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Sample records for regenerating rat liver

  1. Chronological protein synthesis in regenerating rat liver.

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    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.

  2. 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

  3. 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...

  4. 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)

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

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    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

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

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    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.

  7. 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.

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

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    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.

  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. Liver regeneration

    NARCIS (Netherlands)

    Chamuleau, R. A.; Bosman, D. K.

    1988-01-01

    Despite great advances in analysing hemodynamic, morphological and biochemical changes during the process of liver regeneration, the exact (patho)physiological mechanism is still unknown. A short survey of literature is given of the kinetics of liver regeneration and the significance of different

  11. 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...

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

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    Betina Norman Jepsen

    2015-12-01

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

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

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    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.)

  14. 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...

  15. Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

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    Mesut Sipahi

    2015-01-01

    Full Text Available Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations.

  16. Expression of isgylation related genes in regenerating rat liver

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    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.

  17. Restoration of CpG Methylation in The Egf Promoter Region during Rat Liver Regeneration

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    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

  18. 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)

  19. 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.

  20. Nuclear medicine study of regeneration process of the liver after partial hepatectomy in normal rats

    International Nuclear Information System (INIS)

    Nomura, Yasushi

    1990-01-01

    To evaluate regeneration of the liver in rats after partial hepatectomy based on Higgins' and Anderson's method, the present study reports using the morphological and radionuclide technique. The adult Wistar rats over 8 weeks of age were prepared in this study and were injected intravenously with either 99m Tc-N-(2,6 dimethylphenylcarbamoylmethyl) iminodiacetic acid ( 99m Tc-HIDA) or 99m Tc-phytate. Using Fishback equation, the ratio of wet weight liver regeneration was approximately 80% at 14 days after partial hepatectomy. On pathology, the microscopical findings were as follows: congestion and hepatocytes swelling on day 1; diffuse fat deposition and nuclear division on day 2; decreased hepatocytes swelling, fat deposition, and regular alignment of the hepatocytes on day 5; appearance of normal liver on day 7-14. The uptake and excretion ratio of the hepatocytes using 99m Tc-HIDA as a radionuclide technique recovered to the value prior to partial hepatectomy on day 3, and also the hepatic accumulation coefficient of Kupffer cells using 99m Tc-phytate recoverd on day 4. In conclusion, it was found that the functional recovery employed 3-4 days after partial hepatectomy. The present study using two radiopharmaceuticals describes that the radionuclide techniques can facilitate to evaluate the manifest pathological alterations of hepatocytes and Kupffer cells after partial hepatectomy. (author)

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

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    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.

  2. Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

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    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.

  3. TRANEXAMIC ACID ACTION ON LIVER REGENERATION AFTER PARTIAL HEPATECTOMY: EXPERIMENTAL MODEL IN RATS.

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    Sobral, Felipe Antonio; Daga, Henrique; Rasera, Henrique Nogueira; Pinheiro, Matheus da Rocha; Cella, Igor Furlan; Morais, Igor Henrique; Marques, Luciana de Oliveira; Collaço, Luiz Martins

    2016-01-01

    Different lesions may affect the liver resulting in harmful stimuli. Some therapeutic procedures to treat those injuries depend on liver regeneration to increase functional capacity of this organ. Evaluate the effects of tranexamic acid on liver regeneration after partial hepatectomy in rats. 40 rats (Rattus norvegicus albinus, Rodentia mammalia) of Wistar-UP lineage were randomly divided into two groups named control (CT) and tranexamic acid (ATX), with 20 rats in each. Both groups were subdivided, according to liver regeneration time of 32 h or seven days after the rats had been operated. The organ regeneration was evaluated through weight and histology, stained with HE and PCNA. The average animal weight of ATX and CT 7 days groups before surgery were 411.2 g and 432.7 g, and 371.3 g and 392.9 g after the regeneration time, respectively. The average number of mitotic cells stained with HE for the ATX and CT 7 days groups were 33.7 and 32.6 mitosis, and 14.5 and 14.9 for the ATX and CT 32 h groups, respectively. When stained with proliferating cell nuclear antigen, the numbers of mitotic cells counted were 849.7 for the ATX 7 days, 301.8 for the CT 7 days groups, 814.2 for the ATX 32 hand 848.1 for the CT 32 h groups. Tranexamic acid was effective in liver regeneration, but in longer period after partial hepatectomy. Muitas são as injúrias que acometem o fígado e levam a estímulo lesivo. Alguns procedimentos terapêuticos para tratamento dessas lesões dependem da regeneração hepática para aumentar a sua capacidade funcional. Avaliar o efeito do ácido tranexâmico na regeneração hepática após hepatectomia parcial em ratos. Foram utilizados 40 ratos (Rattus norvegicus albinus, Rodentia mammalia) convencionais da linhagem Wistar-UP. Foram divididos aleatoriamente em dois grupos de 20: grupo controle (CT) e grupo ácido tranexâmico (ATX). Cada um deles foi divido em dois subgrupos para avaliar a regeneração hepática no tempo de 32 h e 7 dias do p

  4. Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

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    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

  5. The combined effect of erythropoietin and granulocyte macrophage colony stimulating factor on liver regeneration after major hepatectomy in rats

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    Frangou Matrona

    2010-07-01

    Full Text Available Abstract Background The liver presents a remarkable capacity for regeneration after hepatectomy but the exact mechanisms and mediators involved are not yet fully clarified. Erythropoietin (EPO and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF have been shown to promote liver regeneration after major hepatectomy. Aim of this experimental study is to compare the impact of exogenous administration of EPO, GM-CSF, as well as their combination on the promotion of liver regeneration after major hepatectomy. Methods Wistar rats were submitted to 70% major hepatectomy. The animals were assigned to 4 experimental groups: a control group (n = 21 that received normal saline, an EPO group (n = 21, that received EPO 500 IU/kg, a GM-CSF group (n = 21 that received 20 mcg/kg of GM-CSF and a EPO+GMCSF group (n = 21 which received a combination of the above. Seven animals of each group were killed on the 1st, 3rd and 7th postoperative day and their remnant liver was removed to evaluate liver regeneration by immunochemistry for PCNA and Ki 67. Results Our data suggest that EPO and GM-CSF increases liver regeneration following major hepatectomy when administered perioperatively. EPO has a more significant effect than GM-CSF (p Conclusion EPO, GM-CSF and their combination enhance liver regeneration after hepatectomy in rats when administered perioperatively. However their combination has a weaker effect on liver regeneration compared to EPO alone. Further investigation is needed to assess the exact mechanisms that mediate this finding.

  6. 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.

  7. Effect of Picibanil (OK 432) on the Scavenging Effect of Free Radicals Produced during Liver Regeneration in the Rat

    OpenAIRE

    Okamoto, Ko; Hamazaki, Keisuke; Iwagaki, Hiromi; Orita, Kunzo; Mori, Akitane

    1995-01-01

    We administered a biological response modifier Picibanil (OK-432), attenuated Streptococcus pyogenes, via the dorsal vein of the penis after 70% hepatectomy in rats, and clarified the scavenging effect of Picibanil on free radicals generated in the regenerating liver. A group of 5 rats was intravenously administered with 25 KE/kg of OK-432 after hepatectomy, while the control group was given saline after hepatectomy. Serum levels of aspartate aminotransferase and alanine aminotransferase and ...

  8. 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....

  9. The nuclear pore density in rat liver cells upon regeneration and total body X-ray irradiation

    International Nuclear Information System (INIS)

    Kuz'mina, S.N.; Troitskaya, L.P.; Mirkhamidova, P.A.; Bul'dyaeva, T.V.; Zbarskij, I.B.; Grigor'ev, V.B.; Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Virusologii)

    1979-01-01

    The nuclear pore density has been investigated in rat liver cells in the course of regeneration and X-ray irradiation. It has been found that the number of pore complexes (PC) per nuclear shell (NS) unit area in the liver cells is not constant. In an hour following whole-body irradiation of rats with a regenerating liver at the 1200 R dose the number of PC per 1 μm 2 of the nuclear shell area decreases by 5, 8 times as compared with the PC density in the regenerating liver cells of the irradiated rats, the PC degradation and structural rupture being observed. It has been established by means of the freezing-etching method which enables PC surfaces observation as for cytoplasma as well as for nucleoplasma that the PC peripheral granulas and the central granula consist of subparticles being approximately of the same size. The central granula forms a channel through which the material containing RNA passes from the nucleus to the cytoplasma. On the basis of the fact that the treatement by Triton X-100, disarranging the integrity of the NS membranous structure, preserves PC in relation to the fibrous layer as well as on the basis of the unequal nuclear pore state observed on the platinum-carbon replicas from nuclei splits it is supposed that PC can be formed in the nucleus and then in the course of repening ''built in'' PS

  10. The yield of genome mutations in cells of intact and regenerating rat liver in normal conditions and after γ-irradiation

    International Nuclear Information System (INIS)

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

    1984-01-01

    A comparative study was made of spontaneus and induced polyploidy in cells of resting and regenerating rat liver. Polyploidy was shown to play a major role in the ontogenesis and during regeneration after partial hepatectomy. An essential difference was revealed in the radiation response of cells of intact and regenerating liver with respect to the yield of polyploid cells. This distinction was referped to different effectiveness of the processes of repair and fixation of radiation damages in the actively proliferating and resting cells

  11. Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compared to dietary fat

    International Nuclear Information System (INIS)

    Tanoue, Shirou; Uto, Hirofumi; Kumamoto, Ryo; Arima, Shiho; Hashimoto, Shinichi; Nasu, Yuichiro; Takami, Yoichiro; Moriuchi, Akihiro; Sakiyama, Toshio; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

    2011-01-01

    Highlights: → Hepatic steatosis in rats fed a high fructose diet was less severe than that in rats fed a high fat diet. → Liver regeneration was more impaired in rats fed a high fructose diet than in rats fed a high fat diet. → Dysregulation of genes associated with metabolism may contribute to impairment of liver regeneration. → Regulation of the TGF-β1 level after partial hepatectomy may be impaired in rats fed a high fructose diet. -- Abstract: Hepatic steatosis (HS) has a negative effect on liver regeneration, but different pathophysiologies of HS may lead to different outcomes. Male Sprague-Dawley rats were fed a high fructose (66% fructose; H-fruc), high fat (54% fat; H-fat), or control chow diet for 4 weeks. Based on hepatic triglyceride content and oil red O staining, HS developed in the H-fruc group, but was less severe compared to the H-fat group. Hepatic mRNA expression levels of fatty acid synthase and fructokinase were increased and those of carnitine palmitoyltransferase-1 and peroxisome proliferator-activated receptor-α were decreased in the H-fruc group compared to the H-fat group. Liver regeneration after 70% partial hepatectomy (PHx) was evaluated by measuring the increase in postoperative liver mass and PCNA-positive hepatocytes, and was impaired in the H-fruc group compared to the H-fat and control groups on days 3 and 7. Serum levels of tumor necrosis factor-α, interleukin-6 and hepatocyte growth factor did not change significantly after PHx. In contrast, serum TGF-β1 levels were slightly but significantly lower in the control group on day 1 and in the H-fat group on day 3 compared to the level in each group on day 0, and then gradually increased. However, the serum TGF-β1 level did not change after PHx in the H-fruc group. These results indicate that impairment of liver regeneration after PHx in HS is related to the cause, rather than the degree, of steatosis. This difference may result from altered metabolic gene expression

  12. Liver regeneration after partial hepatectomy in rat is more impaired in a steatotic liver induced by dietary fructose compared to dietary fat

    Energy Technology Data Exchange (ETDEWEB)

    Tanoue, Shirou [Department of Digestive and Lifestyle-Related Diseases, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Uto, Hirofumi, E-mail: hirouto@m2.kufm.kagoshima-u.ac.jp [Department of Digestive and Lifestyle-Related Diseases, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kumamoto, Ryo; Arima, Shiho; Hashimoto, Shinichi; Nasu, Yuichiro; Takami, Yoichiro; Moriuchi, Akihiro; Sakiyama, Toshio; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito [Department of Digestive and Lifestyle-Related Diseases, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

    2011-04-01

    Highlights: {yields} Hepatic steatosis in rats fed a high fructose diet was less severe than that in rats fed a high fat diet. {yields} Liver regeneration was more impaired in rats fed a high fructose diet than in rats fed a high fat diet. {yields} Dysregulation of genes associated with metabolism may contribute to impairment of liver regeneration. {yields} Regulation of the TGF-{beta}1 level after partial hepatectomy may be impaired in rats fed a high fructose diet. -- Abstract: Hepatic steatosis (HS) has a negative effect on liver regeneration, but different pathophysiologies of HS may lead to different outcomes. Male Sprague-Dawley rats were fed a high fructose (66% fructose; H-fruc), high fat (54% fat; H-fat), or control chow diet for 4 weeks. Based on hepatic triglyceride content and oil red O staining, HS developed in the H-fruc group, but was less severe compared to the H-fat group. Hepatic mRNA expression levels of fatty acid synthase and fructokinase were increased and those of carnitine palmitoyltransferase-1 and peroxisome proliferator-activated receptor-{alpha} were decreased in the H-fruc group compared to the H-fat group. Liver regeneration after 70% partial hepatectomy (PHx) was evaluated by measuring the increase in postoperative liver mass and PCNA-positive hepatocytes, and was impaired in the H-fruc group compared to the H-fat and control groups on days 3 and 7. Serum levels of tumor necrosis factor-{alpha}, interleukin-6 and hepatocyte growth factor did not change significantly after PHx. In contrast, serum TGF-{beta}1 levels were slightly but significantly lower in the control group on day 1 and in the H-fat group on day 3 compared to the level in each group on day 0, and then gradually increased. However, the serum TGF-{beta}1 level did not change after PHx in the H-fruc group. These results indicate that impairment of liver regeneration after PHx in HS is related to the cause, rather than the degree, of steatosis. This difference may result

  13. Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model.

    Science.gov (United States)

    Mohamed, Hoda E; Elswefy, Sahar E; Rashed, Laila A; Younis, Nahla N; Shaheen, Mohamed A; Ghanim, Amal M H

    2016-03-01

    Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats. Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 10(6) cells /rat, once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA. © 2016 by the Society for Experimental Biology and Medicine.

  14. Silymarin Accelerates Liver Regeneration after Partial Hepatectomy

    Directory of Open Access Journals (Sweden)

    Jia-Ping Wu

    2015-01-01

    Full Text Available Partial hepatectomy (PHx is a liver regeneration physiological response induced to maintain homeostasis. Liver regeneration evolved presumably to protect wild animals from catastrophic liver loss caused by toxins or tissue injury. Silymarin (Sm ability to stimulate liver regeneration has been an object of curiosity for many years. Silymarin has been investigated for use as an antioxidant and anticarcinogen. However, its use as a supportive treatment for liver damage is elusive. In this study, we fed silymarin (Sm, 25 mg/kg to male Sprague-Dawley rats for 7 weeks. Surgical 2/3 PHx was then conducted on the rats at 6 hrs, 24 hrs, and 72 hrs. Western blot and RT-PCR were conducted to detect the cell cycle activities and silymarin effects on hepatic regeneration. The results showed that silymarin enhanced liver regeneration by accelerating the cell cycle in PHx liver. Silymarin led to increased G1 phase (cyclin D1/pRb, S phase (cyclin E/E2F, G2 phase (cyclin B, and M phase (cyclin A protein and mRNA at 6 hrs, 24 hrs, and 72 hrs PHx. HGF, TGFα, and TGFβ1 growth factor expressions were also enhanced. We suggest that silymarin plays a crucial role in accelerated liver regeneration after PHx.

  15. Transplantation of Porcine Hepatocytes Cultured with Polylactic Acid-O-Carboxymethylated Chitosan Nanoparticles Promotes Liver Regeneration in Acute Liver Failure Rats

    Directory of Open Access Journals (Sweden)

    Zhong Chen

    2011-01-01

    Full Text Available In this study, free porcine hepatocytes suspension (Group A, porcine hepatocytes embedded in collagen gel (Group B, porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel (Group C, and PLA-O-CMC nanoparticles alone (Group D were transplanted into peritoneal cavity of ALF rats, respectively. The result showed that plasma HGF levels were elevated post-transplantation with a peak at 12 hr. The rats in Group C showed highest plasma HGF levels at 2, 6, 12, 24 and 36 hr post-transplantation and lowest HGF level at 48 hr. Plasma VEGF levels were elevated at 48 hr post-transplantation with a peak at 72 hr. The rats in Group C showed highest plasma HGF levels at 48, 72, and 96 hr post-transplantation. The liver functions in Group C were recovered most rapidly. Compared with Group B, Group C had significant high liver Kiel 67 antigen labeling index (Ki-67 LI at day 1 post-HTx (P<.05. Ki-67 LI in groups B and C was higher than that in groups A and D at days 5 and 7 post-HTx. In conclusion, intraperitoneal transplantation of porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel can promote significantly liver regeneration in ALF rats.

  16. Enhancement of liver regeneration and liver surgery

    NARCIS (Netherlands)

    Olthof, P.B.

    2017-01-01

    Liver regeneration allows surgical resection of up to 75% of the liver and enables curative treatment potential for patients with primary or secondary hepatic malignancies. Liver surgery is associated with substantial risks, reflected by considerable morbidity and mortality rates. Optimization of

  17. Vitamin K2-enhanced liver regeneration is associated with oval cell expansion and up-regulation of matrilin-2 expression in 2-AAF/PH rat model.

    Science.gov (United States)

    Lin, M; Sun, P; Zhang, G; Xu, X; Liu, G; Miao, H; Yang, Y; Xu, H; Zhang, L; Wu, P; Li, M

    2014-03-01

    Normal liver has a great potential of regenerative capacity after partial hepatectomy. In clinic, however, most patients receiving partial hepatectomy are usually suffering from chronic liver diseases with severely damaged hepatocyte population. Under these conditions, activation of hepatic progenitor cell (oval cell in rodents) population might be considered as an alternative mean to enhance liver functional recovery. Vitamin K2 has been shown to promote liver functional recovery in patients with liver cirrhosis. In this study, we explored the possibility of vitamin K2 treatment in activating hepatic oval cell for liver regeneration with the classic 2-acetamido-fluorene/partial hepatectomy (2-AAF/PH) model in Sprague-Dawley rats. In 2-AAF/PH animals, vitamin K2 treatment induced a dose-dependent increase of liver regeneration as assessed by the weight ratio of remnant liver versus whole body and by measuring serum albumin level. In parallel, a drastic expansion of oval cell population as assessed by anti-OV6 and anti-CK19 immunostaining was noticed in the periportal zone of the remnant liver. Since matrilin-2 was linked to oval cell proliferation and liver regeneration after partial hepatectomy, we assessed its expression at both the mRNA and protein levels. The results revealed a significant increase after vitamin K2 treatment in parallel with the expansion of oval cell population. Consistently, knocking down matrilin-2 expression in vivo largely reduced vitamin K2-induced liver regeneration and oval cell proliferation in 2-AAF/PH animals. In conclusion, these data suggest that vitamin K2 treatment enhances liver regeneration after partial hepatectomy, which is associated with oval cell expansion and matrilin-2 up-regulation.

  18. Liver regeneration is dependent on the extent of hepatectomy

    DEFF Research Database (Denmark)

    Meier, Michelle; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt

    of liver tissue and blood for liver specific serology. The change in liver weight after PH was evaluated as liver regeneration rate (RR). Histological analyses of liver cell proliferation and proteomic analyses are in progress. The gain in liver weight as well as RR increased significantly with the size......The upper limit for the size of hepatectomy is approximately 90% in rats. The present research project is designed to investigate the molecular pathways leading to either liver regeneration or liver failure after extended hepatectomy. In this first study we investigated the impact of different size...... of hepatectomy on liver regeneration in a rat model. Male Wistar rats were divided into four groups: 30% (n=24), 70% (n=24) and 90% (n=24) partial hepatectomy (PH) was performed together with a SHAM group (n=24). Euthanization took place at postoperative day (POD) 1 (n=8), 3 (n=8), and 5 (n=8) with harvesting...

  19. Kinetics of /sup 3/H-thymidine incorporation into nuclei of cells of the regenerating liver of rats exposed to various doses of x rays

    Energy Technology Data Exchange (ETDEWEB)

    Aksenovich, T I; Polishchuk, A M [AN SSSR, Novosibirsk. Inst. Tsitologii i Genetiki

    1976-01-01

    Action of x radiation on the incorporation of /sup 3/H-thymidine into nuclei of cells of the regenerating liver of rats has been studied. A whole-body exposure of rats to 150 to 300 R has been found to inhibit /sup 3/H-thymidine uptake into DNA of S-cells of the regenerating liver, and this effect can be attributed to the inhibition of DNA synthesis rather than to changes in the concentration of a label in the intracellular pool of DNA precursors. In addition to the DNA synthesis decrease, inhibition of the label uptake into the pool is observed after doses of 600 to 1200 R. On the basis of the data obtained, a hypothesis is proposed that explains the mechanism of inhibition of DNA synthesis under the action of radiation.

  20. Role of liver progenitors in liver regeneration.

    Science.gov (United States)

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

    2015-02-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

  1. Liver Development, Regeneration, and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Janet W. C. Kung

    2010-01-01

    Full Text Available The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

  2. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.J.A.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; Bruin, A. de

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  3. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; de Bruin, A.

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  4. Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16Ink4a) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats

    International Nuclear Information System (INIS)

    Tsuchiya, Takuma; Wang, Liyun; Yafune, Atsunori; Kimura, Masayuki; Ohishi, Takumi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-01-01

    Cell cycle aberration was immunohistochemically examined in relation to preneoplastic liver cell foci expressing glutathione S-transferase placental form (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of p16 Ink4a following exposure to other hepatocarcinogens/promoters and its DNA methylation status were also analyzed during early and late tumor-promotion stages. GST-P + liver cell foci increased cell proliferation and decreased apoptosis when compared with surrounding liver cells. In concordance with GST-P + foci, checkpoint proteins at G 1 /S (p21 Cip1 , p27 Kip1 and p16 Ink4a ) and G 2 /M (phospho-checkpoint kinase 1, Cdc25c and phospho-Wee1) were either up- or downregulated. Cellular distribution within GST-P + foci was either increased or decreased with proteins related to G 2 -M phase or DNA damage (topoisomerase IIα, phospho-histone H2AX, phospho-histone H3 and Cdc2). In particular, p16 Ink4a typically downregulated in GST-P + foci and regenerative nodules at early tumor-promotion stage with hepatocarcinogens facilitating liver cell regeneration and in neoplastic lesions at late tumor-promotion stage with hepatocarcinogens/promoters irrespective of regenerating potential. Hypermethylation at exon 2 of Cdkn2a was detected at both early- and late-stages. Thus, diverse disruptive expression of G 1 /S and G 2 /M proteins, which allows for clonal selection of GST-P + foci, results in the acquisition of multiple aberrant phenotypes to disrupt checkpoint function. Moreover, increased DNA-damage responses within GST-P + foci may be the signature of genetic alterations. Intraexonic hypermethylation may be responsible for p16 Ink4a -downregulation, which facilitates cell cycle progression in early preneoplastic lesions produced by repeated cell regeneration and late-stage neoplastic lesions irrespective of the carcinogenic mechanism.

  5. Comparative Study of Compensatory Liver Regeneration in a Rat Model: Portal Vein Ligation Only versus Sequential Ligation of the Portal Vein and Hepatic Artery

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Soo Young [Dept. of Pathology, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Jeon, Gyeong Sik [Dept. of Radiology, CHA Bundang Medical Center, College of Medicine, CHA University, Seongnam (Korea, Republic of); Lee, Byung Mo [Dept. of Surgery, Seoul Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

    2013-04-15

    To compare the volume change and the regenerative capacity between portal vein ligation (embolization) (PVL) and heterochronous PVL with hepatic artery ligation (HAL) in a rodent model. The animals were separated into three groups: group I, ligation of the left lateral and median portal vein branches; group II, completion of PVL, followed by ligation of the same branches of the hepatic artery after 48 h; control group, laparotomy without ligation was performed. Five rats from each group were sacrificed on 1, 3, 5, and 7 days after the operation. Volume change measurement, liver function tests and immunohistochemical analysis were performed. The volume of the nonligated lobe between groups I and II was not significantly different by day 5 and day 7. Mean alanine aminotransferase and total bilirubin levels were significantly higher in group II, while the albumin level was higher in group I. Both c-kit- and MIB-5-positive cells used in the activity detection of regeneration were more prevalent in group I on day 1, 3, and 5, with statistical significance. There was no operation related mortality. PVL alone is safe and effective in compensatory liver regeneration. Performing both PVL and HAL does not confer any additional benefits.

  6. Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

    NARCIS (Netherlands)

    Jansen, P. L.; Chamuleau, R. A.; van Leeuwen, D. J.; Schipper, H. G.; Busemann-Sokole, E.; van der Heyde, M. N.

    1990-01-01

    Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was

  7. Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

    International Nuclear Information System (INIS)

    Kuwata, Kazunori; Shibutani, Makoto; Hayashi, Hitomi; Shimamoto, Keisuke; Hayashi, Shim-Mo; Suzuki, Kazuhiko; Mitsumori, Kunitoshi

    2011-01-01

    β-Naphthoflavone (BNF) is a strong inducer of cytochrome P450 1A enzymes, and exerts liver tumor-promoting activity through enhancement of oxidative stress responses in rats. This study investigated the role of the tissue environment surrounding hepatocellular preneoplastic lesions in the early tumor-promotion stage by BNF, using enzymatically modified isoquercitrin (EMIQ) as an anti-oxidative chemopreventive agent. Male F344 rats were fed a diet containing BNF (0.5%) for 6 weeks, with or without EMIQ (0.2%) in the drinking water, 2 weeks after initiation with N-diethylnitrosamine, and were subjected to two-thirds partial hepatectomy 1 week after starting BNF-promotion. BNF-treatment increased concentrations of liver thiobarbituric acid-reactive substances, single liver cells expressing glutathione S-transferase placental form or heme oxygenase (HO)-1, and concomitant apoptosis and proliferation of liver cells. Transcript upregulation of anti-oxidative enzymes (Aldh1a1 and Nqo1), cell cycle-related molecules (Cdc20 and Cdkn2b) and inflammation-related molecules including proinflammatory cytokines (Ccl2, Col1a1, Il6, Nos2 and Serpine1) was also evident. Furthermore, BNF increased HO-1-expressing Kupffer cells and liver cells expressing tumor necrosis factor receptor 1 (TNFR1) and the TNFR1-associated death domain. Most of these BNF-induced fluctuations disappeared or were suppressed by EMIQ in conjunction with suppression of tumor-promotion. Tnf transcript levels with BNF were also suppressed by EMIQ. These results suggest that BNF-induced oxidative stress causes single liver cell toxicity, allowing subsequent concomitant apoptosis and regeneration involving inflammatory responses including TNFα-signaling, contributing to tumor promotion. Kupffer cells may act to protect against inflammatory stimuli induced as a result of oxidative cellular stress by BNF, causing proinflammatory cytokine level fluctuations.

  8. Towards a new therapy protocol for liver metastases. Effect of boron compounds and BNCT on normal liver regeneration

    International Nuclear Information System (INIS)

    Cardoso, Jorge E.; Heber, Elisa M.; Trivillin, Veronica A.

    2006-01-01

    The Taormina project developed a new method for BNCT treatment of multifocal unresectable liver metastases based on whole liver autograft. The Roffo Institute liver surgeons propose a new technique based on partial liver autograft that would pose less risk to the patient but would require significant healthy liver regeneration following BNCT. The aim of the present study was to assess the effect of BPA, GB-10 (Na 2 10 B 10 H 10 ) and (GB-10 + BPA) and of BNCT mediated by these boron compounds on normal liver regeneration in the Wistar rat. Normal liver regeneration, body weight, hemogram, liver and kidney function were assessed following partial hepatectomy post administration of BPA, GB-10 or (GB-10 + BPA) and post in vivo BNCT at the RA-6 Reactor. These end-points were evaluated 9 days following partial hepatectomy, the time at which complete liver regeneration occurs in untreated controls. The corresponding biodistribution studies were conducted to perform dosimetric calculations. BPA, GB-10 and (GB-10 + PBA) and in vivo BNCT mediated by these boron compounds in dose ranges compatible with therapy did not cause alterations in the outcome of normal liver regeneration, and did not induce alterations in body weight, hemogram, liver or kidney function. The experimental data available to date support the development of a new BNCT protocol for the treatment of liver metastases that requires the regeneration of normal liver past-BNCT. (author)

  9. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. Fifty-four adult male Wistar rats were randomly

  10. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS: Fifty-four adult male Wistar rats

  11. Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

    International Nuclear Information System (INIS)

    Jansen, P.L.M.; Chamuleau, R.A.F.; Leeuwen, D.J. van; Schippor, H.G.; Busemann-Sokole, E.; Heyde, M.N. van der

    1990-01-01

    Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single photon computed tomography (SPECT), using 99m Tc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurement with the volume of the resected liver mass. Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days, the liver had regenerated maximally to a volume of 75 ± 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 ± 10% for the caffeine clearance and to 100 ± 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. The study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy. 22 refs

  12. 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

  13. Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

    International Nuclear Information System (INIS)

    Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi; Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro; Tamura, Shinji; Kiso, Shinichi; Hayashi, Norio

    2009-01-01

    We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

  14. Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine.

    Science.gov (United States)

    Gilgenkrantz, Hélène; Collin de l'Hortet, Alexandra

    2018-04-16

    Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities. In the setting of chronic liver diseases, a ductular reaction ensues in which liver progenitor cells (LPCs) proliferate in the periportal region. Although these LPCs have the capacity to differentiate into hepatocytes and biliary cells in vitro, their ability to participate in liver regeneration is far from clear. Their expansion has even been associated with increased fibrosis and poorer prognosis in chronic liver diseases. Controversies also remain on their origin: lineage studies in experimental mouse models of chronic injury have recently suggested that these LPCs originate from hepatocyte dedifferentiation, whereas in other situations, they seem to come from cholangiocytes. This review summarizes data published in the past 5 years in the liver regeneration field, discusses the mechanisms leading to regeneration disruption in chronic liver disorders, and addresses the potential use of novel approaches for regenerative medicine. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. The genetic regulation of the terminating phase of liver regeneration

    DEFF Research Database (Denmark)

    Nygård, Ingvild E.; Mortensen, Kim E.; Hedegaard, Jakob

    2012-01-01

    Background After partial hepatectomy (PHx), the liver regeneration process terminates when the normal liver-mass/body-weight ratio of 2.5% has been re-established. To investigate the genetic regulation of the terminating phase of liver regeneration, we performed a 60% PHx in a porcine model. Liver...... biopsies were taken at the time of resection, after three weeks and upon termination the sixth week. Gene expression profiles were obtained using porcine oligonucleotide microarrays. Our study reveals the interactions between genes regulating the cell cycle, apoptosis and angiogenesis, and the role...... of Transforming Growth Factor-β (TGF-β) signalling towards the end of liver regeneration. Results Microarray analysis revealed a dominance of genes regulating apoptosis towards the end of regeneration. Caspase Recruitment Domain-Containing Protein 11 (CARD11) was up-regulated six weeks after PHx, suggesting...

  16. Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

    2013-07-19

    Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

  17. The Effect of Elephantopus scaber L. on Liver Regeneration after Partial Hepatectomy

    Directory of Open Access Journals (Sweden)

    Chin-Chuan Tsai

    2013-01-01

    Full Text Available Liver regeneration after partial hepatectomy (PHx is a physiological response for maintaining homeostasis. The aim of this study is to investigate effects of Elephantopus scaber L.- (ESL- induced liver regeneration on growth factors (HGF and IGF-1, cell cycle regulation, and apoptosis suppressed. In this study, we fed five Chinese medicinal herbs (1 g/kg/day, Codonopsis pilosula (CP, Dangshen, Salvia miltiorrhiza Bunge (SMB, Danshen,, Bupleurum kasi (BK, Chaihu, Elephantopus scaber L. (ESL, Teng-Khia-U, and Silymarin (Sm, 25 mg/kg for 7 days to male Spraue-Dawley rats. Then surgical 2/3 PHx was conducted and liver regeneration mechanisms were estimated on the following 24 hrs and 72 hrs. The activities of growth factors (HGF and IGF-I and cell cycle proteins were measured by Western blot and RT-PCR. Histological analysis and apoptosis were detected by H&E stain and TUNEL. The results showed that extraction of Elephantopus scaber L. (ESL and Silymarin (Sm, positive control were increased protein expression levels of HGF and IGF-1 which leads into cell cycle. These results suggest that the ESL plays a crucial role in cell cycle-induced liver regeneration and apoptosis. These results suggested that the ESL plays a crucial role in cell cycle-induced liver regeneration and suppressed hepatocytes apoptosis.

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

    Directory of Open Access Journals (Sweden)

    Duilio ePagano

    2014-04-01

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

  19. Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases

    Directory of Open Access Journals (Sweden)

    Irina V. Kholodenko

    2017-01-01

    Full Text Available The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable.

  20. The influence of hypothyroidism on liver regeneration: an experimental study in rats A influência do hipotireoidismo na regeneração hepatica: estudo experimental em ratos

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Pessole Biondo-Simões

    2007-01-01

    Full Text Available BACKGROUND: The influence of hypothyroidism in liver regeneration has been a controversial opinions. PURPOSE: The aim of this study is to identify the relationship between hypothyroidism and liver regeneration in rats. METHODS: Forty male Wistar rats divided into two groups of 20 specimens each. One group (C consisted of euthyroid rats, and the other (H of hypothyroid rats. All the animals were anesthetized with xylazine and ketamine and subjected to a longitudinal incision in the anterior cervical region. The thyroid was completely resected in group H and left intact in group C. Ten days after the first surgery, both groups of rats were weighed and submitted to partial hepatectomy, in which the left lateral and median lobes were resected and weighed. Examinations were carried out after 24 hours and, on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in five fields; and the percentage of PCNA-positive nuclei in five fields. RESULTS: Using KWON's formula, the regeneration rate for Group C after 24 hours was 58.49% whereas that for Group H was 50.42% (p=0.0165. After 7 days, the regeneration rate for Group C was 93.04% and Group H 93.74% (p=0.2165. The average number of mitotic figures after 24 hours was 14 ± 1.5 for Group C and 9.8 ± 2.2 for Group H (p=0,00016. After 7 days the corresponding figures were 5.4 ± 1.1 and 5.1 ± 1.2 (p=0,6343. The average number of PCNA-positive nuclei after 24 hours was 13.55 ± 3.84 in Group C and 7.7 ± 2.11 in Group H (p =0,0006. The corresponding figures after 7 days were 3.5 ± 2.39 for Group C and 4.11 ± 1.90 for Group H (p>0.05. CONCLUSION: We conclude that hypothyroidism in rats causes a delay in hepatic regeneration in the first 24 hours, but that after seven days the rate of regeneration is equal to that in euthyroid rats.BACKGROUND: A influência do hipotireoidismo na regeneração hepatica tem opiniões controvérsas. OBJETIVO: Identificar a rela

  1. 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.

  2. The regulation of cytoskeletal and liver-specific gene expression during liver regeneration and primary hepatocyte culture

    International Nuclear Information System (INIS)

    Robinson, G.S.

    1989-01-01

    The focus of this dissertation is to determine what role(s) the extracellular matrix and expression of certain cytoskeletal genes play in the regulation of hepatocyte growth and the maintenance of a differential state. The expression of several cytoskeletal and liver-specific genes was examined during liver regeneration and in hepatocyte cultures maintained in a hormonally-defined, serum-free medium and plated on two different matrices: rat tail collagen and the EHS matrix. During liver regeneration and in hepatocytes cultured on rat tail collagen, there was a dramatic increase in tubulin mRNA levels coincident with but not linked to DNA synthesis. The message levels for other cytoskeletal genes similarly increased, while a decrease was observed in the mRNA levels of the liver-specific genes, serum albumin and alpha 1 inhibitor III. Hepatocytes cultured on the EHS matrix resulted in the maintenance of low levels of cytoskeletal gene expression and high levels of liver-specific gene expression, similar to that observed in the normal liver. Results from subcellar fractionation and two-dimensional gel electrophoresis of 35 S-labelled proteins paralleled the results seen at the mRNA level. Preliminary work suggests that microtubule organization may play a role in the expression of the liver-specific genes which encode secreted proteins. These studies, which compare hepatocytes cultured on collagen or the EHS matrix gel, reveal that both cell-cell and cell-matrix interactions play a major role in the maintenance of the differential phenotype in hepatocytes

  3. Whither prometheus' liver? Greek myth and the science of regeneration.

    Science.gov (United States)

    Power, Carl; Rasko, John E J

    2008-09-16

    Stem-cell biologists and those involved in regenerative medicine are fascinated by the story of Prometheus, the Greek god whose immortal liver was feasted on day after day by Zeus' eagle. This myth invariably provokes the question: Did the ancient Greeks know about the liver's amazing capacity for self-repair? The authors address this question by exploring the origins of Greek myth and medicine, adopting a 2-fold strategy. First, the authors consider what opportunities the ancient Greeks had to learn about the liver's structure and function. This involves a discussion of early battlefield surgery, the beginnings of anatomical research, and the ancient art of liver augury. In addition, the authors consider how the Greeks understood Prometheus' immortal liver. Not only do the authors examine the general theme of regeneration in Greek mythology, they survey several scholarly interpretations of Prometheus' torture.

  4. Efeito do omeprazol e do pantoprazol sobre a regeneração hepática após hepatectomia parcial em ratos Effect of omeprazole and pantoprazole on liver regeneration after partial hepatectomy in rats

    Directory of Open Access Journals (Sweden)

    Gustavo Barreto de Melo

    2003-12-01

    Full Text Available OBJETIVO: Avaliar os efeitos do omeprazol e do pantoprazol sobre a regeneração hepática após hepatectomia parcial. MÉTODOS: Cinqüenta e oito ratos Wistar machos foram divididos em 4 grupos: Grupo SHAM, Grupo HP, Grupo PANTO e Grupo OMEP. Eles foram submetidos a hepatectomia parcial de 67% (Grupos HP, PANTO e OMEP ou laparotomia (Grupo SHAM. Os fígados foram removidos 32 e 56 horas após a operação. Depois, os animais foram sacrificados. Em todos os grupos, as substâncias (solução salina, omeprazol e pantoprazol foram aplicadas diariamente a partir do momento em que foram operados até o sacrifício. RESULTADOS: O índice de mitose no Grupo SHAM não foi significativo. Trinta e duas horas após a hepatectomia, a contagem de mitoses foi de 1,2 ± 1,09 para o Grupo HP, 1,2 ± 1,6 para o Grupo OMEP e 2,6 ± 3,2 para o Grupo PANTO. Na análise após 56 horas, os valores foram 1,6 ± 0,89 para o HP, 2 ± 1,8 para o OMEP e 2,6 ± 0,54 para o PANTO. Esses resultados não foram estatisticamente significativos. CONCLUSÃO: O omeprazol e o pantoprazol, agentes inibidores da bomba de prótons (H+, K+-ATPase, não interferem na regeneração hepática 32 e 56 horas após hepatectomia parcial a 67% em ratos.PURPOSE: To assess the effects of omeprazole and pantoprazole on liver regeneration after partial hepatectomy. METHODS: Fifty eight male Wistar rats were divided into 4 groups: SHAM, HP, PANTO and OMEP Groups. They were submitted to 67% partial hepatectomy (HP, PANTO and OMEP Groups or laparotomy (SHAM Group. Their livers were removed 32 and 56 hours after the operation. Then, the animals were sacrificed. In all groups, the substances (saline solution, omeprazole and pantoprazole were injected once daily from the moment they were operated on until the time of sacrifice. RESULTS: In SHAM Group the mitotic index was not significant. Thirty two hours after hepatectomy, the mitosis index was 1.2 ± 1.09 in HP Group, 1.2 ± 1.6 in OMEP Group and 2

  5. 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.

  6. 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

  7. LIVER AND BONE MARROW STEM/PROGENITOR CELLS AS REGULATORS OF REPARATIVE REGENERATION OF DAMAGED LIVER

    Directory of Open Access Journals (Sweden)

    А. V. Lundup

    2010-01-01

    Full Text Available In this review the modern information about effectiveness of liver insufficiency treatment by stem/ progenitor cells of liver (oval cells and bone marrow (hemopoietic cells and mesenchymal cells was presented. It is shown that medical action of these cells is referred on normalization of liver cell interaction and reorganization of processes of a reparative regeneration in damaged liver. It is believed that application of mesenchymal stromal cells from an autological bone marrow is the most perspective strategy. However, for definitive judgement about regenerative possibilities of the autological bone marrow cells it is necessary to carry out large-scale double blind clinical researches. 

  8. Hepatic regeneration and functional recovery following partial liver resection in an experimental model of hepatic steatosis treated with omega-3 fatty acids

    NARCIS (Netherlands)

    Marsman, H. A.; de Graaf, W.; Heger, M.; van Golen, R. F.; ten Kate, F. J. W.; Bennink, R.; van Gulik, T. M.

    2013-01-01

    Omega-3 fatty acids (FAs) have been shown to reduce experimental hepatic steatosis and protect the liver from ischaemia-reperfusion injury. The aim of this study was to examine the effects of omega-3 FAs on regeneration of steatotic liver. Steatosis was induced in rats by a 3-week

  9. Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis

    International Nuclear Information System (INIS)

    Ilowski, Maren; Kleespies, Axel; Toni, Enrico N. de; Donabauer, Barbara; Jauch, Karl-Walter; Hengstler, Jan G.; Thasler, Wolfgang E.

    2011-01-01

    Research highlights: → ALR decreases cytochrome c release from mitochondria. → ALR protects hepatocytes against apoptosis induction by ethanol, TRAIL, anti-Apo, TGF-β and actinomycin D. → ALR exerts a liver-specific anti-apoptotic effect. → A possible medical usage of ALR regarding protection of liver cells during apoptosis inducing therapies. -- Abstract: Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-β, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-β and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.

  10. Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Ilowski, Maren [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Kleespies, Axel [Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Toni, Enrico N. de [Department of Medicine II, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Donabauer, Barbara [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Jauch, Karl-Walter [Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Hengstler, Jan G. [Leibniz Research Centre for Working Environment and Human Factors, Technical University, Dortmund (Germany); Thasler, Wolfgang E., E-mail: wolfgang.thasler@med.uni-muenchen.de [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany)

    2011-01-07

    Research highlights: {yields} ALR decreases cytochrome c release from mitochondria. {yields} ALR protects hepatocytes against apoptosis induction by ethanol, TRAIL, anti-Apo, TGF-{beta} and actinomycin D. {yields} ALR exerts a liver-specific anti-apoptotic effect. {yields} A possible medical usage of ALR regarding protection of liver cells during apoptosis inducing therapies. -- Abstract: Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-{beta}, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-{beta} and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.

  11. Evaluation of regeneration of liver function in pig model of auxiliary partial liver transplantation

    International Nuclear Information System (INIS)

    Li Jiaxin; Chen Xiaopeng; Rui Ging; Shong Qun; Chen Fangman; Lu Meijing; Chen Yongquan

    2010-01-01

    Objective: To establish a pig model of auxiliary partial liver transplantation and observe the liver function regeneration of host liver and graft. Methods: The portal vein providing for the host liver were gradually contracted; the donor hepatic veins were eng-to-side anastomosed to inferior vena cava in host caudal; graft was transplanted into the space under the host liver, part of receivers relieved portal vein angiography and color Doppler flow imaging was performed 3 days after surgery. Liver function of double livers in relievers was checked up, 3 days and 1 week after surgery respectively. Results: After surgery 10 relievers survived over 1 week, blood enzymology from hepatic vein of grafts 1 week after surgery were not ameliorative significantly compared with those 3 days after surgery (P > 0.05). Blood enzymology indexes from hepatic veins of grafts 1 week after surgery were were improved significantly compared with 3 days after surgery (P < 0.05). The graft did not reveal atrophic and gained favorable function. Conclusion: Favorable regeneration in the auxiliary partial liver transplantation model has achieved. Ideal foundation has been established for simulating and investigating human auxiliary liver transplantation. (authors)

  12. Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure

    Directory of Open Access Journals (Sweden)

    S. V. Gautier

    2017-01-01

    Full Text Available Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH. Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40 via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes

  13. Farnesoid X receptor, the bile acid sensing nuclear receptor, in liver regeneration

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    Guodong Li

    2015-03-01

    Full Text Available The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy (PH model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids (BAs are ligands of farnesoid X receptor (FXR, a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potential use of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.

  14. Regenerated rat skeletal muscle after periodic contusions

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    V.B. Minamoto

    2001-11-01

    Full Text Available In the present study we evaluated the morphological aspect and changes in the area and incidence of muscle fiber types of long-term regenerated rat tibialis anterior (TA muscle previously submitted to periodic contusions. Animals received eight consecutive traumas: one trauma per week, for eight weeks, and were evaluated one (N = 8 and four (N = 9 months after the last contusion. Serial cross-sections were evaluated by toluidine blue staining, acid phosphatase and myosin ATPase reactions. The weight of injured muscles was decreased compared to the contralateral intact one (one month: 0.77 ± 0.15 vs 0.91 ± 0.09 g, P = 0.03; four months: 0.79 ± 0.14 vs 1.02 ± 0.07 g, P = 0.0007, respectively and showed abundant presence of split fibers and fibers with centralized nuclei, mainly in the deep portion. Damaged muscles presented a higher incidence of undifferentiated fibers when compared to the intact one (one month: 3.4 ± 2.1 vs 0.5 ± 0.3%, P = 0.006; four months: 2.3 ± 1.6 vs 0.3 ± 0.3%, P = 0.007, respectively. Injured TA evaluated one month later showed a decreased area of muscle fibers when compared to the intact one (P = 0.003. Thus, we conclude that: a muscle fibers were damaged mainly in the deep portion, probably because they were compressed against the tibia; b periodic contusions in the TA muscle did not change the percentage of type I and II muscle fibers; c periodically injured TA muscles took four months to reach a muscle fiber area similar to that of the intact muscle.

  15. Regeneration of the liver at different periods of mononuclear infiltration induced by zymosan granules

    International Nuclear Information System (INIS)

    Shcherbakov, V.I.; Komlyagina, T.G.; Mayanskii, D.N.

    1985-01-01

    The aim of this investigation was to discover how the liver,with areas of mononuclear infiltration, developing in response to activation of Kupffer cells (KC) by zymosan granules (ZG), regenerates. In the experiments, an intraperitoneal injection of 1 microCi of 3 H-thymidine/g body weight was given to the mice 1 h before sacrifice. Proliferation of hepatocytes and regeneration of the liver were intensified most when partial resection of the liver (PRL) was performed at the peak of mononuclear infiltration of the liver, namely five days after injection of ZG. The data indicate that not only activated KC, but also areas of mononuclear infiltration potentiate hepatocyte regeneration

  16. 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

  17. The effect of hepatoprotective preparations thioctacid and flavobion on histones in intact and regenerating lever in irradiated rats

    International Nuclear Information System (INIS)

    Kozhurkova, M.; Kropachova, E.; Mishurova, R.; Reksa, R.

    1992-01-01

    The changes in concentration, total content of histones and relative proportion of individual histone fractions in intact and regenerating liver were followed in rats after administration of hepatoprotective agents flavobion and thioctacid and after whole-body gamma irradiation with a dose 5.7 Gy. Thioctacid alone caused an increase in histone concentration in intact liver whereas flavobion alone did not produce significant quantitative changes. Irradiation alone decreased markedly the concentration and total content of histones in intact as well as regenerating liver of unprotected rats. Administration of thioctacid or flavobion protected from these quantitative histone changes or alleviated them consideradly. In relative proportion of individual histone fractions, the most profound changes were found in H1 histone after flavobion application

  18. 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

  19. UPF2 is a critical regulator of liver development, function and regeneration

    DEFF Research Database (Denmark)

    Thoren, Lina A; Nørgaard, Gitte A; Weischenfeldt, Joachim

    2010-01-01

    regulatory potential of the NMD pathway in mammals will require the functional assessment of NMD in different tissues. METHODOLOGY/PRINCIPAL FINDINGS: Here we use mouse genetics to address the role of UPF2, a core NMD component, in the development, function and regeneration of the liver. We find that loss....... CONCLUSION/SIGNIFICANCE: Collectively, our data demonstrate the critical role of the NMD pathway in liver development, function and regeneration and highlights the importance of NMD for mammalian biology....... of NMD during fetal liver development is incompatible with postnatal life due to failure of terminal differentiation. Moreover, deletion of Upf2 in the adult liver results in hepatosteatosis and disruption of liver homeostasis. Finally, NMD was found to be absolutely required for liver regeneration...

  20. Oval cell response is attenuated by depletion of liver resident macrophages in the 2-AAF/partial hepatectomy rat.

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    Shuai Xiang

    Full Text Available BACKGROUND/AIMS: Macrophages are known to play an important role in hepatocyte mediated liver regeneration by secreting inflammatory mediators. However, there is little information available on the role of resident macrophages in oval cell mediated liver regeneration. In the present study we aimed to investigate the role of macrophages in oval cell expansion induced by 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH in rats. METHODOLOGY/PRINCIPAL FINDINGS: We depleted macrophages in the liver of 2-AAF/PH treated rats by injecting liposome encapsulated clodronate 48 hours before PH. Regeneration of remnant liver mass, as well as proliferation and differentiation of oval cells were measured. We found that macrophage-depleted rats suffered higher mortality and liver transaminase levels. We also showed that depletion of macrophages yielded a significant decrease of EPCAM and PCK positive oval cells in immunohistochemical stained liver sections 9 days after PH. Meanwhile, oval cell differentiation was also attenuated as a result of macrophage depletion, as large foci of small basophilic hepatocytes were observed by day 9 following hepatectomy in control rats whereas they were almost absent in macrophage depleted rats. Accordingly, real-time polymerase chain reaction analysis showed lower expression of albumin mRNA in macrophage depleted livers. Then we assessed whether macrophage depletion may affect hepatic production of stimulating cytokines for liver regeneration. We showed that macrophage-depletion significantly inhibited hepatic expression of tumor necrosis factor-α and interleukin-6, along with a lack of signal transducer and activator of transcription 3 phosphorylation during the early period following hepatectomy. CONCLUSIONS: These data indicate that macrophages play an important role in oval cell mediated liver regeneration in the 2-AAF/PH model.

  1. 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

  2. Review fantastic medical implications of 3D-printing in liver surgeries, liver regeneration, liver transplantation and drug hepatotoxicity testing: A review.

    Science.gov (United States)

    Wang, Jing-Zhang; Xiong, Nan-Yan; Zhao, Li-Zhen; Hu, Jin-Tian; Kong, De-Cheng; Yuan, Jiang-Yong

    2018-06-07

    The epidemiological trend in liver diseases becomes more serious worldwide. Several recent articles published by International Journal of Surgery in 2018 particularly emphasized the encouraging clinical benefits of hepatectomy, liver regeneration and liver transplantation, however, there are still many technical bottlenecks underlying these therapeutic approaches. Remarkably, a few preliminary studies have shown some clues to the role of three-dimensional (3D) printing in improving traditional therapy for liver diseases. Here, we concisely elucidated the curative applications of 3D-printing (no cells) and 3D Bio-printing (with hepatic cells), such as 3D-printed patient-specific liver models and devices for medical education, surgical simulation, hepatectomy and liver transplantation, 3D Bio-printed hepatic constructs for liver regeneration and artificial liver, 3D-printed liver tissues for evaluating drug's hepatotoxicity, and so on. Briefly, 3D-printed liver models and bioactive tissues may facilitate a lot of key steps to cure liver disorders, predictably bringing promising clinical benefits. This work further provides novel insights into facilitating treatment of hepatic carcinoma, promoting liver regeneration both in vivo and in vitro, expanding transplantable liver resources, maximizing therapeutic efficacy as well as minimizing surgical complications, medical hepatotoxicity, operational time, economic costs, etc. Copyright © 2018. Published by Elsevier Ltd.

  3. 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...

  4. A Rat Model for Muscle Regeneration in the Soft Palate

    Science.gov (United States)

    Carvajal Monroy, Paola L.; Grefte, Sander; Kuijpers-Jagtman, Anne M.; Helmich, Maria P. A. C.; Ulrich, Dietmar J. O.; Von den Hoff, Johannes W.; Wagener, Frank A. D. T. G.

    2013-01-01

    Background Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. Despite successful surgical repositioning of the muscles, optimal function is often not achieved. Scar formation and defective regeneration may hamper the functional recovery of the muscles after cleft palate repair. Therefore, the aim of this study is to investigate the anatomy and histology of the soft palate in rats, and to establish an in vivo model for muscle regeneration after surgical injury. Methods Fourteen adult male Sprague Dawley rats were divided into four groups. Groups 1 (n = 4) and 2 (n = 2) were used to investigate the anatomy and histology of the soft palate, respectively. Group 3 (n = 6) was used for surgical wounding of the soft palate, and group 4 (n = 2) was used as unwounded control group. The wounds (1 mm) were evaluated by (immuno)histochemistry (AZAN staining, Pax7, MyoD, MyoG, MyHC, and ASMA) after 7 days. Results The present study shows that the anatomy and histology of the soft palate muscles of the rat is largely comparable with that in humans. All wounds showed clinical evidence of healing after 7 days. AZAN staining demonstrated extensive collagen deposition in the wound area, and initial regeneration of muscle fibers and salivary glands. Proliferating and differentiating satellite cells were identified in the wound area by antibody staining. Conclusions This model is the first, suitable for studying muscle regeneration in the rat soft palate, and allows the development of novel adjuvant strategies to promote muscle regeneration after cleft palate surgery. PMID:23554995

  5. Platelets prime hematopoietic and vascular niche to drive angiocrine-mediated liver regeneration.

    Science.gov (United States)

    Shido, Koji; Chavez, Deebly; Cao, Zhongwei; Ko, Jane; Rafii, Shahin; Ding, Bi-Sen

    2017-01-01

    In mammals, the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy. How liver regeneration is initiated after mass loss remains to be defined. Here, we report that following liver injury, activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7 + liver sinusoidal endothelial cell (LSEC) and VEGFR1 + myeloid cell, orchestrating hepatic regeneration. After carbon tetrachloride (CCl 4 ) injection or hepatectomy, platelets and CD11b + VEGFR1 + myeloid cells were recruited LSEC, and liver regeneration in both models was impaired in thrombopoietin-deficient ( Thpo -/- ) mice lacking circulating platelets. This impeded regeneration phenotype was recapitulated in mice with either conditional ablation of Cxcr7 in LSEC ( Cxcr7 iΔ/iΔ ) or Vegfr1 in myeloid cell ( Vegfr1 lysM/lysM ). Both Vegfr1 lysM/lysM and Cxcr7 iΔ/iΔ mice exhibited suppressed expression of hepatocyte growth factor and Wnt2, two crucial trophogenic angiocrine factors instigating hepatocyte propagation. Of note, administration of recombinant thrombopoietin restored the prohibited liver regeneration in the tested genetic models. As such, our data suggest that platelets and myeloid cells jointly activate the vascular niche to produce pro-regenerative endothelial paracrine/angiocrine factors. Modulating this "hematopoietic-vascular niche" might help to develop regenerative therapy strategy for hepatic disorders.

  6. Platelets prime hematopoietic–vascular niche to drive angiocrine-mediated liver regeneration

    Science.gov (United States)

    Shido, Koji; Chavez, Deebly; Cao, Zhongwei; Ko, Jane L; Rafii, Shahin; Ding, Bi-Sen

    2017-01-01

    In mammals, the livers regenerate after chemical injury or resection of hepatic lobe by hepatectomy. How liver regeneration is initiated after mass loss remains to be defined. Here we report that following liver injury, activated platelets deploy SDF-1 and VEGF-A to stimulate CXCR7+ liver sinusoidal endothelial cell (LSEC) and VEGFR1+ myeloid cell, orchestrating hepatic regeneration. After carbon tetrachloride injection or hepatectomy, platelets and CD11b+VEGFR1+ myeloid cells were recruited to LSECs, and liver regeneration in both models was impaired in thrombopoietin-deficient (Thpo−/−) mice repressing production of circulating platelets. This impeded regeneration phenotype was recapitulated in mice with either conditional ablation of Cxcr7 in LSEC (Cxcr7iΔ/iΔ) or Vegfr1 in myeloid cell (Vegfr1lysM/lysM). Both Vegfr1lysM/lysM and Cxcr7iΔ/iΔ mice exhibited suppressed expression of hepatocyte growth factor and Wnt2, two crucial trophogenic angiocrine factors instigating hepatocyte propagation. Of note, administration of recombinant thrombopoietin restored the prohibited liver regeneration in the tested genetic models. As such, our data suggest that platelets and myeloid cells jointly activate the vascular niche to produce pro-regenerative endothelial paracrine/angiocrine factors. Modulating this ‘hematopoietic–vascular niche’ might help to develop regenerative therapy strategy for hepatic disorders. PMID:29201496

  7. HIF-1{alpha} is necessary to support gluconeogenesis during liver regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Tajima, Toshihide [Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Goda, Nobuhito, E-mail: goda@waseda.jp [Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Fujiki, Natsuko; Hishiki, Takako; Nishiyama, Yasumasa [Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Senoo-Matsuda, Nanami [Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Shimazu, Motohide [Department of Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998 (Japan); Soga, Tomoyoshi [The Institute for Advanced Biosciences, Keio University, Tsuruoka City, Yamagata 997-0052 (Japan); Yoshimura, Yasunori [Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Johnson, Randall S. [Molecular Biology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093 (United States); Suematsu, Makoto [Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2009-10-02

    Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1{alpha} (HIF-1{alpha}) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72 h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1{alpha} in the regulation of gluconeogenesis under liver regeneration.

  8. HIF-1α is necessary to support gluconeogenesis during liver regeneration

    International Nuclear Information System (INIS)

    Tajima, Toshihide; Goda, Nobuhito; Fujiki, Natsuko; Hishiki, Takako; Nishiyama, Yasumasa; Senoo-Matsuda, Nanami; Shimazu, Motohide; Soga, Tomoyoshi; Yoshimura, Yasunori; Johnson, Randall S.; Suematsu, Makoto

    2009-01-01

    Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1α (HIF-1α) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72 h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1α in the regulation of gluconeogenesis under liver regeneration.

  9. Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice.

    Science.gov (United States)

    Iracheta-Vellve, Arvin; Petrasek, Jan; Gyogyosi, Benedek; Bala, Shashi; Csak, Timea; Kodys, Karen; Szabo, Gyongyi

    2017-07-01

    Inflammation and impaired hepatocyte regeneration contribute to liver failure in alcoholic hepatitis (AH). Interleukin (IL)-1 is a key inflammatory cytokine in the pathobiology of AH. The role of IL-1 in liver regeneration in the recovery phase of alcohol-induced liver injury is unknown. In this study, we tested IL-1 receptor antagonist to block IL-1 signalling in a mouse model of acute-on-chronic liver injury on liver inflammation and hepatocyte regeneration in AH. We observed that inhibition of IL-1 signalling decreased liver inflammation and neutrophil infiltration, and resulted in enhanced regeneration of hepatocytes and increased rate of recovery from liver injury in AH. Our novel findings suggest that IL-1 drives sustained liver inflammation and impaired hepatocyte regeneration even after cessation of ethanol exposure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model.

    Science.gov (United States)

    Murata, Hiroshi; Yagi, Takahito; Iwagaki, Hiromi; Ogino, Tetsuya; Sadamori, Hiroshi; Matsukawa, Hiroyoshi; Umeda, Yuzoh; Haga, Sanae; Takaka, Noriaki; Ozaki, Michitaka

    2007-12-01

    The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH). db/db fatty mice and lean littermates were used for the experiments. Following 70% PH, the survival rate and recovery of liver mass were examined. Liver tissue was histologically examined and analyzed by western blotting and RT-PCR. Of 35 db/db mice, 25 died within 48 h of PH, while all of the control mice survived. Liver regeneration of surviving db/db mice was largely impaired. In db/db mice, mitosis of hepatocytes after PH was disturbed, even though proliferating cell nuclear antigen (PCNA) expression (G1 to S phase marker) in hepatocytes was equally observed in both mice groups. Interestingly, phosphorylation of Cdc2 in db/db mice was suppressed by reduced expression of Wee1 and Myt1, which phosphorylate Cdc2 in S to G2 phase. In steatotic liver, cell-cycle-related proliferative disorders occurred at mid-S phase after PCNA expression. Reduced expression of Wee1 and Myt1 kinases may therefore maintain Cdc2 in an unphosphorylated state and block cell cycle progression in mid-S phase. These kinases may be critical factors involved in the impaired liver regeneration in fatty liver.

  11. Liver regeneration signature in hepatitis B virus (HBV-associated acute liver failure identified by gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Oriel Nissim

    Full Text Available The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC. The dramatic clinical course of acute liver failure (ALF has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV-associated ALF.Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients and submassive hepatic necrosis (SHN; 2 patients. We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7, whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process.Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between

  12. Impact of NKT Cells and LFA-1 on Liver Regeneration under Subseptic Conditions.

    Directory of Open Access Journals (Sweden)

    Ann-Kathrin Jörger

    Full Text Available Activation of the immune system in terms of subseptic conditions during liver regeneration is of paramount clinical importance. However, little is known about molecular mechanisms and their mediators that control hepatocyte proliferation. We sought to determine the functional role of immune cells, especially NKT cells, in response to partial hepatectomy (PH, and to uncover the impact of the integrin lymphocyte function-associated antigen-1 (LFA-1 on liver regeneration in a subseptic setting.Wild-type (WT and LFA-1-/- mice underwent a 2/3 PH and low-dose lipopolysaccharid (LPS application. Hepatocyte proliferation, immune cell infiltration, and cytokine profile in the liver parenchyma were determined.Low-dose LPS application after PH results in a significant delay of liver regeneration between 48h and 72h, which is associated with a reduced number of CD3+ cells within the regenerating liver. In absence of LFA-1, an impaired regenerative capacity was observed under low-dose LPS application. Analysis of different leukocyte subpopulations showed less CD3+NK1.1+ NKT cells in the liver parenchyma of LFA-1-/- mice after PH and LPS application compared to WT controls, while CD3-NK1.1+ NK cells markedly increased. Concordantly with this observation, lower levels of NKT cell related cytokines IL-12 and IL-23 were expressed in the regenerating liver of LFA-1-/- mice, while the expression of NK cell-associated CCL5 and IL-10 was increased compared to WT mice.A subseptic situation negatively alters hepatocyte proliferation. Within this scenario, we suggest an important impact of NKT cells and postulate a critical function for LFA-1 during processes of liver regeneration.

  13. JNK1 induces hedgehog signaling from stellate cells to accelerate liver regeneration in mice.

    Science.gov (United States)

    Langiewicz, Magda; Graf, Rolf; Humar, Bostjan; Clavien, Pierre A

    2018-04-27

    To improve outcomes of two-staged hepatectomies for large/multiple liver tumors, portal vein ligation (PVL) has been combined with parenchymal transection (coined ALPPS; Associated Liver Partition and Portal vein ligation for Staged hepatectomy) to greatly accelerate liver regeneration. In a novel ALPPS mouse model, we have reported paracrine Indian hedgehog (IHH) signaling from stellate cells as an early contributor to augmented regeneration. Here, we sought to identify upstream regulators of IHH. ALPPS in mice was compared against PVL and additional control surgeries. Potential IHH regulators were identified through in silico mining of transcriptomic data. JNK1 activity was reduced through SP600125 to evaluate its effects on IHH signaling. Recombinant IHH was injected after JNK diminution to substantiate their relationship during accelerated liver regeneration. Mining linked Ihh to Mapk8. JNK1 upregulation after ALPPS was validated and preceded the IHH peak. On immunofluorescence, JNK1 and IHH co-localized in ASMA-positive non-parenchymal cells. Inhibition of JNK1 prior to ALPPS surgery reduced liver weight gain to PVL levels and was accompanied by downregulation of hepatocellular proliferation and the IHH-GLI1-CCND1 axis. In JNK1-inhibited mice, recombinant IHH restored ALPPS-like acceleration of regeneration and re-elevated JNK1 activity, suggesting the presence of a positive IHH-JNK1 feedback loop. JNK1-mediated induction of IHH paracrine signaling from HSCs is essential for accelerated regeneration of parenchymal mass. The JNK1-IHH axis is a mechanism unique to ALPPS surgery and may point to therapeutic alternatives for patients with insufficient regenerative capacity. ALPPS, a novel two-staged hepatectomy, induces an unprecedented acceleration of liver regeneration to enable treatment of unresectable liver tumors. Here, we demonstrate JNK1-IHH signaling as a mechanism underlying the regenerative acceleration induced by ALPPS. Copyright © 2018 European

  14. Monocytes with angiogenic potential are selectively induced by liver resection and accumulate near the site of liver regeneration.

    Science.gov (United States)

    Schauer, Dominic; Starlinger, Patrick; Zajc, Philipp; Alidzanovic, Lejla; Maier, Thomas; Buchberger, Elisabeth; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

    2014-10-30

    Monocytes reportedly contribute to liver regeneration. Three subsets have been identified to date: classical, intermediate, non-classical monocytes. The intermediate population and a subtype expressing TIE2 (TEMs) were suggested to promote angiogenesis. In a clinical setting, we investigated which monocyte subsets are regulated after liver resection and correlate with postoperative liver function. In 38 patients monocyte subsets were evaluated in blood and subhepatic wound fluid by flow cytometry before and 1-3 days after resection of colorectal liver metastases. The monocyte-regulating cytokines macrophage colony stimulating factor (M-CSF), transforming growth factor beta 1 (TGFβ1), and angiopoietin 2 (ANG-2) were measured in patient plasma by ELISA. C-reactive protein (CRP) and liver function parameters were retrieved from routine hospital analyses. On post-operative day (POD) 1 blood monocytes shifted to significantly elevated levels of intermediate monocytes. In wound fluid, a delayed surge in intermediate monocytes was detected by POD 3. Furthermore, TEMs were highly enriched in wound fluid as compared to circulation. CRP and M-CSF levels were substantially increased in patient blood after surgery and correlated significantly with the frequency of intermediate monocytes. In addition, liver function parameters showed a significant association with intermediate monocyte levels on POD 3. The reportedly pro-angiogenic subsets of monocytes are selectively increased upon liver resection and accumulate next to the site of liver regeneration. As previously proposed by in vitro experiments, the release of CRP and M-CSF may trigger the induction of intermediate monocytes. The correlation with liver parameters points to a functional involvement of these monocyte populations in liver regeneration which warrants further investigation.

  15. 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

  16. Mitochondrial DNA Unwinding Enzyme Required for Liver Regeneration | Center for Cancer Research

    Science.gov (United States)

    The liver has an exceptional capacity to proliferate. This ability allows the liver to regenerate its mass after partial surgical removal or injury and is the key to successful partial liver transplants. Liver cells, called hepatocytes, are packed with mitochondria, and regulating mitochondrial DNA (mtDNA) copy number is crucial to mitochondrial function, including energy production, during proliferation. Yves Pommier, M.D., Ph.D., of CCR’s Developmental Therapeutics Branch, and his colleagues recently showed that the vertebrate mitochondrial topoisomerase, Top1mt, was critical in maintaining mitochondrial function in the heart after doxorubicin-induced damage. The group wondered whether Top1mt might play a similar role in liver regeneration.

  17. Epidermal growth factor receptor restoration rescues the fatty liver regeneration in mice.

    Science.gov (United States)

    Zimmers, Teresa A; Jin, Xiaoling; Zhang, Zongxiu; Jiang, Yanlin; Koniaris, Leonidas G

    2017-10-01

    Hepatic steatosis is a common histological finding in obese patients. Even mild steatosis is associated with delayed hepatic regeneration and poor outcomes following liver resection or transplantation. We sought to identify and target molecular pathways that mediate this dysfunction. Lean mice and mice made obese through feeding of a high-fat, hypercaloric diet underwent 70 or 80% hepatectomy. After 70% resection, obese mice demonstrated 100% survival but experienced increased liver injury, reduced energy stores, reduced mitoses, increased necroapoptosis, and delayed recovery of liver mass. Increasing liver resection to 80% was associated with mortality of 40% in lean and 80% in obese mice ( P steatosis might promote liver regeneration and survival following hepatic resection or transplantation. Copyright © 2017 the American Physiological Society.

  18. CXC chemokines function as a rheostat for hepatocyte proliferation and liver regeneration.

    Directory of Open Access Journals (Sweden)

    Gregory C Wilson

    Full Text Available Our previous in vitro studies have demonstrated dose-dependent effects of CXCR2 ligands on hepatocyte cell death and proliferation. In the current study, we sought to determine if CXCR2 ligand concentration is responsible for the divergent effects of these mediators on liver regeneration after ischemia/reperfusion injury and partial hepatectomy.Murine models of partial ischemia/reperfusion injury and hepatectomy were used to study the effect of CXCR2 ligands on liver regeneration.We found that hepatic expression of the CXCR2 ligands, macrophage inflammatory protein-2 (MIP-2 and keratinocyte-derived chemokine (KC, was significantly increased after both I/R injury and partial hepatectomy. However, expression of these ligands after I/R injury was 30-100-fold greater than after hepatectomy. Interestingly, the same pattern of expression was found in ischemic versus non-ischemic liver lobes following I/R injury with expression significantly greater in the ischemic liver lobes. In both systems, lower ligand expression was associated with increased hepatocyte proliferation and liver regeneration in a CXCR2-dependent fashion. To confirm that these effects were related to ligand concentration, we administered exogenous MIP-2 and KC to mice undergoing partial hepatectomy. Mice received a "high" dose that replicated serum levels found after I/R injury and a "low" dose that was similar to that found after hepatectomy. Mice receiving the "high" dose had reduced levels of hepatocyte proliferation and regeneration whereas the "low" dose promoted hepatocyte proliferation and regeneration.Together, these data demonstrate that concentrations of CXC chemokines regulate the hepatic proliferative response and subsequent liver regeneration.

  19. Sciatic nerve regeneration in rats subjected to ketogenic diet.

    Science.gov (United States)

    Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

    2016-01-01

    Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

  20. Improved hepatocyte function of future liver remnant of cirrhotic rats after portal vein ligation: a bonus other than volume shifting.

    Science.gov (United States)

    Lin, Kun-Ju; Liao, Chien-Hung; Hsiao, Ing-Tsung; Yen, Tzu-Chen; Chen, Tse-Ching; Jan, Yi-Yin; Chen, Miin-Fu; Yeh, Ta-Sen

    2009-02-01

    Preoperative portal vein embolization is increasingly employed for those with hepatocellular carcinoma and cirrhosis to gain a volume-shifting effect. However, the alterations of histologic architecture and hepatocyte function of future liver remnant (FLR) remain unexplored. Portal vein ligation (PVL) was performed in cirrhotic and noncirrhotic rats. Regeneration indices that include the DNA synthesis index, restituted liver mass, and the redistributed volume ratio were measured. The indocyanine green 15' retention test (ICG-R15), histologic changes, total Knodell score, and activated hepatic stellate cells (HSCs) were measured before and after PVL. Tc-99m sulfur-colloid liver single photon emission computed tomography (SPECT) and diisopropyl iminoacetic acid (DISIDA) SPECT were conducted. The redistributed volume ratio of cirrhotic rats was less than noncirrhotic rats (63% vs 80%, P baseline (6.0 +/- 4.1% vs 15.8 +/- 4.6%, P baseline. The redistributed volume ratio of noncirrhotic and cirrhotic rats based on 99mTc sulfur-colloid SPECT were 79% and 64%, respectively. The clearance T(1/2) of FLR in cirrhotic rats based on DISIDA SPECT was decreased compared with baseline (5.2 +/- 1.9 min vs 8.6 +/- 3.1 min). The regenerated functional liver mass of cirrhotic rats after PVL is less than noncirrhotic rats, whereas the hepatocyte function of FLR in cirrhotic rats is improved relevant to tissue remodeling.

  1. Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2018-01-01

    Full Text Available The liver has the potential to regenerate after injury. It is a challenge to improve liver regeneration (LR after liver resection in clinical practice. Bone morrow-derived mesenchymal stem cells (MSCs have shown to have a role in various liver diseases. To explore the effects of MSCs on LR, we established a model of 70% partial hepatectomy (PHx. Results revealed that infusion of MSCs could improve LR through enhancing cell proliferation and cell growth during the first 2 days after PHx, and MSCs could also restore liver synthesis function. Infusion of MSCs also improved liver lipid accumulation partly via mechanistic target of rapamycin (mTOR signaling and enhanced lipid β-oxidation support energy for LR. Rapamycin-induced inhibition of mTOR decreased liver lipid accumulation at 24 h after PHx, leading to impaired LR. And after infusion of MSCs, a proinflammatory environment formed in the liver, evidenced by increased expression of IL-6 and IL-1β, and thus the STAT3 and Hippo-YAP pathways were activated to improve cell proliferation. Our results demonstrated the function of MSCs on LR after PHx and provided new evidence for stem cell therapy of liver diseases.

  2. Biphasic activation of liver regeneration-associated signals in an early stage after portal vein branch ligation

    International Nuclear Information System (INIS)

    Yokoyama, Shinya; Yokoyama, Yukihiro; Kawai, Toru; Kobayashi, Satoshi; Nagino, Masato; Oda, Koji; Nimura, Yuji; Sokabe, Masahiro

    2006-01-01

    At an early stage in liver regeneration, a variety of factors including transcriptional factors, proinflammatory cytokines, and proto-oncogenes are activated or expressed. However, these responses are affected by surgical stress in the conventional portal vein branch ligation model (PVL). We sought to determine the net activation of early regeneration-associated signals after PVL using a newly developed non-surgical stress PVL model. Male Wistar rats were assigned into two groups, a stress-PVL (sPVL) model with laparotomy and portal vein branch ligation, and a non-stress-PVL (nsPVL) one subjected to portal vein branch ligation 1 week after laparotomy in which the effects of surgical stress were subsided. The activation of transcriptional factors and expression of immediate early genes were analyzed at an early time point (within 24 h) by Western blotting and RT-PCR, respectively. A monophasic upregulation of nuclear factor-κB (NF-κB) and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) peaked at 3 h after sPVL was observed. In contrast, the expression pattern of these factors was biphasic (first peak at 0.5-1 h, second peak at 3-6 h) in nsPVL group. The expression pattern of immediate early genes showed a similar trend between sPVL and nsPVL. cDNA array analysis for the non-ligated lobe at 2 h after PVL revealed a much higher gene activation in sPVL than in nsPVL. These results indicate that previously observed activation pattern of regeneration-associated signals after PVL is significantly affected by the effect of laparotomy and our results using nsPVL model may more accurately represent liver regeneration-associated signal pattern

  3. Structural changes in the regenerating rat thymus after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Tetsuo; Wang, Yu-Hsueh; Hashimoto, Noriko; Tokuda, Nobuko; Sawada, Tomoo [Yamaguchi Univ., Ube (Japan). School of Medicine

    1999-11-01

    The structural changes of the rat thymus after irradiation were examined. Thymocytes regenerate rapidly after irradiation and the mechanism responsible for this rapid regeneration was examined analyzing vascular and immunohistochemical changes in the thymus. Following results were obtained: Vascular fine mesh works in the cortex were destroyed on day 3 after 6 Gy irradiation, while on day 5 these changes appeared to be restored to almost normal. Massive macrophage accumulations were observed in the cortex on day 3-5 after irradiation. This may be due to clean up the damaged thymocytes, although other possibility, as production of cytokines which may contribute to the rapid proliferation must be intensively examined. Immunohistochemical staining with anti MHC class II molecule showed relatively strong staining in the medulla compared to the cortex in the normal thymus, while this finding was reversed and cortex stained heavily compared to the medulla on day 5-7 after irradiation suggesting the importance of the cortical MHC class II positive thymic epithelial cells in regeneration of thymocytes. Anti FTS antibody stained relatively strongly in the irradiated and recovering thymus compared to the normal. These results may partly explain the abrupt proliferation of thymocytes after irradiation and further studies on cytokine message changes and thymic epithelial characterization responsible to produce the cytokines for the effective thymocyte proliteration are on the way of analysis. (author)

  4. Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Takao; Iizuka, Tadashi; Kanamori, Takeshi; Yokoyama, Atsuro [Department of Oral Functional Prosthodontics, Division of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8586 (Japan); Matsumura, Sachiko; Shiba, Kiyotaka [Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, koutou-ku, Tokyo 135-8550 (Japan); Yudasaka, Masako; Iijima, Sumio, E-mail: tkasai@den.hokudai.ac.jp [Nanotube Research Center, National Institute of Advanced Industrial Science and Technology, Central 5, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8565 (Japan)

    2011-02-11

    A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possible medical uses such as in drug delivery systems. It was reported that some kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. However, the effect of CNHs on bone tissue has not been clarified. The purpose of this study was to evaluate the effect of CNHs on bone regeneration and their possible application for guided bone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porous polytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created in rats and covered by a membrane with/without CNHs. At two weeks, bone formation under the membrane with CNHs had progressed more than under that without CNHs and numerous macrophages were observed attached to CNHs. At eight weeks, there was no significant difference in the amount of newly formed bone between the groups and the appearance of macrophages was decreased compared with that at two weeks. Newly formed bone attached to some CNHs directly. These results suggest that macrophages induced by CNHs are related to bone regeneration. In conclusion, the present study indicates that CNHs are compatible with bone tissue and effective as a material for GBR.

  5. Implications of microbiota and bile acid in liver injury and regeneration.

    Science.gov (United States)

    Liu, Hui-Xin; Keane, Ryan; Sheng, Lili; Wan, Yu-Jui Yvonne

    2015-12-01

    Studies examining the mechanisms by which the liver incurs injury and then regenerates usually focus on factors and pathways directly within the liver, neglecting the signaling derived from the gut-liver axis. The intestinal content is rich in microorganisms as well as metabolites generated from both the host and colonizing bacteria. Through the gut-liver axis, this complex "soup" exerts an immense impact on liver integrity and function. This review article summarizes data published in the past 30 years demonstrating the signaling derived from the gut-liver axis in relation to liver injury and regeneration. Due to the intricate networks of implicated pathways as well as scarcity of available mechanistic data, it seems that nutrigenomic, metabolomics, and microbiota profiling approaches are warranted to provide a better understanding regarding the interplay and impact between nutrition, bacteria, and host response in influencing liver function and healing. Therefore elucidating the possible molecular mechanisms that link microbiota alteration to host physiological response and vice versa. Published by Elsevier B.V.

  6. Comparative retention of fission fragment 147Pm in regenerated and fetal liver on induction of chromosome aberrations in these cells

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Zheng Siying; Wang Liuyi; Yang Shujin

    1989-01-01

    The purpose of the present study is to ascertain comparative retention of fission fragment 147 Pm in regenerated and fetal liver on induction of chromosome aberrations in these cells. The results indicated that retention of 147 Pm in regenerated liver was about 700 times than in fetal liver. The cumulative absorption dose in regenerated liver was about 2.87 Gy, while in fetal liver-only 0.004 Gy. Under the same conditions, the incidence rate of chromosome aberrations in regenerated liver cells induced by 147 Pm was 50.2%, and in fetal liver cells-about 28.3%. It should be concluded that the radiosensitivity to 147 Pm was not uniform among the regenerated and fetal liver cells. The study suggested that fetal liver cells show to be more radiosensitive to 147 Pm than regenerated liver cells. Among the type of aberrations in both cells induced by 147 Pm, chromatid breakages were predominant, accompanied with a few chromosome breakages

  7. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

    Directory of Open Access Journals (Sweden)

    Honglei eWeng

    2015-06-01

    Full Text Available Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called second pathway of liver regeneration. The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

  8. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

    Science.gov (United States)

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

  9. Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice

    DEFF Research Database (Denmark)

    Yuan, Haixin; Zhang, Hong; Wu, Xunwei

    2009-01-01

    Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42...... in regulating liver regeneration. Using a mouse model with liver-specific knockout of Cdc42 (Cdc42LK), we studied liver regeneration after partial hepatectomy. Histological analysis, immunostaining, and western blot analysis were performed to characterize Cdc42LK livers and to explore the role of Cdc42 in liver...... regeneration. In control mouse livers, Cdc42 became activated between 3 and 24 hours after partial hepatectomy. Loss of Cdc42 led to a significant delay of liver recovery after partial hepatectomy, which was associated with reduced and delayed DNA synthesis indicated by 5-bromo-2'-deoxyuridine staining...

  10. Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice.

    Directory of Open Access Journals (Sweden)

    Antonino Sgroi

    Full Text Available BACKGROUND: Cytokine administration is a potential therapy for acute liver failure by reducing inflammatory responses and favour hepatocyte regeneration. The aim of this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra during liver regeneration and to study the effect of a recombinant human IL-1ra on liver regeneration. METHODS: We performed 70%-hepatectomy in wild type (WT mice, IL-1ra knock-out (KO mice and in WT mice treated by anakinra. We analyzed liver regeneration at regular intervals by measuring the blood levels of cytokines, the hepatocyte proliferation by bromodeoxyuridin (BrdU incorporation, proliferating cell nuclear antigen (PCNA and Cyclin D1 expression. The effect of anakinra on hepatocyte proliferation was also tested in vitro using human hepatocytes. RESULTS: At 24h and at 48 h after hepatectomy, IL-1ra KO mice had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-1β and MCP-1 and a reduced and delayed hepatocyte proliferation measured by BrdU incorporation, PCNA and Cyclin D1 protein levels, when compared to WT mice. IGFBP-1 and C/EBPβ expression was significantly decreased in IL-1ra KO compared to WT mice. WT mice treated with anakinra showed significantly decreased levels of IL-6 and significantly higher hepatocyte proliferation at 24h compared to untreated WT mice. In vitro, primary human hepatocytes treated with anakinra showed significantly higher proliferation at 24h compared to hepatocytes without treatment. CONCLUSION: IL1ra modulates the early phase of liver regeneration by decreasing the inflammatory stress and accelerating the entry of hepatocytes in proliferation. IL1ra might be a therapeutic target to improve hepatocyte proliferation.

  11. Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.

    Science.gov (United States)

    Viswanathan, Preeti; Sharma, Yogeshwar; Gupta, Priya; Gupta, Sanjeev

    2018-03-05

    Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure. Cellular oxidative stress, DNA damage and cell proliferation events were investigated by mitochondrial membrane potential assays, flow cytometry, fluorescence staining, comet assays and spotted arrays for protein expression after acetaminophen exposures. In experimental groups with acetaminophen toxicity, impaired mitochondrial viability and substantial DNA damage were observed with rapid loss of cells in S and G2/M and cell cycle restrictions or even exit in the remainder. This resulted from altered expression of the DNA damage regulator, ATM and downstream transducers, which imposed G1/S checkpoint arrest, delayed entry into S and restricted G2 transit. Tissues from people with acute liver failure confirmed hepatic DNA damage and cell cycle-related lesions, including restrictions of hepatocytes in aneuploid states. Remarkably, treatment of cells with a cytoprotective cytokine reversed acetaminophen-induced restrictions to restore cycling. Cell cycle lesions following mitochondrial and DNA damage led to failure of hepatic regeneration in acetaminophen toxicity but their reversibility offers molecular targets for treating acute liver failure. © 2018 John Wiley & Sons Ltd.

  12. 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.)

  13. 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.

  14. 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

  15. The Role of Platelets in Liver Inflammation and Regeneration

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    Platelets play a pivotal role in thrombosis and hemostasis, but an increasing variety of extra-hemostatic functions of platelets are being recognized. This review summarizes recent advances in the understanding of the role of platelets in various pathologies involving the liver. In

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. 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.

  1. 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.

  2. Impaired liver regeneration is associated with reduced cyclin B1 in natural killer T cell-deficient mice.

    Science.gov (United States)

    Ben Ya'acov, Ami; Meir, Hadar; Zolotaryova, Lydia; Ilan, Yaron; Shteyer, Eyal

    2017-03-23

    It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important. The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice. Ki-67 and proliferating cell nuclear antigen were used to measure hepatocytes proliferation. Expression of hepatic cyclin B1 and proliferating cell nuclear antigen were evaluated by Western Blot and liver injury was assessed by ALT and histology. Natural killer T cells- deficient or mice injected with anti CD1d antibodies exhibited reduced liver regeneration. These mice were considerably resistant to ConA-induced liver injury. In the absence of NKT cells hepatic proliferating cell nuclear antigen and cyclin B1 decreased in mice injected with Concanvalin A before partial hepatectomy. This was accompanied with reduced serum interleukin-6 levels. Natural killer T cells play an important role in liver regeneration, which is associated with cyclin B1 and interleukin-6.

  3. Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration

    International Nuclear Information System (INIS)

    Panduro, A.; Shalaby, F.; Weiner, F.R.; Biempica, L.; Zern, M.A.; Shafritz, D.A.

    1986-01-01

    During liver regeneration induced by CCl 4 administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl 4 administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal [ 3 H]thymidine incorporation into DNA which peaks at 48 h. Other genes related to liver-specific functions, such as ligandin, alpha 1-antitrypsin, and cytochrome P-450's, as well as general cellular genes pro alpha 1- and pro alpha 2-collagen, beta-actin, and alpha-tubulin, respond in kinetic patterns often distinct from each other and from albumin and alpha-fetoprotein. Changes in the steady-state levels of albumin and alpha-fetoprotein mRNA correlate with changes in transcription, but there is a lag in alpha-fetoprotein mRNA accumulation, which peaks at 72 h following CCl 4 administration. These studies indicate that reciprocal changes in albumin and alpha-fetoprotein gene transcription occur during CCl 4 -induced liver regeneration, leading to changes in the level of these specific mRNAs. These changes precede DNA synthesis and would appear to represent an alteration in differentiated function of hepatocytes in conjunction with the liver regenerative process

  4. The Dilator Naris Muscle as a Reporter of Facial Nerve Regeneration in a Rat Model

    NARCIS (Netherlands)

    Weinberg, J.S.; Kleiss, I.J.; Knox, C.J.; Heaton, J.T.; Hadlock, T.A.

    2016-01-01

    OBJECTIVE: Many investigators study facial nerve regeneration using the rat whisker pad model, although widely standardized outcomes measures of facial nerve regeneration in the rodent have not yet been developed. The intrinsic whisker pad "sling" muscles producing whisker protraction, situated at

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

    Directory of Open Access Journals (Sweden)

    R.R. Guerra

    2009-11-01

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

  6. 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

  7. Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy.

    Science.gov (United States)

    Ezquer, Fernando; Bahamonde, Javiera; Huang, Ya-Lin; Ezquer, Marcelo

    2017-01-28

    The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. However, pre-existing pathological abnormalities, such as hepatic steatosis (HS), inhibits the endogenous regenerative process, becoming an obstacle for liver surgery and living donor transplantation. Recent evidence indicates that multipotent mesenchymal stromal cells (MSCs) administration can improve hepatic function and increase the potential for liver regeneration in patients with liver damage. Since HS is the most common form of chronic hepatic illness, in this study we evaluated the role of MSCs in liver regeneration in an animal model of severe HS with impaired liver regeneration. C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30 weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5 × 10 5 MSCs or vehicle via the tail vein immediately after Hpx. We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice. MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation.

  8. Integrative and comparative genomics analysis of early hepatocellular carcinoma differentiated from liver regeneration in young and old

    Directory of Open Access Journals (Sweden)

    Ozand Pinar T

    2010-06-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is the third-leading cause of cancer-related deaths worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. To identify distinct molecular mechanisms for early HCC we developed a rat model of liver regeneration post-hepatectomy, as well as liver cells undergoing malignant transformation and compared them to normal liver using a microarray approach. Subsequently, we performed cross-species comparative analysis coupled with copy number alterations (CNA of independent early human HCC microarray studies to facilitate the identification of critical regulatory modules conserved across species. Results We identified 35 signature genes conserved across species, and shared among different types of early human HCCs. Over 70% of signature genes were cancer-related, and more than 50% of the conserved genes were mapped to human genomic CNA regions. Functional annotation revealed genes already implicated in HCC, as well as novel genes which were not previously reported in liver tumors. A subset of differentially expressed genes was validated using quantitative RT-PCR. Concordance was also confirmed for a significant number of genes and pathways in five independent validation microarray datasets. Our results indicated alterations in a number of cancer related pathways, including p53, p38 MAPK, ERK/MAPK, PI3K/AKT, and TGF-β signaling pathways, and potential critical regulatory role of MYC, ERBB2, HNF4A, and SMAD3 for early HCC transformation. Conclusions The integrative analysis of transcriptional deregulation, genomic CNA and comparative cross species analysis brings new insights into the molecular profile of early hepatoma formation. This approach may lead to robust biomarkers for the detection of early human HCC.

  9. Regeneration

    Science.gov (United States)

    George A. Schier; Wayne D. Shepperd; John R. Jones

    1985-01-01

    There are basically two approaches to regenerating aspen stands-sexual reproduction using seed, or vegetative regeneration by root suckering. In the West, root suckering is the most practical method. The advantage of having an existing, well established root system capable of producing numerous root suckers easily outweighs natural or artificial reforestation in the...

  10. 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 ...

  11. 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 ...

  12. Expression of liver functions following sub-lethal and non-lethal doses of allyl alcohol and acetaminophen in the rat

    DEFF Research Database (Denmark)

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

    1997-01-01

    BACKGROUND/AIMS: To relate severity of intoxication with allyl alcohol and acetaminophen to modulated hepatic gene expression of liver functions and regeneration. METHODS: Rats fasted for 12 h received acetaminophen 3.5 or 5.6 g per kg body weight, or allyl alcohol 100 or 125 microl by gastric tu...

  13. The circadian optimal time for hepatectomy in the study of liver regeneration.

    Science.gov (United States)

    Souto, M; Llanos, J M

    1985-01-01

    Standardized (light from 0600 to 1800) C3HS mice, hepatectomized at different circadian stages, were killed at 1400 (the peak time of mitotic activity in intact mice). The higher values of mitotic index were those of mice operated at 1400, 48 hr before. The curve of mitotic activity of the regenerating liver of mice operated at 1400 and that of mice operated at 0200 (an opposite time in the circadian stage) are, both, grossly in phase with the curves of mitotic index in young and adult mice liver. The amplitude of the first peak of mitotic activity in mice operated at 0200 was dramatically lower than that of animals operated at 1400. The same applies to hepatocytes as well as to the sinusoid litoral population of cells. It is concluded that 1400 hr, as contrast to 0200 hr, is an optimal time for hepatectomy if one wants to obtain the highest mitotic index first peak during regeneration in a normal phase position (the position of the mitotic index peak in the liver of normal young and adult mice).

  14. 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

  15. Reversal of Liver Fibrosis in Chronic Murine Schistosomiasis ...

    African Journals Online (AJOL)

    In schistosomiasis, healing of parasite egg- induced liver ... greater in liver than in other tissues. It has been reported that ..... biology, diseases, and potentials for therapy. Annul Rev Biochem ... regeneration in cirrhotic rats. J Hepatol, 2002;.

  16. 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)

  17. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S

    2005-01-01

    created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations...... cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment...

  18. Proteome analysis of a hepatocyte-specific BIRC5 (survivin)-knockout mouse model during liver regeneration.

    Science.gov (United States)

    Bracht, Thilo; Hagemann, Sascha; Loscha, Marius; Megger, Dominik A; Padden, Juliet; Eisenacher, Martin; Kuhlmann, Katja; Meyer, Helmut E; Baba, Hideo A; Sitek, Barbara

    2014-06-06

    The Baculoviral IAP repeat-containing protein 5 (BIRC5), also known as inhibitor of apoptosis protein survivin, is a member of the chromosomal passenger complex and a key player in mitosis. To investigate the function of BIRC5 in liver regeneration, we analyzed a hepatocyte-specific BIRC5-knockout mouse model using a quantitative label-free proteomics approach. Here, we present the analyses of the proteome changes in hepatocyte-specific BIRC5-knockout mice compared to wildtype mice, as well as proteome changes during liver regeneration induced by partial hepatectomy in wildtype mice and mice lacking hepatic BIRC5, respectively. The BIRC5-knockout mice showed an extensive overexpression of proteins related to cellular maintenance, organization and protein synthesis. Key regulators of cell growth, transcription and translation MTOR and STAT1/STAT2 were found to be overexpressed. During liver regeneration proteome changes representing a response to the mitotic stimulus were detected in wildtype mice. Mainly proteins corresponding to proliferation, cell cycle and cytokinesis were up-regulated. The hepatocyte-specific BIRC5-knockout mice showed impaired liver regeneration, which had severe consequences on the proteome level. However, several proteins with function in mitosis were found to be up-regulated upon the proliferative stimulus. Our results show that the E3 ubiquitin-protein ligase UHRF1 is strongly up-regulated during liver regeneration independently of BIRC5.

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

    Directory of Open Access Journals (Sweden)

    Ying Zhang

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

  20. 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.

  1. Reference intervals for putative biomarkers of drug-induced liver injury and liver regeneration in healthy human volunteers.

    Science.gov (United States)

    Francis, Ben; Clarke, Joanna I; Walker, Lauren E; Brillant, Nathalie; Jorgensen, Andrea L; Park, B Kevin; Pirmohamed, Munir; Antoine, Daniel J

    2018-05-02

    The potential of mechanistic biomarkers to improve the prediction of drug-induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration as well as to characterize their natural variability and impact of diurnal variation. Serum samples from 200 healthy volunteers were recruited as part of a cross sectional study; of these, 50 subjects had weekly serial sampling over 3 weeks, while 24 had intensive blood sampling over a 24h period. Alanine aminotransferase (ALT), MicroRNA-122 (miR-122), high mobility group box-1 (HMGB1), total keratin-18 (FL-K18), caspase cleaved keratin-18 (cc-K18), glutamate dehydrogenase (GLDH) and colony stimulating factor-1 (CSF-1) were assessed by validated assays. Reference intervals were established for each biomarker based on the 97.5% quantile (90% CI) following the assessment of fixed effects in univariate and multivariable models (ALT 50 (41-50) U/l, miR-122 3548 (2912-4321) copies/µl, HMGB1 2.3 (2.2-2.4) ng/ml, FL-K18 475 (456-488) U/l, cc-K18 272 (256-291) U/l, GLDH 27 (26-30) U/l and CSF-1 2.4 (2.3-2.9) ng/ml). There was a small but significant intra-individual time random effect detected but no significant impact of diurnal variation was observed, with the exception of GLDH. Reference intervals for novel DILI biomarkers have been described for the first time. An upper limit of a reference range might represent the most appropriate method to utilize these data. Regulatory authorities have published letters of support encouraging further qualification of leading candidate biomarkers. These data can now be used to interpret data from exploratory clinical DILI studies and to assist their further qualification. Drug-induced liver injury (DILI) has a big impact on patient health and the development of new medicines. Unfortunately, currently used blood-based tests to assess liver injury and recovery suffer from insufficiencies. Newer blood

  2. 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)

  3. Phosphatase of Regenerating Liver-3 Promotes Motility and Metastasis of Mouse Melanoma Cells

    Science.gov (United States)

    Wu, Xiaopeng; Zeng, Hu; Zhang, Xianming; Zhao, Ying; Sha, Haibo; Ge, Xiaomei; Zhang, Minyue; Gao, Xiang; Xu, Qiang

    2004-01-01

    Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be involved in colorectal carcinoma metastasis with an unknown mechanism. Here we demonstrated that PRL-3 expression was up-regulated in human liver carcinoma compared with normal liver. PRL-3 was also highly expressed in metastatic melanoma B16-BL6 cells but not in its lowly metastatic parental cell line, B16 cells. B16 cells transfected with PRL-3 cDNA displayed morphological transformation from epithelial-like shape to fibroblast-like shape. PRL-3-overexpressed cells showed much higher migratory ability, which could be reversed by specific anti-sense oligodeoxynucleotide and the phosphatase inhibitors sodium orthovanadate or potassium bisperoxo oxovanadate V. Meanwhile, the expression of the catalytically inactive PRL-3 mutations (D72A or C104S) significantly reduced the cell migratory capability. In addition, PRL-3 transfectants demonstrated altered extracellular matrix adhesive property and up-regulated integrin-mediated cell spreading efficiency. Furthermore, we confirmed that PRL-3 could facilitate lung and liver metastasis of B16 cells in an experimental metastasis model in mice, consistent with accelerated proliferation and growth rate both in vitro and in vivo. Together, these observations provide convincing evidence that PRL-3 truly plays a causal role in tumor metastasis. PMID:15161639

  4. Splenectomy after partial hepatectomy accelerates liver regeneration in mice by promoting tight junction formation via polarity protein Par 3-aPKC.

    Science.gov (United States)

    Liu, Guoxing; Xie, Chengzhi; Fang, Yu; Qian, Ke; Liu, Qiang; Liu, Gao; Cao, Zhenyu; Du, Huihui; Fu, Jie; Xu, Xundi

    2018-01-01

    Several experimental studies have demonstrated that removal of the spleen accelerates liver regeneration after partial hepatectomy. While the mechanism of splenectomy promotes liver regeneration by the improvement of the formation of tight junction and the establishment of hepatocyte polarity is still unknown. We analyzed the cytokines, genes and proteins expression between 70% partial hepatectomy mice (PHx) and simultaneous 70% partial hepatectomy and splenectomy mice (PHs) at predetermined timed points. Compared with the PHx group mice, splenectomy accelerated hepatocyte proliferation in PHs group. The expression of Zonula occludens-1 (ZO-1) indicated that splenectomy promotes the formation of tight junction during liver regeneration. TNF-α, IL-6, HGF, TSP-1 and TGF-β1 were essential factors for the formation of tight junction and the establishment of hepatocytes polarity in liver regeneration. After splenectomy, Partitioning defective 3 homolog (Par 3) and atypical protein kinase C (aPKC) regulate hepatocyte localization and junctional structures in regeneration liver. Our data suggest that the time course expression of TNF-α, IL-6, HGF, TSP-1, and TGF-β1 and the change of platelets take part in liver regeneration. Combination with splenectomy accelerates liver regeneration by improvement of the tight junction formation which may help to establish hepatocyte polarity via Par 3-aPKC. This may provide a clue for us that splenectomy could accelerate liver regeneration after partial hepatectomy of hepatocellular carcinoma and living donor liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811

    Directory of Open Access Journals (Sweden)

    Qinlong Liu

    2012-01-01

    Full Text Available Pulmonary complications after liver transplantation (LT often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 μM for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG and quarter-size grafts (QSG, respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5–18 h after LT. At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNFα and IL-1β mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT.

  6. 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

  7. A20 modulates lipid metabolism and energy production to promote liver regeneration.

    Directory of Open Access Journals (Sweden)

    Scott M Damrauer

    2011-03-01

    Full Text Available Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice.We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20 and rAd.βgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV.This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings

  8. 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

  9. Hedgehog pathway mediates early acceleration of liver regeneration induced by a novel two-staged hepatectomy in mice.

    Science.gov (United States)

    Langiewicz, Magda; Schlegel, Andrea; Saponara, Enrica; Linecker, Michael; Borger, Pieter; Graf, Rolf; Humar, Bostjan; Clavien, Pierre A

    2017-03-01

    ALPPS, a novel two-staged approach for the surgical removal of large/multiple liver tumors, combines portal vein ligation (PVL) with parenchymal transection. This causes acceleration of compensatory liver growth, enabling faster and more extensive tumor removal. We sought to identify the plasma factors thought to mediate the regenerative acceleration following ALPPS. We compared a mouse model of ALPPS against PVL and additional control surgeries (n=6 per group). RNA deep sequencing was performed to identify candidate molecules unique to ALPPS liver (n=3 per group). Recombinant protein and a neutralizing antibody combined with appropriate surgeries were used to explore candidate functions in ALPPS (n=6 per group). Indian hedgehog (IHH/Ihh) levels were assessed in human ALPPS patient plasma (n=6). ALPPS in mouse confirmed significant acceleration of liver regeneration relative to PVL (pIhh mRNA, coding for a secreted ligand inducing hedgehog signaling, was uniquely upregulated in ALPPS liver (pIhh plasma levels rose 4h after surgery (pIhh alone was sufficient to induce ALPPS-like acceleration of liver growth. Conversely, blocking Ihh markedly inhibited the accelerating effects of ALPPS. In the small cohort of ALPPS patients, IHH tended to be elevated early after surgery. Ihh and hedgehog pathway activation provide the first mechanistic insight into the acceleration of liver regeneration triggered by ALPPS surgery. The accelerating potency of recombinant Ihh, and its potential effect in human ALPPS may lead to a clinical role for this protein. ALPPS, a novel two-staged hepatectomy, accelerates liver regeneration, thereby helping to treat patients with otherwise unresectable liver tumors. The molecular mechanisms behind this accelerated regeneration are unknown. Here, we elucidate that Indian hedgehog, a secreted ligand important for fetal development, is a crucial mediator of the regenerative acceleration triggered by ALPPS surgery. Copyright © 2016. Published by

  10. 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

  11. 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.

  12. Rat Liver Enzyme Release Depends on Blood Flow-Bearing Physical Forces Acting in Endothelium Glycocalyx rather than on Liver Damage

    Directory of Open Access Journals (Sweden)

    Julieta A. Díaz-Juárez

    2017-01-01

    Full Text Available We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH, apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver “pool.” Moreover, liver enzyme release depended on extracellular calcium entry possibly mediated by stretch-sensitive calcium channels, and this endothelial-mediated mechanotransduction in liver enzyme release was also evidenced by modifying the glycocalyx carbohydrate components, directionality of perfusing flow rate, and the participation of nitric oxide (NO and malondialdehyde (MDA, leading to modifications in the intracellular distribution of these enzymes mainly as nuclear enrichment of “mitochondrial” enzymes. In conclusion, the flow-induced shear stress may provide fine-tuned control of released hepatic enzymes through mediation by the endothelium glycocalyx, which provides evidence of a biological role of the enzyme release rather to be merely a biomarker for evaluating hepatotoxicity and liver damage, actually positively influencing progression of liver regeneration in mammals.

  13. Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

    International Nuclear Information System (INIS)

    Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S.

    1991-01-01

    Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue

  14. Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S. (E. P. Joslin Research Laboratory, Joslin Diabetes Center, Harvard Medical School, Boston, MA (USA))

    1991-07-15

    Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue.

  15. Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats.

    Science.gov (United States)

    Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2016-01-01

    Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. 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

  17. 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

  18. 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 ...

  19. 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

  20. 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 ...

  1. 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

  2. Liver remnant regeneration in donors after living donor liver transplantation. Long-term follow-up using CT and MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Klink, T. [INSELSPITAL - Bern University Hospital (Switzerland). Diagnostic, Interventional, and Pediatric Radiology; University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Diagnostic and Interventional Radiology; Simon, P. [Merciful Brethren Hospital, Trier (Germany). Dept. of Radiology, Neuroradiology, Sonography and Nuclearmedicine; University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Diagnostic and Interventional Radiology; Knopp, C.; Ittrich, H.; Adam, G.; Koops, A. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Diagnostic and Interventional Radiology; Fischer, L. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Dept. of Hepatobiliary Surgery and Transplant Surgery

    2014-06-15

    Purpose: To assess liver remnant volume regeneration and maintenance, and complications in the long-time follow-up of donors after living donor liver transplantation using CT and MRI. Materials and Methods: 47 donors with a mean age of 33.5 years who donated liver tissue for transplantation and who were available for follow-up imaging were included in this retrospective study. Contrast-enhanced CT and MR studies were acquired for routine follow-up. Two observers evaluated pre- and postoperative images regarding anatomy and pathological findings. Volumes were manually measured on contrast-enhanced images in the portal venous phase, and potential postoperative complications were documented. Pre- and postoperative liver volumes were compared for evaluating liver remnant regeneration. Results: 47 preoperative and 89 follow-up studies covered a period of 22.4 months (range: 1 - 84). After right liver lobe (RLL) donation, the mean liver remnant volume was 522.0 ml (± 144.0; 36.1%; n = 18), after left lateral section (LLS) donation 1,121.7 ml (± 212.8; 79.9%; n = 24), and after left liver lobe (LLL) donation 1,181.5 ml (± 279.5; 72.0%; n = 5). Twelve months after donation, the liver remnant volume were 87.3% (RLL; ± 11.8; n = 11), 95.0% (LS; ± 11.6; n = 18), and 80.1% (LLL; ± 2.0; n = 2 LLL) of the preoperative total liver volume. Rapid initial regeneration and maintenance at 80% of the preoperative liver volume were observed over the total follow-up period. Minor postoperative complications were found early in 4 patients. No severe or late complications or mortality occurred. Conclusion: Rapid regeneration of liver remnant volumes in all donors and volume maintenance over the long-term follow-up period of up to 84 months without severe or late complications are important observations for assessing the safety of LDLT donors. (orig.)

  3. Liver remnant regeneration in donors after living donor liver transplantation. Long-term follow-up using CT and MR imaging

    International Nuclear Information System (INIS)

    Klink, T.; University Medical Center Hamburg-Eppendorf, Hamburg; Simon, P.; University Medical Center Hamburg-Eppendorf, Hamburg; Knopp, C.; Ittrich, H.; Adam, G.; Koops, A.; Fischer, L.

    2014-01-01

    Purpose: To assess liver remnant volume regeneration and maintenance, and complications in the long-time follow-up of donors after living donor liver transplantation using CT and MRI. Materials and Methods: 47 donors with a mean age of 33.5 years who donated liver tissue for transplantation and who were available for follow-up imaging were included in this retrospective study. Contrast-enhanced CT and MR studies were acquired for routine follow-up. Two observers evaluated pre- and postoperative images regarding anatomy and pathological findings. Volumes were manually measured on contrast-enhanced images in the portal venous phase, and potential postoperative complications were documented. Pre- and postoperative liver volumes were compared for evaluating liver remnant regeneration. Results: 47 preoperative and 89 follow-up studies covered a period of 22.4 months (range: 1 - 84). After right liver lobe (RLL) donation, the mean liver remnant volume was 522.0 ml (± 144.0; 36.1%; n = 18), after left lateral section (LLS) donation 1,121.7 ml (± 212.8; 79.9%; n = 24), and after left liver lobe (LLL) donation 1,181.5 ml (± 279.5; 72.0%; n = 5). Twelve months after donation, the liver remnant volume were 87.3% (RLL; ± 11.8; n = 11), 95.0% (LS; ± 11.6; n = 18), and 80.1% (LLL; ± 2.0; n = 2 LLL) of the preoperative total liver volume. Rapid initial regeneration and maintenance at 80% of the preoperative liver volume were observed over the total follow-up period. Minor postoperative complications were found early in 4 patients. No severe or late complications or mortality occurred. Conclusion: Rapid regeneration of liver remnant volumes in all donors and volume maintenance over the long-term follow-up period of up to 84 months without severe or late complications are important observations for assessing the safety of LDLT donors. (orig.)

  4. 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

  5. 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.

  6. Mechanisms of blood pressure changes following renal irradiation of intact, adrenalectomized and adrenal regenerating rats

    International Nuclear Information System (INIS)

    Rosenblum, M.

    1976-01-01

    Results are reported from studies on the differences in changes in systolic arterial blood pressure following renal x-irradiation (1100 R) in adrenal-intact, adrenalectomized, and adrenal-regenerating rats and the roles of the kidneys and of the adrenal glands in the blood pressure changes

  7. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A. C.; Huddleston Slater, J. J. R.; Gielkens, P. F. M.; de Jong, J. R.; Grijpma, D. W.; Bos, R. R. M.

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a

  8. Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

    NARCIS (Netherlands)

    van Leeuwen, A.C.; Huddelston Slater, J.J.R.; Gielkens, P.F.M.; de Jong, J.R.; Grijpma, Dirk W.; Bos, R.R.M.

    2012-01-01

    The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague–Dawley rats, a

  9. 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...

  10. DNMT1 is a Required Genomic Regulator for Murine Liver Histogenesis and Regeneration

    DEFF Research Database (Denmark)

    Kaji, Kosuke; Factor, Valentina M; Andersen, Jesper B

    2016-01-01

    as transcriptome and methylation profiling. Regenerative growth was induced by partial hepatectomy and exposure to CCl4 . The impact of Dnmt1 knockdown was also analyzed in hepatic progenitor cell (HPC) lines; proliferation, apoptosis, DNA damage and sphere formation were assessed. Dnmt1 loss in postnatal...... hepatocytes caused global hypomethylation, enhanced DNA damage response and initiated a senescence state causing a progressive inability to maintain tissue homeostasis and proliferate in response to injury. The liver regenerated via activation and repopulation from progenitors due to lineage......-dependent differences in Alb-Cre expression, providing a basis for selection of less mature and therefore less damaged HPC progeny. Consistently, an efficient knockdown of Dnmt1 in cultured HPCs caused severe DNA damage, cell cycle arrest, senescence and cell death. Mx1-Cre-driven deletion of Dnmt1 in adult quiescent...

  11. Expression analysis on 14-3-3 proteins in regenerative liver following partial hepatectomy

    OpenAIRE

    Xue, Deming; Xue, Yang; Niu, Zhipeng; Guo, Xueqiang; Xu, Cunshuan

    2017-01-01

    Abstract 14-3-3 proteins play a vital part in the regulation of cell cycle and apoptosis as signaling integration points. During liver regeneration, the quiescent hepatocytes go through hypertrophy and proliferation to restore liver weight. Therefore, we speculated that 14-3-3 proteins regulate the progression of liver regeneration. In this study, we analyzed the expression patterns of 14-3-3 proteins during liver regeneration of rat to provide an insight into the regenerative mechanism using...

  12. 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.

  13. 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.

  14. ATP Binding cassette transporter gene expression in rat liver progenitor cells

    NARCIS (Netherlands)

    Ros, J.E.; Roskams, T.A.D.; Geuken, M.; Havinga, R.; Splinter, P.L.; Petersen, B.E.; LaRusso, N.F.; Kolk, van der D.M.; Kuipers, F.; Faber, K.N.; Müller, M.R.; Jansen, P.L.M.

    2003-01-01

    Background and aim: Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are

  15. ATP binding cassette transporter gene expression in rat liver progenitor cells

    NARCIS (Netherlands)

    Ros, J. E.; Roskams, T. A. D.; Geuken, M.; Havinga, R.; Splinter, P. L.; Petersen, B. E.; LaRusso, N. F.; van der Kolk, D. M.; Kuipers, F.; Faber, K. N.; Müller, M.; Jansen, P. L. M.

    2003-01-01

    BACKGROUND AND AIM: Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are

  16. ATP binding cassette transporter gene expression in rat liver progenitor cells

    NARCIS (Netherlands)

    Ros, J.E.; Roskams, TAD; Geuken, M; Havinga, R; Splinter, PL; Petersen, BE; LaRusso, NF; van der Kolk, D.M.; Kuipers, F; Faber, KN; Muller, M; Jansen, PLM

    Background and aim: Liver regeneration after severe liver damage depends in part on proliferation and differentiation of hepatic progenitor cells (HPCs). Under these conditions they must be able to withstand the toxic milieu of the damaged liver. ATP binding cassette (ABC) transporters are

  17. Time-course of cadmium-induced acute hepatotoxicity in the rat liver: the role of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Tzirogiannis, Konstantinos N.; Panoutsopoulos, Georgios I.; Hereti, Rosa I.; Alexandropoulou, Katerina N.; Basayannis, Aristidis C.; Mykoniatis, Michael G. [Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias St., 115 27, Athens (Greece); Demonakou, Maria D. [Histopathology Laboratory, Sismanoglion G.D. Hospital, Sismanogliou 1, Marousi, Attiki 151 27 (Greece)

    2003-12-01

    Exposure to toxic metals and pollutants is a major environmental problem. Cadmium is a metal causing acute hepatic injury but the mechanism of this phenomenon is poorly understood. In the present study, we investigated the mechanism and time-course of cadmium-induced liver injury in rats, with emphasis being placed on apoptosis in parenchymal and nonparenchymal liver cells. Cadmium (3.5 mg/kg body weight) was injected intraperitoneally and the rats were killed 0, 9, 12, 16, 24, 48 and 60 h later. The extent of liver injury was evaluated for necrosis, apoptosis, peliosis, mitoses and inflammatory infiltration in hematoxylin-eosin-stained liver sections, and by assaying serum enzyme activities. The number of cells that died via apoptosis was quantified by TUNEL assay. The identification of nonparenchymal liver cells and activated Kupffer cells was performed histochemically. Liver regeneration was evaluated by assaying the activity of liver thymidine kinase and by the rate of {sup 3}H-thymidine incorporation into DNA. Both cadmium-induced necrotic cell death and parenchymal cell apoptosis showed a biphasic elevation at 12 and 48 h and peaked at 48 and 12 h, respectively. Nonparenchymal cell apoptosis peaked at 48 h. Peliosis hepatis, another characteristic form of liver injury, was first observed at 16 h and, at all time points, closely correlated with the apoptotic index of nonparenchymal liver cells, where the lesion was also maximial at 48 h. Kupffer cell activation and neutrophil infiltration were minimal for all time points examined. Based on thymidine kinase activity, liver regeneration was found to discern a classic biphasic peak pattern at 12 and 48 h. It was very interesting to observe that cadmium-induced liver injury did not involve inflammation at any time point. Apoptosis seems to be a major mechanism for the removal of damaged cells, and constitutes the major type of cell death in nonparenchymal liver cells. Apoptosis of nonparenchymal cells is the basis

  18. Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

    Directory of Open Access Journals (Sweden)

    Perry A. Soriano

    2011-01-01

    Full Text Available Introduction. We examined the murine hepatectomy model of liver regeneration (LR in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP injections of a control, oxaliplatin (15 mg/kg, or irinotecan (100 mg/Kg or 250 mg/Kg solution. Hepatectomy (70% was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. -tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, =0.048 with no difference on D7 (=0.21. Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3. Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis.

  19. Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

    Science.gov (United States)

    Soriano, Perry A.; Liu, Nian; Castillo, Erick; Foster, Brock; Artinyan, Avo; Kim, Joseph; Huang, Wendong; Wagman, Lawrence D.

    2011-01-01

    Introduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15 mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solution. Hepatectomy (70%) was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D) 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. T-tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, P = 0.048) with no difference on D7 (P = 0.21). Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg) showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3). Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis. PMID:22164336

  20. 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.

  1. 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...

  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. Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

    Science.gov (United States)

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

  4. Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration.

    Science.gov (United States)

    Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

    2004-07-15

    Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

  5. Immunohistochemical analyses of cell cycle progression and gene expression of biliary epithelial cells during liver regeneration after partial hepatectomy of the mouse.

    Science.gov (United States)

    Fukuda, Tatsuya; Fukuchi, Tomokazu; Yagi, Shinomi; Shiojiri, Nobuyoshi

    2016-05-20

    The liver has a remarkable regeneration capacity, and, after surgical removal of its mass, the remaining tissue undergoes rapid regeneration through compensatory growth of its constituent cells. Although hepatocytes synchronously proliferate under the control of various signaling molecules from neighboring cells, there have been few detailed analyses on how biliary cells regenerate for their cell population after liver resection. The present study was undertaken to clarify how biliary cells regenerate after partial hepatectomy of mice through extensive analyses of their cell cycle progression and gene expression using immunohistochemical and RT-PCR techniques. When expression of PCNA, Ki67 antigen, topoisomerase IIα and phosphorylated histone H3, which are cell cycle markers, was immunohistochemically examined during liver regeneration, hepatocytes had a peak of the S phase and M phase at 48-72 h after resection. By contrast, biliary epithelial cells had much lower proliferative activity than that of hepatocytes, and their peak of the S phase was delayed. Mitotic figures were rarely detectable in biliary cells. RT-PCR analyses of gene expression of biliary markers such as Spp1 (osteopontin), Epcam and Hnf1b demonstrated that they were upregulated during liver regeneration. Periportal hepatocytes expressed some of biliary markers, including Spp1 mRNA and protein. Some periportal hepatocytes had downregulated expression of HNF4α and HNF1α. Gene expression of Notch signaling molecules responsible for cell fate decision of hepatoblasts to biliary cells during development was upregulated during liver regeneration. Notch signaling may be involved in biliary regeneration.

  6. 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...

  7. 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)

  8. Effect of quercetin on paracetamole-induced liver disjunction in irradiated rats

    International Nuclear Information System (INIS)

    Hedayat, I.S.

    2005-01-01

    Nowadays, increasing attention has been given to the role of free radicals generated through oxidation stress. Persons subjected to radiation, such as radiotherapy, consuming analgesic drugs such as paracetamole which accumulates at relatively high concentration in liver, are in need to be investigated to explore the synergetic effects of these stresses. Many radical scavengers, interestingly naturally occurring antioxidants, have been found to be effective in inhibiting the oxidative damage Quercetin, the well known phenolic compound widely present in the plant kingdom, has been investigated for its possible protection effect against gamma irradiation and paracetamole-induced hepatic damage. Data revealed serious effects of oral administration of sublethal dose of paracetamole (500 mg/kg) and/or exposure to 6 Gy whole body gamma irradiation on liver. This damage is reflected by increased hepatic levels of MDA, carbonyl content and ALT activity, associated by decrease in hepatic SOD, catalase and GSH when compared with respective control values. The combination of quercetin with paracetamole and/or gamma irradiation have clearly reduced liver damage. It was noticed that the restoration of peroxides and carbonyls rates has occurred. Quercetin seems to act by activation of the turnover of SOD, catalase and GSH and permitting the capitation of reactive metabolites of paracetamole as well as its ability in quenching free radicals induced by exposure of rats to gamma irradiation, thus improving regeneration in the biological tissues

  9. Glucagon infusion increases rate of purine synthesis de novo in rat liver

    International Nuclear Information System (INIS)

    Itakura, Mitsuo; Maeda, Noriaki; Tsuchiya, Masami; Yamashita, Kamejiro

    1987-01-01

    Based on the parallel increases of glucagon, the second peak of hepatic cAMP, and the rate of purine synthesis de novo in the prereplicative period in regenerating rate liver after a 70% hepatectomy, it was hypothesized that glucagon is responsible for the increased rate of purine synthesis de novo. To test this hypothesis, the effect of glucagon or dibutyryl cAMP infusion on the rate of purine synthesis de novo in rat liver was studied. Glucagon infusion but not insulin or glucose infusion increased the rate of purine synthesis de novo, which was assayed by [ 14 C]glycine or [ 14 C]formate incorporation, by 2.7- to 4.3-fold. Glucagon infusion increased cAMP concentrations by 4.9-fold and 5-phosphoribosyl-1-pyrophosphate concentrations by 1.5-fold in liver but did not change the specific activity of amidophosphoribosyltransferase or purine ribonucleotide concentrations. Dibutyryl cAMP infusion also increased the rate of purine synthesis de novo by 2.2- to 4.0-fold. Because glucagon infusion increased the rate of purine synthesis de novo in the presence of unchanged purine ribonucleotide concentrations, it is concluded that glucagon after infusion or in animals after a 70% hepatectomy is playing an anabolic role to increase the rate of purine synthesis de novo by increasing cAMP and 5-phosphoribosyl-1-pyrophosphate concentrations

  10. Mechanisms of blood pressure changes following renal irradiation of intact, adrenalectomized, and adrenal regenerating rats

    International Nuclear Information System (INIS)

    Rosenblum, M.

    1977-01-01

    This study was conducted to determine the differences in changes in systolic arterial blood pressure following renal x irradiation (1100 R) in adrenal-intact, adrenalectomized, and adrenal-regenerating rats and to elucidate the involvement or roles of the kidneys and of the adrenal glands in the blood pressure changes. The parameters studied included the following: systolic blood pressure; body weight; food and fluid consumption; urine output; plasma and urine electrolytes; sodium balance; plasma renin activity; plasma corticosterone; renal vascular volume; renal vascular permeability (using 125 I-polyvinylpyrrolidone extravasation rate as an indicator); renal blood flow (using 42 K extraction); kidney weight; hematocrit; and total vascular, plasma, and red cell volumes. Renal x irradiation of intact rats caused polydipsia, polyuria, and reduced urine concentrations of sodium and potassium without significantly affecting blood pressure during the period of study (80 days); plasma renin activity was significantly lowered and had a positive correlation with blood volume; an abnormal blood volume-plasma renin activity relationship is suggested. Adrenalectomy caused prolonged hypotension in saline-maintained rats even though their sodium balance was more positive than that in adrenal-intact or adrenal-regenerating rats with normal or elevated blood pressure. The blood pressure of renally irrradiated, adrenalectomized rats was greater than non-irradiated adrenalectomized rats, but with only borderline significance; it is concluded that the absence of the adrenal glands does not affect the degree or duration of the effects of renal irradiation on blood pressure

  11. 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,

  12. 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,

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Med1 subunit of the mediator complex in nuclear receptor-regulated energy metabolism, liver regeneration, and hepatocarcinogenesis.

    Science.gov (United States)

    Jia, Yuzhi; Viswakarma, Navin; Reddy, Janardan K

    2014-01-01

    Several nuclear receptors regulate diverse metabolic functions that impact on critical biological processes, such as development, differentiation, cellular regeneration, and neoplastic conversion. In the liver, some members of the nuclear receptor family, such as peroxisome proliferator-activated receptors (PPARs), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), liver X receptor (LXR), pregnane X receptor (PXR), glucocorticoid receptor (GR), and others, regulate energy homeostasis, the formation and excretion of bile acids, and detoxification of xenobiotics. Excess energy burning resulting from increases in fatty acid oxidation systems in liver generates reactive oxygen species, and the resulting oxidative damage influences liver regeneration and liver tumor development. These nuclear receptors are important sensors of exogenous activators as well as receptor-specific endogenous ligands. In this regard, gene knockout mouse models revealed that some lipid-metabolizing enzymes generate PPARα-activating ligands, while others such as ACOX1 (fatty acyl-CoA oxidase1) inactivate these endogenous PPARα activators. In the absence of ACOX1, the unmetabolized ACOX1 substrates cause sustained activation of PPARα, and the resulting increase in energy burning leads to hepatocarcinogenesis. Ligand-activated nuclear receptors recruit the multisubunit Mediator complex for RNA polymerase II-dependent gene transcription. Evidence indicates that the Med1 subunit of the Mediator is essential for PPARα, PPARγ, CAR, and GR signaling in liver. Med1 null hepatocytes fail to respond to PPARα activators in that these cells do not show induction of peroxisome proliferation and increases in fatty acid oxidation enzymes. Med1-deficient hepatocytes show no increase in cell proliferation and do not give rise to liver tumors. Identification of nuclear receptor-specific coactivators and Mediator subunits should further our understanding of the complexities of metabolic

  19. Shear stress upregulates regeneration-related immediate early genes in liver progenitors in 3D ECM-like microenvironments.

    Science.gov (United States)

    Nishii, Kenichiro; Brodin, Erik; Renshaw, Taylor; Weesner, Rachael; Moran, Emma; Soker, Shay; Sparks, Jessica L

    2018-05-01

    The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs. Two hours of shear stress exposure at ∼4 dyn/cm 2 was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared against static controls. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate the effect of experimental treatments on gene expression. Twenty-nine genes were analyzed, including IEGs and other genes linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress. LPCs maintained an early to intermediate stage of differentiation in spheroid culture in the absence of the hydrogel, and addition of the gel initiated cholangiocyte differentiation programs which were abrogated by the onset of flow. Collectively the flow-upregulated genes fit the pattern of an LPC-mediated proliferative/regenerative response. These results suggest that fluid stresses are potentially important regulators of the LPC-mediated regeneration response in liver. © 2017 Wiley Periodicals, Inc.

  20. 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.

  1. Hyperbaric Oxygen therapy effects on bone regeneration in Type 1 diabetes mellitus in rats.

    Science.gov (United States)

    Dias, Pâmella Coelho; Limirio, Pedro Henrique Justino Oliveira; Linhares, Camila Rodrigues Borges; Bergamini, Mariana Lobo; Rocha, Flaviana Soares; Morais, Richarlisson Borges de; Balbi, Ana Paula Coelho; Hiraki, Karen Renata Nakamura; Dechichi, Paula

    2018-01-29

    The aim of this study was evaluate the effect of HBO on diabetic rats. Twenty rats were distributed into four groups (n = 5): Control (C); Control + HBO (CH); Diabetes (D) and Diabetes + HBO (DH). Diabetes was induced by streptozotocin, and bone defects were created in both femurs in all animals. HBO therapy began immediately after surgery and was performed daily in the CH and DH groups. After 7 days, the animals were euthanized. The femurs were removed, demineralized, embedded in paraffin, and histologic images were analyzed. Qualitative histologic analyses showed more advanced stage bone regeneration in control groups (C and CH) compared with diabetic groups (D and DH). Histomorphometric analysis showed significantly increased bone neoformation in CH compared with the other groups (p  0.05). The mast cell population increased in CH compared with the other groups (C, D, and DH) (p < 0.05). The mast cell population did not differ between D and DH Groups. This study showed that HBO therapy improved early bone regeneration in diabetic rats and increased the mast cell population only in non-diabetic animals. HBO was shown to be important treatment for minimizing deleterious effects of diabetes on bone regeneration.

  2. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver

    DEFF Research Database (Denmark)

    Ding, Bi-Sen; Liu, Catherine H; Sun, Yue

    2016-01-01

    Regeneration of hepatic sinusoidal vasculature is essential for non-fibrotic liver regrowth and restoration of its metabolic capacity. However, little is known about how this specialized vascular niche is regenerated. Here we show that activation of endothelial sphingosine-1-phosphate receptor-1 ...

  3. Effectiveness of Russian current in bone regeneration process in rats

    Directory of Open Access Journals (Sweden)

    Renata Aparecida de Oliveira Lima

    Full Text Available Abstract Introduction: Russian current is an electric current of average frequency that is able to restore the properties of skeletal muscle at a low treatment cost. It is essential to know the effects of Russian current in bone tissue, since electromagnetic energy could be an efficient and low cost method to treat bone disorders. Objective: The aim of the study was to evaluate the effectiveness of Russian current in the consolidation of tibia fracture in adult rats. Methods: 24 adult male Albinus Wistar rats wereused. The animals were divided randomly into two groups: control group (CG, composed of 12 animals, and Intervention Group (IG consisting of 12 animals, both groups were submitted to osteotomy (proximal medial surface of the tibia. The IG underwent an electrical stimulation protocol with Russian current, while the CG did not undergo any kind of intervention. Euthanasia was performed in three animals of each group on the following days: 5, 10, 20, and 30 days of treatment. Results: The results suggested higher primary ossification, intense osteogenic activity, and increased thickness of the periosteum, characterizing more advanced ossification and a greater presence of trabecular bone marrow in rats in the group subjected to the treatment. In this way, we can assign one more beneficial effect to interventions with Russian current, for the treatment of postfracture rehabilitation. Conclusion: In both groups the bone tissue repair process occurred, but in the electrically stimulated group the osteogenesis process was more advanced.

  4. Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.

    Directory of Open Access Journals (Sweden)

    Jiamin Zhang

    Full Text Available Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD. ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group, as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.

  5. The effects of Crataegus aronia var. dentata Browicz extract on biochemical indices and apoptosis in partially hepatectomized liver in rats

    Directory of Open Access Journals (Sweden)

    Nazan Keskin

    2012-08-01

    Full Text Available Crataegus species have been widely used in herbal medicine, especially for the hearth diseases. In the present study, the effect of Crataegus aronia var. dentata Browicz extract on partially hepatectomized rats was investigated with biochemical and TUNEL apoptosis assays. The extracts of the plant at the concentrations of 0.5 and 1 ml/100 g body weight/day were administered orally to the two experimental groups including partially hepatectomized rats for 42 days. At the end of the experimental period, animals were sacrificed, blood was collected for the assessment of serum levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST and gamma-glutamyltransferase (GGT, and the liver tissue was used for TUNEL assay.In biochemical assay, it was found a significant decrease in the levels of serum ALT and AST in the experimental groups. On the other hand, the plant extract did not cause any significant changes in the level of GGT in these groups. In apoptosis assay, TUNEL positive hepatocytes could not be detected in both experimental groups.The present findings can suggest that Crataegus aronia var. dentata Browicz extract can decrease the levels of serum ALT and AST and play a role in apoptosis of hepatocytes in the liver of partially hepatectomized rats. However, further studies are required to confirm the effects of the plant extract on hepatoprotection and apoptosis in the regenerating liver after partial hepatectomy in animal models. 

  6. 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

  7. 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

  8. 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

  9. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

    Science.gov (United States)

    Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

    2017-02-01

    In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. 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

  11. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver.

    Science.gov (United States)

    Ding, Bi-Sen; Liu, Catherine H; Sun, Yue; Chen, Yutian; Swendeman, Steven L; Jung, Bongnam; Chavez, Deebly; Cao, Zhongwei; Christoffersen, Christina; Nielsen, Lars Bo; Schwab, Susan R; Rafii, Shahin; Hla, Timothy

    2016-12-22

    Regeneration of hepatic sinusoidal vasculature is essential for non-fibrotic liver regrowth and restoration of its metabolic capacity. However, little is known about how this specialized vascular niche is regenerated. Here we show that activation of endothelial sphingosine-1-phosphate receptor-1 (S1P 1 ) by its natural ligand bound to HDL (HDL-S1P) induces liver regeneration and curtails fibrosis. In mice lacking HDL-S1P, liver regeneration after partial hepatectomy was impeded and associated with aberrant vascular remodeling, thrombosis and peri-sinusoidal fibrosis. Notably, this "maladaptive repair" phenotype was recapitulated in mice that lack S1P 1 in the endothelium. Reciprocally, enhanced plasma levels of HDL-S1P or administration of SEW2871, a pharmacological agonist specific for S1P 1 enhanced regeneration of metabolically functional vasculature and alleviated fibrosis in mouse chronic injury and cholestasis models. This study shows that natural and pharmacological ligands modulate endothelial S1P 1 to stimulate liver regeneration and inhibit fibrosis, suggesting that activation of this pathway may be a novel therapeutic strategy for liver fibrosis.

  12. Response of mitochondrial function to hypothyroidism in normal and regenerated rat skeletal muscle.

    Science.gov (United States)

    Zoll, J; Ventura-Clapier, R; Serrurier, B; Bigard, A X

    2001-01-01

    Although thyroid hormones induce a well known decrease in muscle oxidative capacity, nothing is known concerning their effects on mitochondrial function and regulation in situ. Similarly, the influence of regeneration process is not completely understood. We investigated the effects of hypothyroidism on mitochondrial function in fast gastrocnemius (GS) and slow soleus (SOL) muscles either intact or having undergone a cycle of degeneration/regeneration (Rg SOL) following a local injection of myotoxin. Thyroid hormone deficiency was induced by thyroidectomy and propylthiouracyl via drinking water. Respiration was measured in muscle fibres permeabilised by saponin in order to assess the oxidative capacity of the muscles and the regulation of mitochondria in situ. Oxidative capacities were 8.9 in SOL, 8.5 in Rg SOL and 5.9 micromol O2/min/g dry weight in GS and decreased by 52, 42 and 39% respectively (P hypothyroid rats. Moreover, the Km of mitochondrial respiration for the phosphate acceptor ADP exhibited a two-fold decrease in Rg SOL and intact SOL by hypothyroidism (P hypothyroidism markedly altered the sensitivity of mitochondrial respiration to ADP but not to creatine in SOL muscles, suggesting that mitochondrial regulation could be partially controlled by thyroid hormones. On the other hand, mitochondrial function completely recovered following regeneration/degeneration, suggesting that thyroid hormones are not involved in the regeneration process per se.

  13. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    Science.gov (United States)

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  14. 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.

  15. Expression of phosphatase of regenerating liver-3 is associated with prognosis of Wilms’ tumor

    Directory of Open Access Journals (Sweden)

    Sun F

    2017-01-01

    Full Text Available Fengyin Sun,1 Wenyi Li,2,3 Lie Wang,2 Changfeng Jiao3 1Department of Pediatric Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, 2Department of General Surgery, Fuzhou General Hospital of Nanjing Command, PLA, Fuzhou, Fujian Province, 3Department of Vascular Surgery, Xinzhou City People’s Hospital, Xinzhou, Shanxi Province, People’s Republic of China Objective: The current study was undertaken to explore the clinical and prognostic value of phosphatase of regenerating liver-3 (PRL-3 expression in Wilms’ tumor. Methods: Seventy-six patients with Wilms’ tumor in Qilu Hospital from January 2003 to July 2009 were enrolled in the study. Protein expression level of PRL-3 was examined by immunohistochemical staining, and the correlation between PRL-3 expression and histopathological parameters, clinical variables, and outcome of patients with Wilms’ tumor were analyzed. Results: We found that 19% of patients with unfavorable histology had tumor recurrence and 16% of patients died following the operation. PRL-3 was expressed in 15 out of 76 tumors (19% and expressed highly in unfavorable histology Wilms’ tumor (P=0.04. PRL-3 protein expression level was correlated to 2.5-fold increase in recurrence rate of Wilms’ tumor (P=0.06 without any statistically significant difference. However, in favorable histology Wilms’ tumor, PRL-3 expression was correlated to an increase of 3.4-fold in recurrence rate (P=0.03. Conclusion: The expression of PRL-3 protein was correlated with an increased recurrence rate of favorable histology Wilms’ tumor. PRL-3 may serve as a promising biomarker for predicting patients with high risk of Wilms’ tumor. Further investigations are warranted to investigate the clinical function of PRL-3 in Wilms’ tumor. Keywords: Wilms’ tumor, prognosis, tumorigenesis, recurrence

  16. Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

    Science.gov (United States)

    Fairchild, C R; Ivy, S P; Rushmore, T; Lee, G; Koo, P; Goldsmith, M E; Myers, C E; Farber, E; Cowan, K H

    1987-11-01

    We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8-fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene.

  17. 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

  18. Partial fast-to-slow conversion of regenerating rat fast-twitch muscle by chronic low-frequency stimulation.

    Science.gov (United States)

    Pette, Dirk; Sketelj, Janez; Skorjanc, Dejan; Leisner, Elmi; Traub, Irmtrud; Bajrović, Fajko

    2002-01-01

    Chronic low-frequency stimulation (CLFS) of rat fast-twitch muscles induces sequential transitions in myosin heavy chain (MHC) expression from MHCIIb --> MHCIId/x --> MHCIIa. However, the 'final' step of the fast-to-slow transition, i.e., the upregulation of MHCI, has been observed only after extremely long stimulation periods. Assuming that fibre degeneration/regeneration might be involved in the upregulation of slow myosin, we investigated the effects of CLFS on extensor digitorum longus (EDL) muscles regenerating after bupivacaine-induced fibre necrosis. Normal, non-regenerating muscles responded to both 30- and 60-day CLFS with fast MHC isoform transitions (MHCIIb --> MHCIId --> MHCIIa) and only slight increases in MHCI. CLFS of regenerating EDL muscles caused similar transitions among the fast isoforms but, in addition, caused significant increases in MHCI (to approximately 30% relative concentration). Stimulation periods of 30 and 60 days induced similar changes in the regenerating bupivacaine-treated muscles, indicating that the upregulation of slow myosin was restricted to regenerating fibres, but only during an early stage of regeneration. These results suggest that satellite cells and/or regenerating fast rat muscle fibres are capable of switching directly to a slow program under the influence of CLFS and, therefore, appear to be more malleable than adult fibres.

  19. 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

  20. 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 ...

  1. 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.

  2. 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.

  3. New nano-hydroxyapatite in bone defect regeneration: A histological study in rats.

    Science.gov (United States)

    Kubasiewicz-Ross, Paweł; Hadzik, Jakub; Seeliger, Julia; Kozak, Karol; Jurczyszyn, Kamil; Gerber, Hanna; Dominiak, Marzena; Kunert-Keil, Christiane

    2017-09-01

    Many types of bone substitute materials are available on the market. Researchers are refining new bone substitutes to make them comparable to autologous grafting materials in treatment of bone defects. The purpose of the study was to evaluate the osseoconductive potential and bone defect regeneration in rat calvaria bone defects treated with new synthetic nano-hydroxyapatite. The study was performed on 30 rats divided into 5 equal groups. New preproduction of experimental nano-hydroxyapatite material by NanoSynHap (Poznań, Poland) was tested and compared with commercially available materials. Five mm critical size defects were created and filled with the following bone grafting materials: 1) Geistlich Bio-Oss ® ; 2) nano-hydroxyapatite+β-TCP; 3) nano-hydroxyapatite; 4) nano-hydroxyapatite+collagen membrane. The last group served as controls without any augmentation. Bone samples from calvaria were harvested for histological and micro-ct evaluation after 8 weeks. New bone formation was observed in all groups. Histomorphometric analysis revealed an amount of regenerated bone between 34.2 and 44.4% in treated bone defects, whereas only 13.0% regenerated bone was found in controls. Interestingly, in group 3, no significant particles of the nano-HA material were found. In contrast, residual bone substitute material could be detected in all other test groups. Micro-CT study confirmed the results of the histological examinations. The new nano-hydroxyapatite provides comparable results to other grafts in the field of bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.

    Science.gov (United States)

    Elzinga, Kate; Tyreman, Neil; Ladak, Adil; Savaryn, Bohdan; Olson, Jaret; Gordon, Tessa

    2015-07-01

    Functional recovery after peripheral nerve injury and surgical repair declines with time and distance because the injured neurons without target contacts (chronic axotomy) progressively lose their regenerative capacity and chronically denervated Schwann cells (SCs) atrophy and fail to support axon regeneration. Findings that brief low frequency electrical stimulation (ES) accelerates axon outgrowth and muscle reinnervation after immediate nerve surgery in rats and human patients suggest that ES might improve regeneration after delayed nerve repair. To test this hypothesis, common peroneal (CP) neurons were chronically axotomized and/or tibial (TIB) SCs and ankle extensor muscles were chronically denervated by transection and ligation in rats. The CP and TIB nerves were cross-sutured after three months and subjected to either sham or one hour 20Hz ES. Using retrograde tracing, we found that ES significantly increased the numbers of both motor and sensory neurons that regenerated their axons after a three month period of chronic CP axotomy and/or chronic TIB SC denervation. Muscle and motor unit forces recorded to determine the numbers of neurons that reinnervated gastrocnemius muscle demonstrated that ES significantly increased the numbers of motoneurons that reinnervated chronically denervated muscles. We conclude that electrical stimulation of chronically axotomized motor and sensory neurons is effective in accelerating axon outgrowth into chronically denervated nerve stumps and improving target reinnervation after delayed nerve repair. Possible mechanisms for the efficacy of ES in promoting axon regeneration and target reinnervation after delayed nerve repair include the upregulation of neurotrophic factors. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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 ...

  11. Tissue-Engineered Tendon for Enthesis Regeneration in a Rat Rotator Cuff Model

    Directory of Open Access Journals (Sweden)

    Michael J. Smietana

    2017-06-01

    Full Text Available Healing of rotator cuff (RC injuries with current suture or augmented scaffold techniques fails to regenerate the enthesis and instead forms a weaker fibrovascular scar that is prone to subsequent failure. Regeneration of the enthesis is the key to improving clinical outcomes for RC injuries. We hypothesized that the utilization of our tissue-engineered tendon to repair either an acute or a chronic full-thickness supraspinatus tear would regenerate a functional enthesis and return the biomechanics of the tendon back to that found in native tissue. Engineered tendons were fabricated from bone marrow-derived mesenchymal stem cells utilizing our well-described fabrication technology. Forty-three rats underwent unilateral detachment of the supraspinatus tendon followed by acute (immediate or chronic (4 weeks retracted repair by using either our engineered tendon or a trans-osseous suture technique. Animals were sacrificed at 8 weeks. Biomechanical and histological analyses of the regenerated enthesis and tendon were performed. Statistical analysis was performed by using a one-way analysis of variance with significance set at p < 0.05. Acute repairs using engineered tendon had improved enthesis structure and lower biomechanical failures compared with suture repairs. Chronic repairs with engineered tendon had a more native-like enthesis with increased fibrocartilage formation, reduced scar formation, and lower biomechanical failure compared with suture repair. Thus, the utilization of our tissue-engineered tendon showed improve enthesis regeneration and improved function in chronic RC repairs compared with suture repair. Clinical Significance: Our engineered tendon construct shows promise as a clinically relevant method for repair of RC injuries.

  12. 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

  13. 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.

  14. 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...

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. The regeneration of rectal epithelium in the rat following wounding with suppositories of polyoxyethylene (23) lauryl ether.

    Science.gov (United States)

    Holyhead, E. M.; Thomas, N. W.; Wilson, C. G.

    1983-01-01

    The regeneration of the epithelial compartments of the rectal mucosa in rats has been quantified at time intervals up to one week following wounding with suppositories of the surfactant polyoxyethylene-(23)-lauryl ether. Regeneration of glandular tissue was complete within one week of the wounding, with new glands arising from residual gland bases and from surface invagination of empty crypt skeletons and underlying granulation tissue. This method of wounding appears to be particularly useful for the study of epithelial regeneration since there was a minimal connective tissue response to the insult. Images Fig. 1 Fig. 2 Fig. 3 Figs 4 and 5 Fig. 6 Fig. 7 PMID:6615712

  20. Liver fibrosis and regeneration in dogs and cats: An immunohistochemical approach

    NARCIS (Netherlands)

    IJzer, J.

    2008-01-01

    In this thesis we focus on liver tissue repair processes in canine and feline hepatitis, on formalin fixed paraffin embedded archival liver specimens. Hepatitis was diagnosed using histological standard criteria, and always includes hepatocellular cell death and an inflammatory infiltrate.

  1. Urtica Dioica Distillate Regenerates Pancreatic Beta Cells in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Gohari, Ali; Noorafshan, Ali; Akmali, Masoumeh; Zamani-Garmsiri, Fahimeh; Seghatoleslam, Atefeh

    2018-01-01

    Background Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as “aragh gazaneh”. In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats. Methods A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups. Results The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered. Conclusion UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells. PMID:29749986

  2. 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.

  3. 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 ...

  4. 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 ...

  5. 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/+

  6. 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.

  7. 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

  8. Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats.

    Science.gov (United States)

    Xu, Lin; Zhou, Shuai; Feng, Guo-Ying; Zhang, Lu-Ping; Zhao, Dong-Mei; Sun, Yi; Liu, Qian; Huang, Fei

    2012-10-01

    With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.

  9. 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.

  10. Identification and Characterization of Mesenchymal-Epithelial Progenitor-Like Cells in Normal and Injured Rat Liver

    Science.gov (United States)

    Liu, Daqing; Yovchev, Mladen I.; Zhang, Jinghang; Alfieri, Alan A.; Tchaikovskaya, Tatyana; Laconi, Ezio; Dabeva, Mariana D.

    2016-01-01

    In normal rat liver, thymocyte antigen 1 (Thy1) is expressed in fibroblasts/myofibroblasts and in some blood progenitor cells. Thy1-expressing cells also accumulate in the liver during impaired liver regeneration. The origin and nature of these cells are not well understood. By using RT-PCR analysis and immunofluorescence microscopy, we describe the presence of rare Thy1+ cells in the liver lobule of normal animals, occasionally forming small collections of up to 20 cells. These cells constitute a small portion (1.7% to 1.8%) of nonparenchymal cells and reveal a mixed mesenchymal-epithelial phenotype, expressing E-cadherin, cytokeratin 18, and desmin. The most potent mitogens for mesenchymal-epithelial Thy1+ cells in vitro are the inflammatory cytokines interferon γ, IL-1, and platelet-derived growth factor-BB, which are not produced by Thy1+ cells. Thy1+ cells express all typical mesenchymal stem cell and hepatic progenitor cell markers and produce growth factor and cytokine mRNA (Hgf, Il6, Tgfa, and Tweak) for proteins that maintain oval cell growth and differentiation. Under appropriate conditions, mesenchymal-epithelial cells differentiate in vitro into hepatocyte-like cells. In this study, we show that the adult rat liver harbors a small pool of endogenous mesenchymal-epithelial cells not recognized previously. In the quiescent state, these cells express both mesenchymal and epithelial cell markers. They behave like hepatic stem cells/progenitors with dual phenotype, exhibiting high plasticity and long-lasting proliferative activity. PMID:25447047

  11. 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

  12. Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

    Science.gov (United States)

    Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

    2015-01-01

    Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

  13. 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)

  14. Differential Expression ESTs Associated with Fluorosis in Rats Liver

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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.

  17. 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)

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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...

  3. 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)

  4. 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)

  5. Hyaluronate acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-10-01

    Full Text Available Yan Zhang, Qin Liu, Ning Yang, Xuegang Zhang Department of Gynecology, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, People’s Republic of China Abstract: Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm, and the medical sodium hyaluronate (MSH group was treated with 1% MSH (0.5 mL. At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99 and the ORC group (1.40±0.97 were significantly lower than those in the control group (3.00±0.82 (P=0.005. Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82 and the ORC group (1.50±1.27 were significantly lower than those in the control group (3.50±0.53 (P=0.001. In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model. Keywords: hyaluronic acid, oxidized regenerated cellulose, adhesion formation, adhesion reformation, rat model 

  6. 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...

  7. β-Cell dedifferentiation, reduced duct cell plasticity, and impaired β-cell mass regeneration in middle-aged rats.

    Science.gov (United States)

    Téllez, Noèlia; Vilaseca, Marina; Martí, Yasmina; Pla, Arturo; Montanya, Eduard

    2016-09-01

    Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replication and individual β-cell size were similarly increased after Px in young and middle-aged animals, and β-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet β-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory β-cell hyperplasia and hypertrophy was retained in middle-aged rats, but β-cell dedifferentiation and impaired duct cell plasticity limited β-cell regeneration. Copyright © 2016 the American Physiological Society.

  8. A Short-Term Exposure to Tributyltin Blocks Leydig Cell Regeneration in the Adult Rat Testis

    Directory of Open Access Journals (Sweden)

    Xiaolong Wu

    2017-10-01

    Full Text Available Background: Tributyltin (TBT is widely used as an antifouling agent that may cause reproductive toxicity. The mechanism of TBT on Leydig cell development is still unknown. The objective of the present study was to investigate whether a brief exposure to low doses of TBT permanently affects Leydig cell development and to clarify the underlying mechanism.Methods: Adult male Sprague Dawley rats were randomly assigned into four groups and gavaged normal saline (control, 0.1, 1.0, or 10.0 mg/kg/day TBT for a consecutive 10 days, respectively. At the end of TBT treatment, all rats received a single intraperitoneal injection of 75 mg/kg ethane dimethane sulfonate (EDS to eliminate all of adult Leydig cells. Leydig cells began a developmental regeneration process on post-EDS day 35. The Leydig cell regeneration was evaluated by measuring serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels on post-EDS day 7, 35, and 56, the expression levels of Leydig cell genes, Leydig cell morphology and number and proliferation on post-EDS day 56.Results: TBT significantly reduced serum testosterone levels on post-EDS day 35 and 56 and increased serum luteinizing hormone and follicle-stimulating hormone levels on post-EDS day 56 at ≥1 mg/kg/day. Immunohistochemical staining showed that there were fewer regenerated Leydig cells in the TBT-treated testis on post-EDS day 56. Further study demonstrated that the mRNA or protein levels of Leydig (Lhcgr, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3 and Sertoli cells (Fshr, Dhh, and Sox9 were significantly down-regulated in the TBT-treated testes when compared to the control. Immunofluorescent staining showed that TBT inhibited Leydig cell proliferation as judged by the reduced number of proliferating cyclin nuclear antigen-positive Leydig cells on post-EDS day 35.Conclusion: The present study demonstrated that a short-term TBT exposure blocked Leydig cell developmental regeneration process via down

  9. A Short-Term Exposure to Tributyltin Blocks Leydig Cell Regeneration in the Adult Rat Testis.

    Science.gov (United States)

    Wu, Xiaolong; Liu, Jianpeng; Duan, Yue; Gao, Shiyu; Lü, Yao; Li, Xiaoheng; Zhu, Qiqi; Chen, Xianwu; Lin, Jing; Ye, Leping; Ge, Ren-Shan

    2017-01-01

    Background: Tributyltin (TBT) is widely used as an antifouling agent that may cause reproductive toxicity. The mechanism of TBT on Leydig cell development is still unknown. The objective of the present study was to investigate whether a brief exposure to low doses of TBT permanently affects Leydig cell development and to clarify the underlying mechanism. Methods: Adult male Sprague Dawley rats were randomly assigned into four groups and gavaged normal saline (control), 0.1, 1.0, or 10.0 mg/kg/day TBT for a consecutive 10 days, respectively. At the end of TBT treatment, all rats received a single intraperitoneal injection of 75 mg/kg ethane dimethane sulfonate (EDS) to eliminate all of adult Leydig cells. Leydig cells began a developmental regeneration process on post-EDS day 35. The Leydig cell regeneration was evaluated by measuring serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels on post-EDS day 7, 35, and 56, the expression levels of Leydig cell genes, Leydig cell morphology and number and proliferation on post-EDS day 56. Results: TBT significantly reduced serum testosterone levels on post-EDS day 35 and 56 and increased serum luteinizing hormone and follicle-stimulating hormone levels on post-EDS day 56 at ≥1 mg/kg/day. Immunohistochemical staining showed that there were fewer regenerated Leydig cells in the TBT-treated testis on post-EDS day 56. Further study demonstrated that the mRNA or protein levels of Leydig ( Lhcgr , Cyp11a1, Hsd3b1, Cyp17a1 , and Hsd17b3 ) and Sertoli cells ( Fshr , Dhh , and Sox9 ) were significantly down-regulated in the TBT-treated testes when compared to the control. Immunofluorescent staining showed that TBT inhibited Leydig cell proliferation as judged by the reduced number of proliferating cyclin nuclear antigen-positive Leydig cells on post-EDS day 35. Conclusion: The present study demonstrated that a short-term TBT exposure blocked Leydig cell developmental regeneration process via down

  10. Fluoride Ion Regeneration of Cyclosarin (GF) From Rat Blood Following Whole-Body Exposure to Lethal Levels of GF Vapor

    National Research Council Canada - National Science Library

    Jakubowski, E. M; Anthony, J. S; Mioduszewski, R. J; Manthei, J. H; Burnett, D. C; Way, R. A; Gaviola, B. I; Scotto, J. A; Muse, W. T; Whalley, C. E

    2003-01-01

    .... Levels of exposure ranged from 2 mg/m3 for 240 min to 41.9 mg/m3 for 10 min. The GF biomarker found in rat plasma and red blood cell samples was regenerated GF, which is the product of adding fluoride ion at pH 4 to the post exposure samples...

  11. Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration

    NARCIS (Netherlands)

    Pedone, Elisa; Olteanu, Vlad-Aris; Marucci, Lucia; Muñoz-Martin, Maria Isabel; Youssef, Sameh A; de Bruin, Alain; Cosma, Maria Pia

    2017-01-01

    In rodents and humans, the liver can efficiently restore its mass after hepatectomy. This is largely attributed to the proliferation and cell cycle re-entry of hepatocytes. On the other hand, bone marrow cells (BMCs) migrate into the liver after resection. Here, we find that a block of BMC

  12. Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.

    Science.gov (United States)

    Bikbova, Guzel; Oshitari, Toshiyuki; Yamamoto, Shuichi

    2013-10-09

    The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Thrombospondin-1 is a novel negative regulator of liver regeneration after partial hepatectomy through transforming growth factor-beta1 activation in mice.

    Science.gov (United States)

    Hayashi, Hiromitsu; Sakai, Keiko; Baba, Hideo; Sakai, Takao

    2012-05-01

    The matricellular protein, thrombospondin-1 (TSP-1), is prominently expressed during tissue repair. TSP-1 binds to matrix components, proteases, cytokines, and growth factors and activates intracellular signals through its multiple domains. TSP-1 converts latent transforming growth factor-beta1 (TGF-β1) complexes into their biologically active form. TGF-β plays significant roles in cell-cycle regulation, modulation of differentiation, and induction of apoptosis. Although TGF-β1 is a major inhibitor of proliferation in cultured hepatocytes, the functional requirement of TGF-β1 during liver regeneration remains to be defined in vivo. We generated a TSP-1-deficient mouse model of a partial hepatectomy (PH) and explored TSP-1 induction, progression of liver regeneration, and TGF-β-mediated signaling during the repair process after hepatectomy. We show here that TSP-1-mediated TGF-β1 activation plays an important role in suppressing hepatocyte proliferation. TSP-1 expression was induced in endothelial cells (ECs) as an immediate early gene in response to PH. TSP-1 deficiency resulted in significantly reduced TGF-β/Smad signaling and accelerated hepatocyte proliferation through down-regulation of p21 protein expression. TSP-1 induced in ECs by reactive oxygen species (ROS) modulated TGF-β/Smad signaling and proliferation in hepatocytes in vitro, suggesting that the immediately and transiently produced ROS in the regenerating liver were the responsible factor for TSP-1 induction. We have identified TSP-1 as an inhibitory element in regulating liver regeneration by TGF-β1 activation. Our work defines TSP-1 as a novel immediate early gene that could be a potential therapeutic target to accelerate liver regeneration. Copyright © 2011 American Association for the Study of Liver Diseases.

  18. 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.

  19. [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.

  20. Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ronghua Wu

    2015-11-01

    Full Text Available Calpain 3 (CAPN3, also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA of gastrocnemius muscle were decreased gradually from 1–14 days and then recovery from 14–28 days. The active form of CAPN3 (~62 kDa protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.

  1. 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

  2. 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.

  3. Regeneration of calvarial defects by a composite of bioerodible polyorthoester and demineralized bone in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1992-01-01

    A study was performed to evaluate regeneration of defects in rat calvaria either unfilled or filled with a bioerodible polyorthoester only, demineralized bone only, or a composite of both. At 4 weeks, histological and radiographic studies showed that defects filled with a composite of bioerodible...... polyorthoester and demineralized bone or demineralized bone alone were bridged by bone. Unfilled defects or defects filled with polyorthoester only did not heal. The polyorthoester caused slight inflammation that subsided by 3 weeks, and only traces of the filler could be detected at 4 weeks. The polyorthoester...... provided local hemostasis when used either alone or in composites with demineralized bone. The composite implant was moldable, easily contoured, and technically easier to use than demineralized bone alone....

  4. 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...

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

    Directory of Open Access Journals (Sweden)

    Mei Liu

    2014-01-01

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

  6. 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.

  7. Liver Regeneration After Portal Vein Embolization Using Absorbable and Permanent Embolization Materials in a Rabbit Model

    NARCIS (Netherlands)

    van den Esschert, Jacomina W.; van Lienden, Krijn P.; Alles, Lindy K.; van Wijk, Albert C.; Heger, Michal; Roelofs, Joris J.; van Gulik, Thomas M.

    2012-01-01

    Objective: To compare the safety and hypertrophy response after portal vein embolization (PVE) using 2 absorbable and 3 permanent embolization materials. Background: Portal vein embolization is used to increase future remnant liver volume preoperatively. Application of temporary, absorbable

  8. 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.

  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. 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...

  16. 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...

  17. 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.

  18. 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

  19. 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)

  20. 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.

  1. 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

  2. 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

  3. [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.

  4. 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.

  5. 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)

  6. Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

    International Nuclear Information System (INIS)

    Woźny, Maciej; Lewczuk, Bogdan; Ziółkowska, Natalia; Gomułka, Piotr; Dobosz, Stefan; Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł

    2016-01-01

    To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg −1 ) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg −1 ) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

  7. Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures

    Energy Technology Data Exchange (ETDEWEB)

    Woźny, Maciej, E-mail: maciej.wozny@uwm.edu.pl [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland); Lewczuk, Bogdan; Ziółkowska, Natalia [Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 13, 10-713 Olsztyn (Poland); Gomułka, Piotr [Department of Ichthyology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 5, 10-719 Olsztyn (Poland); Dobosz, Stefan [Department of the Salmonid Research in Rutki, Inland Fisheries Institute in Olsztyn, Rutki, 83-330 Żukowo (Poland); Łakomiak, Alicja; Florczyk, Maciej; Brzuzan, Paweł [Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn (Poland)

    2016-12-15

    To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28 days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100 μg·kg{sup −1}) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10 μg·kg{sup −1}) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication. - Highlights: • The study presents pathological changes in whitefish during prolonged MC-LR exposure. • After early, severe injury, the damaged liver parenchyma of the fish regenerated. • Endoplasmic reticulum, cytoskeleton, and chromatin were the main targets for MC-LR. • MC-LR did not

  8. 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

  9. 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.

  10. 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.

  11. 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....

  12. 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.

  13. [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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Effect of obeticholic acid on liver regeneration following portal vein embolization in an experimental model

    NARCIS (Netherlands)

    Olthof, P. B.; Huisman, F.; Schaap, F. G.; van Lienden, K. P.; Bennink, R. J.; van Golen, R. F.; Heger, M.; Verheij, J.; Jansen, P. L.; Olde Damink, S. W.; van Gulik, T. M.

    2017-01-01

    The bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic

  19. 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.

  20. 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...

  1. 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

  2. Attenuated lipotoxicity and apoptosis is linked to exogenous and endogenous augmenter of liver regeneration by different pathways.

    Science.gov (United States)

    Weiss, Thomas S; Lupke, Madeleine; Ibrahim, Sara; Buechler, Christa; Lorenz, Julia; Ruemmele, Petra; Hofmann, Ute; Melter, Michael; Dayoub, Rania

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) covers a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Free fatty acids (FFA) induce steatosis and lipo-toxicity and correlate with severity of NAFLD. In this study we aimed to investigate the role of exogenous and endogenous ALR (augmenter of liver regeneration) for FFA induced ER (endoplasmatic reticulum) -stress and lipoapoptosis. Primary human hepatocytes or hepatoma cells either treated with recombinant human ALR (rhALR, 15kDa) or expressing short form ALR (sfALR, 15kDa) were incubated with palmitic acid (PA) and analyzed for lipo-toxicity, -apoptosis, activation of ER-stress response pathways, triacylglycerides (TAG), mRNA and protein expression of lipid metabolizing genes. Both, exogenous rhALR and cytosolic sfALR reduced PA induced caspase 3 activity and Bax protein expression and therefore lipotoxicity. Endogenous sfALR but not rhALR treatment lowered TAG levels, diminished activation of ER-stress mediators C-Jun N-terminal kinase (JNK), X-box binding protein-1 (XBP1) and proapoptotic transcription factor C/EBP-homologous protein (CHOP), and reduced death receptor 5 protein expression. Cellular ALR exerts its lipid lowering and anti-apoptotic actions by enhancing FABP1, which binds toxic FFA, increasing mitochondrial β-oxidation by elevating the mitochondrial FFA transporter CPT1α, and decreasing ELOVL6, which delivers toxic FFA metabolites. We found reduced hepatic mRNA levels of ALR in a high fat diet mouse model, and of ALR and FOXA2, a transcription factor inducing ALR expression, in human steatotic as well as NASH liver samples, which may explain increased lipid deposition and reduced β-oxidation in NASH patients. Present study shows that exogenous and endogenous ALR reduce PA induced lipoapoptosis. Furthermore, cytosolic sfALR changes mRNA and protein expression of genes regulating lipid metabolism, reduces ER-stress finally impeding progression of NASH.

  3. Attenuated lipotoxicity and apoptosis is linked to exogenous and endogenous augmenter of liver regeneration by different pathways.

    Directory of Open Access Journals (Sweden)

    Thomas S Weiss

    Full Text Available Nonalcoholic fatty liver disease (NAFLD covers a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH and cirrhosis. Free fatty acids (FFA induce steatosis and lipo-toxicity and correlate with severity of NAFLD. In this study we aimed to investigate the role of exogenous and endogenous ALR (augmenter of liver regeneration for FFA induced ER (endoplasmatic reticulum -stress and lipoapoptosis. Primary human hepatocytes or hepatoma cells either treated with recombinant human ALR (rhALR, 15kDa or expressing short form ALR (sfALR, 15kDa were incubated with palmitic acid (PA and analyzed for lipo-toxicity, -apoptosis, activation of ER-stress response pathways, triacylglycerides (TAG, mRNA and protein expression of lipid metabolizing genes. Both, exogenous rhALR and cytosolic sfALR reduced PA induced caspase 3 activity and Bax protein expression and therefore lipotoxicity. Endogenous sfALR but not rhALR treatment lowered TAG levels, diminished activation of ER-stress mediators C-Jun N-terminal kinase (JNK, X-box binding protein-1 (XBP1 and proapoptotic transcription factor C/EBP-homologous protein (CHOP, and reduced death receptor 5 protein expression. Cellular ALR exerts its lipid lowering and anti-apoptotic actions by enhancing FABP1, which binds toxic FFA, increasing mitochondrial β-oxidation by elevating the mitochondrial FFA transporter CPT1α, and decreasing ELOVL6, which delivers toxic FFA metabolites. We found reduced hepatic mRNA levels of ALR in a high fat diet mouse model, and of ALR and FOXA2, a transcription factor inducing ALR expression, in human steatotic as well as NASH liver samples, which may explain increased lipid deposition and reduced β-oxidation in NASH patients. Present study shows that exogenous and endogenous ALR reduce PA induced lipoapoptosis. Furthermore, cytosolic sfALR changes mRNA and protein expression of genes regulating lipid metabolism, reduces ER-stress finally impeding progression of NASH.

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

    Directory of Open Access Journals (Sweden)

    Yinrun Ding

    2016-08-01

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

  5. 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.

  6. 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)

  7. The protective effect of NG-nitro-L-arginine methyl ester and insulin on nitric oxide inhibition and pathology in experimental diabetic rat liver

    International Nuclear Information System (INIS)

    Ozden, H.; Guven, G.; Tekin, N.; Akyuz, F.; Gurer, F.; Kucuk, F.; Ustuner, Mehmet C.; Yaylak, F.

    2009-01-01

    Objective was to determine on protective role of NG-nitro-L-arginine methyl ester (L-NAME) and insulin on the liver in streptoozotocin (STZ) induced diabetic rats. This study was performed in the Department of Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey in 2007. Forty male Wistar albino rats were divided into 5 groups. These were untreated, diabetic control, STZ+insulin, STZ+L-NAME and STZ+insulin+L-NAME induced groups. The STZ was intraperitonally injected into 3 groups and includes insulin, L-NAME and their joint administrations as protective agents. The blood glucose and nitric oxide (NO) levels were determined. The tissue samples were obtained at the end of the fourth week. The liver tissue distortions were evaluated using hematoxylin and eosin staining. The serum glucose level was significantly higher in diabetic control (p=0.000), than the untreated group. The focal pseudo lobular structures without vena centralis increased portal fibrillary necrosis and bile duct stenosis with voagulation necrosis of the peripheral hepatocytes were more observed in diabetic group than the protective agent groups. In addition, insulin and L-NAME lead to hepatocyte regeneration and minimal mononuclear cell infiltration was noted. NG-nitro-L-arginine methyl ester inhibits NO level in STZ+L-NAME induced group. NG-nitro-L-arginine methyl ester either alone or with insulin combination significantly attenuates the liver morphological disarrangements in STZ induced diabetic rats. (author)

  8. Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model.

    Science.gov (United States)

    Farrag, Tarik Y; Lehar, Mohamed; Verhaegen, Pauline; Carson, Kathryn A; Byrne, Patrick J

    2007-01-01

    To investigate the effects of platelet rich plasma (PRP) and fibrin sealant (FS) on facial nerve regeneration. Prospective, randomized, and controlled animal study. Experiments involved the transection and repair of facial nerve of 49 male adult rats. Seven groups were created dependant on the method of repair: suture; PRP (with/without suture); platelet poor plasma (PPP) (with/without suture); and FS (with/without suture) groups. Each method of repair was applied immediately after the nerve transection. The outcomes measured were: 1) observation of gross recovery of vibrissae movements within 8-week period after nerve transection and repair using a 5-point scale and comparing the left (test) side with the right (control) side; 2) comparisons of facial nerve motor action potentials (MAP) recorded before and 8 weeks after nerve transection and repair, including both the transected and control (untreated) nerves; 3) histologic evaluation of axons counts and the area of the axons. Vibrissae movement observation: the inclusion of suturing resulted in overall improved outcomes. This was found for comparisons of the suture group with PRP group; PRP with/without suture groups; and PPP with/without suture groups (P .05). The movement recovery of the suture group was significantly better than the FS group (P = .014). The recovery of function of the PRP groups was better than that of the FS groups, although this did not reach statistical significance (P = .09). Electrophysiologic testing: there was a significantly better performance of the suture group when compared with the PRP and PPP without suture groups in nerve conduction velocity (P facial nerve axotomy models occurred when the nerve ends were sutured together. At the same time, the data demonstrated a measurable neurotrophic effect when PRP was present, with the most favorable results seen with PRP added to suture. There was an improved functional outcome with the use of PRP in comparison with FS or no bioactive

  9. Conduction of impulses by axons regenerated in a Schwann cell graft in the transected adult rat thoracic spinal cord.

    Science.gov (United States)

    Pinzon, A; Calancie, B; Oudega, M; Noga, B R

    2001-06-01

    Central nervous system axons regenerate into a Schwann cell implant placed in the transected thoracic spinal cord of an adult rat. The present study was designed to test whether these regenerated axons are capable of conducting action potentials. Following the transection and removal of a 4- to 5-mm segment of the thoracic spinal cord (T8-T9), a polymer guidance channel filled with a mixture of adult rat Schwann cells and Matrigel was grafted into a 4- to 5-mm-long gap in the transected thoracic spinal cord. The two cut ends of the spinal cord were eased into the guidance channel openings. Transected control animals received a channel containing Matrigel only. Three months after implantation, electrophysiological studies were performed. Tungsten microelectrodes were used for monopolar stimulation of regenerated axons within the Schwann cell graft. Glass microelectrodes were used to record responses in the spinal cord rostral to the stimulation site. Evoked responses to electrical stimulation of the axon cable were found in two out of nine Schwann cell-grafted animals. These responses had approximate latencies in the range of those of myelinated axons. No responses were seen in any of the Matrigel-grafted animals. Histological analysis revealed that the two cases that showed evoked potentials had the largest number of myelinated axons present in the cable. This study demonstrates that axons regenerating through Schwann cell grafts in the complete transected spinal cord can produce measurable evoked responses following electrical stimulation. Copyright 2001 Wiley-Liss, Inc.

  10. 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

  11. 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

  12. 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.

  13. Destruction and regeneration of seminiferous tubules after local x-irradiation of testes of the adult rats

    International Nuclear Information System (INIS)

    Kurnosova, T.R.; Rajtsina, S.S.

    1987-01-01

    It was established that the local X-irradiation (1000 R) of testes of the adult rats results in a total destruction of seminiferous tubules. The restitution of the organ structure proceeds via formation of new seminiferous tubules in which spermatogenic epithelium later develops. Rete testis and germ cells preserved in its epithelium from embryogenesis are a source of regeneration material. The results obtained favour the suggestion about the dynamic structure of mammalian testis

  14. 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

  15. 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

  16. Effects of a chitosan membrane coated with polylactic and polyglycolic acid on bone regeneration in a rat calvarial defect

    International Nuclear Information System (INIS)

    Jung, Ui-Won; Song, Kun-Young; Kim, Chang-Sung; Lee, Yong-Keun; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho

    2007-01-01

    The purpose of this study was to evaluate the effects of a chitosan membrane coated with polylactic and polyglycolic acid (PLGA) on bone regeneration in a rat calvarial defect. Surgical implantation of chitosan membranes resulted in enhanced local bone formation at both 2 and 8 weeks. In conclusion, the chitosan membrane coated with PLGA had a significant potential to induce bone formation in the rat calvarial defect model. Within the selected PLGA dose range and observation intervals, there appeared to be no meaningful differences in bone formation

  17. 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)

  18. 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.

  19. 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

  20. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

    Science.gov (United States)

    Gedrange, Tomasz

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions. PMID:27597965

  1. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats.

    Science.gov (United States)

    Gredes, Tomasz; Kunath, Franziska; Gedrange, Tomasz; Kunert-Keil, Christiane

    2016-01-01

    The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

  2. Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

    Directory of Open Access Journals (Sweden)

    Tomasz Gredes

    2016-01-01

    Full Text Available The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen and unmodified (PLA-wt, PCL-wt, were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

  3. Sciatic nerve regeneration in rats by a promising electrospun collagen/poly(ε-caprolactone nerve conduit with tailored degradation rate

    Directory of Open Access Journals (Sweden)

    Jiang Xinquan

    2011-07-01

    Full Text Available Abstract Background To cope with the limitations faced by autograft acquisitions particularly for multiple nerve injuries, artificial nerve conduit has been introduced by researchers as a substitute for autologous nerve graft for the easy specification and availability for mass production. In order to best mimic the structures and components of autologous nerve, great efforts have been made to improve the designation of nerve conduits either from materials or fabrication techniques. Electrospinning is an easy and versatile technique that has recently been used to fabricate fibrous tissue-engineered scaffolds which have great similarity to the extracellular matrix on fiber structure. Results In this study we fabricated a collagen/poly(ε-caprolactone (collagen/PCL fibrous scaffold by electrospinning and explored its application as nerve guide substrate or conduit in vitro and in vivo. Material characterizations showed this electrospun composite material which was made of submicron fibers possessed good hydrophilicity and flexibility. In vitro study indicated electrospun collagen/PCL fibrous meshes promoted Schwann cell adhesion, elongation and proliferation. In vivo test showed electrospun collagen/PCL porous nerve conduits successfully supported nerve regeneration through an 8 mm sciatic nerve gap in adult rats, achieving similar electrophysiological and muscle reinnervation results as autografts. Although regenerated nerve fibers were still in a pre-mature stage 4 months postoperatively, the implanted collagen/PCL nerve conduits facilitated more axons regenerating through the conduit lumen and gradually degraded which well matched the nerve regeneration rate. Conclusions All the results demonstrated this collagen/PCL nerve conduit with tailored degradation rate fabricated by electrospinning could be an efficient alternative to autograft for peripheral nerve regeneration research. Due to its advantage of high surface area for cell attachment, it

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Hyaluronic acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models

    Science.gov (United States)

    Zhang, Yan; Liu, Qin; Yang, Ning; Zhang, Xuegang

    2016-01-01

    Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC) could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each) and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm), and the medical sodium hyaluronate (MSH) group was treated with 1% MSH (0.5 mL). At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99) and the ORC group (1.40±0.97) were significantly lower than those in the control group (3.00±0.82) (P=0.005). Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82) and the ORC group (1.50±1.27) were significantly lower than those in the control group (3.50±0.53) (P=0.001). In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model. PMID:27822014

  14. 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

  15. Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion

    Directory of Open Access Journals (Sweden)

    Sanders Jennifer A

    2012-03-01

    Full Text Available Abstract Background The transcription factor c-myc regulates genes involved in hepatocyte growth, proliferation, metabolism, and differentiation. It has also been assigned roles in liver development and regeneration. In previous studies, we made the unexpected observation that c-Myc protein levels were similar in proliferating fetal liver and quiescent adult liver with c-Myc displaying nucleolar localization in the latter. In order to investigate the functional role of c-Myc in adult liver, we have developed a hepatocyte-specific c-myc knockout mouse, c-mycfl/fl;Alb-Cre. Results Liver weight to body weight ratios were similar in control and c-myc deficient mice. Liver architecture was unaffected. Conditional c-myc deletion did not result in compensatory induction of other myc family members or in c-Myc's binding partner Max. Floxed c-myc did have a negative effect on Alb-Cre expression at 4 weeks of age. To explore this relationship further, we used the Rosa26 reporter line to assay Cre activity in the c-myc floxed mice. No significant difference in Alb-Cre activity was found between control and c-mycfl/fl mice. c-myc deficient mice were studied in a nonproliferative model of liver growth, fasting for 48 hr followed by a 24 hr refeeding period. Fasting resulted in a decrease in liver mass and liver protein, both of which recovered upon 24 h of refeeding in the c-mycfl/fl;Alb-Cre animals. There was also no effect of reducing c-myc on recovery of liver mass following 2/3 partial hepatectomy. Conclusions c-Myc appears to be dispensable for normal liver growth during the postnatal period, restoration of liver mass following partial hepatectomy and recovery from fasting.

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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].

  3. Temporal mapping of CEBPA and CEBPB binding during liver regeneration reveals dynamic occupancy and specific regulatory codes for homeostatic and cell cycle gene batteries

    DEFF Research Database (Denmark)

    Jakobsen, Janus Schou; Waage, Johannes; Rapin, Nicolas

    2013-01-01

    quantified the genome-wide binding patterns of two key hepatocyte transcription factors, CEBPA and CEBPB (also known as C/EBPalpha and C/EBPbeta), at multiple time points during the highly dynamic process of liver regeneration elicited by partial hepatectomy in mouse. Combining these profiles with RNA...... polymerase II binding data, we find three temporal classes of transcription factor binding to be associated with distinct sets of regulated genes involved in the acute phase response, metabolic/homeostatic functions, or cell cycle progression. Moreover, we demonstrate a previously unrecognized early phase......IP experiments involving a panel of central transcription factors and/or by comparison to external ChIP-seq data. Our quantitative investigation not only provides in vivo evidence for the involvement of many new factors in liver regeneration but also points to similarities in the circuitries regulating self...

  4. 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.

  5. A morphometric study on regeneration of the human liver following hepatectomy by computed tomography

    International Nuclear Information System (INIS)

    Okamoto, Eizo; Yamanaka, Naoki

    1983-01-01

    A morphometric study has been carried out on the restoration of remnant hepatic volume (RHV) after various extent of hepatectomy in humans by serial computed tomography in 15 non-cirrhotics, 14 cirrhotics and 7 hepatic failures. Restoration of RHV has been observed only in patients with more than 10 % hepatectomy. In non-cirrhotics with major hepatectomy (RHV less than 600 cm 3 ), an early rapid increasing phase was followed by a subsequent decreasing phase and then a slow increasing phase. Decreasing phase was absent in most non-cirrhotics with moderate hepatectomy (RHV 600-1000 cm 3 ) and cirrhotics. Daily increase rate of RHV during the first posthepatectomy month was inversely proportional to the RHV at operation restoring invariably to 800-900 cm 3 at the end of this month. Termination of regeneration was within 6 months in non-cirrhotics with moderate hepatectomy and from 6 to 12 months in those with major hepatectomy. It was delayed in cirrhotics. RHV has finally attained to an average of 90 % of preoperative hepatic volume in non-cirrhotics and 81 % in cirrhotics. The restoration of RHV was extremely poor in hepatic failures. (author)

  6. 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

  7. 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

  8. 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

  9. External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

    Directory of Open Access Journals (Sweden)

    Terasa Foo

    2013-01-01

    Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

  10. Downregulation of IL6 Targeted MiR-376b May Contribute to a Positive IL6 Feedback Loop During Early Liver Regeneration in Mice

    Directory of Open Access Journals (Sweden)

    Shan Lu

    2015-08-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs are a group of endogenous, small, noncoding RNAs implicated in a variety of biological processes, including cell proliferation, apoptosis, differentiation and metabolism. The present study aims to explore the potential role and molecular mechanism of miR-376b during the early phase of liver regeneration. Methods: MiRNA profiling microarrays were used to assess the changes in miRNA expression. For functional analysis, cell proliferation, apoptosis assays, real time quantitative PCR and westernblot analysis were performed. Results: The comprehensive miRNA expression profiling assays on regenerating liver tissues 4 h after partial hepatectomy (PH showed that three miRNAs (miR-127, miR-376b and miR-494 located in the Dlk1-Gtl2 miRNA cluster were significantly downregulated. In vitro functional studies demonstrated that high-level interleukin 6 (IL6 inhibited the expression of miR-376b, and miR-376b mimics treatment decreased cell proliferation and increased apoptosis. Further target analysis showed that miR-376b reduced the mRNA and protein expression levels of NF-kappa-B inhibitor zeta (NFKBIZ and signal transducers and transcription activators 3 (STAT3. Additionally, IL6-induced miR-376b downregulation would, in turn, increase the expression of IL-6 possibly via a feedback loop involving NFKBIZ or/and STAT3. Conclusion: During the early phase of liver regeneration, miR-376b expression was significantly decreased. Our findings reveal that a regulatory circuitry between miR-376b and IL-6 may exist, which trigger the initiation of liver regeneration.

  11. 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.

  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. 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)

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    International Nuclear Information System (INIS)

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin

    2013-01-01

    Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

  5. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin, E-mail: chengleiyx@126.com

    2013-10-18

    Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

  6. 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.

  7. 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)

  8. 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)

  9. 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.

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

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    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.

  11. 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.

  12. 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

  13. 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)

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

    Directory of Open Access Journals (Sweden)

    Đurašević S.F.

    2010-01-01

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

  15. Use of rat mature adipocyte-derived dedifferentiated fat cells as a cell source for periodontal tissue regeneration

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    Daisuke eAkita

    2016-02-01

    Full Text Available Lipid-free fibroblast-like cells, known as dedifferentiated fat (DFAT cells, can be generated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and can transdifferentiate into various cell types under appropriate culture conditions. The first objective of this study was to compare the multilineage differentiation potential of DFAT cells with that of adipose-derived stem cells (ASCs on mesenchymal stem cellsWe obtained DFAT cells and ASCs from inbred rats and found that rat DFAT cells possess higher osteogenic differentiation potential than rat ASCs. On the other hand, DFAT cells show similar adipogenic differentiation, and chondrogenic differentiation potential in comparison with ASCs. The second objective of this study was to assess the regenerative potential of DFAT cells combined with novel solid scaffolds composed of PLGA (Poly d, l-lactic-co-glycolic acid on periodontal tissue, and to compare this with the regenerative potential of ASCs combined with PLGA scaffolds. Cultured DFAT cells and ASCs were seeded onto PLGA scaffolds (DFAT/PLGA and ASCs/PLGA and transplanted into periodontal fenestration defects in rat mandible. Micro computed tomography analysis revealed a significantly higher amount of bone regeneration in the DFAT/PLGA group compared with that of ASCs/PLGA and PLGA-alone groups at 2, 3 and 5 weeks after transplantation. Similarly, histomorphometric analysis showed that DFAT/PLGA groups had significantly greater width of cementum, periodontal ligament and alveolar bone than ASCs/PLGA and PLGA-alone groups. In addition, transplanted fluorescent-labeled DFAT cells were observed in the periodontal ligament beside the newly formed bone and cementum. These findings suggest that DFAT cells have a greater potential for enhancing periodontal tissue regeneration than ASCs. Therefore, DFAT cells are a promising cell source for periodontium regeneration.

  16. 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.

  17. 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.

  18. Mdivi-1 inhibits astrocyte activation and astroglial scar formation and enhances axonal regeneration after spinal cord injury in rats

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    gang li

    2016-10-01

    Full Text Available After spinal cord injury (SCI, astrocytes become hypertrophic and proliferative, forming a dense network of astroglial processes at the site of the lesion. This constitutes a physical and biochemical barrier to axonal regeneration. Mitochondrial fission regulates cell cycle progression; inhibiting the cell cycle of astrocytes can reduce expression levels of axon growth-inhibitory molecules as well as astroglial scar formation after SCI. We therefore investigated how an inhibitor of mitochondrial fission, Mdivi-1, would affect astrocyte proliferation, astroglial scar formation, and axonal regeneration following SCI in rats. Western blot and immunofluorescent double-labeling showed that Mdivi-1 markedly reduced the expression of the astrocyte marker glial fibrillary acidic protein (GFAP, and a cell proliferation marker, proliferating cell nuclear antigen, in astrocytes 3 days after SCI. Moreover, Mdivi-1 decreased the expression of GFAP and neurocan, a chondroitin sulfate proteoglycan. Notably, immunofluorescent labeling and Nissl staining showed that Mdivi-1 elevated the production of growth-associated protein-43 and increased neuronal survival at 4 weeks after SCI. Finally, hematoxylin-eosin staining and behavioral evaluation of motor function indicated that Mdivi-1 also reduced cavity formation and improved motor function 4 weeks after SCI. Our results confirm that Mdivi-1 promotes motor function after SCI, and indicate that inhibiting mitochondrial fission using Mdivi-1 can inhibit astrocyte activation and astroglial scar formation and contribute to axonal regeneration after SCI in rats.

  19. DNA methylation dynamics in the rat EGF gene promoter after partial hepatectomy

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    Deming Li

    2014-06-01

    Full Text Available Epidermal growth factor (EGF, a multifunctional growth factor, is a regulator in a wide variety of physiological processes. EGF plays an important role in the regulation of liver regeneration. This study was aimed at investigating the methylation level of EGF gene throughout liver regeneration. DNA of liver tissue from control rats and partial hepatectomy (PH rats at 10 time points was extracted and a 354 bp fragment including 10 CpG sites from the transcription start was amplified after DNA was modified by sodium bisulfate. The result of sequencing suggested that methylation ratio of four CpG sites was found to be significantly changed when PH group was compared to control group, in particular two of them were extremely striking. mRNA expression of EGF was down-regulated in total during liver regeneration. We think that the rat EGF promoter region is regulated by variation in DNA methylation during liver regeneration.

  20. Evaluation of a platelet lysate bilayered system for periodontal regeneration in a rat intrabony three-wall periodontal defect.

    Science.gov (United States)

    Babo, Pedro S; Cai, Xinjie; Plachokova, Adelina S; Reis, Rui L; Jansen, John; Gomes, Manuela E; Walboomers, X Frank

    2018-02-01

    With currently available therapies, full regeneration of lost periodontal tissues after periodontitis cannot be achieved. In this study, a combined compartmentalized system was tested, composed of (a) a platelet lysate (PL)-based construct, which was placed along the root aiming to regenerate the root cementum and periodontal ligament, and (b) a calcium phosphate cement composite incorporated with hyaluronic acid microspheres loaded with PL, aiming to promote the regeneration of alveolar bone. This bilayered system was assessed in a 3-wall periodontal defect in Wistar rats. The periodontal healing and the inflammatory response of the materials were scored for a period up to 6 weeks after implantation. Furthermore, histomorphometrical measurements were performed to assess the epithelial downgrowth, the formation of alveolar bone, and the formation of new connective tissue attachment. Our data showed that the stabilization of platelet-origin proteins on the root surface increased the overall periodontal healing score and restricted the formation of long epithelial junctions. Nevertheless, the faster degradation of the cement component with incorporated hyaluronic acid microspheres compromised the stability of the system, which hampered the periodontal regeneration. Overall, in this work, we proved the positive therapeutic effect of the immobilization of a PL-based construct over the root surface in a combined compartmentalized system to assist predictable healing of functional periodontium. Therefore, after optimization of the hard tissue analogue, the system should be further elaborated in (pre)clinical validation studies. Copyright © 2017 John Wiley & Sons, Ltd.

  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. 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

  11. 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.)

  12. 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.

  13. 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...

  14. 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...

  15. 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.

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. Evaluation of the effect of a gamma irradiated DBM-pluronic F127 composite on bone regeneration in Wistar rat.

    Directory of Open Access Journals (Sweden)

    Tamer Al Kayal

    Full Text Available Demineralized bone matrix (DBM is widely used for bone regeneration. Since DBM is prepared in powder form its handling properties are not optimal and limit the clinical use of this material. Various synthetic and biological carriers have been used to enhance the DBM handling. In this study we evaluated the effect of gamma irradiation on the physical-chemical properties of Pluronic and on bone morphogenetic proteins (BMPs amount in DBM samples. In vivo studies were carried out to investigate the effect on bone regeneration of a gamma irradiated DBM-Pluronic F127 (DBM-PF127 composite implanted in the femur of rats. Gamma irradiation effects (25 kGy on physical-chemical properties of Pluronic F127 were investigated by rheological and infrared analysis. The BMP-2/BMP-7 amount after DBM irradiation was evaluated by ELISA. Bone regeneration capacity of DBM-PF127 containing 40% (w/w of DBM was investigated in transcortical holes created in the femoral diaphysis of Wistar rat. Bone porosity, repaired bone volume and tissue organization were evaluated at 15, 30 and 90 days by Micro-CT and histological analysis. The results showed that gamma irradiation did not induce significant modification on physical-chemical properties of Pluronic, while a decrease in BMP-2/BMP-7 amount was evidenced in sterilized DBM. Micro-CT and histological evaluation at day 15 post-implantation revealed an interconnected trabeculae network in medullar cavity and cellular infiltration and vascularization of DBM-PF127 residue. In contrast a large rate of not connected trabeculae was observed in Pluronic filled and unfilled defects. At 30 and 90 days the DBM-PF127 samples shown comparable results in term of density and thickness of the new formed tissue respect to unfilled defect. In conclusion a gamma irradiated DBM-PF127 composite, although it may have undergone a significant decrease in the concentration of BMPs, was able to maintains bone regeneration capability.

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

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    Suzy M. Salama

    2012-01-01

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

  19. 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

  20. 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

  1. 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.

  2. 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)

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. [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.

  10. 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

  11. 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)

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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 ...

  19. 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.

  20. 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

  1. 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.)

  2. 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