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Sample records for rat liver molecular

  1. Alterations in the molecular species of rat liver lecithin by corn-oil feeding to essential fatty acid-deficient rats as a function of time

    NARCIS (Netherlands)

    Golde, L.M.G. van; Pieterson, W.A.; Deenen, L.L.M. van

    1968-01-01

    The present paper describes, as a function of time, the qualitative and quantitative alterations in the molecular species pattern of rat liver lecithin which are observed when corn oil is fed to essential fatty acid-deficient rats. One of the most important changes observed was a very rapid

  2. Insulin-like growth factor-II (IGF II) receptor from rat brain is of lower apparent molecular weight than the IGF II receptor from rat liver

    International Nuclear Information System (INIS)

    McElduff, A.; Poronnik, P.; Baxter, R.C.

    1987-01-01

    The binding subunits of the insulin and insulin-like growth factor-I (IGF I) receptors from rat brain are of lower molecular weight than the corresponding receptor in rat liver, possibly due to variations in sialic acid content. We have compared the IGF II receptor from rat brain and rat liver. The brain receptor is of smaller apparent mol wt (about 10 K) on sodium dodecyl sulfate polyacrylamide gel electrophoresis. This size difference is independent of ligand binding as it persists in iodinated and specifically immunoprecipitated receptors. From studies of wheat germ agglutinin binding and the effect of neuraminidase on receptor mobility, we conclude that this difference is not simply due to variations in sialic acid content. Treatment with endoglycosidase F results in reduction in the molecular size of both liver and brain receptors and after this treatment the aglycoreceptors are of similar size. We conclude that in rat brain tissue the IGF II receptor like the binding subunits of the insulin and IGF I receptors is of lower molecular size than the corresponding receptors in rat liver. This difference is due to differences in N-linked glycosylation

  3. The effect of dietary fat on the molecular species of lecithin from rat liver

    NARCIS (Netherlands)

    Golde, L.M.G. van; Deenen, L.L.M. van

    1966-01-01

    1. 1. Lecithins from the liver of rats maintained on diets devoid of essential fatty acids or supplemented with coconut oil or corn oil revealed significant differences in fatty acid composition, whilst monomolecular films of these lecithin samples exhibited only limited differences in force-area

  4. Molecular mechanisms of toxic effects of fotemustine in rat hepatocytes and subcellular rat liver fractions.

    NARCIS (Netherlands)

    Brakenhoff, J.P.G.; Commandeur, J.N.M.; Wormhoudt, L.W.; Groot, E.J.; Vermeulen, N.P.E.

    1996-01-01

    Fotemustine is a clinically used DNA-alkylating 2-chloroethyl-substituted N-nitrosourea, which sometimes shows signs of haematotoxicity and reversible liver and renal toxicity as toxic side-effects. Mechanistic data on these side-effects are scarce and incomplete. In this study, firstly the

  5. Metabolic alterations by clofibric acid in the formation of molecular species of phosphatidylcholine in rat liver.

    Science.gov (United States)

    Mizuguchi, H; Kudo, N; Kawashima, Y

    2001-10-01

    The mechanism by which p-chlorophenoxyisobutyric acid (clofibric acid) induces striking changes in the proportion of the molecular species of phosphatidylcholine (PC) in rat liver was studied. Treatment of rats with clofibric acid strikingly increased the content of 1-palmitoyl-2-oleoyl (16:0-18:1) PC, but decreased the contents of 1-palmitoyl-2-docosahexaenoyl (16:0-22:6), 1-stearoyl-2-arachidonoyl (18:0-20:4), and 1-stearoyl-2-linoleoyl (18:0-18:2) PC; the drug did not change the content of 1-palmitoyl-2-arachidonoyl (16:0-20:4) PC. The mechanism underlying these changes has been investigated with regard to the in vivo formation of the molecular species of PC by: (i) de novo synthesis, (ii) reacylation, and (iii) methylation of phosphatidylethanolamine (PE). We found that (i) the incorporation of [3H]glycerol, which was injected intravenously, into 16:0-18:1 diacylglycerol (DG) and 16:0-18:1 PC was increased markedly by clofibric acid feeding without changing the substrate specificity of CDP-choline:DG cholinephosphotransferase, (ii) the in vivo formation of 16:0-18:1 and 16:0-20:4 PC from 1-16:0-[3H]glycerophosphocholine (GPC), which was injected intraportally, was increased markedly by clofibric acid feeding, and (iii) the incorporation of [14C]ethanolamine, which was injected intravenously into 16:0-22:6, 18:0-22:6, and 18:0-20:4 PC, was decreased by clofibric acid feeding; the extent of the decrease in 16:0-20:4 PC was less than that of 18:0-20:4 PC. It was concluded, therefore, that (i) clofibric acid selectively increased the content and proportion of 16:0-18:1 PC by enhancing both the CDP-choline pathway and the remodeling of the pre-existing PC molecule, and (ii) the drug kept the content of 16:0-20:4 PC unchanged by stimulating the remodeling of the pre-existing PC molecule, whereas the formation of other more long chain, polyunsaturated molecular species, such as 16:0-22:6, 18:0-22:6, and 18:0-20:4, was decreased owing to the suppression of PE

  6. Molecular classification of liver cirrhosis in a rat model by proteomics and bioinformatics.

    Science.gov (United States)

    Xu, Xiu-Qin; Leow, Chon K; Lu, Xin; Zhang, Xuegong; Liu, Jun S; Wong, Wing-Hung; Asperger, Arndt; Deininger, Sören; Eastwood Leung, Hon-Chiu

    2004-10-01

    Liver cirrhosis is a worldwide health problem. Reliable, noninvasive methods for early detection of liver cirrhosis are not available. Using a three-step approach, we classified sera from rats with liver cirrhosis following different treatment insults. The approach consisted of: (i) protein profiling using surface-enhanced laser desorption/ionization (SELDI) technology; (ii) selection of a statistically significant serum biomarker set using machine learning algorithms; and (iii) identification of selected serum biomarkers by peptide sequencing. We generated serum protein profiles from three groups of rats: (i) normal (n=8), (ii) thioacetamide-induced liver cirrhosis (n=22), and (iii) bile duct ligation-induced liver fibrosis (n=5) using a weak cation exchanger surface. Profiling data were further analyzed by a recursive support vector machine algorithm to select a panel of statistically significant biomarkers for class prediction. Sensitivity and specificity of classification using the selected protein marker set were higher than 92%. A consistently down-regulated 3495 Da protein in cirrhosis samples was one of the selected significant biomarkers. This 3495 Da protein was purified on-chip and trypsin digested. Further structural characterization of this biomarkers candidate was done by using cross-platform matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) peptide mass fingerprinting (PMF) and matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) tandem mass spectrometry (MS/MS). Combined data from PMF and MS/MS spectra of two tryptic peptides suggested that this 3495 Da protein shared homology to a histidine-rich glycoprotein. These results demonstrated a novel approach to discovery of new biomarkers for early detection of liver cirrhosis and classification of liver diseases.

  7. Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.

    Science.gov (United States)

    Alkafafy, Mohamed El-Sayed; Ibrahim, Zein Shaban; Ahmed, Mohamed Mohamed; El-Shazly, Samir Ahmed

    2015-06-01

    The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure. © The Author(s) 2015.

  8. Molecular magnetic resonance imaging of activated hepatic stellate cells with ultrasmall superparamagnetic iron oxide targeting integrin αvβ3 for staging liver fibrosis in rat model

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    Zhang C

    2016-03-01

    Full Text Available Caiyuan Zhang,1,* Huanhuan Liu,1,* Yanfen Cui,1,* Xiaoming Li,1 Zhongyang Zhang,1 Yong Zhang,2 Dengbin Wang1 1Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 2MR Advanced Application and Research Center, GE Healthcare China, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To evaluate the expression level of integrin αvβ3 on activated hepatic stellate cells (HSCs at different stages of liver fibrosis induced by carbon tetrachloride (CCl4 in rat model and the feasibility to stage liver fibrosis by using molecular magnetic resonance imaging (MRI with arginine-glycine-aspartic acid (RGD peptide modified ultrasmall superparamagnetic iron oxide nanoparticle (USPIO specifically targeting integrin αvβ3.Materials and methods: All experiments received approval from our Institutional Animal Care and Use Committee. Thirty-six rats were randomly divided into three groups of 12 subjects each, and intraperitoneally injected with CCl4 for either 3, 6, or 9 weeks. Controls (n=10 received pure olive oil. The change in T2* relaxation rate (ΔR2* pre- and postintravenous administration of RGD-USPIO or naked USPIO was measured by 3.0T clinical MRI and compared by one-way analysis of variance or the Student’s t-test. The relationship between expression level of integrin αvβ3 and liver fibrotic degree was evaluated by Spearman’s ranked correlation.Results: Activated HSCs were confirmed to be the main cell types expressing integrin αvβ3 during liver fibrogenesis. The protein level of integrin αv and β3 subunit expressed on activated HSCs was upregulated and correlated well with the progression of liver fibrosis (r=0.954, P<0.001; r=0.931, P<0.001, respectively. After injection of RGD-USPIO, there is significant difference in ΔR2* among rats treated with 0, 3, 6, and 9 weeks of CCl4 (P<0.001. The accumulation of iron particles in fibrotic liver specimen is

  9. Isolating Lysosomes from Rat Liver.

    Science.gov (United States)

    Pryor, Paul R

    2016-04-01

    This protocol describes the generation of a fraction enriched in lysosomes from rat liver. The lysosomes are rapidly isolated using density-gradient centrifugation with gradient media that retain the osmolarity of the lysosomes such that they are functional and can be used in in vitro assays. © 2016 Cold Spring Harbor Laboratory Press.

  10. Molecular imaging of enhanced Na + expression in the liver of total sleep deprived rats by TOF-SIMS

    Science.gov (United States)

    Chang, Hung-Ming; Chen, Bo-Jung; Wu, Un-In; Huang, Yi-Lun; Mai, Fu-Der

    2008-12-01

    Sleep disorder is associated with metabolic disturbances, which was related to oxidative stress and subsequently sodium overload. Since liver plays important roles in metabolic regulation, present study is aimed to determine whether hepatic sodium, together with oxidative stress, would significantly alter after total sleep deprivation (TSD). Sodium ion was investigated by time-of-flight secondary ion mass spectrometry (TOF-SIMS). Parameter for oxidative stress was examined by heat shock protein-25 (HSP-25) immunohistochemistry. TOF-SIMS spectrum indicated that hepatic Na +/K + ratio counting as 82.41 ± 9.5 was obtained in normal rats. Sodium ions were distributed in hepatocytes with several aggregations. However, following TSD, the intensity for Na +/K + ratio was relatively increased (101.94 ± 6.9) and signals for sodium image were strongly expressed throughout hepatocytes without spatial localization. Quantitative analysis revealed that HSP-25 staining intensity is 1.78 ± 0.27 in TSD rats, which was significantly higher than that of normal ones (0.68 ± 0.15). HSP-25 augmentation suggests that hepatocytes suffer from oxidative stress following TSD. Concerning oxidative stress induced sodium overload would impair metabolic function; enhanced hepatic sodium expression after TSD may be a major cause of TSD relevant metabolic diseases.

  11. Proteomics-Based Identification of the Molecular Signatures of Liver Tissues from Aged Rats following Eight Weeks of Medium-Intensity Exercise

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    Fanghui Li

    2016-01-01

    Full Text Available Physical activity has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. Here, by combining functional and proteomics analyses, we examined how hepatic phenotypes might respond to exercise treatment in aged rats. 16 male aged (20 months old SD rats were divided into exercise and parallel control groups at random; the exercise group had 8 weeks of treadmill training with medium intensity. Whole protein samples of the liver were extracted from both groups and separated by two-dimensional gel electrophoresis. Alternatively objective protein spots with >2-fold difference in expression were selected for enzymological extraction and MS/MS identification. Results show increased activity of the manganese superoxide dismutase and elevated glutathione levels in the livers of exercise-treated animals, but malondialdehyde contents obviously decreased in the liver of the exercise group. Proteomics-based identification of differentially expressed proteins provided an integrated view of the metabolic adaptations occurring in the liver proteome during exercise, which significantly altered the expression of several proteins involved in key liver metabolic pathways including mitochondrial sulfur, glycolysis, methionine, and protein metabolism. These findings indicate that exercise may be beneficial to aged rats through modulation of hepatic protein expression profiles.

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

    International Nuclear Information System (INIS)

    Cimica, Velasco; Batusic, Danko; Haralanova-Ilieva, Borislava; Chen, Yonglong; Hollemann, Thomas; Pieler, Tomas; Ramadori, Giuliano

    2007-01-01

    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

  13. Threonine phosphorylation of rat liver glycogen synthase

    International Nuclear Information System (INIS)

    Arino, J.; Arro, M.; Guinovart, J.J.

    1985-01-01

    32 P-labeled glycogen synthase specifically immunoprecipitated from 32 P-phosphate incubated rat hepatocytes contains, in addition to [ 32 P] phosphoserine, significant levels of [ 32 P] phosphothreonine. When the 32 P-immunoprecipitate was cleaved with CNBr, the [ 32 P] 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 32 P-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

  14. Ectopic Liver Tissue Formation in Rats with Induced Liver Fibrosis

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    Bauyrzhan Umbayev

    2014-12-01

    Full Text Available Introduction: The possible alternative approach to whole-organ transplantation is a cell-based therapy, which can also be used as a "bridge" to liver transplantation.  However, morphological and functional changes in the liver of patients suffering from chronic liver fibrosis and cirrhosis restrict the effectiveness of direct cell transplantation. Therefore, extra hepatic sites for cell transplantation, including the spleen, pancreas, peritoneal cavity, and subrenal capsule, could be a useful therapeutic approach for compensation of liver functions. However, a method of transplantation of hepatocytes into ectopic sites is needed to improve hepatocyte engraftment. Previously published data has demonstrated that mouse lymph nodes can support the engraftment and proliferation of hepatocytes as ES and rescue Fah mice from lethal liver failure. Thus, the aim of the study was to evaluate the engraftment of i.p. injected allogeneic hepatocytes into extra hepatic sites in albino rats with chemically induced liver fibrosis (LF. Materials and methods: Albino rats were randomly divided into 4 groups: (1 intact group (n = 18; (2 rats with induced LF (n = 18; (3 rats with induced LF and transplanted with hepatocytes (n = 18; (4 as a control, rats were treated with cyclosporine A only (n = 18. In order to prevent an immune response, groups 2 and 3 were subjected to immunosuppression by cyclosporine A (25 mg/kg per day. LF was induced using N-nitrosodimethylamine (NDMA, i.p., 10 mg/kg, three times a week for 4 weeks and confirmed by histological analysis of the liver samples. Hepatocytes transplantation (HT was performed two days after NDMA exposure cessation by i.p. injection of 5×106 freshly isolated allogeneic hepatocytes. Liver function was assessed by quantifying blood biochemical parameters (ALT, AST, GGT, total protein, bilirubin, and albumin at 1 week, 1 month, and 2 months after hepatocytes transplantation (HT. To confirm a hepatocytes

  15. Age dependence of rat liver function measurements

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

    1989-01-01

    Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body...... weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver...

  16. Chronological protein synthesis in regenerating rat liver.

    Science.gov (United States)

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

    2015-07-01

    Liver regeneration has been studied for decades; however, its regulation remains unclear. In this study, we report a dynamic tracing of protein synthesis in rat regenerating liver with a new proteomic technique, (35) S in vivo labeling analysis for dynamic proteomics (SiLAD). Conventional proteomic techniques typically measure protein alteration in accumulated amounts. The SiLAD technique specifically detects protein synthesis velocity instead of accumulated amounts of protein through (35) S pulse labeling of newly synthesized proteins, providing a direct way for analyzing protein synthesis variations. Consequently, protein synthesis within short as 30 min was visualized and protein regulations in the first 8 h of regenerating liver were dynamically traced. Further, the 3.5-5 h post partial hepatectomy (PHx) was shown to be an important regulatory turning point by acute regulation of many proteins in the initiation of liver regeneration. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

  18. Coenzyme metabolism in rat liver transketolase

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 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 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

  20. Purification and characterization of rat liver minoxidil sulphotransferase.

    Science.gov (United States)

    Hirshey, S J; Falany, C N

    1990-01-01

    Minoxidil (Mx), a pyrimidine N-oxide, is used therapeutically as an antihypertensive agent and to induce hair growth in patients with male pattern baldness. Mx NO-sulphate has been implicated as the agent active in producing these effects. This paper describes the purification of a unique sulphotransferase (ST) from rat liver cytosol that is capable of catalysing the sulphation of Mx. By using DEAE-Sepharose CL-6B chromatography, hydroxyapatite chromatography and ATP-agarose affinity chromatography, Mx-ST activity was purified 240-fold compared with the activity in cytosol. The purified enzyme was also capable of sulphating p-nitrophenol (PNP) at low concentrations (less than 10 microM). Mx-ST was purified to homogeneity, as evaluated by SDS/PAGE and reverse-phase h.p.l.c. The active form of the enzyme had a molecular mass of 66,000-68,000 Da as estimated by gel exclusion chromatography and a subunit molecular mass of 35,000 Da. The apparent Km values for Mx, 3'-phosphoadenosine 5'-phosphosulphate and PNP were 625 microM, 5.0 microM and 0.5 microM respectively. However, PNP displayed potent substrate inhibition at concentrations above 1.2 microM. Antibodies raised in rabbits to the pure enzyme detected a single band in rat liver cytosol with a subunit molecular mass of 35,000 Da, as determined by immunoblotting. The anti-(rat Mx-ST) antibodies also reacted with the phenol-sulphating form of human liver phenol sulphotransferase, suggesting some structural similarity between these proteins. Images Fig. 5. Fig. 6. Fig. 7. PMID:2241904

  1. Binders of intravenously administered zinc 65 in rat liver cytoplasm

    International Nuclear Information System (INIS)

    Stortenbeek, A.J.; Hamer, C.J.A. van den.

    1976-01-01

    The fate of intravenously injected trace amounts of 65 Zn 2+ in the rat was studied over a period of ten days after injection. Tissue distributions were determined and a special study was made of 65 Zn-binders in liver cytoplasm. A total of six 65 Zn-binding fractions was found and a tentative identification of the main 65 Zn-binders in these six fractions is given using the collected data regarding their apparent molecular weight, time dependent prominence and content of stable zinc

  2. Metallothionein expression during liver regeneration after partial hepatectomy in cadmium-pretreated rats

    Energy Technology Data Exchange (ETDEWEB)

    Margeli, A.P. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Theocharis, S.E. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Yannacou, N.N. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Spiliopoulou, C. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Koutselinis, A. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece))

    1994-10-01

    Metallothionein is a low molecular mass protein inducible mainly by heavy metals, having high affinity for binding cadmium, zinc and copper. In the present study we investigated the expression of metallothionein in regenerating liver, at different time intervals, in cadmium pretreated partially hepatectomized rats. Liver metallothionein is highly expressed during regeneration induced by partial hepatectomy in rats, providing zinc within the rapidly growing tissue. Cadmium pretreatment caused inhibition of the first peak of liver regeneration, while metallothionein expression was markedly more prominent in the liver residues of cadmium-pretreated rats. These results demonstrate that although metallothionein able to bind temporarily metal ions as zinc and cadmium has been highly expressed, the liver regenerative process was inhibited possibly due to the effects of cadmium on other pivotal events necessary to the DNA replication. (orig.)

  3. Molecular Structure of Human-Liver Glycogen.

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    Bin Deng

    Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

  4. Differential Expression ESTs Associated with Fluorosis in Rats Liver

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    Y. Q. He

    2012-01-01

    Full Text Available The fluoride has volcanic activity and abundantly exists in environment combining with other elements as fluoride compounds. Recent researches indicated that the molecular mechanisms of intracellular fluoride toxicity were very complex. However, the molecular mechanisms underlying the effects on gene expression of chronic fluoride-induced damage is unknown, especially the detailed regulatory process of mitochondria. In the present study, we screened the differential expression ESTs associated with fluorosis by DDRT-PCR in rat liver. We gained 8 genes, 3 new ESTs, and 1 unknown function sequence and firstly demonstrated that microsomal glutathione S-transferase 1 (MGST1, ATP synthase H+ transporting mitochondrial F0 complex subunit C1, selenoprotein S, mitochondrial IF1 protein, and mitochondrial succinyl-CoA synthetase alpha subunit were participated in mitochondria metabolism, functional and structural damage process caused by chronic fluorosis. This information will be very helpful for understanding the molecular mechanisms of fluorosis.

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

    International Nuclear Information System (INIS)

    Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

    2006-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Yumin Xu

    Full Text Available 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.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.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.sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

  7. Alanine metabolism in pyridoxine-depleted rat liver

    International Nuclear Information System (INIS)

    Okada, Mitsuko; Abe, Midori

    1976-01-01

    Alanine metabolism in normal and pyridoxine-deficient rats was studied in vivo and in vitro. Incorporation of 14 C-alanine into various liver components was determined and no difference was shown between normal and deficient animals in the incorporation into liver homogenates, lipid, protein and plasma glucose. Using the liver slice system, gluconeogenic activity from alanine or pyruvate was 40% lower in deficient rats compared with the activity of normal rats. However, inhibition was completely removed by the addition of 2-oxoglutarate to alanine. Penicillamine did not affect glucose formation from alanine in the liver slice. (auth.)

  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.

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

    Science.gov (United States)

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

    2016-12-02

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

  10. 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.

  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.

  12. Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2015-02-01

    Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

  13. Synchrotron Based Phase Contrast Tomography of Hyper cholesteromic Rat Liver

    Directory of Open Access Journals (Sweden)

    Fatima A

    2017-05-01

    Full Text Available X-ray phase contrast imaging technique has been applied for the study of morphological variations in soft tissues. The effect of an antioxidant, α-lipoic acid in reducing hypercholesterolemia in rats is investigated. The experiment was conducted to measure serum lipid profile and diameter of vessels in rat liver, as liver is the most vital organ in hypolipidemic activity studies. Methods: Four groups of male Wistar rats, control (Group I, hyperlipidemic (Group II, positive control (Group III and treated Group IV were studied for serum lipid profile and liver vessels with synchrotron X-ray phase tomography. The Group I rats received chow diet, in Group II rats, administration of 20% butter rich diet induced hyperlipidemia. Group III, treated rats received hypolipidemic drug Atorvastatin and Group IV animals received a potent antioxidant DL-α-Lipoic acid. The excised liver tissue immersed in 10% formalin. X-ray phase contrast tomography was performed for comparison of diameter of liver vessels. Results: Among the four group of animals, the diameter of liver vessels was much larger in hypercholesterolemic rat (Group II. The liver vessel diameter comparison with X-ray phase contrast tomography and the lipid profile shows reduction in serum lipids and lipoproteins by ALA treatment.

  14. Liver Gene Expression Profiles of Rats Treated with Clofibric Acid

    Science.gov (United States)

    Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric

    2003-01-01

    Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor α, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci. PMID:14633594

  15. Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

    Science.gov (United States)

    Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

    1989-01-01

    A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

  16. Liver gene expression profiles of rats treated with clofibric acid: comparison of whole liver and laser capture microdissected liver.

    Science.gov (United States)

    Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric

    2003-12-01

    Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor alpha, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci.

  17. Toxicoproteomic assessment of liver responses to acute pyrrolizidine alkaloid intoxication in rats.

    Science.gov (United States)

    Li, Yan-Hong; Tai, William Chi-Shing; Khan, Imran; Lu, Cheng; Lu, Yao; Wong, Wing-Yan; Chan, Wood-Yee; Wendy Hsiao, Wen-Luan; Lin, Ge

    2018-04-03

    A toxicoproteomic study was performed on liver of rats treated with retrorsine (RTS), a representative hepatotoxic pyrrolizidine alkaloid at a toxic dose (140 mg/kg) known to cause severe acute hepatotoxicity. By comparing current data with our previous findings in mild liver lesions of rats treated with a lower dose of RTS, seven proteins and three toxicity pathways of vascular endothelial cell death, which was further verified by observed sinusoidal endothelial cell losses, were found uniquely associated with retrorsine-induced hepatotoxicity. This toxicoproteomic study of acute pyrrolizidine alkaloid intoxication lays a foundation for future investigation to delineate molecular mechanisms of pyrrolizidine alkaloid-induced hepatotoxicity.

  18. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution.

    Directory of Open Access Journals (Sweden)

    Andrea Baiocchini

    Full Text Available Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis. Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

  20. Synthesis of erythrocyte membrane proteins in dispersed cells from fetal rat liver

    International Nuclear Information System (INIS)

    Kitagawa, Yasuo; Murakami, Akihiko; Sugimoto, Etsuro

    1984-01-01

    Protein synthesis in dispersed cells from fetal liver was studied by fluorography of SDS-polyacrylamide gel electrophoresis of a [ 35 S] methionine labeled cell lysate. Synthesis of several proteins with molecular weights ranging from 45,000 to 220,000 was observed during erythropoiesis in fetal liver. Some of these proteins were demonstrated to be erythrocyte membrane proteins because they were immunoprecipitated with antiserum against rat red blood cells and the immunoprecipitation was competitive with non-radioactive proteins solubilized from erythrocyte ghosts. The same antiserum caused agglutination of dispered cells from fetal liver. This supported the possibility that these proteins are translocated onto plasma membranes of the dispersed cells. (author)

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

    NARCIS (Netherlands)

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

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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Influence of Chloramphenicol and Amoxicillin on Rat Liver ...

    African Journals Online (AJOL)

    This study examined the effect of chloramphenicol and amoxicillin on liver microsomal enzymes Ca2+-ATPase and Glucose-6-Phosphatase (G-6-P) and lipid peroxidation in rats. Male Wistar strain rats weighing 120 – 195 g were divided into four groups. Group one, the control group, received physiological saline, group ...

  4. Evaluation of selected parameters of rat liver and kidney function ...

    African Journals Online (AJOL)

    The effects of administration of yohimbine, an aphrodisiac on some functional parameters of rat liver and kidney were investigated. White male albino rats weighing between 200-250g were grouped into two such that one group was orally administered with 14mg/kg body weight on daily basis for 15days while the control ...

  5. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    International Nuclear Information System (INIS)

    Mei, Nan; Arlt, Volker M.; Phillips, David H.; Heflich, Robert H.; Chen, Tao

    2006-01-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32 P-postlabeling and mutant frequency (MF) was determined using the λ Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N 6 -yl]-aristolactam I, 7-[deoxyadenosin-N 6 -yl]-aristolactam II and 7-[deoxyguanosin-N 2 -yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10 8 nucleotides in liver and 95-4598 adducts/10 8 nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10 -6 in liver compared with the MFs of 78-1319 x 10 -6 that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T → T:A transversion was the predominant mutation in AA-treated rats; whereas G:C → A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually

  6. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Nan [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)]. E-mail: nan.mei@fda.hhs.gov; Arlt, Volker M. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Phillips, David H. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Heflich, Robert H. [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Chen, Tao [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)

    2006-12-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by {sup 32}P-postlabeling and mutant frequency (MF) was determined using the {lambda} Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N {sup 6}-yl]-aristolactam I, 7-[deoxyadenosin-N {sup 6}-yl]-aristolactam II and 7-[deoxyguanosin-N {sup 2}-yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10{sup 8} nucleotides in liver and 95-4598 adducts/10{sup 8} nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10{sup -6} in liver compared with the MFs of 78-1319 x 10{sup -6} that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T {sup {yields}} T:A transversion was the predominant mutation in AA-treated rats; whereas G:C {sup {yields}} A:T transition was the main type of mutation in control

  7. Studies on the postnatal development of the rat liver plasma membrane following maternal ethanol ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Rovinski, B

    1984-01-01

    Studies on the developing rat liver and on the structure and function of the postnatal rat liver plasma membrane were carried out following maternal consumption of alcohol during pregnancy and lactation. A developmental study of alcohol dehydrogenase (ADH) indicated that both the activity and certain kinetic properties of the enzyme from the progeny of alcohol-fed and pair-fed mothers were similar. Fatty liver, however, developed in the alcoholic progeny only after ADH appeared on a day 19 of gestation. Further studies on structural and functional changes were then undertaken on the postnatal development of the rat liver plasma membrane. Radioligand binding studies performed using the hapatic alpha{sub 1}-adrenergic receptor as a plasma membrane probe demonstrated a significant decrease in receptor density in the alcoholic progeny, but no changes in binding affinity. Finally, the fatty acid composition of constituent phospholipids and the cholesterol content of rat liver plasma membranes were determined. All these observations suggest that membrane alterations in the newborn may be partially responsible for the deleterious action(s) of maternal alcoholism at the molecular level.

  8. Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

    Directory of Open Access Journals (Sweden)

    Matthew J Robertson

    Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

  9. Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water

    Science.gov (United States)

    Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

    2015-01-01

    Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury. PMID:26316710

  10. Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water.

    Science.gov (United States)

    Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

    2015-01-01

    Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.

  11. 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

  12. Sex Hormone-Related Functions in Regenerating Male Rat Liver

    Science.gov (United States)

    FRANCAVILLA, ANTONIO; EAGON, PATRICIA K.; DiLEO, ALFREDO; POLIMENO, LORENZO; PANELLA, CARMINE; AQUILINO, A. MARIA; INGROSSO, MARCELLO; Van THIEL, DAVID H.; STARZL, THOMAS E.

    2011-01-01

    Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration. PMID:3758617

  13. Modeling the mechanical properties of liver fibrosis in rats.

    Science.gov (United States)

    Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

    2016-06-14

    The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Hepatic injury after whole-liver irradiation in the rat

    International Nuclear Information System (INIS)

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.; Leitch, J.M.

    1985-01-01

    Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study. These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation. The LD/sub 50/30/ day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively. Death is preceded by reduction in liver function as measured by [ 131 I]-labeled rose bengal clearance. Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals. Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days. This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy. It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers

  15. Inhibition of gluconeogenesis in the perfusing liver of irradiated rats

    International Nuclear Information System (INIS)

    Borovikova, G.V.; Dokshina, G.A.; Ermakova, G.N.; Mashkova, N.Yu.

    1981-01-01

    It was shown on the perfusing liver taken from rats on the 1st and 3d days after irradiation in a dose of 18.06x10 -2 C/kg that insulin (400 μunits/ml) and taurine (40 mg%) exerted an inhibiting action on the rate of gluconeogenesi.s and transamination, catalyzed by alanine aminoferase and aspartate aminoferase, in a soluble fraction of the irradiated rat liver. The gluconeogenic capacity and the reactivity of the isolated organ were shown to decrease on the 3d day after irradiation [ru

  16. Mechanism of liver lipid accumulation in X-irradiated rat

    International Nuclear Information System (INIS)

    Aiyar, A.S.; De, A.K.

    1978-01-01

    The incorporation, both in vivo and in vitro, of 14 C-acetate into hepatic lipids, notably the triglyceride and free fatty acid fractions, is greatly reduced following whole-body irradiation and is indicative of significantly reduced lipogenesis. Irradiation results in a several-fold increase in fatty acid oxidation, by the liver in vitro as well as in the whole animal, during the phase of active hepatic lipid accumulation. Small increases in lipoprotein lipase activity of adipose, immediately following irradiation and up to 24 hours, and the attendant marked fall in adipose lipids are suggestive of increased mobilization of peripheral lipids during the early period. However, in view of the fact that maximum lipid accumulations occurs very much later, inflow of extra-hepatic lipid into liver does not appear to be of major etiological significance. There is three-fold experimental evidence in support of an impairment of trigylceride transport from liver being primarily responsible for the build-up of liver lipids: (I) Triton WR-1339 induced hypertriglyceridemia is totally absent in the irradiated rat during the period when liver lipids increase significantly; (II) the rate of disappearance of radioactivity from pre-labeled hepatic lipids is considerably lower in the irradiated rats; and (III) the irradiated rats show decrease in lipoproteins of liver cell-sap and of serum, the latter being more marked and a lowered synthesis of the lipoproteins, as assessed by labeling of the protein moiety. (orig.) [de

  17. Mechanism of liver lipid accumulation in X-irradiated rat

    Energy Technology Data Exchange (ETDEWEB)

    Aiyar, A S; De, A K [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

    1978-03-01

    The incorporation, both in vivo and in vitro, of /sup 14/C-acetate into hepatic lipids, notably the triglyceride and free fatty acid fractions, is greatly reduced following whole-body irradiation and is indicative of significantly reduced lipogenesis. Irradiation results in a several-fold increase in fatty acid oxidation, by the liver in vitro as well as in the whole animal, during the phase of active hepatic lipid accumulation. Small increases in lipoprotein lipase activity of adipose, immediately following irradiation and up to 24 hours, and the attendant marked fall in adipose lipids are suggestive of increased mobilization of peripheral lipids during the early period. However, in view of the fact that maximum lipid accumulations occurs very much later, inflow of extra-hepatic lipid into liver does not appear to be of major etiological significance. There is three-fold experimental evidence in support of an impairment of trigylceride transport from liver being primarily responsible for the build-up of liver lipids: (I) Triton WR-1339 induced hypertriglyceridemia is totally absent in the irradiated rat during the period when liver lipids increase significantly; (II) the rate of disappearance of radioactivity from pre-labeled hepatic lipids is considerably lower in the irradiated rats; and (III) the irradiated rats show decrease in lipoproteins of liver cell-sap and of serum, the latter being more marked and a lowered synthesis of the lipoproteins, as assessed by labeling of the protein moiety.

  18. Evaluation of methanolic extract of Phragmites karka on carbon tetrachloride-induced liver fibrosis in rat

    Directory of Open Access Journals (Sweden)

    Atta ur Rehman

    2017-07-01

    Full Text Available Phragmites karka has been reported for its anti-inflammatory and analgesic activities. Here, extracts of leaf and rhizome of the plant were individually investigated in CCl4-induced hepatofibrosis in male Wistar rats by administering CCl4 intraperitoneally biweekly for 6 weeks. Afterwards the animals were investigated for liver fibrosis at biochemical, molecular and histological levels, and it showed a profound increase (p<0.001 in elevation of serum levels of transaminases, γ-glutamyl transpeptidase, mRNA expression of α smooth muscle actin, collagen and transforming growth factor beta (TGFβ, and extracellular matrix deposition and perilobular necrosis. Both extracts markedly (p<0.001 decreased the elevated levels of these markers. Histopathological investigations also substantiated the above results by exhibiting a decreased in extracellular matrix deposition in post-treatment animals. In conclusion, both extracts had substantially modified the biochemical and molecular markers of liver fibrosis, in addition to histological improvement in architecture of liver.

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

    International Nuclear Information System (INIS)

    Gu Ke; Lai Songtao; Ma Ningyi; Zhao Jiandong; Ren Zhigang; Wang Jian; Liu Jin; Jiang Guoliang

    2011-01-01

    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)

  20. [Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].

    Science.gov (United States)

    Hagymási, Krisztina; Tulassay, Zsolt

    2008-03-23

    Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

  1. Effect of insulin on aldolase turnover in irradiated rat liver

    International Nuclear Information System (INIS)

    Komov, V.P.; Kirillova, N.V.; Bekdzhanyan, A.G.

    1984-01-01

    A study was made of the effect of insulin on the rate of biosynthesis, ''half life'', spontaneous decomposition and transport of aldolase in mitochondria of liver and blood plasma of rats, subjected to whole-body X-irradiation. The hormone injected after irradiation was shown to normalize the rate of spontaneous decay and the time of aldolase functioning

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

    NARCIS (Netherlands)

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

    1965-01-01

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

  3. Decrease in Activities of Selected Rat Liver Enzymes following ...

    African Journals Online (AJOL)

    The effects of the chemical effluent from Soap and Detergent Industry on some rat liver enzymes were investigated. Chemical analyses of both the effluent and tap water which served as the control were carried out before various concentrations of the effluent (5%v/v, 25%v/v, 50%v/v and 100%v/v) were made. The effluent ...

  4. Transport of N-acetylglutamate in rat-liver mitochondria

    NARCIS (Netherlands)

    Meijer, A. J.; van Woerkom, G. M.; Wanders, R. J.; Lof, C.

    1982-01-01

    The permeability properties of the rat-liver mitochondrial membrane for N-acetylglutamate, the activator of carbamoyl-phosphate synthetase (ammonia), were studied. 1. Transport of N-acetylglutamate into the mitochondria was only observed in partially or fully de-energized mitochondria and when the

  5. Liver Iron Contents in Rats after Administration of Certain Iron ...

    African Journals Online (AJOL)

    The effect of consumption of certain iron compounds on liver iron deposition was ... extra iron probably depends on the type of food prepared, .... main groups. Each main group consisted of 4 subgroups. (8 rats per subgroup) which received the same basic diet but differing amounts of iron of a specific type. Each animal was ...

  6. Occurrence of lipids in the liver of the hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Zemanová, Zdeňka; Strnadová, Miluše; Jirsová, Z.; Klusoňová, Petra

    2009-01-01

    Roč. 153, č. 1 (2009), s. 37-40 ISSN 1213-8118 R&D Projects: GA AV ČR(CZ) KJB500110703 Institutional research plan: CEZ:AV0Z50110509 Keywords : lipid histochemistry * liver glucocorticoid metabolism * Prague Hereditary Hypertriglyceridemic rats Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

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

    Directory of Open Access Journals (Sweden)

    Edimar Leandro Toderke

    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.

  8. EFFECT OF THIOPROPANOL ON AMINO ACID TURNOVER AND REDOX STATUS IN ALLOXAN DIABETIC RAT LIVER

    Directory of Open Access Journals (Sweden)

    Vickram

    2016-07-01

    Full Text Available BACKGROUND Decreased cellular thiol levels seen in diabetes mellitus (DM may be in part attributed to increased free radical generation. The free radical mediated oxidative stress has been implicated in the pathogenesis of DM and its complications. The relative deficiency or non-availability of insulin in DM affects the metabolism of biomolecules, specifically the carbohydrate metabolism. The insulin-mimicking actions of various thiols have been studied. In our previous study, we have documented that 3-mercapto- 1-propanol (Thiopropanol, a low molecular weight thiol, at the dosage employed has increased glucose utilisation in alloxandiabetic rat liver tissue probably by favouring utilisation of glucose through glycolysis and HMP pathway. It is known that insulin inhibits gluconeogenesis by inhibiting the key enzymes of the same and by controlling the channelling of amino acids for the glucose biosynthesis through gluconeogenic pathway. A study was undertaken to assess the effects of thiopropanol (TP on amino acid turnover and the redox status in alloxan diabetic rat liver. METHODS Male albino rats weighing 150-250 g were used. Diabetes was induced using alloxan monohydrate. Rats were divided into normal and diabetic groups. Levels of amino acid nitrogen (AAN, alanine, total thiol (-SH groups, TBARS (Thiobarbituric acid reactive substances, and activities of alanine transaminase (ALT and aspartate transaminase (AST were estimated in liver specimens of normal, control-alloxan diabetic and TP-exposed-alloxan-diabetic rats. RESULTS The results showed a significant increase (p<0.001 in AAN levels, alanine levels, and total -SH groups concentration; and a significant decrease (p<0.001 in TBARS levels, ALT and AST activities in TP-exposed-alloxan diabetic liver slices as compared to control-alloxan diabetic liver slices. CONCLUSIONS Hence, it may be concluded that TP, at the concentration employed, inhibits gluconeogenesis from amino acids probably by

  9. Changes at transcriptional level during liver regeneration in the rat

    International Nuclear Information System (INIS)

    Subba Rao, M.N.; Netrawali, M.S.; Pradhan, D.S.; Sreenivasan, A.

    1976-01-01

    A great upheaval in RNA synthetic pattern is known to occur during the early periods after partial hepatectomy. Such changes are being studied in regenerating rat liver with a view to understanding regulatory mechanisms of eukaryotic transcription. Follwoing partial hepatectomy, RNA synthesis is rat liver showed graded increase during 4 to 18 hours. At these time intervals, a significant enhancement could be discerned both in template efficiency of chromatin and in RNA polymerase activity in this tissue. Further examination revealed that the activity of RNA polymerase II (extra-nucleolar enzyme) stimulated to a much greater extent as compared to that of RNA polymerase I (nucleolar enzyme). Partial hepatectomy also resulted in significant alterations in turnovers of chromosomal acidic proteins in liver. 32 P-orthophosphate injected intraperitoneally was used in these studies. (author)

  10. Subcellular distribution of styrene oxide in rat liver

    International Nuclear Information System (INIS)

    Pacifici, G.M.; Cuoci, L.; Rane, A.

    1984-01-01

    The subcellular distribution of ( 3 H)-styrene-7,8-oxide was studied in the rat liver. The compound was added to liver homogenate to give a final concentration of 2 X 10(-5); 2 X 10(-4) and 2 X 10(-3) M. Subcellular fractions were obtained by differential centrifugation. Most of styrene oxide (59-88%) was associated with the cytosolic fraction. Less than 15 percent of the compound was retrieved in each of the nuclear, mitochondrial and microsomal fractions. A considerable percentage of radioactivity was found unextractable with the organic solvents, suggesting that styrene oxide reacted with the endogenous compounds. The intracellular distribution of this epoxide was also studied in the perfused rat liver. Comparable results with those previously described were obtained. The binding of styrene oxide to the cytosolic protein was investigated by equilibrium dialysis and ultrafiltration. Only a small percentage of the compound was bound to protein

  11. Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats.

    Science.gov (United States)

    Sheen, Jiunn-Ming; Chen, Yu-Chieh; Hsu, Mei-Hsin; Tain, You-Lin; Huang, Ying-Hsien; Tiao, Mao-Meng; Li, Shih-Wen; Huang, Li-Tung

    2016-08-20

    Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.

  12. Muscle and liver glycogen, protein, and triglyceride in the rat

    DEFF Research Database (Denmark)

    Richter, Erik; Sonne, Bente; Joensen Mikines, Kari

    1984-01-01

    in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho......-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did...... not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did...

  13. Measurement of binding of adenine nucleotides and phosphate to cytosolic proteins in permeabilized rat-liver cells

    NARCIS (Netherlands)

    Gankema, H. S.; Groen, A. K.; Wanders, R. J.; Tager, J. M.

    1983-01-01

    1. A method is described for measuring the binding of metabolites to cytosolic proteins in situ in isolated rat-liver cells treated with filipin to render the plasma membrane permeable to compounds of low molecular weight. 2. There is no binding of ATP or inorganic phosphate to cytosolic proteins,

  14. Heterogeneous expression of cholesterol 7α-hydroxylase and sterol 27- hydroxylase genes in the rat liver lobulus

    NARCIS (Netherlands)

    Twisk, J.; Hoekman, M.F.M.; Mager, W.H.; Moorman, A.F.M.; Boer, P.A.J. de; Scheja, L.; Princen, H.M.G.; Gebhardt, R.

    1995-01-01

    We investigated the lobular localization and molecular level of expression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase, two key enzymes in bile acid synthesis, in isolated periportal and pericentral hepatocytes and by in situ hybridization of rat liver. Enzyme activity, mRNA, and gene

  15. A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.

    Science.gov (United States)

    Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi-Khansari, Mahmoud

    2017-07-01

    Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system. Tramadol and metabolites concentrations were determined by HPLC-FL. The sharp increase in liver enzymes level in both BDL groups was observed and significant changes were also observed in liver weight and volume. Tramadol metabolites concentration significantly decreased compared with the control and sham group (Pbile duct diseases and the dose of tramadol should be accordingly adjusted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Borax counteracts genotoxicity of aluminum in rat liver.

    Science.gov (United States)

    Turkez, Hasan; Geyikoğlu, Fatime; Tatar, Abdulgani

    2013-10-01

    This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl₃; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl₃ was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl₃ in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity.

  17. 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

  18. Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats.

    Science.gov (United States)

    Tahan, Veysel; Ozaras, Resat; Canbakan, Billur; Uzun, Hafize; Aydin, Seval; Yildirim, Beytullah; Aytekin, Huseyin; Ozbay, Gulsen; Mert, Ali; Senturk, Hakan

    2004-09-01

    Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

  19. Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model

    Directory of Open Access Journals (Sweden)

    Zhu Jin

    2009-07-01

    Full Text Available Abstract Background Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma. Methods A rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues. Results The pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated. Conclusion In this study, we provide the global gene expression profiles during the development and

  20. 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...

  1. Library of molecular associations: curating the complex molecular basis of liver diseases

    Directory of Open Access Journals (Sweden)

    Maass Thorsten

    2010-03-01

    Full Text Available Abstract Background Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. Results We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Conclusion Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

  2. Lipid Peroxidation in Rat Liver using Different Vegetable Oils

    International Nuclear Information System (INIS)

    Eqbal Dauqan; Aminah Abdullah; Halimah Abdullah Sani

    2013-01-01

    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)

  3. In vitro biotransformation of flavonoids by rat liver microsomes

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  4. Serum glucose and liver glycogen in gamma irradiated rats

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Molcanova, A.

    1988-01-01

    Overnight fasted male rats of Wistar strain were irradiated with single whole-body doses of 4.78-7.17-9.57 and 14.35 Gy of gamma rays. After decapitation at intervals 1-28 d (4.78 and 7.17 Gy), 1-7 d (9.57 Gy) and 1-3 d (14.35 Gy) glucose concentration in serum and glycogen concentration in liver of irradiated and non-irradiated animals were determined. The higher was radiation dose the more expressive extent and depth of changes (hyperglycemia, accumulation of glycogen) occured. Blood glucose and liver glycogen may serve as a reliable and dose-dependent biological indicators of metabolic changes in irradiated rats. (author)

  5. Role of the autonomic nervous system in rat liver regeneration.

    Science.gov (United States)

    Xu, Cunshuan; Zhang, Xinsheng; Wang, Gaiping; Chang, Cuifang; Zhang, Lianxing; Cheng, Qiuyan; Lu, Ailing

    2011-05-01

    To study the regulatory role of autonomic nervous system in rat regenerating liver, surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, then expression profiles of regenerating livers at 2 h after operation were detected using Rat Genome 230 2.0 array. It was shown that the expressions of 97 genes in OC, 230 genes in PH, 253 genes in SPH, 187 genes in VPH, and 177 genes in TDPH were significantly changed in biology. The relevance analysis showed that in SPH, genes involved in stimulus response, immunity response, amino acids and K(+) transport, amino acid catabolism, cell adhesion, cell proliferation mediated by JAK-STAT, Ca(+), and platelet-derived growth factor receptor, cell growth and differentiation through JAK-STAT were up-regulated, while the genes involved in chromatin assembly and disassembly, and cell apoptosis mediated by MAPK were down-regulated. In VPH, the genes associated with chromosome modification-related transcription factor, oxygen transport, and cell apoptosis mediated by MAPK pathway were up-regulated, but the genes associated with amino acid catabolism, histone acetylation-related transcription factor, and cell differentiation mediated by Wnt pathway were down-regulated. In TDPH, the genes related to immunity response, growth and development of regenerating liver, cell growth by MAPK pathway were up-regulated. Our data suggested that splanchnic and vagal nerves could regulate the expressions of liver regeneration-related genes.

  6. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, van den G.J.; de Goeij, J.J.M.; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendriks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (<1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  7. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, G.J. van den; Goeij, J.J.M. de; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendruiks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  8. Liver fatty acid binding protein is the mitosis-associated polypeptide target of a carcinogen in rat hepatocytes

    International Nuclear Information System (INIS)

    Bassuk, J.A.; Tsichlis, P.N.; Sorof, S.

    1987-01-01

    Hepatocytes in normal rat liver were found previously to contain a cytoplasmic 14,000-dalton polypeptide (p14) that is associated with mitosis and is the principal early covalent target of activated metabolites of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene). The level of immunohistochemically detected p14 was low when growth activity of hepatocytes was low, was markedly elevated during mitosis in normal and regenerating livers, but was very high throughout interphase during proliferation of hyperplastic and malignant hepatocytes induced in rat liver by a carcinogen (N-2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene). The authors report here that p14 is the liver fatty acid binding protein. The nucleotide sequence of p14 cDNA clones, isolated by screening a rat liver cDNA library in bacteriophage λgt11 using p14 antiserum, was completely identical to part of the sequence reported for liver fatty acid binding protein. Furthermore, the two proteins shared the following properties: size of mRNA, amino acid composition, molecular size according to NaDodSO 4 gel electrophoresis, and electrophoretic mobilities in a Triton X-100/acetic acid/urea gel. The two polypeptides bound oleic acid similarly. Finally, identical elevations of cytoplasmic immunostain were detected specifically in mitotic hepatocytes with either antiserum. The collected findings are suggestive that liver fatty acid binding protein may carry ligands that promote hepatocyte division and may transport certain activated chemical carcinogens

  9. Methyleugenol hepatocellular cancer initiating effects in rat liver.

    Science.gov (United States)

    Williams, Gary M; Iatropoulos, Michael J; Jeffrey, Alan M; Duan, Jian-Dong

    2013-03-01

    Methyleugenol (MEG), a constituent of plants used in the human diet, is hepatocarcinogenic in rodents. In an experiment to elucidate its mode of action in rat liver, male F344 rats were administered MEG intragastrically at 3 doses per week for up to 16 weeks in an initiation phase, after which half the rats were fed 500 ppm phenobarbital (PB) in the diet to promote liver neoplasia and the other half were maintained on control diet for 24 weeks. At 8 and 16 week interim terminations, (32)P-nucleotide postlabeling assay revealed 3 adducts in livers of all MEG groups. The hepatocellular replicating fractions, measured by proliferating cell nuclear antigen immunohistochemistry, were doubled or more in all MEG groups. Hepatocellular altered foci, detected by glutathione S-transferase-placental type (π) immunohistochemistry, were present beginning with the high dose group at 8 weeks and extending to all MEG groups at 16 weeks. At the end of maintenance/promotion phase, the incidences, multiplicity and size of foci was similar between control and low dose groups, while those of mid and high dose groups were increased. Hepatocellular adenomas occurred in the mid and high dose groups, attaining higher multiplicity and size with PB. Thus, MEG had rapid initiating activity, reflecting the formation of DNA adducts and possibly cell proliferation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. P-31 MR spectroscopy of rat liver in situ

    International Nuclear Information System (INIS)

    Grivegnee, A.R.; Masin, F.; Marschalck, C.; Fruhling, J.; Jeanmart, L.

    1988-01-01

    A technique using a three-turn solenoid coil implanted between the two lobes of the liver was used for performing P-31 magnetic resonance spectroscopic measurement of the rat liver in vivo. Stress tests were performed with intraperitoneal and intravenous injections of fructose and glucagon. After intraperitoneal injection of fructose (1 mg/g), an increase in sugar phosphate levels (SP) occurred at the expense of inorganic phosphate (Pi) and adenosine triphosphate (ATP). The intravenous injection of fructose (1 mg/kg) was followed by an early increase in the SP line, which returned to its basal value 15 minutes after injection. The ATP level decreased concomitantly and stayed 20% under the basal level until the end of the experiment. The intravenous injection of glucagon ws followed by an important increase in the SP line, accompanied by a slight decrease in the Pi line without modification of the ATP levels. In conclusion, liver stress tests are feasible in vivo in rats with injection of fructose and glucagon. The results obtained are in concordance with the results obtained in humans. The authors are now performing these tests on pathologic livers

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

    Directory of Open Access Journals (Sweden)

    Van Dyke Rebecca W

    2004-01-01

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

  12. Diet and liver apoptosis in rats: a particular metabolic pathway.

    Science.gov (United States)

    Monteiro, Maria Emilia Lopes; Xavier, Analucia Rampazzo; Azeredo, Vilma Blondet

    2017-03-30

    Various studies have indicated an association between modifi cation in dietary macronutrient composition and liver apoptosis. To explain how changes in metabolic pathways associated with a high-protein, high-fat, and low-carbohydrate diet causes liver apoptosis. Two groups of rats were compared. An experimental diet group (n = 8) using a high-protein (59.46%), high-fat (31.77%), and low-carbohydrate (8.77%) diet versus a control one (n = 9) with American Institute of Nutrition (AIN)-93-M diet. Animals were sacrificed after eight weeks, the adipose tissue weighed, the liver removed for flow cytometry analysis, and blood collected to measure glucose, insulin, glucagon, IL-6, TNF, triglycerides, malondialdehyde, and β-hydroxybutyrate. Statistical analysis was carried out using the unpaired and parametric Student's t-test and Pearson's correlation coeffi ents. Significance was set at p triglycerides lower levels compared with the control group. The results show a positive and significant correlation between the percentage of nonviable hepatocytes and malondialdehyde levels (p = 0.0217) and a statistically significant negative correlation with triglycerides levels (p = 0.006). Results suggest that plasmatic malondialdehyde and triglyceride levels are probably good predictors of liver damage associated with an experimental low-carbohydrate diet in rats.

  13. Elevated mitochondrial gene expression during rat liver regeneration after portal vein ligation.

    Science.gov (United States)

    Shimizu, Y; Suzuki, H; Nimura, Y; Onoue, S; Nagino, M; Tanaka, M; Ozawa, T

    1995-10-01

    We explored the molecular basis of mitochondrial energy production during rat liver regeneration after portal vein ligation. Ligation of the left branch of the portal vein induces an increase in the weight of the nonligated lobe, counterbalancing the reduced weight of the ligated lobe. Using this model, we investigated changes in mitochondrial DNA-binding proteins, mitochondrial DNA, and mitochondrial messenger RNA (mRNA) in rat hepatocytes of the nonligated lobes. The amount of mitochondrial DNA-binding protein increased maximally (200% to 300% of the preoperative level) at 12 hours after the operation, before an increase (390%) in mitochondrial DNA content at 24 hours, and parallel to an increase (240%) in mitochondrial mRNA levels at 12 hours. These results suggest that the energy supply for liver regeneration is achieved through enhancement of mitochondrial DNA replication as well as transcription, in which the mitochondrial DNA-binding proteins probably play regulatory roles. We also found that in the nonligated lobes, mRNA levels of hepatocyte growth factor increased to a detectable level only 12 hours after the operation. These molecular biochemical data help explain why preoperative portal vein embolization, which is a modification of portal vein branch ligation, is an effective method to prevent posthepatectomy liver failure.

  14. Coffee enhances the expression of chaperones and antioxidant proteins in rats with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Salomone, Federico; Li Volti, Giovanni; Vitaglione, Paola; Morisco, Filomena; Fogliano, Vincenzo; Zappalà, Agata; Palmigiano, Angelo; Garozzo, Domenico; Caporaso, Nicola; D'Argenio, Giuseppe; Galvano, Fabio

    2014-06-01

    Coffee consumption is inversely related to the degree of liver injury in patients with nonalcoholic fatty liver disease (NAFLD). Molecular mediators contributing to coffee's beneficial effects in NAFLD remain to be elucidated. In this study, we administrated decaffeinated espresso coffee or vehicle to rats fed an high-fat diet (HFD) for 12 weeks and examined the effects of coffee on liver injury by using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) proteomic analysis combined with mass spectrometry. Rats fed an HFD and water developed panacinar steatosis, lobular inflammation, and mild fibrosis, whereas rats fed an HFD and coffee exhibited only mild steatosis. Coffee consumption increased liver expression of the endoplasmic reticulum chaperones glucose-related protein 78 and protein disulfide-isomerase A3; similarly, coffee drinking enhanced the expression of the mitochondrial chaperones heat stress protein 70 and DJ-1. Furthermore, in agreement with reduced hepatic levels of 8-isoprostanes and 8-hydroxy-2'-deoxyguanosine, proteomic analysis showed that coffee consumption induces the expression of master regulators of redox status (i.e., peroxiredoxin 1, glutathione S-transferase α2, and D-dopachrome tautomerase). Last, proteomics revealed an association of coffee intake with decreased expression of electron transfer flavoprotein subunit α, a component of the mitochondrial respiratory chain, involved in de novo lipogenesis. In this study, we were able to identify by proteomic analysis the stress proteins mediating the antioxidant effects of coffee; moreover, we establish for the first time the contribution of specific coffee-induced endoplasmic reticulum and mitochondrial chaperones ensuring correct protein folding and degradation in the liver. Copyright © 2014 Mosby, Inc. All rights reserved.

  15. Purification of a large molecular weight transglutaminase substrate from liver plasma membranes

    International Nuclear Information System (INIS)

    Slife, C.W.; Morris, G.S.; Tyrrell, D.J.

    1986-01-01

    Transglutaminases are enzymes which catalyze the covalent crosslinking of proteins by forming epsilon(γ-glutamyl)lysine isopeptide linkages. In earlier studies, the authors reported that a large molecular weight protein aggregate in rat liver plasma membranes served as a substrate for a plasma membrane-associated transglutaminase. The enzyme specifically incorporated a lysine analog, [ 3 H]putrescine, into a protein complex which remained at the top of an acrylamide gel upon electrophoresis in SDS and reducing agents. The complex has now been isolated by extracting the plasma membranes with detergent (octylglucoside) resuspending the detergent insoluble residues in 6 M guanidine HCl and chromatographing the residue on a 4% agarose column in 6 M guanidine HCl. Most of the radioactivity is found in the void volume fractions from the column. SDS polyacrylamide gel electrophoresis shows that these fractions contain mostly proteins that do not enter the acrylamide gel. Since this purification procedure is essentially the same as that used to isolate a rat hepatocyte adhesion factor from rat liver plasma membranes it is possible that the large molecular weight transglutaminase substrate and the adhesion factor are contained in the same protein aggregate

  16. Some effects of curry feeding on the rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Opitz, S B

    1981-01-01

    The liver is the major site for the biotransformation and metabolism of most foreign substances that are absorbed into the body via the gastrointestinal tract. The present investigation was undertaken to ascertain whether curry spice constituents, affected liver function. Rats were administered curry powder either intragastrically by intubation, or mixed into their food. Liver function was assessed employing both biochemical and morphological approaches. Two non-invasive tests designed to appraise the in vivo drug-metabolising capabilities of the liver were utilised, viz. the aminopyrine breath test and the measurement of urinary ascorbic acid excretion. The functional integrity of the liver was also assessed by light and electron microscopy. There was no evidence to suggest that curry feeding influenced the hepatic drug-metabolising system as determined by the biochemical studies. The electron microscopical studies did, however, reveal increased activity of the Golgi complex and the lytic compartment. /sup 14/CO/sub 2/ exhalation curves were found to undergo a change in shape from the expected single exponential decay to one in which two phases could be distinguished, which has not been previously reported. Furthermore, in vitro work by other investigators has indicated that aminopyrine and its major metabolites might be involved in a complex series of product-inhibition events. Finally, the occurrence of elongated, dumb-bell shaped mitochondria, with well-defined elaborations of the inner membrane, were noted as a characteristic feature in the hepatocytes situated immediately adjacent to the central venule.

  17. Effects of Exercise Training on Molecular Markers of Lipogenesis and Lipid Partitioning in Fructose-Induced Liver Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Siham Yasari

    2012-01-01

    Full Text Available The present study was designed to investigate the impact of exercise training on lipogenic gene expression in liver and lipid partitioning following the ingestion of a high fructose load. Female rats were exercise-trained for 8 wk or kept sedentary before being submitted to a fasting/refeeding protocol. Rats were further subdivided as follow: rats were fasted for 24 h, refed a standard diet for 24 h, starved for another 24 h, and refed with a standard or a high-fructose diet 24 h before sacrifice. Fructose refeeding was associated with an increase in hepatic lipid content, endocannabinoid receptor 1, sterol regulatory element-binding protein1c, and stearoyl-CoA desaturase1 gene expression in both Sed and TR rats. However, desaturation indexes measured in liver (C16 : 1/C16 : 0 and C18 : 1/C18 : 0 and plasma (C18 : 1/C18 : 0 were higher (P<0.01 in TR than in Sed rats following fructose refeeding. It is concluded that exercise training does not significantly affect fat accumulation and the molecular expression of genes involved in lipogenesis after fasting and fructose refeeding but does modify the partitioning of lipids so as to provide more unsaturated fatty acids in liver without affecting liver fat content.

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

    International Nuclear Information System (INIS)

    Chapman, D.E.; Moore, T.J.; Michener, S.R.; Powis, G.

    1990-01-01

    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

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

    International Nuclear Information System (INIS)

    Braquet, Monique.

    1979-06-01

    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 [fr

  20. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Atrayee Banerjee

    Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  1. Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids.

    Directory of Open Access Journals (Sweden)

    Cyrill Géraud

    Full Text Available Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ, i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

  2. Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct-ligated rat model.

    Science.gov (United States)

    Wang, Ya-Yu; Lin, Shih-Yi; Chen, Wen-Ying; Liao, Su-Lan; Wu, Chih-Cheng; Pan, Pin-Ho; Chou, Su-Tze; Chen, Chun-Jung

    2017-05-23

    In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were orally administrated using gastric gavages. Liver tissues and bloods were collected and subjected to evaluation using histological, molecular, and biochemical approaches. Using a rat model of cholestasis caused by bile duct ligation (BDL), daily oral administration of Glechoma hederacea hot water extracts showed protective effects against cholestatic liver injury, as evidenced by the improvement of serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced transforming growth factor beta-1 (TGF-β1), connective tissue growth factor, and collagen expression, and the anti-fibrotic effects were accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory cell infiltration/accumulation, NF-κB and AP-1 activation, and inflammatory cytokine production. Further studies demonstrated an inhibitory effect of Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) intracellular signaling pathways. The hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of daily Glechoma hederacea extracts supplementation were associated with anti-oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down

  3. The metabolic effects of diuron in the rat liver.

    Science.gov (United States)

    da Silva Simões, Mellina; Bracht, Lívia; Parizotto, Angela Valderrama; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar

    2017-09-01

    A systematic study on the effects of diuron on the hepatic metabolism was conducted with emphasis on parameters linked to energy metabolism. The experimental system was the isolated perfused rat liver. The results demonstrate that diuron inhibited biosynthesis (gluconeogenesis) and ammonia detoxification, which are dependent of ATP generated within the mitochondria. Conversely, it stimulated glycolysis and fructolysis, which are compensatory phenomena for an inhibited mitochondrial ATP generation. Furthermore, diuron diminished the cellular ATP content under conditions where the mitochondrial respiratory chain was the only source of this compound. Besides the lack of circulating glucose due to gluconeogenesis inhibition, one can expect metabolic acidosis due to excess lactate production, impairment of ammonia detoxification and cell damage due to a deficient maintenance of its homeostasis. Some of the general signs of toxicity that were observed in diuron-treated rats can be attributed, partly at least, to the effects of the herbicide on energy metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Analysis of 3-MCPD- and 3-MCPD dipalmitate-induced proteomic changes in rat liver.

    Science.gov (United States)

    Braeuning, Albert; Sawada, Stefanie; Oberemm, Axel; Lampen, Alfonso

    2015-12-01

    3-Monochloropropane-1,2-diol (3-MCPD) and 3-MCPD fatty acid esters are process contaminants in foodstuff which are generated during thermal treatment. Long-term exposure to 3-MCPD or 3-MCPD esters causes toxicity especially in kidney and testis. 3-MCPD esters are efficiently hydrolyzed in the gastrointestinal tract, suggesting that their toxicity is mediated by free 3-MCPD. Combined exposure to free 3-MCPD and 3-MCPD released from 3-MCPD esters might lead to dietary consumption above the tolerable daily intake of 2 μg/kg body weight/day. Suspected mechanisms of 3-MCPD toxicity include the inhibition of glycolysis and oxidative stress. Here, a comparative proteomic approach was followed to analyze the effects of 3-MCPD or 3-MCPD dipalmitate in livers from rats exposed to 10 mg/kg body weight 3-MCPD, an equimolar dose of 3-MCPD dipalmitate, or a 4-fold lower dose of the ester during a 28-day repeated-dose feeding study. Early cellular changes were monitored in the absence of overt toxicity. A comprehensive view of 3-MCPD- or 3-MCPD dipalmitate-triggered proteomic changes in rat liver links to previously proposed mechanisms of toxicity and substantially extends our knowledge on molecular hepatic effects of 3-MCPD. Organ-independent marker proteins altered upon 3-MCPD exposure, for example DJ-1/PARK7, were identified by comparison of the proteomic patterns of kidney, testis and liver. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Effect of triiodothyronine on rat liver chromatin protein kinase

    International Nuclear Information System (INIS)

    Kruh, J.; Tichonicky, L.

    1976-01-01

    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 32 P when incubated with [γ- 32 P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32 P 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.) [de

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

    NARCIS (Netherlands)

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

    1994-01-01

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

  7. Effect of Salvia miltiorrhiza Bge extract on liver cirrhosis in rats | Li ...

    African Journals Online (AJOL)

    Purpose: To explore the effects of Salvia miltiorrhiza Bge.extract(SMBE) on diethylnitrosamine(DEN)- induced liver cirrhosis in rats. Methods: SMBE was obtained by extracting dried Salvia miltiorrhiza Bge. in water. Liver cirrhosis was induced in Wistar rats by injecting diethylnitrosamine in abdominal cavity once a week for ...

  8. Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

    Science.gov (United States)

    Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

    1999-04-01

    Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

  9. Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

    Directory of Open Access Journals (Sweden)

    Nor Aziyah Mat-Rahim

    2017-01-01

    Full Text Available Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08 were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA. These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP and gamma-glutamyl transferase (GGT levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x and level of GGT (more than 2x in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.

  10. Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.

    Science.gov (United States)

    Petrović, Anja; Bogojević, Desanka; Korać, Aleksandra; Golić, Igor; Jovanović-Stojanov, Sofija; Martinović, Vesna; Ivanović-Matić, Svetlana; Stevanović, Jelena; Poznanović, Goran; Grigorov, Ilijana

    2017-11-01

    The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.

  11. A high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats

    Directory of Open Access Journals (Sweden)

    M. Ueno

    2000-12-01

    Full Text Available Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-1/2 in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05. There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 ± 4% (P<0.05 in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-1/2 phosphorylation, to 83 ± 5% (P<0.05 in liver and to 77 ± 4% (P<0.05 in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding.

  12. Portal hypertension and liver cirrhosis in rats: effect of the β3-adrenoceptor agonist SR58611A

    Science.gov (United States)

    Vasina, Valentina; Giannone, Ferdinando; Domenicali, Marco; Latorre, Rocco; Berzigotti, Annalisa; Caraceni, Paolo; Zoli, Marco; De Ponti, Fabrizio; Bernardi, Mauro

    2012-01-01

    BACKGROUND AND PURPOSE β3-Adrenoceptors participate in the regulation of vascular tone in physiological and pathological conditions. We aimed to assess the effect of pharmacological modulation of β3-adrenoceptors on portal pressure (PP) and systemic haemodynamics and their expression in the liver and mesenteric vessels of cirrhotic rats. EXPERIMENTAL APPROACH PP, central venous pressure (CVP) and systemic haemodynamics were invasively assessed in control and CCl4-treated cirrhotic rats before and during infusion of the selective β3-adrenoceptor agonist, SR58611A. Tissue samples were also collected from liver, heart, portal vein and mesenteric artery for immunohistochemistry and molecular biology analysis. The effect of SR58611A on isolated portal vein was assessed. KEY RESULTS At baseline, cirrhotic rats showed portal hypertension, reduced CVP and hyperdynamic circulation. SR58611A induced a significant, dose-dependent decrease in PP in cirrhotic rats, but not in controls. Although both groups manifested a dose-dependent reduction in mean arterial pressure, this effect was associated with decreased cardiac index (CI) and unchanged indicized peripheral vascular resistance (PVRI) in cirrhotic rats and increased CI and decreased PVRI in control animals. Pretreatment with the selective β3-adrenoceptor antagonist SR59230 prevented all SR58611A-induced changes in cirrhotic rats. SR58611A concentration-dependently relaxed portal vein in cirrhotic rats to a significantly greater extent than in healthy rats; pretreatment with SR59230A completely prevented SR58611A-induced cirrhotic portal vein relaxation. Finally, β3-adrenoceptors were identified in the liver, heart and portal vein of cirrhotic and control animals; their expression was increased in cirrhotic rats. CONCLUSIONS AND IMPLICATIONS β3-Adrenoceptors are altered in portal hypertension of experimental cirrhosis and may represent a novel therapeutic target. PMID:22708587

  13. Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism.

    Science.gov (United States)

    Briley-Saebo, Karen C; Johansson, Lars O; Hustvedt, Svein Olaf; Haldorsen, Anita G; Bjørnerud, Atle; Fayad, Zahi A; Ahlstrom, Haakan K

    2006-07-01

    We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.

  14. Bicarbonate sulfate exchange in canalicular rat liver plasma membrane vesicles

    International Nuclear Information System (INIS)

    Meier, P.J.; Valantinas, J.; Hugentobler, G.; Rahm, I.

    1987-01-01

    The mechanism(s) and driving forces for biliary excretion of sulfate were investigated in canalicular rat liver plasma membrane vesicles (cLPM). Incubation of cLPM vesicles in the presence of an inside-to-outside (in, out) bicarbonate gradient but not pH or out-to-in sodium gradients, stimulated sulfate uptake 10-fold compared with the absence of bicarbonate and approximately 2-fold above sulfate equilibrium (overshoot). Initial rates of this bicarbonate gradient-driven [ 35 S]-sulfate uptake were saturable with increasing concentrations of sulfate and could be inhibited by probenecid, N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate, acetazolamide, furosemide, 4-acetamideo-4'-isothiocyanostilbene-2,2'-disulfonic acid, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (IC 50 , ∼40 μM). Cisinhibition of initial bicarbonate gradient-stimulated sulfate uptake and transstimulation of sulfate uptake in the absence of bicarbonate were observed with sulfate, thiosulfate, and oxalate but not with chloride, nitrate, phosphate, acetate, lactate, glutamate, aspartate, cholate, taurocholate, dehydrocholate, taurodehydrocholate, and reduced or oxidized glutathione. These findings indicate the presence of a sulfate (oxalate)-bicarbonate anion exchange system in canalicular rat liver plasma membranes. These findings support the concept that bicarbonate-sensitive transport system might play an important role in bile acid-independent canalicular bile formation

  15. Some factors influencing liver metallothionein levels in rats and mice

    International Nuclear Information System (INIS)

    Jang, T.; Lee, M.

    1981-01-01

    Liver metallothionein (MT) was measured by the 203-mercury binding method of Piotrowski in the livers of rats and mice subjected to bilateral adrenalectomy or to sham adrenalectomy. Sham operation was followed by an increase in the level of MT at 24 hours; this immediately began to decrease, reaching control levels by 7 days. Adrenalectomy was also followed by an increase in MT, but the levels remained elevated for several days before beginning to decline. Mice which were adrenalectomized and allowed to recover for 28 days showed an increase in MT when subjected to sham operation. Ether anaesthesia without an incision did not increase the level of MT. Hypophysectomized mice had higher levels of MT than did controls, and these levels were further increased by sham adrenalectomy. Sprague-Dawley rats showed a similar response to adrenalectomy and to sham operation. It is concluded that the sham operation-induced increase in MT is probably not a result of a stress-induced release of adrenal hormones, but that adrenal hormones may play some role in the degradation or turnover of MT. The pituitary may also have some role in MT turnover

  16. The effects of comfrey derived pyrrolizidine alkaloids on rat liver.

    Science.gov (United States)

    Yeong, M L; Clark, S P; Waring, J M; Wilson, R D; Wakefield, S J

    1991-01-01

    Three groups of young adult rats were fed pyrrolizidine alkaloids derived from Russian comfrey to study the effects of the herb on the liver. Group I animals received a single dose of 200 mg/kg body wt, Group II 100 mg/kg three times a week for 3 weeks and Group III 50 mg/kg three times a week for 3 weeks. All rats showed light and electron-microscopic evidence of liver damage, the severity of which was dose dependent. There was swelling of hepatocytes and hemorrhagic necrosis of perivenular cells. There was a concomitant loss of sinusoidal lining cells with disruption of sinusoidal wall and the sinusoids were filled with cellular debris, hepatocyte organelles and red blood cells. Extravasation of red blood cells was evident. Terminal hepatic venules were narrowed by intimal proliferation, and in Group II and III, reiculin fibres radiated from these vessels. These appearances have been described in veno-occlusive disease due to pyrrolizidine alkaloids from other plant sources such as Senecio and Crotalaria. The safety of comfrey, a widely used herb, in relation to human consumption requires further investigation.

  17. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats

    Directory of Open Access Journals (Sweden)

    Orner Gayle A

    2006-02-01

    Full Text Available Abstract Chlorophyllin (CHL is a promising chemopreventive agent believed to block cancer primarily by inhibiting carcinogen uptake through the formation of molecular complexes with the carcinogens. However, recent studies suggest that CHL may have additional biological effects particularly when given after the period of carcinogen treatment. This study examines the post-initiation effects of CHL towards aflatoxin B1 (AFB1-induced preneoplastic foci of the liver and colon. The single concentration of CHL tested in this study (0.1% in the drinking water had no significant effects on AFB1-induced foci of the liver and colons of rats.

  18. Establishment of a rat model of early-stage liver failure and Th17/Treg imbalance

    OpenAIRE

    LI Dong; LU Zhonghua; GAN Jianhe

    2016-01-01

    ObjectiveTo investigate the methods for establishing a rat model of early-stage liver failure and the changes in Th17, Treg, and Th17/Treg after dexamethasone and thymosin interventions. MethodsA total of 64 rats were randomly divided into carbon tetrachloride (CCl4) group and endotoxin [lipopolysaccharide (LPS)]/D-galactosamine (D-GalN) combination group to establish the rat model of early-stage liver failure. The activities of the rats and changes in liver function and whole blood Th17 and ...

  19. Evaluation of methylmercury biotransformation using rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-09-01

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

  20. Fibronectin binding to gangliosides and rat liver plasma membranes

    Energy Technology Data Exchange (ETDEWEB)

    Matyas, G R; Evers, D C; Radinsky, R; Morre, D J

    1986-02-01

    Binding of fibronectins to gangliosides was tested directly using several different in vitro models. Using an enzyme-linked immunoabsorbent assay (ELISA), gangliosides were immobilized on polystyrene tubes and relative binding of fibronectin was estimated by alkaline phosphatase activity of conjugated second antibody. Above a critical ganglioside concentration, the gangliosides bound the fibronectin (G/sub T1b/ approx. = G/sub D1b/ approx. = G/sub D1a/ > G/sub M1/ >> G/sub M2/ approx. = G/sub D3/ approx. = G/sub M3/) in approximately the same order of efficiency as they competed for the cellular sites of fibronectin binding in cell attachment assays. Alternatively, these same gangliosides bound to immobilized fibronectin. Rat erythrocytes coated with gangliosides G/sub M1/, G/sub D1a/ or G/sub T1b/ bound more fibronectin than erythrocytes not supplemented with gangliosides. Using fibronectin in which lysine residues were radioiodinated, an apparent K/sub d/ for binding to mixed rat liver gangliosides of 7.8 x 10/sup -9/ M was determined. This value compared favorably with the apparent K/sub d/ for attachment of fibronectin to isolated plasma membranes from rat liver of 3.7 x 10/sup -9/ M for fibronectin modified on the tyrosine residue, or 6.4 x 10/sup -9/ M for fibronectin modified on lysine residues. As shown previously by Grinnell and Minter, fibronectin modified on tyrosine residues did not promote spreading and attachment of CHO cells. It did, however, bind to cells. In contrast, lysine-modified fibronectin both bound to cells and promoted cell attachment. Plasma membranes isolated from hepatic tumors in which the higher gangliosides that bind fibronectin were depleted bound 43-75% less (/sup 125/I)fibronectin than did plasma membranes from control livers. The findings were consistent with binding of fibronectins to gangliosides, including the same gangliosides depleted from cell surfaces during tumorigenesis in the rat.

  1. Free methionine supplementation limits alcohol-induced liver damage in rats

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Bode, C.; Bode, J.C.

    1998-01-01

    Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accu...

  2. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

    Directory of Open Access Journals (Sweden)

    Claudio M. Mastroianni

    2014-05-01

    Full Text Available Chronic hepatitis C virus (HCV infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV. Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

  3. Evaluation of rat liver apoptotic and necrotic cell death after cold storage using UW, HTK, and Celsior

    NARCIS (Netherlands)

    Straatsburg, Irene H.; Abrahamse, Salomon L.; Song, Shao W.; Hartman, Robin J.; van Gulik, Thomas M.

    2002-01-01

    Background. The benefit of Celsior in liver graft preservation is controversial. In the isolated perfused rat liver model, we compared the effects of Celsior, University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) preservation solutions on liver cell death. Methods. Rat livers

  4. Binding of triiodothyronine to rat liver nuclear matrix. influence of thyroid hormones on the phosphorylation of nuclear matrix proteins

    International Nuclear Information System (INIS)

    Adylova, A.T.; Atakhanova, B.A.

    1986-01-01

    The interaction of thyroid hormones with rat liver nuclear matrix proteins was investigated. It was shown that the nuclear matrix contains sites that bind triiodothyronine with high affinity (K = 1.07.10 9 M -1 ) and limited capacity (the maximum binding capacity is equal to 28 /SUP a/ .5 fmoles of triiodothyronine per 100 ug protein). Electrophoretic identification of the matrix proteins that bind triiodothyronine was performed. The molecular weight of the main triiodothyronine-binding fraction is 50,000-52,000. It was shown that the administration of triiodothyronine to thyroidectomized rats stimulates the phosphorylation of all the protein fractions of the nuclear matrix

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

    International Nuclear Information System (INIS)

    Komov, V.P.; Strelkova, M.A.

    1975-01-01

    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

  6. Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Takaoki Saneyasu

    2016-01-01

    Full Text Available Tissue and matrix stiffness affect cell properties during morphogenesis, cell growth, differentiation, and migration and are altered in the tissue remodeling following injury and the pathological progression. However, detailed molecular mechanisms underlying alterations of stiffness in vivo are still poorly understood. Recent engineering technologies have developed powerful techniques to characterize the mechanical properties of cell and matrix at nanoscale levels. Extracellular matrix (ECM influences mechanical tension and activation of pathogenic signaling during the development of chronic fibrotic diseases. In this short review, we will focus on the present knowledge of the mechanisms of how ECM stiffness is regulated during the development of liver fibrosis and the molecules involved in ECM stiffness as a potential therapeutic target for liver fibrosis.

  7. Molecular pathways in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Berlanga A

    2014-07-01

    Full Text Available Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV, IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA

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

    Directory of Open Access Journals (Sweden)

    D. V. Grizay

    2015-01-01

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

  9. Biochemical Changes in the Serum and Liver of albino rats exposed ...

    African Journals Online (AJOL)

    Biochemical changes in the serum and liver of albino rats chronically exposed to rats administered 5gk-1 , 7.5gk-1 and 15gk-1 of gasoline , kerosine and crude petroleum(bonny light) respectively were studied. The petroleum samples were administered intraperitoneally and the biochemical changes in the rat serum and the ...

  10. Biochemical changes in the liver, kidney and serum of rat following ...

    African Journals Online (AJOL)

    The effect of repeated administration of cimetidine, an antiulcer agent, twice daily for 7days on the phosphatase (acid and alkaline) and some function indices of rat liver and kidney was investigated. Sixty-four white albino rats were randomly grouped into two, A and B. Group A which consisted of 32 rats served as the ...

  11. In vivo postprandial lipid partitioning in liver and muscle of diabetic rats is disturbed

    NARCIS (Netherlands)

    Prompers, J.J.; Jonkers, R.A.M.; Loon, van L.J.C.; Nicolay, K.

    2012-01-01

    Objective: To study in vivo lipid partitioning in insulin-resistant liver and muscle of diabetic rats using magnetic resonance spectroscopy (MRS). Methods: Four groups of n=6 male Zucker diabetic fatty rats were used for this study: obese, pre-diabetic fa/fa rats and lean, non-diabetic fa/+

  12. Study on Biochemical Indices of Liver Function Tests of Albino Rats ...

    African Journals Online (AJOL)

    bilirubin, ALT (in rats fed with palm and groundnut oil-based diet), AST (in rats fed with coconut ... These results therefore, indicate a compromise in liver of rats administered 10% oil - based diet. ..... medicinal plants II: Effects of Aplotaxis lappa.

  13. Livers from fasted rats acquire resistance to warm and cold ischemia injury.

    Science.gov (United States)

    Sumimoto, R; Southard, J H; Belzer, F O

    1993-04-01

    Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold

  14. Selective inhibition by chloramphenicol of pregnenolone-16 α-carbonitrile-inducible rat liver cytochrome P-450 isozymes

    International Nuclear Information System (INIS)

    Graves, P.E.; Kaminsky, L.S.; Halpert, J.

    1986-01-01

    Pregnenolone-16 α-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effect of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of 14 C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver

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

    International Nuclear Information System (INIS)

    Amer, M.M.; Michael, M.I.

    2010-01-01

    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

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

    International Nuclear Information System (INIS)

    Borgnon, Josephine; Djamouri, Fatima; Lorand, Isabelle; Rico, Virginie Di; Loux, Nathalie; Pages, Jean-Christophe; Franco, Dominique; Capron, Frederique; Weber, Anne

    2005-01-01

    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

  17. Membrane potential of mitochondria from the liver of irradiated rats

    International Nuclear Information System (INIS)

    Fomenko, B.S.; Kaminin, A.N.; Elfimova, I.A.; Akoev, I.G.

    1977-01-01

    Measurements of the membrane potential of rat liver mitochondria 1 hour after irradiation with 800 R dose showed a decrease of its value. The potential decreased against the background of the activation of the generating mechanisms (the electron transport chain and ATP-ases). During energization of the membranes by the electron transport chain similar effect has been observed with different oxidation substrates (NAD linked substrates and succinate). It suggests that similar causative factors are at the basis of the changes observed. It is quite possible that the increase in the rate of both mitochondria respiration and ATP hydrolysis after the irradiation of animals was a consequence of the radiation-induced decrease in the potential value. (author)

  18. Effects of insulin on messenger RNA activities in rat liver

    International Nuclear Information System (INIS)

    Hill, R.E.; Lee, K.L.; Kenney, F.T.

    1981-01-01

    Liver poly(A) RNA, isolated from adrenalectomized rats after insulin treatment, was translated in a nuclease-treated lysate of rabbit reticulocytes and quantitated for both total activity and the capacity to synthesize the insulin-inducible enzyme tyrosine amino-transferase. Analysis of the translated products from poly(A) RNA isolated 1 h after insulin treatment showed a 2.7-fold increase in activity of tyrosine aminotransferase mRNA. During the same interval, the capacity of poly(A) RNA to direct the synthesis of total protein in lysates also changed, showing a 30 to 40% increase in translational activity/unit of RNA. Increased translatability was apparent in all fractions of poly(A) RNA separated by centrifugation on sucrose gradients. Insulin thus appears to mediated a generalized changed in mRNAs leading to increased capacity for translation; induction of tyrosine aminotransferase may reflect unusual sensitivity to this effect of the hormone

  19. Isolation of plasma membrane-associated membranes from rat liver.

    Science.gov (United States)

    Suski, Jan M; Lebiedzinska, Magdalena; Wojtala, Aleksandra; Duszynski, Jerzy; Giorgi, Carlotta; Pinton, Paolo; Wieckowski, Mariusz R

    2014-02-01

    Dynamic interplay between intracellular organelles requires a particular functional apposition of membrane structures. The organelles involved come into close contact, but do not fuse, thereby giving rise to notable microdomains; these microdomains allow rapid communication between the organelles. Plasma membrane-associated membranes (PAMs), which are microdomains of the plasma membrane (PM) interacting with the endoplasmic reticulum (ER) and mitochondria, are dynamic structures that mediate transport of proteins, lipids, ions and metabolites. These structures have gained much interest lately owing to their roles in many crucial cellular processes. Here we provide an optimized protocol for the isolation of PAM, PM and ER fractions from rat liver that is based on a series of differential centrifugations, followed by the fractionation of crude PM on a discontinuous sucrose gradient. The procedure requires ∼8-10 h, and it can be easily modified and adapted to other tissues and cell types.

  20. Purification and characterization of the V1 vasopressin receptor from rat liver

    International Nuclear Information System (INIS)

    Fishman, J.B.; Dickey, B.F.; Attisano, C.; Fine, R.E.

    1987-01-01

    The rat liver V1 vasopressin receptor was purified approximately 21,000-fold from rat liver microsomes. The receptor was solubilized from membranes using the zwitterionic detergent CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate). Since the V1 receptor loses its ability to bind ligand when solubilized, the authors devised a liposome reconstitution system to assay vasopressin binding activity during purification. The purified receptor exhibits a K/sub d/ of 6 nm, when, prior to solubilization, the membranes were exposed to 1 μm vasopressin. This resulted in the association of a pertussis-toxin insensitive guanine-nucleotide binding protein with the receptor during most of the purification procedure. The authors are further characterizing the V1-associated G-proteins. In the absence of this association, the receptor has a K/sub d/ of 30 nM. Crosslinking of 125 I-vasopressin to a partially purified preparation of receptor demonstrated that the receptor had a molecular weight of approximately 68,000 under reducing conditions, and 58,000 under non-reducing conditions. The purification procedure may prove useful in purifying a number of small peptide hormone receptors (e.g., bradykinin, angiotensin II) and perhaps their associated G-proteins as well

  1. Evaluation of usefulness of 99mTc-GSA liver scintigraphy on fatty liver in the rat

    International Nuclear Information System (INIS)

    Kimoto, Mitsunori; Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo; Sakae, Katsuyoshi; Nagaya, Isao; Takeda, Yoshihiro; Hiraki, Yoshio

    1994-01-01

    99m Tc-GSA is a new liver-imaging radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes. We evaluated liver injury induced by fatty infiltration in the rats. Studies were performed in the Wistar rats under control conditions (6 cases), and with choline deficiency diet for 2, 4, 6, 10 and 12 weeks (6 cases respectively). 99m Tc-GSA was administered via the inferior vena cava. Immediately after injection, a dynamic imaging study was performed for 30 min. t 90 (the time at which the liver time-activity curve reached 90% of its peak), K u and K d (calculated by 2 compartment model) were used as parameters which reflect on asialoglycoprotein receptors on the hepatocytes. t 90 prolonged, and K u and K d decreased according to the severity of fatty infiltration. These results suggest that 99m Tc-GSA is useful for evaluating liver injury induced by fatty infiltration. (author)

  2. Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

    Science.gov (United States)

    D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

    2013-05-01

    Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

  3. 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)

    Brooks, A.L.; Guilmette, R.A.; Hahn, F.F.; Jirtle, R.L.

    1985-01-01

    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 238 Pu-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 238 Pu 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

  4. Oxidation of esterified arachidonate by rat liver microsomes

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    International Nuclear Information System (INIS)

    Saling, Simoni Cristina; Comar, Jurandir Fernando; Mito, Márcio Shigueaki; Peralta, Rosane Marina; Bracht, Adelar

    2011-01-01

    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

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

    DEFF Research Database (Denmark)

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

    1985-01-01

    Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had...... 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...

  7. Study in radiation tolerance of damaged liver induced by dimethylaminoazobenzene. Histological study using Wistar rats

    International Nuclear Information System (INIS)

    Izumiyama, Kazutaka; Kodama, Akihisa; Kono, Michio

    1997-01-01

    We studied to determine the tolerable dose of radiation in damaged liver using Wistar male rats aged 4 weeks. A damaged liver group fed on low-protein animal chow containing 0.07% dimethylaminoazobenzene (DAB) ad libitum. Rats feeding on the chow without DAB served as the normal liver group. In both groups, two rats each underwent irradiation of the right half of the liver with doses of 5 Gy, 10 Gy, 15 Gy, or 20 Gy using a 15 MeV electron beam. The animals were sacrificed 2 or 4 weeks after irradiation, and the irradiated and non-irradiated parts of the liver were compared histologically with respect to hepatocellular necrosis, the extent of degeneration, and the degree of inflammatory cell infiltration, as well as the degree of inflammatory cell infiltration and fibrosis in Glisson's capsule. Secondly, in the normal liver group, 6 rats were irradiated with dose of 20 Gy, and in the damaged liver group, 6 rats each were irradiated with doses of 10 Gy, 12 Gy, 15 Gy or 20 Gy, and the same study was performed. In the normal liver group, no histological differences were seen between the irradiated and non-irradiated parts of the liver even when irradiated with 20 Gy dose. In the damaged liver group, there were no differences between the irradiated and non-irradiated parts of the liver in animals given 15 Gy or 10 Gy. In the 12 Gy group, however, one out of three rats each showed more severe changes in the irradiated part at 2 and 4 weeks after irradiation. One out of six rats in the 15 Gy group and four out of six rats in the 20 Gy group died in the first week after irradiation. In the damaged liver group, a single irradiation of up to 10 Gy delivered to one half of the liver was tolerable. At doses of 12 Gy or higher, however, irreversible changes occurred in some animals, and deaths occurred at 15 Gy or 20 Gy. Since even 20 Gy was tolerated in the normal liver group, damaged liver showed a lower tolerance than normal liver. (author)

  8. Homodynamic changes with liver fibrosis measured by dynamic contrast-enhanced MRI in the rat

    International Nuclear Information System (INIS)

    Kubo, Hitoshi; Harada, Masafumi; Ishikawa, Makoto; Nishitani, Hiromu

    2006-01-01

    The purpose of this study was to evaluate the hemodynamic changes of liver cirrhosis in the rat and investigate the relationship between hemodynamic changes and properties of fibrotic change in the liver. Three rats with cirrhosis induced by thioacetamide (TAA), three with disease induced by carbon tetrachloride (CCl 4 ), and three with no treatment were measured on dynamic MRI using a 1.5T scanner. Compartment and moment analysis were used to quantitate hemodynamic changes. Compartment model analysis showed that increased transition speed from vessels to the liver correlated with grade of liver fibrosis. Moment analysis demonstrated that decrease of area under the curve (AUC), mean residence time (MRT), variance of residence time (VRT), half life (T1/2) and increased total clearance (CL) correlated with grade of liver fibrosis. Hemodynamic changes in injured fibrotic liver may be influenced by the grade of fibrosis. Compartment model and moment analysis may be useful for evaluating hemodynamic changes in injured liver. (author)

  9. Effect of starvation, diabetes and insulin on the casein kinase 2 from rat liver cytosol.

    OpenAIRE

    Martos, C; Plana, M; Guasch, M D; Itarte, E

    1985-01-01

    Starvation, diabetes and insulin did not alter the concentration of casein kinases in rat liver cytosol. However, the Km for casein of casein kinase 2 from diabetic rats was about 2-fold lower than that from control animals. Administration of insulin to control rats did not alter this parameter, but increased the Km for casein of casein kinase 2 in diabetic rats. Starvation did not affect the kinetic constants of casein kinases. The effect of diabetes on casein kinase 2 persisted after partia...

  10. EFFECTS OF RESVERATROL ON LIVER FUNCTION OF OBESE FEMALE WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Nádia Araújo Miguel

    2016-07-01

    Full Text Available Resveratrol has antioxidant, anti-inflammatory, lipolytic, and antifibrotic properties, which may be useful in supplementation of obese patients and with liver problems. This study evaluated the effects of 6-week resveratrol supplementation on the lipid profile and liver function of female Wistar rats fed a high-fat diet to induce obesity. Sixty-four Wistar rats were divided into 4 groups (n = 16: the control group (C; the control obese group (CO; the resveratrol group (R; and the resveratrol obese group (RO. At the end of the experiment, the animals were anesthetized for blood collection and subsequent euthanasia for collection of liver biopsy. The parameters for body weight, liver weight, retroperitoneal fat weight, serum lipid and liver profiles and histopathological analysis were evaluated. The 6-week resveratrol administration did not induce weight loss nor did it reduce the lipid profile; however, it decreased the liver enzymes aspartate aminotransferase (AST and alkaline phosphatase (ALP and reduced the incidence of steatosis (75.0% in group RO compared with group CO (81.2%. Thus, we concluded that resveratrol supplementation for the short period of six weeks had a beneficial effect on liver function by reducing hepatic steatosis and the liver enzymes AST and ALP in obese female rats. Keywords: liver function; obesity; rats; resveratrol.

  11. Identification of high-affinity calmodulin-binding proteins in rat liver

    International Nuclear Information System (INIS)

    Hanley, R.M.; Dedman, J.R.; Shenolikar, S.

    1987-01-01

    The Ca 2+ -dependent binding of [ 125 I] calmodulin (CaM) to hepatic proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was utilized to identify CaM binding or acceptor proteins or CAPs. Two proteins of apparent molecular weight of 60,000 (CAP-60) and 45,000 (CAP-45) comprised > 80% of the Ca 2+ -dependent CaM binding in rat liver cytosol. CAP-60 and CAP-45 were partially purified by a variety of chromatographic steps, including affinity chromatography on CaM Sepharose. CAP-60 possessed a native molecular size of 400,000, indicating it to be the CaM-binding subunit of a larger oligomeric complex. In contrast, CAP-45 was monomeric as judged by gel filtration. Neither CAP-60 nor CAP-45 possessed chromatographic properties consistent with known CaM-dependent enzymes reported in the literature. Two-dimensional peptide mapping provided convincing evidence that CAP-60 and CAP-45 were unrelated to other well-characterized CAPs, namely Ca 2+ (CaM)-dependent protein kinase II, calcineurin, or the CaM-dependent cyclic nucleotide phosphodiesterase. The relative abundance and high affinity for CaM could suggest that these novel target proteins, CAP-60 and CAP-45, represent a dominant pathway for CaM action in the mammalian liver

  12. Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration

    DEFF Research Database (Denmark)

    Jelnes, Peter; Santoni-Rugiu, Eric; Rasmussen, Morten

    2007-01-01

    The experimental protocols used in the investigation of stem cell-mediated liver regeneration in rodents are characterized by activation of the hepatic stem cell compartment in the canals of Hering followed by transit amplification of oval cells and their subsequent differentiation along hepatic...... the molecular phenotypes of oval cells in several of the most commonly used protocols of stem cell-mediated liver regeneration-namely, treatment with 2-acetylaminofluorene and partial (70%) hepatectomy (AAF/PHx); a choline-deficient, ethionine-supplemented (CDE) diet; a 3,5-diethoxycarbonyl-1,4-dihydro...... remarkable phenotypic discrepancies exhibited by oval cells in stem cell-mediated liver regeneration between rats and mice and underline the importance of careful extrapolation between individual species....

  13. 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.

  14. Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

    Science.gov (United States)

    Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

    2011-09-01

    A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

  15. 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.

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

    NARCIS (Netherlands)

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

    1969-01-01

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

  17. Diurnal variation in glycogen phosphorylase activity in rat liver. A quantitative histochemical study

    NARCIS (Netherlands)

    Frederiks, W. M.; Marx, F.; Bosch, K. S.

    1987-01-01

    The diurnal variations of the glycogen content and of glycogen phosphorylase activity in periportal and pericentral areas of rat liver parenchyma have been analyzed in periodic acid Schiff (PAS)-stained cryostat sections using quantitative microdensitometry. Glycogen content and phosphorylase

  18. Existence of Inverted Profile in Chemically Responsive Molecular Pathways in the Zebrafish Liver

    Science.gov (United States)

    Zhang, Xun; Li, Hu; Ma, Jing; Zhang, Louxin; Li, Baowen; Gong, Zhiyuan

    2011-01-01

    How a living organism maintains its healthy equilibrium in response to endless exposure of potentially harmful chemicals is an important question in current biology. By transcriptomic analysis of zebrafish livers treated by various chemicals, we defined hubs as molecular pathways that are frequently perturbed by chemicals and have high degree of functional connectivity to other pathways. Our network analysis revealed that these hubs were organized into two groups showing inverted functionality with each other. Intriguingly, the inverted activity profiles in these two groups of hubs were observed to associate only with toxicopathological states but not with physiological changes. Furthermore, these inverted profiles were also present in rat, mouse, and human under certain toxicopathological conditions. Thus, toxicopathological-associated anti-correlated profiles in hubs not only indicate their potential use in diagnosis but also development of systems-based therapeutics to modulate gene expression by chemical approach in order to rewire the deregulated activities of hubs back to normal physiology. PMID:22140468

  19. 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.

  20. [Change in histone proteins in rat liver chromatin during exposure of the animal to functional stress].

    Science.gov (United States)

    Panin, L E; Svechnikova, I G; Maianskaia, N N

    1996-01-01

    Pattern of rat liver histones at intensive physical exercises with preliminary injection of lysosomotropic drugs was studied by method of electrophoresis in PAAG. Elevation of the acetylated forms of histone H4 was revealed. The increased proteolysis of lysine-rich histones (H1, H2A, H2B) was shown in swimming rats previously stimulated by prodigiosan. The possible role of lysosomal proteinases of liver cells in mechanism of chromatine activation is discussed.

  1. Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances.

    Science.gov (United States)

    Dasarathy, Jaividhya; McCullough, Arthur J; Dasarathy, Srinivasan

    2017-08-01

    Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current "deficiency replacement" approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in

  2. Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats.

    Science.gov (United States)

    Kabirifar, Razieh; Ghoreshi, Zohreh-Al-Sadat; Safari, Fatemeh; Karimollah, Alireza; Moradi, Ali; Eskandari-Nasab, Ebrahim

    2017-02-01

    Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. Quercetin is a flavonoid with antifibrotic, and hepatoprotective properties. However, the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood. The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model. We divided male Wistar rats into 4 groups (n=8 for each): sham, sham+quercetin (30 mg/kg per day), BDL, and BDL+quercetin (30 mg/kg per day). Four weeks later, the rats were sacrificed, the blood was collected for liver enzyme measurements and liver for the measurement of Rac1, Rac1-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting, respectively. Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes. Furthermore, the mRNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (Pliver injury through increasing antioxidant capacity of the liver tissue, while preventing the production of Rac1, Rac1-GTP and NOX1 proteins.

  3. Liver polyribosome distribution in intact and adrenalectomized rats exposed to. gamma. radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yatvin, M B; Abdel-Halim, M N [Wisconsin Univ., Madison (USA). Dept. of Radiology; Wisconsin Univ., Madison (USA). Dept. of Human Oncology)

    1978-06-01

    The mechanism(s) by which gamma radiation influences liver polyribosome distribution was studied in groups of intact and adrenalectomized male rats. A shift from light to heavy aggregates occurred in the polyribosomes of both intact and adrenalectomized rats after they were exposed to gamma rays. In irradiated adrenalectomized rats, however, the shift to heavier aggregates was not as great as that which occurred in irradiated adrenal-intact animals. Subcutaneous injection of cortisone acetate (10 mg/100 g body weight) also altered the liver polyribosome patterns of both intact and adrenalectomized rats within 8 hours of its administration. The shift which occurred following cortisone administration, however, was less striking than that seen after irradiation only. Thus, although adrenal glucocorticoids contribute to the radiation-indu ied shift in liver polyribosomes in adrenal-intact rats, other factors appear to be involved, since the shift is also obtained in adrenalectomized animals.

  4. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

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

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Mei Liu

    2014-01-01

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

  7. Mangosteen peel extract reduces formalin-induced liver cell death in rats

    Directory of Open Access Journals (Sweden)

    Afiana Rohmani

    2014-08-01

    Full Text Available Background Formalin is a xenobiotic that is now commonly used as a preservative in the food industry. The liver is an organ that has the highest metabolic capacity as compared to other organs. Mangosteen or Garcinia mangostana Linn (GML peel contains xanthones, which are a source of natural antioxidants. The purpose of this study was to evaluate the effect of mangosteen peel extract on formalin-induced liver cell mortality rate and p53 protein expression in Wistar rats. Methods Eighteen rats received formalin orally for 2 weeks, and were subsequently divided into 3 groups, consisting of the formalin-control group receiving a placebo and treatment groups 1 and 2, which were treated with mangosteen peel extract at doses of 200 and 400 mg/kgBW/day, respectively. The treatment was carried out for 1 week, and finally the rats were terminated. The differences in liver cell mortality rate and p53 protein expression were analyzed. Results One-way ANOVA analysis showed significant differences in liver cell mortality rate among the three groups (p=0.004. The liver cell mortality rate in the treatment group receiving 400 mg/kgBW/day extract was lower than that in the formalin-control group. There was no p53 expression in all groups. Conclusions Garcinia mangostana Linn peel extract reduced the mortality rate of liver cells in rats receiving oral formalin. Involvement of p53 expression in liver cell mortality in rats exposed to oral formalin is presumably negligible.

  8. Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

    DEFF Research Database (Denmark)

    Olsen, Peter Skov; Boesby, S.; Kirkegaard, P.

    2013-01-01

    The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal...... growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner's glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner's glands decreased liver regeneration, whereas removal of the submandibular glands had...... no effect on liver regeneration. Epidermal growth factor antiserum reduced liver regeneration significantly. Oral or s.c. administration of epidermal growth factor had no effect on liver regeneration, whereas epidermal growth factor enhanced the effect of insulin and glucagon on liver regeneration...

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  10. Cell-swelling-induced taurine release from isolated perfused rat liver

    NARCIS (Netherlands)

    Brand, H. S.; Meijer, A. J.; Gustafson, L. A.; Jörning, G. G.; Leegwater, A. C.; Maas, M. A.; Chamuleau, R. A.

    1994-01-01

    Astrocytes and lymphocytes are able to release significant amounts of taurine during periods of hypotonicity to reduce the increase in cell volume. To investigate this mechanism in the liver, we studied the release of free amino acids from isolated perfused rat liver during hypotonicity. The

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

    NARCIS (Netherlands)

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

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

  12. Propranolol inhibits the in vitro conversion of thyroxine into triiodothyronine by isolated rat liver parenchymal cells

    NARCIS (Netherlands)

    van Noorden, C. J.; Wiersinga, W. M.; Touber, J. L.

    1979-01-01

    A model for the in vitro study of the conversion of thyroxine into triiodothyronine using isolated rat liver parenchymal cells is described. Isolated liver cells (mean protein content 18 mg/ml) convert approximately 0.8% of 1.3 microM exogenously added T4 into T3 during thirty minutes incubation.

  13. Comparative Study of the Liver Anatomy in the Rat, Rabbit, Guinea Pig and Chinchilla

    Directory of Open Access Journals (Sweden)

    Florin Gheorghe STAN

    2018-05-01

    Based on detailed study of the macroscopic anatomy of rat, rabbit, guinea pig and chinchilla a proper experimental model in liver research, could be assessed. In this regard, the vascular anatomy of the liver in the mentioned species is of a great importance and it is subject of another report.

  14. The role of xanthine oxidase in ischemia/reperfusion damage of rat liver

    NARCIS (Netherlands)

    Frederiks, W. M.; Bosch, K. S.

    1995-01-01

    Oxygen radicals have been proposed to be involved in the induction of liver cell damage during reperfusion after ischemia. The role of xanthine oxidase in this process and the potential of the antioxidant system have been studied in a model of in vivo ischemia of rat liver followed by 1 h

  15. Antifibrotic and molecular aspects of rifaximin in alcoholic liver disease

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Trebicka, Jonel; Thiele, Maja

    2018-01-01

    Background: Alcoholic liver disease is the leading cause of cirrhosis worldwide. Due to an increase in alcohol overuse, alcoholic liver disease has become an increased burden on health care systems. Abstinence from alcohol remains the cornerstone of alcoholic liver disease treatment; however......, this approach is hampered by frequent relapse and lack of specific therapy for treating advanced cases of liver disease. In the present study, we hypothesized that gut microbiota drive the development of liver fibrosis and that modulation of gut microbiota with the gut-selective, nonabsorbable antibiotic...... promoter of alcoholic liver disease, current results may open new therapeutic avenues and revolutionize the current understanding of chronic liver diseases....

  16. Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats.

    Science.gov (United States)

    Tan, Yi; Kim, Jane; Cheng, Jing; Ong, Madeleine; Lao, Wei-Guo; Jin, Xing-Liang; Lin, Yi-Guang; Xiao, Linda; Zhu, Xue-Qiong; Qu, Xian-Qin

    2017-06-07

    To investigate protective effects and molecular mechanisms of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats. Male ZF rats were fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP1c). Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain (10.1%, P = 0.052) and significantly lowered visceral fat (31.0%, P liver in GTP treated rats. The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.

  17. A comparative study of precision cut liver slices, hepatocytes, and liver microsomes from the Wistar rat using metronidazole as a model substance

    DEFF Research Database (Denmark)

    Sidelmann, U. G.; Cornett, Claus; Tjornelund, J.

    1996-01-01

    1. Metronidazole is metabolized by rat liver in vitro models to form a hydroxy metabolite, an acetic acid metabolite, a glucuronic acid conjugate, and a sulphate conjugate. 2. Four different in vitro systems for investigation of drug metabolism based on liver preparations from the male Wistar rat...

  18. Immunohistochemical study of macrophage migration inhibitory factor in rat liver fibrosis induced by thioacetamide

    OpenAIRE

    Y Hori; S Sato; J Yamate; M Kurasaki

    2009-01-01

    Macrophage migration inhibitory factor (MIF) is a molecule known to regulate macrophage accumulation at sites of inflammation. To elucidate the role of MIF in progression of liver fibrosis, the immunohistochemical localization of MIF and macrophages in the liver were examined. Male Wistar rats received thioacetamide (TA) injections (200 mg/kg, i.p.) for 1 or 6 weeks. In biochemical and histological tests, it was confirmed that liver fibrosis was induced. In immunohistochemical analyses, the e...

  19. Liver insulinase and insulin-like activity of the blood plasma in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhikhareva, A I; Dokshina, G A [Tomskij Gosudarstvennyj Univ. (USSR)

    1975-05-01

    Comparative quantitative analysis of the functional effect of radiation on the activity of liver insulinase of irradiated rats has shown that the insulinase activity of the blood plasma decreases (21-45%) one to three days after the exposure at betatron. Insulinase activity of the liver extracts is also inhibited (16-22%) as compared to intact liver extracts. Twelve days after the exposure and later, insulin-like activity of the plasma and the enzyme activity increase up to 37 per cent.

  20. 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

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

    International Nuclear Information System (INIS)

    Imaeda, Masumi; Yoshida, Yukari; Ohkubo, Yu; Musha, Atsushi; Komachi, Mayumi; Nakano, Takashi; Ishikawa, Hitoshi; Takahashi, Takeo; Nakazato, Yoichi

    2014-01-01

    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)

  2. Application of spectroscopy (1HMRS) to assess liver metabolite concentrations in rats with intrauterine growth restriction.

    Science.gov (United States)

    Wang, Tao; Chen, Pingyang; Bian, Dujun; Chen, Juncao

    2017-04-01

    Proton magnetic resonance spectroscopy ( 1 H-MRS) measurement of liver metabolism in intrauterine growth restriction rats has seldom been reported. This study investigated the application of 1 H-MRS in assessing liver metabolism in newborn pups that experienced intrauterine growth restriction. Intra-uterine growth restriction was established by feeding rats low-protein diets during pregnancy. Newborn pups received conventional magnetic resonance imaging and 1 H-MRS using a 3.0T whole body MR scanner at 3, 8 and 12 weeks post birth. The success rate of 1 H-MRS was 83.33%. Significantly lower body weight, BMI and body length at 3 weeks as well as significantly lower body weight, BMI and waist circumference at 8 and 12 weeks were observed in newborn pups of IUGR rats compared with pups of control rats. Significant differences in ACho/H 2 O, ACr/H 2 O, AGlx/H 2 O and ALipid/H 2 O at 3 and 8 weeks as well as significant differences in ACr/H 2 O, ALipid/H 2 O and AGlx/H 2 O at 12 weeks were observed between pups of control rats and pups of IUGR rats. 1 H-MRS allows noninvasive assessment of liver metabolism in the rat and demonstrated the poor liver development of rats that experienced IUGR.

  3. Dietary Omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver

    NARCIS (Netherlands)

    Griffini, P.; Fehres, O.; Klieverik, L.; Vogels, I. M.; Tigchelaar, W.; Smorenburg, S. M.; van Noorden, C. J.

    1998-01-01

    The effects of Ohm-3 polyunsaturated fatty acids (PUFAs) and Ohm-6 PUFAs on the development of experimentally induced colon carcinoma metastasis in rat liver were investigated quantitatively in vivo. Rats mere kept on either a lon-fat diet or on a fish oil (Ohm-3 PUFAs) or safflower oil (Ohm-6

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

    International Nuclear Information System (INIS)

    Lanza-Jacoby, S.; Tabares, A.

    1990-01-01

    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

  5. [Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].

    Science.gov (United States)

    Qin, Lu-shan; Zhao, Hai-ping; Zhao, Yan-ling; Ma, Zhi-jiel; Zeng, Ling-na; Zhang, Ya-ming; Zhang, Ping; Yan, Dan; Bai, Zhao-fang; Li, Yue; Hao, Qing-xiu; Zhao, Kui-jun; Wang, Jia-bo; Xiao, Xiao-he

    2014-06-01

    To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver. One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis. Compared with the blank control group, all biochemical indices increased in the blank group (P analysis. TA showed stronger improvement of the two common factors than TT. Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

  6. Disposition kinetics of diclofenac in the dual perfused rat liver.

    Science.gov (United States)

    Sahin, Selma; Rowland, Malcolm

    2013-09-01

    This study investigates the hepatic disposition of diclofenac as a function of route of input: portal vein (PV) versus hepatic artery (HA) in the presence of its binding protein, albumin. The in situ dual perfused rat liver was performed using Krebs bicarbonate buffer containing human serum albumin (HSA, 0.25%-1%) at constant PV (12 mL/min) and HA (3 mL/min) flow rates. Bolus doses of [(14) C]-diclofenac and (125) I-labeled HSA were injected randomly into the HA or PV and then, after an appropriate interval, into the alternate vessel. Regardless of route of input and perfusion medium protein concentration, the hepatic outflow profile of diclofenac displayed a characteristic sharp peak followed by a slower eluting tail, indicating that its radial distribution is not instantaneous. Based on the estimated effective permeability-surface area product/blood flow ratio, hepatic uptake of diclofenac is governed by both perfusion and permeability. Fractional effluent recovery (F) increased as unbound diclofenac fraction in the perfusate decreased. Although no significant difference in hepatic clearance of diclofenac as a function of route of delivery at 0.5% and 1% HSA, it was demonstrable at 0.25% HSA (p < 0.001), when the extraction ratio is higher. Copyright © 2013 Wiley Periodicals, Inc.

  7. Effect of heavy water on isolated rat liver mitochondria

    International Nuclear Information System (INIS)

    Huebner, G.

    1981-01-01

    The rate of O 2 consumption by isolated rat liver mitochondria was determined polarographically with a Clark electrode at 25 0 C in the active (state 3), strongly coupled (state 4) and decoupled state of the mitochondria in media containing H 2 16 O, D 2 16 O or H 2 18 O. The results confirm the value of the D 2 O isotope effect in the form on an O 2 -consumption inhibition. In H 2 18 O no isotope effect has been detected in the state of controlled respiration. In contrast, a strongly marked inverse isotope effect has been found in the active state after ADP addition and in the decoupled state after DNP addition. This inverse isotope effect occurs in reactions involving a preceding equilibrium. According to the chemiosmotic hypothesis of oxidative phosphorylation the formation of hydronium ions is part of this reaction. The equilibrium constant k 2 = 0.9774 for the hydronium ion in H 2 16 O and H 2 18 O implies that the formation of the hydronium ion in H 2 18 O is preferred to that in H 2 16 O. The high inverse H 2 18 O isotope effect respiration shows that the formation of H 3 O + contributes to the vectorial proton transport, probably as a preceding equilibrium, and that in the active state of the respiratory chain this reaction may be the rate-determining step. (author)

  8. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); Alegret, Marta; Merlos, Manuel; Roglans, Nuria [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain; Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain

    2011-02-15

    Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights

  9. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

    International Nuclear Information System (INIS)

    Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.; Alegret, Marta; Merlos, Manuel; Roglans, Nuria; Laguna, Juan C.

    2011-01-01

    Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid β-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid β-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights:

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

    NARCIS (Netherlands)

    van Swelm, Rachel P L; Hadi, Mackenzie; Laarakkers, Coby M M; Masereeuw, R.|info:eu-repo/dai/nl/155644033; Groothuis, Geny M M; Russel, Frans G M

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

  11. Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.

    Science.gov (United States)

    Menon, B Rajalakshmy; Rathi, M A; Thirumoorthi, L; Gopalakrishnan, V K

    2010-10-01

    The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity.

  12. Effect of nutritional status on oxidative stress in an ex vivo perfused rat liver.

    Science.gov (United States)

    Stadler, Michaela; Nuyens, Vincent; Seidel, Laurence; Albert, Adelin; Boogaerts, Jean G

    2005-11-01

    Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers. Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies. Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats. In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.

  13. Possibility of sandwiched liver surgery with molecular targeting drugs, cetuximab and bevacizumab on colon cancer liver metastases: a case report

    Directory of Open Access Journals (Sweden)

    Toyama Yoichi

    2012-06-01

    Full Text Available Abstract A 31-year-old man with sigmoid colon cancer with concomitant simultaneous multiple liver metastases had received FOLFIRI (leucovorin, fluorouracil and irinotecan and FOLFOX6 (leucovorin, fluorouracil and oxaliplatin after an ordinary sigmoidectomy. However, his serum carcinoembryonic antigen (CEA level increased rapidly during the fifteen months after the operation while he was on FOLFOX6. Abdominal computed tomography revealed expanding multiple liver tumors. As the third line chemotherapy, a combination therapy of cetuximab with irinotecan was given, which markedly reduced his levels of serum CEA, and the size and number of liver tumors. He underwent lateral segmentectomy of the liver and microwave coagulation of the liver metastases in the remnant liver. Thereafter, a good quality of life with tumor dormancy was obtained for 6 months. However, his serum CEA started to rise again in the absence of liver tumors. Therefore, FOLFOX6 with bevacizumab was chosen as the fourth line chemotherapy, and the serum CEA was reduced with tumor dormancy. A good quality of life was obtained again at 3 years after the first surgery. This report indicates the effectiveness of sandwiched liver surgery with the molecular targeting drugs cetuximab and bevacizumab on multiple liver metastases of colon cancer, and suggests the possibility of a regimen consisting of bevacizumab following cetuximab.

  14. Functional Comparison for Lipid Metabolism and Intestinal and Fecal Microflora Enzyme Activities between Low Molecular Weight Chitosan and Chitosan Oligosaccharide in High-Fat-Diet-Fed Rats.

    Science.gov (United States)

    Chiu, Chen-Yuan; Feng, Shih-An; Liu, Shing-Hwa; Chiang, Meng-Tsan

    2017-07-24

    The present study investigated and compared the regulatory effects on the lipid-related metabolism and intestinal disaccharidase/fecal bacterial enzyme activities between low molecular weight chitosan and chitosan oligosaccharide in high-fat-diet-fed rats. Diet supplementation of low molecular weight chitosan showed greater efficiency than chitosan oligosaccharide in suppressing the increased weights in body and in liver and adipose tissues of high-fat-diet-fed rats. Supplementation of low molecular weight chitosan also showed a greater improvement than chitosan oligosaccharide in imbalance of plasma, hepatic, and fecal lipid profiles, and intestinal disaccharidase activities in high-fat-diet-fed rats. Moreover, both low molecular weight chitosan and chitosan oligosaccharide significantly decreased the fecal microflora mucinase and β-glucuronidase activities in high-fat-diet-fed rats. These results suggest that low molecular weight chitosan exerts a greater positive improvement than chitosan oligosaccharide in lipid metabolism and intestinal disaccharidase activity in high-fat-diet-induced obese rats.

  15. Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis

    DEFF Research Database (Denmark)

    Jonassen, T.E.; Brond, L.; Torp, M.

    2003-01-01

    This study was designed to examine the effect of bilateral renal denervation (DNX) on thick ascending limb of Henle's loop (TAL) function in rats with liver cirrhosis induced by common bile duct ligation (CBL). The CBL rats had, as previously shown, sodium retention associated with hypertrophy...... renal sympathetic nerve activity known to be present in CBL rats plays a significant role in the formation of sodium retention by stimulating sodium reabsorption in the TAL via increased renal abundance of NKCC2....

  16. Effects of aspirin and enoxaparin in a rat model of liver fibrosis.

    Science.gov (United States)

    Li, Chen-Jie; Yang, Zhi-Hui; Shi, Xiao-Liu; Liu, De-Liang

    2017-09-21

    To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

  17. [Age and characteristics of cholesterol biosynthesis in rat liver under normal conditions and during atherogenic loading].

    Science.gov (United States)

    Chaialo, P P

    1977-02-01

    Intraperitoneal injection of C14CH3COONa to normal rats aged 6--8 and 28--32 months revealed a slower dynamics of cholesterol biosynthesis in the liver of old rats at the maximum of the tracer incorporation was lower than in the young ones. Atherogenic diet (0.25 g of cholesterol per 100 g of animal weight for a period of 20 days) was accompanied by an increase in the total cholesterol content and depressio of its biosynthesis in the liver, more pronounced in the young rats. Continued cholesterol administration caused further depression of its biosynthesis, most pronounced (in this case) in the old animals.

  18. Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats.

    Directory of Open Access Journals (Sweden)

    Yuping Wang

    Full Text Available To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense.Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA and collagen III (Col III were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD and malondialdehyde (MDA in liver homogenates were determined. Metallothionein (MT expression was detected by real-time RT-PCR and immunohistochemical techniques.Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT, increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver.Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis.

  19. Dietary Supplementation of Blueberry Juice Enhances Hepatic Expression of Metallothionein and Attenuates Liver Fibrosis in Rats

    Science.gov (United States)

    Wang, Yuping; Cheng, Mingliang; Zhang, Baofang; Nie, Fei; Jiang, Hongmei

    2013-01-01

    Aim To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense. Methods Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques. Results Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver. Conclusion Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis. PMID:23554912

  20. Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats.

    Science.gov (United States)

    Duan, Yun-Fei; An, Yong; Zhu, Feng; Jiang, Yong

    2017-08-15

    Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all Pfatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

  1. 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.

  2. Uptake and intracellular fate of [14C]sucrose-insulin in perfused rat livers

    International Nuclear Information System (INIS)

    Surmacz, C.A.; Wert, J.J. Jr.; Ward, W.F.; Mortimore, G.E.

    1988-01-01

    Insulin was covalently linked to [ 14 C]sucrose by means of cyanuric chloride to provide a label that would remain entrapped within the vacuolar system. The uptake of the conjugate by the perfused rat liver was rapid, competitively inhibited by native insulin, and abolished by alkali denaturation. As assessed by its distribution on self-generating gradients of colloidal silica-povidone, label in lysosome-enriched samples of liver taken at different times after the addition of the conjugate moved progressively during 15 min from the plasma membrane into an intermediate peak and then to dense lysosomal fractions. After 30-60 min, the label had equilibrated throughout the lysosomal-vacuolar system. The initial movement from the plasma membrane to the intermediate peak occurred between 2 and 5 min. Because label in the peak could be physically separated from the lysosomal marker, β-acetylglucosaminidase, by dispersing the sample through the gradient mixture before centrifugation rather than layering it, the authors concluded that the intermediate particles in question were not lysosomal in nature. On gel-filtration chromatography, label extracted from the intermediate peak did not move with insulin but rather as a broad band of lower molecular weight products, suggesting that insulin is subject to early proteolytic attack within a nonlysosomal compartment

  3. Uptake and intracellular fate of [14C]sucrose-insulin in perfused rat livers.

    Science.gov (United States)

    Surmacz, C A; Wert, J J; Ward, W F; Mortimore, G E

    1988-07-01

    Insulin was covalently linked to [14C]sucrose by means of cyanuric chloride to provide a label that would remain entrapped within the vacuolar system. The uptake of the conjugate by the perfused rat liver was rapid (half-life = 2.9 min), competitively inhibited by native insulin, and abolished by alkali denaturation. As assessed by its distribution on self-generating gradients of colloidal silica-povidone, label in lysosome-enriched samples of liver taken at different times after the addition of the conjugate moved progressively during 15 min from the plasma membrane into an intermediate peak and then to dense lysosomal fractions. After 30-60 min, the label had equilibrated throughout the lysosomal-vacuolar system. The initial movement from the plasma membrane to the intermediate peak occurred between 2 and 5 min. Because label in the peak could be physically separated from the lysosomal marker, beta-acetylglucosaminidase, by dispersing the sample through the gradient mixture before centrifugation rather than layering it, we concluded that the intermediate particles in question were not lysosomal in nature. On gel-filtration chromatography, label extracted from the intermediate peak did not move with insulin but rather as a broad band of lower molecular weight products, suggesting that insulin is subject to early proteolytic attack within a nonlysosomal compartment.

  4. Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Ping-Chun Li

    2012-01-01

    Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

  5. Free radical-mediated stimulation of tyrosine-specific protein kinase in rat liver plasma membrane

    International Nuclear Information System (INIS)

    Chan, T.M.; Tatoyan, A.; Cheng, E.; Shargill, N.S.; Pleta, M.

    1986-01-01

    Incorporation of 32 P from (γ- 32 P)-ATP into endogenous proteins of plasma membranes isolated from rat liver was significantly increased by several naphthoquinones including menadione. This apparent stimulation of membrane-associated protein kinase activity by these compounds was most striking (up to 6-7 fold) when the synthetic copolymers containing glutamate and tyrosine residues (4:1) was used as substrate. Since tyrosine residues are the only possible phosphate acceptor in the copolymers, the quinone-stimulated liver membrane protein kinase is most likely tyrosine specific. Although not required for protein kinase activity, dithiothreitol (DTT) was necessary for its stimulation by these quinonoid compounds. Hydrolysis of ATP was not significantly affected by quinones under the experimental conditions. Both menadione and vitamin k 5 increased phosphorylation of plasma membrane proteins of molecular weight 45 and 60 kd. The stimulatory effect of menadione on protein phosphorylation was prevented by the addition of superoxide dismutase. Dihydroxyfumerate, which spontaneously produces various radical species, and H 2 O 2 , also stimulated tyrosine-specific protein phosphorylation. DTT was also required for their full effect. It, therefore, appears that quinonone stimulation of tyrosine-specific protein phosphorylation is mediated by oxygen radicals

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

    Science.gov (United States)

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2016-07-01

    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

  7. Presence of albumin mRNA precursors in nuclei of analbuminemic rat liver lacking cytoplasmic albumin mRNA.

    OpenAIRE

    Esumi, H; Takahashi, Y; Sekiya, T; Sato, S; Nagase, S; Sugimura, T

    1982-01-01

    Analbuminemic rats, which lack serum albumin, were previously found to have no albumin mRNA in the cytoplasm of the liver. In the present study, the existence of nuclear albumin mRNA precursors in the liver of analbuminemic rats was examined by RNA X cDNA hybridization kinetics. Albumin mRNA precursors were present in the nuclei of analbuminemic rat liver at almost normal levels, despite the absence of albumin mRNA from the cytoplasm. Nuclear RNA of analbuminemic rat liver was subjected to el...

  8. Imaging of dihydrofolate reductase fusion gene expression in xenografts of human liver metastases of colorectal cancer in living rats

    Energy Technology Data Exchange (ETDEWEB)

    Mayer-Kuckuk, Philipp; Bertino, Joseph R.; Banerjee, Debabrata [Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); The Cancer Institute of New Jersey, Robert Wood Johnson Medical School/UMDNJ, 195 Little Albany Street, NJ 08903, New Brunswick (United States); Doubrovin, Mikhail; Blasberg, Ronald; Tjuvajev, Juri Gelovani [Department of Neurooncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gusani, Niraj J.; Fong, Yuman [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gade, Terence; Koutcher, Jason A. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Balatoni, Julius; Finn, Ronald [Radiochemistry/Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Akhurst, Tim; Larson, Steven [Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2003-09-01

    Radionuclide imaging has been demonstrated to be feasible to monitor transgene expression in vivo. We hypothesized that a potential application of this technique is to non-invasively detect in deep tissue, such as cancer cells metastatic to the liver, a specific molecular response following systemic drug treatment. Utilizing human colon adenocarcinoma cells derived from a patient's liver lesion we first developed a nude rat xenograft model for colorectal cancer metastatic to the liver. Expression of a dihydrofolate reductase-herpes simplex virus 1 thymidine kinase fusion (DHFR-HSV1 TK) transgene in the hepatic tumors was monitored in individual animals using the tracer [{sup 124}I]2'-fluoro-2'-deoxy-5-iodouracil-{beta}-d-arabinofuranoside (FIAU) and a small animal micro positron emission tomograph (microPET), while groups of rats were imaged using the tracer [{sup 131}I]FIAU and a clinical gamma camera. Growth of the human metastatic colorectal cancer cells in the rat liver was detected using magnetic resonance imaging and confirmed by surgical inspection. Single as well as multiple lesions of different sizes and sites were observed in the liver of the animals. Next, using a subset of rats bearing hepatic tumors, which were retrovirally bulk transduced to express the DHFR-HSV1 TK transgene, we imaged the fusion protein expression in the hepatic tumor of living rats using the tracer [{sup 124}I]FIAU and a microPET. The observed deep tissue signals were highly specific for the tumors expressing the DHFR-HSV1 TK fusion protein compared with parental untransduced tumors and other tissues as determined by gamma counting of tissue samples. A subsequent study used the tracer [{sup 131}I]FIAU and a gamma camera to monitor two groups of transduced hepatic tumor-bearing rats. Prior to imaging, one group was treated with trimetrexate to exploit DHFR-mediated upregulation of the fusion gene product. Imaging in the living animal as well as subsequent gamma

  9. 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)

    Chen Hao; Zhou Yubo; Zhang Ying; Qin Yonggang; Guo Li; Yin Fei; Meng Chunyang; Yang Xiaoyu

    2014-01-01

    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

  10. The mechanisms underlying the hypolipidaemic effects of Grifola frondosa in the liver of rats

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    Yinrun Ding

    2016-08-01

    Full Text Available The present study investigated the hypolipidaemic effects of Grifola frondosa and its regulation mechanism involved in lipid metabolism in liver of rats fed a high-cholesterol diet. The body weights and serum lipid levels of control rats, of hyperlipidaemic rats and of hyperlipidaemic rats treated with oral Grifola frondosa were determined. mRNA expression and concentration of key lipid metabolism enzymes were investigated. Serum cholesterol, triacylglycerol and low-density lipoprotein cholesterol levels were markedly decreased in hyperlipidaemic rats treated with Grifola frondosa compared with untreated hyperlipidaemic rats. mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR, acyl-coenzyme A: cholesterol acyltransferase (ACAT2, apolipoprotein B (ApoB, fatty acid synthase (FAS and acetyl-CoA carboxylase (ACC1 were significantly down-regulated, while expression of cholesterol 7-alpha-hydroxylase (CYP7A1 was significantly up-regulated in the livers of treated rats compared with untreated hyperlipidaemic rats. The concentrations of these enzymes also paralleled the observed changes in mRNA expression. Two-dimensional polyacrylamide gel electrophoresis (2-DE and Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS were used to identify twenty proteins differentially expressed in livers of rats treated with Grifola frondosa compared with untreated hyperlipidemic rats. Of these twenty proteins, seven proteins were down-regulated and thirteen proteins were up-regulated. These findings indicate that the hypolipidaemic effects of Grifola frondosa reflected its modulation of key enzymes involved in cholesterol and triacylglycerol biosynthesis, absorption and catabolic pathways. Grifola frondosa may exert anti-atherosclerotic effects by inhibiting LDL oxidation through down-regulation and up-regulating proteins expression in the liver of rats. Therefore, Grifola frondosa may produce both hypolipidaemic

  11. Elimination of Proteus mirabilis /sup 51/Cr endotoxin from the liver in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lipinska-Piotrowska, I [Akademia Medyczna, Lodz (Poland)

    1977-01-01

    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.

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

    International Nuclear Information System (INIS)

    Lipinska-Piotrowska, I.

    1977-01-01

    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)

  13. Phenobarbital Induces Alterations in the Proteome of Hepatocytes and Mesenchymal Cells of Rat Livers

    Science.gov (United States)

    Klepeisz, Philip; Sagmeister, Sandra; Haudek-Prinz, Verena; Pichlbauer, Melanie; Grasl-Kraupp, Bettina; Gerner, Christopher

    2013-01-01

    Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs) have concentrated on alterations induced in hepatocytes (HCs). A potential role of non-parenchymal liver cells (NPCs) in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB) which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme. PMID:24204595

  14. Phenobarbital induces alterations in the proteome of hepatocytes and mesenchymal cells of rat livers.

    Directory of Open Access Journals (Sweden)

    Philip Klepeisz

    Full Text Available Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs have concentrated on alterations induced in hepatocytes (HCs. A potential role of non-parenchymal liver cells (NPCs in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme.

  15. Liver Proteome in Diabetes Type 1 Rat Model: Insulin-Dependent and -Independent Changes.

    Science.gov (United States)

    Braga, Camila Pereira; Boone, Cory H T; Grove, Ryan A; Adamcova, Dana; Fernandes, Ana Angélica Henrique; Adamec, Jiri; de Magalhães Padilha, Pedro

    2016-12-01

    Diabetes mellitus type 1 (DM1) is a major public health problem that continues to burden the healthcare systems worldwide, costing exponentially more as the epidemic grows. Innovative strategies and omics system diagnostics for earlier diagnosis or prognostication of DM1 are essential to prevent secondary complications and alleviate the associated economic burden. In a preclinical study design that involved streptozotocin (STZ)-induced DM1, insulin-treated STZ-induced DM1, and control rats, we characterized the insulin-dependent and -independent changes in protein profiles in liver samples. Digested proteins were subjected to LC-MS E for proteomic data. Progenesis QI data processing and analysis of variance were utilized for statistical analyses. We found 305 proteins with significantly altered abundance among the control, DM1, and insulin-treated DM1 groups (p < 0.05). These differentially regulated proteins were related to enzymes that function in key metabolic pathways and stress responses. For example, gluconeogenesis appeared to return to control levels in the DM1 group after insulin treatment, with the restoration of gluconeogenesis regulatory enzyme, FBP1. Insulin administration to DM1 rats also restored the blood glucose levels and enzymes of general stress and antioxidant response systems. These observations are crucial for insights on DM1 pathophysiology and new molecular targets for future clinical biomarkers, drug discovery, and development. Additionally, we underscore that proteomics offers much potential in preclinical biomarker discovery for diabetes as well as common complex diseases such as cancer, dementia, and infectious disorders.

  16. Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations.

    Science.gov (United States)

    Tannuri, Ana Cristina A; Coelho, Maria Cecília M; de Oliveira Gonçalves, Josiane; Santos, Maria Mercês; Ferraz da Silva, Luiz Fernando; Bendit, Israel; Tannuri, Uenis

    2012-03-01

    The mechanisms of increased collagen production and liver parenchyma fibrosis are poorly understood. These phenomena are observed mainly in children with biliary obstruction (BO), and in a great number of patients, the evolution to biliary cirrhosis and hepatic failure leads to the need for liver transplantation before adolescence. However, pediatric liver transplantation presents with biliary complications in 20% to 30% of cases in the postoperative period. Intra- or extrahepatic stenosis of bile ducts is frequent and may lead to secondary biliary cirrhosis and the need for retransplantation. It is unknown whether biliary stenosis involving isolated segments or lobes may affect the adjacent nonobstructed lobes by paracrine or endocrine means, leading to fibrosis in this parenchyma. Therefore, the present study aimed to create an experimental model of selective biliary duct ligation in young animals with a subsequent evaluation of the histologic and molecular alterations in liver parenchyma of the obstructed and nonobstructed lobes. After a pilot study to standardize the surgical procedures, weaning rats underwent ligation of the bile ducts of the median, left lateral, and caudate liver lobes. The bile duct of the right lateral lobe was kept intact. To avoid intrahepatic biliary duct collaterals neoformation, the parenchymal connection between the right lateral and median lobes was clamped. The animals were divided into groups according to the time of death: 1, 2, 3, 4, and 8 weeks after surgical procedure. After death, the median and left lateral lobes (with BO) and the right lateral lobe (without BO [NBO]) were harvested separately. A group of 8 healthy nonoperated on animals served as controls. Liver tissues were subjected to histologic evaluation and quantification of the ductular proliferation and of the portal fibrosis. The expressions of smooth muscle α-actin (α-SMA), desmin, and transforming growth factor β1 genes were studied by molecular analyses

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

    International Nuclear Information System (INIS)

    Katz, M.S.

    1988-01-01

    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

  18. Characteristics and significance of D-tagatose-induced liver enlargement in rats: An interpretative review.

    Science.gov (United States)

    Bär, A

    1999-04-01

    This review addresses the issue of asymptomatic liver enlargement in rats. It was necessitated by the observation of significantly increased liver weights in rats fed diets with 10 to 20% D-tagatose, a potential new bulk sweetener, for between 28 and 90 days. Increases of liver size without accompanying histopathological changes or impairment of organ function have been observed in rats in response to the ingestion of various xenobiotic compounds (including some food additives), changes of dietary composition (e.g. , high doses of fructose and sucrose), metabolic aberrations (e.g., diabetes), as well as normal pregnancy and lactation. The underlying mechanism(s) are not yet understood in detail but peroxisome proliferation, microsomal enzyme induction, increased storage of glycogen or lipids, and hyperfunction due to an excessive workload are well-established causes of hepatomegaly in rats. In D-tagatose- and fructose-fed rats, a treatment-related increase of hepatic glycogen storage was identified as a likely cause of the liver enlargement. Dietary levels of 5% and about 15-20% were determined as no-effect levels (NOEL) for D-tagatose- and fructose-induced liver enlargement, respectively. At doses above the NOEL, D-tagatose is about four times more efficient than fructose in inducing liver enlargement. On the other hand, the estimated intake of D-tagatose from its intended uses in food is about four times lower than the actual fructose intake. Consequently, a similar safety margin would apply for both sugars. Considering the similarity of the liver effects in rats of fructose, a safe food ingredient, and D-tagatose, the absence of histopathological changes in rats fed a diet with 20% D-tagatose for 90 days, and the absence of adverse long-term consequences of glycogen-induced liver enlargement in rats, it is concluded that the observed liver enlargement in D-tagatose-fed rats has no relevance for the assessment of human safety of this substance. Copyright 1999

  19. 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.

  20. Rat-liver cholesterol 7α-hydroxylase. Pt. 1

    International Nuclear Information System (INIS)

    Cantfort, J. van; Renson, J.; Gielen, J.

    1975-01-01

    A new assay is described to measure the activity of cholesterol 7α-hydroxylase and compared to the conventional 14 C method used by other investigators. This method is based on the mechanism of the enzymic hydroxylation, i.e. a direct and stereospecific substitution of the 7α-hydrogen by a hydroxyl group. [7α- 3 H]cholesterol is incubated at 37 0 C and in the presence of molecular O 2 , in a medium buffered by potassium phosphate at pH 7.4 and containing liver microsomes (or 9,000 x g supernatant), NADPH, MgCl 2 and cysteamine. Tween-80 (1.5 mg/ml) is used to introduce enough substrate (300 μM) in the incubation mixture to saturate the ezyme (K(m) = 100 μM). Under these conditions the tritiated water released into the incubation medium reflects accurately the enzymic activity. The results obtained with this method are similar to the one obtained with a [4- 14 C]cholesterol technique (r = 0.96; P 3 H]cholesterol method is a complete independence from further metabolism of the first enzymic product, the 7α-hydroxycholesterol, the tritiated water representing the entire cholesterol 7α-hydroxylase activity. (orig.) [de

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

    International Nuclear Information System (INIS)

    Al-Damegh, Mona Abdalla

    2007-01-01

    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)

  2. Vitamin K1 attenuates bile duct ligation-induced liver fibrosis in rats.

    Science.gov (United States)

    Jiao, Kun; Sun, Quan; Chen, Baian; Li, Shengli; Lu, Jing

    2014-06-01

    Vitamin K1 is used as a liver protection drug for cholestasis-induced liver fibrosis in China, but the mechanism of vitamin K1's action in liver fibrosis is unclear. In this study, a model of liver fibrosis was achieved via bile duct ligation in rats. The rats were then injected with vitamin K1, and the levels of serum aspartate aminotransferase, alanine transaminase, total bilirubin and the fibrotic grade score, collagen content, the expressions of α-smooth muscle actin (SMA) and cytokeratin 19 (CK19) were measured on day 28 after ligation. The levels of the biochemical parameters, fibrotic score and collagen content were significantly reduced by treatment with vitamin K1 in bile duct-ligated rats. In addition, α-SMA and CK19 expression was significantly reduced by vitamin K1 treatment in bile duct-ligated rats. These results suggested that vitamin K1 may attenuate liver fibrosis by inhibiting hepatic stellate cell activation in bile duct-ligated rats.

  3. Metabolism of 1-[14C]nitropyrene in isolated perfused rat livers

    International Nuclear Information System (INIS)

    Bond, J.A.; Medinsky, M.A.; Dutcher, J.S.

    1984-01-01

    1-Nitropyrene (1-NP), a constituent of diesel exhaust, is carcinogenic to rats and is a bacterial and mammalian mutagen. Biliary and fecal excretion of 1-NP metabolites are the major routes of excretion in rats, suggesting that hepatic metabolism plays a dominant role in determining the biological fate of 1-NP. The purpose of this investigation was to quantitate 1-[14C]NP metabolites formed in isolated perfused rat livers and excreted in bile from rats. Perfused rat livers displayed a capacity for oxidation, reduction, acetylation, and conjugation of 1-NP (or its metabolites). Reduction of 1-NP followed by N-acetylation was the major metabolic pathway observed in the perfused livers. Acetylaminopyrene (AAP) was the major metabolite detected, with total quantities (150 nmol) accounting for about 60% of the total 1-[14C]NP dose (258 nmol) added to the perfusate. Considerably smaller quantities of aminopyrene and hydroxynitropyrenes were also detected. Livers perfused with 1-[14C]NP excreted about 36 nmol equivalents of 1-[14C]NP (12% of the total 1-NP dose) in bile after 60 min. Some of the biliary metabolites were tentatively identified as metabolites of the mercapturic acid pathway. The spectrum of biliary metabolites was qualitatively identical to that seen in bile from intact rats. Quantities of 14C covalently bound to hepatic macromolecules from perfused livers were 0.4 nmol 1-NP eq/g liver. The data from this study indicate that the liver may be an important site for metabolism of 1-NP

  4. Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor?

    Science.gov (United States)

    Tsao, L I; Su, T P

    1997-02-01

    A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2- 3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor. [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:517-532.]. A high degree of purification of this protein has been achieved in the present study.

  5. 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.

  6. Real time monitoring of rat liver energy state during ischemia.

    Science.gov (United States)

    Barbiro, E; Zurovsky, Y; Mayevsky, A

    1998-11-01

    Hepatic failure is one of the major problems developed during the posttransplantation period. A possible cause of hepatic failure is the prolonged ischemia induced during the implantation procedure. Hepatic ischemia leads to a reduction in oxygen supply, ATP level decline, liver metabolism impairment, and finally organ failure. The purpose of this study was to estimate the functional state of the liver by monitoring liver blood flow and the mitochondrial NADH redox state simultaneously and continuously during in situ liver ischemia followed by reperfusion. Measurements were performed using the multiprobe developed in our laboratory consisting of fibers for the measurement of relative liver blood flow (laser Doppler flowmetry) and mitochondrial redox state (NADH fluorescence). The experimental procedure included the temporary interruption of blood flow to the liver using three types of ischemia, hepatic artery occlusion, portal vein occlusion, and simultaneous occlusion of hepatic artery and portal vein, followed by a reperfusion period. These preliminary experiments showed a significant decrease in liver blood flow, following the three types of liver ischemia, and a significant increase in NADH levels. The probe used in this study incorporates the advantage of monitoring NADH and liver blood flow simultaneously and continuously from the same area on the surface of the liver. Since each of these two parameters is not calibrated in absolute units, the simultaneous monitoring decreases possible artifacts. Also, it will allow us to determine of the coupling between tissue blood flow and oxidative phosphorylation. It is believed that the measurements of respiratory chain dysfunction might predict organ viability in clinical organ transplantation situations. Using this probe may also help to decrease the variability in liver blood flow monitoring since liver blood flow monitoring is supported simultaneously with the mitochondrial redox state, which supplies the

  7. The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

    Science.gov (United States)

    Yang, Yang; He, Qin; Wang, Hong; Hu, Xinyue; Luo, Ying; Liang, Guojuan; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Tian, Xiaoyan; Chen, Qi; Yang, Junqing

    2017-04-04

    The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

  8. Radioprotection of liver lipids of whole-body gamma-irradiated female rats by cystamine

    International Nuclear Information System (INIS)

    Ramanathan, R.; Misra, U.K.

    1976-01-01

    The effect of administration of cystamine (5 mg/100 g body weight) before 1,200 R whole-body gamma irradiation has been studied on irradiation-induced changes in liver and its subcellular fractions'lipids of fasted female rats. Cystamine prevented the irradiation-induced increase in liver triglycerides and liver mitochondrial total phospholipids, but it decreased microsomal total phospholipids and proteins. Cystamine prevented the radiation-induced increased 32 P-radioactivity (counts/min/μmole phospholipid phosphorus) of microsomal phosphatidyl choline. Cystamine prevented the radiation-induced increased uptake of NaH 2 32 PO 4 (counts/min/g liver) in liver microsomal phosphatidyl ethanolamine and supernatant phosphatidyl choline; but in microsomal phosphatidyl choline, cystamine did not do so, but on the other hand it itself increased the uptake in control rats. Cystamine did not prevent the irradiation-induced decreased incorporation of (U- 14 C)glucose into liver triglycerides, total phospholipids and phosphatidyl choline. Cystamine itself decreased the incorporation of (U- 14 C)glucose into liver triglycerides and phosphoglycerides of control rats. (orig.) [de

  9. Fermented Citrus Lemon Reduces Liver Injury Induced by Carbon Tetrachloride in Rats

    Directory of Open Access Journals (Sweden)

    Yi Jinn Lillian Chen

    2018-01-01

    Full Text Available Fermented lemon juice displays a variety of important biological activities, including anti-inflammatory and antioxidant capabilities. The aim of the present study is to investigate hepatic-protective effects of no-sugar-added fermented lemon juice (FLJ for liver inflammation caused by carbon tetrachloride (CCl4 in rats. Rats are divided into six groups: H2O, CCl4 + H2O, CCl4 + silymarin, and CCl4 plus three different FLJ doses by oral administration, respectively. The results show that the contents of plasma ALT and AST, hepatic lipid peroxidation, splenomegaly, and liver water are reduced significantly in rats under FLJ treatment, and pathological examination of liver fibrosis is improved. The reduced hepatic injury by increasing liver soluble protein and glutathione and albumin is observed in FLJ treated groups, and FLJ has comparable efficacies to medicine silymarin in liver therapies. The no-sugar-added FLJ differs from traditional fermentation by adding lots of sugar and prevents any hidden sugar intake while taking it as a complimentary treatment for liver inflammation. The green color and the taste of sourness are both associated with treating and healing the liver based on the five-element theory in traditional Chinese medicine, and the green and sour FLJ may be applied to the ancient theory in preventing hepatic injury accordingly.

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

    International Nuclear Information System (INIS)

    Kuriyama, M.; Yoshida, H.; Suzuki, M.; Fujiyama, J.; Igata, A.

    1990-01-01

    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

  11. Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats.

    Science.gov (United States)

    Khorshid, Hamid Reza Khorram; Azonov, Jahan A; Novitsky, Yury A; Farzamfar, Bardia; Shahhosseiny, Mohammad Hassan

    2008-01-01

    To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels (pliver disease are warranted.

  12. Therapeutic effects of globular adiponectin in diabetic rats with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Ma, Hong; Cui, Fan; Dong, Jing-Jing; You, Guo-Ping; Yang, Xiang-Jiu; Lu, Hua-Dong; Huang, Yan-Ling

    2014-10-28

    To explore the therapeutic role of globular adiponectin (gAd) in high-fat diet/streptozotocin (STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease (NAFLD). Seven rats were fed a basic diet (normal control group; NC) during the experiment. Experimental rats (14 rats) were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus (T2DM) and NAFLD. Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d (gAd-treated group), while the other 7 rats (T2DM/NAFLD group) received 0.9% saline. Plasma biochemical parameters and insulin concentrations were measured. Liver histopathology was examined by hematoxylin-eosin staining. Insulin receptor expression in the liver was analyzed by immunohistochemical staining, Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Compared to the control group, the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin. Plasma glucose and lipid levels were decreased in the gAd-treated group, while serum insulin levels increased. The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group, and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats. Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group (NAS 1.39 ± 0.51 vs 1.92 ± 0.51, P Globular adiponectin exerts beneficial effects in T2DM rats with NAFLD by promoting insulin secretion, mediating glucolipid metabolism, regulating insulin receptor expression and alleviating hepatic steatosis.

  13. Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

    International Nuclear Information System (INIS)

    Theron, C.N.

    1985-03-01

    A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

  14. Antioxidant Effects of Green-Tea on biochemical and Histopathological Changes of liver in Male Rats Poisoned by Malathion Insecticide

    Directory of Open Access Journals (Sweden)

    Rahim Raoofi

    2016-05-01

    Full Text Available Malathion is an organophosphate pesticide which is widely used in agriculture, veterinary and industries. Oxidative stress has been identified as one of Malathion’s main molecular mechanisms of action in plasma, liver, pancreas, muscles and the brain. Green tea (Camellia sinensis, which is the most common drink across the world after water, has many antioxidant properties. The purpose of this research is to investigate the effects of Malathion on the liver and the preventive effects of green tea on Malathion-induced poisoning. Seventy-two Wistar male rats were randomly divided into the control, the sham, and the experimental groups (receiving respectively 40 mg/kg of Malathion; 100, 200, and 400 mg/kg of green tea; and 100, 200, and 400 mg/kg of Malathion and green tea respectively. All injections were performed intraperitoneally for 14 consecutive days. On the 15th day, blood samples were taken from the hearts of the rats to measure serum level of hepatic enzymes, and their liver tissues were removed to be studied. To do the statistical analysis One-way ANOVA test and Duncan’s test at the 5% significance level were used. aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP, Malondialdehyde (MDA and Total Oxidation Capacity(TOC concentrations in the treatment groups with Malathion and green tea extract at 100, 200, and 400 mg/kg doses showed a significant decline compared to the Malathion group(p<0.05, whileTotal Antioxidant Capacity (TAC level showed a significant increase with various doses of green tea and Malathion compared to the Malathion group (p<0.05. Green tea, probably due to its strong antioxidant properties, could improve the destructive effects of Malathion on the rat liver.

  15. Staging of fibrosis in experimental non-alcoholic steatohepatitis by quantitative molecular imaging in rat models

    International Nuclear Information System (INIS)

    Schnabl, Bernd; Farshchi-Heydari, Salman; Loomba, Rohit; Mattrey, Robert F.; Hoh, Carl K.; Sirlin, Claude B.; Brenner, David A.; Behling, Cynthia A.; Vera, David R.

    2016-01-01

    Objectives: The aim of this study was to test the ability of hepatocyte-specific functional imaging to stage fibrosis in experimental rat models of liver fibrosis and progressive NASH. Using ROC analysis we tested the ability of a functional imaging metric to discriminate early (F1) from moderate (F2) fibrosis in the absence and presence of non-alcoholic steatohepatitis, which has not been achieved by any modality other than biopsy. Methods: Galactosyl Human Serum Albumin (GSA) was radiolabeled with the positron-emitter, 68 Ga, and injected (i.v., 45–95 μCi, 1.5 pmol/g TBW) into 44 healthy, 19 DEN-, and 22 CDAA-treated male rats. Quantification of liver function was achieved by calculating T90, defined as the time for the liver to accumulate 90 percent of the [ 68 Ga]GSA plateau value. All livers were excised immediately after imaging and prepared for a “blinded” histologic examination, which included fibrosis and fat content scores. Two sets of fibrosis scores were recorded for all of animals. The dominant fibrosis stage was recorded as the “Dominant Pattern” score and the “Maximum Pattern” score was assigned if a smaller distinct region with a higher fibrosis score was observed. Results: Animals with Dominant Pattern F0–F1 liver fibrosis (D − = 39) demonstrated significantly (P < 0.0001) faster accumulation of [ 68 Ga]GSA (2.40 ± 0.52 min) than those with moderate to advanced Dominant Pattern fibrosis F2 and F4 (D + = 26) (3.48 ± 1.01 min). ROC analysis (F0–F1 vs F2–F4) produced an area under the binormal curve (AUC) of 0.867 ± 0.045. Twenty-seven of the 65 rats had small regions with higher fibrosis scores. Six of these Maximum Pattern scores reclassified the animals from D − to D + . ROC analysis of F0–F1 versus F2–F4 rats without liver fat produced AUCs of 0.881 ± 0.053 for the Dominant Pattern Score and 0.944 ± 0.035 for the Maximum Pattern Score. Conclusions: PET Functional Imaging of [ 68 Ga]GSA accurately discriminates

  16. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.

    Science.gov (United States)

    Koo, Seung-Hoi

    2013-09-01

    Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

  17. Liver lipase and high-density lipoprotein. Lipoprotein changes after incubation of human serum with rat liver lipase.

    Science.gov (United States)

    Groot, P H; Scheek, L M; Jansen, H

    1983-05-16

    Human sera were incubated with rat liver lipase after inactivation of lecithin:cholesterol acyltransferase, and the changes in serum lipoprotein composition were measured. In the presence of liver lipase serum triacylglycerol and phosphatidylcholine were hydrolyzed. The main changes in the concentrations of these lipids were found in the high-density lipoprotein fraction. Subfractionation of high-density lipoprotein by rate-zonal ultracentrifugation showed a prominent decrease in all constituents of high-density lipoprotein2, a smaller decrease in the 'light' high-density lipoprotein3 and an increase in the 'heavy' high-density lipoprotein3. These data support a concept in which liver lipase is involved in high-density lipoprotein2 phospholipid and triacylglycerol catabolism and suggest that as a result of this action high-density lipoprotein2 is converted into high-density lipoprotein3.

  18. Antioxidant and antiapoptotic effects of green tea polyphenols against azathioprine-induced liver injury in rats.

    Science.gov (United States)

    El-Beshbishy, Hesham A; Tork, Ola M; El-Bab, Mohamed F; Autifi, Mohamed A

    2011-04-01

    Green tea polyphenols (GTP) is considered to have protective effects against several diseases. The hepatotoxicity of azathioprine (AZA) has been reported and was found to be associated with oxidative damage. This study was conducted to evaluate the role of GTP to protect against AZA-induced liver injury in rats. AZA was administered i.p. in a single dose (50mgkg(-1)) to adult male rats. AZA-intoxicated rats were orally administered GTP (either 100mgkg(-1)day(-1) or 300mgkg(-1)day(-1), for 21 consecutive days, started 7 days prior AZA injection). AZA administration to rats resulted in significant elevation of serum transaminases (sALT and sAST), alkaline phosphatase (sALP), depletion of hepatic reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx), accumulation of oxidized glutathione (GSSG), elevation of lipid peroxides (LPO) expressed as malondialdehyde (MDA), reduction of the hepatic total antioxidant activity (TAA), decrease serum total proteins and elevation of liver protein carbonyl content. Significant rises in liver tumor necrosis factor-alpha (TNF-α) and caspase-3 levels were noticed in AZA-intoxicated rats. Treatment of the AZA-intoxicated rats with GTP significantly prevented the elevations of sALT, sAST and sALP, inhibited depletion of hepatic GSH, GPx, CAT and GSSG and inhibited MDA accumulation. Furthermore, GTP had normalized serum total proteins and hepatic TAA, CAT, TNF-α and caspase-3 levels of AZA-intoxicated rats. In addition, GTP prevented the AZA-induced apoptosis and liver injury as indicated by the liver histopathological analysis. The linear regression analysis showed significant correlation in either AZA-GTP100 or AZA-GTP300 groups between TNF-α and each of serum ALT, AST, ALP and total proteins and liver TAA, GPX, CAT, GSH, GSSG, MDA and caspase-3 levels. However, liver TNF-α produced non-significant correlation with the serum total proteins in both AZA-GTP100 and AZA-GTP300 groups. In conclusion, our data indicate

  19. The increase of metallothionein content in rat liver induced by x-ray irradiation and its physiological function

    International Nuclear Information System (INIS)

    Shiraishi, Noriyuki; Miyahara, Masanobu; Utsumi, Kozo; Aono, Kaname; Inoue, Bunji.

    1982-01-01

    Whether or not stress promotes peroxidase reaction of lipids in vivo influences the biosynthesis of metallothionein (MT) was studied. After X-ray irradiation rats were exposed to oxygen, and the liver supernatant was examined. The Zn distribution in the liver supernatant fraction of 10,000 in molecular weight, which was attributed to MT in origin, was small in the control group, but was great in the stress group. The amount of Cd found to the 10,000 fraction (Zn in MT is relatively easily replaced by Cd) was extremely smaller in the control group than in the stress group. These data indicate that the amount of Zn is small, with no appreciable presence of MT, in the 10,000 fraction of the control group. The X-ray irradiated group showed a marked increase of Zn 5 and 7 days later, indicating a definite increase of MT, and the group exposed to O 2 showed similar phenomena, suggesting induction of MT synthesis in the rat liver. (Chiba, N.)

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    AIM: In order to study the short-term effect of moderate and severe reduction of liver function by acetaminophen poisoning of different severity on gene expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg body weight acetaminophen intragastrically. The lower dose...... is associated with low mortality; after the higher dose, most rats die at between 12 and 24 h. METHODS: In the morning, 1 1/2, 3, 6, 9, and 12 h after the injection, the rats were killed and RNA was extracted from liver tissue. By slot-blot hybridization mRNA steady-state levels were determined for enzymes...

  1. 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......-6. 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. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of IJS...

  2. Cilostazol attenuates cholestatic liver injury and its complications in common bile duct ligated rats.

    Science.gov (United States)

    Abdel Kawy, Hala S

    2015-04-05

    Cilostazol is a phosphodiesterase III inhibitor increases adenosine 3', 5'-cyclic monophosphate (cyclic AMP) level which inhibits hepatic stellate cell activation. Its pharmacological effects include vasodilation, inhibition of vascular smooth muscle cell growth, inhibition of platelet activation and aggregation. The aim of the current study was to determine the effects of early administration of low dose cilostazol on cholestatic liver injury induced by common bile duct ligation (CBDL) in rat. Male Wistar rats (180-200g) were divided into three groups: Group A; simple laparotomy group (sham). Group B; CBDL, Group C; CBDL rats treated with cilostazol (9mg/kg daily for 21 days). Six rats from each group were killed by the end of weeks one and three after surgery, livers and serum were collected for biochemical and histopathological studies. Aspartate aminotransferase, alanine aminotransferase, gama glutamyl transferase, alkaline phosphatase and total bilirubin serum levels decreased in the cilostazol treated rats, when compared with CBDL rats. The hepatic levels of tumor necrosis factor-alpha, transforming growth factor-beta, and platelet derived growth factor-B were significantly lower in cilostazol treated rats than that in CBDL rats. Cilostazol decreased vascular endothelial growth factor level and hemoglobin content in the livers. Cilostazol significantly lowered portal pressure, inhibited ductular proliferation, portal inflammation, hepatic fibrosis and decreased hepatic hydroxyproline contents. Administration of cilostazol in CBDL rats improved hepatic functions, decreased ductular proliferation, ameliorated portal inflammation, lowered portal hypertension and reduced fibrosis. These effects of cilostazol may be useful in the attenuation of liver injury in cholestasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Regulation of N-nitrosodimethylamine demethylase in rat liver and kidney.

    Science.gov (United States)

    Hong, J Y; Pan, J M; Dong, Z G; Ning, S M; Yang, C S

    1987-11-15

    In previous work, the low Km form of N-nitrosodimethylamine (NDMA) demethylase has been demonstrated to be due to a specific form of cytochrome P-450 (designated as P-450ac) and to be the enzyme required for the metabolic activation of NDMA. The present work deals with the regulation of P-450ac in rat liver during development as well as the mechanism of induction of P-450ac in rat liver and kidney by inducers. NDMA demethylase activity was almost undetectable in the liver of newborn rats, increased after day 4, and remained elevated throughout the first 17 days of the neonatal period. The enhancement of NDMA demethylase activity during development was accompanied by corresponding increases of P-450ac content and P-450ac mRNA levels as determined by Western and slot blot analyses, respectively. No sex differences with respect to this enzyme were observed in the developing rats. Acetone treatment on late-term pregnant rats for 2 days resulted in transplacental inductions of P-450ac and P-450ac mRNA in the newborn rats. Pretreatment of young male rats and adult female rats with acetone or isopropyl alcohol caused increases of NDMA demethylase activity and P-450ac content in the liver but no significant change in the P-450ac mRNA level. These facts suggest the possible existence of a posttranscription regulatory mechanism under these induction conditions. The presence of P-450ac in rat kidney was demonstrated by Western and Northern blot analyses. The renal form of P-450ac seemed to be regulated in a fashion similar to the hepatic P-450ac regarding its response to inducing factors such as fasting and acetone treatment.

  4. Hepatocyte transplants improve liver function and encephalopathy in portacaval shunted rats.

    Science.gov (United States)

    Fogel, Wieslawa Agnieszka; Stasiak, Anna; Maksymowicz, Michał; Kobos, Jozef; Unzeta, Mercedes; Mussur, Miroslaw

    2014-07-01

    Rats with portacaval shunt (PCS) are useful experimental models of human hepatic encephalopathy in chronic liver dysfunction. We have previously shown that PCS modifies amine neurotransmitter systems in the CNS and increases voluntary alcohol intake by rats. Hepatocyte transplantation, used in acute liver failure, has recently also been applied to chronic liver diseases, which prompted us to investigate whether the altered brain amine system and the drinking behavior in long-term shunted rats could be normalized by hepatocyte transplants. Hepatocytes, isolated from syngeneic donors by collagenase digestion, were injected (3 × 10(6) cells/rat) into the pancreatic tail region, 6 months after PCS. Hepatic function was evaluated by measuring urine urea and plasma L-histidine concentrations. A free choice test with two bottles (tap water and 10% ethyl alcohol) was performed for 3 days to assess the rats' preference for alcohol. The rats were euthanized 2 months posttransplantation. Brain histamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured by radioenzymatic assay and by HPLC-EC, respectively, N-tele-methylhistamine by GC/MS while MAOA and MAOB activities by isotopic procedures. Portacaval shunt rats with hepatocyte transplants gave more urea than before transplantation, with lower plasma L-His levels and higher body weight versus the PCS counterparts. Also, those rats consumed less alcohol. The CNS amines and 5-HIAA concentrations, as well as MAO-B activity, being abnormally high in untreated PCS rats, significantly reduced after PCS hepatocyte treatment. The results support the therapeutic values of hepatocyte transplants in chronic liver diseases and the temporary character of PCS-exerted CNS dysfunctions. © 2014 John Wiley & Sons Ltd.

  5. High regenerative capacity of the liver and irreversible injury of male reproductive system in carbon tetrachloride-induced liver fibrosis rat model.

    Science.gov (United States)

    Bubnov, Rostyslav V; Drahulian, Maria V; Buchek, Polina V; Gulko, Tamara P

    2018-03-01

    Liver fibrosis (LF) is a chronic disease, associated with many collateral diseases including reproductive dysfunction. Although the normal liver has a large regenerative capacity the complications of LF could be severe and irreversible. Hormone and sex-related issues of LF development and interactions with male reproductive have not been finally studied. The aim was to study the reproductive function of male rats in experimental CCl 4 -induced liver fibrosis rat model, and the capability for restoration of both the liver and male reproduction system. Studies were conducted on 20 3-month old Wistar male rats. The experimental animals were injected with freshly prepared 50% olive oil solution of carbohydrate tetrachloride (CCl 4 ). On the 8th week after injection we noted the manifestations of liver fibrosis. The rats were left to self-healing of the liver for 8 weeks. All male rats underwent ultrasound and biopsy of the liver and testes on the 8th and 16th weeks. The male rats were mated with healthy females before CCl 4 injection, after modeling LF on the 8th week, and after self-healing of the liver. Pregnancy was monitored on ultrasound. On the 8th week of experiment we observed ultrasound manifestation of advanced liver fibrosis, including hepatosplenomegaly, portal hypertension. Ultrasound exam of the rat testes showed testicular degeneration, hydrocele, fibrosis, scarring, petrifications, size reduction, and restriction of testicular descent; testes size decreased from 1.24 ± 0.62 ml to 0.61 ± 0.13, p  reproductive system and altering of fertility: the offspring of male rats with advanced LF was 4.71 ± 0.53 born alive vs 9.55 ± 0.47 born from mating with healthy males, p  reproductive system.

  6. Production of acetone and conversion of acetone to acetate in the perfused rat liver

    International Nuclear Information System (INIS)

    Gavino, V.C.; Somma, J.; Philbert, L.; David, F.; Garneau, M.; Belair, J.; Brunengraber, H.

    1987-01-01

    The utilization of millimolar concentrations of [2- 14 C]acetone and the production of acetone from acetoacetate were studied in perfused livers from 48-h starved rats. We devised a procedure for determining, in a perfused liver system, the first-order rate constant for the decarboxylation of acetoacetate (0.29 +/- 0.09 h-1, S.E., n = 8). After perfusion of livers with [2- 14 C]acetone, labeled acetate was isolated from the perfusion medium and characterized as [1- 14 C]acetate. No radioactivity was found in lactate or 3-hydroxybutyrate. After 90 min of perfusion with [2- 14 C]acetone, the specific activity of acetate was 30 +/- 4% (n = 13) of the initial specific activity of acetone. We conclude that, in perfused livers from 2-day starved rats, acetone metabolism occurs for the most part via free acetate

  7. Data on body weight and liver functionality in aged rats fed an enriched strawberry diet

    Directory of Open Access Journals (Sweden)

    Francesca Giampieri

    2017-08-01

    Full Text Available Here, we present new original data on the effects of strawberry consumption on body weight and liver status of aged rats. Wistar rats aged 19–21 months were fed a strawberry enriched diet prepared by substituting 15% of the total calories with freeze-dried strawberry powder for two months. Body weight, plasma biomarkers of liver injury (alanine transferase, aspartate aminotransferase and alkaline phosphatase and liver histological analysis were assessed. These data indicate that strawberry supplementation did not interfere with normal animal maintenance and with liver structure and functionality. For further details and experimental findings please refer to the article “Strawberry consumption improves aging-associated impairments, mitochondrial biogenesis and functionality through the AMP-Activated Protein Kinase signaling cascade” in FOOD CHEMISTRY (Giampieri et al., 2017 [1].

  8. Angiotensin converting enzyme (ACE) gene expression in experimentally induced liver cirrhosis in rats.

    Science.gov (United States)

    Shahid, Syed Muhammad; Fatima, Syeda Nuzhat; Mahboob, Tabassum

    2013-09-01

    Angiotensin converting enzyme (ACE) is a key player of Renin Angiotensin System (RAS), involved in conversion of active product, angiotensin-II. Alterations in RAS have been implicated in the pathophysiology of various diseases involving heart, kidney, lung and liver. This study is designed to investigate the association of ACE gene expression in induction of liver cirrhosis in rats. Total 12 male albino Wistar rats were selected and divided in two groups. Control group received 0.9% NaCl, where as Test group received thioacidamide (TAA), dissolved in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight, twice a week for 12 weeks. The rats were decapitated and blood sample was collected at the end of experimental period and used for liver functions, enzyme activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was isolated from excised tissue determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RT-PCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels were significantly high (pACE gene expression after 12 weeks TAA treatment in cirrhotic rats was significantly increased (pACE gene expression. The finding of major up-regulation of ACE in the experimental rat liver provides further insight into the complexities of the RAS and its regulation in liver injury. The development of specific modulators of ACE activity and function, in future, will help determine the role of ACE and its genetic variants in the pathophysiology of liver disease.

  9. Regulation of glutamate dehydrogenase expression in the developing rat liver: control at different levels in the prenatal period

    NARCIS (Netherlands)

    Das, A. T.; Salvadó, J.; Boon, L.; Biharie, G.; Moorman, A. F.; Lamers, W. H.

    1996-01-01

    To study the regulation of the expression of glutamate dehydrogenase (Glu-DH) in rat liver during development, the Glu-DH mRNA concentration in the liver of rats ranging in age from 14 days prenatal development to 3 months after birth was determined. This concentration increased up to two days

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

    International Nuclear Information System (INIS)

    Fernando, Harshica; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Shakeel Ansari, G.A.

    2011-01-01

    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

  11. Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human.

    Science.gov (United States)

    Li, Yan; Zhou, Yanyan; Si, Nan; Han, Lingyu; Ren, Wei; Xin, Shaokun; Wang, Hongjie; Zuo, Ran; Wei, Xiaolu; Yang, Jian; Zhao, Haiyu; Bian, Baolin

    2017-11-01

    Protoberberine alkaloids including berberine, palmatine, jatrorrhizine, coptisine, and epiberberine are major components in many medicinal plants. They have been widely used for the treatment of cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. However, the metabolism of five protoberberine alkaloids among different species has not been clarified previously. In order to elaborate on the in vitro metabolism of them, a comparative analysis of their metabolic profile in rat, rhesus monkey, and human liver microsomes was carried out using ultrahigh-performance liquid chromatography coupled with a high-resolution linear trap quadrupole-Orbitrap mass spectrometer (UHPLC-electrospray ionization-Orbitrap MS) for the first time. Each metabolite was identified and semiquantified by its accurate mass data and peak area. Fifteen metabolites were characterized based on accurate MS/MS spectra and the proposed MS/MS fragmentation pathways including demethylation, hydroxylation, and methyl reduction. Among them, the content of berberine metabolites in human liver microsomes was similar with those in rhesus monkey liver microsomes, whereas berberine in rat liver microsomes showed no demethylation metabolites and the content of metabolites showed significant differences with that in human liver microsomes. On the contrary, the metabolism of palmatine in rat liver microsomes resembled that in human liver microsomes. The content of jatrorrhizine metabolites presented obvious differences in all species. The HR-ESI-MS/MS fragmentation behavior of protoberberine alkaloids and their metabolic profile in rat, rhesus monkey, and human liver microsomes were investigated for the first time. The results demonstrated that the biotransformation characteristics of protoberberine alkaloids among different species had similarities as well differences that would be beneficial for us to better understand the pharmacological activities of protoberberine alkaloids

  12. Adeno-associated viral vector serotype 5 poorly transduces liver in rat models.

    Directory of Open Access Journals (Sweden)

    Paula S Montenegro-Miranda

    Full Text Available Preclinical studies in mice and non-human primates showed that AAV serotype 5 provides efficient liver transduction and as such seems a promising vector for liver directed gene therapy. An advantage of AAV5 compared to serotype 8 already shown to provide efficient correction in a phase 1 trial in patients suffering from hemophilia B, is its lower seroprevalence in the general population. Our goal is liver directed gene therapy for Crigler-Najjar syndrome type I, inherited severe unconjugated hyperbilirubinemia caused by UGT1A1 deficiency. In a relevant animal model, the Gunn rat, we compared the efficacy of AAV 5 and 8 to that of AAV1 previously shown to be effective. Ferrying a construct driving hepatocyte specific expression of UGT1A1, both AAV8 and AAV1 provided an efficient correction of hyperbilirubinemia. In contrast to these two and to other animal models AAV5 failed to provide any correction. To clarify whether this unexpected finding was due to the rat model used or due to a problem with AAV5, the efficacy of this serotype was compared in a mouse and two additional rat strains. Administration of an AAV5 vector expressing luciferase under the control of a liver specific promoter confirmed that this serotype poorly performed in rat liver, rendering it not suitable for proof of concept studies in this species.

  13. Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob Hornstrup Frølunde; Rosenberg, Jacob

    2016-01-01

    INTRODUCTION: Recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is a major cause of mortality. Knowledge on biomarkers may contribute to better surveillance based on the patients' risk of recurrence. Reviewing the literature, we aimed to identify serological...... and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation. METHODS: A literature search was performed in the databases PubMed and Scopus to identify observational studies evaluating serological or molecular biomarkers for recurrence of HCC after LT using adjusted analysis...

  14. Photoaffinity labeling of rat liver ribosomes by N-(2-Nitro-4-azidobenzoyl)puromycin

    International Nuclear Information System (INIS)

    Boehm, H.; Stahl, J.; Bielka, H.

    1979-01-01

    N-(2-nitro-4-azidobenzoyl)-[ 3 H]puromycin (NAB-puromycin) was synthesized as a photoreactive derivative of puromycin in order to detect ribosomal proteins located near the peptidyltransferase centre of rat liver ribosomes. Irradiation of ribosome-NAB-puromycin complexes leads to covalent attachment of the affinity label to proteins of the large ribosomal subunit, in particular to proteins L28/29, and, to a somewhat lower extent, to proteins L4, L6, L10 and L24. The results are discussed in the light of earlier studies performed with other affinity labels that attacked the peptidyltransferase region of rat liver ribosomes. (author)

  15. Blockade of Vascular Adhesion Protein-1 Inhibits Lymphocyte Infiltration in Rat Liver Allograft Rejection

    OpenAIRE

    Martelius, Timi; Salaspuro, Ville; Salmi, Marko; Krogerus, Leena; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

    2004-01-01

    Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174–5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/gro...

  16. Early radiation impairment of the cholesterol metabolism in organelles of rat liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Kaznacherev, Yu S; Kolomiitseva, I K [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

    1975-05-01

    The incorporation of 1-C/sup 14/-acetate into cholesterol of the nuclear, mitochondrial, microsomal and 105000 g-supernatant fractions isolated from the rat liver in norm and 60 min after the exposure to 1200 r has been investigated. An increase has been observed in the label uptake into liver cholesterol of irradiated rats. Intracellular distribution of the newly synthesized (labelled) cholesterol is substantially changed after irradiation: maximum label incorporation into the cholesterol is observed in the 105000 g-supernatant fraction, whereas, normally, the cholesterol of microsomal fraction has the highest specific activity.

  17. Characterization of the somatogenic receptor in rat liver. Hydrodynamic properties and affinity cross-linking

    International Nuclear Information System (INIS)

    Husman, B.; Haldosen, L.A.; Andersson, G.; Gustafsson, J.A.

    1988-01-01

    Rat liver somatogenic receptors have been characterized by gel permeation chromatography, sucrose density gradients in H 2 O and D 2 O, and affinity cross-linking using 125 I-bovine growth hormone (bGH) as a specific somatogenic receptor ligand. Cross-linking of 125 I-bovine growth hormone to a Triton X-100-treated low density fraction isolated from livers of late pregnant rats followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis under reducing conditions showed three major binders with Mr 95,000, 86,000, and 43,000 and a minor binder of Mr 55,000, after correction for bound ligand assuming a 1:1 binding ratio of ligand-receptor. The Mr 86,000, 55,000, and 43,000 species were recovered in the detergent-soluble supernatant after high-speed centrifugation, whereas the Mr 95,000 species remained Triton X-100 insoluble. Detergent-soluble 125 I-bGH-receptor complexes were further analyzed by sedimentation into sucrose density gradients. The sedimentation coefficient was S20,w = 5.2 S and the partial specific volume v = 0.72 ml/g. Gel permeation chromatography on a Sepharose S-400 column indicated a Stokes radius of 61 A for the 125 I-bGH-receptor-Triton X-100 complex. Based on these figures, the molecular weight of the complex was calculated as 131,100. The molecular weight of the ligand-free receptor-Triton X-100 complex was calculated as Mr 109,100. Affinity cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the 61 A peak from Sephacryl S-400 chromatography (cf. above) showed two binding entities, one major and one minor with Mr values 86,000 and 43,000, respectively, in the absence of reductant. When electrophoresis was run in the presence of reductant the Mr 43,000 species was the major binding entity

  18. Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCl(4)-induced liver injury in rats.

    Science.gov (United States)

    Jayakumar, T; Ramesh, E; Geraldine, P

    2006-12-01

    This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom Pleurotus ostreatus on CCl(4)-induced liver damage in male Wistar rats. Intraperitoneal administration of CCl(4) (2ml/kg) to rats for 4 days resulted in significantly elevated (pSALP) compared to controls. In the liver, significantly elevated levels (pSALP levels reverted to near normal, while the hepatic concentration of GSH, CAT, SOD and Gpx were significantly increased (p<0.05) and that of MDA significantly (p<0.05) lowered, when compared to CCl(4)-exposed untreated rats. Histopathological studies confirmed the hepatoprotective effect conferred by the extract of P. ostreatus. These results suggest that an extract of P. ostreatus is able to significantly alleviate the hepatotoxicity induced by CCl(4) in the rat.

  19. LOCALIZATION OF POLYSOME-BOUND ALBUMIN AND SERINE DEHYDRATASE IN RAT LIVER CELL FRACTIONS

    Science.gov (United States)

    Ikehara, Yukio; Pitot, Henry C.

    1973-01-01

    The polysomes involved in albumin and serine dehydratase synthesis were identified and localized by the binding to rat liver polysomes of anti-rat serum albumin and anti-serine dehydratase [125I]Fab dimer and monomer. Techniques were developed for the isolation of undegraded free and membrane-bound polysomes and for the preparation of [125I]Fab monomers and dimers from the IgG obtained from the antisera to the two proteins, rat serum albumin and serine dehydratase. The distribution of anti-rat serum albumin [125I]Fab dimer in the polysome profile is in accordance with the size of polysomes that are expected to be synthesizing albumin. By direct precipitation, it has been demonstrated that nascent chains isolated from the membrane-bound polysomes by puromycin were precipitated by anti-rat serum albumin-IgG at a level of 5–6 times those released from free polysomes. Anti-rat serum albumin-[125I]Fab dimer reacted with membrane-bound polysomes almost exclusively compared to the binding of nonimmune, control [125I]Fab dimer; a significant degree of binding of anti-rat serum albumin-[125I]Fab to free polysomes was also obtained. The [125I]Fab dimer made from normal control rabbit serum does not react with polysomes from liver at all and this preparation will not interact with polysomes extracted from tissues that do not synthesize rat serum albumin. Both anti-serine dehydratase-[125I]Fab monomer and dimer react with free and bound polysomes from livers of animals fed a chow diet or those fed a high 90% protein diet and given glucagon. In the latter instance, however, it is clear that the majority of the binding occurs to the bound polysomes. Furthermore, the specificity of this reaction may be further shown by the use of kidney polysomes that do not normally synthesize serine dehydratase. When these latter polysomes are isolated, even after the addition of crude and purified serine dehydratase, no reaction with anti-serine dehydratase-Fab fragments could be

  20. Protective function of complement against alcohol-induced rat liver damage.

    Science.gov (United States)

    Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

    2004-11-01

    The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

  1. 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.

  2. Molecular cloning and nucleotide sequence of cDNA for human liver arginase

    International Nuclear Information System (INIS)

    Haraguchi, Y.; Takiguchi, M.; Amaya, Y.; Kawamoto, S.; Matsuda, I.; Mori, M.

    1987-01-01

    Arginase (EC3.5.3.1) catalyzes the last step of the urea cycle in the liver of ureotelic animals. Inherited deficiency of the enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, the authors isolated cDNA clones for human liver arginase. Oligo(dT)-primed and random primer human liver cDNA libraries in λ gt11 were screened using isolated rat arginase cDNA as a probe. Two of the positive clones, designated λ hARG6 and λ hARG109, contained an overlapping cDNA sequence with an open reading frame encoding a polypeptide of 322 amino acid residues (predicted M/sub r/, 34,732), a 5'-untranslated sequence of 56 base pairs, a 3'-untranslated sequence of 423 base pairs, and a poly(A) segment. Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying λ hARG6 cDNA insert. RNA gel blot analysis of human liver RNA showed a single mRNA of 1.6 kilobases. The predicted amino acid sequence of human liver arginase is 87% and 41% identical with those of the rat liver and yeast enzymes, respectively. There are several highly conserved segments among the human, rat, and yeast enzymes

  3. Metabonomic evaluation of idiosyncrasy-like liver injury in rats cotreated with ranitidine and lipopolysaccharide

    International Nuclear Information System (INIS)

    Maddox, Jane F.; Luyendyk, James P.; Cosma, Gregory N.; Breau, Alan P.; Bible, Roy H.; Harrigan, George G.; Goodacre, Royston; Ganey, Patricia E.; Cantor, Glenn H.; Cockerell, Gary L.; Roth, Robert A.

    2006-01-01

    Idiosyncratic liver injury occurs in a small fraction of people on certain drug regimens. The cause of idiosyncratic hepatotoxicity is not known; however, it has been proposed that environmental factors such as concurrent inflammation initiated by bacterial lipopolysaccharide (LPS) increase an individual's susceptibility to drug toxicity. Ranitidine (RAN), a histamine-2 receptor antagonist, causes idiosyncratic liver injury in humans. In a previous report, idiosyncrasy-like liver toxicity was created in rats by cotreating them with LPS and RAN. In the present study, the ability of metabonomic techniques to distinguish animals cotreated with LPS and RAN from those treated with each agent individually was investigated. Rats were treated with LPS or its vehicle and with RAN or its vehicle, and urine was collected for nuclear magnetic resonance (NMR)- and mass spectroscopy-based metabonomic analyses. Blood and liver samples were also collected to compare metabonomic results with clinical chemistry and histopathology. NMR metabonomic analysis indicated changes in the pattern of metabolites consistent with liver damage that occurred only in the LPS/RAN cotreated group. Principal component analysis of urine spectra by either NMR or mass spectroscopy produced a clear separation of the rats treated with LPS/RAN from the other three groups. Clinical chemistry (serum alanine aminotransferase and aspartate aminotransferase activities) and histopathology corroborated these results. These findings support the potential use of a noninvasive metabonomic approach to identify drug candidates with potential to cause idiosyncratic liver toxicity with inflammagen coexposure

  4. Hepatoprotective effect of Opuntia dillenii seed oil on CCl4 induced acute liver damage in rat

    Directory of Open Access Journals (Sweden)

    Mohamed Bouhrim

    2018-01-01

    Full Text Available Objective: To investigate the hepatoprotective effect of Opuntia dillenii seed oil (ODSO on CCl4 provoked liver injury in rat. Methods: Animals were treated orally with ODSO at a concentration of 2 mL/kg, once daily for one week before the first intraperitoneal injection of CCl4, and thereafter the administration of the oil was continued for 7 days until the introduction of the second injection of CCl4. Fourteen hours after the last dose of CCl4, rats were sacrificed, and the relative liver weight, weight gain, alkaline phosphatase, aspartate amino transferase, alanine aminotransferase, direct bilirubin, total bilirubin, triglycerides, total cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, plasmatic glucose, urea, creatinine, acid uric and malondialdehyde were determined. Results: The significant increase was found in relative liver weight and plasma levels of alanine aminotransferase, aspartate amino transferase, alkaline phosphatase, total bilirubin, direct bilirubin, triglycerides, very low-density lipoprotein, urea, uric acid and malondialdehyde. Likewise, the significant decrease was indicated in the weight gain and the level of glucose plasmatic, and high-density lipoprotein levels in CCl4 produced liver injury in rats were re-established to normal levels when treated with ODSO. While, no change was observed in the total cholesterol, low-density lipoprotein and creatinine in all animals. Conclusions: We conclude that the ODSO has a protective effect on CCl4-mediated liver injury. Hence, we suggest its inclusion as a preventive control of liver disorders.

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

    International Nuclear Information System (INIS)

    Elkashef, H.S.; Roushdy, H.M.; Saada, H.N.; Abdelsamie, M.

    1986-01-01

    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

  6. Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism.

    Science.gov (United States)

    Ayyar, Vivaswath S; Almon, Richard R; DuBois, Debra C; Sukumaran, Siddharth; Qu, Jun; Jusko, William J

    2017-05-08

    other tissues is sparse. While transcriptomic regulation following methylprednisolone (MPL) dosing has been temporally examined in rat liver, proteomic assessments are needed to better characterize the tissue-specific functional aspects of MPL actions. This study describes a functional pharmacoproteomic analysis of dynamic changes in MPL-regulated proteins in liver and provides biological insight into how steroid-induced perturbations on a molecular level may relate to both adverse and therapeutic responses presented clinically. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2004-12-01

    Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats. 2004 John Wiley & Sons, Ltd.

  8. 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)

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

    International Nuclear Information System (INIS)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Boisgard, R.; Tavitian, B.; Boisgard, R.; Tavitian, B.; Roux, J.; Cales, P.; Clerc, J.

    2008-01-01

    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 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. 131 I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  10. Inhibition of the phospholipid transfer within the organelles of cells in the irradiated rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Kaznacheev, Yu S; Kolomiytseva, I K [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

    1975-01-01

    Phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) exchange between different subcellular fractions of liver has been studied in normal rats and 1 hr after gamma-irradiation of rats at a dose of 1200 R. The rate of PC transfer in microsome-mitochondrion and microsome-nucleus systems is 1.5 to 2 times higher than that of PE. Early after irradiation the rates of PE and PC transfer decrease in both microsome-mitochondrion and microsome-nucleus systems.

  11. Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

    Directory of Open Access Journals (Sweden)

    Elias Adikwu

    2018-03-01

    Full Text Available Objective: Hepatotoxicity is a clinical challenge associated with the use of efavirenz (EFV. This study investigated the effects of n-acetylcysteine (NAC, vitamins C and E on EFV-induced hepatotoxicity in albino rats. Methods: Rats were divided into groups and administered with NAC (20mg/kg, Vit C (50mg/kg, Vit  E (50mg/kg, Vit C+ E and 60mg/kg of EFV respectively. Rats were also divided into groups and pretreated with NAC, Vit C, E, and combined doses of Vit C+E prior to treatment with EFV for 15 days respectively. After drug administration rats were sacrificed and serum was collected and evaluated for liver function parameters. Rats were dissected, liver was collected weighed and evaluated for alkaline phosphatase (ALP, alanine aminotransferase (AST, aspartate aminotransferase (ALT, gamma glutamyl transferase (GGT, lactate dehydrogenase (LDH, malondialdehyde (MDA, super oxide dismutase (SOD, catalase (CAT, glutathione (GSH, gluthatione peroxidase (GPX levels and pathological damage. Results: Effects were not significant (p>0.05 on body and liver weights, however, the levels of AST, ALT, AST, GGT, LDH, CB, TB and MDA were increased significantly (p<0.05 whereas SOD, CAT, SOD, GSH and GPX were decreased significantly (p<0.05 in EFV-treated rats in comparison to control. The liver of EFV-treated rats showed necrosis of hepatocytes. Nevertheless, EFV-induced alterations in the above parameters were significantly (p<0.05 ameliorated in antioxidants pretreated rats.  The combined doses of Vit C and E produced the best and significant (p<0.05 ameliorative effects in comparison to their individual doses. Conclusion: This study shows the prospects of antioxidants as candidates for the treatments of efavirenz-induced hepatotoxicity.

  12. Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

    Science.gov (United States)

    Rigo, Federica; De Stefano, Nicola; Navarro-Tableros, Victor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

    2018-05-01

    The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

  13. Polycyclic hydrocarbon biomarkers confirm selective incorporation of petroleum in soil and kangaroo rat liver samples near an oil well blowout site in the western San Joaquin Valley, California

    International Nuclear Information System (INIS)

    Kaplan, I.; Lu, S.T.; Lee, R.P.; Warrick, G.

    1996-01-01

    Following an accidental oil well blow out at an oil field in the western part of the San Joaquin Valley, soil samples and specimens of Heermann's kangaroo rats (Dipodomys heermanni) were collected from two oil-impacted areas and one control area. Fingerprinting by GC-MS and quantitative evaluation of metabolized petroleum hydrocarbons was performed on oil, soil extracts, and rat livers. A liver from a domestically raised rabbit was used as an experimental control. The results show that there is no significant incorporation of PAHs or low molecular weight n-alkanes (C 13 --C 25 ) into the liver tissues. The C 25 --C 35 n-alkane range for all soil samples, kangaroo rat livers, and rabbit liver, is dominated by a high abundance of C 27 , C 29 , C 31 , and C 33 hydrocarbons typical of epicuticular plant waxes. In all liver tissue samples, squalene, the cholesterol precursor, is the dominant hydrocarbon. Although evidence is lacking for metabolism of PAHs and paraffinic petroleum hydrocarbons, very strong evidence is available for incorporation of a set of polycyclic hydrocarbons (biomarkers) belonging to the terpane, sterane, and monoaromatic and triaromatic sterane families, identified by ion monitoring at 191, 217, 253, and 231 m/z, respectively. Because these hydrocarbons are not known to exist in the biosphere, but are only synthesized during oil- and coal-forming processes, their presence in the liver samples constitutes proof for crude oil incorporation into tissues. This conclusion is further substantiated by the selective incorporation of only the 20S enantiomer of C 28 and C 29 steranes and aromatic steranes into the livers, with the exclusion of the 20R enantiomer. The results from the study conclusively demonstrate that polycyclic hydrocarbon biomarkers provide excellent indices for proof of petroleum exposure and metabolism in some terrestrial herbivores

  14. On the Localisation of d-Tubocurarine in Rat Liver Lysosomes in vivo by Electron Microscopy and Subcellular Fractionation

    NARCIS (Netherlands)

    Weitering, Jeanette G.; Mulder, Gerard J.; Meijer, Dirk K.F.; Lammers, Wim; Veenhuis, Maarten; Wendelaar Bonga, Sjoerd E.

    1975-01-01

    After i.v. injection in the rat, d-tubocurarine is taken up and concentrated by the liver. A method is developed for the visualisation of d-tubocurarine inside the liver cell by electron microscopy. Glutaraldehyde fixed liver blocks were immersed in an ammonium molybdate solution; d-tubocurarine was

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

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    Đurašević S.F.

    2010-01-01

    Full Text Available We tested to see if the additional intake of vitamin E in the form of α-tocopheryl-succinate would improve liver antioxidative protection. Thus, we studied the tissue oxidative status in rats supplemented by two doses of the antioxidant over a four week period of time. Our results confirmed that the additional intake of vitamin E decreased the liver lipid peroxidation level and SOD activity level and preserved its vitamin C content. However, the hydrogen peroxide content and catalase activity remained unchanged, probably due to the mechanism of vitamin E liver metabolism. .

  16. On the postradiation effect of cystamine in rat liver cells

    International Nuclear Information System (INIS)

    Gil'yano, N.Ya.; Malinovskij, O.V.

    1979-01-01

    The effect of cystamine, classical radioprotector introduced prior to and after irradiation has been tested. The protector has been paralelly tested on the regenerating liver in a presynthetic phase of a mitotic cycle (G 1 ). White nonbred male mice have been irradiated with 205 and 6O5 rad on the RUM-11 X-ray apparatus prior to (intact liver) and 6 hours after (regenerating liver) partial hepatectomy. Cystamine has been injected to animals 15 min prior to irradiation and in different periods after irradiation in the concentration of 150 mg/kg of weight. The decrease in the share of cells with asymmetic chromosome transformations (bridges and fragments in the anaphase) has been the protector effectiveness index. It is shown that the protector is effective in the cells of a regenerating liver only when introduced before irradiation, while in the cells of an intact liver it produces a protective effect both prior to and 15 mins after irradiation. Cystamine effectiveness for cells of the intact and regenerating liver has been investigated by introducing it after irradiation of animals with 250 and 305 rad. It has been established that the protector makes it possible to modify the irradiation effect within 20 mins after irradiation in the cells of the intact liver (Go). Cystamine postradiation protection in the cells of the regenerating liver (G 1 ) is low if it is introduced immediately after irradiation (1 min) and is absent after 10 min. The dependence of cystamine postradiation protective effect on the moment of liver cell stimulation has been investigated. It has been shown that the modification of irradiation effect is possible within 5 hrs after irradiation if the protector is introduced 15 min after irradiation of animals with 250 rad. The mechanism of the preparation action is discussed

  17. Adrenal hormones and liver cAMP in exercising rats--different modes of anesthesia.

    Science.gov (United States)

    Winder, W W; Fuller, E O; Conlee, R K

    1983-11-01

    We have compared five different modes of anesthesia (iv and ip pentobarbital sodium, ether, CO2, and cervical dislocation) with respect to their effects on liver glycogen, liver adenosine 3',5'-cyclic monophosphate (cAMP), blood glucose and lactate, plasma corticosterone, norepinephrine, and epinephrine in resting rats and in rats run on a treadmill at 26 m/min for 30 min. Ether, CO2, and cervical dislocation were found to be unsuitable due to the marked elevation in plasma catecholamines seen in both resting and exercising rats. Injection of pentobarbital sodium ip required an average of 8 min before onset of surgical anesthesia as opposed to less than 5 s for iv pentobarbital. Exercising rats anesthetized with ip pentobarbital showed markedly lower plasma catecholamines compared with rats given iv pentobarbital. Hepatic cAMP increased in response to exercise in all groups except the ip pentobarbital group. This is most likely due to the long delay between the end of the exercise and freezing of the liver in the ip pentobarbital-anesthetized animals. We conclude that iv injection of pentobarbital is the most suitable method of anesthesia for obtaining accurate measurements of plasma stress hormones, substrates, and metabolites and of hepatic cAMP and glycogen in resting and exercising rats.

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

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    TUTIK WRESDIYATI

    2008-09-01

    Full Text Available Intracellular antioxidant superoxide dismutase (SOD was reported decreased in the liver and kidney of hypercholesterolemic rats. This study was conducted to observe the effect of seaweed Eucheuma cottonii powder on the profile of blood cholesterol and the level of SOD in liver tissues of hypercholesterolemic rats by using immunohistochemical technique. Twenty male Wistar rats were used for this study. Those rats were divided into four groups; (i negative control group (A, (ii hypercholesterolemia group treated by 5% seaweed powder (B, (iii hypercholesterolemia group treated by 10% seaweed powder (C, and (iv Positive control group or hypercholesterolemia group (D. The experiment was carried out for 35 days. Hypercholesterolemia condition (> 130 mg/dl, except group A, was achieved by feeding the rats with commercial diet containing 1% cholesterol. Drinking water was given ad libitum for 40 days. The results showed that seaweed powder decreased the total cholesterol, low density lipoprotein (LDL, triglyceride, and increased the level of high density lipoprotein (HDL and SOD status in the liver tissues of hypercholesterolemic rats. The treatment of 10% seaweed powder gave better results than that of 5%. These results suggested that dietary fiber such in the seaweed powder has antioxidant activity.

  19. Identification and characterization of metabolites of ASP015K, a novel oral Janus kinase inhibitor, in rats, chimeric mice with humanized liver, and humans.

    Science.gov (United States)

    Nakada, Naoyuki; Oda, Kazuo

    2015-01-01

    1. Here, we elucidated the structure of metabolites of novel oral Janus kinase inhibitor ASP015K in rats and humans and evaluated the predictability of human metabolites using chimeric mice with humanized liver (PXB mice). 2. Rat biological samples collected after oral dosing of (14)C-labelled ASP015K were examined using a liquid chromatography-radiometric detector and mass spectrometer (LC-RAD/MS). The molecular weight of metabolites in human and the liver chimeric mouse biological samples collected after oral dosing of non-labelled ASP015K was also investigated via LC-MS. Metabolites were also isolated from rat bile samples and analyzed using nuclear magnetic resonance. 3. Metabolic pathways of ASP015K in rats and humans were found to be glucuronide conjugation, methyl conjugation, sulfate conjugation, glutathione conjugation, hydroxylation of the adamantane ring and N-oxidation of the 1H-pyrrolo[2,3-b]pyridine ring. The main metabolite of ASP015K in rats was the glucuronide conjugate, while the main metabolite in humans was the sulfate conjugate. Given that human metabolites were produced by human hepatocytes in chimeric mice with humanized liver, this human model mouse was believed to be useful in predicting the human metabolic profile of various drug candidates.

  20. Evaluation of the effects of a VEGFR-2 inhibitor compound on alanine aminotransferase gene expression and enzymatic activity in the rat liver.

    Science.gov (United States)

    Fuentealba, Carmen; Bera, Monali; Jessen, Bart; Sace, Fred; Stevens, Greg J; Trajkovic, Dusko; Yang, Amy H; Evering, Winston

    2011-08-17

    Traditional assessment of drug-induced hepatotoxicity includes morphological examination of the liver and evaluation of liver enzyme activity in serum. The objective of the study was to determine the origin of drug-related elevation in serum alanine aminotransferase (ALT) activity in the absence of morphologic changes in the liver by utilizing molecular and immunohistochemical techniques. Sixteen female Sprague-Dawley rats were divided into 2 groups (control and treated, n = 4 per group) and treated rats were dosed orally twice daily (400 mg/kg/day) for 7 days with a VEGFR-2 compound (AG28262), which in a previous study caused ALT elevation without morphological changes. Serum of both treated and control animals were evaluated on day 3 of treatment and at day 8. Three separate liver lobes (caudate, right medial, and left lateral) were examined for determination of ALT tissue activity, ALT gene expression and morphological changes. ALT activity was significantly (p < 0.01) elevated on day 3 and further increased on day 8. Histologic changes or increase in TUNEL and caspase3 positive cells were not observed in the liver lobes examined. ALT gene expression in the caudate lobe was significantly up-regulated by 63%. ALT expression in the left lateral lobe was not significantly affected. Statistically significant increased liver ALT enzymatic activity occurred in the caudate (96%) and right medial (41%) lobes but not in the left lateral lobe. AG28262, a VEFG-r2 inhibitor, causes an increase in serum ALT, due in part to both gene up-regulation. Differences between liver lobes may be attributable to differential distribution of blood from portal circulation. Incorporation of molecular data, such as gene and protein expression, and sampling multiple liver lobes may shed mechanistic insight to the evaluation of hepatotoxicity.

  1. 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.

  2. 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

  3. Decreased bilirubin transport in the perfused liver of endotoxemic rats

    NARCIS (Netherlands)

    Roelofsen, H.; van der Veere, C. N.; Ottenhoff, R.; Schoemaker, B.; Jansen, P. L.; Oude Elferink, R. P.

    1994-01-01

    Hyperbilirubinemia associated with sepsis is frequently observed in humans. In this study, an experimental rat model was developed to study bilirubin metabolism and transport during endotoxemia. Rats were injected intravenously with a single bolus of lipopolysaccharide (1 mg/kg); after 18 hours, the

  4. DECREASED BILIRUBIN TRANSPORT IN THE PERFUSED LIVER OF ENDOTOXEMIC RATS

    NARCIS (Netherlands)

    ROELOFSEN, H; VANDERVEERE, CN; OTTENHOFF, R; SCHOEMAKER, B; JANSEN, PLM; ELFERINK, RPJO

    1994-01-01

    Background/Aims: Hyperbilirubinemia associated with sepsis is frequently observed in humans. In this study, an experimental rat model was developed to study bilirubin metabolism and transport during endotoxemia. Methods: Rats were injected intravenously with a single bolus of lipopolysaccharide (1

  5. Quantitative evaluation of 99mTc-GSA for fatty liver and ischemia-reperfusion injury in rats

    International Nuclear Information System (INIS)

    Kimoto, Mitsunori

    1996-01-01

    99m Tc-GSA (GSA) liver scintigraphy was performed in rats with fatty liver and ischemia-reperfusion injury to study the usefulness of GSA in evaluating these pathological processes. Fatty liver was produced by feeding rats a choline-deficient diet. The rats with fatty liver were divided into five groups according to the length of the diet (controls, two weeks, six weeks, 10 weeks, and 12 weeks). In the rats dieted for two weeks and six weeks, regional hepatic ischemia was also induced by clamping the left hepatic artery and the left portal vein for 10 minutes, then reperfusion was performed for 15 minutes. GSA was administered via the IVC. t 90 , or the time at which the liver time activity curve reached ninety percent of its peak value, was used as an index of GSA hepatic uptake, Ku and Kd, determined by two compartment analysis, were also used as indices. In rats of the fatty liver group, we confirmed microscopically that various degrees of fatty infiltration existed according to the diet period, and t 90 became significantly longer according to the severity of fatty infiltration. Ku and Kd also decreased according to the severity of fatty infiltration. In the rats with fatty infiltration and ischemia-reperfusion injury, t 90 also increased according to the severity of fatty infiltration, becoming longer than in the rats without ischemia-reperfusion injury. Quantitative analysis of GSA liver scintigraphy was useful for evaluating fatty liver and ischemia-reperfusion injury. (author)

  6. Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment

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    Sana Chakroun

    2017-12-01

    Full Text Available Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50 given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx. Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01 which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

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

    International Nuclear Information System (INIS)

    Abd Elmonem, H.A.

    2014-01-01

    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.

  8. Immunohistochemical analysis of cannabinoid receptor 1 expression in steatotic rat livers.

    Science.gov (United States)

    Zduniak, Krzysztof; Ziółkowski, Piotr; Regnell, Pontus; Tollet-Egnell, Petra; Åkesson, Lina; Cooper, Martin E

    2016-04-01

    The primary aim of the present study was to determine the expression levels of cannabinoid receptor type 1 (CB1) in steatotic rat livers. The secondary aim was to clarify whether steatosis and inflammation are more marked in areas with increased CB1 overexpression. For ethical and economic reasons, the present study investigated tissue from archived liver blocks, which were obtained from 38 rats that had been euthanized during the course of previous research at the Karolinska Institute of the Karolinska University Hospital (Stockholm, Sweden) and Lund University (Malmö, Sweden). Liver tissue fixed in formalin and embedded in paraffin was used that had been sourced from 36 male Sprague Dawley rats (age, 7 weeks) and 2 rats (age, 180 days) lacking normal leptin receptors. The rat liver tissue was stained with antibodies against CB1 and counterstained with hematoxylin. The expression of CB1 and the number of cells overexpressing CB1 were determined. Steatosis was scored according to the Dixon scoring system. CB1 overexpression and steatosis were detected in hepatocytes from all 38 livers sampled. The expression of CB1 was more marked in hepatocytes localized next to portal triads. Near the central veins, the expression was significantly weaker. Steatosis was more marked in areas of increased CB1 overexpression. Lymphocyte infiltration was more commonly observed in areas of increased CB1 overexpression. Therefore, the present results indicate that CB1 receptors are overexpressed in areas with steatosis, and indicate that CB1 in hepatocytes contributes to the formation of steatosis in rats, even prior to its progression to steatohepatitis. These results are consistent with publications reporting that CB1 in hepatocytes increases lipogenesis and contributes to inflammation.

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

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2006-01-01

    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

  10. Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Cheng Jun

    2012-09-01

    Full Text Available Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC. Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV infection. Level of low density lipoprotein receptor (LDL-R and activity of peroxisome proliferator-activated receptor (PPAR α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP, and formation of very low density lipoprotein (VLDL have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN, HMG CoA reductase (HMGCR, liver X receptor (LXR, acetyl-CoA carboxylase 1 (ACC1, hepatic CB (1 receptors, retinoid X receptor (RXR α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

  11. Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

    Science.gov (United States)

    Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

    2018-03-15

    The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

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

    International Nuclear Information System (INIS)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-01-01

    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

  13. Changes of α-glycerophosphate dehydrogenase activity in fatty liver of rats by amino acid imbalance

    International Nuclear Information System (INIS)

    Ogura, Masaji; Katsunuma, Eiichi; Akabane, Tomoko; Ogawa, Seiichi

    1976-01-01

    The previous study on the lipogenesis in the fatty livers of rats, which was induced by feeding the diet with imbalanced amino acid, revealed that the induction of this type of fatty livers was due mainly to the acceleration of triglyceride synthesis by the increase in both synthesis and esterification of fatty acid in the livers. Although many studies have been carried out on the dietary control of α-glycerophosphate dehydrogenase activity in rat livers, the enzyme change in amino acid imbalance has not been reported. In the present study, in order to elucidate the difference in the supply of glycerol moiety of triglyceride due to the imbalance, the change of the α-glycerophosphate dehydrogenase activity in livers was investigated. The experimental diets were 8% casein basal diet and basal + 0.3% DL-methionine imbalanced diet. 5 rats of each group were killed after 0.5 and 10 days on the diet, and the analysis of the lipid content in the livers and the determination of the α-glycerophosphate dehydrogenase activity were carried out. The linear response of the enzyme activity to time and protein concentration was obtained. The development of fatty livers was observed in the imbalanced diet group in the feeding period of 10 days. It was found that the specific activity of the imbalanced diet group increased significantly in 5 and 10 days as compared with that of the basal diet group. The elevation in the enzyme activity may suggest that the supply of α-glycerophosphate for triglyceride synthesis is also increased in this type of fatty livers. (Kako, I.)

  14. 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.

  15. Clofibric Acid Increases the Formation of Oleic Acid in Endoplasmic Reticulum of the Liver of Rats

    OpenAIRE

    広瀬, 明彦; 山崎, 研; 坂本, 武史; 須永, 克佳; 津田, 整; 光本, 篤史; 工藤, なをみ; 川嶋, 洋一

    2011-01-01

    The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [14C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellul...

  16. 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...... as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose...

  17. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism.

    Science.gov (United States)

    Li, Shuang; Wang, S U; Guo, Zhi-Gang; Huang, Ning; Zhao, Fan-Rong; Zhu, Mo-Li; Ma, Li-Juan; Liang, Jin-Ying; Zhang, Yu-Lin; Huang, Zhong-Lin; Wan, Guang-Rui

    2015-11-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

  18. A NOVEL S-ADENOSYL-L-METHIONINE: ARSENIC (III) METHYLTRANSFERASE FROM RAT LIVER CYTOSOL

    Science.gov (United States)

    A Novel S-Adenosyl-L-methionine: Arsenic(III) Methyltransferase from Rat Liver CytosolShan Lin, Qing Shi, F. Brent Nix, Miroslav Styblo, Melinda A. Beck, Karen M. Herbin-Davis, Larry L. Hall, Josef B. Simeonsson, and David J. Thomas S-adenosyl-L-methionine (AdoMet): ar...

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

    International Nuclear Information System (INIS)

    Abdel Motaal, N.A.; Abdel Maguid, A.

    2007-01-01

    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

  20. 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

  1. Effect of D-tagatose on liver weight and glycogen content of rats

    NARCIS (Netherlands)

    Bär, A.; Lina, B.A.R.; Groot, D.M.G. de; Bie, B. de; Appel, M.J.

    1999-01-01

    D-Tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations.

  2. 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.

  3. Rat liver microsomal cytochrome P450-dependent oxidation of 3,5-disubstituted analogues of paracetamol

    NARCIS (Netherlands)

    Bessems, J.G.M.; Koppele, J.M. te; Dijk, P.A. van; Stee, L.L.P. van; Commandeur, J.N.M.; Vermeulen, N.P.E.

    1996-01-01

    1. The cytochrome P450-dependent binding of paracetamol and a series of 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -C(H)3, -C2H5, -iC3H7) have been determined with β-naphthoflavone (βNF)-induced rat liver microsomes and produced reverse type I spectral changes. K(s,app) varied

  4. Control of ketogenesis in the perfused rat liver by the sympathetic innervation

    NARCIS (Netherlands)

    Beuers, U.; BECKH, K.; JUNGERMANN, K.

    1986-01-01

    The regulation of ketogenesis by the hepatic nerves was investigated in the rat liver perfused in situ. Electrical stimulation of the hepatic nerves around the portal vein and the hepatic artery caused a reduction of basal ketogenesis owing to a decrease in acetoacetate release to 30% with

  5. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver.

    NARCIS (Netherlands)

    Oetari, S.; Sudibyo, M.; Commandeur, J.N.M.; Samhoedi, R.; Vermeulen, N.P.E.

    1996-01-01

    The stability of curcumin, as well as the interactions between curcumin and cytochrome P450s (P450s) and glutathione S-transferases (GSTs) in rat liver, were studied. Curcumin is relatively unstable in phosphate buffer at pH 7.4. The stability of curcumin was strongly improved by lowering the pH or

  6. Metabolism and Clearance of T-2 Mycotoxin in Perfused Rat Livers

    Science.gov (United States)

    1986-02-10

    nucleottde system in rat liver. B5ochem. J. 117, 499-503. 4ALLACE, E. 4., PATHRE, S. V., MIROCHA, C. J., ROSISON, T. S., AND FENTON , S. W. (1977). Synthesis...lactating cow. Food Cosmet . Toxicol. 19, 31- 39. YOSHIZAWA, T., SAKAMOTO, T., AND KUWAMWA, K. (1985). Structures of Deepoxytrichothecene mecabolites

  7. 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

    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...

  8. Effects of gamma-irradiation on the glycogen and lipid contents of the rat liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Nahed, R H.A.; Al-Zahaby, Al-Ahmmady, S.; Sanad, S M.K.; Roushdy, H M

    1986-01-01

    Histochemical changes in the glycogen and lipid contents of the rat liver cells were studied at different intervals following whole body gamma-irradiation at the exposure dose level of 600 rads. The glycogen and lipid contents were significantly altered, the changes were time-dependent.

  9. Morphometric analysis of peroxisome proliferation by phthalate esters in rat liver

    NARCIS (Netherlands)

    Dormans JAMA; Jansen EHJM; de Vlugt-van den Koedijk FM; Riool-Nesselaar G

    1992-01-01

    Morphometric analysis was performed on liver sections of rats at light (LM) and electron microscopical (EM) level to demonstrate proliferation of peroxisomes after administration of di (2-ethylhexyl)phthalate at dietary levels of 0, 60, 200, 600, 2000 and 6000 mg/kg diet for 2 weeks. Enzyme

  10. The protective effect of pomegranate extract against cisplatin toxicity in rat liver and kidney tissue.

    Science.gov (United States)

    Bakır, Salih; Yazgan, Ümit Can; İbiloğlu, İbrahim; Elbey, Bilal; Kızıl, Murat; Kelle, Mustafa

    2015-01-01

    The purpose of this study was to perform a histopathological investigation, at the light microscopy level, of the protective effects of pomegranate extract in cisplatin-induced liver and kidney damage in rats. Twenty-eight adult male Wistar albino rats were randomly divided into four groups of seven animals: Group 1: Control; Group 2: Treated for 10 consecutive days by gavage with pomegranate juice (2 ml/kg/day); Group 3: Injected intraperitoneally with cisplatin (8 mg/kg body weight, single dose) onset of the day 5, and Group 4: Treated by gavage with pomegranate juice 10 days before and after a single injection of cisplatin onset of the day 5. After 10 days, the animals were sacrificed and their kidneys and liver tissue samples were removed from each animal after experimental procedures. Cisplatin-induced renal and hepatic toxicity and the effect of pomegranate juice were evaluated by histopatological examinations. In the kidney tissue, pomegranate juice significantly ameliorated cisplatin-induced structural alterations when compared with the cisplatin alone group. But in the liver tissue, although pomegranate juice attenuated the cisplatin-induced toxicity only in two rats, significant improvement was not observed. In conclusion, these results demonstrate that the anti-oxidant pomegranate juice might have a protective effect against cisplatin-induced toxicity in rat kidney, but not in liver. Pomegranate juice could be beneficial as a dietary supplement in patients receiving chemotherapy medications.

  11. Structural and ultrastructural study of rat liver influenced by electromagnetic radiation.

    Science.gov (United States)

    Holovská, K; Almášiová, V; Cigánková, V; Beňová, K; Račeková, E; Martončíková, M

    2015-01-01

    Mobile communication systems are undoubtedly an environmental source of electromagnetic radiation (EMR). There is an increasing concern regarding the interactions of EMR with the humans. The aim of this study was to examine the effects of EMR on Wistar rat liver. Mature rats were exposed to electromagnetic field of frequency 2.45 GHz and mean power density of 2.8 mW/cm2 for 3 h/d for 3 wk. Samples of the liver were obtained 3 h after the last irradiation and processed histologically for light and transmission electron microscopy. Data demonstrated the presence of moderate hyperemia, dilatation of liver sinusoids, and small inflammatory foci in the center of liver lobules. Structure of hepatocytes was not altered and all described changes were classified as moderate. Electron microscopy of hepatocytes revealed vesicles of different sizes and shapes, lipid droplets, and proliferation of smooth endoplasmic reticulum. Occasionally necrotizing hepatocytes were observed. Our observations demonstrate that EMR exposure produced adverse effects on rat liver.

  12. Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

    Science.gov (United States)

    El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

    2016-12-01

    Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

  13. Age-related changes in the endocytic capacity of rat liver Kupffer and endothelial cells

    International Nuclear Information System (INIS)

    Brouwer, A.; Barelds, R.J.; Knook, D.L.

    1985-01-01

    There are many indications that the functional capacity of the reticuloendothelial system (RES) declines with age. The aim of this study was to investigate the cellular basis of age-related changes in the clearance function of the RES. The experiments were focused mainly on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of colloidal material from the circulation. The clearance capacity of the RES was tested clinically and experimentally by intravenous injection of colloids, such as radiolabeled heat-aggregated colloidal albumin. Age-related changes in the endocytosis of 125 I-labeled colloidal albumin (CA) in rats were determined by clearance and organ distribution of different doses of intravenously injected CA, uptake of CA by Kupffer and endothelial liver cells in vivo as determined after isolation of the cells from injected rats and kinetic studies on CA uptake by Kupffer cells in culture. The results show that, at a low dose, the clearance of CA is primarily determined by liver blood flow. At a higher saturating dose, plasma clearance and uptake by the liver are not significantly decreased with age. Endocytosis by endothelial cells, which accounts for about 60% of that of the whole liver, is also unchanged with age. In contrast, a significant decrease in endocytic capacity was observed for Kupffer cells in vivo. This age-related functional decline was also observed in Kupffer cells which were isolated from rats of different ages and maintained in culture

  14. Ganoderma tsugae Hepatoprotection against Exhaustive Exercise-Induced Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Wan-Teng Lin

    2013-01-01

    Full Text Available Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health promotion purposes. This study investigates the hepatoprotective effects of GT on exhaustive exercise-induced liver damage. Twenty-four male Sprague-Dawley rats were randomly divided into four groups and designated as exhaustive exercise only (E, exhaustive exercise with low dosage (EL, medium dosage (EM and high dosage (EH GT at 0, 0.1875, 0.9375 and 1.875 g/kg/day, respectively. After 30 days all rats were euthanized immediately after an exhaustive running challenge on a motorized treadmill. The rat livers were immediately harvested. Evidence of apoptotic liver cell death was revealed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay and caspases mediated cascade events. DNA fragmentation, an apoptosis process, can be examined using TUNEL assay. A few TUNEL-positive hepatocytes, compared to the exercise only group, were observed in the livers from exhaustive animals supplemented with GT. Immunoblot analysis also showed that caspase-6-mediated specific cleavage of lamin A/C was increased significantly in the livers of group E, but was significantly decreased in the EM and EH groups. Our observations demonstrate that GT possesses anti-apoptotic and hepatoprotective potential after exhaustive exercise.

  15. Ganoderma tsugae hepatoprotection against exhaustive exercise-induced liver injury in rats.

    Science.gov (United States)

    Huang, Chi-Chang; Huang, Wen-Ching; Yang, Suh-Ching; Chan, Chih-Chi; Lin, Wan-Teng

    2013-01-29

    Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT) is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health promotion purposes. This study investigates the hepatoprotective effects of GT on exhaustive exercise-induced liver damage. Twenty-four male Sprague-Dawley rats were randomly divided into four groups and designated as exhaustive exercise only (E), exhaustive exercise with low dosage (EL), medium dosage (EM) and high dosage (EH) GT at 0, 0.1875, 0.9375 and 1.875 g/kg/day, respectively. After 30 days all rats were euthanized immediately after an exhaustive running challenge on a motorized treadmill. The rat livers were immediately harvested. Evidence of apoptotic liver cell death was revealed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspases mediated cascade events. DNA fragmentation, an apoptosis process, can be examined using TUNEL assay. A few TUNEL-positive hepatocytes, compared to the exercise only group, were observed in the livers from exhaustive animals supplemented with GT. Immunoblot analysis also showed that caspase-6-mediated specific cleavage of lamin A/C was increased significantly in the livers of group E, but was significantly decreased in the EM and EH groups. Our observations demonstrate that GT possesses anti-apoptotic and hepatoprotective potential after exhaustive exercise.

  16. Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

    Science.gov (United States)

    Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

    1984-04-01

    Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

  17. Hepatoprotective effects of Rauwolfia vomitoria extract on the liver of aduit wistar rats

    Directory of Open Access Journals (Sweden)

    Ezejindu D N

    2013-12-01

    Full Text Available This work focuses primarily on investigating hepatoprotective effects of Rauwolfia vomitoria extract on the liver of adult wistar rats following oral administration. Twenty wistar rats of weights 195 – 215kg were divided into four groups designated as A,B,C and D. Group  A served as the control and were orally administered with 0.4ml of distilled water daily; the experimental groups B,C & D were orally administered with 0.6ml, 0.75ml and 0.81ml of Rauwolfia vomitoria extract for twenty eight days. Twenty four hours after the last administration, the animals were weighed, anasthetized under chloroform vapour and dissected. Liver tissues were removed, weighed and trimmed down for histological studies. The final body weight of the experimental groups (B,C &D increased significantly(P<0.001 with the control. The relative liver weight of the experimental groups B,C &D statistically increased (P<0.001 with the control (A. Histological results showed normal liver architecture in the experimental groups B,C, & D relative to the control (A.  This study therefore suggest that consumption of Rauwolfia vomitoria extract at different doses did not induce hepatotoxicity in the liver of adult wistar rats.

  18. Hydrolysis of triolein in phospholipid vesicles and microemulsions by a purified rat liver acid lipase.

    Science.gov (United States)

    Burrier, R E; Brecher, P

    1983-10-10

    An acid lipase was purified from rat liver lysosomes. Lipase purification involved affinity chromatography, gel filtration, and stabilization of the purified preparation using ethylene glycol and Triton X-100. A molecular weight of 67,000-69,000 was determined independently using density gradient centrifugation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and gel filtration. To study enzyme action, model substrates were prepared by incorporating radiolabeled triolein into either unilamellar vesicles or microemulsions. Substrates were prepared by cosonicating aqueous dispersions of lecithin and triolein. Formation of vesicles or emulsions depended on the relative amount of each lipid and on sonication conditions. Vesicles were prepared at molar ratios between 70:1 and 26:1 (lecithin:triolein) and the microemulsion preparation at a molar ratio of 1:1. The substrate particles were of similar size (220-250 A) as determined by Bio-Gel A-15m chromatography. Hydrolysis of triolein contained in vesicles or emulsions was similar with respect to pH, temperature, and reaction products. Kinetic studies on vesicles with increasing triolein content showed progressively greater Vmax values (0-0.6 mumol/min/mg), and Vmax for the emulsion was 3.1 mumol/min/mg. Addition of human very low or low density lipoprotein produced a dose-dependent inhibition with both substrates. The results show that synthetically prepared microemulsions are stable and effective substrates for the acid lipase and indicate that surface-oriented triolein is hydrolyzed in both preparations.

  19. 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

  20. 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

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

    Science.gov (United States)

    2010-01-01

    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 models is feasible and

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

    International Nuclear Information System (INIS)

    Wang Jingshu; Koyota, Souichi; Zhou, Xiaoping; Ueno, Yasuharu; Ma Li; Kawagoe, Masami; Koizumi, Yukio; Okamoto, Hiroshi; Sugiyama, Toshihiro

    2009-01-01

    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.

  3. Acute effects of organotins on brain, liver and kidney in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, R.S.; Kaur, G.; Srivastava, R.C.; Srivastava, T.N.

    1985-01-01

    Effects of dioctyltin oxide (DOTO) tricyclohexyltin hydroxide (TCHTOH) and tributyltin oxide (TBTO) were examined on some enzymic activities in liver and kidney and biogenic amines level in brain of rats at 24 hours after single subcutaneous administration (25 ..mu..mole/100 g B. Wt.). All the organotin compounds produced a significant increase in the activity of alkaline phosphatase and adenosin triphosphatase and decrease in monoamine oxidase in both liver and kidney. DOTO and TCHTOH were more effective in impairing the activity of succinate dehydrogenase in liver. Concentrations of ..gamma..-aminobutyric acid (GABA) and dopamine were found to be significantly decreased in brain however, acetylcholine concentration remained unaltered. These results suggest that organotin compounds DOTO and TCHTOH are more toxic to rats than TBTO. 30 references, 3 tables.

  4. Factors influencing radiation-induced impairment of rat liver mitochondrial oxidative phosphorylation

    International Nuclear Information System (INIS)

    Alexander, K.C.; Aiyar, A.S.; Sreenivasan, A.

    1975-01-01

    The influence of some experimental conditions on the radiation-induced impairment of oxidative phosphorylation in rat liver mitochondria has been studied. Shielding of the liver during whole body irradiation of the animal does not significantly alter the decreased efficiency of phosphorylation. There exists a great disparity in the in vivo and in vitro radiation doses required for the manifestation of damage to liver mitochondria. While these observations point to the abscopal nature of the radiation effects, direct involvement of the adrenals has been ruled out by studies with adrenalectomised rats. Prior administration of the well known radio-protective agents, serotonin or 2-aminoethyl isothiouronium bromide hydrobromide, is effective in preventing the derangement of mitochondrial function following radioexposure. The hypocholesterolemic drug ethyl-α-p-chlorophenoxy isobutyrate, which is known to influence hepatic mitochondrial turnover, does not afford any significant protection against either mitochondrial damage or the mortality of the animals due to whole body irradiation. (author)

  5. Effect of radiation on the polypeptidsynthetase activity of liver and thymus chromatic of rats

    International Nuclear Information System (INIS)

    Umanskij, S.R.; Matinyan, K.S.; Tokarskaya, V.I.

    1978-01-01

    Irradiation with a dose of 800 rad decreases rapidly the polypeptidsynthetase activity (PPSA) of liver and thymus chromatin of rats. The effect is accounted for by the breakdown of poly (ADP - ribose) involved in activation of amino acids within this system. Two hours after exposure PPSA of the chromatin of both organs is restored. When nuclei or chromatin are irradiated in vitro PPSA progressively decreases with dose increase. 18 hours after partial hepataectomy, PPSA of the chromatin of the regenerating liver is twice as high as that in the controls. Exposure of rats to 800 rad 30 min before operation prevents the PPSA increase in the regenerating liver. Possible mechanisms of radiation disturbance of the chromatin PPSA are discussed

  6. Attenuation of sepsis-induced rat liver injury by epigallocatechin ...

    African Journals Online (AJOL)

    rat model of sepsis established by cercal ligation and puncture (CLP). Methods: Male Wistar ... capacity, resulting in excessive oxidants in cells. [6]. ... Care (NIH publication no. 85-23 ..... estimates of severe sepsis in United States emergency.

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

    International Nuclear Information System (INIS)

    Shankar, T.P.; Drake, S.; Solomon, S.S.

    1987-01-01

    Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125 I-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

  8. S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation.

    Science.gov (United States)

    Tang, Yong; Chu, Hongpeng; Cao, Guojun; Du, Xiaolong; Min, Xiaobo; Wan, Chidan

    2018-03-01

    Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    ANWAR, M.M.; MOHAMED, N.E.

    2009-01-01

    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 CCl 4 . 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 CCl 4 (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 CCl 4 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 CCl 4 treatment minimized the disturbance of the liver functions and liver histology.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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

  11. Immunohistochemical Analysis of Platelet Extract Effects on Liver Injury Induced by CCl4 in Male Rats

    Directory of Open Access Journals (Sweden)

    Zahra Hesami

    2016-01-01

    Full Text Available Backgrounds & objectives: Liver damage results in a large accumulation of external cellular matrix that affects the function of this important body organ in a long term and finally stops its function completely. The growth factors existing in platelet extract are more cost-effective, available, and stable than recombinant ones. To determine whether the platelet extract effects on histological changes in liver injury induced by carbon tetrachloride (CCl4, we used immunohistochemical analysis in male rats. Methods: In this project the 28 male Wistar rats (250-300 g were randomly divided into 4 groups, each consisting of 7 animals. The rats were divided into four experimental groups as follows: the first group (sham intraperitoneally received only olive oil as the solvent of carbon tetrachloride; second group (CCl4 intraperitoneally received carbon tetrachloride dissolved in olive oil (ratio of about 1: 1 at a concentration of 1 ml/kg and a twice a week for eight weeks; third group subcutaneously received only platelet extract at a concentration of 0.5 ml/kg twice a week for three weeks; and fourth group received both CCl4 intraperitoneally for eight weeks and platelet extract subcutaneously for last three weeks. After 8 weeks of trial blood and liver sampling were done. Blood samples sent for enzymatic (AST, ALT tests and liver samples tested for histological and immunohistochemical studies. The data were analyzed using  one-way ANOVA followed by Tukey test by Graph pad Prism 5 software and data were considered significant at p≤ 0.05. Results: The results show that platelet extract causes a significant (p≤ 0.001 decrease in liver enzymes and albumin improves the function of liver. The level of alfa smooth muscle actin (α-SMA as an index of hepatic stellate cell activation was decreased by platelet extract administration which eventually reduced the necrosis and fibrosis induced by carbon tetrachloride in studied rats

  12. [Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat].

    Science.gov (United States)

    Song, Min-ning; Song, Yu-na; Chen, Fu; Luo, Mei-lan

    2007-01-01

    To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(Pliver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26) micromol/L, both Pencephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,Pencephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.

  13. The uptake and release of 18F by rat liver

    International Nuclear Information System (INIS)

    Kruger, B.J.; Patterson, C.M.; Masters, C.J.

    1977-01-01

    18 F was taken up fairly rapidly by liver cells in vitro and in vivo, and released from the cells exponentially. In vitro, this release occurred during the first 90 min, after which it was linear at a rate of approximately 10 per cent per h. Subcellular fractionation of liver slices after incubation with 18 F showed that, regardless of the incubation time and method of washing, at least half of the radioactivity was in the cell sap, but that there was some preferential retention of 18 F by the mitochondria. (author)

  14. Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats.

    Science.gov (United States)

    Shibata, Katsumi; Morita, Nobuya; Kawamura, Tomoyo; Tsuji, Ai; Fukuwatari, Tsutomu

    2015-01-01

    Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically. Niacin and its metabolites in the liver, blood, and urine were affected as expected. Although the concentrations of vitamin B1, pantothenic acid, folate, and biotin in liver and blood were decreased by orotic acid-induced fatty liver, these urinary excretion amounts showed a specific pattern toward increase. Generally, as for the typical urinary excretion of B-group vitamins, these are excreted when the body is saturated. However, the ability to sustain vitamin B1, pantothenic acid, folate, and biotin decreased in fatty liver, which is hypothesized as a specific phenomenon. This metabolic response might occur to prevent an abnormally increased biosynthesis of fatty acids by orotic acid.

  15. The relationship between radiation-induced apoptosis and the expression of cytokines in the rat's liver

    International Nuclear Information System (INIS)

    An, Eun Joo; Lee, Kyung Ja; Rhee, Chung Sik

    2000-01-01

    To determine the role of cytokines in the apoptosis of rat's liver following irradiation. Sprague-Dawley rats were irradiated to entire body with a single dose of 8 Gy. The rats were divided into 5 groups according to the sacrifice day after irradiation. The liver and blood after 1, 3, 5, 7, and 14 days irradiation were sampled for evaluation of mechanism of apoptosis and role of cytokine in relation to radiation-induced tissue damage. The study was composed of microscopic evaluation of liver tissue, in situ detection method for apoptosis, immunohistochemical stain of IL-1, IL-4, IL-6 and TNF, bioassay and radioimmunoassay of IL-6 in liver tissue and blood. Radiation-induced liver damage was noted from first day of radiation, and most severe parenchymal damage associated with infiltration of chronic inflammatory cells was seen in the groups of 5 days after radiation. A number of apoptosis were observed 1 day after radiation on both light microscope and in situ method. Afterwards, the number of apoptosis was gradually diminished. On immunohistochemical study, IL-1 and TNF were expressed 1, 3 days after radiation, but not expressed after that. IL-4 was not expressed in the entire groups. IL-6 was expressed with strong positivity in 1, 3 days after radiation. Bioassay and RIA of IL-6 in liver tissue and blood showed the highest value in 1 day after radiation, and the value is diminished after then. Apoptosis seemed to be the important mechanism of radiation-induced liver damage, and is possibly induced by the release of cytokines, such as IL-1, IL-6, TNF in view the simultaneously increased appearance of apoptosis and cytokines

  16. Cyclic fatty acid monomers from dietary heated fats affect rat liver enzyme activity.

    Science.gov (United States)

    Lamboni, C; Sébédio, J L; Perkins, E G

    1998-07-01

    This study was conducted to investigate the effects of dietary cyclic fatty acid monomers (CFAM), contained in heated fat from a commercial deep-fat frying operation, on rat liver enzyme activity. A partially hydrogenated soybean oil (PHSBO) used 7 d (7-DH) for frying foodstuffs, or 0.15% methylated CFAM diets was fed to male weanling rats in comparison to a control group fed a nonheated PHSBO (NH) diet in a 10-wk experiment. All diets were isocaloric with 15% fat. Animals fed either CFAM or 7-DH diets showed increased hepatic content of cytochrome (cyt.) b5 and P450 and increased activity of (E.C. 1.6.2.4) NADPH-cyt. P450 reductase in comparison to the control rats. In addition, the activities of (E.C. 2.3.1.21) carnitine palmitoyltransferase-I and (E.C. 1.1.1.42) isocitrate dehydrogenase were significantly decreased when compared to that of rats fed the NH diet. A significantly depressed activity of (E.C. 1.1.1.49) glucose 6-phosphate dehydrogenase was also observed for these animals compared to the control rats fed NH diet. Moreover, liver and microsomal proteins were significantly increased when CFAM or 7-DH diets were fed to animals in comparison to controls while liver glycogen was decreased significantly in experimental groups of rats. The results obtained in this study indicate that the CFAM in the diet from either synthetic sources or used fats increase the activity of liver enzyme systems that detoxify them.

  17. Effect of broccoli extract enriched diet on liver cholesterol oxidation in rats subjected to exhaustive exercise.

    Science.gov (United States)

    Cardenia, Vladimiro; Rodriguez-Estrada, Maria Teresa; Lorenzini, Antonello; Bandini, Erika; Angeloni, Cristina; Hrelia, Silvana; Malaguti, Marco

    2017-05-01

    The effect of broccoli extract (BE)-enriched diet was studied in order to evaluate its ability to counteract liver cholesterol oxidation products (COPs) induced by acute strenuous exercise in rats. Thirty-two female Wistar rats were randomly divided into four groups: control diet without exercise (C), BE-enriched diet without exercise (B), control diet with acute exhaustive exercise (S) and BE-enriched diet with acute exhaustive exercise (BS). The study lasted 45days and on the last day, rats of S and BS groups were forced to run until exhaustion on a treadmill. Glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT) and cholesterol oxidation products (COPs) were determined in liver. Exhaustive exercise was clearly responsible for tissue damage, as evidenced by the increase of lactate dehydrogenase (LDH) plasma activity in the S group. Moreover, the exercise protocol reduced CAT activity in liver, while it did not affect GST, GR and GPx. BE-enriched diet raised GST, GR and CAT activities in rats of BS group. The main COPs found were 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, cholestanetriol, 24-hydroxycholesterol and 27-hydroxycholesterol. The BE-enriched diet led to reduced cholesterol oxidation following exhaustive exercise; the highest level of COPs was found in the S group, whereas the BS rats showed the lowest amount. This study indicates that the BE-enriched diet increases antioxidant enzyme activities and exerts an antioxidant effect towards cholesterol oxidation in rat liver, suggesting the use of phytochemicals in the prevention of oxidative damage and in the modulation of the redox environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    Science.gov (United States)

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  19. Molecular modifications of cholesterol metabolism in the liver and the brain after chronic contamination with cesium 137.

    Science.gov (United States)

    Racine, R; Grandcolas, L; Grison, S; Gourmelon, P; Guéguen, Y; Veyssière, G; Souidi, M

    2009-07-01

    Twenty years after Chernobyl accident, the daily ingestion of foodstuff grown on contaminated grounds remains the main source for internal exposure to ionizing radiations, and primarily to cesium 137 ((137)Cs). Though the effects of a long-term internal contamination with radionuclides are poorly documented, several non-cancerous pathologies have been described in this population. However, lipid metabolism was never investigated after chronic internal contamination although disturbances were observed in externally-exposed people. In this regard, we assessed the effects of a chronic ingestion of (137)Cs on hepatic and cerebral cholesterol metabolism. To mimic a chronically-exposed population, rats were given (137)Cs-supplemented water at a post-accidental dose (150 Bq/rat/day) during 9 months. The plasma profile, and brain and liver cholesterol concentrations were unchanged. A decrease of ACAT 2, Apo E, and LXRmRNA levels was recorded in the liver. In the brain, a decrease of CYP27A1 and ACAT 1 gene expression was observed. These results clearly show that cholesterol metabolism is not disrupted by a chronic ingestion of (137)Cs, although several molecular alterations are observed. This work would be interestingly completed by studying the influence of (137)Cs in models likely more sensitive to contaminants, such as the fetus or individuals susceptible to a lipidic disease.

  20. A comparative integrated transcript analysis and functional characterization of differential mechanisms for induction of liver hypertrophy in the rat

    International Nuclear Information System (INIS)

    Boitier, Eric; Amberg, Alexander; Barbie, Valerie; Blichenberg, Arne; Brandenburg, Arnd; Gmuender, Hans; Gruhler, Albrecht; McCarthy, Diane; Meyer, Kirstin; Riefke, Bjoern; Raschke, Marian; Schoonen, Willem; Sieber, Maximilian; Suter, Laura; Thomas, Craig E.; Sajot, Nicolas

    2011-01-01

    The main goal of the present work was to better understand the molecular mechanisms underlying liver hypertrophy (LH), a recurrent finding observed following acute or repeated drug administration to animals, using transcriptomic technologies together with the results from conventional toxicology methods. Administration of 5 terminated proprietary drug candidates from participating companies involved in the EU Innomed PredTox Project or the reference hepatotoxicant troglitazone to rats for up to a 14-day duration induced LH as the main liver phenotypic toxicity outcome. The integrated analysis of transcriptomic liver expression data across studies turned out to be the most informative approach for the generation of mechanistic models of LH. In response to a xenobiotic stimulus, a marked increase in the expression of xenobiotic metabolizing enzymes (XME) was observed in a subset of 4 studies. Accumulation of these newly-synthesized proteins within the smooth endoplasmic reticulum (SER) would suggest proliferation of this organelle, which most likely is the main molecular process underlying the LH observed in XME studies. In another subset of 2 studies (including troglitazone), a marked up-regulation of genes involved in peroxisomal fatty acid β-oxidation was noted, associated with induction of genes involved in peroxisome proliferation. Therefore, an increase in peroxisome abundance would be the main mechanism underlying LH noted in this second study subset. Together, the use of transcript profiling provides a means to generate putative mechanistic models underlying the pathogenesis of liver hypertrophy, to distinguish between subtle variations in subcellular organelle proliferation and creates opportunities for improved mechanism-based risk assessment.

  1. Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

    International Nuclear Information System (INIS)

    Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S.; Wada, H.; Horio, Y.

    1990-01-01

    The hepatic plasma membrane fatty acid-binding protein (h-FABP PM ) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP PM have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP PM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [ 3 H]oleate but not that of [ 35 S]sulfobromophthalein or [ 14 C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABP PM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP PM and mGOT are closely related

  2. Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

    Energy Technology Data Exchange (ETDEWEB)

    Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S. (Mount Sinai School of Medicine, New York, NY (USA)); Wada, H.; Horio, Y. (Univ. of Osaka (Japan))

    1990-05-01

    The hepatic plasma membrane fatty acid-binding protein (h-FABP{sub PM}) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP{sub PM} have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP{sub PM} reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of ({sup 3}H)oleate but not that of ({sup 35}S)sulfobromophthalein or ({sup 14}C)taurocholate. The inhibition of oleate uptake produced by anti-h-FABP{sub PM} can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP{sub PM} and mGOT are closely related.

  3. Effects of human low and high density lipoproteins on the binding of rat intermediate density lipoproteins to rat liver membranes

    International Nuclear Information System (INIS)

    Brissette, L.; Nol, S.P.

    1986-01-01

    Upon incubation with rat liver membranes, radioiodinated rat intermediate density lipoproteins (IDL) interacted with at least two binding sites having a low and a high affinity as demonstrated by the curvilinear Scatchard plots obtained from the specific binding data. The purpose of our work was to identify the nature of these binding sites. Human low density lipoproteins (LDL), contain apolipoprotein B only, and human high density lipoproteins (HDL3), containing neither apolipoprotein B nor E, were both capable of decreasing the specific binding of rat 125 I-IDL. The Scatchard analysis clearly revealed that only the low affinity component was affected by the addition of these human lipoproteins. In fact, the low affinity binding component gradually decreased as the amount of human LDL or HDL3 increased in the binding assay. At a 200-fold excess of human LDL or HDL3, the low affinity binding was totally masked, and the Scatchard plot of the specific 125 I-IDL binding became linear. Only the high affinity binding component was left, enabling a precise measurement of its binding parameters. In a series of competitive displacement experiments in which the binding assay contained a 200-fold excess of human LDL or HDL3, only unlabeled rat IDL effectively displaced the binding of rat 125 I-IDL. We conclude that the low affinity binding of rat IDL to rat liver membranes is due to weak interactions with unspecified lipoprotein binding sites. The camouflage of these sites by human lipoproteins makes possible the study of IDL binding to the high affinity component which likely represents the combined effect of IDL binding to both the remnant and the LDL receptors

  4. Gel-based proteomics of liver cancer progression in rat

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Miller, Leah M; Novikoff, Phyllis M

    2011-01-01

    A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n=18) from six experimental stages were ...

  5. Functional state of perfused liver tissue in X-ray irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Borovikova, G.V.; Dokshina, G.A.; Lapteva, T.A. (Tomskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Biologii i Biofiziki)

    1981-01-01

    The results of studying the functional state of perfused liver tissue isolated from rats after irradiation in the 18.06x10/sup -2/ Kl/kg dose, which has been estimated by transamination process rate catalized alanine-(KF 2.6x1.2, ALT and aspartate by aminotransferases (KF 2.6x1.1, ACT), gluconeogenesis and urea production intensity presented. When comparing the results obtained on the perfused liver deprived of homeostatic body effects it has been found that the liver isolated from the body for the first 24 hours of the radiation sickness development possesses a higher radiation activity which manifests itself in intensification of the processes of gluconeogenesis and transamination with substrate addition. The third 24 hours upon irradiation in the isolated liver the intensity of the gluconeogenesis and transamination processes is attenuated.

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

    International Nuclear Information System (INIS)

    Margeli, A.; Theocharis, S.; Skaltsas, S.; Skopelitou, A.; Kittas, C.; Mykoniatis, M.; Varonos, D.

    1994-01-01

    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 3 H 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)

  7. Liver Progenitor Cell Line HepaRG Differentiated in a Bioartificial Liver Effectively Supplies Liver Support to Rats with Acute Liver Failure

    NARCIS (Netherlands)

    Nibourg, Geert A. A.; Chamuleau, Robert A. F. M.; van der Hoeven, Tessa V.; Maas, Martinus A. W.; Ruiter, An F. C.; Lamers, Wouter H.; Oude Elferink, Ronald P. J.; van Gulik, Thomas M.; Hoekstra, Ruurdtje

    2012-01-01

    A major roadblock to the application of bioartificial livers is the need for a human liver cell line that displays a high and broad level of hepatic functionality. The human bipotent liver progenitor cell line HepaRG is a promising candidate in this respect, for its potential to differentiate into

  8. Effect of thiamine deficiency, pyrithiamine and oxythiamine on pyruvate metabolism in rat liver and brain in vivo

    International Nuclear Information System (INIS)

    Meghal, S.K.; O'Neal, R.M.; Koeppe, R.E.

    1977-01-01

    Rats were fed either a thiamine-deficient diet or diets containing pyrithiamine or oxythiamine. When symptoms of thiamine deficiency appeared, the animals were injected intraperitoneally with [2- 14 C] pyruvate six to twelve minutes prior to sacrifice. Free glutamic and aspartic acids were isolated from liver and brain and degraded. The results indicate that, in thiamine-deficient or oxythiamine-treated rats, pyruvate metabolism in liver and brain is similar to that in normal animals. In contrast, pyrithinamine drastically decreases the oxidative decarboxylation of pyruvate by rat liver. (auth.)

  9. Effect of D-tagatose on liver weight and glycogen content of rats.

    Science.gov (United States)

    Bär, A; Lina, B A; de Groot, D M; de Bie, B; Appel, M J

    1999-04-01

    D-tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations. To determine whether there might be any toxicological relevance to this effect, three studies were conducted in male, adult Sprague-Dawley rats. In the first study, four groups received Purina diet (group A), Purina diet with 20% D-tagatose (group B), SDS diet (group C), or SDS diet with 20% D-tagatose (group D). For groups A and B, the 28-day treatment period was followed by a 14-day recovery period (Purina diet). Food remained available to all animals until the time of sacrifice. Groups of 10 rats were killed on days 14 (groups A and B), 28 (groups A-D), and 42 (groups A and B). Body weights, as well as weights of wet and lyophilized livers, were determined. The lyophilized livers collected on day 28 from groups A and B were analyzed for protein, total lipid, glycogen, DNA, and residual moisture. By day 14, relative wet liver weights had increased by 23% in group B. On day 28, the increase was 38% in group B and 44% in group D. At the end of the recovery period, the increase had diminished to 14% in group B. On day 28, liver glycogen content (in %) was significantly increased, and liver protein, lipid, and DNA contents were significantly decreased in group B compared to group A. Total amounts per liver of protein, total lipid, glycogen, and DNA were significantly increased. In the second study, four groups of 20 rats each received SDS diet with 0, 5, 10, and 20% D-tagatose for 29-31 days. The food was available until the time of sacrifice. At termination, plasma was obtained from 10 rats/group for clinicochemical analyses. Five rats/group were subjected to whole-body perfusion, followed by processing of livers for qualitative and quantitative electron microscopic

  10. 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.

  11. Effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis

    International Nuclear Information System (INIS)

    Che Ying; Wang Shanju; Xu Tingting; Jiang Miaona; Jia Yujie

    2004-01-01

    Objective: To observe the effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis. Methods: SD rat models of liver fibrosis was induced by CCl 4 (n=57). Liver function (GPT, GOT) and serum hepatic fibrosis markers levels (HA, LN, C-IV, PC-III, with RIA) were tested in these models and 10 control rats. Eleven model rats were left untreated, the others were treated with Ganfukang of different concentrations and the above hepatic parameters were again determined after completion of treatment. Results: Lever function was much deteriorated and serum markers levels significantly increased in the model rats (vs controls, P<0.01). After treatment with Ganfukang, the improvement was significant (vs untreated models, P<0.01). Conclusion: Ganfukang is of definite therapeutic value for experimental hepatic fibrosis in rat models. (authors)

  12. Differences in both glycosylation and binding properties between rat and mouse liver prolactin receptors.

    Science.gov (United States)

    Lascols, O; Cherqui, G; Munier, A; Picard, J; Capeau, J

    1994-05-01

    To investigate whether glycanic chains of prolactin receptors (PRL-R) play a role in hormone binding activity, comparison was made of rat and mouse liver solubilized receptors with respect to both their affinity for the hormone and their glycosylation properties. As compared with rat receptors, mouse receptors exhibited a 2-fold higher affinity for human growth hormone (hGH), the hormone being bound by both tissues with a lactogenic specificity. Along with this increased affinity, mouse receptors had a 2 lower M(r) relative to rat receptors (62 kDa versus 64 kDa as measured on hGH cross-linked receptors). These differences could be ascribed to different glycosylation properties of the receptors from the two species, as supported by the followings. 1) After treatment with endoglycosidase F (endo F), rat and mouse PRL-R no longer exhibited any difference in their M(r) (54 kDa for both cross-linked receptors). 2) Neuraminidase treatment increased by 37% the binding of hGH to mouse receptors, but was ineffective on the hormone-binding to rat receptors. Conversely, wheat germ agglutinin (WGA), another sialic acid specific probe, decreased hGH binding to rat receptors by 25%, but had no effect on this process for mouse ones. 3) Marked differences were observed in the recoveries of rat and mouse hormone-receptor (HR) complexes from ricin-1- (RCA1-), concanavalin A- (ConA-) and WGA-immobilized lectins. These differences were reduced (RCA1 and ConA) or abolished (WGA) after rat and mouse receptor desialylation by neuraminidase, a treatment which decreased the M(r) of both receptors by 2 kDa. Taken together, these results strongly suggest that the PRL-R from rat and mouse liver contain biantennary N-linked oligosaccharidic chains with distinct type of sialylation, which may account for their differential hormone-binding affinities.

  13. Effect of 3-keto-1,5-bisphosphonates on obese-liver's rats.

    Science.gov (United States)

    Lahbib, Karima; Touil, Soufiane

    2016-10-01

    Obesity is associated with an oxidative stress status, which is defined by an excess of reactive oxygen species (ROS) vs. the antioxidant defense system. We report in this present work, the link between fat deposition and oxidative stress markers using a High Fat Diet-(HFD) induced rat obesity and liver-oxidative stress. We further determined the impact of chronic administration of 3-keto-1, 5-BPs 1 (a & b) (40μg/kg/8 weeks/i.p.) on liver's level. In fact, exposure of rats to HFD during 16 weeks induced body and liver weight gain and metabolic disruption with an increase on liver Alanine amino transférase (ALAT) and Aspartate aminotransférase (ASAT) concentration. HFD increased liver calcium level as well as free iron, whereas, it provoked a decrease on liver lipase activity. HFD also induced liver-oxidative stress status vocalized by an increase in reactive oxygen species (ROS) as superoxide radical (O 2 ), hydroxyl radical (OH) and Hydrogen peroxide (H 2 O 2 ). Consequently, different deleterious damages as an increase on Malon Dialdehyde MDA, Carbonyl protein PC levels with a decrease in non-protein sulfhydryls NPSH concentrations, have been detected. Interestingly, our results demonstrate a decrease in antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx) and peroxidases (POD). Importantly, 3-keto-1,5-bisphosphonates treatment corrected the majority of the deleterious effects caused by HFD, but it failed to correct some liver's disruptions as mineral profile, oxidative damages (PC and NPSH levels) as well as SOD and lipase activities. Our investigation point that 3-keto-1,5-bisphosphonates could be considered as safe antioxidant agents on the hepatic level that should also find other potential biological applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. The effect of aqueous extract of Avicennia marina (Forsk. Vierh. leaves on liver enzymes' activity, oxidative stress parameters and liver histopathology in male diabetic rats

    Directory of Open Access Journals (Sweden)

    Akram Hamzevi

    2017-12-01

    Full Text Available Background: Avicennia marina has antioxidant and anti-diabetic properties. This study was conducted to examine the effect of aqueous extract of A. marina on liver enzymes' activity, oxidative stress parameters and liver histopathology in diabetic rats. Materials and Methods: In this experimental study, 28 male rats were allocated into the equal groups of control, diabetic control and experimental diabetic 1 and 2. The diabetes in diabetic control and experimental diabetic groups was induced using an intraperitoneal injection of 120 mg/kg alloxan. The experimental diabetic groups received the aqueous extract of A. marina (100 and 200 mg/kg, i.p. in alternate days for one month. Sterile distilled water was injected to the animals of control and diabetic control groups. At the end of the treatment period, serum levels of ALT, AST, GGT and ALP were measured. Then, levels of SOD, GST, CAT and MDA were measured in the liver tissue. The liver sections were prepared and examined by an optical microscope. Results: Results showed that administration of the A. marina extract (100 and 300 mg/kg, ip to the diabetic rats significantly decreased the serum levels of liver enzymes and tissue level of MDA. Also, the activity of the liver tissue's antioxidant enzymes was increased (P<0.05. The A. marina extract dose-dependently decreased liver damages in diabetic rats. Conclusion: Administration of the A. marina extract improves liver tissue oxidative stress indices and decreases the serum level of liver enzymes. Also, A. marina extract improves liver tissue injuries induced by diabetes.

  15. Characterization of liver changes in ZSF1 rats, an animal model of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Marta Borges-Canha

    Full Text Available Background: The non-alcoholic fatty liver disease is the hepatic counterpart of the metabolic syndrome. ZSF1 rats are a metabolic syndrome animal model in which liver changes have not been described yet. Aim: The characterization of liver histological and innate immunity changes in ZSF1 rats. Methods: Five groups of rats were included (n = 7 each group: healthy Wistar-Kyoto control rats (Ctrl, hypertensive ZSF1 lean (Ln, ZSF1 obese rats with a normal diet (Ob, ZSF1 obese rates with a high-fat diet (Ob-HFD, and ZSF1 obese rats with low-intensity exercise training (Ob-Ex. The animals were sacrificed at 20 weeks of age, their livers were collected for: a measurements of the area of steatosis, fibrosis and inflammation (histomorphological analysis; and b innate immunity (toll-like receptor [TLR] 2, TLR4, peroxisome proliferator-activated receptor γ [PPARγ], toll interacting protein [TOLLIP] and inflammatory marker (tumor necrosis factor-alpha [TNFvs], interleukin 1 [IL-1] expression analysis by real-time PCR. Results: Ob, Ob-HFD and Ob-Ex were significantly heavier than Ln and Ctrl animals. Ob, Ob-HFD and Ob-Ex animals had impaired glucose tolerance and insulin resistance. ZSF1 Ob, Ob-HFD and Ob-Ex presented a higher degree of steatosis (3,5x; p < 0.05 than Ctrl or ZSF1 Ln rats. Steatohepatitis and fibrosis were not observed in any of the groups. No differences in expression were observed between Ctrl, Ln and Ob animals (except for the significantly higher expression of TOLLIP observed in the Ob vs Ln comparison. Ob-HFD and Ob-Ex rats showed increased expression of PPARγ and TOLLIP as compared to other groups. However, both groups also showed increased expression of TLR2 and TLR4. Nevertheless, this did not translate into a differential expression of TNFα or IL-1 in any of the groups. Conclusion: The ZSF1 model is associated with liver steatosis but not with steatohepatitis or a significantly increased expression of innate immunity or

  16. Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model

    Directory of Open Access Journals (Sweden)

    Veidal Sanne Skovgård

    2012-12-01

    Full Text Available Abstract Background Accumulation of extracellular matrix (ECM and increased matrix metalloproteinase (MMP activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl4 treated animals with an ELISA detecting a fragment of type III collagen generated in vitro by MMP-9 (C3M, known to be associated with liver fibrosis and to investigate cAMP modulation of MMP activity and liver tissue turnover in this model. Findings In vivo: Rats were treated for 8 weeks with CCl4/Intralipid. Liver slices were cultured for 48 hours. Levels of C3M were determined in the supernatants of slices cultured without treatment, treated with GM6001 (positive control or treated with IBMX (phosphodiesterase inhibitor. Enzymatic activity of MMP-2 and MMP-9 were studied by gelatin zymography. Ex vivo: The levels of serum C3M increased 77% in the CCl4-treated rats at week 8 (p 4-treated animals had highly increased MMP-9, but not MMP-2 activity, compared to slices derived from control animals. Conclusions We have combined an ex vivo model of liver fibrosis with measurement of a biochemical marker of collagen degradation in the condition medium. This technology may be used to evaluate the molecular process leading to structural fibrotic changes, as collagen species are the predominant structural part of fibrosis. These data suggest that modulation of cAMP may play a role in regulation of collagen degradation associated with liver fibrosis.

  17. High expression of liver histone deacetylase 3 contributes to high-fat-diet-induced metabolic syndrome by suppressing the PPAR-γ and LXR-α-pathways in E3 rats.

    Science.gov (United States)

    Li, Dongmin; Wang, Xuan; Ren, Wuchao; Ren, Juan; Lan, Xi; Wang, Feimiao; Li, Hongmin; Zhang, Fujun; Han, Yan; Song, Tianbao; Holmdahl, Rikard; Lu, Shemin

    2011-09-15

    In the previous experiment, we found that there was a different response between E3 rats and DA.1U rats to high-fat-diet-induced metabolic syndrome (HFD-MetS). The aim of this study was to explore the cause and molecular mechanism of the genetic difference in susceptibility to metabolic syndrome in E3 rats as compared with DA.1U rats. Firstly, a 12-week HFD-MetS model in E3 and DA.1U rats was carried out and assessed. Then, the expression of key insulin signaling molecules, metabolic nuclear receptors, metabolic key enzymes and histone deacetylases (Hdacs) was determined by different methods. Finally, the effects of overexpression and disruption of Hdac3 on metabolic nuclear receptors were analyzed in CBRH-7919 cells and primarily-hepatic cells from DA.1U and E3 rats. We found that E3 rats were susceptible, while DA.1U rats were resisted to HFD-MetS. The expression of liver X receptor α,β (LXR-α,β), farnesoid X receptor (FXR), peroxisome proliferator activated receptor γ (PPAR-γ) and cholesterol 7α-hydroxylase (CYP7A1) increased markedly in DA.1U rat liver, whereas they decreased significantly in E3 rats. The expression of Hdac3 increased by HFD treatment in both E3 and DA.1U rat livers, but the constitutive Hdac3 expression was lower in DA.IU rat liver than in E3 rat liver. Importantly, overexpression of Hdac3 could downregulate the expression of LXR-α, PPAR-γ and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from DA.IU rats. On the contrary, disruption of Hdac3 by shRNA upregulated the expression of LXR-α, PPAR-γ and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from E3 rats. The results suggested that a high constitutive expression of Hdac3 inhibiting the expression of PPAR-γ, LXR-α and CYP7A1 in liver contributes to HFD-MetS in E3 rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Photoaffinity labeling of steroid 5 alpha-reductase of rat liver and prostate microsomes

    International Nuclear Information System (INIS)

    Liang, T.; Cheung, A.H.; Reynolds, G.F.; Rasmusson, G.H.

    1985-01-01

    21-Diazo-4-methyl-4-aza-5 alpha-pregnane-3,20-dione (Diazo-MAPD) inhibits steroid 5 alpha-reductase in liver microsomes of female rats with a K/sub i/ value of 8.7 +/- 1.7 nM, and the inhibition is competitive with testosterone. It also inhibits the binding of a 5 alpha-reductase inhibitor, [ 3 H] 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([ 3 H]4-MA), to the enzyme in liver microsomes. The inhibition of 5 alpha-reductase activity and of inhibitor binding activity by diazo-MAPD becomes irreversible upon UV irradiation. [1,2- 3 H]Diazo-MAPD binds to a single high affinity site in liver microsomes of female rats, and this binding requires NADPH. Without UV irradiation, this binding is reversible, and it becomes irreversible upon UV irradiation. Both the initial reversible binding and the subsequent irreversible conjugation after UV irradiation are inhibited by inhibitors (diazo-MAPD and 4-MA) and substrates (progesterone and testosterone) of 5 alpha-reductase, but they are not inhibited by 5 alpha-reduced steroids. Photoaffinity labeled liver microsomes of female rats were solubilized and fractionated by high performance gel filtration. The radioactive conjugate eluted in one major peak at Mr 50,000

  19. Insulin resistance in uremia: Insulin receptor kinase activity in liver and muscle from chronic uremic rats

    International Nuclear Information System (INIS)

    Cecchin, F.; Ittoop, O.; Sinha, M.K.; Caro, J.F.

    1988-01-01

    The authors have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. 125 I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the β-subunit and insulin receptor kinase activity using Glu 80 , Tyr 20 as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristics of the receptors, as determined by electrophoretic mobilities of affinity labeled α-subunit and the phosphorylated β-subunit, were normal in uremia. 125 I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus the data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase

  20. Restoration of CpG Methylation in The Egf Promoter Region during Rat Liver Regeneration

    Science.gov (United States)

    Deming, Li; Ziwei, Li; Xueqiang, Guo; Cunshuan, Xu

    2015-01-01

    Epidermal growth factor (EGF) is an important factor for healing after tissue damage in diverse experimental models. It plays an important role in liver regeneration (LR). The objective of this experiment is to investigate the methylation variation of 10 CpG sites in the Egf promoter region and their relevance to Egf expression during rat liver regenera- tion. As a follow up of our previous study, rat liver tissue was collected after rat 2/3 partial hepatectomy (PH) during the re-organization phase (from days 14 to days 28). Liver DNA was extracted and modified by sodium bisulfate. The methylation status of 10 CpG sites in Egf promoter region was determined using bisulfite sequencing polymerase chain reaction (PCR), as BSP method. The results showed that 3 (sites 3, 4 and 9) out of 10 CpG sites have strikingly methylation changes during the re-organization phase compared to the regeneration phase (from 2 hours to 168 hours, P=0.002, 0.048 and 0.018, respectively). Our results showed that methylation modification of CpGs in the Egf promoter region could be restored to the status before PH operation and changes of methylation didn’t affect Egf mRNA expression during the re-organization phase. PMID:26464832

  1. Induction of rat liver tumor using the Sleeping Beauty transposon and electroporation.

    Science.gov (United States)

    Park, June-Shine; Kim, Bae-Hwan; Park, Sung Goo; Jung, Sun Young; Lee, Do Hee; Son, Woo-Chan

    2013-05-10

    The Sleeping Beauty (SB) transposon system has been receiving much attention as a gene transfer method of choice since it allows permanent gene expression after insertion into the host chromosome. However, low transposition frequency in higher eukaryotes limits its use in commonly-used mammalian species. Researchers have therefore attempted to modify gene delivery and expression to overcome this limitation. In mouse liver, tumor induction using SB introduced by the hydrodynamic method has been successfully accomplished. Liver tumor in rat models using SB could also be of great use; however, dose of DNA, injection volume, rate of injection and achieving back pressure limit the use of the hydrodynamics-based gene delivery. In the present study, we combined the electroporation, a relatively simple and easy gene delivery method, with the SB transposon system and as a result successfully induced tumor in rat liver by directly injecting the c-Myc, HRAS and shp53 genes. The tumor phenotype was determined as a sarcomatoid carcinoma. To our knowledge, this is the first demonstration of induction of tumor in the rat liver using the electroporation-enhanced SB transposon system. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Possible Protective Effect of Kombucha Tea Ferment on Carbon Tetrachloride Induced Liver Damage in Irradiated Rats

    International Nuclear Information System (INIS)

    Gharib, O.A.; Fahim, Th.M.

    2008-01-01

    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 (CCL 4 ) 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 CCL 4 alone and with subsequent y-irradiation. Hepatic pathological changes observed in the CCL 4 -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 CCL 4 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 CCL 4 and/ or radiation exposure intoxication are recoverable upon treatment with KT ferments

  3. [Relation between PMI and FTIR spectral changes in asphyxiated rat's liver and spleen].

    Science.gov (United States)

    Li, Shi-ying; Shao, Yu; Li, Zheng-dong; Zou, Dong-hua; Qin, Zhi-qiang; Chen, Yi-jiu; Huang, Ping

    2012-10-01

    Fourier transform infrared (FTIR) spectroscopy was applied to observe the postmortem degradation process in mechanical asphyxiated rat's liver and spleen for providing a new method of estimating PMI. Rats were sacrificed by mechanical asphyxia and cadavers were kept at (20 +/- 2) degrees C in a control chamber. The liver and spleen were sub-sampled from the same rat at intervals of 0-15 days postmortem and the data were measured by FTIR spectrometer. The different absorbance (A) ratios of peaks were calculated and the curve estimation analysis between absorbance ratios (x) and PMI (y) were performed to establish mathematical models by the statistical software. The band absorbance ratios showed increase, decrease and stable with PMI. The cubic model functions showed the strongest correlation coefficient. Compared with the spleen, the liver showed a higher correlation coefficient. The A1541/A1396 of liver showed the highest correlation coefficient (r=0.966). After 6-7 days postmortem, band absorbance ratios showed a steady period. FTIR spectroscopy can be a new and efficient method to estimate PMI within 7 days.

  4. Hepatoprotective activity of Mentha arvensis Linn. leaves against CCL4 induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Kalpana Patil

    2012-05-01

    Full Text Available Objective: To study the Hepatoprotective activity of ethanol, chloroform and aqueous extracts of Mentha arvensis leaves against CCL4 induced liver damage in rats. Methods: Hepatotoxicity was induced by CCL4 and the biochemical parameters such as serum glutamate pyruvate transminase (sGPT, serum glutamate oxaloacetate transaminase (sGOT, alkaline phosphatase (sALP, serum bilirubin (sB and histopathological changes in liver were studied along with silymarin as standard Hepatoprotective agents. Results: The Phytochemical investigation of the extracts showed presence of flavonoids, steroids, triterpenoids, alkaloids, glycosides, carbohydrates, tannins, phenolic compounds. Treatment of the rats with chloroform, ethanol and aqueous extract with CCL 4 administration caused a significant reduction in the values of sGOT, sGPT, sALP and sB (P<0.01 almost comparable to the silymarin. The Hepatoprotective was confirmed by histopathological examination of the liver tissue of control and treated animals. Conclusions: From the results it can be concluded that Mentha arvensis possesses Hepatoprotective effect against CCL4 induced liver damage in rats.

  5. Protective Effect of Urtica dioica on Liver Injury Induced By Hepatic Ischemia Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Alpaslan TERZİ

    2010-05-01

    Full Text Available Background: This study was designed to investigate the effects of Urtica dioica on liverischemia reperfusion injury in rats. Methods: Thirty male Wistar-albino rats were used in this experimental study. Animals weredivided into three groups as sham operated (group 1, control (group 2, and Urtica dioicatreatment group (group 3. Urtica dioica 2ml/kg were administered intraperitoneally beforeischemia and immediately after the reperfusion. The levels of total antioxidant capacity, totalfree sulfidril group, Total oxidant status, Oxidative stress index, and myeloperoxidase in livertissues were measured. The serum levels of ALT, AST and LDH were also measuredResults: Total antioxidant capacity and total free sulfidril group in liver tissue were significantlyhigher in group 3 than in group 2. Oxidative stress index and myeloperoxidase in liver tissuewere significantly lower in group 3 than the group 2. The levels of liver enzymes in treatmentgroup were significantly lower than those in the control group. Histological tissue damage wasmilder in the treatment group than that in the control group.Conclusion: It is concluded that Urtica dioica increase the antioxidant capacity and decreaseoxidative stress and liver enzymes in the hepatic ischemi reperfusion injury of rats.

  6. Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Yavar Mahmoodzadeh

    Full Text Available The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4.54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups, 4 of them were exposure groups which were respectively administered with 40, 80, and 120 mg/kg of TPE and silymarin for 14 days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120 mg/kg of TPE and silymarin 2, 6, 24, and 48 h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed.Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group.The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4. Keywords: Tanacetum parthenium, Carbon tetrachloride, Oxidative stress, Antioxidant enzymes, Liver damage

  7. Effects of defibrotide, a novel oligodeoxyribonucleotide, on ischaemia and reperfusion injury of the rat liver.

    Science.gov (United States)

    Kim, Kwang Joon; Shin, Yong Kyoo; Song, Jin Ho; Oh, Byung Kwon; Choi, Myung Sup; Sohn, Uy Dong

    2002-02-01

    1. The purpose of this study was to investigate the protective effects of defibrotide, a single-stranded polydeoxyribonucleotide, on ischaemia-reperfusion injury to the liver using a rat model. 2. Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte-endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3. Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4. A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5. We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.

  8. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  9. Molecular classification of fatty liver by high-throughput profiling of protein post-translational modifications.

    Science.gov (United States)

    Urasaki, Yasuyo; Fiscus, Ronald R; Le, Thuc T

    2016-04-01

    We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. Molecular signatures associated with HCV-induced hepatocellular carcinoma and liver metastasis.

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    Valeria De Giorgi

    Full Text Available Hepatocellular carcinomas (HCCs are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis.A diagnostic molecular signature complementing conventional pathologic assessment was identified.

  11. Effect of Vitamin B5 on Liver Enzyme Levels in Bile Duct Ligation Cholestatic Rat Model

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    Fatemeh Sadat Emami

    2017-01-01

    Full Text Available Background and Objectives: Accumulation of toxic bile salts in a bile duct ligation (BDL animal model plays a pivotal role in the induction of liver fibrosis. Vitamin B5 is an essential nutrient, which acts as a cofactor in many detoxification system enzymes. In the present research, the antifibrotic effect of vitamin B5 was investigated on liver cholestasis induced by BDL in rats. Methods: In this experimental study, 72 male Wistar rats were divided into 9 groups: Control, sham-operated, vitamin B5 (5, 50, and 100mg/kg bw, BDL, and BDL+vitamin B5 (5, 50, and 100mg/kg bw. After BDL, rats were given vitamin B5 via intragastric gavage for 28 consecutive days. At the end of the experiment, blood was collected from heart and activity of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and alkaline phosphatase (ALP enzymes, were measured. The data were analyzed using one-way ANOVA test. Results: In the BDL animals, the serum activities of AST, ALT, and ALP significantly increased (p<0.001. Treatment of BDL rats with vitamin B5 significantly attenuated these changes. Conclusion: The results of this study indicated that vitamin B5 has hepatoprotective and antifibrotic effects in the cholestatic liver, which is likely due to the antioxidative and free radical scavenging effects of this vitamin.

  12. 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.

  13. Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers.

    Science.gov (United States)

    Monteiro, Maria Emília L; Xavier, Analucia R; Oliveira, Felipe L; Filho, Porphirio Js; Azeredo, Vilma B

    2016-06-14

    To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers. We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93M diet, and animals in the experimental group received an Atkins-based diet (59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation (SD) assuming unpaired and parametric data; we analyzed differences using the Student's t-test. Statistical significance was set at P diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. Sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group. Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.

  14. A relative study of hepatic perfusion and portal vein pressure in rats with liver cirrhosis

    International Nuclear Information System (INIS)

    Li Jiaping; Yang Jianyong; Chen Wei; Huang Yonghui

    2006-01-01

    Objective: To evaluate spiral CT perfusion in assessing portal vein pressure in rats with different stages of liver cirrhosis. Methods Seventeen rats with early stage of liver cirrhosis, 18 with intermediate stage, 12 with advanced stage, and 13 healthy rats as a control group were selected and recieved hepatic perfusion on a single-row spiral CT scanner. The parameters of hepatic perfusion were calculated using the deconvolution method. The portal vein pressure was measured by multi-physiographer. Results: (1) In study group, the PVP (portal venous perfusion) and THBP (total hepatic blood perfusion) were negatively correlated with FPP, while positively correlated with the HPI (hepatic perfusion index) and MTT (mean transit time). The FPP had a close relation with PVP. The equation, Y 20.671-3.195X, could be conducted with linear regression analysis. (2) According to the linear regression equation mentioned above, the FPP in 47 rats were 16.090±2.150 cmH 2 0, which was highly correlated with the observed valuel6.108±3.662 cmH 2 O (r=0.823 P<0.01). Conclusion: CT perfusion is a new non-invasive and efficient modality for assessment of the portal pressure in liver cirrhosis in various stages. (authors)

  15. Radioimmunological determination of glucokinase turnover in the rat liver

    International Nuclear Information System (INIS)

    Sibrowski, W.

    1980-01-01

    Synthesis and degradation of glucokinase (GK), key enzyme of glucose utilisation has been investigated in vivo in intact and adrenalectomized rats. Four statements can be made: a pure glucose diet stimulates GK synthesis, glucocorticoids have a permissive effect in the induction of GK sythesis, glucocorticoids do not have any effect in themselves, glucocorticoids affect GK degradation. (orig./AJ) [de

  16. 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.

  17. [Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].

    Science.gov (United States)

    Liu, Xu-hua; Chen, Yu; Wang, Tai-ling; Lu, Jun; Zhang, Li-jie; Song, Chen-zhao; Zhang, Jing; Duan, Zhong-ping

    2007-10-01

    To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment. Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure. We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

  18. Tocotrienols Reverse Cardiovascular, Metabolic and Liver Changes in High Carbohydrate, High Fat Diet-Fed Rats

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    Weng-Yew Wong

    2012-10-01

    Full Text Available Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.

  19. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

    Directory of Open Access Journals (Sweden)

    G.B. Peres

    2014-06-01

    Full Text Available 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 10th or the 30th 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 10th, but not on the 30th day. Sulfatase decreased 30% on the 30th 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.

  20. Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

    Science.gov (United States)

    Kober, P M; Filkins, J P

    1981-01-01

    Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

  1. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

    International Nuclear Information System (INIS)

    Peres, G.B.; Juliano, M.A.; Aguiar, J.A.K.; Michelacci, Y.M.

    2014-01-01

    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 th or the 30 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 th , but not on the 30 th day. Sulfatase decreased 30% on the 30 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. 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.

  3. 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.

  4. 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)

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

    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 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

  5. 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.

  6. Effect of radiotherapy on experimental liver regenerative capacities following partial hepatectomy in rats

    International Nuclear Information System (INIS)

    Du Shisuo; Zeng Zhaochong; Tang Zhaoyou; Zhang Zhenyu; Wu Zheng; Shi Liusheng

    2008-01-01

    Objective: To investigate the regenerative capacities and proliferation related cytokines expression of normal and irradiated livers following 70% partial hepatectomy in rats. Methods: 90 male Sprague-Dawley rats were divided into 3 groups. The control group was only received 70% partial hepatectomy. The two irradiated groups were performed a single dose of 4 Gy and 8 Gy photon irradiation respectively followed 70% partial hepatectomy. The remanent liver were excised at 0.5,1.0,2.0,3.0,7.0 and 10.0 d after hepatectomy, and liver regeneration capacities in normal and irradiated rats were evaluated through remanent liver weigh, BrdU incorporation, PCNA labeling, and mitotic indices. The proliferation related cytokines expression were also compared. Results: After radiotherapy and hepatectomy 1 rats died of infection in control group, and two rats in 8 Gy group died of radiation induced enteritis. The original liver weigh is regained within 12 days in control and 4 Gy group, and proliferative speed was lower in 4 Gy group than control group. The weigh of remanent liver in 8 Gy group was significantly lower than the two groups all time points from 2d. The apex of PCNA labeling index was 80.2 ± 7.6%, 71.2 ± 6.5% and 55.3 ± 4.7% in control, 4 Gy and 8 Gy groups respectively at 2d, and 44.2 ± 5.4%, 35.3 ± 5.72% and 5.3 ± 6.9% with BrdU incorporation index. HGF mRNA expression peak of 4 Gy group was significantly lower than in control at 1 d, but no apparent peak value in 8 Gy group. TGF-β1 and TGF-β RII level of radiation groups was apparently higher than the control group at different time points. Meanwhile the p53 protein tend to increase at 1 d then decline with high expression in irradiated groups. Conclusion: Whole radiation can significantly inhibit the regenerative capacities following partial hepatectomy in rats with dose dependent. (authors)

  7. Effects of Combined Anisodamine and Neostigmine Treatment on the Inflammatory Response and Liver Regeneration of Obstructive Jaundice Rats after Hepatectomy

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    Chong-Hui Li

    2014-01-01

    Full Text Available Background. Cholestasis is associated with high rates of morbidity and mortality in patients undergoing major liver resection. This study aimed to evaluate the effects of a combined anisodamine and neostigmine (Ani+Neo treatment on the inflammatory response and liver regeneration in rats with obstructive jaundice (OJ after partial hepatectomy. Materials and Methods. OJ was induced in the rats by bile duct ligation. After 7 days biliary drainage and partial hepatectomy were performed. These rats were assigned to a saline group or an Ani+Neo treatment group. The expressions of inflammatory mediators, liver regeneration, and liver damage were assessed at 48 h after hepatectomy. Results. The mRNA levels of TNF-α, IL-1β, IL-6, MCP-1, and MIP-1α, in the remnant livers, and the serum levels of TNF-α and IL-1β were substantially reduced in the Ani+Neo group compared with saline group (P<0.05. The Ani+Neo treatment obviously promoted liver regeneration as indicated by the liver weights and Ki-67 labeling index (P<0.05. The serum albumin and γ-GT levels and liver neutrophil infiltration also significantly improved in the Ani+Neo group (P<0.05 compared with the saline group. Conclusions. These results demonstrate that the combined anisodamine and neostigmine treatment is able to improve the liver regeneration in rats with OJ by substantially alleviating the inflammatory response.

  8. Nucleolar activity after 3-methylcholanthrene treatment of rat liver cells studied by silver staining procedure

    Energy Technology Data Exchange (ETDEWEB)

    Komaromy, L.; Tigyi, A.

    1986-01-01

    The influence of a single dose of 3-methylcholanthrene (3-MC) was studied in nucleoli of young rat liver cells by means of conventional and ultracytochemical methods. The nucleolar activity was stimulated in the authors experimental conditions: the appearance of the fibrillar centers in the liver cell nucleoli as well as the silver staining protein content of the fibrillar centers and the dense fibrillar component were increased by 3-MC. The results suggest that the activity of ribosomal genes was increased following 3-MC treatment.

  9. Reactivation in vitro of zinc-requiring apo-enzymes by rat liver zinc-thionein

    OpenAIRE

    Udom, Albert O.; Brady, Frank O.

    1980-01-01

    The ability of rat liver zinc-thionein to donate its metal to the apo-enzymes of the zinc enzymes horse liver alcohol dehydrogenase, yeast aldolase, thermolysin, Escherichia coli alkaline phosphatase and bovine erythrocyte carbonic anhydrase was investigated. Zinc-thionein was as good as, or better than, ZnSO4, Zn(CH3CO2)2 or Zn(NO3)2 in donating its zinc to these apo-enzymes. Apo-(alcohol dehydrogenase) could not be reactivated by zinc salts or by zinc-thionein. Incubation of the other apo-e...

  10. Binding of in vivo administrated 125-I-triiodothyronine by the rat liver mitochondria

    International Nuclear Information System (INIS)

    Fiedorowicz, K.; Nauman, A.; Nauman, J.

    1979-01-01

    In vivo administrated 125 I-triiodothyronine ( 125 I-T 3 ) was bound by the rat liver mitochondria. About 10 % of hormone was bound with external mitochondrial membrane while the remaining part with matrix and inner mitochondrial membrane. The highest accumulation of 125 I-T 3 in mitochondria was observed 30 min after injection while in the whole liver homogenate the highest hormone accumulation appeared 15 min post injection. Mitochondrial binding sites have a great capacity for T 3 which makes impossible estimation of the kinetic parameters of triiodothyronine-mitochondrium interaction by means of saturation and displacement of 125 I-T 3 . (author)

  11. Developmental changes in rat liver branched-chain 2-oxo acid dehydrogenase.

    OpenAIRE

    May, E E; May, M E; Aftring, R P; Buse, M G

    1982-01-01

    Branched-chain 2-oxo acid dehydrogenase catalyses the first irreversible step in the degradation of the branched-chain amino acids leucine, isoleucine and valine. With specifically labelled 4-methyl-2-oxo[1-14C]pentanoate as substrate, the enzyme's activity was measured in rat liver homogenates. Activity (per g wet wL of liver or per mg of protein) increased most rapidly during the perinatal period (2 days before to 1 day after birth), reaching approximately adult values by the time of weanin...

  12. Inhibition of ATP synthesis by fenbufen and its conjugated metabolites in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    in the drug induced liver injury (DILI) by fenbufen, the inhibitory effect of fenbufen and its conjugated metabolites on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria was investigated. Fenbufen glucuronide (F-GlcA), fenbufen-N-acetyl cysteine-thioester (F-NAC) and fenbufen...... and fenbufen show any protective effect on fenbufen mediated inhibition of oxidative phosphorylation. Inclusion of NADPH in mitochondrial preparations with fenbufen did not modulate the inhibitory effects, suggesting no role of CYP mediated oxidative metabolites on the ATP synthesis in isolated mitochondria...

  13. Strain-Related Differences on Response of Liver and Kidney Antioxidant Defense System in Two Rat Strains Following Diazinon Exposure

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    Maryam Salehi

    2016-02-01

    Full Text Available Background Diazinon (DZN is one of the most organophosphates that widely used in agriculture and ectoparasiticide formulations. Its extensive use as an effective pesticide was associated with the environmental deleterious effects on biological systems. Objectives The aim of this study was to investigate the potency of DZN to affect serum biochemical parameters and the antioxidant defense system in the liver and kidney of two rat strains. Materials and Methods In this experimental study, 30 female Wistar and 30 female Norway rats were randomly divided into control and DZN groups. DZN group was divided into four subgroups: 25, 50, 100 and 200 mg/kg of DZN administered groups by i.p. injection. The parameters were evaluated after 24 hours. Results At higher doses of DZN, superoxide dismutase, catalase, glutathione S-transferase and lactate dehydrogenase activities and glutathione (GSH and malondialdehyde levels in liver and kidney of Wistar rats were higher than Norway rats. At these concentrations, DZN increased some serum biochemical indices such as liver enzymes activities and levels of urea, uric acid and creatinine in Wistar rat. Conclusions DZN at higher doses alters the oxidant-antioxidant balance in liver and kidney of both rat strains and induces oxidative stress, which is associated with a depletion of GSH and increased lipid peroxidation. However, Wistar rats are found to be more sensitive to the toxicity of DZN compared to Norway rats. In addition, the effect of DZN on liver antioxidant system was more than kidney.

  14. Inhibition by etomoxir of rat liver carnitine octanoyltransferase is produced through the co-ordinate interaction with two histidine residues.

    Science.gov (United States)

    Morillas, M; Clotet, J; Rubí, B; Serra, D; Ariño, J; Hegardt, F G; Asins, G

    2000-10-15

    Rat peroxisomal carnitine octanoyltransferase (COT), which facilitates the transport of medium-chain fatty acids through the peroxisomal membrane, is irreversibly inhibited by the hypoglycaemia-inducing drug etomoxir. To identify the molecular basis of this inhibition, cDNAs encoding full-length wild-type COT, two different variant point mutants and one variant double mutant from rat peroxisomal COT were expressed in Saccharomyces cerevisiae, an organism devoid of endogenous COT activity. The recombinant mutated enzymes showed activity towards both carnitine and decanoyl-CoA in the same range as the wild type. Whereas the wild-type version expressed in yeast was inhibited by etomoxir in an identical manner to COT from rat liver peroxisomes, the activity of the enzyme containing the double mutation H131A/H340A was completely insensitive to etomoxir. Individual point mutations H131A and H340A also drastically reduced sensitivity to etomoxir. Taken together, these results indicate that the two histidine residues, H131 and H340, are the sites responsible for inhibition by etomoxir and that the full inhibitory properties of the drug will be shown only if both histidines are intact at the same time. Our data demonstrate that both etomoxir and malonyl-CoA inhibit COT by interacting with the same sites.

  15. Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I2 production by rat liver cells

    International Nuclear Information System (INIS)

    Levine, Lawrence

    2004-01-01

    Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [ 3 H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I 2 produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I 2 production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I 2 production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

  16. Multi-omic network-based interrogation of rat liver metabolism following gastric bypass surgery featuring SWATH proteomics.

    Science.gov (United States)

    Sridharan, Gautham Vivek; D'Alessandro, Matthew; Bale, Shyam Sundhar; Bhagat, Vicky; Gagnon, Hugo; Asara, John M; Uygun, Korkut; Yarmush, Martin L; Saeidi, Nima

    2017-09-01

    Morbidly obese patients often elect for Roux-en-Y gastric bypass (RYGB), a form of bariatric surgery that triggers a remarkable 30% reduction in excess body weight and reversal of insulin resistance for those who are type II diabetic. A more complete understanding of the underlying molecular mechanisms that drive the complex metabolic reprogramming post-RYGB could lead to innovative non-invasive therapeutics that mimic the beneficial effects of the surgery, namely weight loss, achievement of glycemic control, or reversal of non-alcoholic steatohepatitis (NASH). To facilitate these discoveries, we hereby demonstrate the first multi-omic interrogation of a rodent RYGB model to reveal tissue-specific pathway modules implicated in the control of body weight regulation and energy homeostasis. In this study, we focus on and evaluate liver metabolism three months following RYGB in rats using both SWATH proteomics, a burgeoning label free approach using high resolution mass spectrometry to quantify protein levels in biological samples, as well as MRM metabolomics. The SWATH analysis enabled the quantification of 1378 proteins in liver tissue extracts, of which we report the significant down-regulation of Thrsp and Acot13 in RYGB as putative targets of lipid metabolism for weight loss. Furthermore, we develop a computational graph-based metabolic network module detection algorithm for the discovery of non-canonical pathways, or sub-networks, enriched with significantly elevated or depleted metabolites and proteins in RYGB-treated rat livers. The analysis revealed a network connection between the depleted protein Baat and the depleted metabolite taurine, corroborating the clinical observation that taurine-conjugated bile acid levels are perturbed post-RYGB.

  17. Stimulation of liver IGF-1 expression promotes peak bone mass achievement in growing rats: a study with pomegranate seed oil.

    Science.gov (United States)

    Bachagol, Deepa; Joseph, Gilbert Stanley; Ellur, Govindraj; Patel, Kalpana; Aruna, Pamisetty; Mittal, Monika; China, Shyamsundar Pal; Singh, Ravendra Pratap; Sharan, Kunal

    2018-02-01

    Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis, and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remain unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-day-old growing rats for 90 days by oral gavage. The changes in bone parameters were assessed by micro-computed tomography and histology. Enzyme-linked immunosorbent assay was performed to analyze the levels of serum insulin-like growth factor type 1 (IGF-1). Western blotting from bone and liver tissues was done. Chromatin immunoprecipitation assay was performed to study the histone acetylation levels at IGF-1 gene. The results of the study show that PSO treatment significantly increases bone length, bone formation rate, biomechanical parameters, bone mineral density and bone microarchitecture along with enhancing muscle and brown fat mass. This effect was due to the increased serum levels of IGF-1 and stimulation of its signaling in the bones. Studies focusing on acetylation of histones in the liver, the major site of IGF-1 synthesis, showed enrichment of acetylated H3K9 and H3K14 at IGF-1 gene promoter and body. Further, the increased acetylation at H3K9 and H3K14 was associated with a reduced HDAC1 protein level. Together, our data suggest that PSO promotes the PBM achievement via increased IGF-1 expression in liver and IGF-1 signaling in bone. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities

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    Jun-Ho Lee

    2015-01-01

    Full Text Available Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW compared with hyperglycemic rats. Here, we elucidated the molecular mechanisms underlying the loss of LW in euglycemic-diabetic rats and identified a potential risk in achieving euglycemia by calorie-control. Sprague-Dawley diabetic rats generated by subtotal-pancreatectomy were fed a calorie-controlled diet for 7 weeks to achieve euglycemia using 19 kcal% (19R or 6 kcal% (6R protein-containing chow or fed ad libitum (19AL. The diet in both R groups was isocaloric/kg body weight to the sham-operated group (19S. Compared with 19S and hyperglycemic 19AL, both euglycemic R groups showed lower LWs, increased autophagy, and increased AMPK and caspase-3 and decreased mTOR activities. Though degree of insulin deficiency was similar among the diabetic rats, Akt activity was lower, and PTEN activity was higher in both R groups than in 19AL whose signaling patterns were similar to 19S. In conclusion, euglycemia achieved by calorie-control is deleterious in insulin deficiency due to increased autophagy and apoptosis in the liver via AMPK and caspase-3 activation.

  19. Investigation of Liver Injury of Polygonum multiflorum Thunb. in Rats by Metabolomics and Traditional Approaches

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    Yun-Xia Li

    2017-11-01

    Full Text Available Liver injury induced by Polygonum multiflorum Thunb. (PM have been reported since 2006, which aroused widespread concern. However, the toxicity mechanism of PM liver injury remained unclear. In this study, the mechanism of liver injury induced by different doses of PM after long-term administration was investigated in rats by metabolomics and traditional approaches. Rats were randomly divided into control group and PM groups. PM groups were oral administered PM of low (10 g/kg, medium (20 g/kg, high (40 g/kg dose, while control group was administered distilled water. After 28 days of continuous administration, the serum biochemical indexes in the control and three PM groups were measured and the liver histopathology were analyzed. Also, UPLC-Q-TOF-MS with untargeted metabolomics was performed to identify the possible metabolites and pathway of liver injury caused by PM. Compared with the control group, the serum levels of ALT, AST, ALP, TG, and TBA in middle and high dose PM groups were significantly increased. And the serum contents of T-Bil, D-Bil, TC, TP were significantly decreased. However, there was no significant difference between the low dose group of PM and the control group except serum AST, TG, T-Bil, and D-Bil. Nine biomarkers were identified based on biomarkers analysis. And the pathway analysis indicated that fat metabolism, amino acid metabolism and bile acid metabolism were involved in PM liver injury. Based on the biomarker pathway analysis, PM changed the lipid metabolism, amino acid metabolism and bile acid metabolism and excretion in a dose-dependent manner which was related to the mechanism of liver injury.

  20. Intralipid minimizes hepatocytes injury after anoxia-reoxygenation in an ex vivo rat liver model.

    Science.gov (United States)

    Stadler, Michaela; Nuyens, Vincent; Boogaerts, Jean G

    2007-01-01

    Ischemia-reperfusion injury is a determinant in liver injury occurring during surgical procedures, ischemic states, and multiple organ failure. The pre-existing nutritional status of the liver, i.e., fasting, might contribute to the extent of tissue injury. This study investigated whether Intralipid, a solution containing soybean oil, egg phospholipids, and glycerol, could protect ex vivo perfused livers of fasting rats from anoxia-reoxygenation injury. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Isolated livers were perfused with glucose 5.5 and 15 mM, and two different concentrations of Intralipid, i.e., 0.5:100 and 1:100 (v/v) Intralipid 10%:medium (n = 5 in each group). The experiment consisted of perfusion for 15 min, warm anoxia for 60 min, and reoxygenation during 60 min. Hepatic enzymes, potassium, glucose, lactate, bilirubin, dienes, trienes, and cytochrome-c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in biopsies. Intralipid attenuated transaminases, lactate dehydrogenase, potassium, diene, and triene release in the perfusate (dose-dependant) during the reoxygenation phase when compared with glucose-treated groups. The concentration of cytochrome-c in the medium was the highest in the 5.5-mM glucose group. The glycogen content was low in all livers at the start of the experiment. Intralipid presents, under the present experimental conditions, a better protective effect than glucose in anoxia-reoxygenation injury of the rat liver.

  1. Early histological and functional effects of chronic copper exposure in rat liver.

    Science.gov (United States)

    Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

    2005-10-01

    Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

  2. Regulation of ODC activity in the thymus and liver of rats by adrenal hormones.

    Science.gov (United States)

    Zahner, S L; Prahlad, K V; Mitchell, J L

    1986-01-01

    The activity of L-ornithine decarboxylase (EC 4.1.1.17, ODC) has become a useful indicator of hormone responsiveness. Various regimens of dexamethasone, aldosterone and epinephrine, alone or in combination, were administered to adrenalectomized rats either in acute or chronic doses. In addition, adrenalectomized rats, which were chronically treated with aldosterone and epinephrine, were given a single injection of 50 micrograms dexamethasone and sacrificed at various time intervals after hormone treatment. Hepatic and thymic ODC activity was measured. The expected dexamethasone effect, an increase in hepatic and a decrease in thymic ODC, was observed. This study also revealed that aldosterone induced similar responses in these tissues. Epinephrine had the opposite effect since chronic administration of dexamethasone or aldosterone with epinephrine resulted in control levels of ODC. Furthermore, when aldosterone and epinephrine were chronically administered to adrenalectomized rats, to study the acute effects of dexamethasone on rat thymus and liver, the time course of the response in each tissue was found to be distinct. The influence of the adrenal gland on rat thymus and liver is not restricted only to glucocorticoids, but may also involve other hormones which it secretes.

  3. Effect of dietary lipid, carnitine and exercise on lipid profile in rat blood, liver and muscle.

    Science.gov (United States)

    Karanth, Jyothsna; Jeevaratnam, K

    2009-09-01

    Aim of this study was to investigate the influence of physical exercise on effects of the daily intake of vegetarian diet of either vegetable hydrogenated fat (HF) or peanut oil (PO) with or without carnitine on the lipid profile. Eight groups of male Wistar rats were fed HF-diet (4 groups) or PO-diet (4 groups), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. Plasma triglycerides (TG), total cholesterol (TC), HDL-cholesterol, free fatty acids (FFA), liver and thigh muscle glycogen, total fat (TF), TG, TC and FFA were analyzed. HF-fed rats showed significantly increased plasma TC, VLDL+LDL-cholesterol and TG compared to PO-fed rats, wherein a lowered plasma TC, TG levels in all the groups with significantly increased liver cholesterol and decreased muscle cholesterol was observed. Physical exercise of moderate intensity reduced plasma TC and TG accompanied by significantly reduced tissue TG and cholesterol while FFA and glycogen increased in all the groups. The influence of exercise was less pronounced in carnitine supplemented rats since carnitine could significantly reduce TG in plasma and tissues of sedentary rats. Results from the present study showed that the intake of HF diet significantly increased the plasma and tissue lipid profile and MUFA-rich diet or carnitine supplementation and/or exercise may ameliorate the deleterious effects of HF.

  4. Mutagenicity of the potent rat hepatocarcinogen 6BT to the liver of transgenic (lacI) rats: consideration of a reduced mutation assay protocol.

    Science.gov (United States)

    Lefevre, P A; Tinwell, H; Ashby, J

    1997-01-01

    6-(p-dimethylaminophenylazo)benzothiazole (6BT) is an unusually potent rat hepatocarcinogen, producing large malignant liver tumours after only 2-3 months of dietary administration in a riboflavin-deficient diet. This azocarcinogen has been evaluated in a Big Blue F344 transgenic rat (lacI) gene mutation assay. In a reproduction of the early stages of the carcinogenesis bioassay of this agent, rats were maintained on a riboflavin-deficient diet and were given 10 consecutive daily doses of 6BT (10 mg/kg) by oral gavage. The animals were killed and the livers examined 11 days after the final dose. The livers of 6BT-treated rats showed evidence of hepatocellular hypertrophy in centrolobular areas, with some indication of an increased incidence of mitotic figures. An approximately 10-fold increase in the mutation frequency of DNA isolated from an aliquot of the combined liver homogenates of 6BT-treated rats was observed over that obtained from an equivalent aliquot from control animals. Examination of DNA samples isolated from the livers of individual animals confirmed that 6BT was mutagenic in Big Blue rat livers. These data extend the sensitivity of this transgenic assay to include azo hepatocarcinogens. The determination of mutation frequencies using pooled tissue samples represented a major resource-saving adaptation of the assay protocol in the present study; the general advantages and disadvantages of this practice are discussed.

  5. Comparison of hepatotoxicity and metabolism of butyltin compounds in the liver of mice, rats and guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Shunji; Kashimoto, Takashige; Susa, Nobuyuki; Ishii, Masamitsu; Chiba, Toshikazu [Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Mutoh, Ken-ichiro [Laboratory of Veterinary Anatomy, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Hoshi, Fumio [Laboratory of Veterinary Anatomy, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Suzuki, Takashi [Laboratory of Environmental Health and Toxicology, Kyoto Prefectural University, Hangi-cho, Shimogamo, Sakyo-ku, 606-5822, Kyoto (Japan); Sugiyama, Masayasu [Sugiyama Pharmacy, 1335-1 Shimotama, Tamagawa-cho, 759-3112, Yamaguchi (Japan)

    2003-03-01

    The hepatotoxicity of tributyltin chloride (TBTC) and dibutyltin dichloride (DBTC) was compared among mice, rats and guinea pigs in vivo. Further, the metabolism of these butyltin compounds in the liver was also investigated in these species. The oral administration of TBTC and DBTC to mice induced obvious liver injury, as demonstrated by both serodiagnosis and histopathological diagnosis. The concentrations of TBTC and DBTC that induced hepatotoxicity in mice at 24 h after oral administration were 180 and 60 {mu}mol/kg, respectively. In the case of rats, the liver injury induced by TBTC and DBTC was detected at 24 h by the serodiagnosis, but not by histopathological diagnosis. On the other hand, in guinea pigs, TBTC and DBTC administration did not produce any clear liver injury at 24 h, as evaluated by these two diagnostic methods. Thus, the following ranking was obtained with regard to increasing order of sensitivity to liver injury caused by TBTC and DBTC: mice, rats and guinea pigs. The total butyltin contents in the liver of mice were equivalent at 3 h and 24 h after the administration of TBTC or DBTC; however, the contents in the liver of rats and guinea pigs were relatively lower at 3 h and higher at 24 h than those of mice, although there were no differences between rats and guinea pigs in the total liver butyltin content. Concerning the liver metabolism of these butyltin compounds, the main form of butyltin compounds in these animals treated with TBTC was DBTC within 3 h after oral administration, while the main metabolites at 24 h were different in each species, indicating that the liver metabolism of TBTC might vary by animal type. When the animals were treated with DBTC orally, DBTC was hardly metabolized in the livers of these animals even at 24 h, and the liver levels of DBTC were two times greater in mice and guinea pigs than in rats at 3 h and were lower in mice at 24 h than in rats and guinea pigs. The analysis of cellular distributions of DBTC in

  6. Monooxignase ensymic system of a liver of rats exposed to intravascular laser irradiation of blood

    International Nuclear Information System (INIS)

    Ibadova, G.A.

    1997-01-01

    Experimental study of the dynamic monooxidation of liver enzymic system was carried out on rats with experimental salmonellosis and the influence of the blood intravascular laser irradiation of blood on these enzymes was revealed. It was determined that by experimental salmonellosis oppression of the MOES activity of hepatocytes occurred. The blood intravascular irradiation by He-Ne laser promotes MOES oppression in rats suffered from salmonellosis. IVLIB as well as UV-laser show pronounced effect on the enzymes detoxication protection, mobilize their resistance to endogenic intoxication under the conditions of experimental salmonellosis. (author)

  7. Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

    Directory of Open Access Journals (Sweden)

    Lourdes Sánchez-Sevilla

    2016-10-01

    Full Text Available Abstract Background The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH, by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. Methods This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC, and polyamine levels, were determined. Results Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Conclusions Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased

  8. Expression of isgylation related genes in regenerating rat liver

    Directory of Open Access Journals (Sweden)

    Kuklin A. V.

    2015-10-01

    Full Text Available Our recent studies have revealed the early up-regulated expression of interferon alpha (IFNα in the liver, induced by partial hepatectomy. The role of this cytokine of innate immune response in liver regeneration is still controversial. Aim. To analyze expression of canonical interferon-stimulated genes Ube1l, Ube2l6, Trim25, Usp18 and Isg15 during the liver transition from quiescence to proliferation induced by partial hepatectomy, and acute phase response induced by laparotomy. These genes are responsible for posttranslational modification of proteins by ISGylation. The expression of genes encoding TATA binding protein (TBP and 18S rRNA served as indirect general markers of transcriptional and translational activities. Methods. The abundance of investigated RNAs was assessed in total liver RNA by real time RT–qPCR. Results. Partial hepatecomy induced steady upregulation of the Tbp and 18S rRNA genes expression during 12 hours post-surgery and downregulation or no change in expression of ISGylation-related genes during the first 3 hours followed by slight upregulation at 12 hours. The level of Isg15 transcripts was permanently below that of the control during the prereplicative period. Laparotomy induced a continuous downregulation of Tbp and 18S rRNA expression and early (1–3h upregulation of ISGylation–related transcripts followed by a sharp drop at 6 hours and slight increase/decrease at 12 hours. The changes in the abundance of Ifnα and ISGylation-related mRNAs were oppositely directed at each stage of the response to partial hepatectomy and laparotomy. Conclusion. We suggest that the expression of ISGylation-related genes does not depend on the expression of Ifnα gene after both surgeries. The indirect indices of transcription and translation as well as the expression of ISGylation-relaled genes are principally different in response to partial hepatectomy and laparotomy and argue for the high specificity of innate immune response.

  9. Prebiotic and Synbiotic Modifications of Beta Oxidation and Lipogenic Gene Expression after Experimental Hypercholesterolemia in Rat Liver

    Directory of Open Access Journals (Sweden)

    Claudia C. Alves

    2017-10-01

    Full Text Available Background and aims: Non-alcoholic fatty liver disease (NAFLD is characterized by the presence of fat in hepatocytes because of decreased β-oxidation and increased lipogenesis. Prebiotics, probiotics, and synbiotic have modulatory effects on intestinal microbiota and may influence the gut-liver axis. Our aim was to evaluate the effects of prebiotic, probiotics, and synbiotic on liver histopathology and gene expression related to β-oxidation and lipogenesis after hypercholesterolemia.Methods: Wistar male adult rats (n = 40 were submitted to hypercholesterolemic conditions (HPC (60 days. On Day 30 of HPC, rats were subdivided in 5 groups: negative control (NC: without HPC + Gv (distilled water; positive control (PC: with HPC + Gv (distilled water; prebiotic (PRE: HPC + Gv with prebiotic (Fiber FOS®; probiotic (PRO: HPC + Gv with probiotic strains Gv (Probiatop®; and synbiotic (SYN: HPC + Gv with synbiotic (Simbioflora®. All rats were sacrificed on Day 30 post-treatment. Blood was collected to verify total serum cholesterol, and liver tissue was sampled to verify histopathological changes and gene expression. Gene expression related to ß-oxidation (PPAR-α and CPT-1 and lipogenesis (SREBP-1c, FAS and ME was evaluated in liver tissue using RT-qPCR.Results: PC had higher cholesterol levels when compared to NC. PRE and SYN rats had lower cholesterol levels than PC. PC rats showed more histopathological changes than NC rats; PRE and SYN rats showed fewer alterations than PC rats. PPAR-α was expressed at higher levels in SYN and PC rats compared with PRE and PRO rats. CPT-1 expression was similar in all groups. SREBP-1c was expressed at higher levels in PC rats compared with NC rats; levels were lower in SYN rats compared with PRO rats; levels were lower in PRE rats compared with PC and PRO rats. FAS was expressed at lower levels in PRE rats compared with SYN rats. ME expression was lower in PC rats compared with NC rats.Conclusion: Prebiotic and

  10. Purification and characterization of the reconstitutively active P/sub i//H/sup +/ symporter from rat liver mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, R.S.; Pratt, R.D.; Pedersen, P.L.

    1986-05-01

    A highly purified preparation of reconstitutively active P/sub i//H/sup +/ symporter has been obtained from rat liver mitochondria. The carrier is isolated by extraction of hypotonically shocked mitoplasts with Triton X-114 in the presence of cardiolipin followed by sequential chromatography on hydroxylapatite, DEAE-Sepharose CL-6B, and Affi-Gel 501. Upon incorporation of the final Affi-Gel eluate into phospholipid vesicles, an N-ethylmaleimide (NEM)-sensitive P/sub i//P/sub i/ exchange of greater than 15 ..mu..mol/min/mg protein has been measured. This exchange is characterized by a first order rate constant of 0.85 min/sup -1/ and a t/sub 1/2/ of 49 sec. Furthermore, /sup 32/P/sub i/ uptake into vesicles can be inhibited by SH reagents and by the lysine reactive reagent dansyl chloride. Coomassie-stained SDS polyacrylamide gradient gels verify the high purity of this fraction and indicate the presence of two bands, of nearly equivalent staining intensity, at 33 kDa and 35 kDa. A small amount of higher molecular weight material also appears at approx. 61 kDa. Alkylation of the purified fraction with NEM causes the two lower molecular weight protein bands to migrate as a single species at 35 kDa which binds (/sup 3/H)NEM. It is concluded that the purifed protein represents a nearly homogeneous form of the NEM-sensitive P/sub i//H/sup +/ symporter of rat liver mitochondria. Additionally, the purified carrier appears to contain cysteine and lysine residues that are essential for activity.

  11. Apoptosis Induced in The Brain and Liver of Fetuses And Placenta of Irradiated Pregnant Rats Treated With Antacid Containing Aluminum

    International Nuclear Information System (INIS)

    Ramadan, F.L.; Madkour, N.K.

    2012-01-01

    Aluminum (Al) is widely used in antacid medicine which frequently used by pregnant women. It is of great importance to increase the knowledge about its harmful effects on the fetuses. The present study clarified that administration of antacid containing Al and/or exposure to gamma radiation induced maternal and fetal detrimental impact. Pregnant albino rats were administered antacid containing Al on the gestational days 5th, 7th, 9th, 11th, 13th, 15th and 17th at a dose of 4.5 mg/g and exposed to whole body fractionated gamma radiation (2 Gy) at a dose of 0.5 Gy for 4 times on gestational days 6th, 8th, 10th and 12th of pregnancy. Morphological, biochemical and molecular changes were studied. The investigation was carried out one day prior to parturition (the 20th day of gestation). Antacid containing Al and/or radiation induced growth retardation, intrauterine death, malformations and embryonic resorption. The extent of lipid peroxidase formation as well as glutathione content in the brain and liver tissues of rat fetuses and placenta of pregnant rats were used as sensitive parameters to evaluate tissues damage. Antacid containing Al and/or radiation treatment resulted in decreased total protein content in the maternal placenta tissue. Moreover, the elevation in the lipid peroxidase (malondialdehyde; MDA) was accompanied with decline in the glutathione content (GSH) in the brain and liver tissues of rat fetuses. The activity of a key enzyme of apoptosis namely the caspase-3 was analyzed, which its activation represent a point of no return in apoptosis induction. Apoptosis was confirmed by another important hallmark of programmed cell death such as the DNA fragmentation. Treatment with antacid containing Al and/or gamma irradiation significantly increased caspase-3 activity and DNA fragmentation in maternal placental tissue and fetal brain and liver tissues as compared to control animals. In conclusion, the present investigation showed that the deleterious

  12. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    Science.gov (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  13. Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

    Science.gov (United States)

    Burukoglu, Dilek; Baycu, Cengiz; Taplamacioglu, Fulya; Sahin, Erhan; Bektur, Ezgi

    2016-06-01

    Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration. © The Author(s) 2014.

  14. Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats.

    Science.gov (United States)

    Hamza, Alaaeldin A

    2010-01-01

    This study was carried out to evaluate the effect of Moringa oleifera Lam (Moringa) seed extract on liver fibrosis. Liver fibrosis was induced by the oral administration of 20% carbon tetrachloride (CCl(4)), twice weekly and for 8 weeks. Simultaneously, M.oleifera Lam seed extract (1g/kg) was orally administered daily. The biochemical and histological results showed that Moringa reduced liver damage as well as symptoms of liver fibrosis. The administration of Moringa seed extract decreased the CCl(4)-induced elevation of serum aminotransferase activities and globulin level. The elevations of hepatic hydroxyproline content and myeloperoxidase activity were also reduced by Moringa treatment. Furthermore, the immunohistochemical study showed that Moringa markedly reduced the numbers of smooth muscle alpha-actin-positive cells and the accumulation of collagens I and III in liver. Moringa seed extract showed significant inhibitory effect on 1,1-diphenyl-2-picrylhydrazyl free radical, as well as strong reducing antioxidant power. The activity of superoxide dismutase as well as the content of both malondialdehyde and protein carbonyl, which are oxidative stress markers, were reversed after treatment with Moringa. Finally, these results suggested that Moringa seed extract can act against CCl(4)-induced liver injury and fibrosis in rats by a mechanism related to its antioxidant properties, anti-inflammatory effect and its ability to attenuate the hepatic stellate cells activation. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Arsenic induced apoptosis in rat liver following repeated 60 days exposure

    International Nuclear Information System (INIS)

    Bashir, Somia; Sharma, Yukti; Irshad, M.; Nag, T.C.; Tiwari, Monica; Kabra, M.; Dogra, T.D.

    2006-01-01

    Background: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 μM) concentration. Aim: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. Methods: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5 mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. Results: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. Conclusion: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis

  16. Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity

    International Nuclear Information System (INIS)

    Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J.; Marin, Jose J.G.

    2009-01-01

    Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (- 60%) and TCA-stimulated bile flow (- 55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion ( TCA > DHCA > UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin.

  17. Pathological effects of anabolic steroid (Sustanon® on liver of male rats

    Directory of Open Access Journals (Sweden)

    E.R. Al-Kennany

    2014-06-01

    Full Text Available The present pathological study on the male rats aims to investigate the effects on liver tissue induced by repeated administration of three doses of sustanon for four periods. The experiment was done on the 100 adult male rats randomly divided into five groups 20 rats in each group. The first group is considered as a negative control treated with diet and water only. The second group is considered a positive control treated weekly for 60 days with sesame oil intramuscularly while groups III, IV and V treated with diluted sustanon in 5, 10 and 20 mg/kg body weight intramuscularly weekly for 60 days respectively. Blood was collected in a period 15, 30 and 60 days after treatment for measurements liver function tests ALT (alanine aminotransferase and AST (aspartate aminotransferas enzymes. Then the animals were dissected to take samples in a period 15, 30 and 60 days after treatment for histopathological examination, then 5 rats were lefted in each group in the diet and water for 30 days after last treatment for examination the above mentioned parameters. The results revealed the presence of significantly increasing of liver enzyme activation represented by ALT and AST at level P<0.05 compared with control groups. The value of these levels were higher in group V in a day 60 after treatment and its continue to increase even after stopping treatment and remained on diet and water only for 30 days. Pathologically, all treated groups with sustanon revealed gross and histopathological changes in liver tissue, there were enlargement and congestion gross. Histopathologically, the liver sections elucidate cellular swelling, vacuolar degeneration in the cytoplasm of hepatocytes in addition to fatty change and programmed cell death in all groups during a period 15, 30 and 60 days these changes continue even after stopping the treatment for 30 days but portal fibrosis has been observed.It has been concluded from this study that sustanon in concentration 5, 10

  18. Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

    Directory of Open Access Journals (Sweden)

    Daleya Abdulaziz Bardi

    Full Text Available This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg or ELAP (250 or 500 mg/kg. Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed

  19. Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

    Science.gov (United States)

    Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

    2014-01-01

    This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from

  20. Radioprotective effects of Asparagus racemosus extracts against free radical damage in rat liver mitochondria

    International Nuclear Information System (INIS)

    Boloor, K.K.; Kamat, J.P.; Devasagayam, T.P.A.; Venkatachalam, S.R.

    2000-01-01

    The possible antioxidant effect of the extracts of Asparagus racemosus against membrane damage induced by free radicals generated during γ-radiation was examined in rat liver/brain mitochondria. These extracts displayed significant antioxidant properties in mitochondria against oxidation of both lipids and proteins as assessed by lipid peroxidation, protein oxidation and depletion of thiols. The inhibitory effect of the extracts, rich in polysaccharides like galactose, was more than that of the established antioxidants glutathione and ascorbic acid. (author)

  1. [Structural reorganization and change in the lipid composition of rat liver microsomes in chlorophos poisoning].

    Science.gov (United States)

    Boldeskul, A E; Gubskiĭ, Iu I; Mel'nik, A A; Fal'kovskaia, E N

    1993-01-01

    The influence of chlorophos on the endoplasmatic reticulum of rat liver has been studied using the methods of gas-liquid chromatography and fluorescence. Experiments have demonstrated an increase of lysophosphatidylethanolamine, total phospholipids, unsaturated fatty acids (C20:4 n6, C18:1 n11, C18:1 n7) and a decrease of phosphatidylserine and phosphatidylethanolamine. Changes in microviscosity and surface charge were also shown.

  2. The effect of streptozotocin-induced diabetes on phenylalanine hydroxylase expression in rat liver.

    OpenAIRE

    Taylor, D S; Dahl, H H; Mercer, J F; Green, A K; Fisher, M J

    1989-01-01

    The impact of experimentally induced diabetes on the expression of rat liver phenylalanine hydroxylase has been investigated. A significant elevation in maximal enzymic activity was observed in diabetes. This was associated with significant increases in the amount of enzyme, the phenylalanine hydroxylase-specific translational activity of hepatic RNA and the abundance of phenylalanine hydroxylase-specific mRNA. These changes in phenylalanine hydroxylase expression were not observed when diabe...

  3. Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats

    OpenAIRE

    Menon, B. Rajalakshmy; Rathi, M. A.; Thirumoorthi, L.; Gopalakrishnan, V. K.

    2010-01-01

    The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observ...

  4. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage

    OpenAIRE

    Venditti, Paola; Pamplona Gras, Reinald; Ayala, Victoria; Rosa, R. de; Caldarone, G.; Di Meo, S.

    2006-01-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T-3)- or thyroxine (T-4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most ex...

  5. Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation.

    Science.gov (United States)

    Fechter, Laurence D; Nelson-Miller, Alisa; Gearhart, Caroline

    2008-07-01

    Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.

  6. Virtual determination of liver and muscle glycogen obtained from fed rats and from 24-hour fasted rats

    Directory of Open Access Journals (Sweden)

    V.M.T.T. Trindidade et al

    2014-08-01

    Full Text Available Introduction: Glycogen is the storage polysaccharide of animals, composed by glucoseresidues forming a branched polymer. The liver glycogen metabolism and hepaticgluconeogenesis are important buffer systems of blood glucose in different physiological orpathological situations, such as, during a fast period. Fasting muscle glycogenolysis alsooccurs, however, the release of glucose into the bloodstream is negligible because themuscle doesn’t have the enzyme glucose-6-P phosphatase, which is present in the liver.Objectives: This panel presents a learning object, mediated by computer, which simulatesthe determination of liver and muscle glycogen obtained from fed rats and from 24-hourfasted rats Materials and Methods: At first, cartoons were planned in order to show themethodology procedures and biochemical fundamentals. The most representative imageswere selected, edited, organized in a scene menu and inserted into an animationdeveloped with the aid of the Adobe ® Flash 8 software. The validation of this object wasperformed by the students of Biochemistry I (Pharmacy-UFRGS from the secondsemester of 2009 until the second semester of 2013. Results and Discussion: Theanalysis of students' answers revealed that 83% of them attributed the excellence rate tothe navigation program, to the display format and to the learning help. Conclusion:Therefore, this learning object can be considered an adequate teaching resource as wellas an innovative support in the construction of theoretical and practical knowledge ofBiochemistry. Support: SEAD-UFRGSAvailable at: http://www.ufrgs.br/gcoeb/obtencaodosagemglicogenio/

  7. A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

    Science.gov (United States)

    Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

    2010-04-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

  8. A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

    Science.gov (United States)

    Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

    2010-01-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

  9. DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion

    Energy Technology Data Exchange (ETDEWEB)

    Rabes, H.M.; Kerler, R.; Wilhelm, R.

    1983-01-01

    Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of (/sup 14/C)N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O/sub 6/-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O/sub 6/-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.

  10. Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs

    NARCIS (Netherlands)

    TSAI, A. C.; THIE, G. M.; Lin, C. R.

    1977-01-01

    The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was

  11. Cytotoxicity of retinoic acid, menadione and aflatoxin B1 in rat liver slices using netwell inserts as a culture system

    NARCIS (Netherlands)

    Leeman, W.R.; Gevel, I.A. van de; Rutten, A.A.J.J.L.

    1995-01-01

    Precision-cut rat liver slices were used to develop a new dynamic incubation system in which histomorphology and measurement of the release of lactate dehydrogenase (LDH) and the conversion of MTT were applied to evaluate cytotoxicity. Liver slices, precision-cut using a Krumdieck tissue slicer,

  12. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

    NARCIS (Netherlands)

    Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

  13. Expression and Regulation of the Bile Acid Transporter, OST alpha-OST beta in Rat and Human Intestine and Liver

    NARCIS (Netherlands)

    Khan, Ansar A.; Chow, Edwin C. Y.; Porte, Robert J.; Pang, K. Sandy; Groothuis, Geny M. M.

    The regulation of the OST alpha and OST beta expression was studied in the rat jejunum, ileum, colon and liver and in human ileum and liver by ligands for the farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR) and glucocorticoid receptor (GR) using precision cut tissue

  14. Amelioration of lead toxicity on rat liver with Vitamin C and silymarin supplements

    International Nuclear Information System (INIS)

    Shalan, M.G.; Mostafa, M.S.; Hassouna, M.M.; El-Nabi, S.E. Hassab; El-Refaie, A.

    2005-01-01

    The aim of the present study was to investigate the impact of the combined administration of Vitamin C and silymarin on lead toxicity. Male albino rats were subdivided into three groups: the first was a control group, the second received lead acetate in diet as 500 mg/kg diet daily, the third received the same lead acetate dose and supplemented with Vitamin C (1 mg/100 g body weight) and silymarin (1 mg/100 g body weight) by gastric tube three times per week. Blood samples were taken after 2, 4 and 6 weeks of treatment. Significant lead-induced elevations in serum ALT, AST, GGT and ALP activities were observed after different periods of treatment. However, serum LDLc was decreased. The intensities of RNA and apoptotic fragments of DNA were measured as optical density by Gel-pro program. Lead acetate decreased the intensity of DNA at 6 weeks and induced apoptotic DNA fragments reversibly with time. After 2 weeks of lead administration dilation and congestion of terminal hepatic veins and portal vein branches were observed. Lead also induced hepatocyte proliferation without any localized distribution among zones 1-3. Portal inflammatory infiltrate with disruption of the limiting plates (interface hepatitis), steatosis, apoptosis and mild fibrosis were detected especially by sixth week of lead administration. Combined treatment of lead-exposed animals with Vitamin C and silymarin showed marked improvement of the biochemical, molecular and histopathological findings. These experimental results strongly indicate the protective effect of Vitamin C and silymarin against toxic effects of lead on liver tissue

  15. Amelioration of lead toxicity on rat liver with Vitamin C and silymarin supplements.

    Science.gov (United States)

    Shalan, M G; Mostafa, M S; Hassouna, M M; El-Nabi, S E Hassab; El-Refaie, A

    2005-01-05

    The aim of the present study was to investigate the impact of the combined administration of Vitamin C and silymarin on lead toxicity. Male albino rats were subdivided into three groups: the first was a control group, the second received lead acetate in diet as 500 mg/kg diet daily, the third received the same lead acetate dose and supplemented with Vitamin C (1 mg/100g body weight) and silymarin (1 mg/100g body weight) by gastric tube three times per week. Blood samples were taken after 2, 4 and 6 weeks of treatment. Significant lead-induced elevations in serum ALT, AST, GGT and ALP activities were observed after different periods of treatment. However, serum LDLc was decreased. The intensities of RNA and apoptotic fragments of DNA were measured as optical density by Gel-pro program. Lead acetate decreased the intensity of DNA at 6 weeks and induced apoptotic DNA fragments reversibly with time. After 2 weeks of lead administration dilation and congestion of terminal hepatic veins and portal vein branches were observed. Lead also induced hepatocyte proliferation without any localized distribution among zones 1-3. Portal inflammatory infiltrate with disruption of the limiting plates (interface hepatitis), steatosis, apoptosis and mild fibrosis were detected especially by sixth week of lead administration. Combined treatment of lead-exposed animals with Vitamin C and silymarin showed marked improvement of the biochemical, molecular and histopathological findings. These experimental results strongly indicate the protective effect of Vitamin C and silymarin against toxic effects of lead on liver tissue.

  16. Analysis of purified gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and tandem mass spectrometry.

    Science.gov (United States)

    Fairburn, B; Muthana, M; Hopkinson, K; Slack, L K; Mirza, S; Georgiou, A S; Espigares, E; Wong, C; Pockley, A G

    2006-09-01

    The stress protein gp96 exhibits a number of immunological activities, the majority of studies into which have used gp96 purified from a variety of tissues. On the basis of 1-D gel electrophoresis, the purity of these preparations has been reported to range between 70% and 99%. This study analyzed gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and liquid chromatography electrospray ionization tandem mass spectrometry (MS-MS). The procedure for purifying gp96 was reproducible, as similar protein profiles were observed in replicate gels of gp96 preparations. The purity of the preparations was typically around 70%, with minor co-purified proteins of varying molecular weights and mobilities being present. Dominant bands at 95-100 kDa in preparations from Wistar rats and C57BL/6 mice were identified as gp96 by ECL Western blotting. Multiple bands having similar, yet distinct molecular weights and differing pI mobility on ECL Western blots were confirmed as being gp96 in preparations from Wistar rats using MS-MS. The most striking feature of the 2-D gel analysis was the presence of additional dominant bands at 55 kDa in preparations from Wistar rats, and at 75-90 kDa in preparations from C57BL/6 mice. These were identified as gp96 by ECL Western blotting and, in the case of preparations from Wistar rats, by MS-MS. Although the lower molecular weight, gp96-related molecules might be partially degraded gp96, their reproducible presence, definition and characteristics suggest that they are alternative, species-specific isoforms of the molecule. A 55 kDa protein which exhibited a lower pI value than gp96 was present in all preparations and this was identified as calreticulin, another putative immunoregulatory molecule. This study confirms the reproducibility of the gp96 purification protocol and reveals the presence of multiple gp96 isoforms, some of which likely result from post-translational modifications such as differential glycosylation and

  17. Determination of boron distribution in rat's brain, kidney and liver

    Energy Technology Data Exchange (ETDEWEB)

    Pazirandeh, Ali [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Science and Technology Research Center, AEOI, Tehran (Iran, Islamic Republic of)], E-mail: paziran@khayam.ut.ac.ir; Jameie, Behnam [Neuroscience Lab, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Zargar, Maysam [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2009-07-15

    To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney.

  18. Potency of carcinogens derived from covalent DNA binding and stimulation of DNA synthesis in rat liver

    International Nuclear Information System (INIS)

    Lutz, W.K.; Buesser, M.T.; Sagelsdorff, P.

    1984-01-01

    In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrachloride (all known to be genotoxic via DNA binding) did not affect cell division, whereas several hepatocarcinogens known not to bind to DNA (alpha-HCH, clofibrate, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) gave rise to a dose-dependent stimulation of liver DNA synthesis within 24 h. An equation combining the influences of mitotic stimulation, expressed as dose required to double the control level of DNA synthesis, and DNA binding potency, expressed as the Covalent Binding Index, correlated well with the carcinogenic potency for both classes of hepatocarcinogens

  19. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    Science.gov (United States)

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  20. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

    2013-01-01

    -specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...

  1. Glutathione delays varies as-tocopherol oxidation and subsequent lipid peroxidation in rat liver microsomes

    International Nuclear Information System (INIS)

    Robey, S.; Mavis, R.

    1986-01-01

    A method has been developed for in vitro trace radiolabeling of rat liver microsomes with 3 H-α-tocopherol (αT*) which allows virtually complete oxidation of the αT* under oxidizing conditions. The supernatant of a 16,000 xg centrifugation of homogenized rat liver, containing the cytosolic rat liver vitamin E (VE) transfer protein, was incubated with an ethanolic solution of αT* for 10 minutes at 37 0 C. Labeled microsomes were collected in the washed 100,000 xg pellet. Microsomes were then incubated with 30 μM Fe 2+ in an NADPH-generating system, and both production of malondialdehyde (MDA) (a product of lipid peroxidation) and oxidation of αT* were monitored over a time course in the presence and absence of glutathione (GSH). The results indicate virtually complete oxidation of αT* precedes significant membrane lipid peroxidation, and that addition of 5 mM GSH delays both αT* oxidation and subsequent MDA production. This suggests that the previously observed VE-dependent heat labile inhibition of microsomal lipid peroxidation by GSH involves maintaining membrane levels of α-tocopherol

  2. Effect of Electromagnetic Waves Generated by Base Transiver Station on Liver Enzymes in Female Rats

    Directory of Open Access Journals (Sweden)

    Gholam-Ali Jelodar

    2013-07-01

    Full Text Available Background: This study was investigating the effect of electromagnetic wave generated by mobile and base transceiver station (900 MHz on liver enzymes in both mature and immature female age.Materials and Methods: In this study, 20 rats Sprague Dawley white mature female age 8 to 9 weeks and weight 180 to 200 g and 20 rats immature age 3 to 4 weeks, weight 80 to 100 g, each age group were randomly divided in two groups (control and test. Test groups, were daily for four hours and four different times exposed to electromagnetic waves with signal generator (900 MHz, 5-meter intervals. Control groups were kept at equal condition (themperature and light in laboratory during experiment. After at the end experimental period, blood was collected by heart puncture of all animal. Exposure to EMF generated by BTS had significant effect on liver enzymes composition in mature and immature rats.Results: AST, ALT and ALP in immature-test groups decreased significantly compared with their respective control groups (p<0.05. ALP in mature-test groups increased significantly compared with their respective control groups (p<0.05.Conclusion: These result suggest that exposure to EMF generated by BTS has a deleterious effect on liver enzymes and that this effect is more sever in immature animals.

  3. Protective effect of Sida cordata leaf extract against CCl(4) induced acute liver toxicity in rats.

    Science.gov (United States)

    Mistry, Sunil; Dutt, K R; Jena, J

    2013-04-13

    To investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim. Wister albino rats were divided into 6 groups: Group I served as control; Group II served as hepatotoxic (CCl(4) treated) group; Group III, IV and V served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group VI served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies. Obtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl4 induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies. The results of this study strongly indicate the protective effect of SCLE against CCl(4) induced acute liver toxicity in rats and thereby scientifically support its traditional use. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  4. Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

    Science.gov (United States)

    Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa

    2014-10-01

    The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.

  5. Cytogenetic changes in the liver of progeny of irradiated male rats

    Energy Technology Data Exchange (ETDEWEB)

    Kropacova, K.; Slovinska, L.; Misurova, E. [P.J. Safarik Univ., Kosice (Slovakia)

    2002-06-01

    The transgenerational transmission of radiation damage of rat genom was studied on the basis of cytogenetic changes in somatic cells (hepatocytes). It was found, that the irradiation of rat males with dose of 3 Gy of gamma radiation caused latent cytogenetic damage to the liver, which was expressed during the course of an induced proliferation of hepatocytes (by partial hepatectomy) by lower proliferative activity and a high frequency of chromosomal aberrations. In the progeny of irradiated males (in the F{sub 1} generation), the radiation damage to DNA was manifested by similar changes, i.e. by lower proliferation activity and increase in ''spontaneous'' chromosomal aberration occurrence in liver regeneration after partial hepatectomy. Irradiating the progeny of irradiated males (the total radiation load of the progeny being 3 Gy+3 Gy) caused slighter changes in compared with irradiating the progeny of non-irradiated control males (the total radiation load of the progeny being 0 Gy+3 Gy), which suggests some kind of adaptive response, which was also found in other experimental systems and parameters. An analogous course of RNA and DNA quantitative changes in the liver of the F{sub 0} and F{sub 1} generations of rats confirms the partial transmission of radiation damage of genom to the progeny. (author)

  6. Subchronic exposure to high-dose ACE-inhibitor moexipril induces catalase activity in rat liver.

    Science.gov (United States)

    Adeghate, E; Hasan, M Y; Ponery, A S; Nurulain, S M; Petroianu, G A

    2005-12-01

    The long-term clinical effects of ACE-inhibitors have similarities with those of both fibrates and glitazones, activators of peroxisome proliferator activator receptor (PPAR) alpha and gamma, respectively. The antioxidant enzyme catalase, a heme protein that degrades hydrogen peroxide, is found at high concentrations in peroxisomes. Catalase activity is one of the recognized surrogate markers indicative of PPAR activation in the rat liver. The purpose of the study was to establish the effect of moexipril on catalase activity and to compare it with the effect of both saline controls and that of the known PPAR agonist clofibrate (positive control). Three groups of seven rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day break. The cycle was repeated eight times. After the final cycle (day 56) the animals were sacrificed and liver tissue collected. The number of catalase positive cells in both moexipril group (95% CI 57-61) and clofibrate group (95% CI 72-80) is higher than in controls (95% CI 3-16) (p catalase positive cells in the clofibrate group is higher than in the moexipril group (p inhibitor moexipril induces catalase activity in the rat liver to an extent comparable to fibrates. We suggest that some of the long-term advantages of ACE inhibitor use - beyond mere BP lowering - might be due to a PPAR mediated effect.

  7. Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats.

    Science.gov (United States)

    Oguz, Serhat; Kanter, Mehmet; Erboga, Mustafa; Ibis, Cem

    2013-10-01

    The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL + received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.

  8. Use of 2-octyl cyanoacrylate adhesive in rat liver induced lesion.

    Science.gov (United States)

    Santos, Orlando José dos; Marques, Giancarlo de Souza; Sauaia Filho, Euler Nicolau; Frota, Gustavo Medeiros; Santos, Rayan Haquim Pinheiro; Santos, Rennan Abud Pinheiro

    2012-09-01

    To evaluate the healing process of rat traumatic liver lesion corrected with the use of 2-octyl cyanoacrylate adhesive, compared to the use of biologically absorbable chromed catgut thread suture. Thirty mail adult rats were divided into two groups (15 per group) according to the used method for liver lesion correction as follows: adhesive group (AG), and catgut group (CG); each group being divided into three subsets of five animals (7th, 14th, and 21st day), respectively, according to post-surgery evaluation. All animals were submitted to homogeneous lesion applying synthetic bonding to AG and using chromed catgut suture to CG for lesion correction. Macroscopic and microscopic parameters of healing processes were evaluated. Both groups of animals showed excellent abdominal wall healing, with no evidence of infection, and no abdominal cavity peritonitis or abscess. The presence of adherence was observed in both groups with no statistically significant difference. As to macroscopic evaluation, there was statistically significant difference with respect to specific factors of clinical inflammation (ischemic inflammation and giant celular inflammatory reaction) between animals evaluated on the 10th day (ischemic necrosis and giant cellular inflammatory reaction) among animals evaluated on the 14th day (A14 versus C14). Applying 2-octyl-cyanoacrylate adhesive for correcting rat liver lesion does not change healing process when compared to the use of chromed catgut stitch.

  9. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

    Science.gov (United States)

    Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

    2006-03-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

  10. MOLECULAR MECHANISMS THAT LEAD TO CHOLANGIOCARCINOMA, DURING CHRONIC INFECTION OF LIVER FLUKES

    Directory of Open Access Journals (Sweden)

    A. O. Bogdanov

    2015-01-01

    Full Text Available Cholangiocarcinoma is a malignant tumor, characterized by poor prognosis and a low five-year survival rate. There is a clear correlation between the incidence of opisthorchiasis and high incidence of cholangiocarcinoma in South-East Asia. Liver flukes Clonorchis sinensis and Opisthorchis viverrini are I class carcinogens. There are some endemic regions of opisthorchiasis In the Russian Federation. The most important factor that leads to carcinogenesis during liver fluke infection is chronic inflammation. This review article focuses on the communication of chronic inflammation caused by invasion of liver flukes and cholangiocarcinoma. This paper summarizes the current knowledge about the risk factors for cholangiocarcinoma, as well as knowledge about the molecular aspects of the induction of carcinogenesis by liver flukes.

  11. Glomerular sieving of high molecular weight proteins in proteinuric rats

    International Nuclear Information System (INIS)

    Bertolatus, J.A.; Abuyousef, M.; Hunsicker, L.G.

    1987-01-01

    To characterize the permeability of the glomerular capillary wall to high molecular weight proteins in normal and proteinuric rats, we determined the glomerular sieving coefficients (GSC) of radioiodinated marker proteins of known size and charge by means of a paired label, tissue accumulation method previously validated in this laboratory. In one group of rats (Series A) the GSCs of 125 I-anionic IgG (aIgG-molecular weight [mol wt] 150,000, pI 4.9) and 131 I-neutral IgG (nIgG-pI 7.4 to 7.6) were measured simultaneously. In Series B, the GSC of a second anionic marker, 131 I-human ceruloplasmin (Crp-mol wt 137,000, pI 4.9) was compared to that of 125 I-nIgG. As in the previous report, the labeled proteins were not degraded or deiodinated during the 20 minute clearance period for GSC determination. Within Series A and B, three subgroups of rats were studied: control saline-infused rats, rats made acutely proteinuric by infusion of the polycation hexadimethrine (HDM), and rats with chronic doxorubicin (Adriamycin-Adria) nephrosis. In the control rats, GSCs for the anionic markers aIgG (Series A) or Crp (Series B) were significantly greater than that of nIgG (both series). These large proteins crossed the filtration barrier by a different pathway from that available to smaller neutral molecules the size of albumin, which in our previous study had a much higher GSC than a native, anionic albumin marker. In a third group of control rats only (Series C), the GSCs of native anionic bovine albumin (BSA) and nIgG were compared directly. The GSC of BSA (0.0029) was only slightly larger than the GSC of nIgG (0.0025), indicating that most of the native albumin crosses the glomerular capillary wall via a nonselective pathway similar to that available to nIgG. The results in the control groups are compatible with recently-described heteroporous models of glomerular size selectivity

  12. Study on bone marrow mesenchymal stem cells in repairing of radiation induced acute liver injury of rats

    International Nuclear Information System (INIS)

    Bao Yongxing; Lou Fan; Zhao Huarong; Zhu Huhu; Ma Yan; Wen Hao

    2010-01-01

    Objective: To investigate the role of mesenchymal stem cells in the repair of radiation induced liver injury. Methods: 12 female SD rats were irradiated with 20 Gy 6 MV X-rays on the right lobe of the liver, to establish the model of radiation induced liver injury. The rats were divided randomly into two groups as invention group and control group, and transplanted with 1 ml male mesenchymal suspension or 1 ml normal saline in 4 hours after radiotherapy. The morphological changes of liver were observed. The existence of sex determining gene Y(SRY) and the level of alpha-smooth muscle actin (a-SMA) were detected. Results: Some injury of right lobe liver in two groups were observed, and the injury degree of right lobe liver in intervention group were lower than that of control group. The amount of SRY positive cells in the right lobe liver of intervention group was higher than that in the left lobe liver (t = 3.77, P <0.05). The positive expression rate of a-SMA in right lobe liver of intervention group was lower than that of control group. Conclusions: Acute radiation induced liver injury could lead BMSCs' homing in order to decrease the degree of liver fibrosis. (authors)

  13. Effect of the aqueous extract of Psidium guajava on erythromycin-induced liver damage in rats.

    Science.gov (United States)

    Sambo, N; Garba, S H; Timothy, H

    2009-12-01

    The effect of Psidium guajava extract on erythromycin-induced liver damage in albino rats was investigated using 30 normal rats grouped into six. Group I and II served as the normal and treatment controls that were administered with normal saline and 100 mg/kg body weight of erythromycin stearate daily for 14 days respectively. Rats in group III were administered 450 mg/kg body weight of Psidium guajava only for 7 days while rats in groups IV, V and VI were administered Psidium guajava extract for 7 days and 100mg/kg body weight of erythromycin for 14 days. Histopathological investigation of the liver tissues revealed striking oedema and mild periportal mononuclear cell infiltration of hepatic cords in the liver of rats administered 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract. Pretreatment with 150 mg/kg of Psidium guajava extract showed a slight degree of protection against the induced hepatic injury caused by 100 mg/kg of erythromycin stearate. Biochemical analysis of the serum obtained revealed a significant increase in serum levels of hepatic enzymes measured in the groups administered with 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract compared to the control groups and those pretreated with 150 mg/kg of Psidium guajava extract. This study has shown that the aqueous extract of psidium guajava leaf possesses hepatoprotective property at lower dose and a hepatotoxic property at higher dose but further studies with prolonged duration is recommended.

  14. Subcellular distribution of apolipoprotein E along the lipoprotein synthetic pathway of rat liver

    International Nuclear Information System (INIS)

    Cole, T.G.; Stockhausen, D.C.

    1986-01-01

    Apolipoprotein E (apoE) is synthesized by the liver and is secreted as a component of VLDL. To define the intracellular locations of apoE, liver from 10 nonfasted male rats were removed and subcellular organelles prepared by differential pelleting through sucrose gradients. Mass of apoE was measured by radioimmunoassay. Approximately 10% of total hepatic apoE was recovered in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER) and Golgi fractions. Concentrations of apoE (ng/mg protein) were: homogenate, 302 +/- 59; RER, 653 +/- 251; SER, 1250 +/- 471; Golgi, 11,044 +/- 4291. Total apoE content of each reaction (μg/organelle) was: homogenate (whole liver), 517 +/- 103; RER, 15 +/- 3; SER, 9 +/- 3; Golgi, 28 +/- 8. These data indicate that along the putative pathway of lipoprotein synthesis (RER->SER->Golgi), apoE concentration increases in each successive organelle and that flux of apoE is apparently most rapid through SER. Furthermore, the majority of apoE in the rat liver is apparently not directly associated with the lipoprotein synthetic pathway and may be associated with internalized lipoproteins or may be involved in non-lipoprotein related functions

  15. Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats.

    Science.gov (United States)

    Young, Shun-Chieh; Wang, Chau-Jong; Lin, Jing-Jing; Peng, Pei-Ling; Hsu, Jui-Ling; Chou, Fen-Pi

    2007-01-01

    Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.

  16. Autoserum: An Optimal Supplement for Bone Marrow Mesenchymal Stem Cells of Liver-Injured Rats

    Directory of Open Access Journals (Sweden)

    Qinglin Zhang

    2015-01-01

    Full Text Available Mesenchymal stem cells (MSCs are an attractive source for the clinical cell therapy of liver injury. Although the use of adult serum, platelet lysate, or cord blood serum solves some of the problems caused by fetal bovine serum (FBS, the allogeneic immune response, contamination, and donor-to-donor and donor-to-receptor differences still obstruct the application of MSCs. In this study, the influences of autoserum from liver-injured rats (LIRs and allogeneic serum from healthy rats on the isolation and culture of bone marrow MSCs (BMSCs were examined and compared to FBS. The results showed that BMSCs cultured with autoserum or allogeneic serum exhibited better MSC-specific morphology, lower rate of cell senescent, and higher proliferation kinetics than those with FBS. In addition, autoserum promoted the osteogenic differentiation potential of BMSCs as allogeneic serum did. Although there were no significant differences in proliferation activity, immunophenotypic characterization, and differentiation potential between BMSCs cultured with autoserum and those with allogeneic serum, the potential adverse immunological reactions in patients with allogeneic material transplantation must be considered. We therefore believe that the autoserum from liver-injured patients may be a better choice for MSC expansion to meet the needs of liver injury therapy.

  17. Growth hormone increases and maturation decreases glutamine synthetase turnover rate in rat liver

    International Nuclear Information System (INIS)

    Lin, C.K.

    1985-01-01

    An investigation was made of the effect of hypophysectomy and growth hormone (GH) replacement regimen (1 mg/100 g twice daily for 30 days); and maturation (from 25 up to 90 days) on the liver and brain glutamine synthetase (GS) mass and turnover rates in rats. The first order decay rate of enzyme 14 C radioactivity was determined between 1 and 4 days to obtain the half-life (T/sub 1/2/) of GS. The hepatic GS mass was determined by immunoassay. GS turnover (GS/sub s/) was calculated from T/sub 1/2/ and the GS mass (i.e., K = 0.693/T/sub 1/2/; GS/sub s/ = K x GS mass). It was concluded that: (1) GS specific activity is not decreased by hypophysectomy or increased by GH. These results suggested that observed endocrine induced changes in GS are due to changes in GS mass. (2) The liver GS turnover rate is significantly reduced by hypophysectomy and increased by GH replacement. It was proposed that GH specifically enhances synthesis of GS in the liver. (3) Maturation (25, 40, 60, and 90 days) decreases GS turnover rate in both liver and brain of normal rats. This similar effect of maturation suggests that the observed age induced decline in GS turnover rate is not related to GH in all tissues

  18. Hepatoprotective Effect of Trigona spp. Bee Propolis against Carbon Tetrachloride-Induced Liver Injury in Rat

    Directory of Open Access Journals (Sweden)

    Rachel Amelia

    2016-06-01

    Full Text Available Background: Oxidative stress reaction can cause liver injury. This process can be prevented by antioxidant activities which can break the destructive chain caused by free radical substances in the liver. Propolis produced by Trigona spp. bee is known to have a high level of antioxidant. The aim of this study was to examine the effect of Trigona spp. bee propolis on liver histological toxicity caused by carbon tetrachloride-induced oxidative stress. Methods:This experimental study was conducted in September 2013 at the Animal Laboratory of Departement of Pharmacology and Therapy, Faculty of Medicine Universitas Padjadjaran. Twenty-four healthy male Wistar rats as objects were adapted for one week and randomly divided into 3 groups. Group I was the control negative, group II was given carbon tetrachloride on day 14, group III was given Trigona spp. bee propolis on day 1-14. On day 14, group III was injected CCl4 intraperitoneally. The quantitative data were statistically analyzed using the one way ANOVA and Tukey test with p value < 0.05. Results: Group I showed the liver contained normal cells, without significant injury of the membrane, round and complete nucleus. The average number of liver cell was 464 ± 9.59281 cells/field; group II underwent necrosis and the average of the cells was 146 ± 7.56885 cells/field; group III showed some normal liver cells, and some necrotic area with the normal liver cells average was 263 ± 14.10860 cells/field. The p-value=0.00. Conclusions: Trigona spp. bee propolis has a hepatoprotective effect against CCl4-induced liver injury histologically.

  19. Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats

    Directory of Open Access Journals (Sweden)

    Sayed M. Mizar

    2015-03-01

    Full Text Available Oxidative stress plays a key role in the pathogenesis of hepatic ischemia/reperfusion (I/R-induced injury, one of the leading causes of liver damage post-surgical intervention, trauma and transplantation. This study aimed to evaluate the protective effect of nebivolol and chrysin against I/R-induced liver injury via their vasodilator and antioxidant effects, respectively. Adult male Wister rats received nebivolol (5 mg/kg and/or chrysin (25 mg/kg by oral gavage daily for one week then subjected to ischemia via clamping the portal triad for 30 min then reperfusion for 30 min. Liver function enzymes, alanine transaminase (ALT and aspartate transaminase (AST, as well as hepatic Myeloperoxidase (MPO, total nitrate (NOx, glutathione (GSH and liver malondialdehyde (MDA were measured at the end of the experiment. Liver tissue damage was examined by histopathology. In addition, the expression levels of nitric oxide synthase (NOS subtypes, endothelial (eNOS and inducible (iNOS in liver samples were assessed by Western blotting and confirmed by immunohistochemical analysis. Both chrysin and nebivolol significantly counteracted I/R-induced oxidative stress and tissue damage biomarkers. The combination of these agents caused additive liver protective effect against I/R-induced damage via the up regulation of nitric oxide expression and the suppression of oxidative stress. Chrysin and nebivolol combination showed a promising protective effect against I/R-induced liver injury, at least in part, via decreasing oxidative stress and increasing nitric oxide levels.

  20. Mass spectrometric identification of molecular species of phosphatidylcholine and lysophosphatidycholine extracted from shark liver

    NARCIS (Netherlands)

    Chen, S.; Li, K.W.

    2007-01-01

    The profile and structural characterization of molecular species of phosphatidylcholine (PC) and lysophosphatidylcholine (LysoPC) from shark liver using liquid chromatographic/electrospray ionization mass spectrometry (LC-ESI/MS) and tandem mass spectrometry (MS/MS) are described for the first time

  1. Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

    Science.gov (United States)

    Marcos, Ricardo; Correia-Gomes, Carla

    2016-12-01

    Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

  2. Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats.

    Science.gov (United States)

    Chen, Tao; Hutts, Robert C; Mei, Nan; Liu, Xiaoli; Bishop, Michelle E; Shelton, Sharon; Manjanatha, Mugimane G; Aidoo, Anane

    2005-06-01

    A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.

  3. Physiological covalent regulation of rat liver branched-chain a