liver...

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

    International Nuclear Information System (INIS)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 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

  7. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an e...... stress the heart such as shunt implantation and liver transplantation....

  8. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik Sahl

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an...... stress the heart such as shunt implantation and liver transplantation....

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

    DEFF Research Database (Denmark)

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

    1987-01-01

    -hepatic venous difference of base excess was small and of the same size in all groups, indicating no enhanced production of lactic acid in the liver. Our results do not support the concept that hepatic venous oxygen content is low in alcoholic liver disease and thereby contributes to hypoxic liver damage.......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...

  10. 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.

  11. 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.

  12. Double-dose hepatitis B vaccination in cirrhotic patients on a liver transplant waiting list

    Directory of Open Access Journals (Sweden)

    Patricia R. Bonazzi

    2008-08-01

    Full Text Available Development of immunity to hepatitis B virus in cirrhotic patients waiting for liver transplantation is highly desirable. Though a double-dose regimen is available, little is know about its effectiveness. We examined the efficacy of double-dose hepatitis B virus vaccination in cirrhotic patients waiting for liver transplantation. We studied 43 patients who were waiting for liver transplantation. They were vaccinated with three doses of 40 mg hepatitis B vaccine at 0, 1 and 6 months; the normal dose is 20 mg. Efficacy was measured based on seroconversion of anti-HBs. Global response to the primary vaccination scheme was 67.5% (29 patients. Forty-one per cent of responders had anti-HBs titers above 1,000 IU/mL. No factors were associated with response, based on multivariate analysis. The vaccination scheme of 40 mg at 0, 1 and 6 months was superior to conventional vaccination doses (20 mg for cirrhotic patients on a waiting list for liver transplantation.

  13. 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.

  14. Distribution of nitric oxide synthase in normal and cirrhotic human liver

    Science.gov (United States)

    McNaughton, Lance; Puttagunta, Lakshmi; Martinez-Cuesta, Maria Angeles; Kneteman, Norm; Mayers, Irvin; Moqbel, Redwan; Hamid, Qutayba; Radomski, Marek W.

    2002-01-01

    Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000–10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including α1-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca2+-dependent and –independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca2+-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders. PMID:12482944

  15. 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

  16. 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.

  17. Salvianolate inhibits cytokine gene expression in small intestine of cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Dan-Hong Yang; Zai-Yuan Ye; Bo Jin; Xu-Jun He; Qin Zhang; Wei-Ming Zhou; Wen-Juan Xu; Huo-Xiang Lu

    2011-01-01

    AIM: To study the effect of salvianolate on expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA in small intestine of cirrhotic rats.METHODS: Cirrhosis in rats was induced using CCl4 (0.3 mL/kg).Rats were randomly divided into non-treatment 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 treated for 2 wk.Another 10 healthy rats served as a normal control group.Mortality of cirrhotic rats in each group was evaluated after treatment with salvianolate.Serum samples were taken from portal vein for the detection of endotoxin.Morphological changes in tissue samples from the ileocecum were observed under a light microscope.Expression of TNF-α and IL-6 mRNA in the small intestine of rats was analyzed by real-time reverse-transcriptase polymerase chain reaction.RESULTS: The mortality of cirrhotic rats in the nontreatment group was 37.5%.No cirrhotic rat died in the high-dose salvianolate treatment group.The serum endotoxin level was significantly higher in the non-treatment group than in the salvianolate treatment and normal control groups.The intestinal mucosal and villous atrophy, necrosis and shedding of the intestinal mucosal epithelium, observed in the non-treatment group, were reversed in different salvianolate treatment groups.The TNF-α and IL-6 mRNA expression levels in small intestine were significantly lower in different salvianolate treatment groups than in the non-treatment group.CONCLUSION: Salvianolate can reduce the endotoxin level, ameliorate the injury of intestinal mucosa, and inhibit the expression of TNF-α and IL-6 mRNA in small intestine of cirrhotic rats.

  18. 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

  19. 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.

  20. Expression of extracellular matrix proteoglycans perlecan and decorin in carbon-tetrachloride-injured rat liver and in isolated liver cells.

    OpenAIRE

    Gallai, M.; Kovalszky, I.; Knittel, T.; Neubauer, K; Armbrust, T.; Ramadori, G.

    1996-01-01

    Proteoglycans are important components of the extracellular matrix. They are involved in liver regeneration as well as in liver fibrosis. The distribution and cellular source of proteoglycans under normal as well as pathological conditions is still under debate. Localization of decorin and perlecan was studied in normal, acutely damaged, and cirrhotic liver by histochemistry. Furthermore, their synthesis was analyzed in different liver cell populations isolated from normal rat liver. In norma...

  1. Hepatocellular carcinoma associated with hereditary hemochromatosis occurring in non-cirrhotic liver.

    Science.gov (United States)

    von Delius, S; Lersch, C; Schulte-Frohlinde, E; Fend, F; Dobritz, M; Schmid, R M; Eckel, F

    2006-01-01

    The occurrence of primary hepatocellular carcinoma (HCC) in patients with hereditary hemochromatosis (HH) is well known. Thereby, the development of liver cirrhosis seems to be a prerequisite. Whether or not a hepatic iron overload in the context of hereditary hemochromatosis is an independent risk factor for HCC remains unclear. To date there are only a few reports about HCC arising in non-cirrhotic livers in the presence of HH. We report the case of a 64-year-old man who presented to our outpatient clinic with HCC. Liver cirrhosis could be excluded. Detailed exploration of the patient's history revealed that he had been treated by venesection for about 10 years up to 15 years ago. Subsequent investigations showed an elevated serum ferritin and transferrin saturation. The diagnosis of HH was confirmed by genetic testing, with homozygosity for the Cys282Tyr mutation. The patient received palliative chemotherapy and finally died 15 months after initial diagnosis of HCC. PMID:16397838

  2. Pulmonary Complications in Cirrhotic Candidates for Liver Transplantation

    Directory of Open Access Journals (Sweden)

    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.

  3. Cirrhotic cardiomyopathy.

    Science.gov (United States)

    Milani, A; Zaccaria, R; Bombardieri, G; Gasbarrini, A; Pola, P

    2007-06-01

    Decompensated liver cirrhosis is characterized by a peripheral vasodilation with a low-resistance hyperdynamic circulation. The sustained increase of cardiac work load associated with such a condition may result in an inconstant and often subclinical series of heart abnormalities, constituting a new clinical entity known as "cirrhotic cardiomyopathy". Cirrhotic cardiomyopathy is variably associated with baseline increase in cardiac output, defective myocardial contractility and lowered systo-diastolic response to inotropic and chronotropic stimuli, down-regulated beta-adrenergic function, slight histo-morphological changes, and impaired electric "recovery" ability of ventricular myocardium. Cirrhotic cardiomyopathy is usually clinically latent or mild, likely because the peripheral vasodilation significantly reduces the left ventricle after-load, thus actually "auto-treating" the patient and masking any severe manifestation of heart failure. In cirrhotic patients, the presence of cirrhotic cardiomyopathy may become unmasked and clinically evident by certain treatment interventions that increase the effective blood volume and cardiac pre-load, including surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts (LeVeen) and orthotopic liver transplantation. Under these circumstances, an often transient overt congestive heart failure may develop, with increased cardiac output as well as right atrial, pulmonary artery and capillary wedge pressures. PMID:17383244

  4. 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.

  5. Rat liver insulin receptor

    International Nuclear Information System (INIS)

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  6. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

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

    2014-01-01

    Cirrhosis is known to cause alterations in the systemic haemodynamic system. Cirrhotic cardiomyopathy designates a cardiac dysfunction that includes impaired cardiac contractility with systolic and diastolic dysfunction, as well as electromechanical abnormalities in the absence of other known...... 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...... 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....

  7. Usefulness of radioisotope imaging of macroregenerative nodule in cirrhotic liver: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, S. E.; Kim, S. H.; Jeong, Y. A.; Song, H. H.; Kim, J. Y.; Jeong, S. K.; Park, S. H.; Shin, K. S. [College of Medicine, Catholic Univ., Seoul (Korea, Republic of)

    1997-07-01

    excretion, indicating normal function of hepatocytes. Photomicrography showed macroregenerative nodule. Radioisotope imaging might be useful in the differential diagnosis of macroregenerative nodule from hepatocelluar carcinoma in cirrhotic liver.

  8. A case of primary clear cell hepatocellular carcinoma in a non-cirrhotic liver: an immunohistochemical and ultrastructural study

    OpenAIRE

    Erica Fan Clayton; Emma Elizabeth Furth; Amy Ziober; Theodore Xu; Yuan Yao; Pil Gyu Hwang; Zhanyong Bing

    2012-01-01

    The clear cell variant of hepatocellular carcinoma is a rare entity, occurring at a frequency of less than 10% of hepatocellular carcinoma, with a female prevalence and usually associated with hepatitis C and cirrhosis. We reported a case of primary clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without history of hepatitis. Our examination included gross pathology, histopathology, immunohistochemistry, special stains, and electron microscopy evaluation. The tumor was ...

  9. 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.

  10. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens H

    2010-01-01

    Increased cardiac output was first described in patients with cirrhosis more than fifty years ago. Later, various observations have indicated the presence of a latent cardiac dysfunction, which includes a combination of reduced cardiac contractility with systolic and diastolic dysfunction and......, 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...... cirrhotic patients and it may be normalised by beta-blockers. No specific therapy for cirrhotic cardiomyopathy can be recommended, but treatment should be supportive and directed against the cardiac dysfunction. Future research should better describe the prevalence, impact on morbidity and survival, and...

  11. 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.

  12. Type III procollagen peptide and PZ-peptidase serum levels in pre-cirrhotic liver diseases.

    Science.gov (United States)

    Morelli, A; Vedovelli, A; Fiorucci, S; Angelini, G P; Fini, C; Palmerini, C A; Floridi, A

    1985-05-30

    To obtain a dynamic and non-invasive picture of hepatic fibrosis in pre-cirrhotic liver diseases we measured both the concentration of the N-terminal peptide of procollagen III, as a marker of collagen synthesis, and the activity of PZ-peptidase, an enzyme involved in collagen degradation, in the serum of alcoholic or chronic viral hepatitis patients. Peptide serum levels were similar in chronic persistent hepatitis and controls, but significantly higher in chronic active hepatitis. Chronic persistent hepatitis patients had PZ-peptidase levels higher than controls, but similar to chronic active hepatitis. The increase in collagen synthesis without a parallel increase in collagen degradation seen in chronic active hepatitis could be regarded as a sign of impending cirrhosis, whereas the unbalanced rise in PZ-peptidase observed in chronic persistent hepatitis is consistent with the non-progressive character of this disorder. In alcoholic hepatitis both peptide concentration and PZ-peptidase activity were elevated, thus suggesting that both collagen synthesis and degradation are activated. However, the greater increase in PZ-peptidase than in peptide serum levels seen in some patients seems to indicate a minor tendency to progressive fibrosis or a trend towards resolution. Unlike liver disease patients, normal peptide and PZ-peptidase levels were found in patients with pancreatic fibrosis. Since circulating inhibitors and activators of the PZ-peptidase activity can be excluded, as proved by this study, joint peptide and PZ-peptidase serum measurements would seem to offer a simple reliable non-invasive method for differentiating and monitoring progressive and non-progressive forms of hepatic fibrosis. PMID:3888456

  13. Intestinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction, and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic rats.METHODS: Male Wister rats were fed with a diet containing maize flour, lard, cholesterol, and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide (NO) production inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) intraperitoneally, and an iNOS inhibitor, aminoguanidine hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk, or a HO-1 inhibitor, zinc protoporphyrin (ZnPP) intraperitoneally 12 h prior to killing. Blood, liver and lung tissues were sampled.RESULTS: Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1±1.1 (count/filed) at the 4th wk to 14.5±2.4 (count/filed) at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide (LPS) (0.31±0.08 EU/mL vs control 0.09±0.03 EU/mL),alanine transferase (ALT, 219.1±17.4 U/L vs control 5.9±2.2 U/L) and portal vein pressure. Compared with normal control animals, the number of total cells in bronchoalveolar lavage fluid (BALF) of the cirrhotic rats at the 8th wk was not changed, but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold, protein expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) started to increase significantly at the 4th wk, and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS.NO2-/NO3-was also increased, which was correlated to the increase of iNOS (r

  14. Xiayuxue decoction reduces renal injury by promoting macrophage apoptosis in hepatic cirrhotic rats.

    Science.gov (United States)

    Liu, C; Cai, J; Cheng, Z; Dai, X; Tao, L; Zhang, J; Xue, D

    2015-01-01

    Renal pathological changes in cirrhotic rat have not been extensively reported. The aim of this study was to investigate whether Xiayuxue decoction (XYXD) could attenuate renal injury induced by bile duct ligation (BDL), with special focus on the mechanisms promoting renal macrophage apoptosis. The rats were treated with BDL for 5 weeks and administered 0.36 g/kg XYXD intragastrically from day 1 of initiating BDL. Renal tissue was monitored by hematoxylin-eosin and Sirius red staining. Macrophage infiltration and proinflammatory cytokines such as tumor necrosis factor and chemokine ligand 2 were detected by quantitative polymerase chain reaction. Macrophage apoptosis was detected by double immunofluorescence staining. Blood urea nitrogen, creatinine, and glomerulus diameter increased significantly after a 5-week BDL treatment in XYXD (BDL-XYXD) rats. CD68 and pro-inflammatory cytokine mRNA increased in the kidneys of control (BDL-water) rats. Fluorescence microscopy analysis showed that XYXD promoted apoptosis in renal CD68+ macrophages. Collogen1 (Col 1), pro-fibrogenic cytokines, and α-smooth muscle actin in kidneys of BDL-water rats increased significantly compared to the sham group. XYXD inhibited Col 1 and pro-fibrotic factors in BDL-XYXD rats. Our results demonstrated that XYXD significantly reduced renal injury by, at least in part, promoting macrophage apoptosis in rats with damaged renal histopathology due to BDL-induced cirrhosis. PMID:26400305

  15. Changes in portal blood flow and liver functions in cirrhotics during Ramadan fasting in the summer; a pilot study

    Science.gov (United States)

    Mohamed, Salem Y; Emara, Mohamed H; Hussien, Hala IM; Elsadek, Hany M

    2016-01-01

    Aim: Assessment of short term changes in portal blood flow and long term changes in liver functions in cirrhotic patients who chose to fast during the month of Ramadan in summer. Background: During Ramadan, healthy Muslims obligated to fast from predawn to sunset. Patients and methods: Forty cirrhotic patients intended to fast during the month of Ramadan in the year 2014, were examined by Congestion index (CI) as a non-invasive indicator of short term changes in the portal blood flow, while liver function tests were determined as an indicator of long term changes in liver functions. Results: A total of 38 patients completed the whole month fasting and two patients discontinued fasting due to variceal bleeding. The complicated patients were 7. CI showed a statistically significant increase from fasting to postprandial status (P<0.001), with statistically significant increases from fasting to postprandial status in Child class A (P<0.001), and B (P<0.001). We did not find a statistical significance between patients with complications and those without complications (P=0.6). There was a statistically significant rise in the serum bilirubin after Ramadan. Deterioration noticed as advanced Child classes, development of lower limb edema, increasing ascites, increasing jaundice and overt encephalopathy. Conclusion: Cirrhotic patients showed significant short-term changes in the portal blood flow. However, these changes are not linked to complications or deterioration of liver functions and accommodated especially in patients with Child class A and B. Child class C patients should not fast. PMID:27458510

  16. Cerebral metabolic changes in cirrhotic patients before and after liver transplantation: a MR spectroscopy study

    International Nuclear Information System (INIS)

    Objective: To quantitatively evaluate the metabolic changes in posterior cingulated cortex and left basal ganglia in patients with liver cirrhosis before and after liver Transplantation (LT). Methods: A total of 22 controls and 37 cirrhotic patients listed for LT were enrolled in the study. Brain. MRS (PRESS sequence) and neuropsychological (NP) tests were performed in all subjects. Eighteen patients were followed up at 1 month and 3 month after LT. The NP parameters including number connection test-A (NCT-A), digital symbol test (DST) and symbol digital test (SDT) were measured. MRS metabolic contents were measured automatically at posterior cingulate cortex (PCC) and left basal ganglia (LBG). Independent t-test was used to compare the parameters of NP test and MRS metabolites between the 2 groups, The changes of the parameters before and after LT were compared using analysis of variance. Pearson correlation test was also used to analysis the relationship between NP test parameters and MRS metabolites. Results: (1) Before LT, significant difference of metabolites was found in the PCC between the two groups [NAA/Cr (1.96±0.21, 1.73±0.12), Cho/Cr (0.65±0.12, 0.83±0.09), ml/Cr (0.41± 0.14, 0.72±0.11), Glx/Cr (2.37±0.38, 1.92±0.32) (t=-5.42, 5.96, 8.62, -4.72, P<0.01)]. And statistical significance also were found in LBG between the 2 groups [Cho/Cr (0.63±0.16, 0.77± 0.10), ml/Cr (0.38±0.17, 0.53±0.21), Glx/Cr (1.70±0.36, 1.29±0.30), (t=3.64, 3.07, -4.58, P<0.01)]. (2) Compared with controls, the patients before LT had longer NCT-A reaction time [(58.17±19.12) s, (37.68±8.02) s, t=4.14, P<0.01], lower scores of DST (36.67±9.91, 55.36± 9.27, t=4.60, P<0.01) and SDT (31.67±9.49, 50.73±8.34, t=4.652, P<0.01) before LT. All the scores of NP tests changed significantly at 1 and 3 month after LT compared with those before LT [NCT-A (53.06±12.71) s, (35.72±5.20) s, F=33.554, P<0.01], DST (41.89±8.17, 54.39±5.69, F= 85.772, P<0.01), SDT (37.44±7

  17. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an...

  18. Effects of nitric oxide synthesis inhibitor in long-term treatment onhyperdynamic circulatory state in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Ying Qiu Huang; Shu Dong Xiao; Jian Zhong Mo; De Zhong Zhang

    2000-01-01

    AIM To investigate the effects of low dosage of nitric oxide synthesis (NOS) inhibitor NG-nitro-L-argininemethyl ester (L-NAME) in long-term treatment on hyperdynamic circulatory state in rats with cirrhosis.METHODS Cirrhosis model was induced in male SD rats by injection of 60% CC14 oily solutionsubcutaneously. Cirrhotic rats were treated with L-NAME (0.5 mg·kg-1·d-1) by gavage for two weeks. Meanarterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR),splanchnic blood flow (SBF) and serum NO levels were determinded in L-NAME-treated, L-NAME-untreated cirrhotic rats and controls by using 57Co-Labled microsphere technique and a fluorometric assay,respectively.RESULTS Untreated cirrhotic rats had significantly lower MAP, SVR and higher PP, CO, CI, SBF andNO concentration than controls ( 14.42±0,47 kPa vs 17.05±0.34 kPa, 2.974±0.186 kPa·mL-1·min-1 vs4.234±0.118 kPa·mL-1·min-1, 1.665±0.067 kPa vs 1.123±0.096 kPa, 189.99±9.26 mL/min vs 135.5±3.55 mL/min, 55.89±1.82 mL-1·min-1·100g-1 BW vs 39.68±1.64 mL-1·min-1·100g-1 BW, 4.60±1.25μmol/L vs 0.53±0.26 μmol/L, P<0.01, respectively). In treated cirrhotic rats, L-NAME significantlyattenuated the increase of CO, CI, SBF, NO concentration and the decrease of MAP and SVR. In treatedcirrhotic rats, L-NAME induced a marked decrement of NO concentration than untreated cirrhotic rats(1.471 ±0.907 μmol/L vs 4.204±1.253 μmol/L, P<0.01).CONCLUSION The endogenous NO may play an important role in the changes of hemodynamics pattern incirrhosis,and hyperdynamic circulatory state in rats with cirrhosis can be ameliorated by long-term low doseL-NAME treatment.

  19. 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...

  20. SHSST Cyclodextrin Complex Prevents the Fibrosis Effect on CCl4-Induced Cirrhotic Cardiomyopathy in Rats through TGF-β Pathway Inhibition Effects

    Directory of Open Access Journals (Sweden)

    Cheng-Hsun Yang

    2014-05-01

    Full Text Available Patients with liver cirrhosis also have subtle cardiac structure or function abnormalities. This cardiac dysfunction commonly occurs in 56% of waiting orthotopic liver transplantation (OLT patients and is defined as cirrhotic cardiomyopathy (CCM. Up to now, there is no standard treatment because CCM does not have a solidly established diagnosis and is based on high clinical suspicion. The liver function of CCM is particularly limited, making patients vulnerable to more drug treatments. Here, we use silymarin (100 mg/kg/day, baicalein (30 mg/kg/day, San Huang Shel Shin Tang (SHSST, 30 mg/kg/day and β-cyclodextrin modified SHSST (SHSSTc, 30 and 300 mg/kg/day treatments for a CCl4-induced CCM rat model. The results show that silymarin, baicalein and SHSST treatments can only slightly reduce the collagen accumulation in CCM rat hearts. However, SHSSTc treatment protects the heart in CCM and significantly inhibits collagen acumination and the fibrosis regulating transforming growth factor-β (TGF-β pathway expression. SHSSTc treatments further reduced the heart weight and the ratio between left ventricular weight (LVW and tibia length (TL. This experimental data show that water solubility improved β-cyclodextrin modified Chinese herbal medicine formula (SHSSTc can provide an excellent heart protection effect through TGF-β pathway inhibition.

  1. Embolision of arteriovenous fistula within primary carcinoma of the liver in a cirrhotic patient with portal hypertension and bleeding from oesophageal varices

    International Nuclear Information System (INIS)

    The report concerns a case of primary carcinoma of the liver in a cirrhotic patient with portal hypertension and bleeding esophageal varices. At the angiography a large a-v fistula was found within the tumor. This lesion appeared to be an additional cause of portal hypertension primarily due to liver cirrhosis. In order to diminish a risk of bleeding the embolization of the fistula was successfully performed resulting remarkable decrease of portal blood pressure and reducing the risk of hemorrhage. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis

    International Nuclear Information System (INIS)

    Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-114Cpalmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls

  4. Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Angelico, M.; Alvaro, D.; Cantafora, A.; Masella, R.; Gaudio, E.; Gandin, C.; Ginanni Corradini, S.; Ariosto, F.; Riggio, O.; Capocaccia, L. (II Division of Gastroenterology, University of Rome La Sapienza (Italy))

    1991-07-01

    Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1{sup 14}Cpalmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls.

  5. 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.

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

    International Nuclear Information System (INIS)

    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

  7. Vascular Endothelial Growth Factor And Soluble Adhesion Molecules As A Diagnostic Markers For Spontaneous Bacterial Peritonitis In Cirrhotic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamdia Ezzat Ahmed, (2Ahmed Dorrah,

    2006-03-01

    Full Text Available Spontaneous bacterial peritonitis (SBP is a frequent and severe complication in cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The aim of this study was determine serum and ascitic fluid of soluble-L selectin (s-L Selectin, intracellular adhesion molecule-1 (ICAM-1, Vascular cell adhesion molecule-1 (VCAM-1 and vascular endothelial growth factor (VEGF in cirrhotic patients, and to search for a relationship between them and SBP. This study was performed on 30 cirrhotic patients with SBP. Their ages ranged (from 38-55 years with mean of (32 + 5.5, 30 cirrhotic patients with non-infected ascites; their ages ranged (from 30-52 years with mean of (35 + 6.5. This group considered as cirrhotic control group and 20 healthy control subjects their ages ranged (from 28-55 years with mean of (30 + 7.5. Serum and ascitic fluid of adhesion molecules as well as VEGF levels were significantly higher in cirrhotic patients with SBP as well as cirrhotic patients with non-infected ascites as compared to healthy control group. There were significant increase in serum and ascitic fluid level of leukocyte, PMN and ICAM-1 in SBP as compared to cirrhotic with non-infected ascites. There was non-significant decrease in serum and AF level of VEGF in cirrhotic control group as compared to SBP group. The ascitic fluid PMN and s-L Selectin were higher in culture positive SBP patients particularly in those with gram positive isolates, where these are non-significant increase in serum and ascitic fluid level of VEGF in culture positive SBP than culture negative cases. Positive correlation was found between serum and ascitic fluid level of ICAM-1 in SBP and non-infected cirrhotic group. Also, positive correlation was found between VEGF levels in serum ascetic fluid levels in both cirrhotic groups (SBP and non-infected cirrhotic group. These data suggest that: Significant elevated level of

  8. 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.

  9. 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...... treatment with nucleoside or nucleotide analogs (NUCs) for CHB. Materials and methods. Patients with CHB and advanced fibrosis or cirrhosis prior to treatment with NUCs for at least 1 year were offered inclusion in the study. We measured liver stiffness using transient elastography (TE) at follow-up. TE cut...... duration was 50.5 months. Among patients with cirrhosis prior to treatment, 26 (49%) had liver stiffness below 11.0 kPa at follow-up, suggesting regression of cirrhosis. Among patients with advanced fibrosis (F3) prior to treatment, 10 (77%) had liver stiffness below 8.1 kPa after treatment, suggesting...

  10. 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.

  11. New insights into cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

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

    2013-01-01

    beta-receptor function seem involved in the autonomic and cardiac dysfunction. Cirrhotic cardiomyopathy can be revealed by tissue Doppler imaging but is best demasked by physical or pharmacological stress. Liver transplantation may revert cardiac dysfunction but surgery and shunt insertion may also......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 reduced...

  12. 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.

  13. Percutaneous ethanol injection therapy of adenomatous hyperplastic nodules in cirrhotic liver disease

    International Nuclear Information System (INIS)

    In this study, we treated a total of 23 AHNs in 15 patients with percutaneous ethanol injection (PEI). The treatment included 6 to 8 PEIs, performed on an out-patient basis under sonographic guidance. A 22 G (0.7 mm) spinal needle was used. The total amount of alcohol delivered into each lesion was 8 to 25 ml (mean 14.9 ml). At the end of treatment, complete necrosis of the nodule was proved in all cases by multiple fine-needle biopsies and confirmed by CT and MR findings. During follow-up (9-41 months, mean 24 months) no recurrences were demonstrated. However, HCC occurred elsewhere in the liver of 4 patients and additional AHNs were detected in 2 patients. Thus, PEI proved able to cause complete ablation of AHNs, presumably preventing their malignant transformation. (orig.)

  14. 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 of the......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...

  15. 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

    International Nuclear Information System (INIS)

    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.)

  16. 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.)

  17. 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.

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

    International Nuclear Information System (INIS)

    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

  19. 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...... systems. As the disease progresses, the circulation becomes hyperdynamic, and signs of cardiac, pulmonary, and renal dysfunction are observed, in addition to reduced survival. Infections and an altered cardiac function known as cirrhotic cardiomyopathy may be precipitators for the development of other...

  20. An in vitro and in vivo analysis of the correlation between susceptibility-weighted imaging phase values and R2* in cirrhotic livers.

    Directory of Open Access Journals (Sweden)

    Ran Tao

    Full Text Available OBJECTIVE: To establish a baseline of susceptibility-weighted imaging (SWI phase value as a means of detecting iron abnormalities in cirrhotic liver and to analyze its relationship with R2*. MATERIALS AND METHODS: Sixteen MnCl(2 phantoms, thirty-seven healthy individuals and 87 cirrhotic patients were performed SWI and multi-echo T2*-weighted imaging, and the signal processing in NMR (SPIN software was used to measure the radian on SWI phase images and the R2* on T2* maps. The mean minus two times standard deviation (SD of Siemens Phase Unit (SPU in healthy individuals was designated as a threshold to separate the regions of interest (ROIs into high- and low-iron areas in healthy participants and cirrhotic patients. The SWI phase values of high-iron areas were calculated. The R2* values was measured in the same ROI in both healthy participants and patients. RESULTS: SWI phase values correlated linearly with R2* values in cases of MnCl(2 concentrations lower than 2.3 mM in vitro (r = -0.996, P<0.001. The mean value and SD of 37 healthy participants were 2003 and 15 (SPU, respectively. A threshold of 1973 SPU (-0.115 radians was determined. The SWI phase value and R2* values had a negative correlation in the cirrhotic patients (r = -0.742, P<0.001. However, no similar relationship was found in the healthy individuals (r = 0.096, P = 0.576. Both SWI phase values and R2* values were found to have significant correlations with serum ferritin concentrations in 42 patients with blood samples (r = -0.512, P = 0.001 and r = 0.641, P<0.001, respectively. CONCLUSION: SWI phase values had significant correlations with R2* after the establishment of a baseline on the phase image. SWI phase images may be used for non-invasive quantitative measurement of mild and moderate iron deposition in hepatic cirrhosis in vivo.

  1. 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

  2. Morbidity of surgery in previously undiagnosed cirrhotic patients

    International Nuclear Information System (INIS)

    Background: Undiagnosed cirrhotic patients are frequently encountered during routine and emergency surgery. These patients have a higher incidence of blood loss and wound infection, resulting in prolonged hospital stay. This study was conducted to highlight the possible complications which result in prolonged hospital stay in these patients. Method: A total of 38 patients were incidentally found to have cirrhosis out of a total of 1560 patients who underwent abdominal operation. Diagnosis was confirmed on per-operative liver biopsy and was suspected preoperatively in patient having abnormal liver function test. Per-operative bleeding, postoperative wound infection and hospital stay was compared in cirrhotic and non-cirrhotic patients. Results: The mean blood loss was 310 ml in cirrhotic patients as compared to 205 ml in non-cirrhotic patients which was statistically significant (p-value 0.008). Post-operative infection rate was 21 percentage in cirrhotic patients compared to non-cirrhotic patients 5 percentage. Significance was tested using Pearson Chi square test (0.042). The Average hospital stay was 10 days in cirrhotic patients and 7.5 days in non-cirrhotic patients respectively which was statistically significant (p-value 0.006). Conclusion: There is statistically significant difference in per-operative bleeding, wound infection and hospital stay in cirrhotic and non-cirrhotic patients. (author)

  3. 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

  4. Multidetector-row computed tomography (MDCT) for the diagnosis of hepatocellular carcinoma in cirrhotic candidates for liver transplantation: prevalence of radiological vascular patterns and histological correlation with liver explants

    International Nuclear Information System (INIS)

    To define the prevalence of different multidetector-row computed tomography (MDCT) vascular patterns and their histopathological correlation with liver explants, and to evaluate the accuracy of MDCT for the diagnosis of hepatocellular carcinoma (HCC). We retrospectively reviewed 125 cirrhotic patients imaged by MDCT before liver transplantation. Three main vascular patterns were identified: hypervascular lesion with washout (Hyper-L-Wo), hypervascular lesion without washout (Hyper-L) and non-hypervascular lesion (Hypo-L). Radiological findings were matched with histopathology of explants. Positive predictive value (PPV) and likelihood ratio (LR) were 95% and 18.66, respectively, for Hyper-L-Wo; 45% and 0.82 for Hyper-L; and 75% and 3 for Hypo-L of 20 mm or larger. Overall accuracy of MDCT for detection and characterisation of HCC was 89% and 43%, respectively. Sensitivity of MDCT for detection and characterisation was related to the lesion size, ranging from 78% (lesion smaller than 10 mm) to 98% (larger than 20 mm) and from 9% to 64%, respectively. MDCT established the accurate stage of disease in 46% of the patients, underestimated in 52% and overestimated in 2%. In cirrhotic patients, any Hyper-L-Wo detected by MDCT can be confidently considered to be HCC. Hyper-L larger than 10 mm and Hypo-L of 20 mm or larger are at high risk of HCC. However, even using MDCT and the newest imaging protocols, imaging underestimated the diagnosis of small HCC. (orig.)

  5. Threonine phosphorylation of rat liver glycogen synthase

    International Nuclear Information System (INIS)

    32P-labeled glycogen synthase specifically immunoprecipitated from 32P-phosphate incubated rat hepatocytes contains, in addition to [32P] phosphoserine, significant levels of [32P] phosphothreonine. When the 32P-immunoprecipitate was cleaved with CNBr, the [32P] phosphothreonine was recovered in the large CNBr fragment (CB-2, Mapp 28 Kd). Homogeneous rat liver glycogen synthase was phosphorylated by all the protein kinases able to phosphorylate CB-2 in vitro. After analysis of the immunoprecipitated enzyme for phosphoaminoacids, it was observed that only casein kinase II was able to phosphorylate on threonine and 32P-phosphate was only found in CB-2. These results demonstrate that rat liver glycogen synthase is phosphorylated at threonine site(s) contained in CB-2 and strongly indicate that casein kinase II may play a role in the ''in vivo'' phosphorylation of liver glycogen synthase. This is the first protein kinase reported to phosphorylate threonine residues in liver glycogen synthase

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

    OpenAIRE

    Agustín Martín-Rodríguez; María A. Pérez-San-Gregorio; Elisabeth Domínguez-Cabello; Eduardo Fernández-Jiménez; Ángel Bernardos-Rodríguez

    2014-01-01

    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 recruite...

  7. Liver and spleen stiffness and other noninvasive methods to assess portal hypertension in cirrhotic patients: a review of the literature.

    Science.gov (United States)

    Colecchia, Antonio; Marasco, Giovanni; Taddia, Martina; Montrone, Lucia; Eusebi, Leonardo H; Mandolesi, Daniele; Schiumerini, Ramona; Di Biase, Anna R; Festi, Davide

    2015-09-01

    Portal hypertension (PH) is one of the most important causes of morbidity and mortality in patients with chronic liver disease. PH measurement is crucial to stage and predict the clinical outcome of liver cirrhosis. Measurement of hepatic vein pressure gradient is considered the gold standard for assessment of the degree of PH; however, it is an invasive method and has not been used widely. Thus, noninvasive methods have been proposed recently. We critically evaluated serum markers, abdominal ultrasonography, and particularly liver and spleen stiffness measurement, which represent the more promising methods to stage PH degree and to assess the presence/absence of esophageal varices (EV). A literature search was carried out on MEDLINE, EMBASE, Web of Science, and Scopus for articles and abstracts. The search terms used included 'liver cirrhosis', 'portal hypertension', 'liver stiffness', 'spleen stiffness', 'ultrasonography', and 'portal hypertension serum biomarker'. The articles cited were selected on the basis of their relevance to the objective of the review. The results of available studies indicate that individually, these methods have a mild accuracy in predicting the presence of EV, and thus they cannot substitute endoscopy to predict EV. When these tests were used in combination, their accuracy increased. In addition to the PH staging, several serum markers and spleen stiffness measurement can predict the clinical outcome of liver cirrhosis with a good accuracy, comparable to that of hepatic vein pressure gradient. In the future, noninvasive methods could be used to select patients requiring further investigations to identify the best tailored clinical management. PMID:26020376

  8. 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...

  9. [Cirrhotic cardiomyopathy: a specific entity].

    Science.gov (United States)

    Brondex, A; Arlès, F; Lipovac, A-S; Richecoeur, M; Bronstein, J-A

    2012-04-01

    Cirrhosis is a frequent and severe condition, which is the late stage of numerous chronic liver diseases. It is associated with major hemodynamic alterations characteristic of hyperdynamic circulation and with a series of structural, functional, electrophysiological and biological heart abnormalities termed cirrhotic cardiomyopathy. The pathogenesis of this syndrome is multifactorial. It is usually clinically latent or mild, likely because the peripheral vasodilatation significantly reduces the left ventricle afterload. However, sudden changes of hemodynamic state (vascular filling, surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts and orthotopic liver transplantation) or myocardial contractility (introduction of beta-blocker therapy) can unmask its presence, and sometimes convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome. This entity has been described recently, and its diagnostic criteria are still under debate. To date, current management recommendations are empirical, nonspecific measures. Recognition of cirrhotic cardiomyopathy depends on a high level of awareness for the presence of this syndrome, particularly in patients with advanced cirrhosis who undergo significant surgical, pharmacological or physiological stresses. PMID:22115174

  10. Androgen-linked control of rat liver carbonic anhydrase III.

    OpenAIRE

    Shiels, A.; Jeffery, S; Phillips, I. R.; Shephard, E A; Wilson, C. A.; Carter, N D

    1983-01-01

    The concentration of carbonic anhydrase III (CAIII) in male rat liver was found to be 30 times greater than that in the female. Castration of male rats led to marked reduction in liver CAIII concentrations which could be partially restored to control levels by testosterone replacement. Marked developmental and senescence changes in liver CAIII were also observed in male rats.

  11. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    OpenAIRE

    Aya M Fattouh; El-Shabrawi, Mortada H; Enas H Mahmoud; Wafaa O Ahmed

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue...

  12. 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.

  13. [Adrenal insufficiency in cirrhotic patients].

    Science.gov (United States)

    Orozco, Federico; Anders, María; Mella, José; Antinucci, Florencia; Pagano, Patricia; Esteban, Paula; Cartier, Mariano; Romero, Gustavo; Francini, Bettina; Mastai, Ricardo

    2016-01-01

    Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality. PMID:27576278

  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. Prognostic indicators in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, J H; Nielsen, G

    1988-01-01

    The relationships between portal pressure, liver function and clinical variables on one hand and development of variceal hemorrhage and death on the other were investigated in 58 men with newly diagnosed alcoholic cirrhosis. Portal pressure was determined during hepatic vein catheterization as...... prognosis in alcoholic cirrhotic men may be significantly improved by information about size of esophageal varices and level of portal pressure....

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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. 

  18. Prevalence and severity of hepatopulmonary syndrome and its influence on survival in cirrhotic patients evaluated for liver transplantation.

    Science.gov (United States)

    Pascasio, J M; Grilo, I; López-Pardo, F J; Ortega-Ruiz, F; Tirado, J L; Sousa, J M; Rodriguez-Puras, M J; Ferrer, M T; Sayago, M; Gómez-Bravo, M A; Grilo, A

    2014-06-01

    The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO2 ) oxygen gradient (A-a PO2 ) ≥20 mmHg in the supine position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen. PMID:24730359

  19. Metformin promotes isolated rat liver mitochondria impairment

    OpenAIRE

    Carvalho, Cristina; Correia, Sónia; Santos, Maria,; Seiça, Raquel; Oliveira, Catarina; Moreira, Paula

    2008-01-01

    Abstract Metformin, a drug widely used in the treatment of type 2 diabetes, has recently received attention due to the new and contrasting findings regarding its effects on mitochondrial function. In the present study, we evaluated the effect of metformin in isolated rat liver mitochondria status. We observed that metformin concentrations =8 mM induce an impairment of the respiratory chain characterized by a decrease in RCR and state 3 respiration. However, only metformin concentrations =10 ...

  20. Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis

    Science.gov (United States)

    Zhang, Cheng-Gang; Zhang, Bin; Deng, Wen-Sheng; Duan, Ming; Chen, Wei; Wu, Zhi-Yong

    2016-01-01

    AIM: To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). METHODS: Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson’s trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. RESULTS: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. CONCLUSION: For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to

  1. 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 liv...

  2. 31P-NMR studies on membrane phospholipids in microsomes, rat liver slices and intact perfused rat liver

    NARCIS (Netherlands)

    Kruijff, B. de; Rietveld, A.; Cullis, P.R.

    1980-01-01

    1. 1. The 36.4 and 81 MHz 31P-NMR spectra of isolated rat liver microsomes, rat liver slices and perfused rat liver have been recorded in the 4–40°C temperature range. 2. 2. In isolated microsomes at 37°C the majority of the phospholipids undergo isotropic motion, whereas at 4°C most of the phospho

  3. 31P-NMR studies on membrane phospholipids in microsomes, rat liver slices and intact perfused rat liver

    OpenAIRE

    de Kruijff, B.; Rietveld, A.; Cullis, P.R.

    1980-01-01

    1. 1. The 36.4 and 81 MHz 31P-NMR spectra of isolated rat liver microsomes, rat liver slices and perfused rat liver have been recorded in the 4–40°C temperature range. 2. 2. In isolated microsomes at 37°C the majority of the phospholipids undergo isotropic motion, whereas at 4°C most of the phospholipids give rise to typical ‘bilayer’ spectra. 3. 3. Isolated hydrated rat liver microsomal phosphatidylethanolamine is organised in the hexagonal HII phase above 7°C. 4. 4. The Mn2+ permeability of...

  4. Hepatoblast and mesenchymal cell-specific gene-expression in fetal rat liver and in cultured fetal rat liver cells

    OpenAIRE

    Mansuroglu, Tümen; Dudás, József; Elmaouhoub, Abderrahim; Joza, Tobias; Ramadori, Giuliano

    2009-01-01

    The aim of this study was to determine whether passaged rat fetal liver cells are functional hepatoblasts. Hepatocyte/hepatoblast- and liver myofibroblast-gene-expressions were studied in adult and fetal rat liver tissues as well as in primary and passaged cultures of isolated rat fetal liver cells at both the mRNA and protein level. Desmin- and Alpha-Smooth Muscle Actin (SMA)-positive cells were located in the walls of liver vessels, whereas Desmin-positive/SMA-negative cells were distribute...

  5. 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

    International Nuclear Information System (INIS)

    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−1 100 mL−1, respectively) was significantly less than that in patients without cirrhosis (213 and 174 mL min−1 100 mL−1, respectively; p = 0.0081 and 0.0294, respectively). Arterial perfusion of the spleen (111 mL min−1 100 mL−1) and the body of the pancreas (112 mL min−1 100 mL−1) in patients with cirrhosis was also significantly decreased compared with that in patients without cirrhosis (spleen, 162 mL min−1 100 mL−1, p = 0.0020; body of pancreas, 133 mL min−1 100 mL−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

  6. 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.

  7. Detection of recurrent hepatocellular carcinoma in cirrhotic liver after transcatheter arterial chemoembolization: Value of quantitative color mapping of the arterial enhancement fraction of the liver

    International Nuclear Information System (INIS)

    To investigate the additional diagnostic value of color mapping of the hepatic arterial enhancement fraction (AEF) for detecting recurrent or residual hepatocellular carcinoma (HCC) in patients treated with transcatheter arterial chemoembolization (TACE). Seventy-six patients with 126 HCCs, all of whom had undergone previous TACE, and subsequently, underwent follow-up multiphasic liver CT scans, were included in this study. Quantitative color maps of the AEF of the whole liver were created, by using prototype software with non-rigid registration. The AEF was defined as the ratio of the attenuation increment during the arterial phase to the attenuation increment during the portal phase. Two radiologists independently analyzed the two image sets at a two-week interval, i.e., the multiphasic CT image set and the second image set of the AEF color maps and the CT images. The additional diagnostic value of the AEF color mapping was determined, by the use of the jackknife-alternative free-response receiver-operating-characteristic analysis. The sensitivity and positive predictive values for detecting HCCs of each image set were also evaluated and compared. The reader-averaged figures of merit were 0.699 on the initial interpretation of the MDCT image set, and 0.831 on the second interpretation of the combined image set; the difference between the two interpretations was significant (p value < 0.001). The mean sensitivity for residual or recurrent HCC detection increased from 62.7% on the initial analysis to 82.1% on the second analysis using the AEF color maps (p value < 0.001). The mean positive predictive value for HCC detection was 74.5% on the initial analysis using MDCT, and 71.6% on the second analysis using AEF color mapping. Quantitative color mapping of the hepatic AEF may have the possibility to increase the diagnostic performance of MDCT for the detection of recurrent or residual HCC without the potential risk of radiation-related hazards.

  8. Ideal Experimental Rat Models for Liver Diseases.

    Science.gov (United States)

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  9. Food restriction affects energy metabolism in rat liver mitochondria.

    OpenAIRE

    Dumas, Jean-François; Roussel, Damien; Simard, Gilles; Douay, Olivier; Foussard, Françoise; Malthiery, Yves; Ritz, Patrick

    2004-01-01

    To examine the effect of 50% food restriction over a period of 3 days on mitochondrial energy metabolism, liver mitochondria were isolated from ad libitum and food-restricted rats. Mitochondrial enzyme activities and oxygen consumption were assessed spectrophotometrically and polarographically. With regard to body weight loss (-5%), food restriction decreased the liver to body mass ratio by 7%. Moreover, in food-restricted rats, liver mitochondria displayed diminished state 3 (-30%), state 4-...

  10. Creatine supplementation and oxidative stress in rat liver

    OpenAIRE

    Araújo, Michel B; Moura, Leandro P; Junior, Roberto C Vieira; Junior, Marcelo C; Dalia, Rodrigo A; Sponton, Amanda C; Ribeiro, Carla; Mello, Maria Alice R

    2013-01-01

    Background The objective of this study was to determine the effects of creatine supplementation on liver biomarkers of oxidative stress in exercise-trained rats. Methods Forty 90-day-old adult male Wistar rats were assigned to four groups for the eight-week experiment. Control group (C) rats received a balanced control diet; creatine control group (CCr) rats received a balanced diet supplemented with 2% creatine; trained group (T) rats received a balanced diet and intense exercise training eq...

  11. Mutagenicity of comfrey (Symphytum Officinale) in rat liver.

    Science.gov (United States)

    Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

    2005-03-14

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant. PMID:15726100

  12. Mutagenicity of comfrey (Symphytum Officinale) in rat liver

    OpenAIRE

    MEI, N.; Guo, L.; Fu, P P; Heflich, R H; Chen, T.

    2005-01-01

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

  13. 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.

  14. Differential protein expression in perfusates from metastasized rat livers

    OpenAIRE

    Zhang, Yang; Li, Menglin; Wei, Lilong; Zhu, Lisi; Hu, Siqi; Wu, Shuzhen; Ma, Sucan; Gao, Youhe

    2013-01-01

    Background Liver perfusates exhibit theoretical advantages regarding the discovery of disease biomarkers because they contain proteins that readily enter the blood-stream, and perfusion preserves the disease state in its natural context. The purpose of the study is to explore the value of liver perfusate proteome in the biomarker discovery of liver diseases. Results In this study, 86 differentially expressed proteins were identified in perfusates from isolated rat livers metastasized by Walke...

  15. Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

    OpenAIRE

    An Jiang; Chang Liu; Feng Liu; Yu-Long Song; Quan-Yuan Li; Liang Yu; Yi Lv

    2012-01-01

    AIM: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. METHODS: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4  °C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. ...

  16. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

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

    2015-01-01

    animals died during the study. There were no differences between in body weight, liver weight, liver regeneration rate or biochemical markers at any time during the study. CONCLUSION: The results of this study indicate that stress and the induction of depression-like state do not affect the process 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 a...

  17. Gluconeogenesis in the perfused rat liver.

    Science.gov (United States)

    Hems, R; Ross, B D; Berry, M N; Krebs, H A

    1966-11-01

    1. A modification of the methods of Miller and of Schimassek for the perfusion of the isolated rat liver, suitable for the study of gluconeogenesis, is described. 2. The main modifications concern the operative technique (reducing the period of anoxia during the operation to 3min.) and the use of aged (non-glycolysing) red cells in the semi-synthetic perfusion medium. 3. The performance of the perfused liver was tested by measuring the rate of gluconeogenesis, of urea synthesis and the stability of adenine nucleotides. Higher rates of gluconeogenesis (1mumole/min./g.) from excess of lactate and of urea synthesis from excess of ammonia (4mumoles/min./g. in the presence of ornithine) were observed than are likely to occur in vivo where rates are limited by the rate of supply of precursor. The concentrations of the three adenine nucleotides in the liver tissue were maintained within 15% over a perfusion period of 135min. 4. Ca(2+), Na(+), K(+), Mg(2+) and phosphate were found to be required at physiological concentrations for optimum gluconeogenesis but bicarbonate and carbon dioxide could be largely replaced by phosphate buffer without affecting the rate of gluconeogenesis. 5. Maximal gluconeogenesis did not decrease maximal urea synthesis in the presence of ornithine and ammonia and vice versa. This indicates that the energy requirements were not limiting the rates of gluconeogenesis or of urea synthesis. 6. Addition of lactate, and especially ammonium salts, increased the uptake of oxygen more than expected on the basis of the ATP requirements of the gluconeogenesis and urea synthesis. PMID:5966267

  18. 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. PMID:22807255

  19. 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

  20. Male Rat Susceptibility for Liver and Kidney Injury

    Directory of Open Access Journals (Sweden)

    Sarkawt H. Hamad

    2016-04-01

    Full Text Available The experimental study of this paper was designed to investigate male rat susceptibility to liver injury. A combination of two experimental animal models (Lead acetate for tissue injury (80 mg / L and castration had been used on twenty male rats, they were divided into two groups sham (n = 10; castrated (n = 10. Results revealed that, liver weight reduced significantly (P < 0.05 in sham group in comparison with castrated rats, but kidney weight changed slightly. Also, serum aminotransferase (AST was significantly higher in sham versus castrated rats. Neither alanine aminotransferase (ALT and alkaline phosphatase (ALP nor malondialdehyde (MDA changed. In conclusion, the absence of male sex hormone would delay tissue injury of male rat organs especially liver organ.

  1. Differentiation potential of the fetal rat liver-derived cells.

    OpenAIRE

    Zygmunt Pojda; Jerzy Moraczewski; Tomasz Oldak; Marzena Jastrzewska; Agnieszka Gajkowska; Iwona Grabowska; Eugeniusz K Machaj

    2005-01-01

    Mesenchymal stem cells derived from bone marrow or several fetal tissues can be expanded and differentiated into other cell lines. The fetal liver is the source of early hematopoietic cells and also, as a fetal tissue, may be considered as a source of pluripotent stem cells. The differentiation potential of fetal rat liver cells have been examined. Freshly isolated liver cells from 14-d fetuses were cultured in Dulbecco medium supplemented with 10% FCS. The plastic-adherent cells were then pa...

  2. 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.

  3. Supercooling Preservation Of The Rat Liver For Transplantation

    Science.gov (United States)

    Bruinsma, Bote G.; Berendsen, Tim A.; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L.; Uygun, Korkut

    2015-01-01

    The current standard for liver preservation is limited in duration. Employing a novel subzero preservation technique that includes supercooling and machine perfusion can significantly improve preservation and prolong storage times. By loading rat livers with cryoprotectants to prevent both intra- and extracellular ice formation and protect against hypothermic injury, livers can be cooled to −6 °C without freezing and kept viable for up to 96 hours. Here, we describe the procedures of loading cryoprotectants by means of subnormothermic machine perfusion (SNMP), controlled cooling to a supercooled state, followed by SNMP recovery and orthotopic liver transplantation. PMID:25692985

  4. Value of US in cirrhotic hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Cirrhotic liver hepato carcinoma (HCC) was evaluated with both US and CT. In a group of 600 cirrhotic patients 64 had HCC, which was confirmed at histology in 24 cases, and by disease evolution in the other 40; single focal degeneration was proven in 40 patients, multiple (2, 3 focal lesions), or diffuse degeneration (more than 3 focal lesions) in the remaining 24. Sixteen patients had associated portal thrombosis. US recognized 38/40 single HCC, 22/24 multiple or diffuse lesions, and 11/16 portal vein thromboses. Degeneration was most frequently hypo/isoechoic in small tumors, hyperechoic and mixed in large lesions. When small lesions are hyperechoic their differentiation from both hemangiomas and regeneration noduli is extremely difficult. In such cases CT is mandatory. US diagnostic accuracy is by far superior to that of CT: 95% vs 85% in single lesions and 91.6% vs 87.5% in diffuse forms. Overall accuracy is 93.7% for US and 85.9% for CT. The authors believe that US should be performed every 6 months on cirrhotic patients, so as to allow HCC to be detected in time for radical surgery, while CT should be performed only when doubts persist

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Serial analysis of gene expression (SAGE) in rat liver regeneration

    International Nuclear Information System (INIS)

    We have applied serial analysis of gene expression for studying the molecular mechanism of the rat liver regeneration in the model of 70% partial hepatectomy. We generated three SAGE libraries from a normal control liver (NL library: 52,343 tags), from a sham control operated liver (Sham library: 51,028 tags), and from a regenerating liver (PH library: 53,061 tags). By SAGE bioinformatics analysis we identified 40 induced genes and 20 repressed genes during the liver regeneration. We verified temporal expression of such genes by real time PCR during the regeneration process and we characterized 13 induced genes and 3 repressed genes. We found connective tissue growth factor transcript and protein induced very early at 4 h after PH operation before hepatocytes proliferation is triggered. Our study suggests CTGF as a growth factor signaling mediator that could be involved directly in the mechanism of liver regeneration induction

  12. Stereochemical course of rat liver cysteinesulfinic acid decarboxylase

    International Nuclear Information System (INIS)

    Rat liver homogenate, exhibiting very high cysteinesulfinic acid (CSA) decarboxylase activity, was used to decarboxylate [2-2H1]-L-CSA to [2-2H1]-hypotaurine (HT)2. The latter was desulfurized with Raney nickel to [1-2H1]-ethylamine. A 2H NMR spectrum of the (-)camphanamide derivative of the latter revealed the labeling stereochemistry. Similarly, unlabeled CSA was decarboxylated by rat liver homogenate in a D2O containing medium, and the product HT similarly desulfurized and derivatized. The reactions were followed by use of a new HPLC-based assay for CSA decarboxylase which allows simultaneous measurement of glutamate decarboxylation (which was negligible with rat liver homogenates). The results show that the decarboxylation proceeds with retention of configuration

  13. 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.

  14. Sulphation of the flavonoids quercetin and catechin by rat liver.

    Science.gov (United States)

    Shali, N A; Curtis, C G; Powell, G M; Roy, A B

    1991-07-01

    1. The isolated perfused rat liver forms three sulphated metabolites from each of the flavonoids, quercetin and catechin: these are secreted into the bile and the perfusate. 2. Quercetin gives two double conjugates, containing sulphate and glucuronic acid, and one sulphate: catechin gives one such double conjugate and two sulphates. 3. This sulphation is not inhibited by 60 microM 2,6-dichloro-4-nitrophenol which almost completely inhibits the sulphation of harmol in this perfused liver system. 4. The sulphation of harmol by the perfused liver is not inhibited by the flavonoids. 5. Unfractionated sulphotransferases from rat liver catalyse sulphate conjugation of quercetin and catechin in vitro by a reaction inhibited by pentachlorophenol or dichloronitrophenol: the flavonoids inhibit the sulphation of 4-nitrophenol by this system. 6. The results with the two systems are discussed and shown to be compatible. PMID:1776264

  15. The Need to Handicap the Recipient's Native Liver in the Rat Model of Heterotopic Auxiliary Liver Transplantation

    OpenAIRE

    Ye-Dong Fan; Marleen Praet; Bernard De Hemptinne

    1999-01-01

    In the rat model of heterotopic auxiliary liver transplantation (HALTx), the opinion varies on whether and how the recipient's native liver should be handicapped. To avoid atrophy of the transplanted organ, in this study, two different handicaps were evaluated and their effects on post-operative animal survival and liver biology are described. With a sole portacaval shunt (group 1) all rats survived longer than 3 months. An additional handicap of the liver with either a 68% partial hepatectom...

  16. Expression of ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells

    OpenAIRE

    Piscaglia, Fabio; Dudás, József; Knittel, Thomas; Rocco, Paola; Kobold, Dominik; Saile, Bernhard; Zocco, Maria; Timpl, Rupert; Ramadori, Giuliano

    2009-01-01

    Fibulin-2 has previously been considered as a marker to distinguish rat liver myofibroblasts from hepatic stellate cells. The function of other fibulins in acute or chronic liver damage has not yet been investigated. The aim of this study has been to evaluate the expression of fibulin-1 and -2 in models of rat liver injury and in human liver cirrhosis. Their cellular sources have also been investigated. In normal rat liver, fibulin-1 and -2 were both mainly present in the portal field. Fibuli...

  17. Antidepressant and Anxiolytic Effects of Cod Liver Oil in Rats

    Directory of Open Access Journals (Sweden)

    Tahira Perveen*, Faiza Razi, Saida Haider, Hina Qayyum and Darakhshaan J. Haleem

    2013-01-01

    Full Text Available Cod-liver oil is a rich source of omega 3 fatty acids and has been widely used as omega 3 fatty acids supplementation. Regarding omega-3 fatty acid beneficial effects in humans, this study was designed to investigate the effect of repeated administration of cod-liver oil on the locomotion and behaviors of rats, including depression, anxiety and the 5-Hydroxy tryptamine (5-HT metabolism. After four weeks oral administration of cod-liver oil, open field test was used to measure the locomotor and exploratory activity. Elevated plus maze test was used to measure anxiety. Cod-liver oil significantly increased locomotion and produced anxiolytic effects in rats. Antidepressant effect of cod-liver oil was monitored by forced swim test (FST in which struggling time of test animals was increased significantly. 5-HT turnover also increased significantly following the oral repeated administration of cod liver oil in test animals. The results suggest that cod-liver oil has antidepressant and anti-anxiety effects.

  18. Supercooling preservation and transplantation of the rat liver.

    Science.gov (United States)

    Bruinsma, Bote G; Berendsen, Tim A; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L; Uygun, Korkut

    2015-03-01

    The current standard for liver preservation involves cooling of the organ on ice (0-4 °C). Although it is successful for shorter durations, this method of preservation does not allow long-term storage of the liver. The gradual loss of hepatic viability during preservation puts pressure on organ sharing and allocation, may limit the use of suboptimal grafts and necessitates rushed transplantation to achieve desirable post-transplantation outcomes. In an attempt to improve and prolong liver viability during storage, alternative preservation methods are under investigation. For instance, ex vivo machine perfusion systems aim to sustain and even improve viability by supporting hepatic function at warm temperatures, rather than simply slowing down deterioration by cooling. Here we describe a novel subzero preservation technique that combines ex vivo machine perfusion with cryoprotectants to facilitate long-term supercooled preservation. The technique improves the preservation of rat livers to prolong storage times as much as threefold, which is validated by successful long-term recipient survival after orthotopic transplantation. This protocol describes how to load rat livers with cryoprotectants to prevent both intracellular and extracellular ice formation and to protect against hypothermic injury. Cryoprotectants are loaded ex vivo using subnormothermic machine perfusion (SNMP), after which livers can be cooled to -6 °C without freezing and kept viable for up to 96 h. Cooling to a supercooled state is controlled, followed by 3 h of SNMP recovery and orthotopic liver transplantation. PMID:25692985

  19. Differentiation potential of the fetal rat liver-derived cells.

    Directory of Open Access Journals (Sweden)

    Zygmunt Pojda

    2005-12-01

    Full Text Available Mesenchymal stem cells derived from bone marrow or several fetal tissues can be expanded and differentiated into other cell lines. The fetal liver is the source of early hematopoietic cells and also, as a fetal tissue, may be considered as a source of pluripotent stem cells. The differentiation potential of fetal rat liver cells have been examined. Freshly isolated liver cells from 14-d fetuses were cultured in Dulbecco medium supplemented with 10% FCS. The plastic-adherent cells were then passaged up to 10 times. Freshly isolated cells and cells from every passage were cultured in hematopoiesis-promoting environment that consists of methylcelulose supplemented with FCS, rat IL-3, human IL-6 and Epo. Parallely these cells were incubated in co-culture with rat muscle satellite cells (Dulbecco medium with 10% FCS and 10% HS to examine their myogenic potential. Culture in methylcelulose resulted in a high number of GM and Mix colonies in case of freshly isolated liver cells and the number of colonies decreased according to the number of passages. In case of cells from 4th passage, there ware no hematopoietic colonies in culture. In contrast--freshly isolated cells were not able to fuse with rat satellite cells and form the myotubes. This ability appeared in plastic-adherent cells just from the second passage and increases to 5th passage. The cells from every next passage up to 10th when co-cultured with satellite cells participated in myotube formation at the same high level. This result may suggest that in the 14-d rat liver there exist at least two subpopulations of cells: the non-adherent hematopoietic cell population, and the population of plastic-adherent cells capable of differentiating into myotubes. Since the attempts to redifferentiate hematopoietic subpopulation into myopoiesis, or myopoietic subpopulation into hematopoiesis failed, it may be concluded that at least under our experimental conditions the fetal liver cells do not reveal the

  20. Correlation between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models

    Institute of Scientific and Technical Information of China (English)

    Qing-He Nie; Ya-Fei Zhang; Yu-Mei Xie; Xin-Dong Luo; Bin Shao; Jun Li; Yong-Xing Zhou

    2006-01-01

    AIM: To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immuneinduced and CCL4-induced liver fibrosis models in rats.METHODS: Immune-induced and CCL4-induced liver fibrosis models were established by dexamethasone (0.01 mg) and CCL4 respectively. Serum TIMP-1 level was detected with ELISA, while histopathological grade of liver biopsy was evaluated. Spearman rankcorrelation test was used to analyse the difference of the correlation between the TIMP-1 expression and hepatic fibrosis in the two fibrosis models. Furthermore,in situ hybridization was used to determine the expression difference of TIMP-1 mRNA in the two models.RESULTS: Positive correlation existed between serum TIMP-1 level of immune induced group and the histopathological stages of fibrosis liver of corresponding rats (Spearman rank-correlation test, rs = 0.812, P < 0.05), and the positivein situ hybridization signal of TIMP-1 mRNA was strong. In CCL4-induced liver fibrosis model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant(Spearman rank-correlation test, rs = 0.229, P > 0.05). And compared with immune-induced model,the positive in situ hybridization signal of TIMP-1 mRNA was weaker, while the expression variation was higher in hepatic fibrosis of the same severity.CONCLUSION: The correlations between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models are different. In immune-induced model, serum TIMP-1 level could reflect the severity of liver fibrosis,while in CCL4-induced model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant.

  1. Effects of hypergravity on rat liver regeneration

    Science.gov (United States)

    Feller, D. D.

    1982-01-01

    The effects of centrifugation on liver regrowth were examined by measuring mitotic activity. The results indicate that the increased gravity caused a delay in the onset of mitotic activity and a significant decrease in overall mitotic activity.

  2. Expression of exogenous rat collagenase in vitro and in a rat model of liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Ji-Yao Wang; Jin-Sheng Guo; Chang-Qing Yang

    2002-01-01

    AIM: The present study was conducted to test thehypothesis that the introduction of the collagenase geneinto tissue culture cells and into a rat model of liver fibrosiswould result in the expression of enzymatically active product.METHODS: FLAG-tagged full-length rat collagenase cDNAwas PCR amplified and cloned into a mammalian expressionvector. NIH3T3 cells were then transiently transfected withthis construct. Expression of exogenous collagenase mRNAwas assessed by RT-PCR, and the exogenous collagenasedetected by Western blotting using anti-FLAG monoclonalantibodyEnzymatic activity was detected by gelatinzymography. To determine the effects of exogenouscollagenase production in vivo, the construct was boundto glycosyl-poly-L-lysine and then transduced into rats thathad developed liver fibrosis as a result of CCI4 plus ethanoltreatment. The hepatic expression of the construct and itseffect on the formation of liver fibrosis were demonstratedusing RT-PCR and immunohistochemistry.RESULTS: It was found that exogenously expressed ratcollagenase mRNA could be detected in NTH3T3 cellsfollowing transfection. Enzymatic ally active collagenase couldalso be detected in the culture medium. The recombinantplasmid was also expressed in rat liver after in vivo genetransfer. Expression of exogenous rat collagenase correlatedwith decreased deposition of collagen types I and Ⅲ in thelivers of rats with experimentally induced liver fibrosis.CONCLUSION: The expression of active exogenous ratcollagenase could be achieved in vitro and in vivo. It wassuggested that in vivo expression of active exogenouscollagenase may have therapeutic effects on the formationof liver fibrosis.

  3. 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.

  4. Assessment of thorotrast redistribution in liver tissue of the rat

    International Nuclear Information System (INIS)

    The purpose of this study is to examine gammaspectrometrically and histo-autoradiographically in samples of self-regenerating liver tissue from rats after partial resection of the organ, whether a redistribution of ThO2 is stimulated by the process of regeneration and, if so, whether this redistribution is taking place predominantly at the organ level itself. (orig./MG)

  5. Sirolimus influence on hepatectomy-induced liver regeneration in rats

    Directory of Open Access Journals (Sweden)

    Edimar Leandro Toderke

    2014-06-01

    Full Text Available OBJECTIVE: To evaluate the influence of sirolimus on liver regeneration triggered by resection of 70% of the liver of adult rats. METHODS: we used 40 Wistar rats randomly divided into two groups (study and control, each group was divided into two equal subgroups according to the day of death (24 hours and seven days. Sirolimus was administered at a dose of 1mg/kg in the study group and the control group was given 1 ml of saline. The solutions were administered daily since three days before hepatectomy till the rats death to removal of the regenerated liver, conducted in 24 hours or 7 days after hepatectomy. Liver regeneration was measured by the KWON formula, by thenumber of mitotic figures (hematoxylin-eosin staining and by the immunohistochemical markers PCNA and Ki-67. RESULTS: there was a statistically significant difference between the 24h and the 7d groups. When comparing the study and control groups in the same period, there was a statistically significant variation only for Ki-67, in which there were increased numbers of hepatocytes in cell multiplication in the 7d study group compared with the 7d control group (p = 0.04. CONCLUSION: there was no negative influence of sirolimus in liver regeneration and there was a positive partial effect at immunohistochemistry with Ki-67.

  6. 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.

  7. Aluminium toxicity in the rat liver and brain

    International Nuclear Information System (INIS)

    To investigate the etiology of Alzheimer's disease, we examined the brain and liver tissue uptake of aluminium 5-75 days after aluminium injection into healthy rats. Ten days after the last injection, Al was detected in the brain and the brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Al was also demonstrated in the liver and the liver cell nuclei by PIXE analysis and electron energy loss spectrometry (EELS). The morphological changes of the rat brain examined 75 days after the injection were similar to those which have been reportedly observed in the brain of patients with Alzheimer's disease. These results support the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium in the brain, as well as the nuclei of brain cells. (orig.)

  8. Antiulcer activity of cod liver oil in rats

    Directory of Open Access Journals (Sweden)

    Khare Salaj

    2008-01-01

    Full Text Available Objective: Cod liver oil is used widely as a dietary supplement. The present study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and 1 g/kg, p.o. on gastric and duodenal ulcers. Materials and Methods: The study was carried out on different gastric ulcer models such as acetic acid induced chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using cysteamine hydrochloride (HCl. Ranitidine (50 mg/kg p.o. and misoprostol (100 µg/kg, p.o. were used as standard drugs. Results: Both doses of cod liver oil showed gastric ulcer healing effect in acetic acid induced chronic gastric ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced ulcer. Cod liver oil also produced a significant reduction in the development of stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high dose of cod liver oil (1 g/kg, p.o. was more effective compared to the low dose (0.5 g/kg, p.o.. Conclusion: Cod liver oil increases healing of gastric ulcers and prevents the development of experimentally induced gastric and duodenal ulcers in rats.

  9. 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.

  10. 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.

  11. Ferritin-dependent radical generation in rat liver homogenates

    International Nuclear Information System (INIS)

    The hypothesis of this study was that mammalian ferritin (FER) has the ability of releasing Fe in the tissue to catalyze the generation of free radicals, such as ascorbyl (A·) and hydroxyl radical (·OH), that might lead to the damage of FER itself. The rat liver homogenates exhibited an electron paramagnetic resonance (EPR) signal with the spectral features (aH = 1.88 G, g = 2.0054) of A·. The addition to the reaction medium of isolated rat liver FER increased by 3-fold the EPR signal, as compared to the recorded value in its absence. Isolated microsomes from rat liver incubated during 10 min showed a signal with the spectral features (aH = 15 G, g = 2.0062) of ·OH. The addition of FER in the presence of either ethylenediamine-tetraacetic acid (EDTA) or adenosine-5'-triphosphate (ATP) significantly increased the recorded spectra. The labile Fe pool (LIP) in the homogenate was assessed by EPR. The rat liver homogenates exhibited an EPR signal with the spectral features (g = 4.3) of the Fe2+ and was significantly increased by the addition of FER (3-fold). The oxidation profile of the isolated FER from rat liver was analyzed after incubation with 10 mM ascorbate (AH-). A drastic increase in the width of the band suggested alterations to the protein structure. The FER content of tryptophan (Trp) and thiols was significantly lower when the incubation was performed in the presence of AH- as compared to the recorded effect in its absence. The data in tissue homogenates presented here showed that radical generation is associated to FER Fe release, and moreover that the FER protein itself was affected during this process.

  12. 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.

  13. Novel Bioimaging Techniques of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry for Diagnosis Of Fibrotic and Cirrhotic Liver Disorders

    OpenAIRE

    Weiskirchen, Ralf; Gassler, Nikolaus; Bosserhoff, Anja K; Becker, J. Sabine; Pornwilard, M. M.

    2013-01-01

    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 spe...

  14. Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

    Science.gov (United States)

    Okumura, Shinya; Teratani, Takumi; Fujimoto, Yasuhiro; Zhao, Xiangdong; Tsuruyama, Tatsuaki; Masano, Yuki; Kasahara, Naoya; Iida, Taku; Yagi, Shintaro; Uemura, Tadahiro; Kaido, Toshimi; Uemoto, Shinji

    2016-09-01

    Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD. PMID:27102080

  15. Regenerating Rat Liver: Correlations Between Estrogen Receptor Localization and Deoxyribonucleic Acid Synthesis

    OpenAIRE

    Francavilla, Antonio; Di Leo, Alfredo; Eagon, Patricia K.; Wu, Shi-Quin; Ove, Peter; Van Thiel, David H.; Starzl, Thomas E.

    1984-01-01

    Estrogen receptor activity was quantitated in the cytosol and nucleus of normal rat liver and in regenerating rat liver at several time intervals after 75% hepatectomy. Cytosolic estradiol binding in regenerating liver decreases at 12, 24, and 48 h after hepatectomy and at 48 h is 30% of that in normal rat liver. Nuclear estrogen binding 48 h after surgery is elevated fivefold over normal values. No alterations in affiriity of the receptor for estrogen have been observed. Specificity studies ...

  16. 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-

  17. Ideal Experimental Rat Models for Liver Diseases

    OpenAIRE

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and dive...

  18. 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.

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

    OpenAIRE

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

    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.

  20. Lipid Peroxidation in Rat Liver using Different Vegetable Oils

    International Nuclear Information System (INIS)

    The objective of the study was to evaluate the effect of different vegetable oils (Red Palm Olien (RPO), Palm Olein (PO), Corn Oil (CO) and Coconut Oil on lipid peroxidation of rat liver. One hundred and thirty two Sprague Dawley male rats were randomly divided into two groups. The first group contains seventy two rats were divided into twelve groups of 6 rats per group and were treated with different concentrations of RPO (5 %, 10 % and 15 %) for 2, 4 and 8 weeks. The second group contains sixty male rats were randomly divided into ten groups of 6 rats per group and were treated with 15 % of RPO, PO, CO and COC for 4 and 8 weeks. The results shows that after 8 weeks of treatment the malonaldehyde (MDA) value in RPO group was significantly lower (P≤0.05) than control or vegetable oils studied. These experiments suggested that red palm olein antioxidants present in rat diets may better attenuate peroxyl radical than other vegetable oil studied. (author)

  1. Biochemical changes in rats regenerating liver under irradiation

    International Nuclear Information System (INIS)

    The white female rats were hezato ectomized before irradiation to create conditions comparable with clinical. Rats front abdomen area was irradiated with 14 Gy. It was shown that changes by all indices took place in regenerating and weakly regenerating (irradiated) liver in 2, 4 and 15 days following hepatectomy. The process of irradiation accelerates lipid peroxide oxidation, decreases acid phosphatase activity in gredter degree than in regenerating liver and doesn't influence glucose-6-phosphatase activity in comparison with non-irradiated hepatectomized animals. The studied biochemical indices can be used in formation of test bit to diagnose local radiation injuries of various organs or to characterize modification action. 13 refs.; 1 tab

  2. Endoplasmic reticulum stress in diethylnitrosamine-induced rat liver cancer

    OpenAIRE

    Xiao, Bin; Cui, Li-Min; MA, DONG-JIE; LIU, SHUANG-PING; ZHANG, XUE-WU

    2013-01-01

    To analyze the significance of endoplasmic reticulum stress (ERS) in the development of diethylnitrosamine (DEN)-induced liver cancer in rats, critical regulatory factors in ERS signaling pathways were investigated in the present study. The results showed that the expression of ERS-related proteins gradually increased in the early and mid-term stages of carcinogenesis, while in the later stages, the expression of these proteins did not change significantly after reaching a peak. ERS is involv...

  3. Isolation and purification of rat liver morphine UDP-glucuronosyltransferase

    International Nuclear Information System (INIS)

    The enhancement of rat liver microsomal morphine (M) and 4-hydroxybiphenyl (4-HBP) UDP-glucuronyltransferase (UDPGT) activities by phenobarbital treatment has been proposed to represent increased activity of a single enzyme form, GT-2. They have separated M and 4-HBP UDPGT activities from Emulgen 911-solubilized microsomes obtained from livers of phenobarbital-treated Wistar rats. A sensitive assay procedure was developed to quantify M-UDPGT and 4-HBP-UDPGT activities using 14C-UDP-glucuronic acid (UDPGA) and reversed phase C-18 minicolumns whereby the radioactive glucuronides were differentially eluted from labeled UDPGA. Trisacryl DEAE, and chromatofocusing procedures were employed to separate M-UDPGT and 4-HBP-UDPGT in the presence of exogenous phosphatidylcholine (PC). The PC is necessary to stabilize UDPGT activities. M-UDPGT was isolated to apparent homogeneity and displayed a monomeric molecular weight of 56,000 daltons on SDS-PAGE. It reacted with M but not with 4-HBP, bilirubin, p-nitrophenol, testosterone, androsterone, estrone, 4-aminobiphenyl or α-naphthylamine. 4-HBP-UDPGT did not react with M. Therefore, M and 4-HBP glucuronidations are catalyzed by separate enzymes in rat liver microsomes

  4. Isolation and purification of rat liver morphine UDP-glucuronosyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Puig, J.F.; Tephly, T.R.

    1986-03-05

    The enhancement of rat liver microsomal morphine (M) and 4-hydroxybiphenyl (4-HBP) UDP-glucuronyltransferase (UDPGT) activities by phenobarbital treatment has been proposed to represent increased activity of a single enzyme form, GT-2. They have separated M and 4-HBP UDPGT activities from Emulgen 911-solubilized microsomes obtained from livers of phenobarbital-treated Wistar rats. A sensitive assay procedure was developed to quantify M-UDPGT and 4-HBP-UDPGT activities using /sup 14/C-UDP-glucuronic acid (UDPGA) and reversed phase C-18 minicolumns whereby the radioactive glucuronides were differentially eluted from labeled UDPGA. Trisacryl DEAE, and chromatofocusing procedures were employed to separate M-UDPGT and 4-HBP-UDPGT in the presence of exogenous phosphatidylcholine (PC). The PC is necessary to stabilize UDPGT activities. M-UDPGT was isolated to apparent homogeneity and displayed a monomeric molecular weight of 56,000 daltons on SDS-PAGE. It reacted with M but not with 4-HBP, bilirubin, p-nitrophenol, testosterone, androsterone, estrone, 4-aminobiphenyl or ..cap alpha..-naphthylamine. 4-HBP-UDPGT did not react with M. Therefore, M and 4-HBP glucuronidations are catalyzed by separate enzymes in rat liver microsomes.

  5. Motor vehicle accidents: How should cirrhotic patients be managed?

    OpenAIRE

    2012-01-01

    Motor vehicle accidents (MVAs) are serious social issues worldwide and driver illness is an important cause of MVAs. Minimal hepatic encephalopathy (MHE) is a complex cognitive dysfunction with attention deficit, which frequently occurs in cirrhotic patients independent of severity of liver disease. Although MHE is known as a risk factor for MVAs, the impact of diagnosis and treatment of MHE on MVA-related societal costs is largely unknown. Recently, Bajaj et al demonstrated valuable findings...

  6. Epigenetic changes in the rat livers induced by pyrazinamide treatment

    International Nuclear Information System (INIS)

    Drug-induced liver injury, including drug-induced hepatotoxicity during the treatment of tuberculosis infection, is a major health problem with increasingly significant challenges to modern hepatology. Therefore, the assessment and monitoring of the hepatotoxicity of antituberculosis drugs for prevention of liver injury are great concerns during disease treatment. The recently emerged data showing the ability of toxicants, including pharmaceutical agents, to alter cellular epigenetic status, open a unique opportunity for early detection of drug hepatotoxicity. Here we report that treatment of male Wistar rats with antituberculosis drug pyrazinamide at doses of 250, 500 or 1000 mg/kg/day body weight for 45 days leads to an early and sustained decrease in cytosine DNA methylation, progressive hypomethylation of long interspersed nucleotide elements (LINE-1), and aberrant promoter hypermethylation of placental form glutathione-S-transferase (GSTP) and p16INK4A genes in livers of pyrazinamide-treated rats, while serum levels of bilirubin and activity of aminotransferases changed modestly. The early occurrence of these epigenetic alterations and their association with progression of liver injury specific pathological changes indicate that alterations in DNA methylation may be useful predictive markers for the assessment of drug hepatotoxicity

  7. Effects of Subchronic Aluminum Exposure on Liver Function in Rats

    Institute of Scientific and Technical Information of China (English)

    Bai Chong-sheng; Wang Fan; Zhao Han-song; Li Yan-fei

    2012-01-01

    Effects of subchronic aluminum (Al) exposure on the function of rat liver were investigated in this experiment. A total of 48 male Wistar rats (4 weeks old) were randomly divided into four groups: experimental groups were orally exposed to 64.18, 128.36, 256.72 mg. kg^-1 body weight aluminum trichloride (AlCl3) in drinking water, and the control group with distilled water. The experiment lasted for 120 days. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), the concentration of malondialdehyde (MDA) in serum and liver, and alanine transarninase (ALT) and aspartate aminotransferase (AST) activities in serum were detected in all groups. The results showed that the activities of ALT, AST in serum and the concentrations of MDA in liver in the Al-treated groups significantly increased compared with the control group; the activities of GSH-PX and SOD in high-dose Al-treated group were significantly lower than those in control group. Our findings indicated that subchronic AI exposure could result in injures of lipid peroxidation and function in liver.

  8. [Management of umbilical hernia in cirrhotic patients].

    Science.gov (United States)

    Loriau, J; Manaouil, D; Mauvais, F

    2002-06-01

    The treatment of umbilical hernia in the setting of cirrhosis poses unique and specific management problems due to the pathophysiology of cirrhotic ascites. The high intra-abdominal pressures generated by ascites when applied to areas of parietal weakness are the cause of hernia formation and enlargement. Successful surgical treatment depends on minimization or elimination of ascites. Umbilical rupture and hernia strangulation are the most life-threatening complications of umbilical hernia with ascites and they demand urgent surgical intervention. In non-emergency situations, medical therapy to control ascites should precede hernia repair. When ascites is refractory to medical therapy, treatment will vary depending on whether transplantation is an option. In liver transplantation candidates, hernia repair can be performed at the end of the transplantation procedure. If transplanation is not envisaged, concomitant treatment of both ascites and hernia is best achieved by placement of a peritoneo-venous shunt at the time of the parietal repair. PMID:12391663

  9. Purification and properties of a rat liver protein that specifically inhibits the proliferation of nonmalignant epithelial cells from rat liver.

    OpenAIRE

    McMahon, J. B.; Farrelly, J G; Iype, P. T.

    1982-01-01

    An inhibitor of cell proliferation was purified from rat liver by alcohol precipitation, ultrafiltration, and DEAE-cellulose chromatography. The hepatic proliferation inhibitor was shown to be pure by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, analytical isoelectric focusing, and high-performance liquid chromatography. The hepatic proliferation inhibitor was found to have a molecular weight of 26,000 and an isoelectric point of 4.65. This protein inhibited t...

  10. 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.

  11. 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

    were only slightly affected. Complete metabolic studies, including fecal excretion, showed that the BDL rats had avid renal sodium retention. Treatment of the BDL rats with dexamethasone suppressed endogenous glucocorticoid production, normalized total sodium balance and renal sodium excretion, and...

  12. 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

    2016-01-01

    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. PMID:27340889

  13. Role of trimetazidine in carbon tetrachloride induced liver damage in rats

    OpenAIRE

    Vijay H. Mate; Vijaya A. Pandit; Dileep B. Wani; Priti P. Dhande

    2014-01-01

    Background: Hepatotoxicity by chemicals and drugs is a common clinical problem. Presently very few drugs are showing effectiveness in prevention and treatment of hepatic damage. So in this study, we evaluated the role of trimetazidine in carbon tetrachloride (CCl4) induced liver damage in rats. Objective of current study is to evaluate effects of prophylactic trimetazidine against carbon tetrachloride induced liver damage in rats. Methods: Liver damage was induced in 30 albino rats by CCl4...

  14. 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.

  15. Liver atrophy following portacaval shunt in normal rats: A morphologic and ultrastructural study

    OpenAIRE

    Radosavljević Tatjana; Todorović Vera N.; Boričić Ivan V.; Šikić Branka

    2003-01-01

    The aim of the current study was to examine morphological and ultrastructural changes in the rat liver in an experimental model of chronic liver disease (end-to-side portacaval shunt). The surgical procedure providing an end-to-side portacaval shunt (PCS) was performed in Wistar rats. The liver and pancreas weights were determined 8 weeks after the operation, when liver histology and ultrastructural patterns of hepatocytes were examined. Body weights were not significantly different between t...

  16. "Cold training" affects rat liver responses to continuous cold exposure.

    Science.gov (United States)

    Venditti, Paola; Napolitano, Gaetana; Barone, Daniela; Di Meo, Sergio

    2016-04-01

    Continuous exposure of homeothermic animals to low environmental temperatures elicits physiological adaptations necessary for animal survival, which are associated to higher generation of pro-oxidants in thermogenic tissues. It is not known whether intermittent cold exposure (cold training) is able to affect tissue responses to continuous cold exposure. Therefore, we investigated whether rat liver responses to continuous cold exposure of 2 days are modified by cold training (1h daily for 5 days per week for 3 consecutive weeks). Continuous cold increased liver oxidative metabolism by increasing tissue content of mitochondrial proteins and mitochondrial aerobic capacity. Cold training did not affect such parameters, but attenuated or prevented the changes elicited by continuous cold exposure. Two-day cold exposure increased lipid hydroperoxide and protein-bound carbonyl levels in homogenates and mitochondria, whereas cold training decreased such effects although it decreased only homogenate protein damage in control rats. The activities of the antioxidant enzymes GPX and GR and H2O2 production were increased by continuous cold exposure. Despite the increase in GPX and GR activities, livers from cold-exposed rats showed increased susceptibility to in vitro oxidative challenge. Such cold effects were decreased by cold training, which in control rats reduced only H2O2 production and susceptibility to stress. The changes of PGC-1, NRF-1, and NRF-2 expression levels were consistent with those induced by cold exposure and cold training in mitochondrial protein content and antioxidant enzyme activities. However, the mechanisms by which cold training attenuates the effects of the continuous cold exposure remain to be elucidated. PMID:26808664

  17. In vitro metabolism of [14C]-toluene by human and rat liver microsomes and liver slices

    International Nuclear Information System (INIS)

    Toluene metabolites produced by liver microsomes from six human donors included benzylalcohol (Balc), benzaldehyde (Bald) and benzoic acid (Bacid). Microsomes from only one human donor metabolized toluene to p-cresol and o-cresol. Human liver microsomes also metabolized Balc to Bald. Balc metabolism required NADPH, was inhibited by carbon monoxide, and was decreased at a buffer pH of 10. Balc metabolism was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P450 is responsible for the in vitro metabolism of Balc by human liver microsomes. Toluene metabolites formed by human liver slices and released into the incubation media included hippuric acid, and Bacid. Cresols or cresol-conjugates were not detected in liver slice incubation media from any human donor. Toluene metabolism by human liver was compared to metabolism by comparable liver preparations from male Fischer F344 rats. Rates of toluene metabolism by human liver microsomes and liver slices were 9-fold and 1.3-fold greater than for rat liver, respectively. Covalent binding of toluene to human liver microsomes and liver slices was 21-fold and 4-fold greater than for comparable rat liver preparations. Covalent binding of toluene to human microsomes required NADPH, was significantly decreased by coincubation with 4 mM cysteine or 4 mM glutathione, and radioactivity associated with microsomes was decreased by subsequent digestion of microsomes with protease. These results suggest that toluene metabolism and covalent binding of toluene are underestimated if the male Fischer 344 rat is used as a model for human toluene metabolism

  18. Effects of melatonin on liver of rats with experimental hyperthyroid

    Directory of Open Access Journals (Sweden)

    Oner J.

    2005-01-01

    Full Text Available The aim of this study was to investigate the structural changes that occurred in the liver of rats with experimental hyperthyroidism and the possible effects of melatonin on these changes. The animals were designated as control group (group I, 3,3', 5-Triiodo-I-Thyronine (T3 injected group (group II and T3+ melatonin injected group (group III. At the end of study, tissue specimens were examined for changes in structure. In the T3 injected group dilatation in sinusoids and pale cytoplasm were observed, as well as an increased number of the Kupffer cells and an increased amount of glycogen. In T3 + melatonin injected group, the amount of glycogen was similar to the T3 injected groups while the number of Kupffer cells increased but sinusoid largeness and hepatocyte structure were similar to the control. On electron microscopic examination the mitochondria of T3 injected group were slightly larger than those of the control group. In T3 + melatonin injected group enlargement in the spaces of Disse, increased number of lipid vacuoles of Ito cells and increased number of microvilli of hepatocytes were observed. Kupffer cells were more active in this group. The results of this study indicate that T3 injection causes structural changes in the liver, and melatonin hormone has a small, if any, protective effect on the liver of rats with hyperthyroid.

  19. 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.

  20. The Effect of Seaweed Eucheuma cottonii on Superoxide Dismutase (SOD) Liver of Hypercholesterolemic Rats

    OpenAIRE

    TUTIK WRESDIYATI; ANS BUDI HARTANTA; MADE ASTAWAN

    2008-01-01

    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) hypercholest...

  1. The LEC rat: a model for human hepatitis, liver cancer, and much more.

    OpenAIRE

    M. Mori; Hattori, A.; Sawaki, M; Tsuzuki, N; Sawada, N; Oyamada, M.; Sugawara, N; Enomoto, K.

    1994-01-01

    The LEC rat is an inbred mutant strain with spontaneous hepatitis isolated from Long-Evans rats. Since approximately 40% of LEC rats die of fulminant hepatitis, the rat serves an animal model for studying the pathogenesis and treatment of human fulminant hepatitis. The remaining 60% of LEC rats survive and develop chronic (prolonged) hepatitis and subsequently develop liver cancer. Therefore, the LEC rat serves an important animal model for studying the significance of chronic hepatitis in th...

  2. Effect of irradiation and of cysteamine on rat liver mitochondria

    International Nuclear Information System (INIS)

    The aim of this work was to determine: the effects of a cobalt 60 gamma irradiation received by an animal, the biological repercussions of the preliminary administration of cysteamine to the animal exposed. To this end the amount of damage caused by in vivo irradiation of rats was estimated at three levels: on the whole body; on an important organ, the liver; on a specific organite, the mitochondrion. The methods of investigation used fall mainly within the province of biochemical technology. Studies on the effects of ionizing radiations on rats irradiated for ten days at 900 roentgens showed a generalized attack on the whole system, known as the ''Acute Irradiation Syndrome'' and divisible into three phases: stage one, initial phase involving loss of weight and destruction of the liver. These symptoms appear early and reach a paroxysm on the 4th day after irradiation. Stage two, remission phase (from the 5th to the 8th day) when the weight variations become stabilised. Stage three, last phase, often leading to the death between the 9th and 10th days. During the same 10-day period, on the same irradiated rats, the changes in enzymatic systems were followed in order to estimate the magnitude of peroxidative phenomena within a subcellular particle such as the mitochondrion. The results obtained prove a strong disorganisation of the mitochondrial function

  3. Monitoring of intracellular free calcium in perfused rat liver.

    Science.gov (United States)

    Ruttner, Z; Ligeti, L; Reinlib, L; Hines, K; McLaughlin, A C

    1993-06-01

    Fluorescent calcium indicators have been widely used to assess cytoplasmic calcium concentration in cells. To examine the role of calcium ions on different physiological functions (e.g. in case of liver; bile secretion, glucose metabolism, etc.) there is a need for whole organ studies. We have developed a technique to estimate intracellular free calcium changes in perfused rat liver. Krebs-Henseleit perfused livers were loaded with 7 microM or 35 microM Indo-1/AM. An area 3 mm in diameter and approximately 300 microns in depth was illuminated at 340 nm. Fluorescence was monitored with photomultiplier tubes at 3 wavelengths (400 nm for Ca-bound dye, 504 nm for free dye and 464 nm for NADH). The viability of liver preparations was assessed by measurement of the concentrations of lactate dehydrogenase and alanine aminotransferase in the effluent. Loading of the livers with 7 microM Indo-1/AM via the portal vein resulted in a 5-fold increase of fluorescence at 400 nm. However the dye 'leaked' out of the liver with a half-time of 18 min. Probenecid (a specific anion carrier blocker) inhibited loss of dye in a dose dependent fashion (2.5-10 mM). Transient calcium elevations were observed in response to vasopressin (5-50 nM) at physiological levels, ethanol (0.3-0.8 M) and the calcium ionophore, ionomycin. Certain limitations were apparent with this approach: (1) it was necessary to use an anion carrier blocker to maintain a relatively steady dye concentration; (2) endogenous NADH fluorescence interfered with the calcium signal; and (3) absolute values of calcium concentration could not be determined. PMID:8358770

  4. Effect of cobalt chloride on content of lipids and lipoproteins in serum and liver of rats.

    Science.gov (United States)

    Kaliman, P A; Shalamov, R V; Zagaiko, A L

    1997-07-01

    Lipids and the composition of lipoproteins in blood serum and liver cytosol, total lipid, and phospholipid contents in liver subcellular fractions and the spectrum of microsomal liver lipids were studied in male Wistar rats after a single injection of cobalt chloride. Virtually all lipid and lipoprotein fractions in blood and liver were increased and lipoprotein composition was changes. The lipid composition of liver microsomes did not change under these conditions. Thus, microsomal membranes are stable under developing oxidative stress. PMID:9331964

  5. [Surgical approach to posthepatitic cirrhotic patient today].

    Science.gov (United States)

    Meriggi, F; Forni, E

    1996-01-01

    A posthepatitic cirrhotic patient may undergo elective or urgent abdominal operation for an extra-hepatic or hepatic disease. According to the high postoperative morbidity (61%), surgery is indicated only for symptomatic or complicated cholelithiasis. A surgical procedure for refractory ascites has been devised to create a permanent peritoneo-venous shunt by a one way pressure-sensitive valve (Leveen). The procedure is simple and brings a long lasting relief with recovery in strength and nutrition and improved kidney function. Sclerotherapy is widely used to treat acute variceal bleeding while repeated sclerotherapy is used in the long-term management to eradicate varices. When indicated, liver transplantation is the best treatment to prevent variceal bleeding recurrence. Also portosystemic shunts effectively prevent recurrent variceal bleeding. They are, however, major operations with an important morbidity and mortality, particularly in poor risk patients. The most advocated shunts today are the Warren distal splenorenal shunt and the Sarfeh portacaval shunt using a small diameter prosthetic H-graft. The transjugular intrahepatic portosystemic stent-shunt (TIPSS) is a new treatment for portal hypertension and its complications. From a haemodynamic point of view it allows balanced hepatic perfusion. Postoperative mortality is rare; further bleeding and encephalopathy are reasonably acceptable. The most relevant complications concern dislocation of the prosthesis, stenosis and thrombosis of the shunt, which can be corrected by non-invasive dilatation. Encephalopathy is the main complication of surgical portosystemic shunts. It is usually controlled by protein diet restriction, and administration of lactulose or oral antibiotics. In severe forms the patients may be treated by an oesophageal transection with oesophagogastric devascularization, and by a postoperative suppression of the portosystemic shunt using external maneuvers. Posthepatitic liver cirrhosis is

  6. Affinity labeling of rat liver thyroid hormone nuclear receptor.

    OpenAIRE

    Nikodem, V M; Cheng, S Y; Rall, J. E.

    1980-01-01

    The thyroid hormone receptor from rat liver nuclei has been covalently labeled with the N-bromoacetyl derivatives of L-thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3). Displacement binding studies showed that, in the presence of 100-fold molar excess of unlabeled N-bromoacetyl-T3 or T4, binding of [125I]T3 or [125I]T4 was nearly totally inhibited. Heat inactivation of the receptor (55 degrees C for 15 min) resulted in parallel losses in the binding of T3 (95%) and N-bromoacetyl-T3 (93%). T...

  7. Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria.

    Science.gov (United States)

    Salvi, Mauro; Fiore, Cristina; Armanini, Decio; Toninello, Antonio

    2003-12-15

    Glycyrrhetinic acid, a hydrolysis product of one of the main constituents of licorice, the triterpene glycoside of glycyrrhizic acid, when added to rat liver mitochondria at micromolar concentrations induces swelling, loss of membrane potential, pyridine nucleotide oxidation, and release of cytochrome c and apoptosis inducing factor. These changes are Ca(2+) dependent and are prevented by cyclosporin A, bongkrekic acid, and N-ethylmaleimide. All these observations indicate that glycyrrhetinic acid is a potent inducer of mitochondrial permeability transition and can trigger the pro-apoptotic pathway. PMID:14637195

  8. Xanthine oxidase status in ethanol-intoxicated rat liver.

    Science.gov (United States)

    Abbondanza, A; Battelli, M G; Soffritti, M; Cessi, C

    1989-12-01

    The status of xanthine oxidase in ethanol-induced liver injury has been investigated in the rat, by acute and chronic ethanol treatments. A 38% increase of the enzyme O-form was observed after repeated ethanol administration. Chronic intoxication caused a significant decrease of total xanthine oxidase activity after both prolonged ethanol feeding and life span ethanol ingestion. The intermediate D/O-form of xanthine oxidase (that can act either as an oxidase or as a dehydrogenase, being able to react with O2 as well as with NAD+ as electron acceptor) increased 5.5-fold after prolonged ethanol feeding. PMID:2690670

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

    OpenAIRE

    Amanda Natália Lucchesi; Lucas Langoni Cassettari; César Tadeu Spadella

    2015-01-01

    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 ins...

  11. Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis.

    Directory of Open Access Journals (Sweden)

    Annarein J C Kerbert

    Full Text Available Advanced liver cirrhosis is associated with systemic hemodynamic derangement leading to the development of severe complications associated with increased mortality. Copeptin is a stable cleavage product of the precursor of arginine vasopressin, a key-regulator in hemodynamic homeostasis. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. The present study aimed to assess copeptin, both experimentally and clinically, as a potential biomarker of hemodynamic derangement and to evaluate its prognostic significance in cirrhosis.Two studies were executed: 1 in 18 thioacetamide-induced cirrhotic rats and 5 control rats, plasma copeptin and hemodynamic measurements were performed, 2 in 61 cirrhotic patients, serum copeptin concentration was measured in samples collected at time of registration at the waiting list for liver transplantation. In 46 patients, also a second copeptin measurement was performed during follow-up while registered at the waiting list for liver transplantation. To determine the association of serum copeptin and clinical data with outcome, Cox proportional hazard regression analysis and Kaplan Meier analysis were performed.Plasma copeptin concentration was significantly higher in cirrhotic rats than in controls (1.6 ± 0.5 vs. 0.9 ± 0.1 pmol/L, p< 0.01 and was negatively correlated to the mean arterial blood pressure (r = -0.574, p = 0.013. In cirrhotic patients, serum copeptin concentration was high [11.0 (5.2-24.0 pmol/L] and increased significantly during the time of registration at the waiting list for liver transplantation. MELD and MELD-sodium score were significantly correlated to serum copeptin [MELD: (r = 0.33, p = 0.01, MELD-sodium: (r = 0.29, p = 0.02], also at time of the second copeptin measurement [MELD and MELD-sodium: r = 0.39, p< 0.01]. In cirrhotic humans, serum copeptin concentration was significantly associated with outcome, independently of the MELD

  12. 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.

  13. Effect of triiodothyronine on rat liver chromatin protein kinase

    International Nuclear Information System (INIS)

    1) Injection of triiodothyronine to rats stimulates protein kinase activity in liver chromatin nonhistone proteins. A significant increase was found after two daily injections. A 4-fold increase was observed with the purified enzyme after eight daily injections of the hormone. No variations were observed in cytosol protein kinase activity. Electrophoretic pattern, effect of heat denaturation, effect of p-hydroxymercuribenzoate seem to indicate that the enzyme present in treated rats is not identical to the enzyme in control animals, which suggests that thyroid hormone has induced nuclear protein kinase. Diiodothyronine, 3, 3', 5'-triiodothyronine have no effect on protein kinase. 2) Chromatin non-histone proteins isolated from rats injected with triiodothyronine incorporated more 32P when incubated with [γ-32P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32P incorporation. It is suggested that some of the biological activity of thyroid hormone could be mediated through its effect on chromatin non-histone proteins. (orig.)

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

    OpenAIRE

    Wang, Bin; Zhang, Xiao-Hua; Miao-fan YANG; Xiao-wei WU; Xu, Xiao-Bing; Mei-xia GUO; Min-li LI

    2012-01-01

    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 (...

  15. Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats.

    Science.gov (United States)

    Han, Xiuqing; Liu, Chunhua; Xue, Yong; Wang, Jingfeng; Xue, Changhu; Yanagita, Teruyoshi; Gao, Xiang; Wang, Yuming

    2016-01-01

    We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model. PMID:26775542

  16. Extension collimator design for rat liver irradiation at THOR

    International Nuclear Information System (INIS)

    The renovation for an epithermal neutron beam at the Tsing Hua Open-pool reactor (THOR) had been completed in August 2004. Since the aperture of this facility is 14 cm in diameter, the average whole-body would be large if it is used for rat liver irradiation. To lower the whole-body dose while delivering the same amount of thermal neutrons to the rat liver location, an extension collimator was designed and adopted to provide a suitable beam hole in this article. The extension collimator is a centered conical aperture with inner opening of 14cm diameter and outer opening of various sizes. The effectiveness of the extension collimator was based on MCNP simulation results. They were compared with various materials, various thickness of the extension collimator, and various size of the outer opening. The simulation results indicate that an extension collimator, made of Li2CO3 dispersed in polyethylene (Li-Poly), will reduce the whole-body dose. Other simulations show that a 10cm-thick extension collimator, having a centered conical aperture of 14cm diameter tapering to 4cm diameter, would further reduce the whole-body dose. (author)

  17. Hexachlorobenzene induces deregulation of cellular growth in rat liver

    International Nuclear Information System (INIS)

    Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the biosphere. The aim of the present study was to investigate the effect of HCB on the homeostasis of liver cell growth, analyzing parameters of cell proliferation and apoptosis, in HCB (0.1, 1, 10 and 100 mg/kg body weight)-treated rats, during 4 weeks. Cell proliferation and ERK1/2 phosphorylation, associated with survival mechanisms, were increased at HCB 100 mg/kg. The pesticide increased the number of apoptotic cells, and the activation of caspase-3, -9 and -8, in a dose-dependent manner, suggesting that HCB-induced apoptosis is mediated by caspases. Increased Fas and FasL protein levels indicate that the death receptor pathway is also involved. This process is associated with decreased Bid, and increased cytosolic cytochrome c protein levels. Transforming growth factor-beta1 (TGF-β1) intervenes in apoptotic and/or proliferative processes in hepatocytes. TGF-β1 cDNA and protein levels are dose-dependently increased, suggesting that this cytokine might be involved in HCB-induced dysregulation of cell proliferation and apoptosis. In conclusion, this study reports for the first time that HCB induces loss of the homeostatic balance between cell growth and cell death in rat liver. Induced apoptosis occurs by mechanisms involving signals emanating from death receptors, and the mitochondrial pathway.

  18. Surgical techniques of arterialized orthotopic liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    MA Yi; WANG Guo-dong; GUO Zhi-yong; GUO Zhi-gang; HE Xiao-shun; CHEN Gui-hua

    2007-01-01

    Background Recently, much attention has been paid to hepatic artery reconstruction in rat liver transplantation, which can prevent bile duct ischemia and preserve better liver structure. In this study, three methods of graft arterialization,including sleeve, cuff, and stent anastomosis, were conducted and the results were compared.Methods Orthotopic liver transplantation (OLT) with rearterialization was conducted in 90 rats, which were divided into sleeve, cuff, and stent groups (n=30 in each). Ninety-six rats received OLTs with standardized two-cuff technique without rearterialization as a control. The sleeve technique included an end-to-end anastomosis between the donor common hepatic artery and recipient proper hepatic artery, or between the donor celiac artery and recipient common hepatic artery.Cuff technique involved an anastomosis between the donor common hepatic artery and recipient common hepatic artery.In the stent technique, the recipient hepatic artery and donor hepatic artery were connected using an intraluminal polyethylene stent. The arterial anastomosis time and arterial patency rate in each group were recorded. The liver graft survival and bile duct complication rates were measured.Results The total surgical time of OLT with rearterialization was (118.3±12.9) minutes in the sleeve group, (106.2±11.6)minutes in the cuff, (93.8±10.2) minutes in the stent, and (88.2±9.6) minutes in the control. The corresponding anhepatic phase was (19.6±2.8), (19.2±2.2), (18.6±1.8), and (20.0±2.5) minutes respectively in the sleeve, cuff, stent, and control groups. One-week survival rate was 86.5% in the control, and 86.7% in the groups with rearterialization. No significant difference was detected in the survival rate between them (P>0.05). The incidence of biliary complications in non-rearterialized group (17.7%) was significantly higher than that in the rearterialized group (6.7%, P<0.05). No significant difference was found in the incidence of biliary

  19. 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...... high repopulation potential. METHODS: Dlk-1, a member of the delta-like family of cell surface transmembrane proteins, is highly expressed in human and rodent fetal liver. Dlk-1(+) cells, isolated from ED14 fetal liver using immunomagnetic beads, were examined for their hepatic gene expression profile...... and characteristic properties in vitro and their proliferative and differentiation potential in vivo after transplantation into normal adult rat liver. RESULTS: Rat ED14 FLSPC were purified to 95% homogeneity and exhibited cell culture and gene expression characteristics expected for hepatic stem/progenitor cells...

  20. Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model.

    Science.gov (United States)

    Abe, Hiroyuki; Kamimura, Kenya; Kobayashi, Yuji; Ohtsuka, Masato; Miura, Hiromi; Ohashi, Riuko; Yokoo, Takeshi; Kanefuji, Tsutomu; Suda, Takeshi; Tsuchida, Masanori; Aoyagi, Yutaka; Zhang, Guisheng; Liu, Dexi; Terai, Shuji

    2016-01-01

    Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of ~5 pg/ml (P sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P < 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis. PMID:26730813

  1. Developmentally regulated interactions of liver nuclear factors with the rat phosphoenolpyruvate carboxykinase promoter.

    OpenAIRE

    Trus, M; Benvenisty, N; Cohen, H.; Reshef, L.

    1990-01-01

    A sequential pattern of interactions of trans-acting factors in rat liver with the phosphoenolpyruvate carboxykinase promoter during late development was observed. A liver-enriched factor, possibly AF1, interacted with the promoter in fetal liver, whereas a factor with the characteristics of C/EBP bound the promoter after birth with the onset of the gene expression.

  2. 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.

  3. Comparison of purified bovine heart and rat liver 6-phosphofructo-2-kinase. Evidence for distinct isoenzymes.

    OpenAIRE

    Rider, Mark; Foret, D.; Hue, Louis

    1985-01-01

    Rat liver and bovine heart 6-phosphofructo-2-kinase were purified by the same procedure. Compared with the liver enzyme, the heart enzyme had a smaller apparent Mr, different kinetic properties, was not inactivated by cyclic AMP-dependent protein kinase, and contained less fructose-2,6-bisphosphatase activity. These differences suggest that heart and liver 6-phosphofructo-2-kinase are distinct isoenzymes. Likewise, 6-phosphofructo-2-kinase from rat heart and skeletal muscle was not inactivate...

  4. Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats

    OpenAIRE

    Salama, Suzy M.; Abdulla, Mahmood Ameen; AlRashdi, Ahmed S.; Ismail, Salmah; Alkiyumi, Salim S.; Golbabapour, Shahram

    2013-01-01

    Background Hepatology research has focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Thus, this study evaluated mechanisms of the hepatoprotective activity of Curcuma longa rhizome ethanolic extract (CLRE) on thioacetamide-induced liver cirrhosis in rats. Methods The hepatoprotective effect of CLRE was measured in a rat model of thioacetamide-induced liver cirrhosis over 8 weeks. Hepatic cytochrome P450 2E1 and serum levels of TGF-β1 and TNF-α ...

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

    OpenAIRE

    Schoonderwoerd, Kees; Verhoeven, Adrie; 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 perfusion media before and after passage through the liver. During perfusion with a hepatic-lipase-containing medium the lipase activity in the medium did not change, indicating that there was no net binding of lipase by the live...

  6. Comparison of four physiological models for analysis of glucose wash-in curves in the perfused rat liver

    International Nuclear Information System (INIS)

    Full text: Oxygen diffusion may be involved in the pathogenesis of impaired drug metabolism by the aged (Le Couteur and McLean 1998) and cirrhotic (McLean and Morgan 1991) liver. To measure the barrier for oxygen transfer between the sinusoid and hepatocyte, we developed a carbon monoxide wash-in technique (Le Couteur et al 1999). The modelling of wash-in curves has been investigated much less intensively than multiple indicator dilution experiments, which utilize bolus injection of substrates. To investigate the effectiveness of various physiological models to fit wash-in curves, we performed wash-in experiments on the livers of male Wistar rats perfused in situ and single-pass with Krebs Henseleit buffer. Test perfusate contained 14C-sucrose as the extracellular marker and 3H-glucose. Liver perfusions were performed with background glucose concentrations of 6, 11, 51 or 109 mM. Outflow time-activity curves were analysed using four models. The Vmax and Km, for the influx of glucose were 1.1±0.03 μg/s/ml and 41.1±3.3 mM using the Crone-Renkin early extraction model; 1.4±0.04 μg/s/ml and 36.3±2.6 mM with dispersion model analysis; 1.8±0.1 μg/s/ml and 24.9±4.2 mM using the Goresky distributed model to fit differentiated wash-in curves; and 2.3±0.5 μg/s/ml and 29.3±16.5 mM using compartmental analysis. There was reasonable agreement between the four models and they yielded results that are similar to those reported for glucose uptake in other preparations. The differences between the models probably reflect differences in assumptions about the effects of efflux, mixing of glucose in the compartments and vascular hetereogeneity. The compartmental model that we used previously to examine gas disposition in the perfused liver gave higher estimates for transport than the other three models. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  7. Binding cells of 125I-iodoamphetamine in rat liver

    International Nuclear Information System (INIS)

    We recently reported that transrectal or intestinal portal scintigraphy with 123I-iodoamphetamine (IMP) could be a useful method for the non-invasive and quantitative evaluation of the portosystemic shunt in portal hypertension, but what cells in the liver trap IMP has not been clarified. This study was aimed at elucidating whether IMP was extracted by parenchymal cells, sinusoidal endothelial cells, Kupffer cells or fat storing cells. Each type of liver cell was isolated from rats and cultured. The cells were incubated with 125I-IMP and the radioactivity of the lysate was determined. Nonspecific binding was assessed in the presence of an excess of unlabeled IMP, and specific binding was determined by subtracting the nonspecific from total binding. Specific binding observed in parenchymal cells, endothelial cells and Kupffer cells was 70.2±0.4, 4.2±1.4 and 2.3±0.8 pmol/well, respectively, but no specific binding was observed in fat storing cells. The binding in parenchymal cells was much higher than that in endothelial cells or Kupffer cells (p<0.005). In addition, the binding to parenchymal cells reached equilibrium within 20 min and was not saturable over the concentration range tested (0.5-10 μM). These findings indicate that IMP is mostly extracted by parenchymal cells in the liver. (author)

  8. Proteomic analysis of liver in rats chronically exposed to fluoride.

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    Heloísa Aparecida Barbosa da Silva Pereira

    Full Text Available Fluoride (F is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group. At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS. Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies.

  9. Action of ionizing radiation on catalase synthesis in the rat liver

    International Nuclear Information System (INIS)

    3-amino-1,2,4-triazole was used to study the effect of total-body X-ray irradiation on the rates of catalase synthesis and breakdown in rat liver. It was found that in the interval between hour 22 and hour 144 of radiation sickness, the average rate of catalase synthesis in the liver was 2.6 times lower in rats that received a dose of 800 rads than in control rats

  10. Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

    OpenAIRE

    B. Tang; Qiao, H.; Meng, F.; Sun, X.

    2007-01-01

    Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats...

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

    International Nuclear Information System (INIS)

    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 max and T1/2 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.)

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

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    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.

  13. RADiation repair of rat liver by olive oil administration through sulfhydryl groups and superoxide dismutase

    International Nuclear Information System (INIS)

    Sulfhydryl group contents and superoxide dismutase activity were measured in rat liver homogenates of control, irradiated rats (group ι) and olive oil treated rats before (group π) and after irradiation (group tri). The liver superoxide dismutase activity was significantly decreased in the irradiated and olive oil treated rats with no significant changes in sulfhydryl groups in both groups of animals. In case of rats treated with olive oil post-irradiation (group tri), both sulfhydryl groups content and superoxide dismutase activity level showed marked increase up to the seventh day. These results imply a repair mechanism; involving both sulfhydryl groups and superoxide dismutase activity.3 fig.,1 tab

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

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    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.

  15. 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

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    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

  16. Partial splenic artery embolization in cirrhotic patients

    OpenAIRE

    Hadduck, Tyson A; McWilliams, Justin P.

    2014-01-01

    Splenomegaly is a common sequela of cirrhosis, and is frequently associated with decreased hematologic indices including thrombocytopenia and leukopenia. Partial splenic artery embolization (PSE) has been demonstrated to effectively increase hematologic indices in cirrhotic patients with splenomegaly. This is particularly valuable amongst those cirrhotic patients who are not viable candidates for splenectomy. Although PSE was originally developed decades ago, it has recently received increase...

  17. The Use of Statin Substitutes to Improve the Lipid Profile in Liver Dysfunctional Male Albino Rats

    International Nuclear Information System (INIS)

    More attention has been drawn to different strategies for prevention of cardiovascular associated with liver dysfunction. The aim of the present study is to compare between statin and free fat- milk supplemented with multivitamins in hyperlipidaemic male rats with or without liver dysfunction induced by CCl4. The animals were allocated to 7 equal experimental groups (16 rats each): control group, hypercholesterolemic group, hypercholestero-lemic-statin group, hypercholesterolemic-free fat milk-multivitamins group, hypercholesterolemic-CCl4 group, hypercholesterolemic-CCl4-statin group, and hypercholesterolemic-CCl4- fat-free milk-multivita-mins group. After one month half of the rats of each group were decapitated and the rest of the animals were decapitated after two months. Lipid profile, relative liver weight, liver function, CPK and LDH were determined. The effectiveness of statin drug in the management of blood lipids was confirmed without improving or worsening liver functions. Meanwhile, this effectiveness worsened in hypercholesterolemic rats treated with CCl4 as compared to hypercholesterolemic group. Administration of fat-free milk with multivitamins, as an alternative remedy for statin drug, has improved lipid profile in hypercholesterolemic rats and it revealed no changes in liver enzymes in hypercholesterolemic rats with liver dysfunction indicating the favorable use of them as hypolipotropic agent without affecting liver metabolism

  18. VEGF-sdf1 recruitment of CXCR7+ bone marrow progenitors of liver sinusoidal endothelial cells promotes rat liver regeneration.

    Science.gov (United States)

    DeLeve, Laurie D; Wang, Xiangdong; Wang, Lei

    2016-05-01

    In liver injury, recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (sprocs) is necessary for normal liver regeneration. Hepatic vascular endothelial growth factor (VEGF) is a central regulator of the recruitment process. We examine whether stromal cell-derived factor 1 [sdf1, or CXC ligand 12 (CXCL12)] acts downstream from VEGF to mediate recruitment of BM sprocs, what the sdf1 receptor type [CXC receptor (CXCR)-4 or CXCR7] is on sprocs, and whether sdf1 signaling is required for normal liver regeneration. Studies were performed in the rat partial hepatectomy model. Tracking studies of BM sprocs were performed in wild-type Lewis rats that had undergone BM transplantation from transgenic enhanced green fluorescent protein-positive Lewis rats. Knockdown studies were performed using antisense oligonucleotides (ASOs). Expression of sdf1 doubles in liver and liver sinusoidal endothelial cells (LSECs) after partial hepatectomy. Upregulation of sdf1 expression increases proliferation of sprocs in the BM, mobilization of CXCR7(+) BM sprocs to the circulation, and engraftment of CXCR7(+) BM sprocs in the liver and promotes liver regeneration. Knockdown of hepatic VEGF with ASOs decreases hepatic sdf1 expression and plasma sdf1 levels. When the effect of VEGF knockdown on sdf1 is offset by infusion of sdf1, VEGF knockdown-induced impairment of BM sproc recruitment after partial hepatectomy is completely attenuated and liver regeneration is normalized. These data demonstrate that the VEGF-sdf1 pathway regulates recruitment of CXCR7(+) BM sprocs to the hepatic sinusoid after partial hepatectomy and is required for normal liver regeneration. PMID:26939868

  19. 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

  20. Follistatin allows efficient retroviral-mediated gene transfer into rat liver

    International Nuclear Information System (INIS)

    Retroviral vectors are widely used tools for gene therapy. However, in vivo gene transfer is only effective in dividing cells, which, in liver, requires a regenerative stimulus. Follistatin is effective in promoting liver regeneration after 90% and 70% hepatectomy in rats. We studied its efficacy on liver regeneration and retroviral-mediated gene delivery in 50% hepatectomized rats. When human recombinant follistatin was infused into the portal vein immediately after 50% hepatectomy, hepatocyte proliferation was significantly higher than in control 50% hepatectomized rats. A single injection of virus particles administered 23 h after follistatin infusion resulted in more than 20% gene transduction efficiency in hepatocytes compared to 3% in control rats. It is concluded that a single injection of follistatin induces onset of proliferation in 50% hepatectomized rats and allows efficient retroviral-mediated gene transfer to the liver

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

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    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.

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

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    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.

  3. Selective portal vein embolization with ethanol in treatment of implanted liver tumor in rats

    International Nuclear Information System (INIS)

    Objective: To evaluate the feasibility, safety and efficacy of selective portal vein embolization (SPVE) in treatment of liver tumor in rats and to provide the groundwork for its future clinical applications. Methods: 24 healthy rats underwent the embolization. Pre- and post-SPVE portogram and liver chemical profile were obtained. Four rats were sacrificed at 10 min, 7, 14, 21 and 28 days respectively following follow-up portography. The liver, heart, lungs and kidneys were examined macroscopically and microscopically. Fifteen rats implanted with Walker-256 tumor sized from 3 to 10 mm in liver were scanned with MRI and portography pre-SPVE taken. Post-SPVE 3 rats were examined with MRI for each group at the same interval as above and the lives were examined microscopically. Results: (1) The blood flow to the target portal branches were immediately halted after SPVE. These vessels remained occluded without collateral formation up to 28 days. (2) The liver indexes and BUN level increased after embolization, but returned to normal within 21 d. Macroscopic and microscopic changes were not found in the heart, lungs or kidneys. (3) In the healthy rats, the affected segment was atrophic and the remaining liver underwent compensatory hypertrophy. Histologic examination revealed that the targeted portal veins were coagulated, the endothelium were degenerated and the local hepatocytes were necrotic after embolization. (4) In the rats with implanted liver tumor, the affected segment including the tumor was necrotic and atrophic. The tumors were completely necrotic, and no viable tumor cell was seen under microscope in 12 among the 15 rats. Three tumors 10 mm in diameter were not completely necrotic. Part of tumor cells were still alive and infiltrated into the surrounding liver. Conclusion: SPVE with ethanol is effective in the treatment of small liver tumor in rats. However, in case of bigger tumors involving several segments, SPVE should be combined with other treatment

  4. Uptake and clearance of plutonium-238 from intact liver and liver cells transplanted into fat pads of F344/N rats

    International Nuclear Information System (INIS)

    An understanding of the role of liver cells and the intact liver in plutonium biokinetics is needed. Liver cells were isolated from rats, injected into fat pads of recipient rats, and allowed 21 days to form cell colonies. Rats then received a single intraperitoneal injection of 1 μCi 238Pu-citrate and were serially sacrificed. Uptake, retention, and distribution of Pu in intact liver and in liver cells growing in fat pads were determined. Intact liver cells took up about twice as much 238Pu as liver cells transplanted into fat pads. However, the retention kinetics of Pu were similar for both the liver cells in the fat pads and the intact liver cells when the retention was expressed as activity per cell. 4 references, 1 figure, 1 table

  5. Hepatoprotective effect of N-acetyl -L-cysteine on Cl4 - induced liver damage in rats under oxidative stress of radiation exposure

    International Nuclear Information System (INIS)

    Hepato protective properties of N-acetyl-L-cysteine (NAC) were investigated in rats under stress of radiation exposure in case of liver cirrhosis injury induced by carbon tetrachloride (CCl4) (tetrachloromethane). N-acetyl-L-cysteine treatment showed regression of cirrhosis in the liver tissue with significant inhibition of the increased liver malondialdehyde, triacylglycerols and cholesterol. Simultaneously, N-acetyl-L-cysteine suppressed the increase in plasma activities of aminotransferases (ALT, AST), alkaline phosphatase and billirubin, which are considered as markers of liver functional state. Status of oxidative/anti oxidative profile was the mechanistic approach to the nature of protection by N-acetyl-L-cysteine. Results revealed amelioration to a great extent in blood glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH) and catalase. Whole body exposure of rats to gamma-rays (four doses each of 4 Gy/dose/week) caused increases in lipid peroxides accompanied by depression of reduced glutathione (GSH). This decrease is probably due to the damages produced by the lipid peroxides. The activities of antioxidant enzymes; superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were inhibited, which might be due to the increase of the superoxide radical and H2O2 and were accompanied also by a fall in glucose-6-phosphate dehydrogenase (G6PHD) activity. The excessive production of free radicals and lipid peroxides might cause leakage of cytosolic enzymes such as aminotransferases (AST and ALT) and alkaline phosphatase. Pretreatment with NAC (150 mg/kg) in saline for 7 days prevented the radiation-induced damage to an appreciable extent. From the results, it may be concluded that NAC is effective in protecting from the damages caused by gamma radiations in case of cirrhotic liver and its prospects as an adjuvant to radiotherapy should be considered. The anti fibrotic effect recorded in

  6. Oxidation of esterified arachidonate by rat liver microsomes

    International Nuclear Information System (INIS)

    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-14C) was incorporated into rat liver microsomes and NADPH-supported peroxidation was carried out at 370C 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 A2 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 Fe3+ and since product formation is unaffected in the presence of carbon monoxide

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

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    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.

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

    International Nuclear Information System (INIS)

    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 μM, 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 μM, 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 α-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: ► We investigated how juglone acts on liver metabolism. ► The actions on hepatic gluconeogenesis, glycolysis and ureogenesis. ► Juglone stimulates glycolysis and ureagenesis and inhibits gluconeogenesis. ► The cellular ATP content is diminished. ► Juglone can

  9. Interaction of human lactoferrin with the rat liver

    International Nuclear Information System (INIS)

    Binding of human lactoferrin (hLf) by purified rat liver plasma membranes was studied to clarify whether the liver possesses specific hLf receptors. The binding was rapid between 4 degrees and 37 degrees C, with a pH optimum close to 5.0. At 22 degrees C and in glycine-NaOH (5 mM, pH 7.4) containing 150 mM NaCl and 0.5% albumin, 1 microgram of membrane bound a maximum of 11.8 ng hLf. The dissociation constant of the interaction was 1.6 X 10(-7) M. Other proteins of high isoelectric points (lactoperoxidase, lysozyme, and particularly salmine sulfate) and a piperazine derivative inhibited hLf binding in a concentration- dependent manner. In contrast, monosaccharides (galactose, N- acetylgalactosamine, mannose, and fucose) were ineffective. By omitting NaCl from the incubation buffer, binding was increased 3.6-fold. Erythrocyte ghosts bound hLf less firmly and alveolar macrophages more firmly than hepatic plasma membranes. Liver cell fractionations performed after the intravenous injection of labeled hLf showed that approximately 88% of the hepatic radioligand was associated with parenchymal cells. When binding was expressed per unit of cell volume, however, more hLf was present in nonparenchymal than in parenchymal cells, implying that the above value was determined by the relative cell masses rather than affinities alone. It is concluded that the binding of hLf by hepatic plasma membranes is electrostatic, i.e., is mediated by the cationic nature of the ligand, and that it is explicable in terms of a ''specific nonreceptor interaction'' of the generalized type proposed by Cuatrecasas and Hollenberg

  10. 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

    identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control...... rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats....... Compensatory changes in hormone or substrate levels explaining the lack of effect of liver denervation were not found. In rats with intact adrenals, the plasma epinephrine concentration was increased after 2.5 min of running. It is concluded that, in rats carrying out exercise of moderate intensity...

  11. 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.

  12. Radiation-induced alteration of gene expression in rat liver

    International Nuclear Information System (INIS)

    Exposure of rats to high dose of γ-radiation (200 Gy) significantly enhanced the ability of mitochondria to accumulate and retain exogenously added Ca2+ one hour after irradiation. 48 hours after irradiation no differences in Ca2+ transporting parameters between mitochondria from control and irradiated animals were found. The stability of mitochondrial membrane potential - the driving force for Ca2+ accumulation and retention, depends on the expression of bcl-2 gene, whose product not only participates in the regulation of Ca2+ fluxes in, but also demonstrates antioxidant properties. The overexpression of this gene was shown to protect cell mitochondria against oxidative stress. However, the investigation of bcl-2 expression in rat liver did not show any significant changes neither 1 nor 48 hours after irradiation. Taking into account that the damage of mitochondria induced action of oxygen radicals and Ca2+ can be prevented by antioxidants, the expression of genes encoded superoxiddismutase and catalase was studied. Expression was gradually stimulated. However, under conditions employed in experiments, direct changes. Presumably this can be explained by a post-translational regulation of the activity of these enzymes. (authors)

  13. L -Carnitine and Melatonin Reverse CCl4 Induced Liver Fibrosis In Rats (Histological and Histochemical Studies

    Directory of Open Access Journals (Sweden)

    Fatma, A. Morsy, Abdel Razik, H. Farrag and Sonya, L. El-Sharkawy

    2004-12-01

    Full Text Available Carbontetrachloride (CCl4 is closely related chemically to chloroform and likewise in hepatic poisons. This study was designed to evaluate the effects of carbon tetrachloride on liver of male rats and the reversing effects of L-carnitine and melatonin on established liver fibrosis. A total of 72 adult male albino rats were used in this study. The animals were divided into six groups. Group (1 animals of the first group were kept as control andtreated with paraffin oil twice weekly for eight weeks. Group (2 rats of the second group were injected with CCl4 intraperitoneally at 0.15 ml per rats (diluted 1:1 in liquid paraffin twice weekly for eight weeks to produced liver fibrosis. Group (3 following establishment with CCl4 which induced liver fibrosis, the rats were treated with L-carnitine at a dose level of 50 mg/kg for four weeks. Group (4 rats with liver fibrosis were injected intraperitoneally with melatonin at dose level of 10 mg/kg for four weeks. The fifth and sixth groups were given L-carnitine and/or melatonin at dose levels of 50 mg/kg and 10 mg/kg respectively for four weeks. Histological changes in the liver of rats treated with CCl4 including liver fibrosis, architecture distortion and appearance of many pseudolobule. The fibrous tissues run in septa between the nodules. The liver damage varied from one area to another and varied from moderate fibrosis to cirrhosis. Quantitative measurement of the severity of liver fibrosis (area damage was achieved by using computerized image analysis (Leica image showed that highly significant increase in area of fibrosis was recorded in the case of rats treated with CCl4 only. Quantitative DNA image analysis showed that 3% of aneuploid cells could be noticed in liver of rats treated with CCl4 only. Histochemical results of rats treated with CCl4 showed highly significant increase in grey level of mucopolysaccharides and protein levels. No histological and histochemical changes could be noticed in

  14. 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.

  15. Liver atrophy following portacaval shunt in normal rats: A morphologic and ultrastructural study

    Directory of Open Access Journals (Sweden)

    Radosavljević Tatjana

    2003-01-01

    Full Text Available The aim of the current study was to examine morphological and ultrastructural changes in the rat liver in an experimental model of chronic liver disease (end-to-side portacaval shunt. The surgical procedure providing an end-to-side portacaval shunt (PCS was performed in Wistar rats. The liver and pancreas weights were determined 8 weeks after the operation, when liver histology and ultrastructural patterns of hepatocytes were examined. Body weights were not significantly different between the groups 8 weeks after the operation. Liver weight was significantly lower in PCS rats than in control and sham operated (SHAM rats. The same was observed when liver weight was expressed as a percentage of body weight. Pancreas weight was significantly greater in PCS than in control and SHAM rats. Liver histology in rats with PCS showed glycogen depletion and sinusoidal dilatation around the hepatic vein. Kupffer's cells were filled with haemosiderin. The hepatocytes surrounding the portal space exhibited degenerative and microvesicular fatty changes. Multiplication of the biliary ductules in the portal space was present. Atrophy of hepatocytes occurred in other parenchymal zones and apoptopic hepatocytes were seen more frequently in rats with PCS. The ultrastructural characteristics of hepatocyte cell lesions in rats with PCS at the end point of our experiment included reduction and fragmentation of rough endoplasmic reticulum with destroyed or dilated cisternae and few polysomes accompanied by proliferation of smooth endoplasmic reticulum. The present study suggests that end-to-side PCS in rats causes liver atrophy and that the morphological and ultrastructural changes in the hepatocytes partially explain the metabolic and endocrine abnormalities.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Purification and some characteristics of liver cytosol cornin, an antimitotic substance from rat liver cytosol

    Directory of Open Access Journals (Sweden)

    Inaba,Kozo

    1977-06-01

    Full Text Available Further purification and characterization are reported on rat cytosol cornin (RLCC, an antimitotic substance. Fraction I (purified RLCC was purified more than 10-fold from crude RLCC with Sephadex G-50 column chromatography and showed a remarkable inhibitory effect on division of inseminated sea urchin eggs and mouse fibroblast cells. Fraction I was observed as one spot, and the molecular weight was estimated to be about 25,000 by thin layer gel filtration. Fraction I contained protein (92% and RNA (8%, but the antimitotic activity was scarcely affected by treatment by pancreatic RNase. The protein of Fraction I was separated into two bands by SDS-polyacrylamide gel electrophoresis, and the molecular weight was estimated as 10,000 and 15,000, respectively. The 50% inhibition dose of Fraction I on the first division of inseminated sea urchin eggs and on proliferation of mouse L cells was about 2.5 X 10(-5 g/ml and 5 X 10(-4 g/ml, respectively. The yield of fraction I was about 35 mg from 100 g rat liver.

  18. CHLORAL HYDRATE DECREASES GAP JUNCTION COMMUNICATION IN RAT LIVER EPITHELIAL CELLS

    Science.gov (United States)

    Chloral hydrate decreases gap junction communication in rat liver epithelial cells Gap junction communication (GJC) is involved in controlling cell proliferation and differentiation. Connexins (Cx) that make up these junctions are composed of a closely related group of m...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Predictive value of POSSUM score in surgery of acute abdomen in cirrhotic patients

    OpenAIRE

    Banu, P; Popa, F; Constantin, VD; Balalau, C

    2013-01-01

    Abstract Introduction: As liver cirrhosis has an increasing incidence in the general population and the life expectancy for these patients has increased, surgery procedures practiced for acute abdomen in such category of patients are more frequent. Aim: To evaluate the predictive value of POSSUM score in cirrhotic patients undergoing abdominal surgery in emergency cases. Material and method: A prospective study based on 115 consecutive patients with liver cirrhosis hospitalized and operated i...

  1. Low Molecular Weight Heparin in Portal Vein Thrombosis of Cirrhotic Patients: Only Therapeutic Purposes?

    OpenAIRE

    Raffaele Licinio; Mariabeatrice Principi; Giuseppe Losurdo; Nicola Maurizio Castellaneta; Enzo Ierardi; Alfredo Di Leo

    2014-01-01

    Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the reduction in the hepatic synthesis of procoagulant proteins. However, with the progression of liver disease, the cirrhotic patient undergoes a high rate of thrombotic phenomena in the portal venous system. Although the progression of liver failure produces a reduction in the synthesis of anticoagulant molecules, a test able to detect the patients with hemostatic balance shifting towards hypercoagulability has not yet...

  2. Reduction of 3-mercaptopyruvate in rat liver is catalyzed by lactate dehydrogenase.

    OpenAIRE

    Ohta,Jun; Ubuka,Toshihiko

    1989-01-01

    It has been assumed that the in vivo reduction of 3-mercaptopyruvate, an intermediate of cysteine metabolism, to 3-mercaptolactate is catalyzed by lactate dehydrogenase (EC 1.1.1.27) though no definitive evidence has been presented. In order to examine this assumption, reduction of 3-mercaptopyruvate and its inhibition were studied using rat liver homogenate, lactate dehydrogenase purified from rat liver and anti-lactate dehydrogenase antiserum. Reduction of 3-mercaptopyruvate was actively ca...

  3. Polyploidization delay in rat hepatocytes under liver growth inhibition by hypokinesia

    Science.gov (United States)

    Faktor, V. M.; Malyutin, V. F.; Li, S. Y.; Brodskiy, V. Y.

    1981-01-01

    A study of young rats, weighing 55 to 59 g, after being for 10 days in conditions of limited mobility, shows a retardation of body growth as well as that of liver growth. The decrease in the rate of growth is accompanied by a reduction of cell proliferation and by delay polyploidization of hepatocytes in the liver of experimental rats. The materials, methods, and results of research are discussed.

  4. MORPHOMETRIC CHARACTERISTIC OF RATS LIVER UNDER PRE-SLAUGHTER STRESS AND USAGE OF BIOLOGICALLY ACTIVE SUBSTANCES

    OpenAIRE

    Grabovskyi S. S.; Grabovska O. S.

    2015-01-01

    We have studied morphometric parameters of rats’ liver under stress conditions using the biologically active substances of plant and animal origin: spleen, Echinacea and Chinese lemon extracts, sprouted grain. Aerosol introduction of spleen extract to the rats feed for five days before slaughter was caused to liver morphological state moderate deviation, indicating the antistressors properties of polyamines contained in this extract. The results of model experiment on rats can be used ...

  5. Pyrazole prevention of CC14-induced ultrastructural changes in rat liver.

    OpenAIRE

    Bernacchi, A. S.; de Castro, C. R.; De Toranzo, E. G.; Marzi, A.; de Ferreyra, E. C.; de Fenos, O. M.; Castro, J.A.

    1980-01-01

    Carbon tetrachloride (CC14) administration to rats leads to an early dilatation, vesiculation and disorganization of the liver endoplasmic reticulum (ER). This hepatotoxin also causes detachment of ribosomes from ER membranes, dilatation of the Golgi cisternae and occasionally dilatation of the perinuclear membrane. Prior treatment of the rats with pyrazole completely prevents CC14- induced ultrastructural alterations observed in liver at 3 h. This drug is known to decrease the intensity of t...

  6. Histological changes in the liver of fetuses of pregnant rats following citalopram administration

    OpenAIRE

    Zeynab Mohammadi; Mahnaz Azarnia; Ghadireh Mirabolghasemi; Abdolhossein Shiravi; Zohreh Mohammadi

    2013-01-01

    Objective: Depression is a dilapidating disorder, which may occur during pregnancy. Citalopram is an antidepressant drug often prescribed to pregnant women. The purpose of the present study is to determine whether maternal administration of citalopram affects fetal liver histology. Materials and Methods: Pregnant Wistar albino rats were treated with citalopram (10 or 20 mg/kg/day). A control group received no treatment. Rat fetal liver samples were obtained on day 18 of gestation and eval...

  7. 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.

  8. PPARα agonists up-regulate organic cation transporters in rat liver cells

    International Nuclear Information System (INIS)

    It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-α agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARα agonists in livers of rats and in Fao cells. We conclude that PPARα agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Rat liver tolerance for partial resection and intraoperative radiation therapy: Regeneration is radiation dose dependent

    International Nuclear Information System (INIS)

    We studied the feasibility of delivering a large single dose of intraoperative radiation as an adjuvant to partial hepatic resection. Intraoperative radiation therapy (IORT) was delivered to the remaining liver of 84 rats after partial hepatectomy to determine the acute and chronic effects of treatment on blood chemistry values, histology, survival, hepatic regeneration, and cellular appearance of the normal liver. Transient elevations in SGOT, SGPT, and alkaline phosphatase were attributed both to hepatectomy and to liver parenchymal damage induced by IORT. Microscopic examination upon necropsy, performed at frequent intervals post-treatment revealed hepatic capsular thickening with some alteration of liver architecture mainly underneath the capsule, with localized inflammation and some areas of necrosis. Survival in all groups was 100% at 45 days. Liver weight increase proved to be dose-dependent and displayed a bisphasic pattern. This study demonstrated that IORT is a feasible adjunct to surgical resection of the liver in the rat model

  11. Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, R.A.; Crews, F.T. (Department of Pharmacology, University of Texas, Austin (USA))

    1991-03-01

    The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of (3H)prazosin and (3H)AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.

  12. Ginkgo biloba extract reverses CCl4-induced liver fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Jun Luo; Jie-Ping Yu; Zhao-Hong Shi; Li Wang

    2004-01-01

    AIM: To study the reversing effect of Ginkgo biloba extract (GbE) on established liver fibrosis in rats.METHODS: Following confirmation of CCl4-induced liver fibrosis, GbE or saline was administrated to the rats for 4 weeks. The remaining rats received neither CCl4 nor GbE as normal control. The four groups were compared in terms of serum enzymes, tissue damage, expression of αSMA and tissue inhibitor-1 of metalloproteinase (TIMP-1) and metalloproteinase-1 (MMP-1).RESULTS: Compared with saline-treated group, liver fibrosis rats treated with GbE had decreased serum total bilirubin (P<0.01) and aminotransferase levels (P<0.01) and increased levels of serum albumin (P<0.01). Microscopic studies revealed that the livers of rats receiving GbE showed allieviation in fibrosis (P<0.05) as well as expression of αSMA (P<0.01). The liver collagen and reticulum contents were lower in rats treated with GbE than saline-treated group (P<0.01). RT-PCR revealed that the level of TIMP-1 decreased while the level of MMP-1 increased in GbE group.CONCLUSION: Administration of GbE improved CCl4-induced liver fibrosis. It is possibly attributed to its effect of inhibiting the expression of TIMP-1 and promoting the apoptosis of hepatic stellate cells.

  13. Possible Role of Humoral Immunity on Liver Dysfunction in Male Albino Rats

    International Nuclear Information System (INIS)

    Fifty male albino rats were used in this study to correlate liver function after curcumin or/and malathion intake with the levels of immunoglobulin G (IgG) and immunoglobulin M (IgM). The rats were divided into four groups, the first was the control group, the second was given malathion in drinking water (200 ppm), the third was administrated curcumin orally (70 mg/kg b.w.) 5 times /week while the fourth group received both malathion and curcumin with the same previous concentrations. Liver state was evaluated every 10 days by estimating prothrombine time (P.T.) and concentration (PC) and albumin level from blood taken from the retroorbital vein of 5 rats of the malathion group. After 40 days when there is prolongation of P.T. and hypoalbuminemia, ten rats from each group were decapitated. Liver enzymes, total protein, glucose, insulin, IgG and IgM were estimated. The data revealed that there is an increase of liver enzymes, glucose, insulin, and immunoglobulins (IgG) and (IgM) in malathion group and positive correlation between liver enzymes and immunoglobulins. These results denoted that the increase of immunoglobulins after malathion intake had no beneficial effects on the prognosis of liver condition, on the contrary, it may worsen liver state if there is some element of auto immunity, as well as the study proved that turmeric has the potential to improve the toxic effects of Malathion, whether on the functions of the liver or immune globulins.

  14. High affinity binding of [3H]cocaine to rat liver microsomes

    International Nuclear Information System (INIS)

    ]3H]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 [3H]cocaine binding. On the other hand, chronic administration of cocaine reduced [3H]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 [3H]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 [3H]cocaine binding to liver with a different rank order of potency than their displacement of [3H]cocaine binding to striatum. This high affinity [3H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

  15. DIFFERENTIAL-EFFECTS OF METABOLIC-INHIBITORS ON CELLULAR AND MITOCHONDRIAL UPTAKE OF ORGANIC CATIONS IN RAT-LIVER

    NARCIS (Netherlands)

    STEEN, H; MARING, JG; MEIJER, DKF

    1992-01-01

    The effects of several metabolic inhibitors on the uptake of tri-n-butylmethylammonium (TBuMA) were studied in isolated rat liver mitochondria, isolated rat hepatocytes and isolated perfused rat livers, in order to characterize further the mechanisms for carrier-Mediated uptake and cellular accumula

  16. Glutathione treatment protects the rat liver against injury after warm ischemia and Kupffer cell activation

    OpenAIRE

    Bilzer, M.; Baron, A; Schauer, R.; Steib, C.; Ebensberger, S.; Gerbes, Alexander L.

    2002-01-01

    Background/Aim: The generation of reactive oxygen species by activated Kupffer cells (KC) may contribute to reperfusion injury of the liver during liver transplantation or resection. The aim of our present studies was to investigate (1) prevention of hepatic reperfusion injury after warm ischemia by administration of the antioxidant glutathione (GSH) and (2) whether GSH confers protection through influences on KC toxicity. Methods: Isolated perfused rat livers were subjected to 1 h of warm is...

  17. Protective effect of whey proteins against nonalcoholic fatty liver in rats

    OpenAIRE

    Hamad, Essam M; Taha, Soad H; Abou Dawood, Abdel-Gawad I; Sitohy, Mahmoud Z; Abdel-Hamid, Mahmoud

    2011-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from hepatic steatosis to end-stage liver disease. It is the most common liver disease and its prevalence is increasing worldwide. In the present study, the effect of whey proteins on some parameters of NAFLD was investigated. Results Oral administration of the studied whey proteins products reduced the final body weight of rats. There was a significant reduction effect (P <...

  18. Toxicity Effect of Nigella Sativa on the Liver Function of Rats

    OpenAIRE

    Mohamad Hafanizam Bin Hassan; Latiffah Abdul Latiff; Saadat Parhizkar; Mohammad Aziz Dollah

    2013-01-01

    Purpose: The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue. Methods: Twenty four male Sprague Dawley rats were allotted randomly to four groups including: control (taking normal diet); low dose (supplemented with 0.01 g/kg/day Nigella sativa); normal dose (supplemented with 0.1 g/kg/day Nigella sativa) and high dose (supplemente...

  19. Protective effect of whey proteins against nonalcoholic fatty liver in rats

    OpenAIRE

    Sitohy Mahmoud Z; Abou Dawood Abdel-Gawad I; Taha Soad H; Hamad Essam M; Abdel-Hamid Mahmoud

    2011-01-01

    Abstract Background Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from hepatic steatosis to end-stage liver disease. It is the most common liver disease and its prevalence is increasing worldwide. In the present study, the effect of whey proteins on some parameters of NAFLD was investigated. Results Oral administration of the studied whey proteins products reduced the final body weight of rats. There was a significant reduction ef...

  20. 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.

  1. 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.

  2. 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

  3. Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats

    International Nuclear Information System (INIS)

    Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury. (author)

  4. 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.

  5. MANAGEMENT OF PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. Korean red ginseng extract suppresses the progression of alcoholic fatty liver in a rat model

    International Nuclear Information System (INIS)

    Alcoholic fatty liver (AFL) is the most common liver disease among Korean men, and Korean red ginseng has been used as a folk medicine to diverse diseases in Korea. Therefore, we examined if Korean red ginseng extract (KRG) could be a suppressive agent on AFL in a rat model or not. Experimental rats were fed the Lieber DeCarli diet with 36% of energy intake from ethanol, and divided into three groups which daily co-administered KRG 0, 700 and 1400 mg/kg for six weeks, respectively. Naive rats were fed iso-caloric control diet without ethanol and KRG. We investigated histopathological hepatic characteristics, hepatic and plasma lipid concentrations, hepatic hydroxyproline contents, heart/liver radioactivity ratio of 201Thallium and liver/body weight of the rats at the end point. Ethanol intake brought about steatotic, inflammatory, necrotic and fibrotic changes of livers significantly, and it also lead the rats to increase hepatic triglyceride and hydroxyproline contents, plasma total cholesterol and low density lipoprotein cholesterol levels, and liver/body weight. However, co-administration of KRG 1400 mg/kg suppressed fat accumulation and fibrotic initiation in AFL rat model significantly. It was also inclined to attenuate inflammatory cell infiltration, hydroxyproline accumulation, and increasing liver/body weight, even though plasma lipid levels and heart/liver ratios were not successfully improved by six-week-long intakes of KRG. In conclusions, co-administration of KRG 1400 mg/kg could significantly suppress steatosis in AFL rat model, and it might need longer ingestion of KRG than six weeks to improve plasma lipid imbalance. (author)

  8. Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

    Energy Technology Data Exchange (ETDEWEB)

    Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical College, Philadelphia, PA (USA))

    1990-04-01

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.

  9. 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

  10. 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...

  11. Effects of Guiyuanfang and autologous transplantation of bone marrow stem cells on rats with liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Mao Wu; Lian-Da Li; Hong Liu; Ke-Yong Ning; Yi-Kui Li

    2005-01-01

    AIM: To investigate the therapeutic effects of Guiyuanfang and bone marrow stem cells (BMSCs) on rats with liver fibrosis.METHODS: Liver fibrosis model was induced by carbon tetrachloride, ethanol, high lipid and assessed biochemically and histologically. Liver function and hydroxyproline contents of liver tissue were determined.Serum hyaluronic acid (HA) level and procollagen Ⅲ level were performed by radioimmunoassay. The VG staining was used to evaluate the collagen deposit in the liver.Immunohistochemical SABC methods were used to detect transplanted BMSCs and expression of urokinase plasminogen activator (uPA).RESULTS: Serum transaminase level and liver fibrosis in rats were markedly reduced by Guiyuanfang and BMSCs. HA level and procollagen Ⅲ level were also reduced obviously,compared to model rats (HA: 47.18±10.97 ng/mL,48.96±14.79 ng/mL; PCⅢ: 22.48±5.46 ng/mL, 26.90±3.35ng/mL; P<0.05).Hydroxyproline contents of liver tissue in both BMSCs group and Guiyuanfang group were far lower than that of model group (1 227.2±43.1 μg/g liver tissue, 1390.8±156.3 μg/g liver tissue; P<0.01). After treatment fibrosis scores were also reduced. Both Guiyuanfang and BMSCs could increase the expression of uPA. The transplanted BMSCs could engraft, survive, and proliferate in the liver.CONCLUSION: Guiyuanfang protects against liver fibrosis.Transplanted BMSCs may engraft, survive, and proliferate in the fibrosis livers indefinitely. Guiyuanfang may synergize with BMSCs to improve recovery from liver fibrosis.

  12. 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

    Seventy-three euthyroid male patients with alcoholic cirrhosis of the liver were randomly allocated to oral testosterone (200 mg t.i.d.) or placebo and followed for up to 36 months. Triiodothyronine (T3), tetraiodothyronine (T4), thyroxine binding globulin (TBG) and T4/TBG ratio were determined...... 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...... of sex hormone receptors in their liver....

  13. Localization of Ga-67 in rat liver cell, 2

    International Nuclear Information System (INIS)

    The intracellular behaviour of Ga-67 was studied after intravenous injection of Ga-67 citrate to the rat. The mechanisms of cellular uptake was investigated by observing the time course of the radionuclide in subcellular liver cell fractions. For this purpose, we have developed a continuous isopycnic rate-zonal ultracentrifugation system capable of successively fractionating the homogenate according to isopycnic and rate-zonal principles. To collect the cell nuclei, a special technique, which consisted of supplementing the outer sucrose layer with cesium chloride to increase density, was applied to trap nuclei with isopycnic equilibrium. We isolated cell nuclei, mitochondria, lysosomes and peroxysomes, micro-somes and the cell supernatant in sufficiently purified state. With this technique, the intracellular localization of Ga-67 was studied. At 30 minutes after intravenous injection, radioactivity was found mainly in the cell supernatant, the radioactivity peak corresponded to sedimentation coefficient of 5S. However, after 24 hours, the radioactivity was localized in the heavier fraction containing lysosomes and heavy endoplasmic reticulum, and it was found that further moving of Ga-67 did not take place thereafter. No intranuclear localization was observed. Furthermore, we found no radioactivity of Ga-67 associated with ferritin in the course of migration of Ga-67 in the cytosol. Therefore, it is concluded that gallium is stored entirely in the above mentioned organella, and ferritin is not participating in gallium transport and storage. (author)

  14. The substrate-dependent photoinactivation of urocanase from rat liver

    International Nuclear Information System (INIS)

    Rat liver urocanase was readily inactivated by near-UV light in the presence of the substrate. Irradiation of substrate or enzyme alone was ineffective. The purpose of this study was to examine the conditions which influenced this inactivation and to investigate the mechanism. The urocanase concentration needed for 50% of the maximum inactivation for a 15 min irradiation was 0.09 μMU. Temperatures from 0 to 300C during irradiation had little influence. Inactivation occurred at -750C, which indicated a photochemical reaction. The pH had little influence on inactivation. Photoinactivation was the same in nitrogen and air. Dialysis experiments showed that unbound small molecules were probably not involved. Inactivated enzyme did not inhibit active enzyme. Chelators, reducing agents, and pyridoxal phosphate did not affect the inactivation. Visible light was not effective. An action spectrum was established with the aid of a monochromator. The action spectrum had a peak at 280 nm and a shoulder extending from 300 to 340 nm which rules out flavins, pyridoxal phosphate, a simple protein, and free urocanase as the chromophore. The results suggest that this photochemical process is not photodynamic action. It appears that only substrate and enzyme are needed for this photoinactivation. The enzyme-substrate complex may be the chromophore. (author)

  15. Purification and characterization of cysteine aminotransferase from rat liver cytosol.

    Directory of Open Access Journals (Sweden)

    Akagi,Reiko

    1982-06-01

    Full Text Available Cysteine aminotransferase (L-cysteine: 2-oxoglutarate aminotransferase, EC 2.6.1.3 was purified over 400-fold from the high-speed supernatant fraction of rat liver. The purified enzyme was homogeneous as judged by gel filtration, isoelectric focusing and disc electrophoresis. The molecular weight of the enzyme was about 74,000 by gel filtration and the isoelectric point was 6.2 (4 degrees C. The enzyme catalyzed transamination between L-cysteine and 2-oxoglutarate and the reverse reaction. The optimum pH was 9.7. The Km value for L-cysteine was 22.2 mM, and that for 2-oxoglutaric acid was 0.06 mM. L-Aspartate was a potent inhibitor of the cysteine aminotransferase reaction. The enzyme was very active toward L-alanine 3-sulfinic acid at pH 8.0, and was also very active toward L-aspartic acid (Km = 1.6 mM. Ratios of activities for L-aspartic acid and L-cysteine were essentially constant during the purification of the enzyme. Evidence based on substrate specificity, enzyme inhibition, and physicochemical properties indicates that cytosolic cysteine aminotransferase is identical with cytosolic aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1.

  16. Lysosomal phospholipids from rat liver after treatment with different drugs.

    Science.gov (United States)

    Tjiong, H B; Lepthin, J; Debuch, H

    1978-01-01

    Rats were treated with 5 different drugs p-ethoxyacetanilide (I), indometacin (II) and nor-amidopyrine-methanesulfonate (III), O,O'-bis(diethylaminoethyl)hexestrol(IV) and choloroquine (V) for 3 - 4 weeks. Liver cell fractions were isolated by discontinuous gradient centrifugation and the specific activity of acid phosphatase was determined in each. Lysosomal fractions contained widely varying amounts of this marker enzyme, indicating that the concentration of lysosomes within these fractions differed. The amounts and patterns of phospholipids reflected this fact. Since we assumed bis(monoacylglycero)phosphate [(MAG)2-P; synonym:lysobisphosphatidic acid] is a marker lipid for secondary lysosomes, we expected and found significant quantities of this acidic phospholipid only in those lysosomal fractions which were also rich in acid phosphatase activity. 12% of the lysosomal phospholipids from animals receiving the hexestrol derivative (IV), and 19% of those from the chloroquine (V) experiment were present as (MAG)2P. The fatty acid compositions of this lysosomal phospholipid were not the same in all lysosome fractions. The more (MAG)2P present in the lysosomes, the more unsaturated are the fatty acids. Thus, after treatment with chloroquine, more than 90% of the fatty acids from (MAG)2P are unsaturated; C22:6 represents about 70% of the total. PMID:627402

  17. Effects of Stevia rebaudiana natural products on rat liver mitochondria.

    Science.gov (United States)

    Kelmer Bracht, A; Alvarez, M; Bracht, A

    1985-03-15

    The effects of several natural products extracted from the leaves of Stevia rebaudiana on rat liver mitochondria were investigated. The compounds used were stevioside (a non-caloric sweetener), steviolbioside, isosteviol and steviol. Total aqueous extracts of the leaves were also investigated. S. rebaudiana natural products inhibited oxidative phosphorylation, ATPase activity NADH-oxidase activity, succinate-oxidase activity, succinate dehydrogenase, and L-glutamate dehydrogenase. The ADP/O ratio was decreased. Substrate respiration (state II respiration) was increased at low concentrations (up to 0.5 mM) and inhibited at higher concentrations (1 mM or more). In uncoupled mitochondria, inhibition of substrate respiration was the only effect observed. Net proton ejection induced by succinate and swelling induced by several substrates were inhibited. Of the compounds investigated, the sweet principle stevioside was less active. It was concluded that, in addition to the inhibitory effects, S. rebaudiana natural products may also act as uncouplers of oxidative phosphorylation. The possible physiologic consequences of the ingestion of stevioside and S. rebaudiana aqueous extracts are discussed. PMID:2858211

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Determination of arsenic in subcellular fractions of rat liver by ENAA

    International Nuclear Information System (INIS)

    The concentration of arsenic in subcellular fractions of rat liver is determined by differential centrifugation combined with epithermal neutron activation analysis (ENAA). The analytical quality has been verified by analysis of some standard reference materials. The results show that the distribution of As in subcellular fractions of rat liver cells is not homogeneous. The highest concentration of As is found in microsome, while the lowest content is found in nuclei for arsenic poisoned rat. The lowest content of As is noted in mitochondria of contrast rats. The differences of As contents in subcellular fractions of lives cells between arsenic poisoned and normal rats are compared by means of t-test and exceedingly significant differences are found (P<0.001). In As poisoned rat, the As content in microsome is significantly higher than that in other subcellular fractions (P<0.05), except lysosome

  20. 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,

  1. Attenuation of portal hypertension by natural taurine in rats with liver cirrhosis

    OpenAIRE

    Jian Liang, Xin Deng, Zhi-Xiu Lin, Li-Chun Zhao, Xi-Liu Zhang

    2009-01-01

    AIM: To investigate the inhibitory effect of natural taurine (NTau) on portal hypertension (PHT) in rats with experimentally-induced liver cirrhosis (LC).METHODS: Experimentally-induced LC Wistar rats (20 rats/group) were treated with either oral saline or oral NTau for 6 consecutive weeks. Evaluation parameters included portal venous pressure (PVP), portal venous resistance (PVR), portal venous flow (PVF), splanchnic vascular resistance (SVR) and mean arterial pressure (MAP). Vasoactive subs...

  2. Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative Stress in Rats

    OpenAIRE

    Mallikarjuna Korivi; Chien-Wen Hou; Chih-Yang Huang; Shin-Da Lee; Ming-Fen Hsu; Szu-Hsien Yu; Chung-Yu Chen; Yung-Yang Liu; Chia-Hua Kuo

    2012-01-01

    Despite regular exercise benefits, acute exhaustive exercise elicits oxidative damage in liver. The present study determined the hepatoprotective properties of ginsenoside-Rg1 against exhaustive exercise-induced oxidative stress in rats. Forty rats were assigned into vehicle and ginsenoside-Rg1 groups (0.1 mg/kg bodyweight). After 10-week treatment, ten rats from each group performed exhaustive swimming. Estimated oxidative damage markers, including thiobarbituric acid reactive substance (TBA...

  3. Therapeutic Effects of Melatonin On Liver And Kidney Damages In Intensive Exercise Model of Rats.

    Science.gov (United States)

    Gedikli, Semin; Gelen, Volkan; Sengul, Emin; Ozkanlar, Seckin; Gur, Cihan; Agırbas, Ozturk; Cakmak, Fatih; Kara, Adem

    2015-01-01

    Extensive exercise induces inflammatory reactions together with high production of free radicals and subsequent liver and kidney tissues damage. This study was designed to investigate for effects of melatonin on liver and kidney tissues in the extensive exercise exposed rats and non-exercised rats. In this research, 24-male Sprague-Dawley rats were divided into four groups. For exercise rat model, the rats were exposed to slow pace running with the velocity of 10 m/min for 5 minutes for five days just before the study. And for last ten days after adaptation period, the exercise was improved as 15 min with the speed of 20 m/min and intra-peritoneal melatonin injection has been performed to the melatonin treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease in the parameters of kidney and liver enzymes in exercise-group and an increase in the parameters of serum, liver and kidney enzymes in the group that melatonin-exercise-group. As for histological analysis, while it is observed that there are cellular degenerations in the liver and kidney tissues with exercise application, a decrease has been observed in these degenerations in the group that melatonin was applied. At the end of the research, it has been determined that exercise application causes some damages on liver and kidney, and these damages were ameliorated with melatonin treatment. PMID:26310355

  4. Caloric Restriction Prevents Lead-Induced Oxidative Stress and Inflammation in Rat Liver

    OpenAIRE

    Mustafa Mohammadi; Rana Ghaznavi; Rana Keyhanmanesh; Hamid Reza Sadeghipour; Roya Naderi; Hossein Mohammadi

    2014-01-01

    The aim of the present study is to investigate the effects of caloric restriction on liver of lead-administered rat. Male Sprague-Dawley rats were randomly divided into two groups: Ad libitum fed group (AL, free access to normal rat chow) and caloric restriction group (CR, fed 65% of AL animals' food intake). After 6 weeks, half of the animals of each group were injected lead acetate and the other half were injected saline. Liver tissue samples were collected at the end of the experiments. Gl...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Oxidative stress associated with pathological lesions in the liver of rats experimentally infected by Fasciola hepatica.

    Science.gov (United States)

    Bottari, Nathieli B; Mendes, Ricardo E; Lucca, Neuber J; Schwertz, Claiton I; Henker, Luan C; Olsson, Débora C; Piva, Manoela M; Sangoi, Manuela; Campos, Luízi P; Moresco, Rafael N; Jaques, Jeandre A; Da silva, Aleksandro S

    2015-12-01

    The aim of this study was to analyze the antioxidant status and oxidative profile in serum and liver of rats experimentally infected with Fasciola hepatica and its relationship with pathological findings. Twenty-four rats were divided into two groups: group A consisted of 12 healthy rats and group B of 12 rats infected orally with 20 metacercaria of F. hepatica. At days 20 and 150 post-infection (PI), blood and liver samples of six animals from each group were collected. The protein oxidation (AOPP technique: advanced oxidation protein products) and antioxidants (FRAP technique: ferric reducing antioxidant power) levels were measured in serum and liver. Furthermore, nitrite/nitrate (NOx) levels and lipid peroxidation (TBARS technique: thiobarbituric acid reactive substances) were measured in liver. AOPP and FRAP levels were increased (P < 0.05) in serum and liver of infected animals in acute and chronic infection when compared with healthy animals. The same occurred with TBARS and NOx levels in the liver (P < 0.05). Histopathology revealed periportal fibrous hepatitis, composed of an abundant inflammatory infiltrate in portal spaces on infected animals, as well as bile duct hyperplasia. The results found seem to be related to the host free radical production demonstrated in serum samples and liver due to the parasite infection. PMID:26311170

  7. 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.

  8. 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.

  9. 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.

  10. Mercury-selenium interactions in relation to histochemical staining of mercury in the rat liver

    DEFF Research Database (Denmark)

    Baatrup, E; Thorlacius-Ussing, O; Nielsen, H L;

    1989-01-01

    Selenium has been suggested to enhance the histochemical staining of mercury when sections of tissue are subjected to the silver-enhancement method. In the present study, histochemical staining patterns of mercury in tissue sections of rat livers were compared with the actual content of organic and...... inorganic Hg in the livers, in both the presence and the absence of Se. Rats were injected intravenously with 5 micrograms of Hg g-1 body weight as methyl [203Hg] mercury chloride (MeHg) or as [203Hg]mercuric chloride (Hg2+). After 2 h, half the rats received an additional intraperitoneal injection of 2...... micrograms of Se g-1 body weight as sodium [75Se]selenite. All the rats were killed 1 h later. Homogenized liver samples were prepared for mercury analysis by two different methods: alkaline digestion and ultrasonic disintegration. Quantitative chemical analysis based on benzene extraction of the...

  11. Effect of curcuma longa L. on fatty liver induced by oxytetracycline in albino rats.

    Directory of Open Access Journals (Sweden)

    Eman G.E. Helal , Samia M. Abd El-Wahab and Ghada A. Zedan

    2011-04-01

    Full Text Available Background: Curcuma longa has been shown to be a potent anti-inflammatory, antioxidant and anticarcinogenic agent. The present investigation aimed at examining the possible potential protective effect of curcuma against oxytetracyclin-induced fatty liver in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. Material and Methods: Albino rats were divided into two major groups, 15 rats for each. The first group was divided into three sub-groups: a control, b fatty liver group; that was injected intraperitonealy with oxytetracycline ( 120mg/kg for three consecutive days resulting in steatosis and c curcuma treated group; which was treated with curcuma ( 0.4 % of diet for 30 days after fatty liver induction . All animals were scarified after 33 days of the beginning of the experiment. The second group was divided into three subgroups: a control, b fatty liver group and c drug protection group; which received curcuma for 15 days before induction of fatty liver, then sacrificed after induction of fatty liver (3 days. Blood samples were collected for biochemical analysis. Liver specimens were obtained and fixed in 10 % formalin for histological study. Results: Fatty liver groups showed high significant increase in serum glucose, cholesterol, triglycerides, LDL cholesterol, ALT, AST, GGT, LDH, total protein, albumin, globulin, urea and creatinine while HDL cholesterol and A/G ratio were significantly decreased compared to control group. Histopathological changes were detected in liver tissue of fatty liver rats. The treatment with curcuma ameliorated the biochemical parameters and histological changes. The pre-treatment with curcuma before the induction of fatty liver also ameliorated the results but they did not turn back to the normal values. Conclusion: It is recommend to using curcuma as diet additive for fatty liver patients or those people who have hyperlipidemic family history.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Brain cholinergic impairment in liver failure.

    Science.gov (United States)

    García-Ayllón, María-Salud; Cauli, Omar; Silveyra, María-Ximena; Rodrigo, Regina; Candela, Asunción; Compañ, Antonio; Jover, Rodrigo; Pérez-Mateo, Miguel; Martínez, Salvador; Felipo, Vicente; Sáez-Valero, Javier

    2008-11-01

    The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (~30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected. In agreement with the human data, AChE activity in brain cortical extracts of bile duct ligated (BDL) rats was increased (~20%) compared to controls. A hyperammonemic diet did not result in any further increase of AChE levels in the BDL model, and no change was observed in hyperammonemic diet rats without liver disease. Portacaval shunted rats which display increased levels of cerebral ammonia did not show any brain cholinergic abnormalities, confirming that high ammonia levels do not play a role in brain AChE changes. A selective increase of tetrameric AChE, the major AChE species involved in hydrolysis of acetylcholine in the brain, was detected in both cirrhotic humans and BDL rats. Histological examination of BDL and non-ligated rat brains shows that the subcellular localization of both AChE and choline acetyltransferase, and thus the accessibility to their substrates, appears unaltered by the pathological condition. The BDL-induced increase in AChE activity was not parallelled by an increase in mRNA levels. Increased AChE in BDL cirrhotic rats leads to a pronounced decrease (~50-60%) in the levels of acetylcholine. Finally, we demonstrate that the AChE inhibitor rivastigmine is able to improve memory deficits in BDL rats. One week treatment with rivastigmine (0.6 mg/kg; once a day, orally, for a week) resulted in a 25% of inhibition in the enzymatic activity of AChE with no change in protein composition, as assessed by sucrose density gradient

  14. 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.

  15. Modification of radiation-induced latent injury of rat liver by thioctacid and flavobion

    International Nuclear Information System (INIS)

    The effect of hepatoprotective drugs (flavobion and thioctacid) and a single whole-body irradiation (5,7 Gy of gamma radiation) on the regeneration of rat liver was examined. Liver regeneration was estimated on the basis of chosen morphological parameters on hour 30 after partial hepatectomy. Rediation-induced latent injury to intact rat liver 30 min bedore partial hepatectomy manifested in remaining regenerating liver by slowing-down of the increase in liver weight, cellularity and inhibition of the mitotic activity and in more frequent chromosome aberrations. Both hepatoprotective agents, especially thioctacid, used i.p. 60 min before irradiation, i. e. 90 min before partial hepatectomy, alleviate the manifestations of latent injury in this low proliferating organ as indicated by an increase in cellularity and mitotic index as compared with unprotected animals. Furthermore, the preparations tested decreased the frequency of radiation-induced chromosome aberrations

  16. Repair effect of transplantation of bone marrow mesenchymal stem cells on liver injury in severe burned rats and its mechanism

    International Nuclear Information System (INIS)

    Objective: To investigate the repair effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) on liver injury in severe burned rats, and to clarify its mechanism. Methods: The BMSCs of rats were isolated, cultured, amplified, identified, and labeled in vitro. 30 Wistar rats were randomly divided into normal control group (n=10), model group (n=10) and cell therapy group (n=10). The burned rat model was established. The BMSCs labeled by chlormethyl-benzamidodialkylcarbocyanine (CM-Dil) were transplanted into the rats in cell therapy group by retro-orbital intravenous injection and the saline was injected into the rats in model group. The general status of all rats were observed. The liver tissues of rats were obtained 2 weeks after transplantation, and the pathohistological changes were observed and the pathohistological scores were detected; the apoptotic rate of liver cells was detected by TUNEL method; the engraftment of BMSCs in liver tissues of the rats was observed under laser scanning confocal microscope. Results: 2 weeks after transplantation, the rats in model group were obviously malaise dispirited and the rats in cell therapy group showed obviously better, and the body weight of the rats in cell therapy group was higher than that in model group (P<0.05). The pathohistological results showed the normal liver lobules of the rats in model group disappeared, and the liver cords disordered, and some liver sinusoids dilated and congested, lymphocytes infiltrated with occasional focal aggregating, and cell edema was found, cytoplasm loose and steatosis were seen in liver tissue. However, the pathohistological changes of liver tissue of the rats in cell therapy group were significantly better than those in model group. The pathohistological score of the rats in cell therapy group was significantly lower than that in model group (P<0.05). The TUNEL staining results showed that there were lots of apoptotic liver cells in liver tissue of the rats in

  17. Insulin Radioimmunoassay for Clinical Research in Psychiatric, Pancreatic, Cirrhotic and Irradiated Patients

    International Nuclear Information System (INIS)

    A modified Hales-Randle method for insulin radioimmunoassay is described. An insulin response curve was established in normal cases after glucose loading. Pathological changes were then investigated in patients and animals before and after therapeutic, operative and radiological procedures. Four representative groups of this material will be illustrated. (1) Psychotic patients (acute and chronic schizophrenics, neurotics and depressives) were examined with the aim of learning about the variable effects produced by insulin shock-therapy, as well as for biochemical diagnosis purposes in psychotics. Highest insulin response curves were found in chronic schizophrenics with improvement after insulin therapy. Schizophrenics without improvement presented different curves. Lowest insulin values were found in acute schizophrenia. Depressives and anxiety neurotics showed insulin tolerance curves similar to those of non-psychotic patients. (2) Pancreatic patients. Special attention was paid to pancreatic carcinoma (insulinoma excepted). In most cases of pancreatic carcinoma a very low and flat insulin tolerance curve was found. The above findings may be of a diagnostic importance in this condition, which is clinically hardly recognized. (3) Liver cirrhotic patients. A special group of shunt operated patients was investigated. The study was performed on eight liver cirrhotics before and after porto-caval or reno-splenal shunt operation. The plasma insulin level was examined in the vena cava, renal and cubital blood. The influence of tolbutamide was analysed. The normally occurring retention of insulin by normal hepatic tissue was found to be considerably disturbed. Other interesting changes were observed. (4) The plasma insulin level in the radiologically exposed. Experimental and clinical studies were performed, with insulin doses before and after radiation. Whole body X-ray exposure (300 rads) to rats resulted in a rapid lowering of insulin or its disappearance. Recovery was

  18. Elimination of Proteus mirabilis 51Cr endotoxin from the liver in rats

    International Nuclear Information System (INIS)

    Using isotope methods, elimination of the endotoxin of Proteus mirabilis labelled with chromium (CrEPm) from the liver of rats was studied. The following studies were carried out: intravital exploration of the liver with a scintillation probe, measurements of radioactivity of organs and excreted urine and stools, scintigraphy of the liver, binding of CrEPm by subcellular fractions of hepatocytes, and the influence of selected drugs (polymyxin and hydrocortisone) on elimination of CrEPm from the liver and organelles of hepatocytes. (author)

  19. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

  2. Food restriction modulates β-adrenergic-sensitive adenylate cyclase in rat liver during aging

    International Nuclear Information System (INIS)

    Adenylate cyclase activities were studied in rat liver during postmaturational aging of male Fischer 344 rats fed ad libitum or restricted to 60% of the ad libitum intake. Catecholamine-stimulated adenylate cyclase activity increased by 200-300% between 6 and 24-27 mo of age in ad libitum-fed rats, whereas in food-restricted rats catecholamine response increased by only 58-84% between 6 and 30 mo. In ad libitum-fed rats, glucagon-stimulated enzyme activity also increased by 40% between 6 and 12 mo and in restricted rats a similar age-related increase was delayed until 18 mo. β-Adrenergic receptor density increased by 50% between 6 and 24 mo in livers from ad libitum-fed but not food-restricted rats and showed a highly significant correlation with maximal isoproterenol-stimulated adenylate cyclase activity over the postmaturational life span. Age-related increases in unstimulated (basal) adenylate cyclase activity and nonreceptor-mediated enzyme activation were retarded by food restriction. The results demonstrate that food restriction diminishes a marked age-related increase in β-adrenergic-sensitive adenylate cyclase activity of rat liver. Alterations of adrenergic-responsive adenylate cyclase with age and the modulatory effects of food restriction appear to be mediated by changes in both receptor and nonreceptor components of adenylate cyclase

  3. 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.

  4. Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats.

    Science.gov (United States)

    Singh, Nandita; Kamath, Vasudeva; Narasimhamurthy, K; Rajini, P S

    2008-09-01

    Our earlier studies have shown that extracts derived from potato peel (PPE) are rich in polyphenols and possess strong antioxidant activity both in vitro and in vivo. The objective of the present study was to investigate its potential to offer protection against acute liver injury in rats. Rats pretreated with PPE (oral, 100mg/kgb.w./day for 7 days) were administered a single oral dose carbon tetrachloride (CCl(4), 3ml/kg b.w., 1:1 in groundnut oil) and sacrificed 8h of post-treatment. Hepatic damage was assessed by employing biochemical parameters (transaminase enzyme levels in plasma and liver [AST-aspartate transaminase; ALT-alanine transaminase, LDH-lactate dehydrogenase]). Further, markers of hepatic oxidative damage were measured in terms of malondialdehyde (MDA), enzymic antioxidants (CAT, SOT, GST, GPX) and GSH (reduced glutathione) levels. In addition, the CCl(4)-induced pathological changes in liver were evaluated by histopathological studies. Our results demonstrated that pretreatment of rats with PPE significantly prevented the increased activities of AST and ALT in serum, prevented the elevation of hepatic MDA formation as well as protected the liver from GSH depletion. PPE pretreatment also restored CCl(4)-induced altered antioxidant enzyme activities to control levels. The protective effect of PPE was further evident through the decreased histological alterations in liver. Our findings provide evidences to demonstrate that PPE pretreatment significantly offsets CCl(4)-induced liver injury in rats, which may be attributable to its strong antioxidant propensity. PMID:21791371

  5. The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

    International Nuclear Information System (INIS)

    Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

  6. Imaging feature changes of rats with implanted liver cancer after electrochemotherapy

    International Nuclear Information System (INIS)

    Objective: To study the changes of imaging features of rats with implanted liver cancer before and after electrochemotherapy (EChT). Methods: Immediate cancerous ascites injection method was used to form rats liver cancer model. The imaging features of rats with implanted liver cancer, including tumor size, density, border, enhancement and signal were observed with CT and MRI respectively. Results: The characteristic imagings showed all these rats bearing single, round tumor in liver seven days later. Low density lesions were seen in pre-contrast scans and tumor border intensification were seen on contrast scans. Low signal lesions were found in MRI T1WI and high signal lesions were revealed on MRI T2WI. Seven days after EchT, low density lesions were seen in pre-contrast scan and non-enhanced appearances were seen in contrast scan by CT. High signal and mixed signal lesion were seen in MRI T1WI and relative low signal lesion were seen in MRI T2WI. Conclusions: Imaging features analysis is useful to assess the therapeutic effect on rats with implanted liver cancer before and after EChT

  7. Experimental study of electrochemotherapy on implanted liver tumor cells apoptosis of rats

    International Nuclear Information System (INIS)

    Objective: To compare the effects of electrochemotherapy (EChT) on implanted liver tumor cells apoptosis of rats. Methods: Immediate cancerous ascites injection method was used for the formation of rats liver tumor model and then followed by rats liver tumor treatment with EChT. Tumor size, necrosis and apoptosis indexes were observed after one week by imaging or pathologic method. The results were compared with those of control group. Results: Before EChT, rats liver tumor volume appeared as (100 ± 6) mm3 and turned to be (125 ± 10) mm3 one week after EChT, which were significantly smaller than those of the control group [(190 ± 11) mm3], P<0.05. Apoptosis indexes were 9.625 ± 1.172 and 3.523 ± 0.894 in EChT group and control group respectively (P<0.01). Tumor necrosis in EChT group increased significantly than those of the control group. Conclusions: The growth of rats liver tumor is obviously inhibited through inducing apoptosis and promoting necrosis by EChT

  8. Expression of liver carnitine palmitoyltransferase I and II genes during development in the rat.

    Science.gov (United States)

    Thumelin, S; Esser, V; Charvy, D; Kolodziej, M; Zammit, V A; McGarry, D; Girard, J; Pegorier, J P

    1994-01-01

    The enzyme activity and the expression (protein and mRNA concentrations) of genes encoding for hepatic carnitine palmitoyl-transferases (CPT) I and II were studied during neonatal development, in response to nutritional state at weaning and during the fed-starved transition in adult rats. The activity, the protein concentration and the level of mRNA encoding CPT I are low in foetal-rat liver and increase 5-fold during the first day of extra-uterine life. The activity and gene expression of CPT I are high during the entire suckling period, in the liver of 30-day-old rats weaned at 20 days on to a high-fat diet and in the liver of 48 h-starved adult rats. The activity and CPT I gene expression are markedly decreased in the liver of rats weaned on to a high-carbohydrate diet. By contrast, the activity, the protein concentration and the level of mRNA encoding CPT II are already high in the liver of term foetuses and remain at this level throughout the suckling period, irrespective of the nutritional state of the animals either at weaning or in the adult. Images Figure 1 Figure 2 PMID:8002965

  9. 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.

  10. Kupffer cell-mediated exacerbation of methimazole-induced acute liver injury in rats.

    Science.gov (United States)

    Akai, Sho; Uematsu, Yasuaki; Tsuneyama, Koichi; Oda, Shingo; Yokoi, Tsuyoshi

    2016-05-01

    Methimazole (MTZ), an anti-thyroid drug, is known to cause liver injury in humans. It has been demonstrated that MTZ-induced liver injury in Balb/c mice is accompanied by T helper (Th) 2 cytokine-mediated immune responses; however, there is little evidence for immune responses associated with MTZ-induced liver injury in rats. To investigate species differences in MTZ-induced liver injury, we administered MTZ with a glutathione biosynthesis inhibitor, L-buthionine-S,R-sulfoximine (BSO), to F344 rats and subsequently observed an increase in plasma alanine aminotransferase (ALT) and high-mobility group box 1 (HMGB1), which are associated with hepatic lesions. The hepatic mRNA expression of innate immune-related genes significantly increased in BSO- and MTZ-treated rats, but the change in Th2-related genes was not much greater than the change observed in the previous mouse study. Moreover, an increase in Kupffer cells and an induction of the phosphorylation of extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) proteins were accompanied by an increase in Toll-like receptor 4 (TLR4) expression, indicating that Kupffer cell activation occurs through HMGB1-TLR4 signaling. To elucidate the mechanism of liver injury in rats, gadolinium chloride, which inactivates the function of Kupffer cells, was administered before BSO and MTZ administration. The gadolinium chloride treatment significantly suppressed the increased ALT, which was accompanied by decreased hepatic mRNA expression related to innate immune responses and ERK/JNK phosphorylation. In conclusion, Kupffer cell-mediated immune responses are crucial factors for the exacerbation of MTZ-induced liver injury in rats, indicating apparent species differences in the immune-mediated exacerbation of liver injury between mice and rats. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26177832

  11. Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model.

    Science.gov (United States)

    Sil, Rajarshi; Ray, Doel; Chakraborti, Abhay Sankar

    2015-11-01

    Glycyrrhizin, a major constituent of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate insulin resistance, hyperglycemia, dyslipidemia, and obesity in rats with metabolic syndrome. Liver dysfunction is associated with this syndrome. The objective of this study is to investigate the effect of glycyrrhizin treatment on metabolic syndrome-induced liver damage. After induction of metabolic syndrome in rats by high fructose (60%) diet for 6 weeks, the rats were treated with glycyrrhizin (50 mg/kg body weight, single intra-peritoneal injection). After 2 weeks of treatment, rats were sacrificed to collect blood samples and liver tissues. Compared to normal, elevated activities of serum alanine transaminase, alkaline phosphatase and aspartate transaminase, increased levels of liver advanced glycation end products, reactive oxygen species, lipid peroxidation, protein carbonyl, protein kinase Cα, NADPH oxidase-2, and decreased glutathione cycle components established liver damage and oxidative stress in fructose-fed rats. Activation of nuclear factor κB, mitogen-activated protein kinase pathways as well as signals from mitochondria were found to be involved in liver cell apoptosis. Increased levels of cyclooxygenase-2, tumor necrosis factor, and interleukin-12 proteins suggested hepatic inflammation. Metabolic syndrome caused hepatic DNA damage and poly-ADP ribose polymerase cleavage. Fluorescence-activated cell sorting using annexin V/propidium iodide staining confirmed the apoptotic hepatic cell death. Histology of liver tissue also supported the experimental findings. Treatment with glycyrrhizin reduced oxidative stress, hepatic inflammation, and apoptotic cell death in fructose-fed rats. The results suggest that glycyrrhizin possesses therapeutic potential against hepatocellular damage in metabolic syndrome. PMID:26400710

  12. 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.

  13. Effects of nitric oxide synthase inhibitor in two-week oral treatment on hyperdynamic circulatory state in cirrhotic rats%一氧化氮合酶抑制剂口服两周治疗对肝硬化大鼠高动力循环状态的影响

    Institute of Scientific and Technical Information of China (English)

    黄颖秋; 萧树东; 莫剑忠; 张德中

    2000-01-01

    To investigate the effects of low dosage of nitric oxide synthase (NOS) inhibitor Nc-nitro -L-arginine methyl ester ( L-NAME) in two-week treatment on the hyperdynamic circulatory state 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 L-NAME ( 0.5 mg·kg-1·d-1) by gavage for two weeks. Mean arterial pressure ( AP ), portal pressure(PP), cardiac output ( CO ), cardiac index ( CI ), splanchnic vascular resistance ( SVR ), splanchnic blood flow(SBF) and serum nitrite levels were determined in L-NAME-treated, L-NAME-untreated cirrhotic rats and controls by using 57Co-labled microsphere technique and a fluorometric assay, respectively. RESULTS: Untreated cirrhotic rats had significantly lower MAP, SVR and higher PP, CO, CI, SBF and nitrite concentration than those of the controls (all,P< 0.01 ). In treated cirrhotic rats, L-NAME significantly attenuated the increase of CO, CI, SBF, nitrite concentration and the decrease of MAP and SVR. In treated cirrhotic rats, L-NAME induced a marked decrease of nitrite concentration than untreated cirrhotic rats[(1.471±0.907)μmol/L vs (4.204±1.253) μmol/L, P<0.01]. CONCLUSION: The endogenous NO may play an important role in the changes of hemodynamics pattern in cirrhosis, and hyperdynamic circulatory state in rats with cirrhosis can be ameliorated by oral two-week administration of lower dose of L-NAME.%目的:观察小剂量一氧化氮合酶(N0S)抑制剂N-硝基-L-精氨酸甲酯(L-NAME)连续2周治疗对肝硬化大鼠高动力循环状态的影响.方法:用60%四氯化碳油性溶液皮下注射SD大鼠制造肝硬化大鼠模型.对肝硬化大鼠,用L-NAME(0.5mg·kg·d-1)胃管内注入连续治疗2周.用57Co同位素微球技术分别测定L-NAME治疗组、未治疗组及正常对照组的平均动脉压(MAP)、门静脉压(PP)、心输出量(C0)、心脏指数(CI)、内脏血管阻力(SVR)及内脏

  14. 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

  15. 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.

  16. A mode of action for induction of liver tumors by Pyrethrins in the rat

    International Nuclear Information System (INIS)

    High doses of Pyrethrins produce liver tumors in female rats. To elucidate the mode of action for tumor formation, the hepatic effects of Pyrethrins have been investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats' diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and 42 days followed by 42 days of reversal. As a positive control, rats were also fed diets containing 1200-1558 ppm sodium Phenobarbital (NaPB) for 7 and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased liver weights, which were associated with hepatocyte hypertrophy. Hepatocyte replicative DNA synthesis was also increased by treatment with Pyrethrins and NaPB. The treatment of male and female rats with Pyrethrins and NaPB produced significant increases in hepatic microsomal cytochrome P450 (CYP) content and a marked induction of CYP2B-dependent 7-pentoxyresorufin O-depentylase and testosterone 16β-hydroxylase activities. Significant increases were also observed in CYP3A-dependent testosterone 6β-hydroxylase activity. The hepatic effects of Pyrethrins were dose-dependent in female rats with 100 ppm being a no effect level and on cessation of treatment were reversible in both sexes. This study demonstrates that Pyrethrins are mitogenic CYP2B form inducers in rat liver. The mode of action for Pyrethrins-induced rat liver tumor formation appears to be similar to that of NaPB and some other non-genotoxic CYP2B inducers of hepatic xenobiotic metabolism

  17. 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.

  18. Ameliorative Effects of Pomegranate Peel Extract against Dietary-Induced Nonalcoholic Fatty Liver in Rats.

    Science.gov (United States)

    Al-Shaaibi, Siham N K; Waly, Mostafa I; Al-Subhi, Lyutha; Tageldin, Mohamed H; Al-Balushi, Nada M; Rahman, Mohammad S

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is associated with oxidative stress. In this study, we investigated the potential protective effect of pomegranate (Punica granatum L.) peel extract (PPE) against oxidative stress in the liver of rats with NAFLD. Sprague-Dawley rats were fed a high fat diet (HFD), 20% corn oil, or palm oil for 8 weeks in the presence or absence of PPE. The control group was fed a basal diet. The progression of NAFLD was evaluated histologically and by measuring liver enzymes (alanine transaminase and aspartate transaminase), serum lipids (triglycerides and total cholesterol), and oxidative stress markers. The HFD feeding increased the body weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of PPE ameliorated the hepatic morphology, reduced body weight, improved liver enzymes, and inhibited lipogenesis. Furthermore, PPE enhanced the cellular redox status in the liver tissue of rats with NAFLD. Our findings suggest that PPE could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. PPE might be considered as a potential lead material in the treatment of NAFLD and obesity through the modulation of lipid metabolism. PMID:27069901

  19. 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; Kabiri, Yaschar; 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; Adamski, Jerzy; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H J; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz; Zischka, Hans

    2016-07-01

    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

  20. Effect of Gadolinium Chloride on Liver Regeneration Following Thioacetamide-Induced Necrosis in Rats

    Directory of Open Access Journals (Sweden)

    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.

  1. 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. PMID:26767369

  2. Lysosomal acid lipase deficiency in rats: Lipid analyses and lipase activities in liver and spleen

    International Nuclear Information System (INIS)

    We report the biological characterization of an animal model of a genetic lipid storage disease analogous to human Wolman's disease. Affected rats accumulated cholesteryl esters (13.3-fold), free cholesterol (2.8-fold), and triglycerides (5.4-fold) in the liver, as well as cholesteryl esters (2.5-fold) and free cholesterol (1.33-fold) in the spleen. Triglycerides did not accumulate, and the levels actually decreased in the spleen. Analysis of the fatty acid composition of the cholesteryl esters and triglycerides showed high percentages of linoleic acid (18:2) and arachidonic acid (20:4) in both organs, especially in the liver. No accumulation of phospholipids, neutral glycosphingolipids, or gangliosides was found in the affected rats. Acid lipase activity for [14C]triolein, [14C]cholesteryl oleate, and 4-methyl-umbelliferyl oleate was deficient in both the liver and spleen of affected rats. Lipase activity at neutral pH was normal in both liver and spleen. Heterozygous rats showed intermediate utilization of these substrates in both organs at levels between those for affected rats and those for normal controls, although they did not accumulate any lipids. These data suggest that these rats represent an animal counterpart of Wolman's disease in humans

  3. Aldosterone metabolism in the isolated perfused liver of female and male rats

    International Nuclear Information System (INIS)

    A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-[4-14C]aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate [4-14C]aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes

  4. Enhanced expression of glucose-regulated protein 78 correlates with malondialdehyde levels during the formation of liver cirrhosis in rats

    Science.gov (United States)

    ZHANG, YUN; ZHANG, HUIYING; ZHAO, ZHONGFU; LV, MINLI; JIA, JIANTAO; ZHANG, LILI; TIAN, XIAOXIA; CHEN, YUNXIA; LI, BAOHONG; LIU, MINGSHE; HAN, DEWU; JI, CHENG

    2015-01-01

    The aim of the present study was to explore the role of glucose-regulated protein 78 (GRP78) in the development of liver cirrhosis promoted by intestinal endotoxemia in rats. Fifty-one male Wistar rats were randomly divided into the liver cirrhosis 4-week, 6-week and 8-week groups and the normal control group at each time point. Liver cirrhosis was induced by employing multiple pathogenic factors in the rats. Blood and liver tissues were collected. The levels of alanine aminotransferase (ALT), homocysteine, endotoxin and tumor necrosis factor-α (TNF-α) in the plasma, and TNF-α, malondialdehyde (MDA) and procollagen type III peptide (PIIIP) in the liver tissues were determined. The mRNA and protein expression levels of GRP78 in the liver were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Morphological changes were observed through hematoxylin and eosin and van Gieson staining of the liver. Liver cirrhosis caused marked histopathological changes to the livers of the rats. Following significant increases in the levels of ALT, homocysteine, endotoxin and TNF-α in the plasma, and TNF-α, MDA and PIIIP in the liver tissues of all experimental groups with the progression of liver cirrhosis, the mRNA and protein expression levels of GRP78 also gradually increased. In addition, correlation analysis indicated that the enhanced expression of GRP78 correlated with the MDA levels of the rats during the formation of liver cirrhosis. PMID:26668603

  5. Nonalcoholic fatty liver disease progression in rats is accelerated by splenic regulation of liver PTEN/AKT

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. Transcription Profiles of Marker Genes Predict The Transdifferentiation Relationship between Eight Types of Liver Cell during Rat Liver Regeneration

    Directory of Open Access Journals (Sweden)

    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.

  8. Hromonal regulation of sex differentiated liver carcinogenesis in the rat

    OpenAIRE

    Liao, Dezhong

    1996-01-01

    Endocrine factors influence cancer development in a variety of reproductive and non-reproductive tissues and organs. The incidence of liver cancer is higher in men than in women and long temm administration of androgens and estrogens has been reported to increase the risk for liver cancer formation, supporting the importance of hormonal factors in the etiology of this tumor. Hormonal effects on liver carcinogenesis have been demonstrated also in experimental animals. In the resistant hepatocy...

  9. 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.

  10. 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

    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...... with placebo, low dose dexamethasone, high dose dexamethasone or low dose anti-CD163 dexamethasone. Subsequently, the rats underwent 70% partial hepatectomy. The two sets were evaluated on postoperative day 2 or 5, respectively. Blood was drawn for circulating markers of inflammation and liver cell damage...

  11. Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats

    Science.gov (United States)

    Chai, Ning-Li; Zhang, Xiao-Bin; Chen, Si-Wen; Fan, Ke-Xing; Linghu, En-Qiang

    2016-01-01

    AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation in the treatment of liver fibrosis. METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine (DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin (IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells (KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were co-cultured with KCs in vitro to assess the effects of UC-MSCs on KCs’ phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UC-MSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs. RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the co-culture system resulted in decreased KC mobilization. CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.

  12. Microvesicular fatty liver in rats with resembling Reye's syndrome induced by 4-pentenoic acid.

    Science.gov (United States)

    Sakaida, N; Senzaki, H; Shikata, N; Morii, S

    1990-09-01

    To produce an animal model of Reye's syndrome (RS), 20 adult male Wistar rats were given 10 repeated i.p. injections of 50 mg/kg 4-pentenoic acid (PA) each separated by an 8-h interval. Then, 90 min after the tenth dose, they were given a final i.p. injection of 150 mg/kg PA. Thirteen control animals were injected with vehicle only using the same time schedule. More than half the animals in each group were fed a common diet, but the others were fasted during the terminal 10-h stage. All rats were sacrificed 30 min after the last injection. At the terminal stage, in comparison with the vehicle-injected controls, hypolipemia, hypoglycemia and high titers of serum ammonia and urea N were estimated significantly in the PA-treated rats fed throughout the whole period. Hypolipemia and hypoglycemia were more prominent in the terminally fasted group than the group fed continuously. Only in the PA-treated rats fed throughout the whole period moderate morphological signs of microvesicular fatty liver were exhibited. Ultracytochemical findings and biochemical determinations showed that the major lipids in the microvesicular fatty livers were triglycerides. Morphometric analysis revealed distinct hepatic mitochondrial swelling in the PA-treated rats. Therefore, the above treatment with PA was able to induce microvesicular fatty liver in rats with resembling RS, which were fed throughout the treatment procedure, but not in the terminally fasted rats. PMID:2260472

  13. Di(2-ethylhexyl) phthalate exacerbates non-alcoholic fatty liver in rats and its potential mechanisms.

    Science.gov (United States)

    Chen, Hao; Zhang, Wang; Rui, Bei-Bei; Yang, Si-Min; Xu, Wei-Ping; Wei, Wei

    2016-03-01

    Di(2-ethylhexyl) phthalate (DEHP) may be responsible for inducing alterations similar to those encountered in nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate the detrimental effects and possible mechanisms of DEHP on fatty liver rats directly through triggering the disorder of liver lipid metabolism or indirectly by hepatotoxic effect. Considering these effects, DEHP may play a significant role in the pathogenesis of NAFLD. In this study, high-fat diet was used to induce NAFLD in rats for eight weeks. DEHP treated groups received (0.05, 5, 500mg/kg daily, respectively) dose by gavage during the whole experiment period. Our results indicated that the detrimental effects of DEHP on high-fat diet induced NAFLDs were mediated via increasing lipid accumulation in the liver and causing lipid peroxidation and inflammation. PMID:26773359

  14. Local proliferation and extrahepatic recruitment of liver macrophages (Kupffer cells) in partial-body irradiated rats

    International Nuclear Information System (INIS)

    The relative significance of local proliferation and extrahepatic recruitment of Kupffer cells was investigated by partial-body irradiation before the induction of macrophage hyperplasia by zymosan. There was no difference in growth of the Kupffer cells population between nonirradiated rats and rats irradiated with the liver shielded, whereas irradiation of the liver with the rest of the body (bone marrow) shielded resulted in strong inhibition of growth (-61%). Splenectomy combined with bone marrow irradiation inhibited growth to a lesser extent as compared to liver irradiation (-38%). Monocyte and other leukocyte numbers were strongly reduced in peripheral blood and their accumulation in the liver was completely prevented by bone marrow irradiation. Our results demonstrate that local proliferation of resident Kupffer cells represents the predominant source for their increased number during hyperplasia

  15. Assessment of intestinal permeability and absorption in cirrhotic patients with ascites using combined sugar probes.

    Science.gov (United States)

    Zuckerman, Marc J; Menzies, Ian S; Ho, Hoi; Gregory, Gavin G; Casner, Nancy A; Crane, Roger S; Hernandez, Jesus A

    2004-04-01

    Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects

  16. Exercises in hot and humid environment caused liver injury in a rat model.

    Directory of Open Access Journals (Sweden)

    DongLiang Li

    Full Text Available To investigate injury pattern during intense exercises in hot and humid environment particularly on liver in a rat exertional heat stroke model.We randomly divided 30 rats into a control group (CG, a normal temperature (25±2°C, 60%±5% humidity exercise group (NTEG and a high temperature and high humidity (35±2°C, 80%±10% humidity exercising group (HTEG, each comprising 10 animals. The NTEG and HTEG rats were forced to run in a treadmill for 1 hour maximum at 20 rpm. We analyzed liver cells of all three groups with JC-1 dye and flow cytometry for apoptosis rates in addition to liver tissue 8 - hydroxy deoxyguanosine (8 - OhdG and blood serum IL-6, tumor necrosis factor alpha (TNF-α, alanine aminotransferase ALT, aspartate amino transferase (AST, serum creatinine (CREA, blood urea nitrogen (BUN, lactate dehydrogenase (LDH, creatine phosphate kinase (CK concentrations.Compared with NTEG rats, beside reduced exercise tolerance (60±5 vs. 15±3 minutes (p = 0.002 the 8-OhdG liver tissue concentrations were significantly higher (p = 0.040 in the HTEG rats. The HTEG developed more organ tissue damage and cellular fragmentations of liver cells. In both exercise groups TNF-α and IL-6 serum concentrations were enhanced significantly (p<0.001 being highest in the HTEG animals. Serum ALT, AST, LDH, CREA, BUN and CK concentrations were significantly enhance in both exercise groups.In our exertional heat stroke rat model, we found tissue damage particularly in livers during exercises in hot and humid environment that was related to inflammation, oxidative stress and apoptosis.

  17. Indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography: Assessment of the additional diagnostic value of contrast-enhanced ultrasound in the non-cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    Quaia, Emilio, E-mail: quaia@units.it; De Paoli, Luca; Angileri, Roberta; Cabibbo, Biagio; Cova, Maria Assunta

    2014-03-15

    Objective: To assess the additional diagnostic value of contrast-enhanced ultrasound (CEUS) in the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography (CT). Methods: Fifty-five solid hepatic lesions (1–4 cm in diameter) in 46 non-cirrhotic patients (26 female, 20 male; age ± SD, 55 ± 10 years) underwent CEUS after being detected on contrast-enhanced CT which was considered as non-diagnostic after on-site analysis. Two blinded independent readers assessed CT and CEUS scans and were asked to classify retrospectively each lesion as a malignant or benign based on reference diagnostic criteria for the different hepatic lesion histotypes. Diagnostic accuracy and confidence (area – A{sub z} – under ROC curve) were assessed by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (n = 30 lesions), histology (n = 7 lesions), or US follow-up (n = 18 lesions) as the reference standards. Results: Final diagnoses included 29 hemangiomas, 3 focal nodular hyperplasias, 1 hepatocellular adenoma, and 22 metastases. The additional review of CEUS after CT images improved significantly (P < .05) the diagnostic accuracy (before vs after CEUS review = 49% [20/55] vs 89% [49/55] – reader 1 and 43% [24/55] vs 92% [51/55] – reader 2) and confidence (A{sub z}, 95% Confidence Intervals before vs after CEUS review = .773 [.652–.895] vs .997 [.987–1] – reader 1 and .831 [.724–.938] vs .998 [.992–1] – reader 2). Conclusions: CEUS improved the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced CT by identifying some specific contrast enhancement patterns.

  18. Indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography: Assessment of the additional diagnostic value of contrast-enhanced ultrasound in the non-cirrhotic liver

    International Nuclear Information System (INIS)

    Objective: To assess the additional diagnostic value of contrast-enhanced ultrasound (CEUS) in the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography (CT). Methods: Fifty-five solid hepatic lesions (1–4 cm in diameter) in 46 non-cirrhotic patients (26 female, 20 male; age ± SD, 55 ± 10 years) underwent CEUS after being detected on contrast-enhanced CT which was considered as non-diagnostic after on-site analysis. Two blinded independent readers assessed CT and CEUS scans and were asked to classify retrospectively each lesion as a malignant or benign based on reference diagnostic criteria for the different hepatic lesion histotypes. Diagnostic accuracy and confidence (area – Az – under ROC curve) were assessed by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (n = 30 lesions), histology (n = 7 lesions), or US follow-up (n = 18 lesions) as the reference standards. Results: Final diagnoses included 29 hemangiomas, 3 focal nodular hyperplasias, 1 hepatocellular adenoma, and 22 metastases. The additional review of CEUS after CT images improved significantly (P < .05) the diagnostic accuracy (before vs after CEUS review = 49% [20/55] vs 89% [49/55] – reader 1 and 43% [24/55] vs 92% [51/55] – reader 2) and confidence (Az, 95% Confidence Intervals before vs after CEUS review = .773 [.652–.895] vs .997 [.987–1] – reader 1 and .831 [.724–.938] vs .998 [.992–1] – reader 2). Conclusions: CEUS improved the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced CT by identifying some specific contrast enhancement patterns.

  19. Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver

    DEFF Research Database (Denmark)

    Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Grønbæk, Henning; Hamilton-Dutoit, Stephen Jacques; Nyengaard, Jens Randel; Funch-Jensen, Peter; Mortensen, Frank Viborg

    2013-01-01

    Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver......Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver...

  20. Engineered Three-Dimensional Liver Mimics Recapitulate Critical Rat-Specific Bile Acid Pathways

    OpenAIRE

    Detzel, Christopher J.; Kim, Yeonhee; Rajagopalan, Padmavathy

    2010-01-01

    A critical hepatic function is the maintenance of optimal bile acid (BA) compositions to achieve cholesterol homeostasis. BAs are rarely quantified to assess hepatic phenotype in vitro since existing analytical techniques have inadequate resolution. We report a detailed investigation into the biosynthesis and homeostasis of eight primary rat BAs in conventional in vitro hepatocyte cultures and in an engineered liver mimic. The three-dimensional (3D) liver mimic was assembled with layers of pr...

  1. Rat liver transplantation without preservation of "phrenic ring"using double cuff method

    Institute of Scientific and Technical Information of China (English)

    Yong Jiang; Yu-Dong Qiu; Xiao-Ping Gu; Xin-Hua Zhu; Yi-Tao Ding

    2004-01-01

    AIM: To develop a double cuff method for rat liver transplantation without preservation of"phrenic ring" to shorten the portal vein clamping time.METHODS: "Phrenic ring" was completely excluded from the donor liver, and end to end anastomosis of suprahepatic inferior vena cava was performed.RFSULTS: The portal vein clumping time was shortened to 10.6 min, the successful rate was 83.1%.CONCLUSION: This method can simplify the operation and shorten the portal vein clumping time.

  2. Effects of Fructus Piperis Longi extract on fibrotic liver of gamma-irradiated rats

    Directory of Open Access Journals (Sweden)

    El-Kabany Hanan

    2009-01-01

    Full Text Available Abstract Background A major biomarker for liver fibrosis is transglutaminase which catalyzes cross-linking of epsilon-amines and alpha-glutamyl residues among amino acids leading to fibrosis. Fructus Piperis Longi is a common herb used in Chinese medicine. The present study evaluates the role of the ethanol extract of Fructus Piperis Longi in the modulation of liver function in liver fibrosis. Methods Plf extract (50 mg/kg was force-fed to rats every other day 7 days before administration of thioacetamide and/or gamma irradiation. Thioacetamid 200 mg/kg was intraperitoneally administered to rats twice per week for four weeks. Rats were gamma irradiated (2 Gy/week up to a total dose of 8 Gy. Administration of Plf ext was extended during thioacetamid and/or irradiation treatment. Animals were sacrificed. Biochemical parameters in homogenised liver were tested. Results A significant increase in transglutaminase activity and collagen content was recorded in the liver of thioacetamid-treated and/or irradiated rats. Significant increases in lipid peroxides, lipid hydroperoxides and conjugated dienes associated to significant decreases of reduced glutathione content, superoxide dismutase and catalase activities were also recorded. Administration of Plf ext treatment reduced the severity of liver fibrosis and oxidative damage which was substantiated by amelioration of liver function detected by a decrease in serum aspartate aminotransaminase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase activities and bilirubin (total, direct and indirect content. Conclusion Treatment of the ethanolic extract of Fructus Piperis Longi ameliorated the increase of the activity of tTG enzyme and enhanced antioxidant activities in fibrotic liver.

  3. Hepatoprotective effects of Rubus coreanus miquel concentrates on liver injuries induced by carbon tetrachloride in rats

    OpenAIRE

    Chae, Hyun-Jung; Yim, Jung-Eun; Kim, Kyung-Ah; Chyun, Jong-Hee

    2014-01-01

    As well-being foods pursuing healthy life are becoming popular, interest in Rubus coreanus Miquel (RCM) fruit, a type of Korean blackberry, is increasing due to its medicinal actions including protecting the liver, brightening the eyes, and alleviating diabetes. This study was carried out to evaluate the hepatoprotective effects of RCM concentrates on liver injuries induced by carbon tetrachloride (CCl4) in rats. RCM, produced in June ~ July 2008 at Chunbook, Gochang (South Korea), was finely...

  4. A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats

    OpenAIRE

    Aroor Annayya R; Roy Lowery J; Restrepo Ricardo J; Mooney Brian P; Shukla Shivendra D

    2012-01-01

    Abstract Background Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol- binge were compared. Results The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-bi...

  5. Lipidomic changes in rat liver after long-term exposure to ethanol

    International Nuclear Information System (INIS)

    Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD. - Highlights: → Long term exposure to ethanol was studied. → A nuclear magnetic resonance (NMR) spectroscopy based lipidomic approach was used. → We examined the clustering pattern of the NMR data with principal component analysis. → NMR data were compared with histology and

  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. 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.

  8. Evaluation of S-values and dose distributions for (90)Y, (131)I, (166)Ho, and (188)Re in seven lobes of the rat liver

    OpenAIRE

    Xie, Tianwu; Liu, Qian; Zaidi, Habib

    2012-01-01

    Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with a tissue composition assumed to be similar to that of human liver tissue. However, the rat liver is composed of several lobes having different anatomical and chemical characteristics. To assess the overall ...

  9. Enhanced expression of glucose-regulated protein 78 correlates with malondialdehyde levels during the formation of liver cirrhosis in rats

    OpenAIRE

    Zhang, Yun; Zhang, Huiying; Zhao, Zhongfu; Lv, Minli; Jia, Jiantao; Zhang, Lili; Tian, Xiaoxia; Chen, Yunxia; Li, Baohong; LIU, MINGSHE; Han, Dewu; Ji, Cheng

    2015-01-01

    The aim of the present study was to explore the role of glucose-regulated protein 78 (GRP78) in the development of liver cirrhosis promoted by intestinal endotoxemia in rats. Fifty-one male Wistar rats were randomly divided into the liver cirrhosis 4-week, 6-week and 8-week groups and the normal control group at each time point. Liver cirrhosis was induced by employing multiple pathogenic factors in the rats. Blood and liver tissues were collected. The levels of alanine aminotransferase (ALT)...

  10. Effect of low temperature on metabolism of rat liver slices and epididymal fat pads.

    Science.gov (United States)

    Hillyard, L. A.; Entenman, C.

    1973-01-01

    Study of low temperature effects on the metabolism of radioisotope-tagged glucose and palmitate in rat liver slices and epididymal fat pads. The obtained data suggest that the oxidative capacity of rat liver and adipose tissue is maintained at low temperatures to a greater degree than the synthetic capacity. It was concluded that sufficient energy can be produced at 17 C for maintenance of essential tissue functions by these two tissues but that the energy requirements may not be met at 7 C.

  11. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    OpenAIRE

    Zhao, Z. G.; L. L. Zhang; C.Y. Niu; J. Zhang

    2014-01-01

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg...

  12. Purification and characterization of the protein kinase eEF-2 isolated from rat liver cells

    International Nuclear Information System (INIS)

    The elongation factor 2 (eEF-2) protein kinase was isolated from rat liver cells, purified and partly characterized. It was found that the enzyme exists in an inactive form in the homogenate of rat liver. The active fraction of kinase eEF-2 was obtained after removal of the inhibitory substance by hydroxyapatite column chromatography. The purified enzyme is an electrophoretically homogeneous protein with relative molecular mass of approximately 90000 and isoelectric point, pI=5.9. The enzyme specifically phosphorylates the elongation factor eEF-2 in the presence of calmodulin and Ca2+. (author). 15 refs, 5 figs, 1 tab

  13. Mechanism of Hepatoprotective Effect of Boesenbergia rotunda in Thioacetamide-Induced Liver Damage in Rats

    OpenAIRE

    Salama, Suzy M.; Mahmood A. Abdulla; AlRashdi, Ahmed S.; Hadi, A. Hamid A.

    2013-01-01

    Background. Researchers focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Objectives. Evaluating the hepatoprotective activity of Boesenbergia rotunda (BR) rhizome ethanolic extract on thioacetamide-induced liver cirrhosis in rats. Methods. Male Sprague-Dawley rats were intraperitoneally injected with 200 mg/kg TAA 3 times/week and daily oral administration of 250 mg/kg, 500 mg/kg of BR extract, and 50 mg/kg of the reference drug Silymarin for ...

  14. [Alterations of prooxidant-antioxidant system of rat liver at ethanol and tetracycline action].

    Science.gov (United States)

    Nedoshytko, Kh Iu

    2013-01-01

    The state of antioxidant system and fatty acid composition of lipids in the liver tissues of rats of different sex at the ethanol and tetracycline action and at the influence of biologically active additives (BAA) "Alpha + Omega" at a dose of 0.5 mg/kg b.w. per os was investigated. It was found that the contet of lipid peroxidation products in the liver was increased at the action of 40% ethanol at a dose of 7 ml/kg b.w. per os and tetracycline--500 mg/kg and more profound at their joint using. However, the content of diene conjugates was stronger increased in the liver of females at the action of ethanol, while in the liver of males at the action of tetracycline (P tetracycline and more profound at their joint usage (P tetracycline unidirectionally changed fatty acid composition of total lipids of rat liver, but at the ethanol action the changes were more expressed in females while at the tetracycline action in males. The application during 14 days of BAA "Alpha + Omega" to male and female rats with an acute tetracycline damage at subacute ethanol action led to partial normalization of prooxidant-antioxidant system and the relative content of total lipids fatty acids of the liver of both sexes animals. PMID:24479333

  15. Protection from radiation induced changes in liver and serum transaminase of whole body gamma irradiated rats

    International Nuclear Information System (INIS)

    Whole body gamma irradiation of rats with a dose of 5.5 Gy induced significant changes in the activity of liver and serum transaminase. The results indicated that this radiation dose caused a significant increase in the activity of serum Got and GPT on the third and seventh days after irradiation. This was followed by significant decreases on the fourteenth post-irradiation day. The activity of Got returned to is control activity, while the activity of GPT was significantly above the control on the twenty ones post-irradiation day. The activity of Got, in the liver of irradiated rats was elevated during the post-irradiation days, but on the twenty one day activity was about the normal value. The activity of liver GPT firstly decreased and then increased very much but attained the control level on the fourteenth after irradiation. The intraperitoneal injection of testosterone-vitamin E mixture 10 days before whole body gamma irradiation caused complete recovery for the activity of liver and serum Got. No indication of remarkable recovery in the case of GPT activity was recorded either in liver or in serum of irradiated rats. The applied mixture could protect against radiation induced changes in Got activity of liver and serum but could not protect or ameliorate the changes which occurred in the activity of GPT of the two tissues. 2 tab

  16. Glyco-poly-L-lysine is better than liposomal delivery of exogenous genes to rat liver

    Institute of Scientific and Technical Information of China (English)

    Chang Qing Yang; Ji Yao Wang; Bo Ming He; Jian Jun Liu; Jin Sheng Guo

    2000-01-01

    AIM To compare the effects of liposomes and glyco-poly-L-lysine on liver targeted uptake and expression of plasmid in rat liver. METHODS After binding with lipofectamine or galactose-terminal glyco-poly- L-lysine, the plasmid could be expressed in eukaryotic cells when injected into Wistar rats by intravenous route. At different time intervals after the injection, the distribution and expression of the plasmid in liver of rats were observed and compared using in situ hybridization and immunohistochemistry. RESULTS The expression of the plasmid binding to liposomes or G-PLL could be markedly observed 24 h later, and began to decrease one week later, but it still could be observed up to three weeks. Both liposomes and G-PLL could deliver the plasmid to the liver effectively, but the effect of the latter was better than the former concerning the distribution and expression of the plasmid targeted uptake in the liver. CONCLUSION G-PLL is better than liposome as the targeted carrier for delivering exogenous genes to the liver.

  17. Specific estrogen-binding protein of rat liver and sex steroid metabolism

    International Nuclear Information System (INIS)

    Model experiments were conducted to study the effect of a highly purified preparation of specific estrogen-binding protein (SEBP) on the intensity of estradiol and testosterone metabolism under the influence of enzymes in liver homogenate from female rats, not containing SEBP. The liver of mature female rats was homogenized in two volumes of 50 mM Tris-HCl buffer, pH 7.5, containing 600 mg% of glucose. The tritium-steroid was preincubated for 15 min at 0-4 C with 0-4 microg of the preparation of SEBP (200 microl). A standard preparation of partially purified SEBP was obtained from liver cystosol of mature male rats; affinity chromatography on estradiolagarose was used. It is shown that SEBP can really take part in regulation of the dynamics of sex steroids in the liver. E1 did not affect the metabolic rate of H 3-E2 by liver homogenate from females, but caused marked acceleration of H 3-E2 metabolism by male liver homogenate

  18. 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.

  19. 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

  20. 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)

  1. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    International Nuclear Information System (INIS)

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III α, 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 131I 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. 131I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  2. A Pleuroperitoneal Bleb Mimicking an Intrathoracic Mass in a Cirrhotic Patient: Three Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Ho; Lee, Kyung Hee; Cho, Soon Gu; Jeon, Yong Sun [Inha University Hospital, Incheon (Korea, Republic of)

    2009-07-15

    In a cirrhotic patient, an increase in intra-abdominal pressure due to the presence of ascites might lead to a small pleuroperitoneal bleb of the peritoneum from congenital defects in the hemithorax. This lesion may appear as an intrathoracic mass as seen on a simple chest radiograph. A CT image may be helpful to differentiate an ascitic pleuroperitoneal bleb from an intrathoracic mass. We present three cases of a pleuroperitoneal bleb in patients with liver cirrhosis and ascites.

  3. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    OpenAIRE

    Baran, Halina; Staniek, Katrin; Bertignol-Spörr, Melanie; Attam, Martin; Kronsteiner, Carina; Kepplinger, Berthold

    2016-01-01

    Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochond...

  4. Protective Effect of Nigella Sativa Against Diabetic Complications on The Liver in White Male Rats

    OpenAIRE

    Nassar Ayoub Abdellatif

    2013-01-01

    Aim of the work: The effect of diabetes on the liver is associated with histological changes. The aim of the present study was to evaluate the histological changes following administration of nigella sativa (NS) in the streptozotocin (STZ) induced diabetes mellitus in rats. Materials and Methods: Thirty six male white rats (n=36), weighing (180–230 g) were taken for this study. The animals were divided into 3 groups: 1- Normal control group. 2- Diabetic group. 3- Diabetic group treated by ...

  5. Cholinesterase activity in rat liver and serum during experimentally induced inflammation.

    Science.gov (United States)

    Simon, G; Budavári, I

    1977-01-01

    Cholinesterase activity of albino rats with acute local oedematous inflammation induced by turpentine, croton oil or Freund's adjuvant was elevated in the liver homogenate but decreased in the serum. Aprotinin administration prevented the decrease of serum activity. In the oedema fluid of rats treated with croton oil an enzyme with cholinester splitting activity was detected and it was shown to be identical with serum cholinesterase (EC 3. 1. 1. 8.). PMID:311577

  6. Protective Effects of Agmatine against Chlorpromazine- Induced Toxicity in the Liver of Wistar Rats

    OpenAIRE

    Dejanović Bratislav; Stevanović Ivana; Ninković Milica; Stojanović Ivana; Lavrnja Irena; Radičević Tatjana

    2016-01-01

    The metabolic pathways of chlorpromazine (CPZ) toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM) prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p.) for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution), the CPZ group (CPZ,...

  7. Alterations in the Rat Serum Proteome During Liver Injury from Acetaminophen Exposure

    OpenAIRE

    Merrick, B. Alex; Bruno, Maribel E.; Madenspacher, Jennifer H.; Wetmore, Barbara A.; Foley, Julie; Pieper, Rembert; Zhao, Ming; Makusky, Anthony J.; McGrath, Andrew M.; ZHOU, JEFF X.; Taylor, John; Tomer, Kenneth B.

    2006-01-01

    Changes in the serum proteome were identified during early, fulminant and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, non-injury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 hr to 120 hr. Two-dimensional gel electrophoresis of immunodepleted serum separated about 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum ALT/AST levels and histopatho...

  8. Investigation of liver tissue and biochemical parameters of adult wistar rats treated with Arctium lappa L.

    OpenAIRE

    Fabrícia de Souza Predes; Sérgio Luis Pinto da Matta; Juliana Castro Monteiro; Tânia Toledo de Oliveira

    2009-01-01

    This study was carried out to evaluate the effects of Arctium lappa L. (burdock) on the liver of adult male Wistar rats as measured by light microscopy and biochemical parameters. The rats received the extract in water bottles at doses of 10 or 20 g/L daily for 40 days. There were no significant changes in the plasma levels of albumin, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT), total protein, total cholesterol, urea, uric acid, triacylglycerol,...

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

    OpenAIRE

    Gaurav Lodhi; Singh, Hemant K.; PANT, KAMLESH K.; Rao, Ch V; Zeashan Hussain

    2012-01-01

    Summary. In the present study, galls of Quercus infectoria possessing potent antioxidant and antiinflammatory properties were evaluated for their hepatoprotective effect against carbon tetrachloride (CCl4) induced hepatotoxicity in rats. Subcutaneous injection of CCl4, administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and tumor necrosis factor alpha (TNF-α). Histological analysis of the liver of these rats re...

  10. DMPD: Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnonparenchymal and parenchymal cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11367531 Functions of anaphylatoxin C5a in rat liver: direct and indirect actions o...ol. 2001 Mar;1(3):469-81. (.png) (.svg) (.html) (.csml) Show Functions of anaphylatoxin C5a in rat liver: di...31 Title Functions of anaphylatoxin C5a in rat liver: direct and indirect actions onnonparenchymal and paren

  11. Dose Timing Effect of FK-506 on Liver Regeneration in Partially Hepatectomized Rats

    OpenAIRE

    Ohtake, Masahiro; KOYAMA, SHUNTARO; Sakaguchi, Takeo; Tsukada, Kazuhiro; Yoshida, Keisuke; Muto, Terukazu

    1992-01-01

    The dose timing effect of FK-506 (FK) on liver regeneration was examined in 66% hepatectomized rats. FK at a dose of 0.1 mg/kg/day was given for three days starting on three different dates: 2 days before hepatectomy (FKI), 1 day before hepatectomy (FKII) and the day of hepatectomy (FKIII). Liver regeneration was evaluated by liver weight as a percentage of the body weight (LRR) and the mitotic index of the hepatocyte (MI) in the 3 days following hepatectomy. No significant change in LRR with...

  12. The influence of vitamin E supplementation on the oxidative status of rat liver

    Directory of Open Access Journals (Sweden)

    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. .

  13. Up-regulated Reg proteins induced by Interleukin-22 treatment ameliorate acute liver injury in rat model

    OpenAIRE

    Zhang, Hong-Bin; Luo, Hong-Chun; Xin, Xiao-Juan; Zeng, Ai-Zhong

    2015-01-01

    Background: The regenerating gene (Reg), encoding lectin-related protein, was originally isolated from a rat regenerating pancreatic islets. Interleukin-22 (IL-22), a recently identified cytokine, is produced by Th 17 cells and natural killer cells. Both of them have been shown to play an important role in controlling tissue repair. But, it is unclear whether the IL-22/Reg axis is involved in liver regeneration and the improvement of liver function in a rat model of acute liver injury. Aims: ...

  14. Impact of ovariectomy, high fat diet, and lifestyle modifications on oxidative/antioxidative status in the rat liver

    OpenAIRE

    Vuković, Rosemary; Blažetić, Senka; Oršolić, Ivana; Heffer, Marija; Vari, Sandor G.; Gajdoš, Martin; Krivošíková, Zora; Kramárová, Patrícia; Kebis, Anton; Has-Schön, Elizabeta

    2014-01-01

    Aim To estimate the impact of high fat diet and estrogen deficiency on the oxidative and antioxidative status in the liver of the ovariectomized rats, as well as the ameliorating effect of physical activity or consumption of functional food containing bioactive compounds with antioxidative properties on oxidative damage in the rat liver. Methods The study was conducted from November 2012 to April 2013. Liver oxidative damage was determined by lipid peroxidation levels expressed in terms of th...

  15. Histological Effects of Oral Administration of Artesunate on the Liver in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Dr. Al-Hassan M. Izunya

    2010-07-01

    Full Text Available This experiment was designed to study the histological effects of oral administration of normal anddouble normal doses of artesunate on the histology of the liver in wistar rats. The rats were divided into threegroups (A, B and C of five rats each. A and B served as the treatment groups, while C served as the controlgroup. Group A rats were given 4 mg/kg b.w of artesunate daily for 3 days followed by 2 mg/kg b.w daily fornext for 4 days. Group B rats were given 8 mg/kg2 b.w of artesunate daily for 3 days followed by 4 mg/kg b.wdaily for next 4 days, while group C rats were given only distilled water. The rats were fed with grower's mashpurchased from Edo feeds and Flour M ill Ltd, Ewu, Edo state and were given water ad libitum. On day eightof the experiment, the rats were weighed and sacrificed by cervical dislocation. The livers were carefullydissected out and quickly fixed in 10% formal saline for histological studies. The histological findings after Hand E method showed sinusoidal congestion with cytoplasmic vacuolation (hepatocyte oedema and mildinflammation of the portal tracts. Our study suggests that artesunate at normal dose has a toxic effect on theliver cells and could be a potential hepatotoxic drug. It is therefore recommended that further studies aimedat corroborating these observations be carried out and self-medication with artesunate should be discouraged.

  16. 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

  17. The Effect of Seaweed Eucheuma cottonii on Superoxide Dismutase (SOD Liver of Hypercholesterolemic Rats

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. The beneficial effect of α-tocopherol on liver regeneration after partial hepatectomy on rats

    Directory of Open Access Journals (Sweden)

    Al Dohayan Abdullah

    1999-01-01

    Full Text Available Liver, a unique organ, is the only organ which has the ability to regenerate after partial hepatectomy. It can return to normal mass several weeks after 70% partial hepatectomy. The exact mechanism responsible for regeneration is yet to be known. This needs further investigation. The aim of this study is to examine the role of oxygen free radicals (OFRs such as superoxide (0 - 2 , hydroxyl radicals (H202 or OH - in liver regeneration after partial hepatectomy (< 70%. To evaluate the effect of antioxidant on liver regeneration, rats were pre-treated intramuscularly with α-tocopherol (vitamin E daily for 3 weeks, and continued for 3 weeks post partial hepatectomy (< 70% liver weight, rat body weight were determined in both control (untreated and treated groups. The present results showed significant increase in liver weight in vitamin E treated group compared to control. The results of this paper might be useful in throwing some light on the role of oxygen free radical scavengers and antioxidants upon liver regeneration. This would have a therapeutic utilization in patients with liver problems.

  20. Effects of quercetin on polychlorinated biphenyls-induced liver injury in rats

    Directory of Open Access Journals (Sweden)

    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. The role of glucocorticoids in sodium retention in cirrhotic patients

    DEFF Research Database (Denmark)

    Hansen, Martin Højmark; Kristensen, Steffen Skott; Schaffalitzky de Muckadell, Ove B;

    2012-01-01

    sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. Methods. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout...... interval of 14 days separated the two periods. After a basal period of 36 h, dexamethasone (0.5 mg every 6 h) or placebo was given for two days. Urine was collected for 12 h periods, and the concentrations of sodium, potassium, creatinine, cortisol and cortisol metabolites were determined. Blood samples...... for hemoglobin, glucose, sodium, potassium, creatinine, aldosterone and cortisol were obtained daily. Results. Dexamethasone treatment decreased S-cortisol 92.3% (82.9-93.4%) (median and range) compared with that in the basal period. Natriuresis (dexamethasone - placebo) increased 55.1 (-26...

  2. Expression of Basic Fibroblast Growth Factor in Rat Liver Fibrosis and Hepatic Stellate Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The expression of basic fibroblast growth factor (bFGF) in rat liver fibrosis and hepatic stellate cells (HSCs) and the relationship between the expression of bFGF and rat liver fibrogenesis were studied. Sixty male SD rats (230-260 g) were divided into 4 groups randomly (the 0 week group, 1 week group, 4 week group and 8 week group). Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride. The sections of rats' liver in each group were tested by VanGieson (V-G) staining and immunohistochemistry. The expression of bFGF mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). HSCs were isolated by the combined methods of collagenase Ⅳ perfusion and density gradient centrifugation. The expression of bFGF protein in cultured HSCs was detected by Western blot. Images of immunohistochemistry detec tion, agarose gel electrophoresis of RT-PCR and SDS-polyacrylamide gel electrophoresis of Western blot were analyzed semiquantitatively by image-analyzing system. The results were analyzed by statistics. The results showed that the fibers were gradually increased in the sections of rat liver with the prolongation of the model induction. At the end of the 8th weeks, liver fibrosis was formed.The expression of bFGF detected by immunohistochemistry showed a similar tendency of gradual increase. At the end of the 8th weeks, the bFGF expression could be observed in many regions in sections and the strongest expression was in interstitial cells including HSCs and some hepatocytes in regions around the portal area and central veins. Also there was moderate expression widely in extracellular matrix (ECM). In RT-PCR detection and Western blot detection of HSCs cultured in vitro, the similar tendency of gradual increase was evident either. It is suggested that bFGF is related with liver fibrosis of rats closely and may be a fibrogenesis factor of liver. bFGF possibly regulates liver fibrogenesis through regulating metabolism of extracellular

  3. 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.

  4. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver

    Directory of Open Access Journals (Sweden)

    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

  5. Antioxidant Role of Pomegranates on Liver and Brain Tissues of Rats Exposed to an Organophosphorus Insecticide

    International Nuclear Information System (INIS)

    Toxicities of organophosphorus insecticides cause oxidative damage on many organs such as the liver and brain due to generation of reactive oxygen species. Pomegranate is among the richest fruit in poly - phenols. The aim of this study was to compare between the antioxidant strength of pomegranate juice (PJ) and pomegranate molasses (PM) and their effects on alanine transferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total protein (TP) in liver and levels of malondialdehyde (MAD), reduced glutathione (GSH) and nitric oxide (NO) in rat liver and brain tissues exposed to 1/10 LD 50 diazinon (DI). Six groups each of 6 male albino rats were used comprising control, DI, PJ, PM, PJ + DI and PM + DI for 15 days. The activities of ALT, AST, and TP concentration in liver have been increased due to treatment of rats with DI. These increases restored to normalcy when rats were supplemented with PJ or PM with DI. The results demonstrate that treatment with DI induced significant increase in MDA and NO concentrations and significant decrease in GSH levels of liver and brain tissues. The administration of PJ or PM along with DI significant decrease in MDA and NO levels and significant increase in GSH level compared to DI-group. The present study suggest that PJ or PM has a potential protective effect as it can elevate antioxidant defense system, lessens induced oxidative dam - ages and protect the brain and liver tissue against DI-induced toxicity. In addition, comaring PJ with PM it was noticed that PJ had higher antioxidant activity as evidenced by increased GSH content and decreased NO level in the liver by greater extend than PM.

  6. Influence of heme oxygenase-1 expression on immune liver fibrosis induced by cobalt protoporphyrin in rats

    Institute of Scientific and Technical Information of China (English)

    Fei Wang; Zhi-Jun Duan; Ying-Jie Sun

    2009-01-01

    AIM: To investigate the effect of heme oxygenase-1 (HO-1) expression on immune liver fibrosis induced by cobalt protoporphyrin (CoPP) in rats. METHODS: An immune liver fibrosis model of rat was established by administering human serum albumin (HSA). The rats were divided into CoPP, liver fibrosis and normal control groups. Rats in the CoPP group received intraperitoneal CoPP concurrently with HSA. Expression of HO-1 protein was observed by Western blotting and immunohistochemistry. Hematoxylin and eosin (HE) staining was performed to assess fibrosis proliferation and distribution, proliferation extent of fibroblasts, and alterations in hepatocytes and inflammatory cells. Type Ⅰ and Ⅲ collagens were detected with Van Gieson's (VG) staining and Foot's reticular fiber staining, respectively. In addition, spindle-shaped cells existing at perisinusoidal locations beyond portal and septa areas were investigated with HE staining.RESULTS: Western blotting and immunohistochemistry showed that the expression of HO-1 protein was higher in the CoPP group than in the liver fibrosis group (P < 0.05). Compared with the liver fibrosis group, the serological index of hepatic fibrosis in the CoPP group decreased significantly (P < 0.05). HE, VG and Foot's staining revealed that administration of CoPP reduced the extent of hepatic fibrosis. The levels of serological indicators and the number of spindle-shaped cells at perisinuous locations beyond the portal and septa areas were reduced in the CoPP group. Only a few inflammatory cells were seen around the portal areas and central veins in the CoPP group. CONCLUSION: Increased endogenous HO-1 may suppress liver fibrosis by protecting liver cells,inhibiting inflammatory cell infiltration and hepatic stellate cell transformation.

  7. Exendin-4 attenuates brain death-induced liver damage in the rat.

    Science.gov (United States)

    Carlessi, Rodrigo; Lemos, Natalia E; Dias, Ana L; Brondani, Leticia A; Oliveira, Jarbas R; Bauer, Andrea C; Leitão, Cristiane B; Crispim, Daisy

    2015-11-01

    The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates. PMID:26334443

  8. 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

  9. The Mr 28,000 gap junction proteins from rat heart and liver are different but related

    OpenAIRE

    Nicholson, Bruce J.; Gros, Daniel B.; Kent, Stephen B. H.; Hood, Leroy E.; Revel, Jean-Paul

    1985-01-01

    The sequence of the amino-terminal 32 residues of the rat heart Mr 28,000 gap junction protein presented here allows, for the first time, a sequence comparison of gap junctional proteins from different tissues (heart and liver). Comparison of the rat heart gap junction protein sequence and that available from rat liver reveals 43% sequence identity and conservative changes at an additional 25% of the positions. Both proteins exhibit a hydrophobic domain which could represent a transmembrane s...

  10. Age-Related Pseudocapillarization of the Liver Sinusoidal Endothelium Impairs the Hepatic Clearance of Acetaminophen in Rats

    OpenAIRE

    Mitchell, Sarah J.; Huizer-Pajkos, Aniko; Cogger, Victoria C; McLachlan, Andrew J.; Le Couteur, David G; Jones, Brett; de Cabo, Rafael; Hilmer, Sarah N.

    2011-01-01

    We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer 14C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pas...

  11. 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.

  12. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I

    Science.gov (United States)

    Zhang, Ludi; Shao, Yanjiao; Li, Lu; Tian, Feng; Cen, Jin; Chen, Xiaotao; Hu, Dan; Zhou, Yan; Xie, Weifen; Zheng, Yunwen; Ji, Yuan; Liu, Mingyao; Li, Dali; Hui, Lijian

    2016-01-01

    Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah−/− rats. The Fah−/− rats faithfully represented major phenotypic and biochemical manifestations of human HT1, including hypertyrosinemia, liver failure, and renal tubular damage. More importantly, the Fah−/− rats developed remarkable liver fibrosis and cirrhosis, which have not been observed in Fah mutant mice or pigs. Transplantation of wild-type hepatocytes rescued the Fah−/− rats from impending death. Moreover, the highly efficient repopulation of hepatocytes in Fah−/− livers prevented the progression of liver fibrosis to cirrhosis and in turn restored liver architecture. These results indicate that Fah−/− rats may be used as an animal model of HT1 with liver cirrhosis. Furthermore, Fah−/− rats may be used as a tool in studying hepatocyte transplantation and a bioreactor for the expansion of hepatocytes. PMID:27510266

  13. 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.

  14. Some of the Regenerative Properties of the Aqueos Extract of Ocimum sanctum on the Cytoarchitecture of the Liver of Adult Female Wistar Rats Following Paracetamol Induced Liver Damage

    OpenAIRE

    S.B. Mesole; Y.G. Mohammed; C. Nyaribo; J. Olusakin; A.O. Okpanachi

    2012-01-01

    The aim of the present study is to investigate some of the regenerative properties of Ocimum sanctum on the cytoarchitecture of the liver of adult female wistar rats following paracetamol induced liver damage. There is a lack of good hepatoregenerative drugs in modern medicine to aleviate and treat drug-induced liver damage. Leaves of sacred holy basil, also called Green Tulsi (Ocimum sanctum), belonging to family Lamiaceae are used traditionally for their hepatoregenerative effect. We wanted...

  15. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

    OpenAIRE

    de Silva, R N; Bueno, P.G.; L.R.S. Avó; Nonaka, K.O.; H.S. Selistre-Araújo; A.M.O. Leal

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subj...

  16. Apoptotic bone marrow CD34+ cells in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Shuang-Suo Dang; Wen-Jun Wang; Ning Gao; Shun-Da Wang; Mei Li; La-Yang Liu; Ming-Zhun Sun; Tao Dong

    2011-01-01

    AIM: To access the frequency and level of apoptotic CD34+ cells isolated from the marrow fluid of patients with post-hepatitis cirrhosis.METHODS: The frequency of bone marrow CD34+ cells and apoptotic bone marrow CD34+ cells in 31 in-patients with post-hepatitis cirrhosis (cirrhosis group), and 15 out-patients without liver or blood disorders (control group) was calculated by flow cytometry. Pa-rameters were collected to evaluate liver functions of patients in cirrhosis group.RESULTS: The percentage of normal bone marrow CD34+ cells was 6.30% ± 2.48% and 1.87% ± 0.53% (t = 3.906, P < 0.01) while that of apoptotic marrow CD34+ cells was 15.00% ± 15.81% and 5.73% ± 1.57% (t = 2.367, P < 0.05) in cirrhosis and control groups, re-spectively. The percentage of apoptotic marrow CD34+ cells was 6.25% ± 3.30% and 20.92 ± 18.5% (t = 2.409, P < 0.05) in Child-Pugh A and Child-Pugh B + C cirrhotic patients, respectively. The percentage of late apoptotic marrow CD34+ cells was positively correlated with the total bilirubin and aspartate aminotransferase serum levels in patients with cirrhosis.CONCLUSION: The status of CD34+ marrow cells in cirrhotic patients may suggest that the ability of he-matopoietic progenitor cells to transform into mature blood cells is impaired.

  17. Alpha-Lipoic acid counteracts the promoted oxidative DNA damage in the liver of septic rats

    International Nuclear Information System (INIS)

    Viral, parasitic infections and chemical carcinogens are among the etiological factors of liver cancer. It seems important to study the initiating and promoting agents to evaluate the etiology and prevention of such life threatening disease. Intestine-derived bacteria product, lipopolysaccharide (LPS), is mainly detoxified by the liver. It has shown to induce a state of oxidative DNA damage is not fully investigated. Increased oxidative DNA damage and rate of cell proliferation may initiate or even promote cancer. In the present work, the capability of LPS to induce 8-hydroxydeoxyguanosine (8-HDG), a specific DNA adduct for oxidative DNA damage, in rat livers is tested. Furthermore, a possible protective effect of alpha lipoic acid (ALA) is also assessed. Investigated parameters are liver contents of glutathione (GSH), lipid peroxides (MDA), nitric oxide (NO) and 8-HDG in the liver-extracted DNA. Serum activities of ALT, AST and GGT as liver-function markers as well as IL2 are assessed. Moreover, liver histology is examined. LPS was given doses of 1, 3, 5, 7 and 9 mg/kg once i.p. while, the rat mortality was examined 24 hours later. ALA was given in doses of 50, 100 and 200 mg/kg once i.p. 3h before LPS is found to be 5mg/kg. LPS increased the level of 8-HDG, MDA and NO in the liver. It also induced acute liver necrosis and inflammatory cell infiltration as shown in liver-histopathology and in the significant increase in the activities of ALT, AST and GGT. LPS increased the serum level of IL2 as well. The dose 200mg/kg of ALA revealed a 100% protection against LPS-induced lethality. It also, prevented the LPS-induced increase in 8-HDG in liver extracted DNA, the liver contents of MDA and NO. ALA also rescued the LPS-induced GSH depletion. It corrected the liver function as shown by the prevention of increases in the activity of ALT, AST and GGT with a remarkable improvement in the liver histology. Moreover, it prevented the increase in serum level of IL2. These

  18. Proton nuclear magnetic resonance and pattern recognition analysis of liver extracts from rats under different anesthetics

    International Nuclear Information System (INIS)

    Although general anesthesia is widely used in the surgical arena, the mechanisms by which general anesthetics act remain unclear. We previously described alterations in gene expression ratios in hepatic tissue taken from rats treated with anesthetics. Consequently, it is considered that anesthetics influence liver metabolism. Thus, the goal of this study was to use pattern recognition analysis of proton nuclear magnetic resonance spectra to visualize changes in liver metabolic phenotypes in response to widely used intravenous anesthetics (propofol and dexmedetomidine) and inhalational anesthetics (sevoflurane and isoflurane). Rats were randomized into 13 groups (n = 6 in each group), and each group received one of following agents: propofol, dexmedetomidine, sevoflurane, isoflurane, or no anesthetic (control group). The liver was directly removed from rats immediately after or 24 h or 48 h after a 6-h period of anesthesia. Hydrophilic compounds were extracted from the liver and were analyzed with proton nuclear magnetic resonance spectroscopy. All spectral data were processed and analyzed by principal component analysis for comparison of metabolite profiles. Data were visualized by plotting principal component (PC) scores. In the plots, each point represents an individual sample. Each group was clustered separately on the plots, and the PC scores of the propofol group were clearly distinct from those of the control group and other anesthetic groups. The difference in PC scores was more pronounced immediately after completion of anesthesia when compared with 24 or 48 h after completion of anesthesia. Although the effect of intravenous anesthetics on the liver dissipated over time, the effect of inhalational anesthetics persisted. Propofol, dexmedetomidine, sevoflurane and isoflurane exert different effects on liver metabolism. In particular, liver metabolism was markedly altered after exposure to propofol. The effect of anesthesia on the liver under propofol or

  19. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    International Nuclear Information System (INIS)

    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

  20. 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.

  1. Exploring an animal model of amodiaquine-induced liver injury in rats and mice.

    Science.gov (United States)

    Liu, Feng; Cai, Ping; Metushi, Imir; Li, Jinze; Nakayawa, Tetsuya; Vega, Libia; Uetrecht, Jack

    2016-09-01

    Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4(+) T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance. PMID:27416278

  2. Effects of estrogen on hyperglycemia and liver dysfunction in diabetic male rats

    OpenAIRE

    Ahmed, Marwa A; Hassanein, Khaled M A

    2012-01-01

    Objective: To study the possible beneficial effect of estrogen (17β-estradiol E2) on hyperglycemia, oxidative stress and liver dysfunctions in STZ-induced diabetic rats. A total of 40 albino male rats were randomly divided into four groups: a control group (I), a diabetic group (II), a group given 17β estradiol (E2) for 15 days (III), and a diabetic group given E2 for 30 days (IV). Diabetes was induced in the rats by 65 mg/kg streptozosin (STZ) via an intraperitoneal (i.p.) injection. E2 was ...

  3. Comparison of therapeutic effects of electrochemotherapy and radiofrequency ablation on rats with implanted liver cancer

    International Nuclear Information System (INIS)

    Objective: To compare the therapeutic effects of electrochemotherapy (EChT) and radiofrequency ablation (RFA) on rats with implanted liver cancer. Methods: Immediate cancerous ascites injection method was utilized for creation of rats liver cancer model and followed by treatment with EchT and RFT respectively. Tumor size, necrosis and apoptosis were observed one week later by imaging and pathology. The results were compared with those of control group. The survival times were observed also. Results: Before treatment, all rats average liver tumor volume was (100 ± 6) mm3. One week after treatment, average tumor volumes in EChT group [(125 ± 10) mm3] and RFA group [(143 ± 12) mm3] were significantly smaller than those of control group [(190 ± 11) mm3], but tumor volume showed significant statistical difference between EChT group and RFA group. Necrosis, apoptosis and survival times in EChT group and RFA group were significantly higher than those of control group. Conclusions: EChT or RFA could promote tumor necrosis, induce apoptosis, inhibit tumor growth and prolong the survival time of rats with implanted liver cancer

  4. DIBROMOETHANE EFFECTS ON THE INDUCTION OF GAMMA-GLUTAMYL-TRANSPEPTIDASE POSITIVE FOCI IN RAT LIVER

    Science.gov (United States)

    The initiating and promoting activities of 1.2-dibromoethane in rat liver were investigated using the enzyme-altered foci bioassay. The incidence of gamma-glutamyl-transpeptidase (GGT)-positive foci was used as an early histochemical marker for hepatocarcinogenesis. To determine ...

  5. Effect of fipronil on energy metabolism in the perfused rat liver.

    Science.gov (United States)

    de Medeiros, Hyllana Catarine Dias; Constantin, Jorgete; Ishii-Iwamoto, Emy Luiza; Mingatto, Fábio Erminio

    2015-07-01

    Fipronil is an insecticide used to control pests in animals and plants that can causes hepatotoxicity in animals and humans, and it is hepatically metabolized to fipronil sulfone by cytochrome P-450. The present study aimed to characterize the effects of fipronil (10-50μM) on energy metabolism in isolated perfused rat livers. In fed animals, there was increased glucose and lactate release from glycogen catabolism, indicating the stimulation of glycogenolysis and glycolysis. In the livers of fasted animals, fipronil inhibited glucose and urea production from exogenous l-alanine, whereas ammonia and lactate production were increased. In addition, fipronil at 50μM concentration inhibited the oxygen uptake and increased the cytosolic NADH/NAD⁺ ratio under glycolytic conditions. The metabolic alterations were found both in livers from normal or proadifen-pretreated rats revealing that fipronil and its reactive metabolites contributed for the observed activity. The effects on oxygen uptake indicated that the possible mechanism of toxicity of fipronil involves impairment on mitochondrial respiratory activity, and therefore, interference with energy metabolism. The inhibitory effects on oxygen uptake observed at the highest concentration of 50μM was abolished by pretreatment of the rats with proadifen indicating that the metabolites of fipronil, including fipronil sulfone, acted predominantly as inhibitors of respiratory chain. The hepatoxicity of both the parent compound and its reactive metabolites was corroborated by the increase in the activity of lactate dehydrogenase in the effluent perfusate in livers from normal or proadifen-pretreated rats. PMID:25943759

  6. Inhibitory effect of metformin on oxidation of NADH-dependent substrates in rat liver homogenate

    Czech Academy of Sciences Publication Activity Database

    Páleníčková, E.; Cahová, M.; Drahota, Zdeněk; Kazdová, L.; Kalous, M.

    2011-01-01

    Roč. 60, č. 5 (2011), s. 835-839. ISSN 0862-8408 R&D Projects: GA MZd NS10504 Institutional research plan: CEZ:AV0Z50110509 Keywords : Metformin * mitochondrial respiration * rat liver homogenate Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.555, year: 2011

  7. EFFECT OF MULTIGLYCOSIDES OF TRIPTERYGIUM WILFORDH (GTW) ON RAT TESTIS, HEART, LIVER AND KIDNEY

    Institute of Scientific and Technical Information of China (English)

    ZHOULan-Fang; LEIHai-Peng

    1989-01-01

    Adult male Wistar rats were given GTW orally at 50 rag/kg or 20 mg / kg for 4 or 5 weeks. Control animals were given the vehicle only. ARer treatment, testis, heart, liver and kidney were removed and examined. The scminiferous tubules of the treated

  8. Hepatoprotective Effects of Panus giganteus (Berk. Corner against Thioacetamide- (TAA- Induced Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Wei-Lun Wong

    2012-01-01

    Full Text Available Panus giganteus, a culinary and medicinal mushroom consumed by selected indigenous communities in Malaysia, is currently being considered for large scale cultivation. This study was undertaken to investigate the hepatoprotective effects of P. giganteus against thioacetamide- (TAA- induced liver injury in Sprague-Dawley rats. The rats were injected intraperitoneally with TAA thrice weekly and were orally administered freeze-dried fruiting bodies of P. giganteus (0.5 or 1 g/kg daily for two months, while control rats were given vehicle or P. giganteus only. After 60 days, rats administered with P. giganteus showed lower liver body weight ratio, restored levels of serum liver biomarkers and oxidative stress parameters comparable to treatment with the standard drug silymarin. Gross necropsy and histopathological examination further confirmed the hepatoprotective effects of P. giganteus. This is the first report on hepatoprotective effects of P. giganteus. The present study showed that P. giganteus was able to prevent or reduce the severity of TAA-induced liver injury.

  9. Effect of gastrin on liver regeneration after partial hepatectomy in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Olsen, P S

    1990-01-01

    Gastrin has been shown to be an important trophic hormone for the mucosa of the stomach and the proximal intestine. In the present study the effect of gastrin on liver regeneration after partial hepatectomy in rats was investigated. After partial hepatectomy a significant rise in the concentration...

  10. Protective role of garlic against gamma radiation induced histological and histochemical changes in rat liver

    International Nuclear Information System (INIS)

    The present work was planned to evaluate the radioprotective effect of garlic (Allium sativum) against the hazardous action of gamma radiation on liver of rat one and ten days post-exposure. Garlic was orally administered (100 mg/ kg body wt) to rats daily for two weeks before exposure to single dose whole body gamma-irradiation (5Gy). The results showed that exposure of rats to gamma- irradiation caused massive portal infiltration with inflammatory cells, dilatation of blood sinusoids, an increase in the number of Kupffer cells, vacuolation of some hepatocytes as well as pyknosis and karyolysis of hepatic nuclei in the liver tissue. Histochemical examination of liver one day post- irradiation illustrated weak to moderate glycogen particles. While, on ten days post-irradiation, a strong activity for glycogen was detected. The disturbance in carbohydrate metabolism is closely related to the radiation induced histological damage in the liver tissue. Administration of garlic for 2 weeks pre-irradiation reduced the radiation induced histopathological changes and showed marked protection against the tissue damaging effect of radiation. It could be concluded that treatment of rats with garlic before exposure to gamma-irradiation offered a noticeable radioprotective effect of the studied organ

  11. Viability of the vascularly perfused, recirculating rat intestine and intestine-liver preparations

    Energy Technology Data Exchange (ETDEWEB)

    Hirayama, H.; Xu, X.; Pang, K.S. (Univ. of Toronto, Ontario (Canada))

    1989-08-01

    Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid ({sup 14}C)glucose absorption against a concentration gradient and a lack of ({sup 3}H)-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.

  12. 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.

  13. 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.

  14. Protection Effect of Kallistatin on Carbon Tetrachloride-Induced Liver Fibrosis in Rats via Antioxidative Stress

    Science.gov (United States)

    Huang, Xiaoping; Wang, Xiao; Lv, Yinghui; Xu, Luli; Lin, Junsheng; Diao, Yong

    2014-01-01

    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. PMID:24558397

  15. Rat liver glutathione S-transferase activity stimulation following acute cadmium or manganese intoxication

    International Nuclear Information System (INIS)

    The effect of cadmium or manganese administration on rat liver glutathione S-transferase (GST) has been investigated. The activity of this enzyme in liver cytosol, where almost all the cellular activity is present, had increased by more than 36% 24 h after a single i.p. injection of CdCl2 (2.5 mg kg-1 b.w.) or MnCl2 (2.0 mg kg-1 b.w.). After shorter and longer time intervals, a lower enzyme activity stimulation was observed in both cases. When liver cytosol was incubated for 10 min with 75 μM CdCl2 or 40 μM MnCl2, no effect was observed on enzyme activity. The increase in GST following cadmium or manganese administration was blocked by prior administration of actinomycin D, indicative of a possible transcription-dependent response. The liver soluble GST from both control and metal-treated rats was not at all affected by Vitamin E, in the range of 20-300 μM. By contrast, hematin was seen to be a competitive inhibitor of this liver enzyme from both types of rats by using CDNB as substrate and the Ki value was equal to 0.22 μM. The possibility that under the conditions used class alpha GST isoenzymes are affected by cadmium or manganese is discussed

  16. Relationship of 24-hour ambulatory blood pressure and heart rate with markers of hepatic function in cirrhotic patients

    OpenAIRE

    Stergiou George S; Dourakis Spyros P; Alexopoulou Alexandra; Tzamouranis Dimitris G

    2010-01-01

    Abstract Background There is evidence that in cirrhotic patients, certain hemodynamic parameters, such as blood pressure and heart rate, are related to the severity of liver disease. This study investigated whether non-invasive 24-hour ambulatory blood pressure and heart rate are more closely associated with markers of liver disease severity than conventional office measurements. Methods Ambulatory patients with cirrhosis underwent office blood pressure and heart rate measurements, 24-hour am...

  17. 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

    Directory of Open Access Journals (Sweden)

    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.

  18. Efficacy of Boesenbergia rotunda Treatment against Thioacetamide-Induced Liver Cirrhosis in a Rat Model

    Directory of Open Access Journals (Sweden)

    Suzy M. Salama

    2012-01-01

    Full Text Available Background. Experimental research in hepatology has focused on developing traditional medicines into potential pharmacological solutions aimed at protecting liver from cirrhosis. Along the same line, this study investigated the effects of ethanol-based extract from a traditional medicine plant Boesenbergia rotunda (BR on liver cirrhosis. Methodology/Results. The BR extract was tested for toxicity on 3 groups of rats subjected to vehicle (10% Tween 20, 5 mL/kg and 2g/kg and 5g/kg doses of the extract, respectively. Next, experiments were conducted on a rat model of cirrhosis induced by thioacetamide injection. The rats were divided into five groups and, respectively, administered orally with 10% Tween-20 (5 mL/kg (normal control group, 10% Tween-20 (5 mL/kg (cirrhosis control group, 50 mg/kg of silymarin (reference control group, and 250 mg/kg and 500 mg/kg of BR extract (experimental groups daily for 8 weeks. The rats in normal group were intraperitoneally injected with sterile distilled water (1 mL/kg 3 times/week, and those in the remaining groups were injected intraperitoneally with thioacetamide (200 mg/kg thrice weekly. At the end of the 8 weeks, the animals were sacrificed and samples were collected for comprehensive histopathological, coagulation profile and biochemical evaluations. Also, the antioxidant activity of the BR extract was determined and compared with that of silymarin. Data from the acute toxicity tests showed that the extract was safe to use. Histological analysis of the livers of the rats in cirrhosis control group revealed uniform coarse granules on their surfaces, hepatocytic necrosis, and lymphocytes infiltration. But, the surfaces morphologically looked much smoother and the cell damage was much lesser in those livers from the normal control, silymarin and BR-treated groups. In the high-dose BR treatment group, the livers of the rats exhibited nearly normal looking lobular architecture, minimal inflammation

  19. Expression and localization of regenerating gene I in a rat liver regeneration model

    International Nuclear Information System (INIS)

    Regenerating gene (Reg) I has been identified as a regenerative/proliferative factor for pancreatic islet cells. We examined Reg I expression in the regenerating liver of a rat model that had been administered 2-acetylaminofluorene and treated with 70% partial hepatectomy (2-AAF/PH model), where hepatocyte and cholangiocyte proliferation was suppressed and the hepatic stem cells and/or hepatic progenitor cells were activated. In a detailed time course study of activation of hepatic stem cells in the 2-AAF/PH model, utilizing immunofluorescence staining with antibodies of Reg I and other cell-type-specific markers, we found that Reg I-expressing cells are present in the bile ductules and increased during regeneration. Reg I-expressing cells were colocalized with CK19, OV6, and AFP. These results demonstrate that Reg I is significantly upregulated in the liver of the 2-AAF/PH rat model, accompanied by the formation of bile ductules during liver regeneration.

  20. Pyrazole prevention of CC14-induced ultrastructural changes in rat liver.

    Science.gov (United States)

    Bernacchi, A. S.; de Castro, C. R.; de Toranzo, E. G.; Marzi, A.; de Ferreyra, E. C.; de Fenos, O. M.; Castro, J. A.

    1980-01-01

    Carbon tetrachloride (CC14) administration to rats leads to an early dilatation, vesiculation and disorganization of the liver endoplasmic reticulum (ER). This hepatotoxin also causes detachment of ribosomes from ER membranes, dilatation of the Golgi cisternae and occasionally dilatation of the perinuclear membrane. Prior treatment of the rats with pyrazole completely prevents CC14- induced ultrastructural alterations observed in liver at 3 h. This drug is known to decrease the intensity of the irreversible binding of CC14 reactive metabolites to cellular constituents without modifying the intensity of the CC14- induced lipid peroxidation, either in vitro or in vivo, as measured by the diene conjugation procedure or by decreases inthe arachidonic acid content of microsomal phospholipids. Results suggest that interaction of reactive metabolites rather than lipid peroxidation mediates deleterious effects of CCl4 on the liver ER. Images Fig. 1 Fig. 2 Fig. 3 PMID:7448119

  1. Alkaline phosphatase activity in plasma and liver of rats submitted to chronic exposure to fluoride

    Directory of Open Access Journals (Sweden)

    Mileni da Silva Fernandes

    2011-12-01

    Full Text Available The aim of this study was to compare the effect of fluoride (F on alkaline phosphatase activity in the liver and plasma of the rats. Four groups of male Wistar rats (n=6, which received drinking water containing 5, 15 or 50 ppm F or deionized water (control throughout the experiment were included in the study. The animals were euthanized and had their tissues and blood plasma collected for the analysis of fluoride and alkaline phosphatase. There was an increase in F concentration in most tissues in the animals treated with higher F concentrations, except for the heart. The alkaline phosphatase assay showed an increase in the activity in the liver and blood plasma of the animals treated with fluoride concentrations of 15 and 50 ppm (p<0.05. This study suggested that F at a concentration of 50 ppm in drinking water promotes increased the activity of alkaline phosphatase in the liver and blood plasma.

  2. Liver-protecting and fibrosis-resisting effect of Ganxianning on rats withspleen deficiency and stagnation of Liver-qi

    Institute of Scientific and Technical Information of China (English)

    Zhen Qiu Guo; Xiao Wei Zhao; Xin Yu Chen

    2000-01-01

    AIM To study the liver-protecting and fibrosis-resisting effect of Ganxianning (GXN) and its mechanism.METHODS Model of carbon tetrachloride hepatic injury fibrosis rats was reproduced. In the experimentthere were six groups, the treatment groups with GXN's large, moderate and small dose (GXNb, GXNm andGXNs), the treatment group with colchicine, the blank model group and normal control group. The course of treatment was 30 days, then the rats were killed with their blood and liver tested.RESULTS In treatment groups, alanine aminotransferase (ALT) was lower than that in the model group(P<0.01), and albumin (Alb) higher than that in the model (P<0.01). Hydroxylproline (Hyp) and redcell membrane C3B receptor garland in GXNb's and GXNm's groups were lower and circulation complex(CIC) was slightly higher. Fibrinogen (Fb) in both colchicine and model groups was higher than that innormal group and the difference was significant (P<0.05, P<0.01). Compared with model group, acid-α-naphthyl acetate esterase (ANAE) increased in GXNb's and GXNm's groups (P<0.05, P<0.01). Underlight and electron microscopes, level of hepatic fibrosis of GXN groups was much lower than that of themodel group, P<0.01, and their difference was very significant. In GXNms group, liver cell was normal onthe whole and its chromatin was more than the model group and its nucleolus was evident.CONCLUSION GXN has rather good functions of protecting liver and resisting fibrosis, and thesefunctions are related to the increase of ANAE and C3b, decrease of CIC and Fb. and improvement of bodyimmunity function.

  3. Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

    DEFF Research Database (Denmark)

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

    1985-01-01

    The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized...... concentration and rates of production and utilization of glucose were similar in denervated rats and control rats. Also hepatic glycogen depletion was similar in the groups. The lack of effect of denervation could not be ascribed to compensating changes in hormone or substrate levels. In adrenodemedullated rats...... lack of glucose recovery from hypoglycemia was accompanied by delayed normalization of glucose clearance. In fed rats, activity in hepatic autonomic nerves is not a primary mechanism increasing glucose production during acute hypoglycemia. Epinephrine enhances glucose recovery by decreasing glucose...

  4. CLONING AND ANALYSIS OF THE GENOMIC DNA SEQUENCE OF AUGMENTER OF LIVER REGENERATION FROM RAT

    Institute of Scientific and Technical Information of China (English)

    董菁; 成军; 王勤环; 施双双; 王刚; 斯崇文

    2002-01-01

    Objective.To search for genomic DNA sequence of the augmenter of liver regeneration (ALR) of rat.Methods.Polymerase chain reaction (PCR) with specific primers was used to amplify the sequence from the rat genome.Results.A piece of genomic DNA sequence and a piece of pseudogene of rat ALR were identified.The lengths of the gene and pseudogene are 1508 bp and 442 bp,respectively.The ALR gene of rat includes 3 exons and 2 introns.The 442 bp DNA sequence may represent a pseudogene or a ALR related peptide.Predicted amino acid sequence analysis showed that there were 14 different amino acid residues between the gene and pseudogene.ALR related peptide is 84 amino acid residues in length and relates closely to ALR protein.Conclusion.There might be a multigene family of ALR in rat.

  5. Ethanol-induced impairment of hepatic glycoprotein secretion in the isolated rat liver perfusion model

    International Nuclear Information System (INIS)

    The authors have previously shown that acute administration of ethanol inhibits hepatic glycoprotein secretion in vivo. This ethanol-induced effect appears to be mediated by its reactive metabolite, acetaldehyde. Since hormonal influences and vascular changes can not be controlled in vivo during ethanol administration, they investigated the effect of ethanol in the isolated perfused liver model. Rat liver from fed animals was perfused with oxygenated KRB at 3 ml/min/g liver for 4 hrs. Since ethanol inhibits proteins synthesis in vitro, protein acceptor pool size was equalized in both ethanol and control perfused livers with 1 mM cycloheximide. 3H-glucosamine was used to label hepatic secretory glycoproteins in the perfusate. Colchicine, a known inhibitor of protein secretion, impaired the secretion of labeled glycoproteins with a concomitant retention of these export proteins in the liver; therefore, confirming the authors secretory model. Ethanol (50 mM) inhibited the appearance of glucosamine-labeled glycoproteins by 60% into the perfusate as compared to control livers. Pretreatment of animals with cyanamide (an aldehyde dehydrogenase inhibitor) further potentiated this effect of ethanol in the isolated perfused liver. These data suggest that ethanol inhibits hepatic glycoprotein secretion in the isolated liver perfusion model, and this ethanol-induced impairment appears to be mediated by acetaldehyde

  6. Natural killer (NK) activity of pit cells perfused from livers of rats treated with ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Albornoz, L.; Jones, J.M.; Crutchfield, C.; Veech, R.L. (National Inst. of Alcohol Abuse and Alcoholism, Rockville, MD (United States) Univ. of Arkansas Medical Sciences, Little Rock (United States))

    1991-03-11

    The liver is the major site of ethanol (ETOH) metabolism. Liver sinusoids contain lymphocytes with NK activity. The authors treated LEW rats for 2 weeks with i.p. injection of 1.25 ml 25% ETOH/kg 3 times/week and 5% ETOH in drinking water. Livers were perfused at 5-fold physiological pressure and cells obtained were banded on 1.077 density Ficoll. Their cytotoxicity was tested against {sup 51}Cr-labeled YAC-1 or U937 and compared to spleen and blood lymphocytes. In untreated rats, pit cell NK activity was 2-fold that of splenic lymphocytes and 4-fold that of blood lymphocytes. Compared to controls, ETOH-treated rats exhibited a 30 to 90% rise in pit cell NK activity detected with YAC-1 or U937 targets. The pit cell enhanced NK activity in ETOH-treated rats was further increased if polyinosinicpolycytidilic acid was injection i.p. 18 hours before the assay. Blood and spleen lymphocyte NK activity of ETOH-treated rats was also greater than in controls. There was no evidence that ETOH merely redistributed lymphocytes among the tissues. Although ETOH acutely inhibits NK activity in vitro, chronic ETOH increases in vivo.

  7. Direct and indirect effects of kisspeptin on liver oxidant and antioxidant systems in young male rats.

    Science.gov (United States)

    Aydin, M; Oktar, S; Yonden, Z; Ozturk, O H; Yilmaz, B

    2010-06-01

    Kisspeptin is a recently discovered hypothalamic peptide which plays an important role in the central control of reproductive functions. We have investigated direct and indirect effects of kisspeptin on the liver oxidative stress in young male rats. Twenty-four rats were divided into four groups (n = 6/group). First group served as control and received saline. Kisspeptin-10 was administered to the animals in the second group (20 nmol/rat/day), for a period of 7 days. Rats were given only one dose gosereline (0.9 mg/rat), a GnRH agonist in the third group. The last group received kisspeptin-10 with gosereline. The activities of catalase, superoxide dismutase (SOD), xanthine oxidase (XO), adenosine deaminase (AD) and level of malondialdehyde were studied in liver tissue. Serum samples were separated for total antioxidant capacity (TAC), total oxidant status (TOS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, blood urea nitrogen (BUN), colesterol, high-density lipoprotein (HDL) and triglyceride. Kisspeptin increased the activities of SOD and catalase (p < 0.05). When compared to the control group, the levels of malondialdehyde, TOS and AST were lower, but levels of BUN, cholesterole, HDL and AD were higher in the other three groups (p < 0.05). In conclusion, our findings suggest that kisspeptin may have antioxidant and thus protective effects on the liver tissue. PMID:20517893

  8. Dimethoate-induced effects on antioxidant status of liver and brain of rats following subchronic exposure

    International Nuclear Information System (INIS)

    Dimethoate, an organophosphate pesticide, is used in controlling the pests of a variety of crops. The study was carried out to understand the role of dimethoate in inducing oxidative stress leading to generation of free radicals and alterations in antioxidant enzymes and scavengers of oxygen free radicals. The effects of subchronic exposure of dimethoate in the production of oxidative stress were evaluated in male Wistar rats in the present study. Dimethoate was administered orally at doses 0.6, 6, and 30 mg/kg for 30 days in these rats. The results indicated an increase in levels of hepatic Cytochrome P450, lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase in liver and brain at doses 6 and 30 mg/kg. There were no significant changes in the level of glucose-6-phosphate dehydrogenase activity except in liver at 30 mg/kg. A decrease in glutathione was observed at 30 and 6 mg/kg in both liver and brain. Glutathione-S-transferase increased at 30 and 6 mg/kg in liver and 30 mg/kg in brain. Erythrocyte acetylcholinesterase was inhibited at 30 and 6 mg/kg doses. Dose-dependent histopathological changes were seen in both liver and brain. This study concludes that oxidative stress due to dimethoate may be ascribed to induction of Cytochrome P450, inhibition of AChE and disturbance in activities of GSH and GST enzymes causing lipid peroxidation and histological and electron microscopic changes in liver and brain

  9. Influence Of Whey Protein For Abrogating Liver Injury In Female Rats

    International Nuclear Information System (INIS)

    The objective of this study was to determine the possible benefits of whey protein concentrate (44% protein, 5% fat and 4.6% ash in dry weight) against liver injury induced by CCl4 . It was carried out by evaluating the effect of the daily feeding of female rats on diet containing 15% whey protein instead of soybean protein for four weeks on some biochemical and histological changes in liver of female rats.The data showed that injection with CCl4 (1 ml /kg body weight 3 times / week) caused significant decrease in body weight with disturbances in liver functions as significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and bilirubin and significant decrease in serum albumin, FT3 and an increase in AFP levels. A marked significant decrease in glutathione content and significant increase in lipid peroxidation was also observed in hepatic tissues. The histological examination revealed that CCl4 treatment showed marked degenerative changes in liver hepatocytes and sinusoids.The results also showed that feeding on diet containing whey protein for two or four weeks during CCl4 treatment minimized the disturbance of the liver functions and liver histology.

  10. Chronic effect of gabapentin on liver function in adult male rats.

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Meshkibaf

    2013-12-01

    Full Text Available Gabapentin (GPN is a new antiepileptic agent currently in used as add-on therapy in adult patients suffering from partial seizures. The extent of liver damage at different dosage and long term treatment with GPN is not yet clear. Therefore this study was undertaken to find out the possibility of liver damage by this drug. Adult male (Wistar rats of 180-220 g were administered intraperitoneally with GPN (20 or 100 mg/kg for 45 days. After the experimental period, the liver function tests were carried out in control and experimental groups. The activity of liver enzymes, with 20 mg/kg of GPN were not significantly different from the control group but, the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, direct bilirubin and total bilirubin were enhanced significantly with 100 mg/kg of GPN. Total protein and albumin decreased in this group as compared with control animals. The histopathology of the liver parenchymal cells also showed minute foci of necrosis in a few rats treated with high dose of GPN, whereas, at therapeutic dose the histopathology and biochemical indices showed almost normal values. At therapeutic dose GPN is a safer drug with regards to liver function and hepatocellular damage as compared with other antiepileptic drugs.

  11. Mechanism of Hepatoprotective Effect of Boesenbergia rotunda in Thioacetamide-Induced Liver Damage in Rats.

    Science.gov (United States)

    Salama, Suzy M; Abdulla, Mahmood A; Alrashdi, Ahmed S; Hadi, A Hamid A

    2013-01-01

    Background. Researchers focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Objectives. Evaluating the hepatoprotective activity of Boesenbergia rotunda (BR) rhizome ethanolic extract on thioacetamide-induced liver cirrhosis in rats. Methods. Male Sprague-Dawley rats were intraperitoneally injected with 200 mg/kg TAA 3 times/week and daily oral administration of 250 mg/kg, 500 mg/kg of BR extract, and 50 mg/kg of the reference drug Silymarin for 8 weeks. At the end of the experiment, Masson's trichrome staining was used to measure the degree of liver fibrosis. Hepatic antioxidant enzymes (CAT and GPx), nitrotyrosine, cytochrome (P450 2E1), matrix metalloproteinase (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), and urinary 8-hydroxyguanosine were measured. Serum levels of transforming growth factor TGF- β 1, nuclear transcription factor NF- κ B, proinflammatory cytokine IL-6, and caspase-3 were evaluated. Serum protein expression and immunohistochemistry of proapoptotic Bax and antiapoptotic Bcl-2 proteins were measured and confirmed by immunohistochemistry of Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA). Results. BR treatment improved liver histopathology, immunohistochemistry, and biochemistry, triggered apoptosis, and inhibited cytokines, extracellular matrix proteins, and hepatocytes proliferation. Conclusion. Liver cirrhosis progression can be inhibited by the antioxidant and anti-inflammatory activities of BR ethanolic extract while preserving the normal liver status. PMID:23997791

  12. Efficacy of grape seed and skin extract against doxorubicin-induced oxidative stress in rat liver.

    Science.gov (United States)

    Mokni, Meherzia; Hamlaoui, Sonia; Kadri, Safouen; Limam, Ferid; Amri, Mohamed; Marzouki, Lamjed; Aouani, Ezzedine

    2015-11-01

    Doxorubicin (Dox) is an anthracycline used in chemotherapy, although it causes toxicity and oxidative stress. Grape seed and skin extract (GSSE) is a mixture of polyphenolic compounds with antioxidant properties. To evaluate the hepato-toxicity of Dox on healthy rats as well as the protective effect of GSSE, rats were treated with GSSE (500mg/kg bw) during 8 days. At the 4th day of treatment, they received a single dose of Dox (20 mg/kg bw). After the treatment (9th day), livers were collected and processed for oxidative stress status. Dox increased MDA (+ 900%), decreased catalase (-60%) and increased peroxidase (+90%) and superoxide dismutase (+100%) activities. In this latter case Dox mainly increased the iron isoform. Furthermore Dox altered intracellular mediators as catalytic free iron (-75%), H₂O₂(-75%) and calcium (+30%). Dox also affected liver function by elevating plasma triacylglycerol and transaminases and liver morphology by altering its typical architecture. Importantly all Dox-induced liver disturbances were alleviated upon GSSE treatment. Dox induced liver toxicity and an oxidative stress mainly characterized by increased lipoperoxidation but not protein carbonylation. GSSE efficiently protected the liver from Dox-induced toxicity and appeared as a safe adjuvant that could be incorporated into chemotherapy protocols. PMID:26639474

  13. Quantification of Hepcidin-related Iron Accumulation in the Rat Liver.

    Science.gov (United States)

    Böser, Preethne; Mordashova, Yulia; Maasland, Mark; Trommer, Isabel; Lorenz, Helga; Hafner, Mathias; Seemann, Dietmar; Mueller, Bernhard K; Popp, Andreas

    2016-02-01

    Hepcidin was originally detected as a liver peptide with antimicrobial activity and it functions as a central regulator in the systemic iron metabolism. Consequently suppression of hepcidin leads to iron accumulation in the liver. AbbVie developed a monoclonal antibody ([mAb]; repulsive guidance molecule [RGMa/c] mAb) that downregulates hepcidin expression by influencing the RGMc/bone morphogenetic protein (BMP)/neogenin receptor complex and causes iron deposition in the liver. In a dose range finding study with RGMa/c mAb, rats were treated with different dose levels for a total of 4 weekly doses. The results of this morphometric analysis in the liver showed that iron accumulation is not homogenous between liver lobes and the left lateral lobe was the most responsive lobe in the rat. Quantitative hepcidin messenger RNA analysis showed that the left lateral lobe was the most responsive lobe showing hepcidin downregulation with increasing antibody dose. In addition, the morphometric analysis had higher sensitivity than the chemical iron extraction and quantification using a colorimetric assay. In conclusion, the Prussian blue stain in combination with semi-quantitative and quantitative morphometric analysis is the most reliable method to demonstrate iron accumulation in the liver compared to direct measurement of iron in unfixed tissue using a colorimetric assay. PMID:26839325

  14. Retinol and retinyl esters in parenchymal and nonparenchymal rat liver cell fractions after long-term administration of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, M.; Blomhoff, R.; Helgerud, P.; Solberg, L.A.; Berg, T.; Norum, K.R.

    1985-09-01

    Chronic ethanol consumption reduces the liver retinoid store in man and rat. We have studied the effect of ethanol on some aspects of retinoid metabolism in parenchymal and nonparenchymal liver cells. Rats fed 36% of total energy intake as ethanol for 5-6 weeks had the liver retinoid concentration reduced to about one-third, as compared to pair-fed controls. The reduction in liver retinoid affected both the parenchymal and the nonparenchymal cell fractions. Plasma retinol level was normal. Liver uptake of injected chylomicron (3H)retinyl ester was similar in the experimental and control group. The transport of retinoid from the parenchymal to the nonparenchymal cells was not found to be significantly retarded in the ethanol-fed rats. Despite the reduction in total retinoid level in liver, the concentrations of unesterified retinol and retinyl oleate were increased in the ethanol fed rats. Hepatic retinol esterification was not significantly affected in the ethanol-fed rats. Since our study has demonstrated that liver uptake of chylomicron retinyl ester is not impaired in the ethanol-fed rat, we suggest that liver retinoid metabolism may be increased.

  15. Retinol and retinyl esters in parenchymal and nonparenchymal rat liver cell fractions after long-term administration of ethanol

    International Nuclear Information System (INIS)

    Chronic ethanol consumption reduces the liver retinoid store in man and rat. We have studied the effect of ethanol on some aspects of retinoid metabolism in parenchymal and nonparenchymal liver cells. Rats fed 36% of total energy intake as ethanol for 5-6 weeks had the liver retinoid concentration reduced to about one-third, as compared to pair-fed controls. The reduction in liver retinoid affected both the parenchymal and the nonparenchymal cell fractions. Plasma retinol level was normal. Liver uptake of injected chylomicron [3H]retinyl ester was similar in the experimental and control group. The transport of retinoid from the parenchymal to the nonparenchymal cells was not found to be significantly retarded in the ethanol-fed rats. Despite the reduction in total retinoid level in liver, the concentrations of unesterified retinol and retinyl oleate were increased in the ethanol fed rats. Hepatic retinol esterification was not significantly affected in the ethanol-fed rats. Since our study has demonstrated that liver uptake of chylomicron retinyl ester is not impaired in the ethanol-fed rat, we suggest that liver retinoid metabolism may be increased

  16. Single photon emission computed tomography and statistical parametric mapping analysis in cirrhotic patients with and without minimal hepatic encephalopathy

    International Nuclear Information System (INIS)

    The early diagnosis and treatment of cognitive impairment in cirrhotic patients is needed to improve the patients' daily living. In this study, alterations of regional cerebral blood flow (rCBF) were evaluated in cirrhotic patients using statistical parametric mapping (SPM). The relationships between rCBF and neuropsychological test, severity of disease and biochemical data were also assessed. 99mTc-ethyl cysteinate dimer single photon emission computed tomography was performed in 20 patients with non-alcoholic liver cirrhosis without overt hepatic encephalopathy (HE) and in 20 age-matched healthy subjects. Neuropsychological tests were performed in 16 patients; of these 7 had minimal HE. Regional CBF images were also analyzed in these groups using SPM. On SPM analysis, cirrhotic patients showed regions of significant hypoperfusion in the superior and middle frontal gyri, and inferior parietal lobules compared with the control group. These areas included parts of the premotor and parietal associated areas of the cortex. Among the cirrhotic patients, those with minimal HE had regions of significant hypoperfusion in the cingulate gyri bilaterally as compared with those without minimal HE. Abnormal function in the above regions may account for the relatively selective neuropsychological deficits in the cognitive status of patients with cirrhosis. These findings may be important in the identification and management of cirrhotic patients with minimal HE. (author)

  17. Effects of Insulin Treatment on Intracellular Lipid Metabolism in Liver of Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Lulu; WANG Yongbo; ZHOU Min; WANG Baoping

    2006-01-01

    The effects and the mechanism of insulin treatment on intracellular lipid metabolism in liver of diabetic rats were evaluated. Type 2 diabetic rats were induced by injecting the streptozotocin (25 mg/kg) and fat rich food. According to the results of oral glucose tolerance test (OGTT)and glucose-induced insulin secretion test (IRT), the rats were divided into two groups: untreated group (UT) and insulin-treated group (IT). Normal rats (NC) served as controls. The treatment with either Humulin N (4-6 U/kg every day), or saline lasted for 4 weeks. Body weight, OGTT,IRT, blood lipids, intracellular lipids in liver, hepatic fatty acid oxidation and the activity of fatty acid synthase (FAS) were detected. The change of liver histology was observed. The insulin sensitivity index (ISI) was applied to assess the status of insulin resistance. The results showed that as compared with NC group, the plasma and hepatic intracellular Triglyceride (TG), total cholesterol (TC) and free fatty acids (FFAs) were increased significantly in UT group (P<0.05), and lipid droplets could be seen dispersedly in the liver specimens, the hepatic fatty acid oxidation was increased markedly (P<0.05), while the fatty acid synthase activity decreased (P<0.05). Insulin treatment resulted in a further accumulation of lipids in liver by 55.7 %, 19.87 % and 22.2 % increase in TG, TC, FFAs respectively. The size of hepatocytes was enlarged and the cells were filled with fat drops. Plasma lipids showed little decrease and still significantly higher than those in NC group after the insulin treatment. Meanwhile, insulin treatment was companied by 20 % decrease in the rate of fatty acid oxidation and 31% increase in hepatic FAS activity compared to UT group. It was concluded that treatment with insulin on type 2 diabetic rat increases hepatic intracellular lipid accumulation by inhibiting hepatic fatty acid oxidation and activating FAS.

  18. Effects of sodium arsenate exposure on liver fatty acid profiles and oxidative stress in rats.

    Science.gov (United States)

    Kharroubi, Wafa; Dhibi, Madiha; Haouas, Zohra; Chreif, Imed; Neffati, Fadoua; Hammami, Mohamed; Sakly, Rachid

    2014-02-01

    The present study aimed to evaluate the effect of arsenic on liver fatty acids (FA) composition, hepatotoxicity and oxidative status markers in rats. Male rats were randomly devised to six groups (n=10 per group) and exposed to sodium arsenate at a dose of 1 and 10 mg/l for 45 and 90 days. Arsenate exposure is associated with significant changes in the FA composition in liver. A significant increase of saturated fatty acids (SFA) in all treated groups (p<0.01) and trans unsaturated fatty acids (trans UFA) in rats exposed both for short term for 10 mg/l (p<0.05) and long term for 1 and 10 mg/l (p<0.001) was observed. However, the cis UFA were significantly decreased in these groups (p<0.05). A markedly increase of indicator in cell membrane viscosity expressed as SFA/UFA was reported in the treated groups (p<0.001). A significant increase in the level of malondialdehyde by 38.3 % after 90 days of exposure at 10 mg/l was observed. Compared to control rats, significant liver damage was observed at 10 mg/l of arsenate by increasing plasma marker enzymes after 90 days. It is through the histological investigations in hepatic tissues of exposed rats that these damage effects of arsenate were confirmed. The antioxidant perturbations were observed to be more important at groups treated by the high dose (p<0.05). An increase in the level of protein carbonyls was observed in all treated groups (p<0.05). The present study provides evidence for a direct effect of arsenite on FA composition disturbance causing an increase of SFA and TFAs isomers, liver dysfunction and oxidative stress. Therefore, arsenate can lead to hepatic damage and propensity towards liver cancer. PMID:23949113

  19. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver.

    Science.gov (United States)

    Azzouz, Inès; Trabelsi, Hamdi; Hanini, Amel; Ferchichi, Soumaya; Tebourbi, Olfa; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-01-01

    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. PMID:24403828

  20. Identification and differential expression of microRNAs associated with fat deposition in the liver of Wistar rats with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Zhang, Deqing; Wang, Yuqian; Ji, Zhibin; Wang, Zhonghua

    2016-07-01

    The exact mechanism underlying hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) is not clear. Clarifying the full repertoire of microRNAs (miRNAs) in NAFLD rat liver would enhance our understanding of NAFLD pathogenesis. In this study, miRNA expression levels were analyzed in liver tissue from NAFLD Wistar rats, with normal Wistar rats as negative controls. Small RNA libraries were constructed for each sample. A total of 173 conservative miRNAs and 68 potential miRNA candidates were identified. Significant differences in the expression levels of 101 conserved miRNAs were identified between the two groups. The results of GO annotation and KEGG pathway analysis revealed that some miRNAs were likely involved in the process of liver fat deposition. This study represents the first global miRNA profiling of NAFLD Wistar rat livers, and expands the miRNA repertoire for normal livers. Our findings suggest that miRNAs play important roles in liver fat deposition. PMID:26971813

  1. [Effect of space flight on the Kosmos-1129 biosatellite on enzyme activity of the rat liver].

    Science.gov (United States)

    Nemeth, S; Tigranian, R A

    1983-01-01

    After the 18.5 day Cosmos-1129 flight the activity of 7 glucocorticoid-stimulated enzymes of the rat liver was measured. Immediately postflight the activity of tyrosine aminotransferase, tryptophan pyrolase and serine dehydrogenase increased. These enzymes rapidly (within several hours) react to increased glucocorticoids. The activity of aspartate and alanine aminotransferases also increased. These enzymes require many days of a continuous effect of glucocorticoids. The glycogen concentration in the rat liver also grew. At R + 6 the activity of tryptophan pyrolase and serine dehydrogenase decreased and that of the other enzymes returned to normal. The immobilization stress applied postflight led to an increased activity of tyrosine aminotransferase and tryptophan pyrolase. This study gives evidence that after space flight rats are in an acute stress state, evidently, produced by the biosatellite recovery. PMID:6620954

  2. Dual-contrast MR imaging of liver cancer in rats.

    Science.gov (United States)

    Weissleder, R; Saini, S; Stark, D D; Wittenberg, J; Ferrucci, J T

    1988-03-01

    MR contrast agents increase hepatic tumor conspicuity, as measured in terms of contrast-to-noise (C/N) ratios. With an animal model of hepatic metastases from breast cancer, IV administration of Gd-DTPA (0.2 mmol/kg) shows a biphasic time response, transiently increasing the signal intensity of liver relative to tumor, with C/N ratio magnitudes increasing from -5.7 to -16.3 (SE 250/20); after a delay, the signal intensity of tumor increases relative to liver with a reversal of the C/N sign from negative to positive and an increase in the C/N magnitude to +25.0. IV administration of ferrite particles (0.05 mmol Fe/kg) shows a monophasic time response, increasing signal intensity of tumor relative to liver from +1.5 to +49.5 (SE 500/30). When both contrast agents were administered together (dual-contrast technique), the tumor-liver C/N magnitude reached a maximum of +67.8 (SE 500/30) 12 min after drug infusion. Analysis of individual contrast and noise factors contributing to this technique revealed a strong correlation between the signal intensity of liver and the signal intensity of ghost artifacts, which increase after administration of Gd-DTPA (r = .89) and decrease after administration of ferrite (r = 1.0). Dual-contrast imaging shows a synergistic addition of contrast and suppression of noise from ghost artifacts, maximizing the C/N and increasing the conspicuity of focal liver lesions. PMID:3257610

  3. Microarray analysis in rat liver slices correctly predicts in vivo hepatotoxicity

    International Nuclear Information System (INIS)

    The microarray technology, developed for the simultaneous analysis of a large number of genes, may be useful for the detection of toxicity in an early stage of the development of new drugs. The effect of different hepatotoxins was analyzed at the gene expression level in the rat liver both in vivo and in vitro. As in vitro model system the precision-cut liver slice model was used, in which all liver cell types are present in their natural architecture. This is important since drug-induced toxicity often is a multi-cellular process involving not only hepatocytes but also other cell types such as Kupffer and stellate cells. As model toxic compounds lipopolysaccharide (LPS, inducing inflammation), paracetamol (necrosis), carbon tetrachloride (CCl4, fibrosis and necrosis) and gliotoxin (apoptosis) were used. The aim of this study was to validate the rat liver slice system as in vitro model system for drug-induced toxicity studies. The results of the microarray studies show that the in vitro profiles of gene expression cluster per compound and incubation time, and when analyzed in a commercial gene expression database, can predict the toxicity and pathology observed in vivo. Each toxic compound induces a specific pattern of gene expression changes. In addition, some common genes were up- or down-regulated with all toxic compounds. These data show that the rat liver slice system can be an appropriate tool for the prediction of multi-cellular liver toxicity. The same experiments and analyses are currently performed for the prediction of human specific toxicity using human liver slices

  4. Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A Metabolomics Investigation

    Directory of Open Access Journals (Sweden)

    Xiaxia Cai

    2016-03-01

    Full Text Available Background: Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Methods: Five groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water, alcohol control group (basal diet, 50% alcohol (v/v, dextrose control group (basal diet, isocaloric amount of dextrose, and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg−1 respectively, 50% alcohol (v/v. The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS was applied to identify liver metabolite profiles. Results: Nucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid, as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, l-leucine, alanyl-leucine and l-phenylalanine. Conclusion: These data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury.

  5. Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARalpha in rat liver.

    Science.gov (United States)

    Carlsson, L; Lindén, D; Jalouli, M; Oscarsson, J

    2001-10-01

    The aim of this study was to investigate the interaction between long-chain fatty acids (LCFA) and growth hormone (GH) in the regulation of liver fatty acid binding protein (LFABP) and peroxisome proliferator-activated receptor-alpha (PPARalpha). Cultured rat hepatocytes were given oleic acid (OA; 500 microM) and GH (100 ng/ml) for 3 days. LFABP mRNA increased 3.6-fold by GH and 5.7-fold by OA, and combined incubation with GH and OA increased LFABP mRNA 17.6-fold. PPARalpha mRNA was decreased 50% by GH, but OA had no effect. Hypophysectomized (Hx) female rats were treated with L-thyroxine, cortisol, GH, and dietary fat for 7 days. PPARalpha mRNA levels were three- to fourfold higher in Hx than in normal female rats. GH decreased PPARalpha mRNA 50% in Hx rats. Dietary triglycerides (10% corn oil) increased LFABP mRNA and cytosolic LFABP about twofold but had no effect on PPARalpha mRNA in Hx rats. GH and dietary triglycerides had an additive effect on LFABP expression. Dietary triglycerides increased mitochondrial hydroxymethylglutaryl-CoA synthase mRNA only in the presence of GH. The diet increased serum triglycerides in Hx rats, and GH treatment prevented this increase. Addition of cholesterol to the diet did not influence LFABP levels but mitigated increased hepatic triglyceride content. In summary, these studies show that GH regulates LFABP expression independently of PPARalpha. Moreover, GH has different effects on PPARalpha-responsive genes and does not counteract the effect of LCFA on the expression of these gene products. PMID:11551854

  6. Effect of Zingiber officinale on fatty liver induced by oxytetracycline in albino rats

    Directory of Open Access Journals (Sweden)

    Eman G.E. Helal* , Samia M. Abd El-Wahab* , Atef M. Moussa Sharaf**

    2012-01-01

    Full Text Available Fatty liver causes were markedly increased in Egyptian people throughout last years. People prefer to use the medicinal plants instead of using chemical compounds because they are cheap and have few side effects compared to chemical compounds. Ginger is a natural dietary rhizome with anti-oxidative, anti-inflammatory, and anti-carcinogenic activities. The aim of this study was to evaluate the possible potential therapeutic and protective effects of Zingiber officinale (ginger against oxytetracyclin-induced fatty liver in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. Material and Methods: Albino rats were divided into two major groups, 15 rats for each. The first group was divided into three sub-groups: a control, b fatty liver group; that was injected intraperitonealy with oxytetracycline (120mg/kg for three consecutive days and c ginger treated group; which was treated with ginger water extract (125 mg/kg for 30 days after fatty liver induction . All animals were scarified after 33 days of the beginning of the experiment. The second group was divided into three subgroups: a control, b fatty liver group; that was injected intraperitonealy with oxytetracycline (120 mg/kg for three consecutive days and c ginger protective group; which received ginger for 15 days before induction of fatty liver, then sacrificed after induction of fatty liver (3 days. Blood samples were collected for biochemical analysis. Liver specimens were obtained and fixed in 10% formalin for histological study. Results: Fatty liver groups showed high significant increase in serum glucose, cholesterol, triglycerides, LDL cholesterol, ALAT, ASAT, GGT, LDH, urea, creatinine and A/G ratio while total protein, albumin, globulin and HDL cholesterol were significantly decreased compared to control group. These biochemical changes were accompanied with histopathological alterations in fatty liver tissue. The treatment

  7. Effect of Cichorium intybus L. on fatty liver induced by oxytetracycline in albino rats.

    Directory of Open Access Journals (Sweden)

    Eman G.E. Helal* , Samia M. Abd El-Wahab* , Atef M.Moussa Sharaf**

    2011-10-01

    Full Text Available Background: Fatty liver is now one of the most common diseases in Egypt. People prefer to use the medicinal plants instead of using chemical compounds because they are cheap and have few side effects compared to chemical compounds.The current investigation was carried out to examine the possible potential therapeutic and protective effects of Cichorium intybus (chicory against oxytetracyclin-induced fatty liver in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. Material and Methods: Albino rats were divided into two major groups, 15 rats for each. The first group was divided into three sub-groups: a control, b fatty liver group; that was injected intraperitonealy with oxytetracycline (120mg/kg for three consecutive days resulting in steatosis and c chicory treated group; which was treated with chicory water extract (70 mg/kg for 30 days after fatty liver induction . All animals were scarified after 33 days of the beginning of the experiment. The second group was divided into three subgroups: a control, b fatty liver group; that was injected intraperitonealy with oxytetracycline (120mg/kg for three consecutive days and c drug protection group; which received chicory for 15 days before induction of fatty liver, then sacrificed after induction of fatty liver (3 days. Blood samples were collected for biochemical analysis. Liver specimens were obtained and fixed in 10% formalin for histological study. Results: Fatty liver groups showed high significant increase in serum glucose, cholesterol, triglycerides, LDL cholesterol, ALAT, ASAT, GGT, LDH, urea, creatinine and A/G ratio while total protein, albumin, globulin and HDL cholesterol were significantly decreased compared to control group. These biochemical changes were accompanied with histopathological alterations in fatty liver tissue. The treatment with chicory ameliorated most of the evaluated biochemical parameters and improved the

  8. Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat.

    Directory of Open Access Journals (Sweden)

    Ismail Ben Mosbah

    Full Text Available Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP, a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging

  9. Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat.

    Science.gov (United States)

    Ben Mosbah, Ismail; Mouchel, Yann; Pajaud, Julie; Ribault, Catherine; Lucas, Catherine; Laurent, Alexis; Boudjema, Karim; Morel, Fabrice; Corlu, Anne; Compagnon, Philippe

    2012-01-01

    Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS) upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP), a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg) group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO) production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging, this preservation

  10. Phenotypic and functional characterization of macrophages with therapeutic potential generated from human cirrhotic monocytes in a cohort study

    Science.gov (United States)

    Moore, Joanna K.; Mackinnon, Alison C.; Wojtacha, Dvina; Pope, Caroline; Fraser, Alasdair R.; Burgoyne, Paul; Bailey, Laura; Pass, Chloe; Atkinson, Anne; Mcgowan, Neil W.A.; Manson, Lynn; Turner, Mark L.; Campbell, John D.M.; Forbes, Stuart J.

    2015-01-01

    Background aims Macrophages have complex roles in the liver. The aim of this study was to compare profiles of human monocyte-derived macrophages between controls and cirrhotic patients, to determine whether chronic inflammation affects precursor number or the phenotype, with the eventual aim to develop a cell therapy for cirrhosis. Methods Infusion of human macrophages in a murine liver fibrosis model demonstrated a decrease in markers of liver injury (alanine transaminase, bilirubin, aspartate transaminase) and fibrosis (transforming growth factor-β, α-smooth muscle actin, phosphatidylserine receptor) and an increase in markers of liver regeneration (matrix metalloproteinases [MMP]-9, MMP-12 and TNF-related weak inducer of apoptosis). CD14+ monocytes were then isolated from controls. Monocytes were matured into macrophages for 7 days using a Good Manufacturing Practice–compatible technique. Results There was no significant difference between the mean number of CD14+ monocytes isolated from cirrhotic patients (n = 9) and controls (n = 10); 2.8 ± SEM 0.54 × 108 and 2.5 ± 0.56 × 108, respectively. The mean yield of mature macrophages cultured was also not significantly different between cirrhotic patients and controls (0.9 × 108 ± 0.38 × 108, with more than 90% viability and 0.65 × 108 ± 0.16 × 108, respectively. Maturation to macrophages resulted in up-regulation of a number of genes (MMP-9, CCL2, interleukin [IL]-10 and TNF-related weak inducer of apoptosis). A cytokine and chemokine polymerase chain reaction array, comparing the control and cirrhotic macrophages, revealed no statistically significant differences. Conclusions Macrophages can be differentiated from cirrhotic patients' apheresis-derived CD14 monocytes and develop the same pro-resolution phenotype as control macrophages, indicating their suitability for clinical therapy. PMID:26342993

  11. New physiologically-relevant liver tissue model based on hierarchically cocultured primary rat hepatocytes with liver endothelial cells.

    Science.gov (United States)

    Xiao, Wenjin; Perry, Guillaume; Komori, Kikuo; Sakai, Yasuyuki

    2015-11-01

    To develop an in vitro liver tissue equivalent, hepatocytes should be cocultured with liver non-parenchymal cells to mimic the in vivo physiological microenvironments. In this work, we describe a physiologically-relevant liver tissue model by hierarchically organizing layers of primary rat hepatocytes and human liver sinusoidal endothelial cells (TMNK-1) on an oxygen-permeable polydimethylsiloxane (PDMS) membrane, which facilitates direct oxygenation by diffusion through the membrane. This in vivo-mimicking hierarchical coculture was obtained by simply proceeding the overlay of TMNK-1 cells on the hepatocyte layer re-formed on the collagen immobilized PDMS membranes. The comparison of hepatic functionalities was achieved between coculture and sandwich culture with Matrigel, in the presence and absence of direct oxygenation. A complete double-layered structure of functional liver cells with vertical contact between hepatocytes and TMNK-1 was successfully constructed in the coculture with direct oxygen supply and was well-maintained for 14 days. The hepatocytes in this hierarchical culture exhibited improved survival, functional bile canaliculi formation, cellular level polarization and maintenance of metabolic activities including Cyp1A1/2 activity and albumin production. By contrast, the two cell populations formed discontinuous monolayers on the same surfaces in the non-oxygen-permeable cultures. These results demonstrate that (i) the direct oxygenation through the PDMS membranes enables very simple formation of a hierarchical structure consisting of a hepatocyte layer and a layer of TMNK-1 and (ii) we may include other non-parenchymal cells in this format easily, which can be widely applicable to other epithelial organs. PMID:26304784

  12. Effect of cadmium pretreatment on liver regeneration after partial hepatectomy in rats

    International Nuclear Information System (INIS)

    In this study we examined the effect of cadmium pretreatment, administered 24 h before partial hepatectomy, on the liver regenerative process in rats, at different time intervals. The rate of 3H thymidine incorporation into hepatic DNA and the activity of the enzyme thymidine kinase were used as indices of liver proliferative capacity. Thymidine kinase, the rate-determining enzyme of DNA biosynthesis, was suppressed during the first hours following partial hepatectomy in the liver of cadmium pretreated animals. DNA biosynthesis was also strongly decreased in cadmium pretreated animals, by delaying the first peak of liver regeneration, compared with the partially hepatectomized ones. Biochemical parameters, mitotic index and proliferating cell nuclear antigen staining were also coestimated. The above data suggest that cadmium pretreatment suppressed the hepatic regenerative process, probably due to the inhibition of thymidine kinase. (orig./MG)

  13. Brain death induces apoptosis in donor liver of the rat

    NARCIS (Netherlands)

    van der Hoeven, JAB; Moshage, H; Schuurs, T; Nijboer, M; van Schilfgaarde, R; Ploeg, RJ

    2003-01-01

    Background. A difference in short- and long-term function between living-related and cadaveric donor organs is consistently shown in kidney- and liver-transplant studies. We hypothesize that this is caused by induction of apoptosis and inflammation of the potential graft because of the phase of brai

  14. Identification of ginkgolide B metabolites in urine and rat liver cytochrome P450 enzymes responsible for their formation in vitro

    Institute of Scientific and Technical Information of China (English)

    Dian-lei WANG; Yan LIANG; Wei-dong CHEN; Lin XIE; Guang-ji WANG; Xiao-dong LIU

    2008-01-01

    Aim:To identify metabolites of ginkgolide B in rat urine,the predominant metabo-lism of ginkgolide B and the major cytochrome (CYP) P450 enzymes responsible for the metabolism of ginkgolide B in rat liver microsomes.Methods:A liquid chromatography quadrupole mass spectrometer and liquid chromatography ion-trap-time-of-flight mass spectrometer with electrospray ionization in negative-ion mode were used for the structure elucidation of metabolites in rat urine and liver microsome incubation.Various selective CYP450 inhibitors were applied to inves-tigate their effects on the metabolism of ginkgolide B and the formation of the major metabolite in rat liver microsomes.Results:Three metabolites were identi-fied in rat urine.One hydroxyl metabolite of ginkgolide B were identified in rat liver microsomes,and quinidine uncompetitively inhibited the formation of the metabolite;its inhibitor constant (Ki) value for the inhibition of hydroxyl metabo-lite was estimated to be 8 μmol/L,whileα-naphthoflavone,ketoconazole,sulfaphenazole,and diethyidithiocarbamate had no inhibitory effects.Conclusion:Ginkgolide B was metabolized to its hydroxyl metabolite in rats,and CYP2D6 was the major rat CYP isoform responsible for the ginkgolide B metabolism in rat liver microsomes.

  15. Effects of Short Term Exposure of Atrazine on the Liver and Kidney of Normal and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Dinesh Babu Jestadi

    2014-01-01

    Full Text Available The present study evaluates the effects of short term (15 days exposure of low dose (300 μg kg−1 of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine on antioxidant status and markers of liver and kidney damage in normal (nondiabetic and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg−1 could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats.

  16. Establishment of a liver cancer model induced by DENA in Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Objective: To explore the feasible approach for establishment of a liver cancer model induced by N-nitrosodiethylamine (DENA) with Sprague-Dawley rat, and to provide ideal animal model for imaging diagnosis and interventional therapy. Methods: One-hundred and forty male SD rats were administrated with 0.95 g/L DENA for l0 weeks, and MRI was performed for inspecting pathological changes of rat livers on the following week. When the liver tumor was proved then the rat will be the candidate for sequential procedures, otherwise the animal continued under observation until next MRI examination after 4 weeks. DSA was done in 64 rats for detecting blood supply of liver tumors. Animals were sacrificed with an overdose of chloral hydrate, The representative tumor tissues were fixed in 10% formalin and 2.5% glutaraldehyde for light and electron microscopy analysis respectively. Alpha fetoprotein (AFP) and hepatocyte were assaied by immunohistochemistry technique in order to identify intrinsic trait of the harvested tumors. Results: The earliest induced tumor was detected on 11th week and the latest was on 20th week by MRI, and the median period was 13.9 weeks. Tumor size ranged from 2 mm to 40 mm in diameter. The rate of single and multi-induced tumor was 9.7% (7/72) and 90.3% (65/72), respectively. 87.7% (57/65) of the induced multiple tumors was with hepatocirrhosis and 18.1% of these tumors combined with extrahepatic neoplasm or metastasis. Plenty blood supply was proved by DSA in most of those tumors. Tumors not only derived from hepatocyte but also manifested positive expression of AFP. Histological types of these tumors include hepatocellular carcinoma (HCC) (92.0%, 66/72), intrahepatic cholangiocarcinoma (ICC) (4.0%, 3/72), and combined HCC and ICC (4.0%, 3/72), respectively. Electro-microscope analysis indicated that cytoplasm and organelle of induced tumors were abnormal distinctly compared with those of non-carcinomatous cells. Conclusion: DENA can induce ideal rat

  17. Laminin A, B1, B2, S and M subunits in the postnatal rat liver development and after partial hepatectomy

    DEFF Research Database (Denmark)

    Wewer, U M; Engvall, E; Paulsson, M; Yamada, Y; Albrechtsen, R

    1992-01-01

    The expression of laminin subunits (A, B1, B2, S and M) in the perisinusoidal space of the rat liver was studied in early postnatal life, in the adult, and after partial hepatectomy. In the perisinusoidal space of the normal adult rat, laminin was detected with polyclonal antibodies only in small...... liver (biliary ducts and blood vessels) irrespective of the age of animals exhibited B1, B2 and S immunoreactivity. Laminin A was restricted to the larger blood vessels and could not be detected in the biliary ducts. In the adult rat, immunoreactivity for the A-like M subunit was absent except for some...... neonatal rats as compared to adult rats. S-laminin mRNA could readily be demonstrated in neonatal rat livers by Northern blot analysis, whereas A and M could not. Expression of S and M-laminin transcripts were demonstrated by polymerase chain reaction, but we were unable to obtain a laminin A product...

  18. Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats

    Science.gov (United States)

    Mei, Nan; Guo, Lei; Liu, Ruqing; Fuscoe, James C; Chen, Tao

    2007-01-01

    Background Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats. Results Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a P-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail. Conclusion The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks

  19. Effects of soy components on blood and liver lipids in rats fed high-cholesterol diets

    Institute of Scientific and Technical Information of China (English)

    Ching-Yi Lin; Cheng-Yu Tsai; Shyh-Hsiang Lin

    2005-01-01

    AIM: To assess the effects of soy protein, isoflavone, and saponin on liver and blood lipid in rats that consumed high-cholesterol diets.METHODS: High-cholesterol diets (1%) with or without soy material were fed to 6-wk-old male Sprague-Dawley rats for 8 wk. Blood lipids, liver lipids, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) levels were measured. The in vitro bile acid-binding ability of soy materials was analyzed.RESULTS: The results of in vitro studies showed that soy protein isolate had a significantly higher bile acid-binding ability (8.4±0.8%) than soy saponin (3.1±0.7%) and isoflavone (1.3±0.4%, P<0.05). On the other hand, at the end of the experimental period, rats that consumed soy protein diets had lower GOT and GPT levels than rats that consumed casein under high-cholesterol diets.Rats that consumed soy protein also had lower total cholesterol (TC) levels in the liver than those that consumed casein under high-cholesterol diets. Rats that consumed the soy protein diet containing both saponin and isoflavone had lower hepatic TC level than those that consumed the soy protein diet without isoflavone alone.The effect of different types of proteins on triglyceride was not significant.CONCLUSION: Consumption of soy provided benefits to control lipid levels under high-cholesterol dieting conditions in this rat model of hypercholesterolemia. The major component that reduced hepatic TC was not saponin, but possibly isoflavone.

  20. Effect of Pomegranate Hull Extract on Liver Neoplastic Changes in Rats: More than an Antioxidant.

    Science.gov (United States)

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Abd El-Fattah, Eslam E

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. The current work was designed to elucidate the molecular mechanisms underlying the antitumorigenic effect of pomegranate hull extract (PHE) in livers of rats exposed to the hepatocarcinogen diethyl nitrosamine (DENA) with emphasis on oxidative stress, proliferation, and apoptosis. Male albino rats were divided into three groups: normal control, DENA group, and PHE group. PHE was given to rats orally 3 times weekly for 10 wk, 4 wk before and 6 wk after DENA (200 mg/kg, single i.p. dose). The results indicated a prophylactic effect of PHE against neoplastic changes in the liver, which was evidenced by the decrease of tumor size, liver index, and the anti-apoptotic protein Bcl-2; and the increase of glutathione. PHE group also showed decreased expression of liver cyclin D1 and β-catenin genes compared with DENA group. It is proved that PHE has antitumorigenic effect and could be a candidate for anticancer drugs. PMID:27383944

  1. Radiobiological effect of abdominal X-ray hypo-fraction irradiation on Wistar rats liver

    Institute of Scientific and Technical Information of China (English)

    Peng Qi; Yongheng An; Hongsheng Yu; Xinjia He

    2012-01-01

    Objective: The aim of our study was to investigate the impact of abdominal hypo-fraction irradiation on liver dam-age in rats so as to provide a reference for its clinical application. Methods: A total of 100 Wistar rats were equally randomized to five groups as control, 4 Gy, 6 Gy, 8 Gy and 12 Gy group, and the corresponding fractionated doses were offered. Liver functions were examined at the 2nd, 4th, 6th, 8th and 10th week after irradiation. Morphological changes were observed by HE staining. Expressions of Bcl-2 and Bax were examined by immunohistochemical technique. Results: In all irradiation groups, hepatocellular swell, degeneration, necrosis and even hepatic fibrosis could be seen. The differences of the liver coef-ficient, Glutamyl pyruvic transaminase (GPT), Glutamyl oxaloacetic transaminase (GOT) were significant among the groups and different time points (F = 11.833–781.972, F = 20.857–264.692, P < 0.001). Expressions of Bcl-2 and Bax were signifi-cantly different between each group (F = 211.607, 116.577; P < 0. 001), and between each time point (F = 54.083, 68.749; P < 0. 001). Conclusion: Compare with conventional fraction, abdominal hypo-fraction irradiation may cause radiation damage to rat liver, being dose-and-time dependent. Up-regulation of activating apoptosis protein Bax and down-regulation of inhibiting apoptosis protein Bcl-2 may involve in the process.

  2. Effect of Platelet-Rich Plasma on CCl4-Induced Chronic Liver Injury in Male Rats.

    Science.gov (United States)

    Hesami, Zahra; Jamshidzadeh, Akram; Ayatollahi, Maryam; Geramizadeh, Bita; Farshad, Omid; Vahdati, Akbar

    2014-01-01

    Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1 mL/kg, i.p. 1 : 1 in olive oil) twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5 mL/kg, s.c.) two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP. PMID:24707405

  3. Differentiation of rat bone marrow stem cells in liver after partial hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Yu-Tao Zhan; Yu Wang; Lai Wei; Bin Liu; Hong-Song Chen; Xu Cong; Ran Fei

    2006-01-01

    AIM: To investigate the differentiation of rat bone marrow stem cells in liver after partial hepatectomy.METHODS: Bone marrow cells were collected from the tibia of rat with partial hepatectomy, the medial and left hepatic lobes were excised. The bone marrow stem cells (Thy+CD3-CD45RA- cells) were enriched from the bone marrow cells by depleting red cells and fluorescence-activated cell sorting. The sorted bone marrow stem cells were labeled by PKH26-GL in vitro and autotransplanted by portal vein injection. After 2wk, the transplanted bone marrow stem cells in liver were examined by the immunohistochemistry of albumin (hepatocyte-specific marker).RESULTS: The bone marrow stem cells (Thy+CD3-CD45RA- cells) accounted for 2.8% of bone marrow cells without red cells. The labeling rate of 10μM PKH26-GL on sorted bone marrow stem cells was about 95%.There were sporadic PKH26-GL-labeled cells among hepatocytes in liver tissue section, and some of the cells expressed albumin.CONCLUSION: Rat bone marrow stem cells can differentiate into hepatocytes in regenerative environment and may participate in liver regeneration after partial hepatectomy.

  4. Possible Protective Effect of Kombucha Tea Ferment on Carbon Tetrachloride Induced Liver Damage in Irradiated Rats

    International Nuclear Information System (INIS)

    This study has shown that administration of kombucha ferment tea (KT) to rats improved the damage caused in livers of animals treated with toxic chemicals such as carbon tetrachloride (CCL4) and/ or exposed to y-irradiation. This work was undertaken to evaluate the possible protective effects of treatment with KT ferment in rat liver after a long-term treatment with CCL4 alone and with subsequent y-irradiation. Hepatic pathological changes observed in the CCL4-treated rats included increased serum alanine transaminase (ALT) , aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) activities as well as concentration of bilirubin in addition to a decrease in the concentration of serum albumin and total antioxidant capacity (TAC). Consistent with these changes, the increase in oxidative stress markers expressed as malondialdehyde (MDA) concentration and depletion in glutathione (GSH) contents in liver was observed. 24 h after the last dose of KT administration in a group of animals treated with CCL4 and/ or radiation exposure cessation, the pathological changes were recovered. These results demonstrate that most of the pathological alterations in the liver in response to CCL4 and/ or radiation exposure intoxication are recoverable upon treatment with KT ferments

  5. Influence of psyllium preparations on plasma and liver lipids of cholesterol-fed rats.

    Science.gov (United States)

    Kritchevsky, D; Tepper, S A; Klurfeld, D M

    1995-01-01

    Rats were fed a semi purified diet containing 0.5% cholesterol and 10% fiber (cellulose, pectin, psyllium seed and defatted psyllium husk). One additional group of rats was fed cholesterol (0.5%) as part of a fiber-free diet and another was fed the fiber free diet without cholesterol. Cellulose had virtually no effect on serum or liver lipids. Pectin had a lipid lowering effect. Psyllium seed exerted an effect on total serum cholesterol equal to that of pectin but gave higher levels of HDL-cholesterol. The effects of psyllium seed on liver lipids were more pronounced than those of pectin. Defatted psyllium husk feeding virtually normalized liver size and serum triglyceride levels and produced lower serum total cholesterol levels and higher HDL-cholesterol than observed in normal controls. Defatted psyllium husk feeding also yielded liver lipid values which were in the normal range. Fecal wet and dry weights were significantly higher in rats fed either psyllium preparation. PMID:8833230

  6. Toxicity Effect of Nigella Sativa on the Liver Function of Rats

    Directory of Open Access Journals (Sweden)

    Mohamad Hafanizam Bin Hassan

    2013-02-01

    Full Text Available Purpose: The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue. Methods: Twenty four male Sprague Dawley rats were allotted randomly to four groups including: control (taking normal diet; low dose (supplemented with 0.01 g/kg/day Nigella sativa; normal dose (supplemented with 0.1 g/kg/day Nigella sativa and high dose (supplemented with 1 g/kg/day Nigella sativa. All of supplements administered in powder form mixed with rats’ pellet for 28 days. To assess liver toxicity, liver enzymes measurement and histological study were done at the end of supplementation. Results: The finding revealed that there was no significant change in serum alanine aminotransferase (ALT and aspartate aminotransferase (AST between treatment groups. Histopathological study showed very minimal and mild changes in fatty degeneration in normal and high doses of Nigella sativa treated group. Inflammation and necrosis were absent. Conclusion: The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg supplemented for a period of 28 days resulted no changes in liver enzymes level and did not cause any toxicity effect on the liver function.

  7. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  8. Homogeneous distribution of phosphofructokinase in the rat liver acinus: a quantitative histochemical study.

    Science.gov (United States)

    Frederiks, W M; Marx, F; van Noorden, C J

    1991-10-01

    A quantitative histochemical method was developed for the demonstration in rat liver of the activity of phosphofructokinase, one of the enzymes assumed to be rate-limiting for glycolysis. The procedure was based on the reduction of a tetrazolium salt as final electron acceptor and a multistep reaction using the exogenous or endogenous auxiliary enzymes aldolase, triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase. The highest activity was found in unfixed cryostat sections of rat liver when the incubation medium contained 17% (wt/vol) polyvinyl alcohol, 100 mmol/L Tris-maleate buffer (pH 8.4), 20 mmol/L fructose-6-phosphate, 2 mmol/L ATP, 2 mmol/L MgCl2, 5.9 mmol/L NAD+, 0.47 mmol/L 1-methoxyphenazine methosulfate, 5 mmol/L sodium azide and 5 mmol/L Nitro BT. The addition of auxiliary enzymes was not necessary to demonstrate maximum activity in rat liver. The specificity of the reaction was proven by the absence of any specific (test minus control) reaction when the incubation was performed in the presence of 25 mmol/L phosphoenolpyruvate, a competitive inhibitor of phosphofructokinase. Cytophotometric analysis revealed that linear relationships exist between the amount of specific reaction product formed and incubation time and the section thickness. The Km values for fructose-6-phosphate and the Vmax values were not significantly different in periportal and pericentral areas of livers from either normally fed or 24-hr-fasted rats. The homogeneous distribution of phosphofructokinase activity in the liver acinus is in line with biochemical findings using hepatocytes isolated from the two different areas showing that these cells contained similar amounts of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1833303

  9. Attenuation of portal hypertension by natural taurine in rats with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Jian Liang; Xin Deng; Zhi-Xiu Lin; Li-Chun Zhao; Xi-Liu Zhang

    2009-01-01

    AIM: To investigate the inhibitory effect of natural taurine (Ntau) on portal hypertension (PHT) in rats with experimentally-induced liver cirrhosis (LC).METHODS: Experimentally-induced LC Wistar rats (20 rats/group) were treated with either oral saline or oral Ntau for 6 consecutive weeks. Evaluation parameters included portal venous pressure (PVP), portal venous resistance (PVR), portal venous flow (PVF), splanchnic vascular resistance (SVR) and mean arterial pressure (MAP). Vasoactive substance levels including nitric oxide (NO), nitric oxide synthase (NOS) and cyclic guanosine monophosphate (cGMP) were also measured.Histological investigation of type Ⅰ and Ⅲ collagen (COL Ⅰ and Ⅲ) and transforming growth factor-β1 (TGF-β1) was also performed. RESULTS: Treatment with Ntau (1) significantly decreased PVP, PVR and PVF, and increased MAP and SVP; (2) markedly increased the vascular compliance and reduced the zero-stress of the portal vein; (3) markedly decreased the amount of NO and cGMP and activity of NOS; and (4) improved the pathological status of the liver tissue and reduced the expression of COL Ⅰ, COL Ⅲ and TGF-β1. CONCLUSION: Ntau inhibited the LC-induced PHT by improving hyperdynamic circulation, morphology of liver and biomechanical properties of the portal vein in experimentally-induced LC rats.

  10. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    1981-01-01

    The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

  11. 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. PMID:26528730

  12. Application of near-infrared time-resolved spectroscopy to rat liver - a preliminary report for surgical application

    International Nuclear Information System (INIS)

    The applicability of near-infrared time-resolved spectroscopy to rat liver surgery was investigated. First, the technical reliability in determining the absorption coefficient (μa) and reduced scattering coefficient (μs) of the liver was checked. Next, boundary effects in determining μa and μs' of the rat liver were examined. Finally, changes in μa and μs' of rat liver with ischaemia were directly measured by TRS. Our TRS system showed that the μa value held a linear correlation with the ink concentration in a lipid emulsion until μa reached 1.2 cm-1, while the μs' was fairly independent. The μa values of blood-free rat liver and blood-containing rat liver at 780 nm were observed to be 0.43cm-1 and 0.67cm-1 by using the matching method, indicating that TRS is reliable in determining μa and μs' of the liver. Possible errors in μa and μs' determination due to the boundary effects of the rat liver were as small as 7%, when the μa value was as high as observed for the liver. The oxygen saturation of haemoglobin (SO2) was changed from 64.9% to 8.0%, and the haemoglobin content (THB) from 189.1 μM to 131.6 μM by ischaemia. μs' dynamically changed in the range 7.06cm-1 to 11.36cm-1. We conclude that time-resolved measurement is applicable in the high-μa region observed in the liver, and can give quantitative estimations of SO2 and THB in the liver. (author)

  13. Clinical usefulness of Tc-99M pertechnetate per-rectal portal scintigraphy in evaluation the severity of portal hypertension in cirrhotic patients

    International Nuclear Information System (INIS)

    Objectives: Variceal hemorrhage is a potentially life-threatening complication in cirrhotic patients. Identification of patients at high risk for bleeding is particularly important. The aim of this study was to determine the clinical usefulness of per-rectal portal scintigraphy in evaluation the severity of portal hypertension in cirrhotic patients in terms of correlation between cirrhosis and classic indicators of hepatic functional reserve and identifying the difference of the portal shunt index (PSI) of the bleeding esophageal varices group and non-bleeding esophageal varices group. Material and methods: Portal circulations in 15 healthy volunteer's and in 67 patients with cirrhosis were evaluated by Tc-99m pertechnetate per-rectal p. ortal scintigraphy. Tc-99m pertechnetate (550 MBq) was instilled into the upper rectum, and dynamic images were taken. Radioactivity curves of the liver and the heart were generated sequentially. Through the analysis of these curves, the PSI was determined by calculating the ratio of counts of the liver to counts of the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. Results: The results, expressed as PSI were: 13.63 +/- 6.28 % in healthy subjects and 66.32+/-22.80 % in cirrhotic patients. Of these, the PSIs were 56036 +/- 27.14 % in 31 cirrhotic patients without esophageal varices, and 74.89 +/- 13.62 % in 36 cirrhotic patients with esophageal varices. The PSI was significantly lower in cirrhotic patients without bleeding esophageal vances (BEV) than those with BEV (p=0.001). The PSI calculated with this method was correlated with the serum albumin, the serum bilirubin and the Child-Pugh's score. Conclusion: The Tc-99m pertechnetate per-rectal portal scintigraphy has clinical usefulness as a relatively non-invasive method of choice for quantitative evaluating the severity of portal hypertension in cirrhotic patients. (authors)

  14. PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptidein rat liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Uwe Grutzner; Melanie Keller; Michael Bach; Alexandra K Kiemer; Herbert Meissner; Manfred Bilzer; Stefan Zahler; Alexander L Gerbes; Angelika M Vollmar

    2006-01-01

    AIM: To investigate the in vivo effect of atrial natriuretic peptide (ANP) and its signaling pathway during orthotopic rat liver transplantation.METHODS: Rats were infused with NaCl, ANP (5 μg/kg), wortmannin (WM, 16 μg/kg), or a combination of both for 20 min. Livers were stored in UW solution (4°C) for 24 h, transplanted and reperfused. Apoptosis was examined by caspase-3 activity and TUNEL staining.Phosphorylation of Akt and Bad was visualized by Western blotting and phospho-Akt-localization by confocai microscopy.RESULTS: ANP-pretreatment decreased caspase-3activity and TUNEL-positive cells after cold ischemia,indicating antiapoptotic effects of ANP in vivo. The antiapoptotic signaling of ANP was most likely caused by phosphorylation of Akt and Bad, since pretreatment with PI 3-kinase inhibitor WM abrogated the ANP-induced reduction of caspase-3 activity. Interestingly, analysis of liver tissue by confocal microscopy showed translocation of phosphorylated Akt to the plasma membrane of hepatocytes evoked by ANP.CONCLUSION: ANP activates the PI-3-kinase pathway in the liver in vivo leading to phosphorylation of Bad,an event triggering antiapoptotic signaling cascade in ischemic liver.

  15. Protective effects of garcinol on dimethylnitrosamine-induced liver fibrosis in rats.

    Science.gov (United States)

    Hung, Wei-Lun; Tsai, Mei-Ling; Sun, Pei-Pei; Tsai, Chen-Yu; Yang, Chin-Chou; Ho, Chi-Tang; Cheng, An-Chin; Pan, Min-Hsiung

    2014-11-01

    Garcinol, a polyisoprenylated benzophenone derivative, mainly isolated from Garcinia indica fruit rind, has been suggested to exhibit many biological benefits including antioxidative, anti-inflammatory, and anti-tumor activities. The aim of this study is to evaluate the protective effects of garcinol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. The administration of DMN for six consecutive weeks resulted in the decrease of body weights, the elevation of serum aminotransferases, as well as histological lesions in livers. However, oral administration of garcinol remarkably inhibited the elevation of aspartate transaminase (AST) and relieved liver damage induced by DMN. Furthermore, our results revealed that garcinol not only effectively reduced the accumulation of extracellular matrix (ECM) components but also inhibited the expression of α-smooth muscle actin (α-SMA) in livers. The expression of transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad 2 and Smad 3 were also suppressed by garcinol supplementation. In conclusion, our current study suggested that garcinol exerted hepatoprotective and anti-fibrotic effects against DMN-induced liver injury in rats. PMID:25183344

  16. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

    Science.gov (United States)

    Tanvir, E M; Afroz, R; Chowdhury, Maz; Gan, S H; Karim, N; Islam, M N; Khalil, M I

    2016-09-01

    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals. PMID:26519480

  17. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

    International Nuclear Information System (INIS)

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved

  18. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

    Directory of Open Access Journals (Sweden)

    R.N. Silva

    2014-09-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C and high-fat (HF diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim or a sedentary group (C-Sed and HF-Sed. Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

  19. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats.

    Science.gov (United States)

    Silva, R N; Bueno, P G; Avó, L R S; Nonaka, K O; Selistre-Araújo, H S; Leal, A M O

    2014-09-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved. PMID:25075578

  20. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

    Energy Technology Data Exchange (ETDEWEB)

    Silva, R.N. [Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Bueno, P.G. [Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Avó, L.R.S. [Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Nonaka, K.O.; Selistre-Araújo, H.S. [Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Leal, A.M.O. [Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

    2014-07-25

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

  1. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Peres, G.B. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Juliano, M.A. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Biofísica, São Paulo, SP, Brasil, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Aguiar, J.A.K.; Michelacci, Y.M. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-05-09

    It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10{sup th} or the 30{sup th} day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10{sup th}, but not on the 30{sup th} day. Sulfatase decreased 30% on the 30{sup th} day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.

  2. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

    Directory of Open Access Journals (Sweden)

    Stéphanie Lacotte

    Full Text Available Liver transplantation for hepatocellular carcinoma (HCC results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01, increased liver function tests (p<0.01, the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005, which was related to an increased natural killer (NK cell frequency (p<0.05 and a higher monocyte/macrophage activation level (p<0.01. Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005, and liver monocyte/macrophage activation levels (p<0.01 were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05 and on NK c