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Sample records for canalicular rat liver

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

    Energy Technology Data Exchange (ETDEWEB)

    Meier, P.J.; Valantinas, J.; Hugentobler, G.; Rahm, I. (University Hospital, Zurich (Switzerland))

    1987-10-01

    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 ({sup 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{prime}-isothiocyanostilbene-2,2{prime}-disulfonic acid, and 4,4{prime}-diisothiocyanostilbene-2,2{prime}-disulfonic acid (IC{sub 50}, {approximately}40 {mu}M). 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.

  2. Evidence for carrier-mediated chloride/bicarbonate exchange in canalicular rat liver plasma membrane vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Meier, P.J.; Knickelbein, R.; Moseley, R.H.; Dobbins, J.W.; Boyer, J.L.

    1985-04-01

    To determine whether anion exchangers might play a role in hepatic bile formation, the authors looked for the presence of Cl/sup -/:OH/sup -/ and Cl/sup -/:HCO3/sup -/ exchange in highly purified canalicular (c) and basolateral (bl) rat liver plasma membrane (LPM) vesicles. In cLPM vesicles, a pH gradient stimulated /sup 36/Cl- uptake twofold above values obtained during pH-equilibrated conditions. When 50 mM HCO3/sup -/ was also present inside the vesicles, the same pH gradient resulted in Cl/sup -/ uptake to levels fourfold above pH- and HCO3--equilibrated controls and two- to threefold above Cl- equilibrium. Initial rates of both pH and HCO3/sup -/ gradient-stimulated Cl/sup -/ uptake were completely inhibited by 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). A valinomycin-induced K/sup +/ diffusion potential (inside positive) also stimulated Cl/sup -/ uptake in cLPM, but this conductive Cl- pathway was insensitive to DIDS. The DIDS-sensitive, pH and HCO3- gradient-stimulated Cl/sup -/ uptake demonstrated: saturation with Cl/sup -/; partial inhibition by bumetanide (26%), furosemide (33%), probenecid (37%), and 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (49%); cis-inhibition by chloride and nitrate but not by sulfate and various organic anions, and independence from the membrane potential. These data demonstrate the presence of an electroneutral Cl/sup -/:OH/sup -/ and Cl/sup -/:HCO3/sup -/ exchanger in rat liver canalicular membranes that favors Cl/sup -/:HCO3/sup -/ exchange. In contrast, no evidence was found for the presence of a Cl/sup -/:HCO3/sup -/ (OH/sup -/) exchange system in blLPM vesicles.

  3. Tauroursodeoxycholic acid inserts the bile salt export pump into canalicular membranes of cholestatic rat liver

    NARCIS (Netherlands)

    Dombrowski, Frank; Stieger, Bruno; Beuers, Ulrich

    2006-01-01

    Ursodeoxycholic acid exerts anticholestatic effects in chronic cholestatic liver disease in humans as well as in experimental animal models of cholestasis. Its taurine conjugate, TUDCA, was recently shown to stimulate insertion of the apical conjugate export pump, Mrp2 (ABCC2), into canalicular

  4. Liver Inflammation Relates to Decreased Canalicular Bile Transporter Expression in Pediatric Onset Intestinal Failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Jalanko, Hannu; Pakarinen, Mikko P

    2017-02-23

    Although liver disease is a major complication of parenteral nutrition (PN) for intestinal failure (IF), its pathogenesis remains unclear. We investigated potential molecular mechanisms of liver injury in pediatric onset IF. Liver expression of canalicular phospholipid (ABCB4), bile acid (ABCB11), and sterol (ABCG5/8) transporters, their upstream regulators LXR and FXR as well as pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor (TNF) were investigated among patients with IF [age median 3.8 (IQR 1.2 to 11)] in relation to biochemical and histologic liver injury, PN, serum plant sterols, fibroblast growth factor 19, and α-tocopherol. Patients receiving PN currently (n = 18) showed more advanced liver injury than patients after weaning off PN (n = 30). Histologic portal inflammation strongly segregated PN-dependent (44%) from weaned off patients (3%, P = 0.001) and coupled with progression of cholestasis and liver fibrosis. Patients with portal inflammation demonstrated markedly induced liver RNA expression of IL6 and TNF, repression of FXR and its canalicular bile transporter target gene RNA expression, including ABCB4 and ABCB11 as well as decreased protein expression of ABCB11 and ABCB4. Furthermore, upregulation of LXR and ABCG5/8 RNA expression was suppressed in patients with portal inflammation. Current PN, increased serum levels of plant sterols stigmasterol, avenasterol, and sitosterol along with serum citrulline, a marker of enterocyte mass, predicted portal inflammation. In pediatric onset IF, current PN delivery synergistically with intestinal compromise promote liver inflammation, which associates with progression of biochemical and histologic liver injury, while reducing expression of canalicular bile transporters.

  5. Radixin is required to maintain apical canalicular membrane structure and function in rat hepatocytes.

    Science.gov (United States)

    Wang, Wei; Soroka, Carol J; Mennone, Albert; Rahner, Christoph; Harry, Kathy; Pypaert, Marc; Boyer, James L

    2006-09-01

    Ezrin-radixin-moesin proteins are cross-linkers between the plasma membrane and actin filaments. Radixin, the dominant ezrin-radixin-moesin protein in hepatocytes, has been reported to selectively tether multidrug-resistance-associated protein 2 to the apical canalicular membrane. However, it remains to be determined if this is its primary function. An adenovirus-mediated short interfering RNA (siRNA) was used to down-regulate radixin expression in collagen sandwich-cultured rat hepatocytes and morphologic and functional changes were characterized quantitatively. In control cultures, an extensive bile canalicular network developed with properly localized apical and basolateral transporters that provided for functional excretion of fluorescent cholephiles into the bile canalicular lumina. siRNA-induced suppression of radixin was associated with a marked reduction in the canalicular membrane structure as observed by differential interference contrast microscopy and F-actin staining, in contrast to control cells exposed to adenovirus encoding scrambled siRNA. Indirect immunofluorescence showed that apical transporters (multidrug-resistance-associated protein 2, bile salt export pump, and multidrug-resistance protein 1) dissociated from their normal location at the apical membrane and were found largely associated with Rab11-containing endosomes. Localization of the basolateral membrane transporter, organic anion transporting polypeptide 2 (Oatp2), was not affected. Consistent with this dislocation of apical transporters, the biliary excretion of glutathione-methylfluorescein and cholylglycylamido-fluorescein was decreased significantly in the radixin-deficient cells, but not in the control siRNA cells. Radixin is essential for maintaining the polarized targeting and/or retaining of canalicular membrane transporters and is a critical determinant of the overall structure and function of the apical membrane of hepatocytes.

  6. Altered expression and function of canalicular transporters during early development of cholestatic liver injury in Abcb4-deficient mice

    Science.gov (United States)

    Mennone, Albert; Soroka, Carol J.; Boyer, James L.

    2014-01-01

    Deficiency of ABCB4 is associated with several forms of cholestasis in humans. Abcb4−/− mice also develop cholestasis, but it remains uncertain what role other canalicular transporters play in the development of this disease. We examined the expression of these transporters in Abcb4−/− mice compared with their wild-type littermate controls at ages of 10 days and 3, 6, and 12 wk. Elevated plasma bile acid levels were already detected at 10 days and at all ages thereafter in Abcb4−/− mice. The expression of Bsep, Mrp2, Atp8b1, Abcg5, and Abcg8 liver proteins did not change at 10 days, but Bsep, Mrp2, and Atp8b1 were reduced, whereas Abcg5 and Abcg8 expression were increased in Abcb4−/− mice at all later ages. Lower bile acid concentrations were also detected in the bile of 6-wk-old Abcb4−/− mice. Immunofluorescence labeling revealed distorted canalicular architecture in the liver tissue by 12 wk in Abcb4−/− mice. Whereas Bsep and Mrp2 remained associated with the apical membrane, Atp8b1 was now localized in discrete punctuate structures adjacent to the canalicular membrane in these mice. Expression of Bsep mRNA was increased in the livers of 10-day-old Abcb4−/− mice, whereas Ost-α was decreased. By 12 wk, Bsep, Mrp2, and Abcg5 mRNA were all increased, whereas Ost-α and Ntcp were reduced. These findings indicate that canalicular transporters that determine the formation of bile are altered early in the development of cholestasis in Abcb4−/− mice and may contribute to the pathogenesis of cholestasis in this disorder. PMID:24481602

  7. Kinetic analysis of hepatobiliary transport for conjugated metabolites in the perfused liver of mutant rats (EHBR) with hereditary conjugated hyperbilirubinemia.

    Science.gov (United States)

    Takenaka, O; Horie, T; Kobayashi, K; Suzuki, H; Sugiyama, Y

    1995-11-01

    Previously, we found that the biliary excretion of the 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) glucuronide is severely impaired in Eisai hyperbilirubinemic rats (EHBR), while that of sulfate remains normal (Takenaka et al., J. Pharmacol. Exp. Ther., 274: 1362-1369, 1995). The purpose of the present study is to clarify the mechanisms for impairment of the biliary excretion of E3040 glucuronide in EHBR. We kinetically analyzed the disposition of the conjugates in the perfused liver at steady state. The uptake of the conjugates into the isolated canalicular membrane vesicles (CMVs) was also examined. At steady state, the bile/liver unbound concentration ratios of the conjugates were 40-400 in both rat strains, indicating a highly concentrated process. The biliary excretion clearance (CLu,bile) of the glucuronide, defined for the unbound concentration in the liver, was decreased in EHBR to 1/30 of that in normal rats, whereas the CLu,bile of the sulfate was comparable between the two rat strains. In vitro, the transport of E3040 glucuronide into CMV prepared from SD rats exhibited the ATP dependency, whereas minimal effect of ATP was observed on the uptake of the glucuronide into CMV from EHBR. In contrast, the uptake of E3040 sulfate was comparable between SD rats and EHBR. Furthermore, ATP did not stimulate the uptake of sulfate into the CMVs. It was suggested (1) that the excretion of E3040 glucuronide across the bile canalicular membrane is mediated by the primary active transporter which is defective in EHBR and (2) that the bile canalicular transport system for E3040 sulfate is different from that for the glucuronide in that the former remains normal in EHBR.

  8. OSMOTICALLY LYSED RAT LIVER MITOCONDRIA

    Science.gov (United States)

    Vasington, Frank D.; Greenawalt, John W.

    1968-01-01

    Osmotically lysed rat liver mitochondria have been utilized for a study of the biochemical and ultrastructural properties in relation to divalent ion accumulation. Osmotic lysis of mitochondria by suspension and washing in cold, distilled water results in the extraction of about 50% of the mitochondrial protein, the loss of the outer mitochondrial membrane, an increase in respiration, and a marked decrease in the ability to catalyze oxidative phosphorylation. Nevertheless, except for a decrease in the ability to accumulate Sr2+ by an ATP-supported process, these lysed mitochondria retain full capacity to accumulate massive amounts of divalent cations by respiration-dependent and ATP-supported mechanisms. The decreased ability of osmotically lysed mitochondria to accumulate Sr2+ by an ATP-energized process does not appear to be due to a loss or inactivation of a specific Sr2+-activated ATPase. The energy-dependent accumulation processes in lysed mitochondria show an increased sensitivity to inhibition by monovalent cations. Extraction of cytochrome c from osmotically lysed mitochondria results in a complete loss of phosphorylation and the respiration-dependent accumulation of Ca2+; a lesser, but significant, decrease in the ATP-supported accumulation of Ca2+ also was observed. The addition of cytochrome c fully restores the respiration-dependent accumulation of Ca2+ to the level present in unextracted, osmotically lysed mitochondria. The ATP-supported process is not affected by the addition of cytochrome c to extracted mitochondria, indicating that cytochrome c is not involved in ion transport energized by ATP. The osmotically lysed mitochondria are devoid of outer membranes and contain relatively little matrix substance. The accumulation of Ca2+ and Pi by lysed mitochondria under massive loading conditions is accompanied by the formation of electron-opaque deposits within the lysed mitochondria associated with the inner membranes. This finding suggests that the

  9. Increased liver regeneration rate and decreased liver function after synchronous liver and colon resection in rats

    OpenAIRE

    Okada Masaki; Funch-Jensen Peter; Knudsen Anders; Mortensen Frank; Sasanuma Hideki; Nagai Hideo; Yasuda Yoshikazu

    2009-01-01

    Abstract Background The surgical strategy for the treatment of colorectal cancer and synchronous liver metastases remains controversial. The aim of the present study was to investigate the effects of colonic resection on liver function and regeneration in a rat model. Methods Ninety-six Sprague-Dawley rats were block-randomized into six groups: Group I had a laparotomy performed. Group II had 1 cm colon resected and anastomosed. Group III and V had 40% or 70% of the liver resected, respective...

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

    NARCIS (Netherlands)

    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

  11. Taurolithocholic acid exerts cholestatic effects via phosphatidylinositol 3-kinase-dependent mechanisms in perfused rat livers and rat hepatocyte couplets.

    Science.gov (United States)

    Beuers, Ulrich; Denk, Gerald U; Soroka, Carol J; Wimmer, Ralf; Rust, Christian; Paumgartner, Gustav; Boyer, James L

    2003-05-16

    Taurolithocholic acid (TLCA) is a potent cholestatic agent. Our recent work suggested that TLCA impairs hepatobiliary exocytosis, insertion of transport proteins into apical hepatocyte membranes, and bile flow by protein kinase Cepsilon (PKCepsilon)-dependent mechanisms. Products of phosphatidylinositol 3-kinases (PI3K) stimulate PKCepsilon. We studied the role of PI3K for TLCA-induced cholestasis in isolated perfused rat liver (IPRL) and isolated rat hepatocyte couplets (IRHC). In IPRL, TLCA (10 micromol/liter) impaired bile flow by 51%, biliary secretion of horseradish peroxidase, a marker of vesicular exocytosis, by 46%, and the Mrp2 substrate, 2,4-dinitrophenyl-S-glutathione, by 95% and stimulated PI3K-dependent protein kinase B, a marker of PI3K activity, by 154% and PKCepsilon membrane binding by 23%. In IRHC, TLCA (2.5 micromol/liter) impaired canalicular secretion of the fluorescent bile acid, cholylglycylamido fluorescein, by 50%. The selective PI3K inhibitor, wortmannin (100 nmol/liter), and the anticholestatic bile acid tauroursodeoxycholic acid (TUDCA, 25 micromol/liter) independently and additively reversed the effects of TLCA on bile flow, exocytosis, organic anion secretion, PI3K-dependent protein kinase B activity, and PKCepsilon membrane binding in IPRL. Wortmannin also reversed impaired bile acid secretion in IRHC. These data strongly suggest that TLCA exerts cholestatic effects by PI3K- and PKCepsilon-dependent mechanisms that are reversed by tauroursodeoxycholic acid in a PI3K-independent way.

  12. Liver cell proliferation after partial hepatectomy in rats with liver metastases

    NARCIS (Netherlands)

    de Jong, KP; Brouwers, MAM; Huls, GA; Bun, JCAM; Wubbena, AS; Nieuwenhuis, P; Slooff, MJH; Dam, A.

    OBJECTIVE: To validate proliferating cell nuclear antigen (PCNA) expression and flow cytometry as proliferation markers in regenerating rat liver containing metastases. STUDY DESIGN: Rats containing colorectal liver metastases were killed at various days after 70% partial hepatectomy or a sham

  13. 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...

  14. Ozone inhalation modifies the rat liver proteome☆

    Science.gov (United States)

    Theis, Whitney S.; Andringa, Kelly K.; Millender-Swain, Telisha; Dickinson, Dale A.; Postlethwait, Edward M.; Bailey, Shannon M.

    2013-01-01

    Ozone (O3) is a serious public health concern. Recent findings indicate that the damaging health effects of O3 extend to multiple systemic organ systems. Herein, we hypothesize that O3 inhalation will cause downstream alterations to the liver. To test this, male Sprague-Dawley rats were exposed to 0.5 ppm O3 for 8 h/day for 5 days. Plasma liver enzyme measurements showed that 5 day O3 exposure did not cause liver cell death. Proteomic and mass spectrometry analysis identified 10 proteins in the liver that were significantly altered in abundance following short-term O3 exposure and these included several stress responsive proteins. Glucose-regulated protein 78 and protein disulfide isomerase increased, whereas glutathione S-transferase M1 was significantly decreased by O3 inhalation. In contrast, no significant changes were detected for the stress response protein heme oxygenase-1 or cytochrome P450 2E1 and 2B in liver of O3 exposed rats compared to controls. In summary, these results show that an environmentally-relevant exposure to inhaled O3 can alter the expression of select proteins in the liver. We propose that O3 inhalation may represent an important unrecognized factor that can modulate hepatic metabolic functions. PMID:25544660

  15. Ozone inhalation modifies the rat liver proteome.

    Science.gov (United States)

    Theis, Whitney S; Andringa, Kelly K; Millender-Swain, Telisha; Dickinson, Dale A; Postlethwait, Edward M; Bailey, Shannon M

    2014-01-01

    Ozone (O3) is a serious public health concern. Recent findings indicate that the damaging health effects of O3 extend to multiple systemic organ systems. Herein, we hypothesize that O3 inhalation will cause downstream alterations to the liver. To test this, male Sprague-Dawley rats were exposed to 0.5ppm O3 for 8h/day for 5 days. Plasma liver enzyme measurements showed that 5 day O3 exposure did not cause liver cell death. Proteomic and mass spectrometry analysis identified 10 proteins in the liver that were significantly altered in abundance following short-term O3 exposure and these included several stress responsive proteins. Glucose-regulated protein 78 and protein disulfide isomerase increased, whereas glutathione S-transferase M1 was significantly decreased by O3 inhalation. In contrast, no significant changes were detected for the stress response protein heme oxygenase-1 or cytochrome P450 2E1 and 2B in liver of O3 exposed rats compared to controls. In summary, these results show that an environmentally-relevant exposure to inhaled O3 can alter the expression of select proteins in the liver. We propose that O3 inhalation may represent an important unrecognized factor that can modulate hepatic metabolic functions. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Ozone inhalation modifies the rat liver proteome

    Directory of Open Access Journals (Sweden)

    Whitney S. Theis

    2014-01-01

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

  17. Increased liver regeneration rate and decreased liver function after synchronous liver and colon resection in rats.

    Science.gov (United States)

    Sasanuma, Hideki; Mortensen, Frank Viborg; Knudsen, Anders Riegels; Funch-Jensen, Peter; Okada, Masaki; Nagai, Hideo; Yasuda, Yoshikazu

    2009-12-24

    The surgical strategy for the treatment of colorectal cancer and synchronous liver metastases remains controversial. The aim of the present study was to investigate the effects of colonic resection on liver function and regeneration in a rat model. Ninety-six Sprague-Dawley rats were block-randomized into six groups: Group I had a laparotomy performed. Group II had 1 cm colon resected and anastomosed. Group III and V had 40% or 70% of the liver resected, respectively. Additionally Group IV and VI had 1 cm colon resected and anastomosed, respectively. Body weight was recorded on postoperative day 0, 3, 5 and 7. Rats were sacrificed on postoperative day 7 by rapid collection of blood from the inferior vena cava, and endotoxin levels were measured. Remnant liver function was evaluated by means of branched amino acids to tyrosine ratio. Liver regeneration was calculated by (liver weight per 100 g of the body weight at sacrifice/preoperative projected liver weight per 100 g of the body weight) x 100. The total number of complications was significantly higher in Group VI than Group I, III, IV, and V. Body weight and branched amino acids to tyrosine ratio were both significantly lower in rats that had simultaneous colonic and liver resection performed. Hepatic regeneration rate was significantly higher in the simultaneous colectomy group. Systemic endotoxin levels were unaffected by simultaneous colectomy on postoperative day 7. In our model morbidity seems to be related to the extent of hepatic resection. In rats undergoing liver resection, simultaneous colectomy induced a higher degree of hepatic regeneration rate. Body weight changes and branched amino acids to tyrosine ratio were negatively affected by simultaneous colectomy.

  18. Liver retinol and carotenoid concentration of rats experimentally ...

    African Journals Online (AJOL)

    This study investigated the liver retinol and carotenoid concentration of rats experimentally infected with Trypanosoma brucei. Results of the liver retinol determination showed that T. brucei infection led to a progressively significant (P < 0.01) depletion of liver retinol concentration (body vitamin A status) of infected rats from ...

  19. Characterization of the rat developmental liver transcriptome.

    Science.gov (United States)

    Chapple, Richard H; Tizioto, Polyana C; Wells, Kevin D; Givan, Scott A; Kim, JaeWoo; McKay, Stephanie D; Schnabel, Robert D; Taylor, Jeremy F

    2013-04-16

    Gene regulation and transcriptome studies have been enabled by the development of RNA-Seq applications for high-throughput sequencing platforms. Next generation sequencing is remarkably efficient and avoids many issues inherent in hybridization-based microarray methodologies including the exon-specific dependence of probe design. Biologically relevant transcripts including messenger and regulatory RNAs may now be quantified and annotated regardless of whether they have previously been observed. We used RNA-Seq to investigate global patterns of gene expression in early developing rat liver. Liver samples from timed-pregnant Lewis rats were collected at six fetal and neonatal stages [embryonic day (E)14, E16, E18, E20, postnatal day (P)1, P7], transcripts were sequenced using an Illumina HiSeq 2000, and data analysis was performed with the Tuxedo software suite. Genes and isoforms differing in abundance were queried for enrichment within functionally related gene groups using the Functional Annotation Tool of the DAVID Bioinformatics Database. While hematopoietic gene expression is initiated by E14, hepatocyte maturation is a gradual process involving clusters of genes responsible for response to nutrients and enzymes responsible for glycolysis and fatty acid catabolism. Following birth, a large cluster of differentially abundant genes was enriched for mitochondrial gene expression and cholesterol synthesis indicating that by 1 wk of age, the liver is engaged in lipid sensing and bile production. Clustering results for differentially abundant genes and isoforms were similar with the greatest difference for the E14/E16 comparison. Finally, a bioinformatic approach was used to annotate 1,307 novel liver transcripts assembled from sequences that aligned to intergenic regions of the rat genome.

  20. Liver function of Streptozotocin- Induced Diabetic Rats Orally ...

    African Journals Online (AJOL)

    This study evaluated the liver status of STZ- induced diabetic rats treated with aqueous root-bark extract of T. tetraptera for 35 days. Twenty-four (24) rats in four groups (normal control, diabetic control, T. tetraptera treated STZ induced diabetic rats at 150 mg/kg b. w. and T. tetraptera treated STZ-diabetic rats at 300 mg/kg ...

  1. Mechanism of secretion of biliary lipids. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol.

    Science.gov (United States)

    Gregory, D H; Vlahcevic, Z R; Schatzki, P; Swell, L

    1975-01-01

    The role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lipids was investigated by using the isolated perfused rat liver model. Labeled lecithin precursors ((3H)-palmitic acid, (14C)linoleic acid, (3H)choline, and 32PO4) and a cholesterol precursor ((3H)mevalonic acid) were administered with and without sodium taurocholate. The incorporation pattern of these labeled precursors into linoleyl and arachidonyl lecithins and cholesterol fractions of microsomes, bile canaliculi, and bile were examined at 30-min intervals up to 90 min. Marker enzymes and electron microscopy indicated that isolated subfractions of plasma membranes were enriched with bile canaliculi (less than 10 percent microsomal contamination). Taurocholate significantly stimulated the incorporation of 32PO4, (3H)choline, (3H)palmitic acid, and (14C)linoleic acid into linoleyl and arachidonyl lecithin with parallel incorporation curves for microsomal and bile canalicular membranes throughout the 90-min study period. During the 30-60-min period, however, these same lecithin fractions in bile significantly exceeded the specific activity of the membrane lecithins. The enzyme CDP-choline diglyceride transferase was virtually absent from canaliculi relative to microsomes, indicating that canaliculi lack the capacity for de novo lecithin synthesis. Incorporation of (3H)mevalonic acid into membranous and biliary cholesterol followed a pattern similar to that for lecithin. These data provide evidence that (a) biliary lecithin and cholesterol are derived from a microsomal subpool regulated by the flux of enterohepatic bile acids, (b) the role of the bile canalicular membranes with respect to biliary lipids is primarily transport rather than synthesis, and (c) lecithin and cholesterol are transported together from microsomes to bile. The findings are consistent with the existence of a cytoplasmic lipid complex within the hepatocyte which is actively involved in the

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

    African Journals Online (AJOL)

    Liver Iron Contents in Rats after Administration of Certain Iron Compounds. CP van Wyk, DJ Robbins. Abstract. The effect of consumption of certain iron compounds on liver iron deposition was studied in rats, in each case at 4 dietary iron levels ranging from 70 to 206 mg/100 g diet. In one of two series the basic diet was ...

  3. Oncostatin M regulates membrane traffic and stimulates bile canalicular membrane biogenesis in HepG2 cells

    NARCIS (Netherlands)

    Van der Wouden, Johanna M.; Van IJzendoorn, Sven C.D.; Hoekstra, Dick

    2002-01-01

    Hepatocytes are the major epithelial cells of the liver and they display membrane polarity: the sinusoidal membrane representing the basolateral surface, while the bile canalicular membrane is typical of the apical membrane. In polarized HepG2 cells an endosomal organelle, SAC, fulfills a prominent

  4. 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.

  5. Effect of intensive insulin treatment on the liver in hyperglycemic rats with liver injury

    Directory of Open Access Journals (Sweden)

    Jun-xun MA

    2014-01-01

    Full Text Available Objective To reproduce a liver injury model in hyperglycemic rats, and investigate the effect of intensive insulin therapy on the liver. Methods Streptozotocin (STZ and D-gal were injected to reproduce hyperglycemic liver injury model in rats. These rats were divided into intensive insulin group (with blood glucose controlled at 6-8mmol/L and conventional treatment group (with blood glucose 9-12mmol/L. Before and 1, 3, 5, 7 days after the reproduction of the model, the rats were sacrificed, and alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, total protein, alkaline phosphatase were determined. The pathological sections of the liver tissues from the model rats and normal rats were made, they were examined after HE staining. Electron microscopic examination was also performed for the liver tissue of the 7-d models. Results Liver injury model of rats with hyperglycemia was successfully reproduced. Intensive insulin therapy can reduce the death risk in model rats. The mortality of rats was lower in intensive insulin group than in conventional treatment group (P<0.01. After intensive insulin therapy, ALT, AST, T-Bil and ALP decreased, while albumin and total protein increased (P<0.01 or P<0.05. HE staining and transmission electron microscopy revealed that degeneration and necrosis of hepatocytes were ameliorated. Conclusion The liver injury model of rats with hyperglycemia has been successfully reproduced. Intensive insulin therapy can decrease the mortality of model rats and reduce the degree of rat liver injury, and the results show a prospect for clinical application. DOI: 10.11855/j.issn.0577-7402.2013.01

  6. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme.

    Science.gov (United States)

    Bertone, V; Tarantola, E; Ferrigno, A; Gringeri, E; Barni, S; Vairetti, M; Freitas, I

    2011-02-08

    Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT). Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS). However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20) that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1), frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but most hepatocytes

  7. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

    Directory of Open Access Journals (Sweden)

    V. Bertone

    2011-02-01

    Full Text Available Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT. Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS. However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20 that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1, frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but

  8. [Metabolism of nicousamide in rat and human liver in vitro].

    Science.gov (United States)

    Sheng, Li; Hu, Jin-ping; Chen, Hui; Li, Yan

    2008-09-01

    This paper is aimed to study the metabolic kinetics of nicousamide in rat liver microsomes and cytosol and to identify the major metabolite and drug metabolizing enzymes involved in the metabolism of nicousamide in rat and human liver microsomes by selective inhibitors in vitro. The concentration of nicousamide was determined by HPLC-UV method. The metabolite of nicousamide in rat and human liver microsomes was isolated and identified by LC-MS/MS. The major metabolite of nicousamide in rat and human liver microsomes was identified to be 3-(3'-carboxy-4'-hydroxy-anilino-carbo-)-6-amino-7-hydroxy-8-methyl-coumarin (M1). The metabolite of nicousamide in rat plasma, urine, bile and liver was consistent with M1. The metabolism of nicousamide can be catalyzed by several reductases, including CYP450 reductases, cytochrome b5 reductases and CYP2C6 in rat liver microsomes, as well as xanthine oxidase and DT-diaphorase in rat liver cytosol.

  9. Liver fibrosis impairs hepatic pharmacokinetics of liver transplant drugs in the rat model.

    Science.gov (United States)

    Zou, Yu-Hong; Liu, Xin; Khlentzos, Alexander M; Asadian, Peyman; Li, Peng; Thorling, Camilla A; Robertson, Thomas A; Fletcher, Linda M; Crawford, Darrell H G; Roberts, Michael S

    2010-01-01

    This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl(4)-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver. The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models. The results showed a marked increase in the liver fibrosis index for CCl(4)-treated rats compared to controls (pdrugs were significantly lower (pdrugs were significantly longer (pdrugs across the basolateral membrane and their metabolic clearance and were in a manner similar to those previously found for another group of drugs.

  10. 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 ...

  11. 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 ...

  12. Biochemical effects on the liver and kidney of rats administered ...

    African Journals Online (AJOL)

    The effects of aqueous extract of ximenia Americana stem bark on liver and kidney of albino rats was investigated. Different doses of the crude extract were administered to rats for 30 consecutive days. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of treated animals significantly ...

  13. Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets

    NARCIS (Netherlands)

    Roelofsen, H; Soroka, CJ; Keppler, D; Boyer, JL

    The canalicular membrane of rat hepatocytes contains an ATP-dependent multispecific organic anion transporter, also named multidrug resistance protein 2, that is responsible for the biliary secretion of several amphiphilic organic anions. This transport function is markedly diminished in mutant rats

  14. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  15. 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

  16. Inflammatory Stress Potentiates Emodin-Induced Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Can eTu

    2015-10-01

    Full Text Available Herbal medicines containing emodin, widely used for the treatment of hepatitis in clinic, have been reported with hepatotoxicity in individuals. A modest inflammatory stress potentiating liver injury has been linked to the idiosyncratic drug-induced liver injury (IDILI. In this study, we investigated the hypothesis that lipopolysaccharide (LPS interacts with emodin could synergize to cause liver injury in rats. Emodin (ranging from 20, 40 to 80 mg/kg, which is in the range of liver protection, was administered to rats, before LPS (2.8 mg/kg or saline vehicle treatment. The biochemical tests showed that non-toxic dosage of LPS coupled with emodin caused significant increases of plasma ALT and AST activities as compared to emodin alone treated groups (P<0.05. In addition, with LPS or emodin alone could not induce any changes in ALT and AST activity, as compared with the control group (0.5% CMC-Na treatment. Meanwhile, the plasma proinflammatory cytokines, TNF-α, IL-1β, and IL-6 increased significantly in the emodin/LPS groups compared to either emodin groups or the LPS (P<0.05. Histological analysis showed that liver damage was only found in emodin/LPS cotreatmented rat livers samples. These results indicate that non-toxic dosage of LPS potentiates the hepatotoxicity of emodin. This discovery raises the possibility that emodin and herbal medicines containing it may induce liver injury in the inflammatory stress even in their therapeutic dosages.

  17. Isolation and Culture of Single Cell Types from Rat Liver.

    Science.gov (United States)

    Zhang, Qidi; Qu, Ying; Li, Zhenghong; Zhang, Qingqing; Xu, Mingyi; Cai, Xiaobo; Li, Fei; Lu, Lungen

    2016-01-01

    There have been few reports on the simultaneous isolation of multiple liver cell populations thus far. As such, this study was aimed at establishing a protocol for the simultaneous separation of hepatocytes (HCs), hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) from the rat liver and assessing the in vitro culture of these cells. Single-cell suspensions from the liver were obtained by ethylene glycol tetraacetic acid/collagenase perfusion. After low-speed centrifugal separation of HCs, pronase was added to the nonparenchymal cell fraction to eliminate the remaining HCs. Subsequently, HSCs, LSECs and KCs were purified by two steps of density gradient centrifugation using Nycodenz and Percoll in addition to selective attachment. Pronase treatment increased the HSC yield (1.5 ± 0.2 vs. 0.7 ± 0.3 cells/g liver, p cultured in vitro. LSEC apoptosis began on day 3 and reached a maximum on day 7. A few surviving LSECs began proliferating and split to form a cobblestone, sheet-like appearance on day 14. The LSECs on day 14 lost fenestrations but retained scavenger function. Thus, viable and purified liver cells were obtained with a high yield from the rat liver using the developed method, which may be useful for studying the physiology and pathology of the liver in the future. © 2016 S. Karger AG, Basel.

  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...... hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human hepatocellular...... carcinoma (HCC) and we identify novel candidate proteomic aberrations for further analysis in human HCC. In particular, increased levels of HSP70, HSP90, AKR1B1, AKR7A3, GCLM, ANXA5, VDBP, RGN and SULT1E1 were associated specifically with rat hepatomas, or with liver cancer progression in rat. In addition...

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

    Directory of Open Access Journals (Sweden)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2006-05-21

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

  1. Nonalcoholic fatty liver sensitizes rats to carbon tetrachloride hepatotoxicity.

    Science.gov (United States)

    Donthamsetty, Shashikiran; Bhave, Vishakha S; Mitra, Mayurranjan S; Latendresse, John R; Mehendale, Harihara M

    2007-02-01

    This study tested whether hepatic steatosis sensitizes liver to toxicant-induced injury and investigated the potential mechanisms of hepatotoxic sensitivity. Male Sprague-Dawley rats were fed a methionine- and choline-deficient diet for 31 days to induce steatosis. On the 32nd day, administration of a nonlethal dose of CCl4 (2 mL/kg, intraperitoneally) yielded 70% mortality in steatotic rats 12-72 hours after CCl4 administration, whereas all nonsteatotic rats survived. Neither CYP2E1 levels nor covalent binding of [14C] CCl4-derived radio-label differed between the groups, suggesting that increased bioactivation is not the mechanism for this amplified toxicity. Cell division and tissue repair, assessed by [3H]thymidine incorporation and proliferative cell nuclear antigen assay, were inhibited in the steatotic livers after CCl4 administration and led to progressive expansion of liver injury culminating in mortality. The hypothesis that fatty hepatocytes undergo cell cycle arrest due to (1) an inability to replenish ATP due to overexpressed uncoupling protein-2 (UCP-2) or (2) induction of growth inhibitor p21 leading to G1/S phase arrest was tested. Steatotic livers showed 10-fold lower ATP levels due to upregulated UCP-2 throughout the time course after CCl4 administration, leading to sustained inhibition of cell division. Western blot analysis revealed an up-regulation of p21 due to overexpression of TGF beta1 and p53 and down-regulation of transcription factor Foxm 1b in steatotic livers leading to lower phosphorylated retinoblastoma protein. Thus, fatty hepatocytes fail to undergo compensatory cell division, rendering the liver susceptible to progression of liver injury. Impaired tissue repair sensitizes the steatotic livers to hepatotoxicity.

  2. Metabolism and covalent binding of [14C]toluene by human and rat liver microsomal fractions and liver slices.

    Science.gov (United States)

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

    1990-01-01

    The in vitro metabolism of [14C]toluene by liver microsomes and liver slices from male Fischer F344 rats and human subjects has been compared. Rat liver microsomes produced only benzyl alcohol from toluene. Liver microsomes from human subjects metabolized toluene to benzyl alcohol, benzaldehyde, and benzoic acid. Liver microsomes from one human donor also produced p-cresol and o-cresol. The overall rate of toluene metabolism by human liver microsomes was 9-fold greater than by rat liver microsomes. Human liver microsomal metabolism of benzyl alcohol to benzaldehyde required NADPH and was inhibited by carbon monoxide and high pH (pH 10). but was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P-450, rather than alcohol dehydrogenase, was responsible for the metabolism of benzyl alcohol to benzaldehyde. Human and rat liver slices metabolized toluene to hippuric acid and benzoic acid. The overall rate of toluene metabolism by human liver slices was 1.3-fold greater than by rat liver slices. Cresols and cresol conjugates were not detected in human or rat liver slice incubations. Covalent binding of [14C]toluene to human liver microsomes and slices was 21-fold and 4-fold greater than to the comparable rat liver preparations. Covalent binding did not occur in the absence of NADPH, was significantly decreased by coincubation with cysteine, glutathione, or superoxide dismutase, and was unaffected by coincubation with lysine. Protease and ribonuclease digestion decreased the amount of toluene covalently bound to human liver microsomes by 78% and 27% respectively. Acid washing of human liver microsomes had no effect on covalent binding.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Acute effects of 2-nitropropane on rat liver and brain.

    Science.gov (United States)

    Zitting, A; Savolainen, H; Nickels, J

    1981-11-01

    Intraperitoneal injection (50 mg/kg) of 2-nitropropane (2-NP) induced lipid accumulation, centrilobular necrosis, degranulation of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum and mitochondrial abnormalities in rat liver 24 h after exposure. These pathological changes were accompanied by elevated serum alanine aminotransferase (ALAT) levels. Hepatic glutathione content increased rapidly in exposed rats. 2-NP depressed markedly hepatic cytochrome P-450 and microsomal monooxygenase activity while the enzyme, epoxide hydratase, UDP-glucuronosyltransferase and cytosolic glutathione peroxidase were enhanced. 2-NP caused an increase of acetylcholine esterase activity in the brain. This effect was also detected in synaptosomes isolated from exposed rats. The results suggest peroxidative damage in the cells.

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

    Directory of Open Access Journals (Sweden)

    Edimar Leandro Toderke

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

  5. The Restriction Endonuclease Cleavage Map of Rat Liver Mitochondrial DNA

    NARCIS (Netherlands)

    Bakker, H.; Holtrop, M.; Terpstra, P.

    1977-01-01

    Mitochondrial DNA from rat liver contains six sites for cleavage by the restriction endonucleases Hind III and EcoRI. A large stretch of DNA, comprising about 40% of the mitochondrial genome is not cleaved by either of the enzymes; eight cleavage sites are located on a DNA stretch of 35% of the

  6. Effect of thiols on lipid peroxidation in rat liver microsomes

    NARCIS (Netherlands)

    Haenen, G R; Vermeulen, N P; Timmerman, H; Bast, A

    1989-01-01

    The stimulatory or inhibitory effects of various thiol compounds on in vitro lipid peroxidation by iron-ascorbate in rat liver microsomes were determined. Glutathione had no measurable pro-oxidant capacity, in contrast, it protected against lipid peroxidation. N-Acetyl l-cysteine and

  7. 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

  8. Changes in rat liver mitochondrial lipids in vitamin A deficiency

    Indian Academy of Sciences (India)

    tribpo

    Abstract. The alterations in the lipid profiles of rat liver mitochondria due to vita- min A deficiency were studied. The amount of total lipids and phospholipids were decreased with a concomitant increase in triglycerides and cholesterol levels in mito- chondria, isolated from vitamin Α-deficient animals. Of particular significance ...

  9. 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 ...

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

    African Journals Online (AJOL)

    e.g. home-brewed beer may contain iron lactate. We have ... foods (e.g. mahewll and home-made beer) under conditions causing ... De-ionised water was offered ad lib. At the end of a 21-day experimental period the rats were killed with ether and the livers excised for deter- mination of the non-haemoglobin iron content.

  11. Regulatory effect of divalent cations on rat liver alkaline ...

    African Journals Online (AJOL)

    The concentration-dependent stimulation of rat liver alkaline phosphatase (ALP) catalyzed hydrolysis of para- nitrophenylphosphate (pNPP) was studied. ALP displayed some activity even in the absence of exogenous Mg2+. Kinetic analyses show that activation by Mg2+ is exerted at the Vmax level without necessarily ...

  12. Proteasome Inhibitor Up Regulates Liver Antioxidative Enzymes in Rat Model of Alcoholic Liver Disease

    Science.gov (United States)

    Bardag-Gorce, Fawzia; Oliva, Joan; Lin, Andrew; Li, Jun; French, Barbara A.; French, Samuel W.

    2010-01-01

    Oxidative stress occurs in the liver of rats fed alcohol chronically due to ethanol metabolism by CYP2E1, causing liver injury. The proteasome is considered as an antioxidant defense in the cell because of its activity in removing damaged and oxidized proteins, but a growing body of evidence shows that proteasome inhibitor treatment, at a non toxic low dose, provides protection against oxidative stress. In the present study, rats were fed ethanol for 4 weeks and were treated with the proteasome inhibitor PS-341 (Bortezomib, Velcade®). Exposure to proteasome inhibitor elicited the elevation of antioxidative defense by enhancing the levels of mRNA and protein expression transcripts of glutathione reductase (GSR), glutathione synthetase (GSS), glutathione peroxidase 2 (GPX2), and superoxide dismutase 2 (SOD2) in the liver of rats fed ethanol chronically, while ethanol alone did not increase these genes mRNA. Our results also showed that glutamate cysteine ligase catalytic subunit (GCLC), a rate-limiting enzyme in glutathione biosynthesis, was also up regulated in the liver of rats fed ethanol and injected with PS-431. Nrf2 mRNA level was significantly decreased in the liver of ethanol fed rats, as well as in the livers of animal fed ethanol and treated with proteasome inhibitor, indicating that the mechanism by which proteasome inhibitor up regulates the antioxidant response element is not due to regulation of Nrf2. However, ATF4, a major regulator of antioxidant response elements, was significantly up regulated by proteasome inhibitor treatment. The beneficial effects of proteasome inhibitor treatment also reside in the reversibility of the drug because the proteasome activity was significantly increased 72h post treatment. In conclusion, proteasome inhibitor treatment used at a non toxic low dose has potential protective effects against oxidative stress due to chronic ethanol feeding. PMID:21036165

  13. Involvement of a cyclic adenosine monophosphate-dependent signal in the diet-induced canalicular trafficking of adenosine triphosphate-binding cassette transporter g5/g8.

    Science.gov (United States)

    Yamazaki, Yasuhiro; Yasui, Kenta; Hashizume, Takahiro; Suto, Arisa; Mori, Ayaka; Murata, Yuzuki; Yamaguchi, Masahiko; Ikari, Akira; Sugatani, Junko

    2015-10-01

    The adenosine triphosphate-binding cassette (ABC) half-transporters Abcg5 and Abcg8 promote the secretion of neutral sterol into bile. Studies have demonstrated the diet-induced gene expression of these transporters, but the regulation of their trafficking when the nutritional status changes in the liver remains to be elucidated. Here, we generated a novel in vivo kinetic analysis that can monitor the intracellular trafficking of Abcg5/Abcg8 in living mouse liver by in vivo transfection of the genes of fluorescent protein-tagged transporters and investigated how hypernutrition affects the canalicular trafficking of these transporters. The kinetic analysis showed that lithogenic diet consumption accelerated the translocation of newly synthesized fluorescent-tagged transporters to intracellular pools in an endosomal compartment and enhanced the recruitment of these pooled gene products into the bile canalicular membrane in mouse liver. Because some ABC transporters are reported to be recruited from intracellular pools to the bile canaliculi by cyclic adenosine monophosphate (cAMP) signaling, we next evaluated the involvement of this machinery in a diet-induced event. Administration of a protein kinase A inhibitor, N-(2-{[3-(4-bromophenyl)-2-propenyl]amino}ethyl)-5-isoquinolinesulfonamide, decreased the canalicular expression of native Abcg5/Abcg8 in lithogenic diet-fed mice, and injection of a cAMP analog, dibutyryl cAMP, transiently increased their levels in standard diet-fed mice, indicating the involvement of cAMP signaling. Indeed, canalicular trafficking of the fluorescent-tagged Abcg5/Abcg8 was enhanced by dibutyryl cAMP administration. These observations suggest that diet-induced lipid loading into liver accelerates the trafficking of Abcg5/Abcg8 to the bile canalicular membrane through cAMP signaling machinery. © 2015 by the American Association for the Study of Liver Diseases.

  14. 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 diet in rats.

  15. Tratamiento Quirúrgico de las interrupciones canaliculares Surgical treatment of canalicular disruptions

    Directory of Open Access Journals (Sweden)

    Nereyda Martínez Suárez

    1999-06-01

    Full Text Available Realizamos un estudio de 52 pacientes operados en nuestro centro con el diagnóstico de sección canalicular de urgencia o antigua durante un período de 5 años. Agrupamos a los pacientes de acuerdo con posibles agentes etiológicos, las técnicas quirúrgicas utilizadas y el tipo de tutor empleado. Entre los agentes etiológicos encontramos con mayor frecuencia los traumatismos, respecto al sitio de la interrupción canalicular observamos que en el grupo de mayor incidencia (los traumatismos fue en el 1/3 interno del canalículo inferior, mientras que en el resto de los grupos de otras etiologías este factor no fue significativo. Con relación a la técnica quirúrgica empleada, prevaleció la repermeabilización bicanalicular de fijación externa con la sonda Wordt Pigtail "rabo de cochino" en el 92,5 % de las repermeabilizaciones realizadas en los casos de urgencia, utilizándose en el 80 % de ellos los tubos de silicona de grado médico como tutores intracanaliculares. Finalmente se evaluó el restablecimiento anatómico y funcional, correspondiendo la mejor evolución al respecto a los grupos de etiología traumática (de urgencia y a los de causa desconocidaA study of 52 patients operated on in our center with the diagnosis of old urgent canalicular section in a period of 5 years was conducted. Patients were grouped accarding to possible etiological agents, the surgical techniques used and the type of guide utilized. Traumatisms were more frequently found among the etiological agents. As regards the site of canalicular disruption it was observed that in the group of highest incidence (traumatisms it occurred in the internal third of the lower canaliculus, whereas in the rast of the groups with other etiologics this factor was hot significant. As for the surgical technique used, it prevailed the bicanalicular repermeation of external fixation with the Wordt Pigtail Stent in 92,5 % of the repermeating carried out in the urgency cases

  16. Cellular immunolocalization of alpha-fetoprotein in rat liver.

    Science.gov (United States)

    Woods, J A

    1983-10-01

    Increased synthesis of alpha-fetoprotein (AFP) was induced in rat liver by the administration of 3'-methyl-4-dimethyl-aminoazobenzene. The indirect immunoperoxidase technique was used to detect AFP. Cellular localization of AFP was studied using a number of different fixation procedures. Serial sections stained with immunoglobulin served to determine the extent of diffusion of serum proteins into liver cells during fixation. Background staining was minimized when Lillie's neutral buffered formalin plus acetic acid was used as the fixative. After 3'-methyl-4-dimethylaminoazobenzene ingestion, bile duct cell proliferation occurred. The serum AFP was positive in all rats after 17 days on the diet. In rats with AFP-positive sera the immunohistochemical reaction in mature hepatocytes was positive while bile duct cells and small hepatocytes were negative for AFP.

  17. 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...

  18. [Effect of emodin on rejection of liver transplantation in rats].

    Science.gov (United States)

    Jing, He; Lin, Shengzhang; Yang, Xiao

    2009-06-01

    To investigate the mechanism of Emodin on the role of acute rejection in rat liver transplantation. Forty-eight pairs of orthotopic liver transplantation model were established with inbred rats which were randomly divided into 3 groups: Control group (BN --> BN), acute rejection group (Lewis --> BN) and emodin group (Lewis --> BN). Six recipients in each group were randomly collected and contents of TNF-alpha and IL-10 in the peripheral blood were detected with ELISA on Day 1, 3, 5 and 7 separately after transplantation and histopathological evaluation was made to detect the differences among groups after the livers were taken out on day 7. The other 10 in each group were protected to evaluate the animation and life time. The average meso-life time in emodin group (25.6 days) is significantly longer (P < 0.05) than acute rejection group (10.9 days). Compared with the acute rejection group, Emodin group shows up less rejection in the histopathological evaluation (P < 0.01), less TNF-alpha (P < 0.05) and a significant up-regulation of IL-10 in the peripheral blood (P < 0.05 after day 3). Emodin can inhibit the acute rejection of liver transplantation in rats model effectively and it may play the role with reduction of TNF-alpha and upregulation of IL-10.

  19. Sesamolin inhibits lipid peroxidation in rat liver and kidney.

    Science.gov (United States)

    Kang, M H; Naito, M; Tsujihara, N; Osawa, T

    1998-06-01

    Although the sesame lignans, sesaminol and sesamolinol, have been shown to possess antioxidative activity, less is known about the metabolism and antioxidative properties of sesamolin, a major constituent of sesame oil. To determine the ability of sesamolin to act as an antioxidant in vivo, we fed rats a diet containing 1% sesamolin for 2 wk and studied its metabolism and its effects on oxidative stress. About 75% of the ingested sesamolin was excreted unmetabolized in feces, but it was not detected in urine. Sesamolin and its metabolites, sesamol and sesamolinol, were excreted primarily as sulfates and glucuronides. The amount of sesamolin and its metabolites was lower in the plasma than in the liver or kidneys. When we compared rats fed a diet containing 1% sesamolin for 14 d with those fed a control diet, we found that liver weight was significantly greater in the former group. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances, was significantly lower in the kidneys and liver of the sesamolin-fed rats than in the controls. In addition, the amount of 8-hydroxy-2'-deoxyguanosine excreted in the urine was significantly lower in the sesamolin-fed rats. These results suggest that sesamolin and its metabolites may contribute to the antioxidative properties of sesame seeds and oil and support our hypothesis that sesame lignans reduce susceptibility to oxidative stress.

  20. CHARACTERISTICS OF RAT LIVER EXPOSED TO NANOPARTICLES OF LEAD COMPOUNDS.

    Science.gov (United States)

    Omelchuk, S; Aleksijchuk, V; Sokurenko, L; Blagaia, A; Prudchenko, S

    2016-12-01

    In recent times, the lead becomes great importance in environmental pollution, including its nanoparticles. In the literature, there is little data on the changes in the liver after the exposure with lead nanoparticles. The purpose of this study was the identification and determination of macroscopic, microscopic, and biochemical changes of the structural elements of the rat's liver exposed to the action of lead compounds. The study was carried out on 60 male Wistar rats. The first and second groups of animals were intraperitoneally injected with colloidal solution of nanoparticles of Lead Sulfide size of 10 nm and 30 nm, and the third group was intraperitoneally injected with a solution of nitrate lead. Macroscopic, histological, histochemical, biochemical methods and gas chromatography were used to identify the changes of fatty acids metabolism. The experiment has found that body weights of animals in all tested groups were decreased after 6 weeks of lead nanoparticles injection, while relative liver weight was increased. Levels of total lipids and cholesterol, total protein and albumin in the blood serum in study groups have decreased, and the level of triglycerides and glucose have increased. Moderate dystrophic changes were observed in the histological examinations of the liver, and this was confirmed by morphometric and densitometric parameters. Changes of fatty acid composition of lipids of the liver exposed to nanoparticles were the result of increasing arachidonic fatty acid content and reduction of the stearic fatty acid content. Thus, it has been proven by the experiment that the effect of lead nanoparticles depends on their size.

  1. Protective Effect of Silybin in Rats Liver Toxicity

    Directory of Open Access Journals (Sweden)

    Roxana Popescu

    2010-05-01

    Full Text Available Silybin is a flavonoid extracted from the herb Armurariu (Silybum marianum and has the potential efficacy in the treatment of liver disease. The aims of this study were to investigate the effect of alcohol and CCl4 on liver histology and the capacity of silybin to ameliorate the hepatotoxicity. Thirty adult male Wistar rats were used in the study. Liver toxicity was induced by dietary alcohol administration and CCl4 intra-peritoneal injection. The protective effect of silibin was investigated by co-administration of silybin with these toxic agents. Hepatocellular and extracellular matrix integrity was determined by histopathological and immunohistochemical study. Hematoxylin- Eosin and trichrome stains sections were studied in each case. For immunohistochemistry we used monoclonal anticollagen IV primary antibody. Light microscopic evaluation of liver tissues shows that control and silibin treated groups has normal liver structure. In the toxicity groups, HE and trichromic staining showed hepatocellular necrosis, inflammatory infiltrate and proliferating collagen fibers. Immunoexpression of collagen IV was variable. In the control group, we found negative expression. Collagen IV displays positive immunoreaction in hepatotoxicity groups, at the level of the areas rich in inflammatory infiltrate and with degenerative aspect. After this study, we can conclude that silybin, in rats, has protective effects.

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

    Science.gov (United States)

    Alvizouri, M

    1993-01-01

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

  3. [An expression analysis of miR-200a in serum and liver tissue during the process of liver cancer development in rats].

    Science.gov (United States)

    Xia, Ning; Gao, Yuan; Wang, Xing; Liu, Weihui; Yang, Jiandong; Wang, Tao; Zhao, Ge; Li, Haimin

    2014-06-01

    To explore whether microRNA-200a (miR-200a) could be used as a novel biomarker of liver cancer using a rat model system. Diethylnitrosamine abdominal injection was applied to induce liver cancer in the F344 rat strain (n =40); ten unmodeled rats served as controls. In addition, human subjects with normal healthy liver (n =10), liver cirrhosis (n =10), and liver cancer (n =10) were enrolled in the study. Blood samples from both rats and patients and rats' livers were collected for analysis. Real-time quantitative PCR and enzyme-linked immunosorbent assay were used respectively to measure the expressions of serum miR-200a and alpha-fetoprotein (AFP) for all rat and human subjects. In situ hybridization was used to detect the miR-200a expression in the rats' livers. Comparison of normal rats and the liver cancer modeled rats showed that the latter had significantly lower expression of miR-200a (P less than 0.05), with decreasing expression following the progression of liver injury to cancer (liver cirrhosis rats less than early liver cancer rats less than advanced liver cancer rats); in contrast, the AFP levels were significantly higher in the liver cancer modeled rats only at the early and advanced stages of the liver cancer (P less than 0.05). These suggested that miR-200a expression decreases during the developmental process of liver cancer, while AFP expression increases distinctly at the stage of tumor formation. Analysis of the human subjects' clinical samples showed that miR-200a expression was decreased in both liver cirrhosis patients and liver cancer patients (vs. normal liver subjects, P less than 0.05), while AFP showed abnormal expression only in the patients with liver cancer. Comparison of the normal rats and modeled rats using in situ hybridization showed the positive rates for miR-200a expression were 1.00% +/- 0.01% in rats with normal liver, 0.37% +/- 0.03% in rats with fibrotic liver, 0.14% +/- 0.01% in rats with cirrhotic liver, 0.05% +/- 0.00% in

  4. Prevention of taurolithocholate-induced hepatic bile canalicular distortions by HPLC-characterized extracts of artichoke (Cynara scolymus) leaves.

    Science.gov (United States)

    Gebhardt, R

    2002-09-01

    The effects of water-soluble extracts of artichoke (Cynara scolymus L.) leaves on taurolithocholate-induced cholestatic bile canalicular membrane distortions were studied in primary cultured rat hepatocytes using electron microscopy. Artichoke extracts at concentrations between 0.08 and 0.5 mg/ml were able to prevent the formation of bizarre canalicular membrane transformations in a dose-dependent manner when added simultaneously with the bile acid. However, prevention also occurred when the hepatocytes were preincubated with the extracts, indicating that absorption of the bile acid to components of the extracts was not involved. These results demonstrate that artichoke leaf extracts exert a potent anticholestatic action at least in the case of taurolithocholate. This effect may contribute to the overall hepatoprotective influence of this herbal formulation.

  5. 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...

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

    Science.gov (United States)

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

    2011-05-01

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

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

    African Journals Online (AJOL)

    http://dx.doi.org/10.4314/tjpr.v16i12.11. Original Research Article. Attenuation of sepsis-induced rat liver injury by epigallocatechin gallate via suppression of oxidative stress-related inflammation. Jian-xin Yang1, Yu-lin Li1*, Ning-chuan Shi2. 1Department of Emergency, The Second Affiliated Hospital, College of Medicine, ...

  8. Protective effect of Radix Bupleuri extract against liver cirrhosis in rats

    African Journals Online (AJOL)

    Purpose: To explore the effect of Radix Bupleuri extract (RBE) on diethylnitrosamine (DEN)-induced liver cirrhosis in rats. Methods: Rats were injected with DEN once a week for 8 weeks to induce liver cirrhosis. Some DENinduced rats were also treated with RBE, which was obtained by extracting dried Radix Bupleuri in ...

  9. 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,

  10. Quercetin Reverses Rat Liver Preneoplastic Lesions Induced by Chemical Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Gabriela Carrasco-Torres

    2017-01-01

    Full Text Available Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas. Our results showed that quercetin downregulates the expression of EGFR and modulates this signaling pathway in spite of the activated status of EGFR as detected by the upregulation of this receptor, with respect to that observed in control rats. Besides, quercetin affects the phosphorylation status of Src-1, STAT5, and Sp-1. The better status of the liver after the treatment with quercetin could also be confirmed by the recovery in the expression of IGF-1. In conclusion, we suggest that quercetin reversed preneoplastic lesions by EGFR modulation and the activation state of Src, STAT5, and Sp1, so as the basal IGF-1.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    . Rat ED14 FLSPC are alpha-fetoprotein(+)/cytokeratin-19(+) or alpha-fetoprotein(+)/cytokeratin-19(-) and contain all of the normal liver repopulation capacity found in fetal liver. Hematopoietic stem cells, a major component in crude fetal liver cell preparations that engraft in other organs......BACKGROUND & AIMS: Previously, we showed high-level, long-term liver replacement after transplantation of unfractionated embryonic day (ED) 14 fetal liver stem/progenitor cells (FLSPC). However, for clinical applications, it will be essential to transplant highly enriched cells, while maintaining...... and characteristic properties in vitro and their proliferative and differentiation potential in vivo after transplantation into normal adult rat liver. RESULTS: Rat ED14 FLSPC were purified to 95% homogeneity and exhibited cell culture and gene expression characteristics expected for hepatic stem/progenitor cells...

  12. Liver regeneration in trypsin-fed partially hepatectomized rats.

    Science.gov (United States)

    Gershbein, L L

    1993-01-01

    Young adult Sprague-Dawley rats were partially hepatectomized (two-thirds organ removal) and administered a basal diet supplemented with various animal- and plant-derived enzymes (trypsin, alpha-chymotrypsin, pepsin, lipase, alpha-amylase, malt diastase, ficin and bromelain) over a post-operative period of up to 10 days. Porcine or bovine dialyzed and lyophilized crystalline trypsin products containing 2400-3200 NF u/mg in addition to enteric-coated tablets with trypsin to chymotrypsin in a ratio of 6:1, were tested at supplementary levels of up to 4980 u/g ration. With the weight of tissue regenerated or the liver increment as indicator, trypsin in excess of 1000-1200 u/g ration proved inhibitory. This effect did not extend to alpha-chymotrypsin (levels of up to 4000 u/g diet) and the remaining 6 enzyme products specified above, nor to the s.c. injection of trypsin daily at 12,860 u/rat for the 1st 7 days. The last route promoted little change in increment with soy bean trypsin inhibitor (8.0 mg/rat daily for days 1 to 9). When a portion of the group fed a trypsin supplement of 2000 u/g was injected with phenobarbital i.p. at 80 mg/kg daily on each of the last 3 days, the resulting liver increment rose to the control range. As with lysine and arginine, acids of pertinence in tryptic proteolysis, no significant change was elicited by feeding a diet supplemented with peptone from tryptic digestion of casein. The enzyme-containing diets fed to sham-operated rats over a similar interval, did not affect the wet- or dry-liver weight per 100 g body weight. Microsomal parameters as total protein, cytochrome P-450 and the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase of livers from the partially hepatectomized or sham-operated rats fed trypsin and the other enzyme diets, presented no significant changes in the respective levels. The possible action of dietary trypsin in conjunction with inhibitors and growth factors controlling liver regeneration is

  13. Effect of dichloromethylene diphosphonate on liver regeneration following thioacetamide-induced necrosis in rats

    OpenAIRE

    Bautista, Mirandeli; del Rio, María Ángeles Gómez; Benedí, Juana; Sánchez-Reus, María Isabel; Morales-González, José A.; Téllez-López, Ana María; López-Orozco, Maricela

    2013-01-01

    AIM: To study the effect of dichloromethylene diphosphonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA).

  14. [Influence of exogenous putrescine on the function of liver and apoptosis of liver cells in rats].

    Science.gov (United States)

    Zhou, Yueping; Rong, Xinzhou; Fan, Guicheng; Liu, Sirong; Wei, Yaming

    2014-02-01

    To explore the influence of exogenous putrescine on the function of liver and apoptosis of liver cells in rats. Ninety healthy clean SD rats were divided into control group (C, n = 10, intraperitoneally injected with 2 mL normal saline), low dosage putrescine group (LP, n = 40), and high dosage putrescine group (HP, n = 40) according to the random number table. Rats in the latter two groups were intraperitoneally injected with approximately 2 mL putrescine (2.5 or 5.0 g/L) with the dosage of 25 or 50 µg/g. Ten rats from group C at post injection hour (PIH) 24 and 10 rats from each of the latter two groups at PIH 24, 48, 72, 96 were sacrificed. Heart blood was obtained for determination of serum contents of ALT and AST. Liver was harvested for gross observation and histomorphological observation with HE staining. Apoptosis was shown with in situ end labeling, and apoptosis index (AI) was calculated. Data among the three groups and those at different time points within one group were processed with one-way analysis of variance or Welch test; LSD or Dunnett's T3 test was used for paired comparison; factorial design analysis of variance of two factors was applied for data between group LP and group HP. (1) No obvious abnormality was observed at gross observation of liver of rats in each group. Liver tissue of rats in group C was normal. Light edema was observed occasionally in liver of rats in groups LP and HP, but necrotic cells were not seen. (2) Content of ALT at PIH 24, 48, 96 and content of AST at PIH 72 and 96 in group LP were respectively (38 ± 10), (45 ± 6), (34 ± 4), (207 ± 18), (196 ± 19) U/L, and content of ALT at PIH 72 and 96 and content of AST at PIH 24, 72, 96 in group HP were respectively (38 ± 6), (48 ± 5), (213 ± 43), (209 ± 40), (230 ± 29) U/L. They were significantly higher than those of rats in group C [(29 ± 5), (163 ± 42) U/L, with P values all below 0.01]. There were statistically significant differences between group LP and group

  15. Synergistic liver toxicity of copper and retrorsine in the rat.

    Science.gov (United States)

    Morris, P; O'Neill, D; Tanner, S

    1994-11-01

    To investigate the possible synergy between copper and retrorsine (a pyrrolizidine alkaloid) as a cause of Indian Childhood Cirrhosis, four groups of male Wistar rats were fed the following diets from weaning: A. Normal diet; B. Copper loaded (2 g CuSO4/kg diet); C. Retrorsine supplemented (Expt 1:25 mg/kg body weight/week by gavage, Expt 2:25 mg/kg food initially then 15 mg/kg food after 4 weeks); and D. Copper and retrorsine as above. Serial plasma samples were assayed for aminotransferases, albumin and bilirubin. Liver samples at biopsy and sacrifice provided samples for copper analysis and histology. Results showed that copper and retrorsine together significantly increased liver damage compared with feeding either alone as assessed by: 1. Increased mortality rate; 2. Decreased plasma albumin and increased plasma bilirubin (mainly conjugated) indicative of hepatocyte dysfunction; 3. Massive liver copper accumulation, and 4. Increased liver damage histologically. Thus retrorsine caused liver copper accumulation, and together copper and retrorsine led to severe hepatic dysfunction, characterised by hypoalbuminaemia and conjugated hyperbilirubinaemia. Plant alkaloids secreted in milk by grazing animals and copper from brass vessels may together produce Indian Childhood Cirrhosis.

  16. Retinol esterification in cultured rat liver cells.

    Science.gov (United States)

    Drevon, C A; Blomhoff, R; Rasmussen, M; Kindberg, G M; Berg, T; Norum, K R

    1985-01-01

    Retinol esterification was examined in cultured hepatocytes and stellate cells from the rat. Esterification of [3H]retinol was linear for 2 h in both cell types. By increasing the concentration of retinol in the medium, there was a marked increase in retinol esterification in both cell types. The capacity for esterification of retinol was in the same order of magnitude in the two cell types at 3.5 microM-retinol in the medium. This represents a rate of retinol esterification which far exceeds that required to esterify the amount of retinol absorbed in the intestine. It was demonstrated in particulate homogenates from cultured hepatocytes that the esterification of retinol was dependent on acyl-CoA. Addition of 25-hydroxycholesterol or mevalonolactone promoted an increase in cholesterol esterification, whereas retinol esterification was unaffected, suggesting that cholesterol and retinol are esterified by two different enzymes. Some 80% of vitamin A in cultured hepatocytes is retinyl esters, mostly retinyl palmitate. By adding 87 microM-retinol in the medium the cells accumulated 100-fold free retinol and 2.5-3.0-fold retinyl esters within 1 h. When retinol-loaded cells were incubated without retinol, there was a marked decrease especially in free but also in esterified retinol. In the presence of 1 mM-oleic acid in the medium the amount of retinyl oleate was twice that in control cells. PMID:4062867

  17. [Proliferation and cell death of hepatocytes in regenerating rat fetal liver].

    Science.gov (United States)

    El'chaninov, A V; Bol'shakova, G B

    2012-01-01

    Proliferation and death of hepatocytes in regenerating liver of 17-day white rat fetuses were investigated. During 2 days after liver resection (20%), animals were sacrificed every 3 h. In experimental groups, the index of Ki67-positive hepatocytes increased sharply in 15 h after liver resection. In all experimental and control groups, the ratio of the metaphase, the longest phase of mitosis, and index to mitotic index remained unchanged, indicating identical duration of hepatocytes mitoses in regenerating liver. In the regenerating and intact liver hepatocytes labeled with antibodies to caspase 3 were not detected. Thus, resection of 20% rat fetal liver did not contribute to increased apoptosis of hepatocytes.

  18. The effect of extrahepatic cholestasis on liver regeneration after partial hepatectomy in the rat

    NARCIS (Netherlands)

    Aronson, D. C.; Chamuleau, R. A.; Frederiks, W. M.; Bosman, D. K.; Oosting, J.

    1995-01-01

    Liver regeneration after partial hepatectomy was studied in four groups of rats: control rats (n = 12), rats with 1 week of common bile duct obstruction (n = 11), rats with restoration of bile flow after 1 week of obstruction (n = 9) and a sham-operated group (n = 7). Parameters of DNA

  19. Determination of free choline and phosphorylcholine in rat liver.

    Science.gov (United States)

    Barak, A J; Tuma, D J

    1979-03-01

    A simple procedure for determination of levels of free choline and phosphorylcholine in hepatic tissue is outlined. The method makes use of the enzyme acid phosphatase to liberate choline from phosphorylcholine and incorporates the ability of choline to react with potassium triiodide to yield choline periodide for the measurement of choline and phosphorylcholine in liver. The method is accurate for both entities (recovery of 97-100% for choline and 92-98% for phosphorylcholine). For phosphorylcholine, the method is markedly simpler than other methods previously described and the results for normally fed rats are of the same order of magnitude. The applicability of the method was shown when it was demonstrated that diets containing different amounts of choline influenced the level of choline and phosphorylcholine in liver.

  20. NF-κB induced the donor liver cold preservation related acute lung injury in rat liver transplantation model.

    Directory of Open Access Journals (Sweden)

    An Jiang

    Full Text Available We have observed at our clinical work that acute lung injury (ALI often occurs in patients transplanted with donor livers persevered for long time. So, we conducted this study to investigate the influence of cold preservation time (CPT of donor liver on ALI induced by liver transplantation (LT, and further study the role of nuclear factor-κB (NF-κB in the process.Wistar rats were used as donors and recipients to establish orthotopic rat liver transplantation models. Donor livers were preserved at 4°C for different lengths of time. The effect of NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC, on ALI was detected. All samples were harvested after 3 h reperfusion. The severity of liver injury was evaluated first. The expressions of tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β in liver tissue and liver outflow serum were measured respectively. The severity indexes of ALI, the activity of NF-κB and inhibitor-κBα (I-κBα in lung/liver were measured accordingly.With the prolonged liver CPT, the liver damage associated indexes and ALI-related indexes all increased significantly. TNF-α and IL-1β in liver outflow serum increased accordingly, and the activity of NF-κB in liver/lung increased correspondingly. All these ALI-associated indexes could be partially reversed by the use of PDTC.Extended CPT aggravates the damage of donor liver and induces the expressions of TNF-α and IL-1β in liver. These inflammatory factors migrate to lung via liver outflow blood and activate NF-κB in lung, inducing ALI finally. NF-κB may play a critical role in LT-related ALI. Patients with or at risk of ALI may benefit from acute anti-inflammatory treatment with PDTC.

  1. Hepatic intralobular mapping of fructose metabolism in the rat liver.

    OpenAIRE

    S. P. Burns; Murphy, H C; Iles, R A; Bailey, R A; Cohen, R D

    2000-01-01

    Detailed mapping of glucose and lactate metabolism along the radius of the hepatic lobule was performed in situ in rat livers perfused with 1.5 mM lactate before and during the addition of 5 mM fructose. The majority of fructose uptake occurred in the periportal region; 45% of fructose taken up in the periportal half of the lobular volume being converted into glucose. Periportal lactate uptake was markedly decreased by addition of fructose. Basal perivenous lactate output, which was derived f...

  2. Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.

    Science.gov (United States)

    Wang, Renxue; Liu, Lin; Sheps, Jonathan A; Forrest, Dana; Hofmann, Alan F; Hagey, Lee R; Ling, Victor

    2013-08-15

    The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice.

  3. Dynamic mechanical analysis to assess viscoelasticity of liver tissue in a rat model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Zhang, Xinyu; Gao, Xuehua; Zhang, Pengpeng; Guo, Yanrong; Lin, Haoming; Diao, Xianfen; Liu, Yingxia; Dong, Changfeng; Hu, Yaxin; Chen, Siping; Chen, Xin

    2017-06-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in both developed and developing countries. A noninvasive method of detecting early stage NAFLD and distinguishing non-alcoholic steatohepatitis (NASH) from simple steatosis (SS) would be useful. The over-accumulation of fat in hepatocytes alters the physical microstructure and chemical contents of the liver tissue. This study included dynamic mechanical analysis (DMA) testing on liver samples from a rat model of NAFLD to determine whether the tissue shows any significant changes in viscoelasticity due to the histological changes. Liver steatosis was induced in 57 rats by gavage feeding of a high fat emulsion; 12 rats received a standard diet only and served as controls. Each rat provided 2 or 3 samples for DMA tests. The shear modulus and loss modulus were measured at 9 frequency points evenly-spaced in the range from 1Hz to 41Hz. The phase velocity of shear wave was calculated from the measured modulus. Multivariate T2 test was used to assess the significance of intra-group difference. The results showed significant changes (p livers with moderate to severe (S2 to S4) steatosis in comparison with livers without steatosis (S0), while the loss modulus demonstrated significant changes earlier in stage S1, indicating that fat accumulation affects the mechanical properties of liver, particularly viscosity. However, no significant differences were observed between the steatosis grades. These results also suggest that mild inflammation may affect the mechanical properties, which requires further verification. These findings provide new information about the mechanical properties of livers with NAFLD in low frequency range and suggest that it is possible to distinguish normal livers from livers with NAFLD. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Lim, Tong-Hye; Nor-Amdan, Nur-Asyura

    2017-01-01

    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. PMID:28280515

  5. 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.

  6. 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 ...

  7. Histopathology and cell culture characteristics of liver cells from grc- and grc+ rats given diethylnitrosamine.

    Science.gov (United States)

    Smith, G J; Kunz, H W; Dunsford, H A; Gill, T J

    1990-04-01

    The histopathological response and cell culture characteristics of liver cells from the R16 (grc-) strain of rats, which carries an MHC-linked deletion, were examined one week after a single intraperitoneal injection of 200 mg/kg body weight diethylnitrosamine (DEN) and were compared with the response of liver cells from wild type (grc+) rats. The DEN exposure induced hydropic/vacuolar changes in the parenchymal cells and a limited proliferation of oval cells in the periportal areas of the livers of both grc+ and grc- rats. Primary culture of collagenase-digested livers consisted of parenchymal, bile ductular and oval-related cells as determined by cell-specific immunohistochemistry. Subpassaged cells from grc+ rats exhibited oval cell ultrastructural morphology, inducible histochemical staining for gamma-glutamyl transpeptidase (GGT), and DEN-associated onset of anchorage-independent growth. Primary cultures of liver cells from R16 rats consistently failed to form cell strains upon subpassage.

  8. Oral contraceptives worsen endotoxin-induced liver injury in rats.

    Science.gov (United States)

    Konno, Akira; Enomoto, Nobuyuki; Takei, Yoshiyuki; Hirose, Miyoko; Ikejima, Kenichi; Sato, Nobuhiro

    2002-08-01

    Oral contraceptives are widely used; however, these drugs occasionally cause liver injury. Recently, it was reported that estriol worsens alcoholic liver injury by the mechanism involving activation of Kupffer cells as a result of gut-derived endotoxin. However, the relationship between oral contraceptives and endotoxin-induced liver injury has not been elucidated. Here we show that oral contraceptives sensitize Kupffer cells via a mechanism dependent on increased gut permeability to endotoxin. Female Wistar rats (200-250 g) were given intraperitoneally a combination of estradiol (35 ng/kg of 17 alpha-Ethynylestradiol) and progesterone (2 microg/kg of Norethindrone), each dose being similar to that contained in oral contraceptives (EP treatment). After 24 hr, a sublethal dose of lipopolysaccharide (LPS; 5 mg/kg) was injected via the tail vein. In some experiments, antibiotics (150 mg/kg/day of polymyxin B and 450 mg/kg/day of neomycin) were administered orally for 4 days before EP treatment. Gut permeability was measured in isolated segments of ileum by translocation of horseradish peroxidase. Kupffer cells were isolated and cultured in RPMI 1640 + 10% fetal bovine serum for 24 hr. After addition of LPS (100 ng/ml) to the culture medium, intracellular calcium concentration ([Ca2+](i) ) was measured with fura-2. Liver histology in rats given EP treatment intraperitoneally followed by an injection of LPS (5 mg/kg) 24 hr later revealed pronounced liver damage with massive necrosis. Whereas mean values of alanine aminotransferase (ALT) in the control, nontreated rats were 30 +/- 6 IU/liter, ALT increased to 75 +/- 21 IU/liter 24 hr after LPS injection. This increase was aggravated 6-fold (483 +/- 118 IU/liter; p< 0.05) by EP treatment. The EP treatment-induced increase in ALT was completely blocked by antibiotics (82 +/- 26 IU/liter; p< 0.05). Gut permeability was increased approximately 10-fold with EP treatment. This increase in gut permeability was not altered by

  9. Isolation, propagation, and characterization of rat liver serosal mesothelial cells.

    Science.gov (United States)

    Faris, R A; McBride, A; Yang, L; Affigne, S; Walker, C; Cha, C J

    1994-12-01

    Although rat liver epithelial cell (RLEC) lines have been developed by a number of laboratories, the identity of the clonogenic nonparenchymal progenitors is unknown. To provide insight into the derivation of RLEC, we immunoisolated serosal liver mesothelial cells (LMC) and bile duct epithelial cells and attempted to propagate each epithelial cell population using culture conditions routinely employed to establish RLEC lines. Briefly, the selective reactivity of LMC with two bile duct cell surface markers, OC.2 and BD.2, was exploited to develop an immunocytochemical technique to isolate LMC. Livers were collagenase dissociated, the mesothelial capsule was "peeled" and digested with pronase to destroy contaminating hepatocytes, and rare biliary ductal epithelial cells were immunodepleted using OC.2. LMC were subsequently isolated by selective binding to magnetic beads adsorbed with BD.2 and cultured in supplemented Waymouths 752/1 media containing 10% fetal calf serum. Proliferating BD.2+ LMC rapidly formed epithelial-like monolayers that could be continuously subcultured after trypsinization. In contrast, attempts to establish cell lines from purified OC.2+ bile duct epithelial cells were unsuccessful. Results from reverse transcriptase polymerase chain reaction analysis confirmed that LMC expressed Wilms' tumor transcripts, a lineage marker for mesodermally-derived cells. In summary, our findings clearly demonstrate that LMC can be continuously propagated using culture conditions routinely employed to establish RLEC lines, an observation that supports the contention that some RLEC lines may be derived from LMC.

  10. 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.

  11. Effect of Salvia miltiorrhiza Bge extract on liver cirrhosis in rats

    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 ... Liver cirrhosis is a common pathological consequence of chronic liver disease, ... antioxidation, anti-aging, antihypoxic, antifatigue, anti-inflammatory, anti-hepatic fibrosis, ...

  12. Reduction of dimethylarsinic acid to the highly toxic dimethylarsinous acid by rats and rat liver cytosol.

    Science.gov (United States)

    Németi, Balázs; Gregus, Zoltán

    2013-03-18

    Dimethylarsinic acid (DMAs(V)), the major urinary metabolite of inorganic arsenic, is weakly cytotoxic, whereas its reduced form, dimethylarsinous acid (DMAs(III)), is highly toxic. Although glutathione S-transferase omega 1 (GSTO1) and arsenic methyltransferase have been shown or thought to catalyze DMAs(V) reduction, their role in DMAs(V) reduction in vivo, or in cell extracts is uncertain. Therefore, the reduction of DMAs(V) to DMAs(III) in rats and in rat liver cytosol was studied to better understand its mechanism. To assess DMAs(V) reduction in rats, a novel procedure was devised based on following the accumulation of red blood cell (RBC)-bound dimethylarsenic (DMAs), which represents DMAs(III), in the blood of DMAs(V)-injected anesthetized rats. These studies indicated that rats reduced DMAs(V) to DMAs(III) to a significant extent, as in 90 min 31% of the injected 50 μmol/kg DMAs(V) dose was converted to DMAs(III) that was sequestered by the circulating erythrocytes. Pretreatment of rats with glutathione (GSH) depletors (phorone or BSO) delayed the elimination of DMAs(V) and the accumulation of RBC-bound DMAs, whereas the indirect methyltransferase inhibitor periodate-oxidized adenosine was without effect. Assessment of DMAs(V)-reducing activity of rat liver cytosol revealed that reduction of DMAs(V) required cytosolic protein and GSH and was inhibited by thiol reagents, GSSG and dehydroascorbate. Although thioredoxin reductase (TRR) inhibitors (aurothioglucose and Sb(III)) inhibited cytosolic DMAs(V) reduction, recombinant rat TRR plus NADPH, alone or when added to the cytosol, failed to support DMAs(V) reduction. On ultrafiltration of the cytosol through a 3 kDa filter, the reducing activity in the retentate was lost but was largely restored by NADPH. Such experiments also suggested that the reducing enzyme was larger than 100 kDa and was not GSTO1. In summary, reduction of DMAs(V) to the highly toxic DMAs(III) in rats and rat liver cytosol is a GSH

  13. Laparoscopic liver surgery in the rat: description of a new technique.

    Science.gov (United States)

    Kuntz, C; Reinshagen, S; Bay, F; Schmehding, M; Schwalbach, P

    2000-11-01

    We devised a safe and simple method of liver resection with a wire loop in a small animal model. Herein the method is evaluated and combined with a tumor model for further immunological, oncological, and laparoscopic research. With the aid of a wire loop and an adapted electric generator, a liver lobe resection can be performed through three trocars (first trocar: camera; second and third trocars: instruments). This operative procedure was evaluated in 10 rats (group 1). In a second group of ACI rats, a Morris hepatoma (1 mm(3)) was induced. After 11 days, a liver lobe resection was performed. One week after the resection an autopsy and a histological examination were performed in all animals. Ten ACI rats underwent laparoscopic liver resection to evaluate the operative technique with the wire loop (group 1). All rats returned to normal feeding and activity on the 1st postoperative day. There were no deaths. At autopsy, the resection area was inconspicuous, without any sign of hematoma or bilioma. In the second group, 10 days after tumor induction, the induced hepatoma was increased (1 cm(3)) and localized in the left liver lobe. In all rats, the liver lobe was resected without touching or laceration of the tumor. At autopsy, the resection area was inconspicuous. No tumors were found in the histological workup of liver and lungs. This model of laparoscopic liver resection in the rat allows a safe and simple liver lobectomy, including a total tumor resection. It should also facilitate basic oncological, immunological, and laparoscopic research.

  14. Open canalicular system of platelets in porcine stress syndrome.

    Science.gov (United States)

    Basrur, P K; Bouvet, A; McDonell, W N

    1988-07-01

    A study was undertaken to test whether a previously reported alteration in platelet morphology could be of predictive value for the detection of stress-susceptibility in pigs. Platelets from 20 normal pigs, nine pigs classified as stress-susceptible on the basis of their response to halothane challenge, and 11 siblings of halothane reactors belonging to two different breeds were subjected to electron microscopic examination. A quantitative analysis of electron micrographs, based on the extent of dilatation of the open canalicular system in platelets and the percentage of affected platelets, revealed that halothane reactor pigs could be distinguished from normal animals on the basis of their open canalicular system score. The discrete nature of the score categories in siblings indicates that platelet alteration may be an inherent component of the porcine stress syndrome and suggests that some of the false negatives in the halothane test may be identified as stress-susceptible on this criterion. Further studies involving a larger number of halothane reactors and siblings are needed to ascertain the consistency of the open canalicular system features and eventually, to develop a simple test system based on platelet alterations for the detection of stress-susceptibility in pigs.

  15. ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained.

    Science.gov (United States)

    Cai, Shi-Ying; Gautam, Samir; Nguyen, Trong; Soroka, Carol J; Rahner, Christoph; Boyer, James L

    2009-03-01

    Progressive familial intrahepatic cholestasis 1 (PFIC1) results from mutations in ATP8B1, a putative aminophospholipid flippase. Conflicting hypotheses have been proposed for the pathogenesis of PFIC1. The aim of this study was to determine whether ATP8B1 deficiency produces cholestasis by altering the activity of the farnesoid X receptor (FXR) or by impairing the structure of the canalicular membrane. ATP8B1/Atp8b1 was knocked down in human and rat hepatocytes and Caco2 cells using adenoviral and oligonucleotide small interfering RNAs. ATP8B1 messenger RNA and protein expression was greatly reduced in human and rat cells. In contrast, FXR expression and several FXR-dependent membrane transporters (bile salt export pump [BSEP], multidrug resistance-associated protein [MRP] 2) were unchanged at messenger RNA or protein levels in ATP8B1-deficient cells, whereas Mrp3 and Mrp4 were up-regulated in rat hepatocytes. FXR activity remained intact in these cells, as evidenced by 6alpha-ethyl chenodeoxycholic acid-mediated induction of small heterodimer partner, BSEP, and multidrug-resistant protein (MDR) 3/Mdr2. Fluorescent substrate excretion assays indicate that Bsep function was significantly reduced in Atp8b1-deficient rat hepatocytes, although Bsep remained localized to the canalicular membrane. Exposure to the hydrophobic bile acid CDCA resulted in focal areas of canalicular membrane disruption by electron microscopy and luminal accumulation of NBD-phosphatidylserine, consistent with the function of Atp8b1 as an aminophospholipid flippase. ATP8B1 deficiency predisposes to cholestasis by favoring bile acid-induced injury in the canalicular membrane but does not directly affect FXR expression, which may occur in PFIC1 as a secondary phenomenon associated with cholestasis.

  16. 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.

  17. Detection of CAIII mRNA in rat skeletal muscle and liver by in situ hybridization

    NARCIS (Netherlands)

    Kelly, C. D.; Carter, N. D.; de Boer, P.; Jeffery, S.; Moorman, A. F.; Smith, A.

    1991-01-01

    We carried out a variety of in situ methods of hybridization on rat liver and rat skeletal muscle using 35S-labeled or biotin-labeled rat carbonic anhydrase III (CAIII) cDNA clone. The methods were compared and evaluated. Use of the biotin system produced defined but nonspecific results which were

  18. 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 ...

  19. Effect of zidovudine on the liver function of adult albino wistar rats ...

    African Journals Online (AJOL)

    Zidovudine is a type of antiretroviral drug used for the treatment of human immunodeficiency virus (HIV) infection. This study investigated its effect on liver enzymes in adult male albino rats. Fifteen male albino rats weighing between 180-250g were used for the study. The rats were subdivided into a control (A) and two test ...

  20. 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 ...

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

    NARCIS (Netherlands)

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

    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 (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-03-11

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

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

    Science.gov (United States)

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

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group). Copyright © 2013 John Wiley & Sons, Ltd.

  4. 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.

  5. Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol.

    Science.gov (United States)

    McMorris, T C; Elayadi, A N; Yu, J; Hu, Y; Kelner, M J

    1999-09-01

    Acylfulvenes are a potent class of antitumor agents derived from illudin S, a fungal sesquiterpene. Illudin S possesses antitumor activity but has a poor therapeutic index. Acylfulvene is 100-fold less toxic against human lung adenocarcinoma cells than illudin S, but inhibits tumor growth in human xenografts, opposite to illudin S. An analog of acylfulvene, MGI 114 (hydroxymethylacylfulvene), shows much greater efficacy, producing complete tumor regression in xenograft models. MGI 114 is currently in phase II clinical trials. Cytotoxicity of MGI 114, like that of illudin S, is believed to involve both chemical reaction and enzymatic reduction. Enzymatic reduction by a cytosolic NADPH-dependent enzyme (from rat liver) produced an aromatic metabolite similar to that formed from illudin S. However, the reaction occurred more slowly. In addition, four new metabolites were isolated, two hydroxylated derivatives and two in which the primary allylic hydroxyl was replaced by hydride. All retained the reactive centers of the parent MGI 114.

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

    Directory of Open Access Journals (Sweden)

    Zheng Han

    2013-12-01

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

  7. Salidroside alleviates oxidative stress in the liver with non- alcoholic steatohepatitis in rats.

    Science.gov (United States)

    Yang, Ze-ran; Wang, Hui-fang; Zuo, Tie-cheng; Guan, Li-li; Dai, Ning

    2016-04-14

    Nonalcoholic steatohepatitis (NASH) is characterized by fat accumulation in the hepatocyte, inflammation, liver cell injury, and varying degrees of fibrosis, and can lead to oxidative stress in liver. Here, we investigated whether Salidroside, a natural phenolic antioxidant product, can protect rat from liver injury during NASH. NASH model was established by feeding the male SD rats with high-fat and high-cholesterol diet for 14 weeks. Four groups of male SD rats including, normal diet control group, NASH model group, and Salidroside treatment group with150mg/kg and 300 mg/kg respectively, were studied. Salidroside was given by oral administration to NASH in rats from 9 weeks to 14 weeks. At the end of 14 weeks, liver and serum were harvested, and the liver injury, oxidative stress and histological features were evaluated. NASH rats exhibited significant increases in the following parameters as compared to normal diet control rats: fat droplets with foci of inflammatory cell infiltration in the liver. ALT, AST in serum and TG, TC in hepatocyte elevated. Oxidative responsive genes including CYP2E1 and Nox2 increased. Additionally, NASH model decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to NASH model group, treatment rats with Salidroside effectively reduced lipid accumulation, inhibited liver injury in a does-dependent manner. Salidroside treatment restored antioxidant enzyme levels, inhibited expression of CYP2E1 and Nox2 mRNA in liver, which prevented the initial step of generating free radicals from NASH. The data presented here show that oral administration of Salidroside prevented liver injury in the NASH model, likely through exerting antioxidant actions to suppress oxidative stress and the free radical-generating CYP2E1 enzyme, Nox2 in liver.

  8. 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.

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

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    Qinlong Liu

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

  10. The effect of Korean red ginseng on liver regeneration after 70% hepatectomy in rats.

    Science.gov (United States)

    Kwon, Young-Sam; Jang, Kwang-Ho

    2004-02-01

    The effect of Korean red ginseng (KRG) on morphologic change and function of the liver was investigated after 70% hepatectomy in rats. The liver weight and hepatocyte proliferation of the KRG treated groups significantly increased compared to those of the control group. KRG inhibited the increase of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and the number and area of lipid droplets. On the basis of these results, it could be concluded that KRG accelerated the liver regeneration and ameliorated liver injury after hepatectomy in rats.

  11. Liver regeneration studies with rat hepatocytes in primary culture.

    Science.gov (United States)

    Michalopoulos, G; Cianciulli, H D; Novotny, A R; Kligerman, A D; Strom, S C; Jirtle, R L

    1982-11-01

    Adult rat parenchymal hepatocytes in primary culture can be induced to enter into DNA synthesis and mitosis. The optimal conditions for hepatocyte replication are low plating density (less than 10,000 cells/sq cm) and 50% serum from two-thirds partially hepatectomized rats (48 hr after hepatectomy). Approximately 80% of the hepatocytes enter the cell cycle, and most of these cells go through mitosis. The replicating hepatocytes remain positive for glucose-6-phosphatase and negative for gamma-glutamyl transpeptidase, and they accumulate fat, in analogy to regenerating liver. Most of the replicating hepatocytes enter into multiple consecutive rounds of DNA synthesis. Dose-response studies between control animal serum and hepatocyte labeling index indicate that in unoperated animals the serum contains substances stimulatory as well as inhibitory for hepatic growth, with the inhibitory effect prevailing at high concentrations. After partial hepatectomy, the inhibitory activity disappears whereas the hepatopoietin activity reaches almost 90% of maximal biological effectiveness at 25% serum concentration. Addition of hormones to the system shows that the hepatopoietin activity is not identical to epidermal growth factor, platelet-derived growth factor, thyroxine, glucagon, or hydrocortisone. Norepinephrine abolishes the difference between control and hepatectomized serum but does not restore hepatopoietin activity when added to heat-inactivated serum. The results show that this system of replicating hepatocytes can be used to investigate the trophic factors that control growth of normal and neoplastic hepatocytes.

  12. Alteration of rat liver microsomal monooxygenase activities by gasoline treatment

    Energy Technology Data Exchange (ETDEWEB)

    Brady, J.F.; Xiao Fang; Gapac, J.M.; Ning, S.M.; Yang, C.S. (Rutgers - the State Univ., Piscataway, NJ (USA). Dept. of Chemical Biology and Pharmacognosy)

    1990-11-01

    Previous work has shown an increase in rat liver enzyme activities after chronic exposure to gasoline vapor. In the present study, male Sprague-Dawley rats were pretreated with unleaded gasoline at 1 and 5 ml/kg, i.p., and selected hepatic microsomal monooxygenase activities were determined at 18, 48, and 72 h. At 18 h, moderate increases were observed in P450 content (1.3-fold), cytochrome c-reductase activity (1.25-fold), and in N-nitrosodimethylamine demethylation rate (1.25- to 1.6-fold). Pentoxyresorufin dealkylase activity (an activity displayed primarily by P450IIB1) was significantly elevated at 18 and 48 h (30- to 60-fold), and ethoxyresorufin dealkylase activity (an activity displayed by P450 IA1) was elevated (2- to 4-fold). Immunoblot analysis revealed no change in P450IIE1 at these time points, but an elevation in P450IIB1 in agreement with the pentoxyresorufin dealkylase activity measurements. (orig.).

  13. The liver protective effect of methylprednisolone on a new experimental acute-on-chronic liver failure model in rats.

    Science.gov (United States)

    Hu, Chao; Shen, Shiqiang; Zhang, Aimin; Ren, Bo; Lin, Fusheng

    2014-10-01

    Acute-on-chronic liver failure is a severe, life-threatening entity and the comprehension of this disease is incomplete. Currently, a reasonable surgical model of acute-on-chronic liver failure is still lacking. The aim of this study was to establish a new model of acute-on-chronic liver failure in rats and to investigate the protective effects of methylprednisolone on this model. An obstructive jaundice model in rats was established. Two weeks later, the animals were subjected to a choledochoduodenostomy and a reduced-size hepatic ischaemia/reperfusion injury. Animals were randomly divided into a control group, a methylprednisolone injected via the tail vein group and a methylprednisolone injected via the portal vein group. The survival rates and serum levels of alanine transaminase, aspartate aminotransferase, total bilirubin, tumour necrosis factor alpha, and interferon gamma of the rats were measured and the pathological changes in liver tissues were observed. The survival rate was significantly improved in the methylprednisolone treatment groups. Serum levels of the biochemical indexes were the lowest in the portal vein injection group. Liver tissues under microscopy presented severe pathological injury in the control group. This model could be useful for further research into acute-on-chronic liver failure and methylprednisolone may be a potential therapeutic agent for this disease. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  14. Prolonged exposure of cholestatic rats to complete dark inhibits biliary hyperplasia and liver fibrosis.

    Science.gov (United States)

    Han, Yuyan; Onori, Paolo; Meng, Fanyin; DeMorrow, Sharon; Venter, Julie; Francis, Heather; Franchitto, Antonio; Ray, Debolina; Kennedy, Lindsey; Greene, John; Renzi, Anastasia; Mancinelli, Romina; Gaudio, Eugenio; Glaser, Shannon; Alpini, Gianfranco

    2014-11-01

    Biliary hyperplasia and liver fibrosis are common features in cholestatic liver disease. Melatonin is synthesized by the pineal gland as well as the liver. Melatonin inhibits biliary hyperplasia of bile duct-ligated (BDL) rats. Since melatonin synthesis (by the enzyme serotonin N-acetyltransferase, AANAT) from the pineal gland increases after dark exposure, we hypothesized that biliary hyperplasia and liver fibrosis are diminished by continuous darkness via increased melatonin synthesis from the pineal gland. Normal or BDL rats (immediately after surgery) were housed with light-dark cycles or complete dark for 1 wk before evaluation of 1) the expression of AANAT in the pineal gland and melatonin levels in pineal gland tissue supernatants and serum; 2) biliary proliferation and intrahepatic bile duct mass, liver histology, and serum chemistry; 3) secretin-stimulated ductal secretion (functional index of biliary growth); 4) collagen deposition, liver fibrosis markers in liver sections, total liver, and cholangiocytes; and 5) expression of clock genes in cholangiocytes. In BDL rats exposed to dark there was 1) enhanced AANAT expression/melatonin secretion in pineal gland and melatonin serum levels; 2) improved liver morphology, serum chemistry and decreased biliary proliferation and secretin-stimulated choleresis; and 4) decreased fibrosis and expression of fibrosis markers in liver sections, total liver and cholangiocytes and reduced biliary expression of the clock genes PER1, BMAL1, CLOCK, and Cry1. Thus prolonged dark exposure may be a beneficial noninvasive therapeutic approach for the management of biliary disorders.

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

    Science.gov (United States)

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

    2006-01-01

    AIM: To investigate the role of metallothionein and proliferating cell nuclear antigen (PCNA) on the morphological and biochemical effects of zinc sulfate in ethanol-induced liver injury. METHODS: Wistar albino rats were divided into four groups. Group I; intact rats, group II; control rats given only zinc, group III; animals given absolute ethanol, group IV; rats given zinc and absolute ethanol. Ethanol-induced injury was produced by the 1 mL of absolute ethanol, administrated by gavage technique to each rat. Animals received 100 mg/kg per day zinc sulfate for 3 d 2 h prior to the administration of absolute ethanol. RESULTS: Increases in metallothionein immunoreactivity in control rats given only zinc and rats given zinc and ethanol were observed. PCNA immunohistochemistry showed that the number of PCNA-positive hepatocytes was increased significantly in the livers of rats administered ethanol + zinc sulfate. Acute ethanol exposure caused degenerative morphological changes in the liver. Blood glutathione levels decreased, serum alkaline phosphatase and aspartate transaminase activities increased in the ethanol group when compared to the control group. Liver glutathione levels were reduced, but lipid peroxidation increased in the livers of the group administered ethanol as compared to the other groups. Administration of zinc sulfate in the ethanol group caused a significant decrease in degenerative changes, lipid peroxidation, and alkaline phosphatase and aspartate transaminase activities, but an increase in liver glutathione. CONCLUSION: Zinc sulfate has a protective effect on ethanol-induced liver injury. In addition, cell proliferation may be related to the increase in metallothionein immunoreactivity in the livers of rats administered ethanol + zinc sulfate. PMID:16865776

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

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    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.

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

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    Amanda Natália Lucchesi

    2015-01-01

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

  18. Effect of unfiltered coffee on carbon tetrachloride-induced liver injury in rats.

    Science.gov (United States)

    Poyrazoglu, Orhan Kursat; Bahcecioglu, Ibrahim Halil; Ataseven, Huseyin; Metin, Kerem; Dagli, Adile Ferda; Yalniz, Mehmet; Ustundag, Bilal

    2008-12-01

    To assess the role of unfiltered coffee upon carbon tetrachloride (CCl(4)) induced hepatotoxicity in rats. All rats were randomly divided into control group, CCl(4)-treated, unfiltered coffee-treated and CCl(4)/unfiltered coffee-treated. Hepatic damage was induced by repeated intraperitoneal injections of CCl(4) every other day. Unfiltered coffee was given as drinking fluid for 8 days starting the day before CCl(4) administration. Liver enzymes, plasma and liver tissue malondialdehyde were analyzed. Histopathological evaluation of liver sections was performed. Serum aminotransferase level significantly increased in CCl(4)/unfiltered coffee-treated group compared to CCl(4)-treated group, as well as, lipid peroxidation products in the plasma and liver tissue. In addition, histopathological findings including inflammation and necrosis were significantly confirmed these findings. Unfiltered coffee potentiates acute liver injury in rats with CCl(4)-induced hepatotoxicity.

  19. Reduced phallotoxin uptake by livers of young compared with adult rats.

    Science.gov (United States)

    Walli, A K; Wieland, E; Faulstich, H; Wieland, T

    1979-07-01

    Using [3H]-demethylphalloin as a tracer the uptake of phallotoxins by the liver of young (6, 12, 16 days old) and adult rats was determined in relation to the dose of toxin administered. The maximum amount taken up by the livers of the young rats was only about 50% of that in adults. Nevertheless, with a dose as high as 55 mg/kg body weight the toxin concentration in the young liver reached more than 30 micrograms/g, being markedly higher than the minimum concentration (approximately 20 micrograms/g) required to cause irreversible damage of the liver in adult rats and death of the animals. This suggests that the tolerance of young rats to phallotoxins cannot solely be explained by the reduced uptake of the toxin.

  20. 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.

  1. Rat liver arginase system under acetaminophen-induced toxic injury and protein deprivation

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    H. P. Kopylchuk

    2017-04-01

    Full Text Available Arginase activity and L-arginine content in both cytosolic and mitochondrial fractions of rat liver cells under the conditions of toxic injury on the background of protein deprivation was studied. The most significant reduction of arginase activity in liver cells and depletion of L-arginine pool was found in rats with toxic acetaminophen-induced liver injury maintained on the ration balanced by all nutrients as well as in protein deficiency rats. It was concluded that reduction of the arginase activity in the cytosolic fraction of rat liver cells, combined with simultaneous decrease of L-arginine content, may be considered as one of the mechanisms of ornithine cycle disturbance. The decline of activity of mitochondrial isoform of arginase II, for certain, is related with activation of NO-synthase system.

  2. Lack of therapeutic improvement of liver fibrosis in rats by dexamethasone in spite of ascites amelioration.

    Science.gov (United States)

    Ki, Sung Hwan; Choi, Dal Woong; Kim, Choon Won; Kim, Sang Geon

    2005-02-28

    Pathophysiology of liver fibrosis (LF) includes hepatic parenchymal cell destruction and connective tissue formation. Although dexamethasone has been used in the liver diseases, there is controversy over the beneficial effects of dexamethasone on LF. Previous studies showed that CCAAT/enhancer binding protein-beta (C/EBPbeta) activation contributes to hepatocyte regeneration and dissolution of fibrosis and that dexamethasone activates C/EBPbeta whereas C/EBPbeta-mediated gene induction by dexamethasone is antagonized by a corepressor. The present study investigated the possible therapeutic effect of dexamethasone for the treatment of LF in rats. We injected rats with multiple doses of dimethylnitrosamine (DMN) for 4 weeks and then used the LF rats to determine whether dexamethasone treatment therapeutically improved liver functions and resolved fibers accumulated in the liver. Dexamethasone (100 microg/kg, po, three times per week for 4 weeks) failed to restore the body weight gain and liver weight decreased by LF. The body weight gain reduced during LF was further decreased by dexamethasone treatment. Animals were subjected to blood biochemical, liver histopathological and immunochemical analyses. Although dexamethasone treatment significantly reduced ascites in LF rats, the plasma albumin and total protein levels decreased in fibrotic rats were not restored. Impaired liver functions during LF including elevated plasma aminotransferases and bilirubin levels along with GSTA2 repression were not recovered by dexamethasone. Dexamethasone failed to decrease the fibrosis score and to eliminate the extracellular matrix and alpha-smooth muscle actin accumulated in the fibrotic liver. The results of the present study showed that dexamethasone ameliorated ascites in LF rats but failed to improve the liver functions and fiber accumulation, and that the possible beneficial effect of dexamethasone might result from anti-inflammatory effect but not from liver improvement.

  3. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats

    OpenAIRE

    Shaqura, Mohammed; Mohamed, Doaa M.; Aboryag, Noureddin B.; Bedewi, Lama; Dehe, Lukas; Treskatsch, Sascha; Shakibaei, Mehdi; Schaefer, Michael; Mousa, Shaaban A

    2017-01-01

    Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for th...

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

    OpenAIRE

    Azzouz I; Trabelsi H.; Hanini A; Ferchichi S; Tebourbi O; Sakly M; Abdelmelek H

    2013-01-01

    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 presen...

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

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    Hongchao Zhou

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

  6. Characterization of the phospholipid requirement of a rat liver beta-glucosidase.

    OpenAIRE

    Basu, A; Glew, R H

    1984-01-01

    The lipid requirement of membrane-bound rat liver beta-glucosidase was investigated using 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate. The enzyme was solubilized and delipidated by sequential extraction of a crude lysosomal fraction from rat liver lysosomes with sodium cholate and ice-cold butan-1-ol. Neither saturated nor unsaturated phosphatidylcholine activated this enzyme. In contrast, acidic phospholipids like phosphatidylglycerol (PtdGro) and phosphatidylserine (PtdSer)...

  7. 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...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  9. The inositol 1,4,5-trisphosphate receptor is localized on specialized sub-regions of the endoplasmic reticulum in rat liver.

    Science.gov (United States)

    Lièvremont, J P; Hill, A M; Hilly, M; Mauger, J P

    1994-01-01

    Inositol 1,4,5-trisphosphate (InsP3) is involved in the mobilization of Ca2+ from intracellular non-mitochondrial stores. In rat liver, it has been shown that the InsP3-binding site co-purifies with the plasma membrane. This suggests that in the liver the InsP3 receptor (InsP3R) associates with plasma membrane. We studied the subcellular distribution of the liver InsP3R by measuring the maximal binding capacity of [3H]InsP3 and using antibodies against the 14 C-terminal residues of the type 1 InsP3R. The antibodies recognized a large amount of an InsP3R protein of 260 kDa in a membrane fraction which is also enriched with [3H]InsP3-binding sites and with markers of the basal, the lateral and the bile-canalicular membrane and the plasma-membrane Ca2+ pump (PMCA). The fractions enriched in markers of the endoplasmic reticulum (ER) and the Ca2+ pump of the ER (SERCA2b) contained low levels of InsP3 receptors. The immunofluorescent labelling of cultured hepatocytes with anti-InsP3R antibodies indicated that the receptor is concentrated in the perinuclear area and in some regions near the plasma membrane. The fraction enriched with InsP3R is also contaminated with markers of the ER and with SERCA2b. It was exposed to alkaline medium (pH 10.5) to extract endogenous actin and membrane-associated proteins before being subfractionated by Percoll-gradient centrifugation. The alkaline treatment allowed partial separation of the markers of the ER from the markers of the plasma membrane. The InsP3R was recovered in the heavy subfraction, which was also enriched with markers for the ER and with the SERCA2b and contained low levels of markers of the plasma membrane. These data indicate that the InsP3R is neither localized on the plasma membrane itself nor homogeneously distributed on the ER membrane. This supports the view that part of the receptor is localized on a specialized sub-region of the ER which interacts with the plasma membrane. Images Figure 2 Figure 3 Figure 4 Figure

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

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    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.

  11. [Effects of infrasound exposure on several enzymes activities of spleen and liver in rats].

    Science.gov (United States)

    Chen, Yao-ming; Ye, Lin; Gao, Shuang-bin; Zhu, Dong-hai; Luo, Weng-jing; Liu, Xiu-hong; Chen, Jing-yuan; Chen, Jing-zao

    2004-05-01

    To investigate the changes of several enzymes activities in the spleen and liver of rats after exposure to 8 Hz 130 dB infrasound for different time. Thirty-five male SD rats were randomly divided into five groups. Rats of group 1 served as control, rats from group 2 to 5 were exposed to 8 Hz 130 dB infrasound, 2 hours per day, for 1 wk, 2 wk, 3 wk, and 4 wk, respectively. The changes of enzymes activities in spleen and liver of rats were observed. Monoamine oxidase activities in spleen were significantly increased at 1 wk and 2 wk, it was decreased at 3 wk, and increased again at 4 wk (P < 0.05). There were no changes in the liver compared with the control group. Glutathione peroxides activities in spleen were significantly increased at 4 wk (P < 0.05) and it also increased in liver at 1 wk (P < 0.05). Superoxide dismutase activities in spleen were increased significantly from 1 wk to 4 wk, but there were no markedly changes in liver. The level of malondialdehyde in spleen were increased at 3 wk and 4 wk. In the liver, it were increased at 1 wk and 2 wk, and decreased at 3 wk, but it increased again at 4 wk (P < 0.05). The results indicated that lipid peroxidation and oxygen free radicals in spleen and liver were increased after infrasound exposure and it might induce the damage in tissue or cells.

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

    Directory of Open Access Journals (Sweden)

    Afiana Rohmani

    2015-12-01

    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.

  13. 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.

  14. Circadian signatures in rat liver: from gene expression to pathways

    Directory of Open Access Journals (Sweden)

    DuBois Debra C

    2010-11-01

    Full Text Available Abstract Background Circadian rhythms are 24 hour oscillations in many behavioural, physiological, cellular and molecular processes that are controlled by an endogenous clock which is entrained to environmental factors including light, food and stress. Transcriptional analyses of circadian patterns demonstrate that genes showing circadian rhythms are part of a wide variety of biological pathways. Pathway activity method can identify the significant pattern of the gene expression levels within a pathway. In this method, the overall gene expression levels are translated to a reduced form, pathway activity levels, via singular value decomposition (SVD. A given pathway represented by pathway activity levels can then be as analyzed using the same approaches used for analyzing gene expression levels. We propose to use pathway activity method across time to identify underlying circadian pattern of pathways. Results We used synthetic data to demonstrate that pathway activity analysis can evaluate the underlying circadian pattern within a pathway even when circadian patterns cannot be captured by the individual gene expression levels. In addition, we illustrated that pathway activity formulation should be coupled with a significance analysis to distinguish biologically significant information from random deviations. Next, we performed pathway activity level analysis on a rich time series of transcriptional profiling in rat liver. The over-represented five specific patterns of pathway activity levels, which cannot be explained by random event, exhibited circadian rhythms. The identification of the circadian signatures at the pathway level identified 78 pathways related to energy metabolism, amino acid metabolism, lipid metabolism and DNA replication and protein synthesis, which are biologically relevant in rat liver. Further, we observed tight coordination between cholesterol biosynthesis and bile acid biosynthesis as well as between folate biosynthesis

  15. Liver blood flow measurement in the rat. The electromagnetic versus the microsphere and the clearance methods

    NARCIS (Netherlands)

    Daemen, M. J.; Thijssen, H. H.; van Essen, H.; Vervoort-Peters, H. T.; Prinzen, F. W.; Struyker Boudier, H. A.; Smits, J. F.

    1989-01-01

    This study describes the simultaneous measurement of hepatic arterial and portal venous blood flow in the pentobarbital anesthetized rat by means of electromagnetic flowmeters. Hepatic arterial flow was 0.21 +/- 0.02 mL/min/g liver, and portal venous flow was 1.53 +/- 0.19 mL/min/g liver (n = 20).

  16. 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:

  17. Cassia alata alters Liver Structure in Rat | Amao | African Journal of ...

    African Journals Online (AJOL)

    Casia alata is a common plant in South West and its parts are freely used as herbs by the natives. Concomitantly, the prevalence of chronic liver disease is on the increase, thus the study was designed to investigate the effects of its crude extract on the rat liver structure. The methanolic extract of Cassia alata was ...

  18. PROLIFERATION OF RAT-LIVER MACROPHAGES IN-VITRO - INFLUENCE OF HEMATOPOIETIC GROWTH-FACTORS

    NARCIS (Netherlands)

    HOEDEMAKERS, RMJ; SCHERPHOF, GL; DAEMEN, T

    We examined the effects of several hemopoietic growth factors on proliferation of rat liver macrophages in vitro. The proliferative response of liver macrophages to hemopoietic growth factors was assayed on the basis of [methyl-H-3]thymidine uptake. Macrophage colony-stimulating factor and

  19. 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

    involved in metabolic liver functions, i.e. ureagenesis, gluconeogenesis, and drug metabolism, for acute phase proteins, "house-keeping" proteins, and for proteins related to liver regeneration. Results were expressed as per cent of the level in similarly fasted, untreated rats of the same stock RESULTS...

  20. 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.

  1. 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

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

    OpenAIRE

    Liu, Mei; Zheng, Su-Jun; Xu, Weihong; Zhang, Jianying; Chen, Yu; Duan, Zhongping

    2014-01-01

    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 ...

  3. A Modified Apparatus for Dual, Sterilized, Isolated Perfusion of the Rat Liver

    OpenAIRE

    Liu, Tao; Walsh, Thomas R.; Mischinger, Hans; Rao, Prakash N.; Chelvakumar, Premalatha; Rubin, Randy; Starzl, Thomas E.

    1990-01-01

    The isolated perfused rat liver (IPRL) has proven to be a useful model for the study of physiology and pathology of the liver. For research in nonparenchymal cell (NPC) function that includes measurement of cytokine production (eg, TNF), it is necessary to have a sterilized perfusion system. We have modified the IPRL apparatus so as to be able to perform sterile perfusions of two livers simultaneously. The perfusion apparatus is a recirculating closed system in which the oxygenator is a plast...

  4. Differing uptake of emulsion triglyceride by the fed and fasted rat liver.

    OpenAIRE

    Quarfordt, S H; Hanks, J; Shelburne, F; Schirmer, B

    1982-01-01

    The recycling perfusion of a fasted rat liver with an apoprotein E-enriched synthetic triglyceride emulsion revealed a significantly greater hepatic uptake of both the apoprotein and the triglyceride than did the liver of a chow-fed animal. This greater hepatic triglyceride uptake by the perfused fasted liver in comparison to the fed was also noted for emulsions containing no added apoprotein or supplemented with both the E and CIII-1 proteins. However, no difference in the uptake of the trig...

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

    NARCIS (Netherlands)

    STEEN, H; MARING, JG; MEIJER, DKF

    1992-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ranjbar

    2014-09-01

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

  7. [Study of coenzyme Q10 in the liver of preeclampsia pregnant rats].

    Science.gov (United States)

    Lin, S H; Yan, J Y

    2016-08-25

    To investigate the protective effect of coenzyme Q10 (CoQ10) in the liver of preeclampsiapregnant rats and the potential etiology. Fifty pregnant SD rats were equally divided into the normal pregnant (NP) group (n=10) and the preeclampsia (PE) group (n=40) randomly. The PE rats (n=40) were equally divided into four groups randomly, distilled water (DW) group, CoQ10 group, CoQ10 combined magnesium(CM) group and magnesium (Mg) group were established by treating the preeclampsia rats on day 15 to 21 of gestation with different measures. As for all the 50 rats, systolic blood pressure (SBP) of rat tail was detected on day 10, 15 and 21 of gestation respectively, 24 hours proteinuria analysis were detected on day 10, 15 and 21 of gestation respectively, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in blood andsuperoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), caspase-3, Bcl-2 and Bax protein expression in liver tissue were detected by western blot assay on day 21 of gestation. (1) SBP and 24 hours proteinuria analysis: there was no statistic difference among all the five groups on day 10 of gestation (P>0.05). Whereas, SBP and 24 hours proteinuria analysis were significantly higher in CoQ10 group, CoQ10 combined CM group, CM group and DW group than that in NP group on day 15, 21 of gestation (Papoptosis levles were upregulated in PE pregnant liver tissues. CoQ10 could effectively protect the liver by improving the liver functions and decreasing the apoptosis of liver cells in PE pregnant rats, and markedly decrease the oxidative stress and apoptosis in the livers. The protective roles of CoQ10 in liver might through its function of anti-oxidative stress and inhibiting cell apoptosis by regulating the balance of Bcl-2/Bax.

  8. Delayed and short course of rapamycin prevents organ rejection after allogeneic liver transplantation in rats.

    Science.gov (United States)

    Hamdani, Salim; Thiolat, Allan; Naserian, Sina; Grondin, Cynthia; Moutereau, Stéphane; Hulin, Anne; Calderaro, Julien; Grimbert, Philippe; Cohen, José Laurent; Azoulay, Daniel; Pilon, Caroline

    2017-10-14

    To test whether a delayed and short course of rapamycin would induce immunosuppressive effects following allogeneic orthotopic liver transplantation (OLT) in rats. Allogeneic OLTs were performed using Dark Agouti livers transplanted into Lewis recipients, and syngeneic OLTs were performed using the Lewis rat strain. Rapamycin (1 mg/kg per day) was administered by gavage from day 4 to day 11 post-transplantation. Lymphocyte cellular compartments were analyzed by flow cytometry in draining lymph nodes, non-draining lymph nodes and the spleen at days 11 and 42 in rapamycin-treated rats, untreated control rats and syngeneic grafted rats. Skin grafts from Dark agouti or from F344 RT were performed at day 30 on liver grafted rats treated with rapamycin. An 8-d course of rapamycin treatment initiated 4 d following transplantation resulted in the survival of grafted rats for more than 100 d. In contrast, untreated rats died of liver failure within 13 to 21 d. The analysis of the cellular compartment revealed an increase in two cellular subpopulations, specifically myeloid-derived suppressor cells (MDSCs) and CD8+CD45RClow T cells, without major modifications in the regulatory T cell (Treg) compartment in treated rats in the early stages after grafting. We evaluated the ability of treated rats to reject third-party allogeneic skin grafts to confirm their immune competence. In contrast, when skin was collected from rats syngeneic to the grafted liver, it was not rejected. Our results demonstrate that short and delayed rapamycin treatment allows for tolerance in allogeneic OLT. The results also allowed for the identification of the mechanisms of tolerance induced by rapamycin by identifying MDSCs and CD8+CD45RClow T cells as associated with the state of tolerance.

  9. Metabolism of antitumor acylfulvene by rat liver cytosol.

    Science.gov (United States)

    McMorris, T C; Elayadi, A N; Yu, J; Kelner, M J

    1999-01-01

    Illudins are novel compounds from which a potent class of antitumor agents, called acylfulvenes, have been synthesized. The model illudin, illudin S, has marked in vitro and in vivo toxicity but displays a poor therapeutic index. The toxicity of illudin S is believed to involve a combination of enzymatic reduction and chemical reaction. Enzymatic reduction by a cytosolic NADPH-dependent enzyme produces an aromatic metabolite, as does reaction with thiols. Acylfulvene is formed from illudin S by reverse Prins reaction. Acylfulvene is 100-fold less toxic in vitro and in vivo than illudin S but possesses marked antitumor efficacy in vivo, thus displaying opposite properties from illudin S. For this reason we investigated the in vitro metabolism of acylfulvene. Incubation of acylfulvene with NADPH and rat liver cytosol yielded two metabolites. One metabolite, the aromatic product, is similar to that obtained with illudin S in this in vitro system and was anticipated. The other metabolite, the hydroxylated product, was not expected and no corresponding metabolite for illudin S could be detected. The production of this hydroxylated metabolite from acylfulvene may explain, in part, the increased antitumor activity of novel acylfulvenes as compared with the illudins.

  10. Stereoselective degradation of tebuconazole in rat liver microsomes.

    Science.gov (United States)

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

    2012-01-01

    The aim of this study was to assess the stereoselectivity of two tebuconazole [(RS)-1-p-chlorophenyl-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol] enantiomers in in vitro system (rat liver microsomes). The analytes were extracted with acetic ether and concentrations were determined by high performance liquid chromatography (HPLC) with a cellulose tris(3,5-dimethylphenylcarbamate)-based chiral stationary phase. The degradation of rac-tebuconazole (15 μM) followed first-order kinetics, and the degradation of the S-tebuconazole (t(1/2) = 22.31 min) was faster than that of the R-tebuconazole (t(1/2) = 48.76 min), but no significant difference between the enantiomers was found in the respective incubation (7.5 μM for each). Kinetic assays showed that the K(m) was different between the two enantiomers (K(mR) = 14.83 ± 2.19, K(mS) = 12.23 ± 2.72). The interaction results revealed that there was competitive inhibition between S- and R-form, and there was a significant difference between the IC(50) of R- to S-tebuconazole and S- to R-tebuconazole (IC(50R/S)/IC(50S/R) = 4.98). Copyright © 2011 Wiley Periodicals, Inc.

  11. Protective effects of vitamin D3 against d-galactosamine-induced liver injury in rats.

    Science.gov (United States)

    Colakoglu, Neriman; Kuloglu, Tuncay; Ozan, Enver; Kocaman, Nevin; Dabak, Durrin Ozlem; Parlak, Gozde

    2016-08-01

    In this study, we examined liver damage induced by d-galactosamine (d-GaIN) and the protective effects of vitamin D3 in relation to d-GaIN toxicity. Twenty Wistar albino rats were used in this study. The rats were divided into four groups. Group I rats were used as the control group. Group II rats were given a single intraperitoneal injection of d-GaIN. Group III rats were given a single intraperitoneal injection of d-GaIN, intramuscular vitamin D3 for five days. Group IV rats were given intramuscular vitamin D3 for five days. All of rats were euthanized by cervical decapitation on the fifth day of experiment. Upon completion of the experiment, a midsaggital incision was performed, and the livers of all rats were removed and fixed. The livers were processed to perform TUNEL technique and histochemical staining. During the microscope examination, we observed inflamatory cell infiltration, sinusoidal dilatation, and apoptotic bodies due to d-GaIN exposure. In addition, glycogen content of the group II hepatocytes was significantly decreased. Vitamin D3 treatment provided better structural apperance of the livers in group III. TUNEL positive cells were extremly pervasive in the group II livers. The study found group III TUNEL positive cells at a reduced rate in relation to group II due to vitamin D3 treatment. This findings indicate that d-GaIN causes inflamation in the liver. This inflamation triggers the apoptotic process gradually. Vitamin D3 has potency to decrease the severity of d-GaIN-caused structural liver damage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 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

    . Compensatory changes in hormone or substrate levels explaining the lack of effect of liver denervation were not found. In rats with intact adrenals, the plasma epinephrine concentration was increased after 2.5 min of running. It is concluded that, in rats carrying out exercise of moderate intensity...

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

    Science.gov (United States)

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

    2016-01-01

    The synchrotron radiation X-ray fluorescence technique (SRXRF) was applied to the determination of K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb, and Sr concentrations in the liver and lungs in Wistar rats. The animals in the experiment included (1) healthy rats, (2) rats with alimentary obesity (AO), and (3) rats with alimentary obesity that were being given zinc sulphate with water for a long time (АО+Zn). Each group was divided into two subgroups. The experiment with the first subgroup was terminated with the animals in the state of physiological hunger and subsequent retrieval of liver and lung tissue, while the animals of the second subgroup were sacrificed two hours after ingestion of lard. The rats in physiological hunger manifested intergroup differences in the content of the bioelements (BEs) neither in the liver nor in the lungs. The rats with AO, as compared with the healthy animals, demonstrated in physiological hunger redistribution of inter-element correlations (IECs), which is an indirect reflection of sustained metabolic disorder. Additional zinc in the rats' ration did not affect their body weight and the concentration of the BEs (including zinc) in the liver and the lungs. However, the IECs in the tissues of these animals in physiological hunger also changed. This redistribution differed from that in the rats with AO. The IECs soon after ingestion of lard also changed, which also reflects sustained changes in the metabolism in the animals. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

    African Journals Online (AJOL)

    all users

    The petroleum samples were administered intraperitoneally and the biochemical changes in the rat serum and the liver wree monitored ... water freely. Twelve rats were sacrificed at the end of each month for the three months study. The levels of the parameters viz: Aspartate transaminase (AST). Alanine phosphatase (ALP) ...

  15. [Chinese herbal medicine Xiayuxue Decoction inhibits liver angiogenesis in rats with carbon tetrachloride-induced liver fibrosis].

    Science.gov (United States)

    Du, Jin-xing; Liu, Ping; Sun, Ming-yu; Tao, Qing; Zhang, Li-jun; Chen, Gao-feng; Hu, Yi-yang; Liu, Cheng-hai; Xu, Lie-ming

    2011-08-01

    To evaluate the effects of Xiayuxue Decoction, a compound traditional Chinese medicine, on liver angiogenesis in rats with carbon tetrachloride (CCl(4))-induced liver fibrosis. Liver cirrhosis was induced by intraperitoneal injection of 50% CCl(4)-olive oil solution at the dose of 1 mL/kg body weight, twice per week for 9 consecutive weeks. After 3- and 6-week injection, 6 rats in the normal group and 6 rats in the model group were randomly sacrificed for dynamic observation. The survival rats of model group were randomly divided into model group (n=15) and Xiayuxue Decoction group (n=11). Six normal rats were used as a normal control. Xiayuxue Decoction was administered orally starting from the 7th week for 3 weeks. At the end of the ninth week, animals were sacrificed and liver tissues were harvested to measure histological changes, activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 and protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), von Willebrand factor (vWF), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR2), complement decay-accelerating factor (DAF) and α-smooth muscle actin (α-SMA) in the liver tissues. Compared with the normal group, liver injury, fatty degeneration and collagen deposition were evidently observed in the model group and protein expressions of CD31, vWF, VEGF, VEGFR2, DAF and α-SMA were gradually increased. In addition, the activities of MMP-2 and MMP-9 in liver tissues were enhanced in the model group (Pliver injury, fatty degeneration and collagen deposition were markedly inhibited by Xiayuxue Decoction; protein expressions of CD31, vWF, VEGF, VEGFR2,α-SMA and DAF and activities of MMP-2 and MMP-9 in the liver tissues were decreased in the Xiayuxue Decoction group (Pliver cirrhosis induced by CCl(4). Xiayuxue Decoction inhibits the angiogenesis by decreasing the activities of MMP-2 and MMP-9, inhibiting the activation of hepatic stellate cells, and

  16. Induction of liver microsomal UDP-glucuronyltransferase in the rat administered with a plant phenol, eugenol.

    Science.gov (United States)

    Yokota, H; Yuasa, A

    1990-02-01

    UDP-glucuronyltransferase activity toward xenobiotics in rat liver microsomes was increased about 2.6-fold by administration of a eugenol (4-allyl-2-methoxyphenol). Km value of the induced enzyme toward UDP-glucuronic acid, however, did not change. Immunoblotting analysis revealed that the amount of UDP-glucuronyltransferase protein was increased in the microsomes of eugenol-treated rat liver. In vitro translation assay showed that the level of translatable mRNA encoding this enzyme increased in the liver. These results indicate that mRNA specific for production of UDP-glucuronyltransferase has accumulated, presumably by de novo synthesis in response to a plant phenol, eugenol.

  17. OXIDATIVE STRESS IN LIVER TISSUE OF RAT INDUCED BY CHRONIC SYSTEMIC HYPOXIA

    Directory of Open Access Journals (Sweden)

    Abdul Halim S

    2009-06-01

    Full Text Available Adaptation mechanism to hypoxia in living organisms increases reactive oxygen species (ROS formation that could exceed the capacity of anti oxidant. Gluthatione (GSH in which highest concentration present in liver, plays an important role in maintaining the intracellular redox equilibrium and protect tissues from oxidative stress. The aim of this study was to observe tissue response of rat that was exposed to chronic systemic hypoxia by analyzing the oxidative stress in liver tissue. Twenty male Sprague-Dawley rats were induced by chronic systemic hypoxia by kept them in hypoxic chamber (10% O2:90% N2 for 1, 3, 7 and 14 day(s. All rats were sacrificed with ether anesthesia after hypoxia treatment. Liver tissues were analyzed using parameters of oxidative stress, malondialdehyde (MDA with tBARS test, and endogenous antioxidant, glutathione reduced form (GSH. The study showed that chronic systemic hypoxia induction caused oxidative stress in liver tissue, which was shown by increased concentration of MDA in liver tissue (nmol/mg liver tissue. Concentration of MDA in liver tissue was increased significantly on day-1, day-3, day-7 and day-14 compared to control group (ANOVA, LSD, p<0.05. The differences between day-3, day-7 and day-14 was not significant. In contrast, liver GSH content (µg/mg liver protein was progressively decreased significantly since day-1 of hypoxia until the end of experiment (ANOVA, LSD, p<0.05. Statistical analysis revealed that there is a strong correlation between MDA and GSH concentration in liver tissue (Pearson = - 0.993. It was concluded that oxidative stress present in liver tissue of rat induced by chronic systemic hypoxia

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

    Directory of Open Access Journals (Sweden)

    Ibrahim Halil Bahcecioglu

    2015-08-01

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

  19. [Mutagenic Activity of Four Aminoazo Compounds with Different Carcinogenicity for Rat Liver in the Ames Test].

    Science.gov (United States)

    Frolova, T S; Sinitsyna, O I; Kaledin, V I

    2015-01-01

    In this paper in the bacterial Ames test we compared the mutagenicity of four aminoazo compounds, previously studied by other researchers and used for activation of rat liver enzymes, with the carcinogenicity in the rat liver. It was found that in the Ames test they have mutagenic activity, however, this activity does not correlate quantitatively with rat sensitivity to their hepatocarcinogenic action. Thus, the most active carcinogen 3'-methyl-4-dimethylaminoazobenzene causes mutations almost 2.5 times less than weakly carcinogenic ortho-aminoazotoluene, and exactly the same number of mutations as non-carcinogenic N,N-diethyl-4-aminoazobenzene.

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

    Science.gov (United States)

    Zhang, Hongmei; Dong, Yan; Su, Qing

    2017-02-01

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

  1. 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

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

    Science.gov (United States)

    Ghaffarian-Bahraman, Ali; Shahroozian, Ibrahim; Jafari, Abbas; Ghazi-Khansari, Mahmoud

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ali Ghaffarian-Bahraman

    2014-12-01

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

  4. 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.

  5. 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......Selenium has been suggested to enhance the histochemical staining of mercury when sections of tissue are subjected to the silver-enhancement method. In the present study, histochemical staining patterns of mercury in tissue sections of rat livers were compared with the actual content of organic...... and inorganic Hg in the livers, in both the presence and the absence of Se. Rats were injected intravenously with 5 micrograms of Hg g-1 body weight as methyl [203Hg] mercury chloride (MeHg) or as [203Hg]mercuric chloride (Hg2+). After 2 h, half the rats received an additional intraperitoneal injection of 2...

  6. Effect of sesame oil on serum and liver lipid profiles in the rat.

    Science.gov (United States)

    Satchithanandam, S; Chanderbhan, R; Kharroubi, A T; Calvert, R J; Klurfeld, D; Tepper, S A; Kritchevsky, D

    1996-01-01

    In our previous study (Satchithanandam, S., Reicks, M., Calvert, R.J., Cassidy, M.M. and Kritchevsky, D. (1993) J. Nutr. 123, 1852-1858), we found that the absorption of lymphatic cholesterol by rats fed diets containing 24% sesame oil was about 50% less than that by rats fed the control diet containing no sesame oil. The effect of sesame oil on serum cholesterol levels was not determined at that time. In the present study, three groups of male Wistar rats (75-100 g) were fed a control diet or a diet containing 12 or 24% sesame oil. To increase serum cholesterol levels, 1% cholesterol and 0.5% cholic acid were added to each diet. After rats were fed for 4 weeks, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride levels were measured in the serum. Liver weight and cholesterol and triglyceride levels were determined. Liver cholesterol levels were significantly lower in rats fed the 24% sesame oil diet, and the liver lipid level was significantly higher in the 24% sesame oil-fed group, compared with levels in the group fed the control diet. Liver weights and esterified cholesterol and liver triglyceride levels were not significantly different among the groups. Levels of serum total cholesterol and LDL-cholesterol were significantly lower in rats fed the 24% sesame oil diet, compared with levels in the control group. Serum triglyceride and HDL-cholesterol levels did not differ significantly among the groups. The mechanism by which a diet containing 24% sesame oil reduces levels of serum and liver cholesterol, liver LDL cholesterol, and liver lipids is not known. However, the high degree of unsaturation (85%) of sesame oil and the presence of linoleic acid may be important factors.

  7. 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

    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......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......; liver tissue was sampled for analysis of regeneration rate and proliferation index. Results: The high dose dexamethasone group had significantly lower body and liver weight than the placebo and anti-CD163-dex groups. There were no differences in liver regeneration rates between groups. Hepatocyte...

  8. Heat-Induced Changes in Perfused Rat Liver,

    Science.gov (United States)

    1981-09-28

    Hepatic injury resulting from heatstroke (1,6,7,8) or occurring with thermotherapy for cancer (9) has stimulated the use of the isolated perfused liver...liver perfusion. Int Bartosek 1, Guaitani At Miller Li#ed s. Isolated Liver Perfusion and its Applications . Now York: Raven Press, 19731 11-51. 12

  9. Photoaffinity labelling of nucleoside-transport proteins in plasma membranes isolated from rat and guinea-pig liver.

    OpenAIRE

    Wu, J S; Young, J D

    1984-01-01

    Nitrobenzylthioinosine (NBMPR) was employed as a probe of the nucleoside transporters from rat and guinea-pig liver. Purified liver plasma membranes prepared on self-generating Percoll density gradients exhibited 16-fold (rat) and 10-fold (guinea pig) higher [3H]NBMPR-binding activities than in crude liver homogenates (3.69 and 14.7 pmol/mg of protein for rat and guinea-pig liver membranes respectively, and 0.23 and 1.47 pmol/mg of protein for crude liver homogenates respectively). Binding to...

  10. 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

  11. The Mechanisms Underlying the Hypolipidaemic Effects of Grifola frondosa in the Liver of Rats

    Science.gov (United States)

    Ding, Yinrun; Xiao, Chun; Wu, Qingping; Xie, Yizhen; Li, Xiangmin; Hu, Huiping; Li, Liangqiu

    2016-01-01

    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 G. 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 G. 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 20 proteins differentially expressed in livers of rats treated with G. frondosa compared with untreated hyperlipidemic rats. Of these 20 proteins, seven proteins were down-regulated, and 13 proteins were up-regulated. These findings indicate that the hypolipidaemic effects of G. frondosa reflected its modulation of key enzymes involved in cholesterol and triacylglycerol biosynthesis, absorption, and catabolic pathways. G. frondosa may exert anti-atherosclerotic effects by inhibiting LDL oxidation through down-regulation and up-regulating proteins expression in the liver of rats. Therefore, G. frondosa may produce both hypolipidaemic and anti-atherosclerotic effects, and potentially

  12. Correction of liver disease following transplantation of normal rat hepatocytes into Long-Evans Cinnamon rats modeling Wilson's disease.

    Science.gov (United States)

    Irani, A N; Malhi, H; Slehria, S; Gorla, G R; Volenberg, I; Schilsky, M L; Gupta, S

    2001-03-01

    To establish the efficacy of cell therapy in Wilson's disease, we used the Long-Evans Cinnamon (LEC) rat model with atp7b gene mutation and copper toxicosis. Several groups of LEC rats were established, including animals pretreated with retrorsine to exacerbate copper toxicosis and inhibit proliferation in native hepatocytes followed by partial hepatectomy to promote liver repopulation. Hepatocytes from normal, syngeneic LEA rats were transplanted intrasplenically. Animal survival, biliary copper excretion, and hepatic copper were determined. The magnitude of liver repopulation was demonstrated by measuring serum ceruloplasmin and hepatic atp7b mRNA. Long-term survival in LEC rats treated with retrorsine, partial hepatectomy, and cell transplantation was up to 90%, whereas fewer than 10% of animals pretreated with retrorsine, without cell therapy, survived, P Wilson's disease.

  13. INTRACELLULAR DISTRIBUTION OF ALKALINE PHOSPHATASE IN RAT LIVER CELLS

    Science.gov (United States)

    Emery, Arthur J.; Dounce, Alexander L.

    1955-01-01

    1. Cytochemical studies of the intracellular distribution of alkaline phosphatase in rat liver have been made, using a fractionation procedure recently developed in this laboratory (8) and a similar but modified method not described previously. Aqueous media were used in both cases. 2. The alkaline phosphatase was found to consist of two forms, one of which is strongly activated by magnesium and one of which is not sensitive to this metal. 3. The form of the enzyme that is not activated by magnesium occurs mainly in the nuclear fraction, where it seems to be rather firmly bound. Some of this form of the enzyme is also found in the microsomes, but very little if any occurs in the soluble supernatant fraction. 4. The form of alkaline phosphatase which is activated by magnesium occurs mainly in the soluble supernatant fraction, but what is believed are significant amounts also occur in nuclei. A significant portion of this form of the enzyme can be extracted from the isolated nuclei with cold, isotonic saline solution. Some activity of this form of the enzyme is also found in the microsomal fraction. 5. Mitochondria appear to contain relatively little alkaline phosphatase of either kind. 6. The concept of a porous nuclear membrane has been invoked to explain some of the results obtained in this work. It is postulated that part at least of the form of the enzyme that is activated by magnesium is free to diffuse back and forth through pores in the nuclear membrane, whereas this is considered not to be possible for the form of the enzyme that is insensitive to magnesium as a result of the firm binding of the latter to nuclear substance. PMID:13242596

  14. The effects of modified sini decoction on liver injury and regeneration in acute liver failure induced by D-galactosamine in rats.

    Science.gov (United States)

    Luo, Jianxing; Zhang, Yang; Hu, Xiaoyu; Zhong, Sen; Chen, Guo; Wang, Yanyan; Lin, Wu; Yi, Cheng; Zhu, Hong

    2015-02-23

    Modified sini decoction (MSND) is a well-known traditional Chinese medical formula that has been used to treat cardiovascular and liver diseases for many years. We investigated the effects of MSND on acute liver failure and identified the possible mechanisms of these effects. Acute liver failure was induced by intraperitoneal injection of d-galactosamine (d-GalN) into specific pathogen-free male Wistar rats. Next, the rats were treated with Stronger Neo-Minophagen C and MSND via gavage. Biochemical parameters, histological changes in the liver, the survival of rats and the mRNA levels of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), high mobility group box 1 (HMGB1) caspase-3 and proliferating cell nuclear antigen (PCNA) were analyzed. MSND prolonged the survival times of the acute liver failure rats. The biochemical parameters were improved, and necrosis in the liver tissues was reduced by both Stronger Neo-Minophagen C (SNMC) and MSND, but MSND induced greater effects. The mRNA expressions of HMGB1, TLR4, NF-κB, and Caspase-3 were remarkably decreased, and the expression of PCNA was remarkably increased by SNMC and MSND, and the effects of MSND were greater. MSND protected the liver and increased the survival rate of acute liver failure rats. These effects were likely mediated by the inhibitions of the inflammatory reaction and apoptosis and the promotion of liver tissue regeneration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Intestinal flora imbalance results in altered bacterial translocation and liver function in rats with experimental cirrhosis.

    Science.gov (United States)

    Zhang, Wei; Gu, Yurong; Chen, Youming; Deng, Hong; Chen, Lubiao; Chen, Sui; Zhang, Genglin; Gao, Zhiliang

    2010-12-01

    The intestinal microflora plays a major role in human health. Intestinal flora imbalances are seen in clinical settings, such as cirrhosis, in which bacterial translocation (BT) results in migration of bacteria or bacterial products from the intestinal lumen to extraintestinal sites. In this study, we explored the effect of alterations in gut flora on BT and liver function in cirrhotic rats. In this study, we used a carbon tetrachloride-induced cirrhotic rat model to compare the abundance of major aerobic and anaerobic bacterial species in healthy and cirrhotic rats. We used antibiotic (norfloxacin) and different probiotic treatments to change the status of gut flora in the cirrhotic rats and evaluated BT, liver function, and endotoxemia in the different models. We found higher levels of Enterobacteriaceae in cirrhotic rats when compared with healthy rats. Bifidobacteria treatment resulted in lower levels of Enterobacteriaceae along with increased levels of Lactobacillus when compared with the normal saline group. Both Bifidobacteria and Enterococcus treatments resulted in lower endotoxin levels than in the normal saline group. Gut flora imbalances in cirrhotic rats result in significant changes in BT and liver function in cirrhotic rats.

  16. Maternal separation on the ethanol-preferring adult rat liver structure.

    Science.gov (United States)

    Rosa-Toledo, Olegário; Almeida-Chuffa, Luiz G; Martinez, Marcelo; Felipe-Pinheiro, Patricia F; Padovani, Carlos R; Martinez, Francisco E

    2015-01-01

    Background and rationale for the study. We designed to test whether there is interaction of maternal separation (MS) on the ethanol-preferring rats liver structure. The UCh rat pups were separated daily from their mothers during the stress hyporesponsive period (SHRP), between four and 14 days-old, always at the same time for four hours in a cage containing eight subdivisions, one for each pup. Subsequently, rats that presented the highest (UChB) and the lowest (UChA) ethanol (EtOH) consumption were selected to the study. Both UChB and UChA rats received 10% (v/v) EtOH and distilled water ad libitum until the end of the experiment (120 days-old). The liver was collected to histological routine for morphometric and stereological analyses, and immunohistochemistry. There was an interaction of MS and EtOH on the liver: increased liver mass, peritubular vessels, stellate cell numbers, steatosis and cell death, decreased necrosis, sinusoidal capillary diameters and cell proliferation. While there was a decrease in FSH, testosterone and 5α-di-hidrotestosterone, and increasing corticosterone and cholesterol. There is interaction of MS and EtOH on the liver structure, dependent on the amount of EtOH intake. Furthermore, the interaction of stress and drugs can increase or decrease their effects on the liver or indirectly via hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes.

  17. Ecklonia cava polyphenol protects the liver against ethanol-induced injury in rats.

    Science.gov (United States)

    Takahashi, Mai; Satake, Naoko; Yamashita, Haruka; Tamura, Akiko; Sasaki, Mio; Matsui-Yuasa, Isao; Tabuchi, Masaki; Akahoshi, Yasumitsu; Terada, Masaki; Kojima-Yuasa, Akiko

    2012-07-01

    The development of alcoholic liver disease is a complex process that involves both the parenchymal and non-parenchymal cells of the liver. We examined the effect of an Ecklonia cava extract on ethanol-induced liver injury. Isolated hepatocytes and hepatic stellate cells (HSCs) were incubated with ethanol. Ecklonia cava polyphenol (ECP) was added to the cultures that had been incubated with ethanol. Male Wistar rats were fed a diet that included 0.02% or 0.2% ECP or no ECP. For a period of 3 weeks, the animals were given drinking water containing 5% ethanol and were also treated with carbon tetrachloride (CCl4) (0.1 ml/kg of body weight). In the cultured hepatocytes, the ECP treatment suppressed the ethanol-induced increase in cell death by maintaining intracellular glutathione (GSH) levels. In HSCs, ECP treatment suppressed the ethanol-induced increases in type I collagen and α-smooth muscle actin expression by maintaining intracellular levels of reactive oxygen species and GSH. We examined the effects of ECP on serum AST and ALT activity, as well as the progression of liver fibrosis in rats treated with ethanol and CCl4. ECP treatment suppressed plasma AST and ALT activities in the ethanol- and CCl4-treated rats. ECP treatment fully protected the rats against ethanol- and CCl4-induced liver injury. ECP may be a candidate for preventing ethanol-induced liver injury. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat.

    Science.gov (United States)

    Jiang, Wei; Guo, Mei-Hua; Hai, Xin

    2016-12-14

    To evaluate the hepatoprotective effect of lycopene (Ly) on non-alcoholic fatty liver disease (NAFLD) in rat. A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC) in serum and low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), free fatty acid (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450 (CYP) 2E1 in rat liver were determined by immunohistochemistry analysis. A significant decrease was observed in the levels of serum AST (2.07-fold), ALT (2.95-fold), and the blood lipid TG (2.34-fold) and TC (1.66-fold) in the dose of 20 mg/kg Ly-treated rats (P liver homogenates, respectively (P liver fats and reversed histopathological changes, all in a dose-dependent manner (P < 0.05, P < 0.01). This study suggests that Ly has a protective effect on NAFLD, down-regulates expression of TNF-α, and that CYP2E1 may be one of the action mechanisms for Ly.

  19. [Effects of Chinese herbal medicine Xiaopi Pill in preventing rats from dimethylnitrosamine-induced liver fibrosis].

    Science.gov (United States)

    Zhang, Xiao; Ning, Bing-bing; Ren, Shuang; Zhang, Li-jun; Zhang, Wen-meng; Chen, Jia-mei; Chen, Gao-feng; Zhang, Hua; Mu, Yong-ping; Liu, Ping

    2012-11-01

    To explore the intervention effects of Xiaopi Pill (XPW), a compound traditional Chinese herbal medicine, on the development progress of dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Liver fibrosis model was established by intraperitoneal injection of 0.5% DMN 2 mL/kg thrice a week for 4 weeks. Rats were divided into control group given saline and treatment group given XPW during the 3rd week of DMN injections. Rats were sacrificed at the end of the experiment, and then liver histological changes, liver function and mRNA expression of the liver fibrosis-associated markers were observed. (1) At the end of the 2nd and 4th weeks of DMN injection, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) increased significantly in rats (Pliver were found at the end of the 4th week, including a complete round structure of false flocculus round, meantime, the hydroxyproline content of hepatic tissue was increased significantly at the end of the 2nd and 4th weeks (Pliver fibrosis in rats can be suppressed by XPW; the mechanism may be associated with inhibition of the activated hepatic stellate cells.

  20. Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats.

    Science.gov (United States)

    Gargouri, M; Magné, C; Ben Amara, I; Ben Saad, H; El Feki, A

    2017-02-28

    Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.

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

    Science.gov (United States)

    Sipahi, Mesut; Şahin, Sevinç; Arslan, Ergin; Börekci, Hasan; Metin, Bayram; Cantürk, Nuh Zafer

    2015-01-01

    Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations. PMID:26457000

  2. 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.

  3. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

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    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.

  4. Liver myofibroblasts of murine origins express mesothelin: Identification of novel rat mesothelin splice variants.

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    Michel Fausther

    Full Text Available Liver myofibroblasts are specialized effector cells that drive hepatic fibrosis, a hallmark process of chronic liver diseases, leading to progressive scar formation and organ failure. Liver myofibroblasts are increasingly recognized as heterogeneous with regards to their origin, phenotype, and functions. For instance, liver myofibroblasts express cell markers that are universally represented such as, ItgαV and Pdgfrβ, or restricted to a given subpopulation such as, Lrat exclusively expressed in hepatic stellate cells, and Gpm6a in mesothelial cells. To study liver myofibroblasts in vitro, we have previously generated and characterized a SV40-immortalized polyclonal rat activated portal fibroblast cell line called RGF-N2 expressing multiple mesothelin mRNA transcripts. Mesothelin, a cell-surface molecule expressed in normal mesothelial cells and overexpressed in several cancers such as, mesothelioma and cholangiocarcinoma, was recently identified as a key regulator of portal myofibroblast proliferation, and fibrosis progression in the setting of chronic cholestatic liver disease. Here, we identify novel mesothelin splice variants expressed in rat activated portal fibroblasts. RGF-N2 portal fibroblast cDNA was used as template for insertion of hemagglutinin tag consensus sequence into the complete open reading frame of rat mesothelin variant coding sequences by extension PCR. Purified amplicons were subsequently cloned into an expression vector for in vitro translation and transfection in monkey COS7 fibroblasts, before characterization of fusion proteins by immunoblot and immunofluorescence. We show that rat activated portal fibroblasts, hepatic stellate cells, and cholangiocarcinoma cells express wild-type mesothelin and additional splice variants, while mouse activated hepatic stellate cells appear to only express wild-type mesothelin. Notably, rat mesothelin splice variants differ from the wild-type isoform by their protein properties and

  5. Effect of dichloromethylene diphosphonate on liver regeneration following thioacetamide-induced necrosis in rats

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    Bautista, Mirandeli; del Rio, María Ángeles Gómez; Benedí, Juana; Sánchez-Reus, María Isabel; Morales-González, José A; Téllez-López, Ana María; López-Orozco, Maricela

    2013-01-01

    AIM: To study the effect of dichloromethylene diphosphonate (DMDP), a selective Kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mechanisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P < 0.05) different compared with that of the TA group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that Kupffer cells are involved in TA-induced liver, as well as in postnecrotic proliferative liver states. PMID:23898371

  6. Dose-related effects of dexamethasone on liver damage due to bile duct ligation in rats.

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    Eken, Halil; Ozturk, Hayrettin; Ozturk, Hulya; Buyukbayram, Huseyin

    2006-09-07

    To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. A total of 40 male Sprague-Dawley rats, weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10) were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the two-week period, biochemical and histological evaluations were processed. The mean serum bilirubin and liver enzyme levels significantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group. Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not significantly lower in the high-dose corticosteroid group as compared to the low-dose group. Thus, low-dose corticosteroid provides a significant reduction of liver damage without increased side effects, while high dose is associated not with lower fibrosis but with increased side effects.

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

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

    2017-04-04

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

  8. Regeneration and Cell Recruitment in an Improved Heterotopic Auxiliary Partial Liver Transplantation Model in the Rat.

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    Ono, Yoshihiro; Pérez-Gutiérrez, Angelica; Yovchev, Mladen I; Matsubara, Kentaro; Yokota, Shinichiro; Guzman-Lepe, Jorge; Handa, Kan; Collin de l'Hortet, Alexandra; Thomson, Angus W; Geller, David A; Yagi, Hiroshi; Oertel, Michael; Soto-Gutierrez, Alejandro

    2017-01-01

    Auxiliary partial liver transplantation (APLT) in humans is a therapeutic modality used especially to treat liver failure in children or congenital metabolic disease. Animal models of APLT have helped to explore therapeutic options. Though many groups have suggested improvements, standardizing the surgical procedure has been challenging. Additionally, the question of whether graft livers are reconstituted by recipient-derived cells after transplantation has been controversial. The aim of this study was to improve experimental APLT in rats and to assess cell recruitment in the liver grafts. To inhibit recipient liver regeneration and to promote graft regeneration, we treated recipients with retrorsine and added arterial anastomosis. Using green fluorescence protein transgenic rats as recipients, we examined liver resident cell recruitment within graft livers by immunofluorescence costaining. In the improved APLT model, we achieved well-regenerated grafts that could maintain regeneration for at least 4 weeks. Regarding the cell recruitment, there was no evidence of recipient-derived hepatocyte, cholangiocyte, or hepatic stellate cell recruitment into the graft. Macrophages/monocytes, however, were consistently recruited into the graft and increased over time, which might be related to inflammatory responses. Very few endothelial cells showed colocalization of markers. We have successfully established an improved rat APLT model with arterial anastomosis as a standard technique. Using this model, we have characterized cell recruitment into the regenerating grafts.

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

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    Cai, Xiaxia; Bao, Lei; Wang, Nan; Xu, Meihong; Mao, Ruixue; Li, Yong

    2016-03-31

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

  10. Effects of testosterone administration on liver structure and function in aging rats.

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    Nucci, Ricardo Aparecido Baptista; Teodoro, Ana Caroline de Souza; Krause Neto, Walter; Silva, Wellington de Assis; de Souza, Romeu Rodrigues; Anaruma, Carlos Alberto; Gama, Eliane Florencio

    2017-06-01

    Aging males have a decrease in testosterone levels, by which the testosterone treatment may influence in a negatively fashion the liver. This study aimed to analyze the effects of aging with or without testosterone administration on the liver components of animals. Wistar rats were divided into three groups: 20 months' group (G20), 24 months' group (G24), group treated with testosterone for 16 weeks (GT). All groups were sacrificed at 24 months except for G20 that was sacrificed at 20 months. Aging and testosterone treatment alters the body weight (BW), liver weight (LW) and relative liver weight. Besides, testosterone increased the mitogen capacity of hepatocytes. Nonetheless, we reinforce the negative effects of testosterone on old animals' liver as chronic hepatic congestion and/or cholestasis. In addition, we observed that testosterone plays an important role on hepatic glycogen stores. Our study showed many implications for the knowledge about the effects of aging with or without testosterone administration on old animals' liver.

  11. Measurement of bioimpedance and cell viability during ischemia-reperfusion in the rat liver.

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    Ahn, H; Shin, H; Yun, S; Kim, J; Choi, J

    2005-01-01

    During liver resection and liver transplant, liver is damaged by ischemia-reperfusion injury. Until now, there is no approved method to measure or predict the extent of liver injury during the operation. This is the preliminary study to make the real time monitoring system by quantification of bioimpedance and ischemiareperfusion reperfusion injury in liver. Sprague-Dawley rats were subjected to different periods of 70% partial hepatic ischemia (30, 60, 90 and 120minutes ischemia) and reperfusion. We measured changes of liver tissue bioimpedance (120Hz-100KHz) every five minutes. Cell viability was assessed by metabolic capacity of fatty acid (palmitic acid metabolic rate), ATP content and histological examination (H/E and TUNEL stain) at every 30 minutes interval during ischemia.

  12. The role of ghrelin on apoptosis, cell proliferation and oxidant-antioxidant system in the liver of neonatal diabetic rats.

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    Koyuturk, Meral; Sacan, Ozlem; Karabulut, Sezin; Turk, Neslihan; Bolkent, Sehnaz; Yanardag, Refiye; Bolkent, Sema

    2015-07-01

    Ghrelin is a multifunctional peptide hormone which stimulates appetite and regulates glucose metabolism and adipogenesis. The purpose of this study was to investigate whether ghrelin has protective effects in the liver of streptozocin (STZ) diabetic rats or not. Wistar-type neonatal rats were divided into four groups: I. Controls, II. Ghrelin administrated controls, III. STZ-diabetic rats, and IV. Ghrelin administrated diabetic rats. On the second day after birth, 100 mg/kg STZ was administered intraperitoneally in a single dose to induce diabetes in rats. 100 µg/kg/day ghrelin was administrated to rats subcutaneously for 4 weeks. Ghrelin administration improved histopathologic changes in STZ-diabetic liver. Obestatin immunoreactivity has been shown in livers of neonatal rats. The immunoreactivity of obestatin increased in diabetic rats and a decline was observed in ghrelin administrated diabetic rats. Caspase 8 and 3 immunoreactivities increased in diabetic rats; however, ghrelin administration differently affected caspases 8 and 3 immunoreactivities. Proliferating cell nuclear antigen immunoreactivities decreased in diabetic rats and in ghrelin administrated diabetic rats. Serum alanine (P diabetic rats compared to the diabetic rats. Gamma glutamyl transferase activity (P diabetic rats compared to the diabetic rats. The response of antioxidants including glutathione levels, catalase and superoxide dismutase activities were altered in ghrelin administrated diabetic rats. Our findings indicate that ghrelin administration affects hepatic functions in neonatal diabetic rats and might be considered as a therapeutic agent. © 2015 International Federation for Cell Biology.

  13. Fresh garlic amelioration of high-fat-diet induced fatty liver in albino rats.

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    Qamar, Aisha; Siddiqui, Asma; Kumar, Hemant

    2015-10-01

    To observe the effect of fresh garlic on high-fat-diet-induced fatty liver changes. The experimental study was conducted at the Jinnah Postgraduate Medical Centre, Karachi, from October to November 2008, and comprised adult albino rats weighing 200-240g each. The rats were divided into 5 groups according to dietary regimen for eight weeks each. Group A received control diet; Group B received high saturated fat diet; Group C received high unsaturated fat diet; Group D received high saturated fat diet with fresh garlic; and Group E received high unsaturated fat diet with garlic for 8 weeks. Liver tissue slides were stained with Oil red-O and haematoxylin and Periodic acid-Schiff-haematoxylin. The 50 rats in the study were divided into five groups of 10(20%) each. There was marked deposition of fat in hepatocyte along with marked decrease in glycogen content in liver of rats in Groups B and C, with Group B showing more marked changes. The changes in fat and glycogen content were reversed and ameliorated close to Group A in rats belonging to Groups D and E. Fresh garlic minimised the high-fat-diet-induced fatty liver changes in rats.

  14. Role of NF-kappaB as effector of IPC in donor livers before liver transplantation in rats.

    Science.gov (United States)

    Li, X-C; Ma, Y-F; Wang, X-H

    2006-06-01

    The objective of this study was to investigate the effect of ischemic preconditioning (IPC) on NF-kappaB activity during reperfusion early after liver transplantation in rats. Male Sprague-Dawley (SD) rats were used as donors and recipients of orthotopic liver transplantations. The donor liver was stored 2 hours in Ringer's solution at 4 degrees C preimplantation. IPC was performed by clamping of the portal vein and hepatic artery of the donor for 10 minutes followed by reperfusion for 10 minutes before harvesting. At 1, 2, 4, and 6 hours after portal vein reperfusion, graft samples were obtained to determine hepatic levels of NF-kappaB activity, tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule (ICAM)-1. Blood samples were obtained to measure serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). After liver transplantation without IPC, serum levels of ALT and LDH increased significantly compared with the sham-operated group. Among the IPC group, serum ALT and LDH decreased significantly. NF-kappaB activity in the graft increased within 6 hours after transplantation. Among the IPC group, NF-kappaB activity was significantly attenuated. Hepatic levels of TNF-alpha and ICAM-1 were significantly elevated in the non-IP group but both were reduced in the IPC group. IPC downregulated TNF-alpha and ICAM-1 expression in the graft, most likely through decreased NF-kappaB activation, and attenuated neutrophil infiltration after reperfusion.

  15. Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate.

    Science.gov (United States)

    Fiala, E S; Sohn, O S; Li, H; El-Bayoumy, K; Sodum, R S

    1997-09-01

    We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2-nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane-induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.

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

    Science.gov (United States)

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

    2016-01-01

    AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation in the treatment of liver fibrosis. METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine (DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin (IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells (KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were co-cultured with KCs in vitro to assess the effects of UC-MSCs on KCs’ phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UC-MSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs. RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the co-culture system resulted in decreased KC mobilization. CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN. PMID:27468195

  17. Proliferative effect of aqueous extract of Hyptis fructicosa on liver regeneration after partial hepatectomy in rats.

    Science.gov (United States)

    Lima, Sônia Oliveira; Viana, Luciano da Costa; Santana, Fábio Rafael Teixeira de; Zucoloto, Ségio; Albuquerque Junior, Ricardo Luiz de; Gomes, Margarete Zanardo

    2012-01-01

    To evaluate the effect of aqueous extract of Hyptis fructicosa on hepatic regeneration after partial hepatectomy in rats. Sixteen rats were divided in two groups: C (Control Group) and HF (Whose rats received aqueous extract of Hyptis fructicosa during 4 days using the dose of 100 mg/kg/day). On the consecutive day of this treatment, the animals of both groups underwent hepatectomy of about 67% of liver. Twenty four hours later, they were sacrificed, and the remaining mass of liver was removed and prepared to be studied through the PCNA immunohistochemical technique. The liver regeneration index of HF group was 53.56 ± 18.91%, while in C group was 21.12 ± 8.29% (p=0.0003). These results show that the administration of aqueous extract of Hyptis fructicosa using the dose of 100mg/kg/day increased the hepatocyte proliferation in the group HF.

  18. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    Science.gov (United States)

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-04-01

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H 2 O 2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  19. The effect of avocado oils on some liver characteristics in growing rats.

    Science.gov (United States)

    Werman, M J; Mokady, S; Neeman, I; Auslaender, L; Zeidler, A

    1989-05-01

    The effects of various avocado oils on some liver characteristics were studied in growing rats. The rats were fed diets containing 10% (w/w) avocado oil for 4 wk. In comparison with rats fed refined oil obtained from cored fruit by centrifugal separation, rats fed unrefined avocado oil obtained by solvent extraction from the intact fruit, or refined avocado oil containing avocado-seed oil, showed significant growth inhibition, an increase in the amount of hepatic lipids (identified as steatosis by histopathological examination), and a decrease in levels of triglycerides in blood. Rats fed the refined oil containing unsaponifiable material prepared from unrefined oil from the intact fruit showed similar responses. Fatty livers were not induced by feeding rats unrefined avocado oil obtained from intact fruit by centrifugal separation, although a significant decrease in blood triglycerides was observed. There were no significant differences between groups in serum total protein, albumin or bilirubin content or in alanine aminotransferase activity. However, serum alkaline phosphatase activity was increased in rats fed the seed oil, the unrefined solvent-extracted oil from intact fruit, or the unsaponifiables, and aspartate aminotransferase activity was significantly increased in the group fed avocado-seed oil. These data suggest that consumption of avocado oil extracted from intact fruit may cause changes in liver metabolism.

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

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    Bouwens, L.; Knook, D.L.; Wisse, E.

    1986-06-01

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

  1. 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].

  2. Excretion of fetal biliverdin by the rat placenta-maternal liver tandem.

    Science.gov (United States)

    Briz, Oscar; Macias, Rocio I R; Perez, Maria J; Serrano, Maria A; Marin, Jose J G

    2006-03-01

    Fetal liver immaturity is accompanied by active heme catabolism. Thus fetal biliary pigments must be excreted toward the mother by the placenta. To investigate biliverdin handling by the placenta-maternal liver tandem, biliverdin-IXalpha was administered to 21-day pregnant rats through the jugular vein or the umbilical artery of an in situ perfused placenta. Jugular administration resulted in the secretion into maternal bile of both bilirubin and biliverdin (3:1). However, when biliverdin was administered to the placenta, most of it was transformed into bilirubin before being transferred to the maternal blood. Injecting Xenopus laevis oocytes with mRNA from rat liver or placenta enhanced their ability to take up biliverdin, which was inhibited by estradiol 17beta-d-glucuronide. The expression of three OATP isoforms in this system revealed that they have a varying degrees of ability to transport biliverdin (Oatp1/1a1 > Oatp2/1a4 > Oatp4/1b2). The abundance of their mRNA in rat trophoblast was Oatp1/1a1 > Oatp4/1b2 > Oatp2/1a4. The expression of biliverdin-IXalpha reductase in rat placenta was detected by RT-PCR/sequencing and Western blot analysis. The relative abundance of biliverdin-IXalpha reductase mRNA (determined by real-time quantitative RT-PCR) was fetal liver > placenta > maternal liver. Common bile duct ligation in the last week of pregnancy induced an upregulation of biliverdin-IXalpha reductase in maternal liver but had no effect on fetal liver and placenta. In conclusion, several members of the OATP family may contribute to the uptake of fetal biliverdin by the rat placenta. Before being transferred to the mother, biliverdin is extensively converted into bilirubin by biliverdin-IXalpha reductase, whose expression is maintained even though bilirubin excretion into maternal bile is impaired.

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

    Directory of Open Access Journals (Sweden)

    DongLiang Li

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

  4. Dietary Egg Yolk Supplementation Improves Low-Protein-Diet-Induced Fatty Liver in Rats.

    Science.gov (United States)

    Erami, Kazuo; Tanaka, Yasutake; Kawamura, Sayaka; Miyago, Motonori; Sawazaki, Ai; Imaizumi, Katsumi; Sato, Masao

    2016-01-01

    Egg yolk is an important source of nutrients and contains different bioactive substances. In the present study, we studied the benefits of egg yolk in preventing low-protein-diet-induced fatty liver in rats. Rats were fed the following diets, which were based on the AIN-76 formula, for 2 wk: an adequate-protein diet containing 20% casein (C), a low-protein diet containing 5% casein (LP-C), a low-protein diet supplemented with 12.5% egg yolk (LP-EY), and a low-protein diet supplemented with 4.1% egg yolk oil (LP-EYO). The low-protein diets were adjusted to contain 4.13% protein and 4.7% lipids. The LP-C diet resulted in a greater increase in the liver trigriceride (TG) and the vacuolation and a greater decrease in the serum TG and free fatty acid (FFA) than did the C diet. These deviations in the serum and liver TG, serum FFA levels and the liver histopathology were corrected in rats fed the LP-EY diet but not in those fed the LP-EYO diet. Compared to rats fed the LP-C diet, although the activities of lipogenesis-related enzymes (fatty acid synthase, glucose-6-phosphate dehydrogenase, and malic enzyme) decreased in rats fed both of the LP-EY and LP-EYO diets, the level of the microsomal TG transfer protein (MTP) increased only in rats fed the LP-EY diet. Collectively, these results suggest that dietary egg yolk supplementation decreases the LP diet-induced accumulation of TG in the liver by increasing transport of TG in the liver, and egg yolk oil alone is not sufficient enough to bring about these benefits.

  5. Biochemical effects on the liver and kidney of rats administered ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-18

    Aug 18, 2008 ... in renal disease, malnutrition, albuminuria and terminal liver failure. Although the concentration of the serum albumin is reduced in severe liver diseases, that of the globulins is usually increased so that the total protein concentration is rarely low. Reduction in serum proteins observed in the present work ...

  6. Unbound liver concentration is the true inhibitor concentration that determines cytochrome P450-mediated drug-drug interactions in rat liver.

    Science.gov (United States)

    Iwasaki, Shinji; Hirabayashi, Hideki; Funami, Miyuki; Amano, Nobuyuki

    2017-06-01

    1. In order to identify the best inhibitor concentration for the accurate prediction of magnitude of a hepatic cytochrome P450 (CYP)-mediated drug-drug interaction (DDI), the DDI between nifedipine, the CYP substrate probe, and fluconazole, ketoconazole, or ritonavir, the CYP inhibitors, in in situ rat liver perfusion system and rats were investigated. 2. In in situ system, the intrinsic clearance (CLint) of nifedipine was decreased after co-infusion of the CYP inhibitors. The decrease in in situ CLint of nifedipine was most comparable to that in in vitro CLint in rat liver microsomes calculated by using the unbound liver concentrations of inhibitors ([I]liver,u). The ratios of unbound liver concentration to unbound hepatic vein concentration (Kp,uu) of ketoconazole and ritonavir were 4.0-8.0 and 18.4-21.1, suggesting a concentrative uptake of them into liver. 3. In rats, the DDI effects of orally administered nifedipine with constant infusion of the inhibitors were investigated. The most accurate prediction of magnitude of DDI was achieved when [I]liver,u was applied as the inhibitor concentration. 4. These results indicated that [I]liver,u is the most reliable inhibitor concentration for CYP-mediated DDI and it is necessary to consider the concentrative uptake of inhibitors into liver for the quantitative prediction of DDI.

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

    Directory of Open Access Journals (Sweden)

    El-Kabany Hanan

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Grønbæk, Henning

    2013-01-01

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

  9. Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury

    Science.gov (United States)

    Amersi, Farin; Buelow, Roland; Kato, Hirohisa; Ke, Bibo; Coito, Ana J.; Shen, Xiu-Da; Zhao, Delai; Zaky, Joseph; Melinek, Judy; Lassman, Charles R.; Kolls, Jay K.; Alam, J.; Ritter, Thomas; Volk, Hans-Dieter; Farmer, Douglas G.; Ghobrial, Rafik M.; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy W.

    1999-01-01

    We examined the effects of upregulation of heme oxygenase-1 (HO-1) in steatotic rat liver models of ex vivo cold ischemia/reperfusion (I/R) injury. In the model of ischemia/isolated perfusion, treatment of genetically obese Zucker rats with the HO-1 inducer cobalt protoporphyrin (CoPP) or with adenoviral HO-1 (Ad-HO-1) significantly improved portal venous blood flow, increased bile production, and decreased hepatocyte injury. Unlike in untreated rats or those pretreated with the HO-1 inhibitor zinc protoporphyrin (ZnPP), upregulation of HO-1 by Western blots correlated with amelioration of histologic features of I/R injury. Adjunctive infusion of ZnPP abrogated the beneficial effects of Ad-HO-1 gene transfer, documenting the direct involvement of HO-1 in protection against I/R injury. Following cold ischemia/isotransplantation, HO-1 overexpression extended animal survival from 40% in untreated controls to about 80% after CoPP or Ad-HO-1 therapy. This effect correlated with preserved hepatic architecture, improved liver function, and depressed infiltration by T cells and macrophages. Hence, CoPP- or gene therapy–induced HO-1 prevented I/R injury in steatotic rat livers. These findings provide the rationale for refined new treatments that should increase the supply of usable donor livers and ultimately improve the overall success of liver transplantation. J. Clin. Invest. 104:1631–1639 (1999). PMID:10587527

  10. Primary cultures of endothelial cells of the rat liver: a model for ultrastructural and functional studies.

    Science.gov (United States)

    de Leeuw, A M; Barelds, R J; de Zanger, R; Knook, D L

    1982-01-01

    A new isolation and purification procedure for endothelial cells of the rat liver and the conditions for large scale survival of these cells in maintenance culture are reported. Cells isolated by this new method and cultured with homologous rat serum on a collagen matrix show the restoration of several ultrastructural characteristics typical of rat liver endothelial cells in situ, including the broad cytoplasmic extensions that contain the sieve plates. These fenestrated cytoplasmic projections, which cover the liver sinusoids in vivo, are well preserved and are reformed in a manner reminiscent of the situation in situ. Reformation of specific membrane receptors is indicated by the reappearance of the capacity to take up horseradish peroxidase by adsorptive endocytosis, a characteristic that is lost during the cell isolation procedure. From the results obtained in this study, maintenance culture of rat liver endothelial cells seems to be a promising system for studying the regulation of pore size of the fenestrated sieve plates by alcohol and certain hormones, for studying the interaction of endothelial cells with other liver cells and tumor cells, and for studying the mechanisms of adsorptive endocytosis.

  11. Persistent gene expression in rat liver in vivo by repetitive transfections using HVJ-liposome.

    Science.gov (United States)

    Hirano, T; Fujimoto, J; Ueki, T; Yamamoto, H; Iwasaki, T; Morisita, R; Sawa, Y; Kaneda, Y; Takahashi, H; Okamoto, E

    1998-04-01

    Most viral vectors are highly immunogenic and are of limited use for somatic gene therapy that requires repetitive administrations. We have developed a highly efficient gene transduction procedure useful for repetitive transfections using liposome containing hemagglutinating virus of Japan (HVJ-liposome). The Escherichia coli beta-galactosidase (beta-gal) gene was embodied in HVJ-liposome, and introduced directly into the caudal lobe of rat liver that was transiently isolated from a systemic circulation. A 116 kDa beta-gal protein was detected in transfected rat liver tissues by Western blot analysis and it was expressed in more than two-thirds of the liver by histological staining. It was found that the transfection efficiency was not affected by repetitive transfections. In support of these findings, antibody response to HVJ-liposome detected in the rat sera was weak and transient. Furthermore, cytotoxic T lymphocytes were not elicited against autologous rat hepatocytes that were transfected in vivo using HVJ-liposome. Thus, our results demonstrate that the isolation of a target liver from systemic circulation and the direct administration of foreign genes using HVJ-liposomes are useful for high gene transduction and persistent gene expression in the liver.

  12. 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.

  13. Trichostatin A protects against intestinal injury in rats with acute liver failure.

    Science.gov (United States)

    Zhang, Qian; Yang, Fan; Li, Xun; Zhang, Hai-Yue; Chu, Xiao-Gang; Zhang, Hong; Wang, Lu-Wen; Gong, Zuo-Jiong

    2016-09-01

    Histone deacetylase (HDAC) inhibitors have been widely applied in the clinic as anticancer drugs against multiple neoplasms and proved their anti-inflammation under different pathology recently. Trichostatin A (TSA) is an HDAC inhibitor specific in class I and II HDAC enzymes. The aim of the present study was to elucidate the protective effects of TSA on acute liver failure (ALF) in rats and its potential mechanism. A total of 18 female Sprague-Dawley rats were separated into control, model, and TSA groups. We used Western blotting to determine the expression of HDACs, inflammatory cytokines, and acetylation of histone in liver and small intestine. The gene expression of inflammatory factors and Cox-2 was detected by a polymerase chain reaction. Colonic motility was assessed by spatiotemporal mapping. Histologic analysis and immunohistochemistry were performed. Intestinal permeability examination and levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were also observed. ALF procedure caused harm to histology of liver and small intestine, increased the intestinal permeability and serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin. It also interrupted the normal organization of colonic motor patterns by hurting enteric nervous system and pacemaker cells. Along with the decrease of inflammatory factors in ALF rats by TSA administration, all the damage to the liver, the small intestine, and the colon was repaired. TSA alleviates the lesion in liver, as well as in small intestine and colon in ALF rats by directly inhibiting inflammatory response. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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.

  15. THE EXCHANGE OF CONNECTIVE TISSUE BIOPOLYMERS IN THE LIVER OF ALLOXAN DIABETIC RATS

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    S. V. Lomaeva

    2013-01-01

    Full Text Available Aim. Study of the exchange of liver and blood plasma biopolymers of alloxan diabetic rats.Materials and Methods. Diabetes mellitus was modeled in rats by single subcutaneous injection of alloxan tetrahydrate (170 mg per100 gbody weight. Blood glucose, glycosylated hemoglobin were controlled and morphometric study of the pancreas was carried out for the verification of the model. A month later, concentration of glycosaminoglycans, free hydroxyproline and the level of hyaluronidase and collagenolytic activity in plasma were determined. The total concentration of collagen, glycosaminoglycans, and their fractions, the level of hyaluronidase and collagenolytic activity in rat liver homogenate were measured.Results. The level of all the parameters of interest in the liver and blood plasma increased on 30 day after alloxan injection, the accumulation of glycosaminoglycans in the liver occurred mainly due to unsulfonated fraction.Conclusion. The development of experimental diabetes in rats is accompanied by activation of both decay processes and synthesis of biopolymers studied. Accumulation of total collagen and glycosaminoglycans was observed in rats’ liver, which probably lead to the fibrosis changes in it.

  16. Aloe vera gel protects liver from oxidative stress-induced damage in experimental rat model.

    Science.gov (United States)

    Nahar, Taslima; Uddin, Borhan; Hossain, Shahdat; Sikder, Abdul Mannan; Ahmed, Sohel

    2013-05-07

    Aloe vera is a semi-tropical plant of Liliaceae family which has a wide range of applications in traditional medicine. In the present study, we sought to investigate the heptaoprotective potential of Aloe vera gel as a diet supplement. To achieve this goal, we have designed in vitro and in vivo experimental models of chemical-induced liver damage using male Sprague-Dawley rat. In the in vitro model, its effect was evaluated on Fenton's reaction-induced liver lipid peroxidation. Co-incubation with gel significantly reduced the generation of liver lipid peroxide (LPO). Next, to see the similar effect in vivo, gel was orally administered to rats once daily for 21 successive days. Following 1 hour of the last administration of gel, rats were treated with intra-peritoneal injection of CCl4. Dietary gel showed significant hepatoprotection against CCl4-induced damage as evident by restoration of liver LPO, serum transaminases, alkaline phosphatase, and total bilirubin towards near normal. The beneficial effects were pronounced with the doses used (400 and 800 mg/kg body weight). Besides, we did not observe any significant drop in serum albumin, globulin as well as total protein levels of gel-administered rats. Histopathology of the liver tissue further supported the biochemical findings confirming the hepatoprotective potential of dietary gel.

  17. Liver oxidation and inflammation in Fa/Fa rats fed glucomannan/spirulina-surimi.

    Science.gov (United States)

    Vázquez-Velasco, Miguel; González-Torres, Laura; López-Gasco, Patricia; Bastida, Sara; Benedí, Juana; Sánchez-Reus, María Isabel; González-Muñoz, María José; Sánchez-Muniz, Francisco J

    2014-09-15

    The effect of high-fat squid-surimi diets enriched in glucomannan or glucomannan-spirulina on lipemia, liver glutathione status, antioxidant enzymes and inflammation biomarkers was determined in Zucker Fa/Fa rats. Groups of eight rats each received for 7weeks the squid-surimi control (C), glucomannan-enriched squid-surimi (G) and glucomannan-spirulina enriched squid-surimi (GS). Liver weight, cytochrome P450 7A1 expression and cholesterolemia were decreased in G and GS vs. C, improving glutathione red-ox index (pspirulina kept those hypocholesterolemic and antioxidant effects but reduced the inflammation observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Interacting effects of L-carnitine and malonyl-CoA on rat liver carnitine palmitoyltransferase.

    OpenAIRE

    Bird, M. I.; Saggerson, E D

    1985-01-01

    Malonyl-CoA significantly increased the Km for L-carnitine of overt carnitine palmitoyltransferase in liver mitochondria from fed rats. This effect was observed when the molar palmitoyl-CoA/albumin concentration ratio was low (0.125-1.0), but not when it was higher (2.0). In the absence of malonyl-CoA, the Km for L-carnitine increased with increasing palmitoyl-CoA/albumin ratios. Malonyl-CoA did not increase the Km for L-carnitine in liver mitochondria from 24h-starved rats or in heart mitoch...

  19. Oxidative stress in rat liver during acute cadmium and ethanol intoxication

    OpenAIRE

    Radosavljević Tatjana; Mladenović Dušan; Ninković Milica; Vučević Danijela; Boričić Ivan; Ješić-Vukićević Rada; Šljivančanin Tamara; Lopičić Srđan; Todorović Vera

    2012-01-01

    The aim of our study was to investigate the effects of binge drinking on prooxidant/antioxidant system in rat liver in acute cadmium (Cd) intoxication. In experiment male Wistar rats were used and divided into following groups: 1. control, 2. ethanol-treated group, in five subsequent doses of 2 g/kg administered by orogastric tube, 3. Cd-treated group in a single dose of 2.5 mg/kg intraperitoneally, 4. group that received Cd 12 hours after the last dose of ethanol. Blood and liver sampl...

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

    Science.gov (United States)

    Nedoshytko, Kh Iu

    2013-01-01

    The state of antioxidant system and fatty acid composition of lipids in the liver tissues of rats of different sex at the ethanol and tetracycline action and at the influence of biologically active additives (BAA) "Alpha + Omega" at a dose of 0.5 mg/kg b.w. per os was investigated. It was found that the contet of lipid peroxidation products in the liver was increased at the action of 40% ethanol at a dose of 7 ml/kg b.w. per os and tetracycline--500 mg/kg and more profound at their joint using. However, the content of diene conjugates was stronger increased in the liver of females at the action of ethanol, while in the liver of males at the action of tetracycline (P glutathione content by 39 and 38% (P ethanol and tetracycline and more profound at their joint usage (P ethanol and tetracycline unidirectionally changed fatty acid composition of total lipids of rat liver, but at the ethanol action the changes were more expressed in females while at the tetracycline action in males. The application during 14 days of BAA "Alpha + Omega" to male and female rats with an acute tetracycline damage at subacute ethanol action led to partial normalization of prooxidant-antioxidant system and the relative content of total lipids fatty acids of the liver of both sexes animals.

  1. Bees' honey protects the liver of male rats against melamine toxicity.

    Science.gov (United States)

    El Rabey, Haddad A; Al-Seeni, Madeha N; Al-Solamy, Suad M

    2013-01-01

    The protective effect of natural bees' honey to the liver of male albino rats against melamine toxicity was studied. Melamine supplementation at a dose of 20000 ppm in the diet for 28 days induced adverse effects on the liver, decreased serum total protein and increased liver enzyme: alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Histological changes of the melamine supplemented group showed necrosis in the hepatic tissues around the central veins of the liver and precipitation of melamine crystals. Treating the male albino rats (that were presupplemented regularly with 20000 ppm melamine) with natural bees' honey at a dose of 2.5 g/kg body weight for 28 days improved both liver functions and increased serum protein. In addition, a positive impact on the shape of the cells after treatment with honey compared to the positive melamine supplemented group was observed. In conclusion, the results of this study revealed that the use of natural bees' honey has the ability to protect the liver of rats against the toxic effects of melamine.

  2. Bees' Honey Protects the Liver of Male Rats against Melamine Toxicity

    Directory of Open Access Journals (Sweden)

    Haddad A. El Rabey

    2013-01-01

    Full Text Available The protective effect of natural bees' honey to the liver of male albino rats against melamine toxicity was studied. Melamine supplementation at a dose of 20000 ppm in the diet for 28 days induced adverse effects on the liver, decreased serum total protein and increased liver enzyme: alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Histological changes of the melamine supplemented group showed necrosis in the hepatic tissues around the central veins of the liver and precipitation of melamine crystals. Treating the male albino rats (that were presupplemented regularly with 20000 ppm melamine with natural bees' honey at a dose of 2.5 g/kg body weight for 28 days improved both liver functions and increased serum protein. In addition, a positive impact on the shape of the cells after treatment with honey compared to the positive melamine supplemented group was observed. In conclusion, the results of this study revealed that the use of natural bees' honey has the ability to protect the liver of rats against the toxic effects of melamine.

  3. Investigation of Metastasis-Related Genes: A Rat Model Mimicking Liver Metastasis of Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Hassan Adwan

    2017-07-01

    Full Text Available Liver is the main target of colorectal cancer (CRC metastasis. Currently, the number of reports is small, which describe changes in gene expression supporting liver metastasis. Here, a rat model was used for analyzing mRNA modulations during liver colonization and compared with available literature. In the model, CC531 rat CRC cells were injected via a mesenteric vein into isogenic WAG/Rij rats and re-isolated at early, intermediate, advanced, and terminal stages of liver colonization. These cells were used for RNA isolation. Microarrays were used for analyzing mRNA profiles of expression. The number of deregulated genes is comparatively large and only part of it has been studied so far. As reported to date, claudins and insulin-like growth factor-binding proteins (IGFBPs were found to be deregulated. The fact that the chosen method is efficient is confirmed by the study of claudins and IGFBPs, which show altered expression in the initial stages of liver colonization and then return to normalcy. In addition, cadherin was described to be downregulated in epithelial–mesenchymal transition models. It can, therefore, be concluded that the models used are helpful in finding genes, which are instrumental for metastatic liver colonization.

  4. [Effect of different approaches of lentiviral vector transfection on target gene expression in rat liver].

    Science.gov (United States)

    Zhao, Yingpeng; Li, Li; Ma, Jingpan; Bai, Jianhua; Liu, Qiyu

    2014-01-01

    To investigate the optimal approach of lentiviral vector transfection for effective delivery of exogenous gene into the liver. The lentiviral vector was delivered via the ileocolic vein of the ileocecus (portal vein group) or via the caudal vein of SD rats. The effect gene transfection into the liver was assessed by observing the expression of green fluorescence protein expression carried by the lentiviral vector, silencing of LXRα mRNA expression mediated by RNA interference, and liver transaminase changes. The efficiency and safety of the two approaches of transfection were evaluated. All the rats receiving lentiviral transfection survived. In the portal vein group, abundant green fluorescence was detected in the liver at 96 h following the transfection and lasted till 14 days, whereas only weak fluorescence was observed in the caudal vein group. The results of RT-PCR demonstrated a significant higher rate of LXRα knock-down in portal vein group than in caudal vein group (0.135∓0.002 vs 0.713∓0.036, Ptransfection into the liver, and puncture from the ileocolic vein of ileocecus can guarantee the survival of rats and improve the transfection efficiency without causing liver injury.

  5. 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.

  6. The comparative influence of anesthetics on the in vitro proton NMR relaxation times in rat liver.

    Science.gov (United States)

    Scheindlin, B; Jacobs, D O; Settle, R G; Wolf, G L; Rombeau, J L

    1985-01-01

    To determine the effect of anesthetics on liver relaxation times in rat, two experiments were performed. In the first experiment, normal and protein-depleted rats underwent total hepatectomy under ether anesthesia or following decapitation. In the second experiment, livers were excised from normal rats under ketamine or pentobarbital anesthesia, or following decapitation. Hepatic T1 and T2 were measured for all animals using a RADX 10 MHz spin analyzer. Ketamine produced T1 values significantly different from decapitation. Ketamine, pentobarbital, and ether in normal animals all produced T2 values significantly different from decapitation. It is apparent that anesthetization of rats prior to in vitro measurement of hepatic relaxation times is not equivalent to decapitation; nor are the anesthetics examined equivalent to one another.

  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. Protective effects of Centella asiatica leaf extract on dimethylnitrosamine-induced liver injury in rats

    Science.gov (United States)

    Choi, Myung-Joo; Zheng, Hong-Mei; Kim, Jae Min; Lee, Kye Wan; Park, Yu Hwa; Lee, Don Haeng

    2016-01-01

    Oxidative stress in liver injury is a major pathogenetic factor in the progression of liver damage. Centella asiatica (L.) Urban, known in the United States as Gotu kola, is widely used as a traditional herbal medicine in Chinese or Indian Pennywort. The efficacy of Centella asiatica is comprehensive and is used as an anti-inflammatory agent, for memory improvement, for its antitumor activity and for treatment of gastric ulcers. The present study investigated the protective effects of Centella asiatica on dimethylnitrosamine (DMN)-induced liver injury in rats. The rats in the treatment groups were treated with Centella asiatica at either 100 or 200 mg/kg in distilled water (D.W) or with silymarin (200 mg/kg in D.W) by oral administration for 5 days daily following intraperitoneal injections of 30 mg/kg DMN. Centella asiatica significantly decreased the relative liver weights in the DMN-induced liver injury group, compared with the control. The assessment of liver histology showed that Centella asiatica significantly alleviated mass periportal ± bridging necrosis, intralobular degeneration and focal necrosis, with fibrosis of liver tissues. Additionally, Centella asiatica significantly decreased the level of malondialdehyde, significantly increased the levels of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase and catalase, and may have provided protection against the deleterious effects of reactive oxygen species. In addition, Centella asiatica significantly decreased inflammatory mediators, including interleukin (IL)-1β, IL-2, IL-6, IL-10, IL-12, tumor necrosis factor-α, interferon-γ and granulocyte/macrophage colony-stimulating factor. These results suggested that Centella asiatica had hepatoprotective effects through increasing the levels of antioxidant enzymes and reducing the levels of inflammatory mediators in rats with DMN-induced liver injury. Therefore, Centella asiatica may be useful in preventing liver damage. PMID:27748812

  9. Tocotrienols Reverse Cardiovascular, Metabolic and Liver Changes in High Carbohydrate, High Fat Diet-Fed Rats

    OpenAIRE

    Weng-Yew Wong; Hemant Poudyal; Leigh C. Ward; Lindsay Brown

    2012-01-01

    Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carboh...

  10. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats

    OpenAIRE

    Demir, Şule; Ünübol, Mustafa; Aypak, Serap Ünübol; İpek, Emrah; Aktaş, Serdar; Ekren, Gamze Sevri; Yılmaz, Murat; Tunca, Recai; Güney, Engin

    2016-01-01

    It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD) pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA) for ...

  11. Cell Kinetics of Regenerating Liver After 70% Hepatectomy in Rats - 2-Color Flow Cytometric Analysis

    OpenAIRE

    Tamura, Jun; Tanaka, Junji; Fujita, Ken-Ichi; Yoshida, Masanori; Kasamatsu, Takayuki; Arii, Shigeki; Tobe, Takayoshi

    1992-01-01

    Two-color flow cytometric (FCM) analysis using anti-bromodeoxyuridine (BrdU) monoclonal antibody (MoAb) was used to investigate the cell kinetics of regenerating liver after 70% partial hepatectomy in rats. Three peaks were seen in DNA histograms of rat hepatocyte nuclei, corresponding to diploid(2c), tetraploid(4c), and octaploid(8c). These proportions changed in the course of regeneration which were clearly demonstrated by DNA histograms using flow cytometry. The proportion of d...

  12. Ring-Oxidative Biotransformation and Drug Interactions of Propofol in the Livers of Rats

    Science.gov (United States)

    Tai, Yu-Ting; Lin, Yi-Ling; Chang, Chia-Chen; Cherng, Yih-Giun; Don, Ming-Jaw; Chen, Ruei-Ming

    2015-01-01

    Propofol, an intravenous anesthetic agent, is widely used for inducing and maintaining anesthesia during surgical procedures and for sedating intensive care unit patients. In the clinic, rapid elimination is one of the major advantages of propofol. Meanwhile, the biotransformation and drug interactions of propofol in rat livers are still little known. In this study, we evaluated the ring-oxidative metabolism of propofol in phenobarbital-treated rat livers and possible drug interactions. Administration of phenobarbital to male Wistar rats significantly increased levels of hepatic cytochrome P450 (CYP) 2B1/2 and microsomal pentoxyresorufin O-dealkylase (PROD) activity. Analyses by high-performance liquid chromatography and liquid chromatography mass spectroscopy revealed that propofol was metabolized by phenobarbital-treated rat liver microsomes into 4-hydroxypropofol. In comparison, PROD activity and 4-hydroxy-propofol production from propofol metabolism were suppressed by orphenodrine, an inhibitor of CYP2B1/2, and a polyclonal antibody against rat CYP2B1/2 protein. Furthermore, exposure of rats to propofol did not affect the basal or phenobarbital-enhanced levels of hepatic CYP2B1/2 protein. Meanwhile, propofol decreased the dealkylation of pentoxyresorufin by phenobarbital-treated rat liver microsomes in a concentration-dependent manner. Taken together, this study shows that rat hepatic CYP2B1/2 plays a critical role in the ring-oxidative metabolism of propofol into 4-hydroxypropofol, and this anesthetic agent can inhibit CYP2B1/2 activity without affecting protein synthesis. PMID:25710017

  13. 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. .

  14. Effect of patulin on the kinetic properties of the enzyme aldolase studied in rat liver.

    Science.gov (United States)

    Sakthisekaran, D; Shanmugasundaram, E R

    1990-01-01

    The toxic nature of the secondary metabolite has been studied in rats. Changes in the concentration of a few key enzymes in carbohydrate metabolism have also been studied. In this, liver aldolase concentration was found to be significantly lowered. Since aldolase is one of the important bifunctional enzymes of glycolysis, it has been isolated and purified and studied on its kinetic properties were made. The kinetic studies did not show any significant variations in the properties of liver aldolase of normal and patulin treated animals. These results suggest that most probably, patulin toxicosis inhibits the biosynthesis of liver aldolase.

  15. 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

  16. Nonlinear disposition kinetics of a novel antifolate, MX-68, in rats.

    Science.gov (United States)

    Han, Y H; Kato, Y; Sugiyama, Y

    1999-10-01

    The excretion and tissue distribution kinetics of a novel antifolate, MX-68, were evaluated under conditions of a continuous steady-state infusion in Sprague-Dawley rats (SDRs). The biliary excretion clearance defined with respect to the hepatic concentration (CL(bile, h)) was much lower in Eisai hyperbilirubinemic rats with a hereditary deficiency in canalicular multispecific organic anion transporter than that in SDRs, suggesting the involvement of canalicular multispecific organic anion transporter in its transport across the bile canalicular membrane. The CL(bile, h) in SDRs increased as the infusion rate increased; this can be largely explained by saturation of the intracellular binding of MX-68. On the other hand, the urinary excretion clearance defined with respect to the renal concentration (CL(urine, k)) was comparable for the two strains but showed an increase and subsequent decrease as the renal concentration increased. This nonlinear profile was also found even when the CL(urine, k) was normalized by the unbound fraction in kidney. Therefore, this kinetic profile represents the saturation of both reabsorption and secretion. Reabsorption of MX-68 in kidney was supported by its saturable transport by renal brush border membrane vesicles at an inward H(+) gradient. The liver-to-plasma unbound concentration ratio decreased as the steady-state plasma concentration increased, suggesting that MX-68 is taken up by a saturable mechanism or mechanisms. Thus, the saturation of transport systems across several plasma membranes and intracellular binding in both the liver and kidney produce the nonlinear disposition of MX-68.

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

    OpenAIRE

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

    2014-01-01

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

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

    Lifescience Database Archive (English)

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

  19. Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats

    Science.gov (United States)

    Davidson, Alec J.; Stokkan, Karl-Arne; Yamazaki, Shin; Menaker, Michael

    2002-01-01

    The mammalian Per1 gene is an important component of the core cellular clock mechanism responsible for circadian rhythms. The rodent liver and other tissues rhythmically express Per1 in vitro but typically damp out within a few cycles. In the liver, the peak of this rhythm occurs in the late subjective night in an ad lib-fed rat, but will show a large phase advance in response to restricted availability of food during the day. The relationship between this shift in the liver clock and food-anticipatory activity (FAA), the circadian behavior entrained by daily feeding, is currently unknown. Insulin is released during feeding in mammals and could serve as an entraining signal to the liver. To test the role of insulin in the shift in liver Per1 expression and the generation of FAA, per-luciferase transgenic rats were made diabetic with a single injection of streptozotocine. Following 1 week of restricted feeding and locomotor activity monitoring, liver was collected for per-luc recording. In two separate experiments, FAA emerged and liver Per1 phase-shifted in response to daytime 8-h food restriction. The results rule out insulin as a necessary component of this system.

  20. Effect of endotoxin tolerance on drug hepatotoxicity: amelioration of taurolithocholate cholestasis in the perfused rat liver.

    Science.gov (United States)

    Utili, R; Adinolfi, L E; Gaeta, G B; Tripodi, M F; Alvaro, D

    1987-01-01

    Induction of endotoxin tolerance may cause resistance not only to endotoxin itself but also to the hepatotoxic effects of other membrane-active agents. To further study this effect, we tested whether endotoxin tolerance could ameliorate the adverse effects of taurolithocholate (TLCA) which causes cholestasis by altering liver plasma membrane organization. Isolated perfused rat livers from endotoxin-tolerant rats had a lower basal bile flow than control livers. However, a bolus addition of TLCA at 3 X 10(-5) or 5 X 10(-5) M in the perfusate caused a marked and prolonged decrease of bile flow in controls, but only a transient and significantly less pronounced diminution of bile flow in endotoxin-tolerant livers. Likewise, TLCA caused a significantly lower alteration of hepatocyte membrane permeability, as measured by sucrose permeability studies, in endotoxin-tolerant livers than in controls. Analysis of bile acid composition of bile from endotoxin-tolerant livers demonstrated that they excreted greater amounts of total bile acids, in particular TLCA and taurocholate, than controls. These results demonstrated a protective effect of endotoxin-tolerance against TLCA toxicity which may result from an altered interaction of TLCA with liver membranes and an increased clearance of TLCA.

  1. Oxidative stress in rat liver during acute cadmium and ethanol intoxication

    Directory of Open Access Journals (Sweden)

    Radosavljević Tatjana

    2012-01-01

    Full Text Available The aim of our study was to investigate the effects of binge drinking on prooxidant/antioxidant system in rat liver in acute cadmium (Cd intoxication. In experiment male Wistar rats were used and divided into following groups: 1. control, 2. ethanol-treated group, in five subsequent doses of 2 g/kg administered by orogastric tube, 3. Cd-treated group in a single dose of 2.5 mg/kg intraperitoneally, 4. group that received Cd 12 hours after the last dose of ethanol. Blood and liver samples were collected for determination of oxidative stress parameters, 24 hours after treatment. When administered in combination, ethanol and Cd induced a more pronounced increase in serum and liver malondialdehyde level than either of these substances alone (p<0.01. Liver manganese superoxide dismutase (MnSOD activity was increased both in ethanol and Cd-treated group (p<0.01, while liver copper/zinc superoxide dismutase (Cu/ZnSOD activity was elevated in Cd group only. However, when administered in combination, ethanol and Cd induced a more pronounced decrease in liver MnSOD and Cu/ZnSOD activity 24 hours after treatment (p<0.01. Based on our study, it can be concluded that ethanol may act sinergistically with Cd in inducing lipid peroxidation and reduction in liver SOD activity.

  2. Transplantation of umbilical cord mesenchymal stem cells via different routes in rats with acute liver failure.

    Science.gov (United States)

    Zheng, Sheng; Yang, Juan; Yang, Jinhui; Tang, Yingmei; Shao, Qinghua; Guo, Ling; Liu, Qinghua

    2015-01-01

    This study aimed to compare the therapeutic efficacy of transplantation of human umbilical cord mesenchymal stem cells (hUCMSC) in different routes in acute hepatic failure (ALF) in rats. hUCMSCs were isolated and identified by detection of surface antigens via flow cytometry. In T group and H group, ALF rats received hUCMSC transplantation through the tail vein and intrahepatic injection, respectively. In hUCMSC group, healthy rats received hUCMSCs transplantation via the tail vein. In ALF group, rats received injection of normal saline through the tail vein. The TBil and ALT in ALF rats with and without transplantation were significantly higher than in healthy rats (Pcells, and liver pathology was improved in T group and H group as compared to ALF group. At 3 d after transplantation, CK18 expression was detectable in both H group and T group. At 1 w and 2 w, the mRNA expressions of CK8, CK18 and AFP in H group and T group were significantly different from those in ALF group (Pstem cells were comparable between H group and T group (P>0.05). hUCMSCs transplantation can improve the liver function and promote the liver repair following ALF. hUCMSCs transplantation via tail vein has similar therapeutic efficacy to that through intrahepatic injection.

  3. Ischemic Postconditioning Assessment in the Liver of Rats Undergoing Mesenteric Ischemia and Reperfusion.

    Science.gov (United States)

    dos Santos, Carlos Henrique Marques; Aydos, Ricardo Dutra; Nogueira, Ed; Miiji, Luciana Nakao Odashiro; Cassino, Pedro Carvalho; Alves, Isadora Ishaq; Calheiros, Nádia Meneguesso; Garcia, Milena

    2016-01-01

    Ischemic postconditioning is a method that shows evidence of efficacy in minimizing reperfusion injury; however, its effectiveness in preventing injuries in distant organs is still unknown, especially in those who have undergone mesenteric ischemia and reperfusion. To evaluate the effect of ischemic postconditioning in preventing reperfusion injury in the liver of rats submitted to mesenteric ischemia and reperfusion, comparing two different methods of ischemic postconditioning. 30 Wistar male rats were used, distributed into three groups: Group A: Ten rats submitted to intestinal ischemia for 30 minutes followed by reperfusion for 60 minutes; Group B: Ten rats subjected to ischemia and reperfusion; after ischemia, two cycles of reperfusion (two minutes each) interleaved with two cycles of ischemia (two minutes each); and Group C: Ten rats subjected to ischemia and reperfusion; after ischemia, four cycles of reperfusion (30 seconds each) interspersed with four cycles of ischemia (30 seconds each). After the experiment, the left lobe of the liver was resected for subsequent histological analysis, using the following classification: grade 1 - centrilobular congestion; grade 2 - centrilobular congestion with some degeneration of hepatocytes in one or two central veins; and grade 3 - multifocal centrilobular congestion and degeneration of portal hepatocytes. The mean degree of liver damage found was 1.8 in group A, 1.7 in group B and 1.3 in group C. There was no statistically significant difference between the groups. Ischemic postconditioning was unable to minimize reperfusion injury in rats undergoing mesenteric ischemia and reperfusion.

  4. 31P-NMR SPECTROSCOPY OF RAT LIVER DURING SIMPLE STORAGE OR CONTINUOUS HYPOTHERMIC PERFUSION1

    Science.gov (United States)

    Rossaro, Lorenzo; Murase, Noriko; Caldwell, Cary; Farghali, Hassan; Casavilla, Adrian; Starzl, Thomas E.; Ho, Chien; Van Thiel, David H.

    2010-01-01

    SUMMARY The ATP content and intracellular pH (pHi)3 of isolated rat liver before, during, and after cold preservation in either UW-lactobionate (UW, n=10) or Euro-Collins (EC, n=8) solutions were monitored using phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. The 31P-NMR spectra were obtained on a 4.7-Tesla system operating at 81 MHz. Fructose metabolism, liver enzyme release, O2 consumption, and rat survival after liver transplantation were also evaluated. During simple cold storage (SCS), the ATP level declined to undetectable levels with both preservation solutions while the pHi declined to approximately 7.0. In contrast, during continuous hypothermic perfusion (CHP), hepatic ATP levels remained measurable during the 24-hour EC preservation and actually increased significantly (p>0.01) during UW preservation. After reperfusion at 37°C with Krebs-lactate, the SCS livers treated with EC differed significantly from the UW livers in terms of their ATP and pHi as well as their response to a fructose challenge. In contrast, livers undergoing CHP demonstrated similar behaviors with both solutions. These results demonstrate an increase in the hepatic ATP content during CHP which occurs with UW but is not seen with EC. On the other hand, only livers that were simply stored with UW achieved significant survival after transplant, while CHP livers were affected by vascular damage as demonstrated by fatal thrombosis after transplant. These data suggest that ATP content is not the only determinant of good liver function although a system of hypothermic perfusion might further improve liver preservation efficacy should injury to vascular endothelium be avoided. PMID:1402332

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Hepatoprotective efficacy of gallic acid during Nitrosodiethylamine-induced liver inflammation in Wistar rats

    Directory of Open Access Journals (Sweden)

    Uzma Latief

    2016-08-01

    Full Text Available Gallic acid (GA, a popular phenolic acid is found in gallnuts, grapes, pomegranates, tea and oak bark. It possesses anti-cancer, anti-bacterial, anti-depressant, anti-asthmatic and anti-obesity effects. N′-Nitrosodiethylamine (NDEA is a well-known hepatotoxin, carcinogen and mutagen. In this study, we have examined the hepatoprotective effect of gallic acid against liver inflammation induced by NDEA in Wistar rats. Hepatic damage in the animals was induced by 10 ml kg−1 b.wt of 1% NDEA (i.p. solution in normal saline once in a week. Another group received GA supplement (i.p. in 100 mg kg−1 b.wt wk−1. Animals belonging to control group were administered equal amounts of saline or GA. LPO, SOD and membrane-bound ATPase (Ca2+- and Mg2+-ATPase activities were determined in liver homogenate of control and treated rats. Alterations in liver architecture were assessed by H&E and Masson’s trichrome stainings of 5 μm thick liver sections. Immunohistochemistry (IHC was performed to localize the inflammatory marker, Cyclooxygenase-2 (COX-2. Our results demonstrate a significant increase in malondialdehyde, and decrease in SOD and ATPases (Ca2+/Mg2+ in NDEA-treated rats. Histopathology data showed inflammation, activated HSCs, deposition of collagen, periportal as well as bridging fibrosis in NDEA-treated liver specimens. Immunohistochemistry of NDEA-treated liver sections exhibited COX-2 positive cells. Gallic acid supplement revert the hepatic functioning in rats injured with NDEA probably by inducing Nrf2-mediated antioxidant enzymes and attenuating the inflammatory mediators COX-2 through NF-κB inhibition pathway. Therefore, gallic acid supplement may be a useful promising bioagent in combating liver injury.

  7. Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition.

    Science.gov (United States)

    Wu, Hao; Qiu, Yong; Shu, Ziyang; Zhang, Xu; Li, Renpeng; Liu, Su; Chen, Longquan; Liu, Hong; Chen, Ning

    2016-12-01

    To explore hepatoprotective role and underlying mechanisms of Trillium tschonoskii Maxim (TTM), 36 rats were randomly divided into control, CCl4-induced liver injury model, and biphenyl dimethyl dicarboxylate (DDB) and low-, moderate-, and high-dose TTM treatment groups. After CCl4-induced model establishment, the rats from DDB and TTM groups were administrated with DDB at 0.2 g/kg per day and TTM at 0.1, 0.5, and 1.0 g/kg per day, while the rats from control and model groups were administrated with saline. After 5 days of treatments, all rats were sacrificed for determining serum ALT and AST levels and liver index, examining histopathological changes in liver through HE and TUNEL staining, and evaluating TNF-α and IL-6 mRNA expression by real-time PCR, and caspase-3, Bcl-2, and Bax expression by Western blot. Results indicated that CCl4 could induce acute liver injury and abnormal liver function in rats with obvious hepatomegaly, increased liver index, high ALT and AST levels, up-regulated TNF-α and IL-6, and overexpressed Bax and caspase-3. However, DDB and TTM could execute protective role in CCl4-induced liver injury in rats through reducing ALT and AST levels, rescuing hepatomegaly, down-regulating inflammatory factors and inhibiting hepatocyte apoptosis in a dose-dependent manner. Therefore, TTM has obvious protective role in CCl4-induced liver injury of rats through inhibiting hepatocyte apoptosis.

  8. Histochemical studies of the effects of monosodium glutamate on the liver of adult wistar rats.

    Science.gov (United States)

    Eweka, Ao; Igbigbi, Ps; Ucheya, Re

    2011-01-01

    Monosodium glutamate (MSG) is a commonly used food additive and there is growing concern that excitotoxins such as MSG play a critical role in the development of several hepatic disorders. The histochemical effect of monosodium glutamate was investigated on the liver of adult Wistar rats. Adult male Wistar rats (n = 24), with an average weight of 230 g were randomly assigned into two treatment groups, (A & B) (n=16) and Control (C) (n=8). The rats in the treatment groups (A & B) received 0.04mg/kg and 0.08mg/kg of monosodium glutamate thoroughly mixed with the grower's mash, respectively on a daily basis for forty-two days. The 0.04mg/kg and 0.08mg/kg monosodium glutamate doses were chosen and extrapolated in this experiment based on the previous work done with the additive. The control group (C) received equal amount of feed (Growers' mash) without monosodium glutamate added for the same period. The rats were given water ad libitum. Both the treatment and control rats were sacrificed by cervical dislocation on day forty-three of the experiment. The Liver was carefully dissected out and quickly fixed in Bouin's fluid for histochemical studies, while blood was collected for estimation of total protein, albumin, transaminasese (aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological findings showed changes like dilatation of the central vein, which contained lysed red blood cells, cyto-architectural distortions of the hepatocytes, atrophic and degenerative changes on the liver of the animals that received feed incoporated with monosodium glutamate. Furthermore, the biochemical parameters were significantly higher in the test than control groups (P monosodium glutamate mixed in their feed. These findings showed that monosodium glutamate consumption may have some deleterious effects on the liver of adult Wistar rats at higher doses and by extension may affect the functions of the liver.

  9. The liver and kidney expression of sulfate anion transporter sat-1 in rats exhibits male-dominant gender differences

    OpenAIRE

    Brzica, Hrvoje; Breljak, Davorka; Krick, Wolfgang; Lovrić, Mila; Burckhardt, Gerhard; Burckhardt, Birgitta; Sabolić, Ivan

    2008-01-01

    The sulfate anion transporter (sat-1, Slc26a1) has been cloned from rat liver, functionally characterized, and localized to the sinusoidal membrane in hepatocytes and basolateral membrane (BLM) in proximal tubules (PT). Here, we confirm previously described localization of sat-1 protein in rat liver and kidneys and report on gender differences (GD) in its expression by immunochemical, transport, and excretion studies in rats. The ∼85-kDa sat-1 protein was localized to the sinusoidal membrane ...

  10. Effect of Oyster mushroom in Paracetamol Induced Toxicity of Liver in Wistar albino Rats

    Directory of Open Access Journals (Sweden)

    Afroza Khanam Sumy

    2014-09-01

    Full Text Available Backgroud: Liver is an important metabolic organ. It has wide range of functions including detoxification, storage of glycogen, vitamins A, D and B12, production of several coagulation factors, growth factors such as insulin-like growth factor-1 (IGF-1, angiotensinogen, and biochemicals necessary for digestion (bile. Its damage occurs due to its multidimensional functions, various xenobiotics and oxidative stress leading to distortion of all of its functions. Oyster mushroom which is excellently edible and nutritious has got free radical scavenging activity, and so may be considered as a hepatoprotective agent. Objective: To observe the hepatoprotective effect of Oyster mushroom (Pleurotus florida against paracetamol induced liver damage in Wistar albino rats. Materials and Methods: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC, Dhaka from 1st July 2009 to 30th June 2010. Thirty four Wistar albino rats, aged 90 to 120 days, weighing between 150 to 210 grams were used for the study. After acclimatization for 14 days, they were divided into two groups –– control group (Group A and experimental group (Group B, mushroom-pretreated and paracetamol-treated group. Control group was again subdivided into Group A1 (baseline control group and Group A2 (paracetamol-treated control group. Animals of all groups received basal diet for 30 consecutive days. In addition, Group A1 rats received propylene glycol (2 mL/kg body weight orally only on 30th day, Group A2 rats received single dose of paracetamol suspension (750 mg/kg body weight orally only on 30th day and Group B rats received mushroom extract (200 mg/kg body weight orally for 30 consecutive days and paracetamol suspension (750 mg/kg body weight orally only on 30th day. All the animals were sacrificed on 31st day. Then liver specimens were collected. Histology of liver was done by using standard laboratory procedure. Statistical

  11. 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.

  12. Gender Different Response to Immunonutrition in Liver Cirrhosis with Sepsis in Rats

    Directory of Open Access Journals (Sweden)

    Chi-Yi Chen

    2012-03-01

    Full Text Available Females with sepsis have a better prognosis than males, while those of both genders with cirrhosis have a high mortality. Impaired immunity accompanies liver cirrhosis. The potential association between sex and immunologic response of cirrhotic rats in sepsis following immunonutrition was investigated. One hundred and forty-three rats were randomly divided into groups. Liver cirrhosis was produced by weekly feeding of CCl4 for 8 weeks. Among them, 24 male and 19 female underwent castration one month before studying. The rats were fed with either immune enhancing diet or control diet for five days, then sepsis was induced with cecal ligation and two holes puncture. Main outcomes included mortality and serum cytokines (IL-1β, 6, and 10. Comparisons were made both within and between genders. Cirrhotic non-castrated male rats showed a significant decrease in mortality (64.1% vs. 32.1%, p = 0.032 with better survival than control diet following immune enhancing diet. Lower mortality of cirrhotic non-castrated female rats was found after immune enhancing diet (69.6% vs. 52.1%, p = 0.365. Cirrhotic castrated male rats showed a lower mortality (44.4% following immune enhancing diet, and cirrhotic castrated female rats also showed significantly lower mortality and better survival than control diet after immune enhancing diet (87.5% vs. 33.3%, p = 0.004. Plasma concentrations of IL-1β were higher in non-oophorectomized female rats fed with control diet compared to immune enhancing diet. Non-orchidectomized males and non-oophorectomized females exhibited similar increases in IL-10 after immune enhancing diet. Our results demonstrated that immunonutrition was more beneficial for male than female cirrhotic rats following sepsis. Though orchidectomy was not found to be more advantageous for the normal male rats in sepsis, immunonutrition seemed to be as important as sex hormone for female rats in sepsis.

  13. Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury

    OpenAIRE

    Amersi, Farin; Buelow, Roland; Kato, Hirohisa; Ke, Bibo; Coito, Ana J.; Shen, Xiu-Da; Zhao, Delai; Zaky, Joseph; Melinek, Judy; Lassman, Charles R.; Kolls, Jay K.; Alam, J.; Ritter, Thomas; Volk, Hans-Dieter; Farmer, Douglas G.

    1999-01-01

    We examined the effects of upregulation of heme oxygenase-1 (HO-1) in steatotic rat liver models of ex vivo cold ischemia/reperfusion (I/R) injury. In the model of ischemia/isolated perfusion, treatment of genetically obese Zucker rats with the HO-1 inducer cobalt protoporphyrin (CoPP) or with adenoviral HO-1 (Ad-HO-1) significantly improved portal venous blood flow, increased bile production, and decreased hepatocyte injury. Unlike in untreated rats or those pretreated with the HO-1 inhibito...

  14. The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease.

    Science.gov (United States)

    King, Adrienne L; Mantena, Sudheer K; Andringa, Kelly K; Millender-Swain, Telisha; Dunham-Snary, Kimberly J; Oliva, Claudia R; Griguer, Corinne E; Bailey, Shannon M

    2016-10-01

    Mitochondrial dysfunction and bioenergetic stress play an important role in the etiology of alcoholic liver disease. Previous studies from our laboratory show that the primary methyl donor S-Adenosylmethionine (SAM) minimizes alcohol-induced disruptions in several mitochondrial functions in the liver. Herein, we expand on these earlier observations to determine whether the beneficial actions of SAM against alcohol toxicity extend to changes in the responsiveness of mitochondrial respiration to inhibition by nitric oxide (NO), induction of the mitochondrial permeability transition (MPT) pore, and the hypoxic state of the liver. For this, male Sprague-Dawley rats were pair-fed control and alcohol-containing liquid diets with and without SAM for 5 weeks and liver hypoxia, mitochondrial respiration, MPT pore induction, and NO-dependent control of respiration were examined. Chronic alcohol feeding significantly enhanced liver hypoxia, whereas SAM supplementation attenuated hypoxia in livers of alcohol-fed rats. SAM supplementation prevented alcohol-mediated decreases in mitochondrial state 3 respiration and cytochrome c oxidase activity. Mitochondria isolated from livers of alcohol-fed rats were more sensitive to calcium-mediated MPT pore induction (i.e., mitochondrial swelling) than mitochondria from pair-fed controls, whereas SAM treatment normalized sensitivity for calcium-induced swelling in mitochondria from alcohol-fed rats. Liver mitochondria from alcohol-fed rats showed increased sensitivity to NO-dependent inhibition of respiration compared with pair-fed controls. In contrast, mitochondria isolated from the livers of SAM treated alcohol-fed rats showed no change in the sensitivity to NO-mediated inhibition of respiration. Collectively, these findings indicate that the hepato-protective effects of SAM against alcohol toxicity are mediated, in part, through a mitochondrial mechanism involving preservation of key mitochondrial bioenergetic parameters and the

  15. Metabolism of aildenafil in vivo in rats and in vitro in mouse, rat, dog, and human liver microsomes.

    Science.gov (United States)

    Li, Yan; Wu, Linan; Gu, Yuan; Si, Duanyun; Liu, Changxiao

    2014-06-01

    Aildenafil, 1-{[3-(6, 7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4, 3-d] primidin-5-yl)-4-ethoxyphenyl] sulfonyl}-cis-3, 5-dimethylpiperazine, a phosphodiesterase type V enzyme inhibitor (PDE5I), is under development for treatment of erectile dysfunction (ED). The purpose of this study was to elucidate metabolism of aildenafil in vivo in rats and in vitro in mouse, rat, dog, and human liver microsomes. Thirty-one phase I metabolites have been found by LTQ/Orbitrap hybrid mass spectrometry in rat urine, faeces, and bile after oral administration. Major biotransformation pathways of aildenafil included N-dealkylation of the piperazine ring, hydroxylation and dehydrogenation, aliphatic hydroxylation and loss of alkyl group of piperazine ring. Minor pathways involved hydroxylation on the phenyl ring, pyrazole N-demethylation, O-deethylation, loss of piperazine ring (cleavage of N-S bond) and dehydrogenation on the piperazine ring. Similar metabolic pathways of aildenafil were observed in the incubations of liver microsomes from mouse, rat, and dog as well as from human. The depletion rate of parent drug in mouse and rat liver microsomes was significantly different from that in human liver microsomes. The cytochrome P450 reaction phenotyping analysis was conducted using isozyme-specific inhibitors. The results indicated that CYP3A was the main isoenzyme involved in oxidative metabolism of aildenafil. Overall, these in vitro and in vivo findings should provide valuable information on possible metabolic behaviours of aildenafil in humans. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Iron bioavailability of rats fed liver, lentil, spinach and their mixtures.

    Science.gov (United States)

    Rewashdeh, Abdullah Y; El-Qudah, Jafar M; Al-Dmoor, Hanee; Al-Qudah, Maisa M; Mamkagh, Amer M; Tarawneh, Khaled A; Hawari, Azmi D; Dababneh, Basem F; Al-Bakheit, Alaa A; Haddad, Moawya A

    2009-02-15

    To study the effects of dietary iron source (basal diet-FeSO4 x 7H2O, liver, lentil, spinach, liver + lentil, liver+spinach and lentil+spinach) on iron bioavailability, fifty-six Albino Sprague Dawley derived male 21 days old rats were fed on iron-deficient diet (7.8 mg Fe kg(-1) diet) and the mentioned seven iron containing diets (40 mg Fe kg(-1) diet) for 10 days. Rats fed liver diet showed higher iron apparent absorption (52.1%), hemoglobin (Hb) gain (0.94 g/100 mL), Hb-iron gain (1.2 mg), Hb-regeneration efficiency (HRE%) (50.8%), relative efficiency of HRE% (106.5%), packed cell volume gain (2.22%) and mean corpuscular hemoglobin concentration (0.64 g dL(-1)). Liver resulted in an increase in these parameters when mixed with lentil and spinach diets. However, rats fed iron free diet showed the higher dry matter absorption.

  17. Dehydroepiandrosterone (DHEA) Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model.

    Science.gov (United States)

    Hakkak, Reza; Bell, Andrea; Korourian, Soheila

    2017-03-20

    Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA) is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on liver steatosis, body weight gain, and serum DHEA, DHEA sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) levels. Female Zucker rats were randomly assigned to either a control diet or a control diet with DHEA supplementation for 155 days. Livers were collected for histological examination. Serum was collected to measure DHEA, DHEA-S, IGF-1, and IGFBP-3. Our results show that DHEA-fed rats had significantly less liver steatosis (p DHEA feeding caused significant decreases (p DHEA and DHEA-S. Our results suggest that DHEA feeding can protect against liver steatosis by reducing body weight gain and modulating serum IGF-1 and IGFBP-3 levels in an obese breast cancer rat model.

  18. 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.

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

    Science.gov (United States)

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

    2016-12-01

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

  20. Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats.

    Science.gov (United States)

    Cachón, Andrés Uc; Quintal-Novelo, Carlos; Medina-Escobedo, Gilberto; Castro-Aguilar, Gaspar; Moo-Puc, Rosa E

    2017-03-04

    Several studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl 4 )-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl 4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl 4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl 4 -induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl 4 -induced liver damage in rats.

  1. Ageratum conyzoides attenuates alcohol induced liver toxicity in male Wistar rats.

    Science.gov (United States)

    Ogunlade, B; Yama, O E; Saalu, L C; Clement, A B

    2013-01-01

    Ageratum conyzoides (AC) is unique for its antioxidant activity and protective role to tissues. However this property is yet to be demonstrated in animals administered toxic alcohol concentrations. To determine the effect of AC extract on the oxidative stress, liver enzymes and histology. Twenty four male rats (190-230 g) were divided into three groups of eight rats. Group A (control) administered distilled water. Group B (ethanol group) received 10 g/kg body weight of ethanol. Group C (ethanol + AC group) were treated with ethanol (as above) and AC (250 mg/kg body weight) concurrently. Total experimental duration was 35 days at the end of which animals were euthanized by cervical dislocation. Liver and blood samples were taken and processed for: microscopic studies, estimation of activities of liver enzymes [alanine aminotransferase (AST), aspartate aminotransferase (ALT) and alkaline phosphatase (ALP)], Malondialdehyde (MDA) and antioxidants [Superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) and Catalase (CAT)] respectively. Compared to control, the rats treated with ethanol had significantly increased liver enzymes and MDA levels but these were decreased in ethanol + AC group compared to the ethanol group. The histologies of concurrent ethanol + AC treated group were similar to control groups. AC protects the liver against alcohol induced damage.

  2. 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

  3. Evidence for two enzymatic pathways for omega-oxidation of docosanoic acid in rat liver microsomes

    NARCIS (Netherlands)

    Sanders, Robert-Jan; Ofman, Rob; Valianpour, Fredoen; Kemp, Stephan; Wanders, Ronald J. A.

    2005-01-01

    We studied the omega-oxidation of docosanoic acid (C22:0) in rat liver microsomes. C22:0 and 22-hydroxy-docosanoic acid (omega-hydroxy-C22:0) were used as substrates, and the reaction products were analyzed by electrospray ionization mass spectrometry. In the presence of NADPH, omega-oxidation of

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

    African Journals Online (AJOL)

    Study on Biochemical Indices of Liver Function Tests of Albino Rats Supplemented with Three. Sources of Vegetable Oils. 1K.E. Imafidon and *2L. .... fixed in 10% neutral formalin, dehydrated embedded in paraffin, sectioned and stained with hematoxylin and eosin. Statistical Analysis. All data were expressed as mean± ...

  5. Effects of Aqueous Stem Extract of Massularia Acuminata on Some Liver Function Indices of Male Rats

    Directory of Open Access Journals (Sweden)

    Musa Toyin Yakubu

    2012-09-01

    Full Text Available Background: Massularia acuminata has been claimed to be used in managingseveral ailments in folk medicine and in some instances substantiated withscientific data. This however has been without recourse to its safety. Therefore,aqueous stem extract of M. acuminata was evaluated for its effects on somefunction indices of the liver of male rats.Methods: Sixty, male rats were grouped into 4 (A, B, C and D such that Group A(control was orally administered 1cm3 of distilled water while those in groups B, Cand D received orally 1 cm3 of extract corresponding to 250, 500 and 1000 mg/kgbody weight respectively. Some biochemical parameters of liver function wereevaluated in the animals after 1, 7 and 21 daily doses.Results: The extract significantly decreased (P<0.05 the activity of alkalinephosphatase in the liver of rats throughout the experimental period. This decreasewas accompanied by corresponding increase in the serum enzyme. In contrast, allthe doses of the extract increased the activities of both the AST and ALT in the liverand serum aspartate aminotransferase and alanine aminotransferase as well asthe concentrations of serum total bilirubin, protein and albumin.Conclusion: This study has revealed that the aqueous stem extract of Massulariaacuminata at the doses of 250-1000 mg/kg body weight hampered the normalfunctioning of the liver of male rats and is therefore not safe for oral consumption atthe doses investigated.

  6. 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

  7. Hepatoprotective activity of cinnamon ethanolic extract against CCI4-induced liver injury in rats.

    Science.gov (United States)

    Eidi, Akram; Mortazavi, Pejman; Bazargan, Maryam; Zaringhalam, Jalal

    2012-01-01

    The inner bark of cinnamon (Cinnamomum zeylanicum L.) is commonly used as a spice and has also been widely employed in the treatment and prevention of disease. The aim of the present study is to evaluate the protective effect of cinnamon bark extract against carbon tetrachloride (CCl4)-induced liver damage in male Wistar rats. Administration with cinnamon extracts (0.01, 0.05 and 0.1 g/kg) for 28 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. In addition, treatment of cinnamon extract resulted in markedly increased the levels of superoxide dismutase and catalase enzymes in rats. The histopathological studies in the liver of rats also supported that cinnamon extract markedly reduced the toxicity of CCl4 and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that cinnamon extract acts as a potent hepatoprotective agent against CCl4 induced hepatotoxicity in rats.

  8. Hepatoprotective activity of cinnamon ethanolic extract against CCI4-induced liver injury in rats

    Science.gov (United States)

    Eidi, Akram; Mortazavi, Pejman; Bazargan, Maryam; Zaringhalam, Jalal

    2012-01-01

    The inner bark of cinnamon (Cinnamomum zeylanicum L.) is commonly used as a spice and has also been widely employed in the treatment and prevention of disease. The aim of the present study is to evaluate the protective effect of cinnamon bark extract against carbon tetrachloride (CCl4)-induced liver damage in male Wistar rats. Administration with cinnamon extracts (0.01, 0.05 and 0.1 g/kg) for 28 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. In addition, treatment of cinnamon extract resulted in markedly increased the levels of superoxide dismutase and catalase enzymes in rats. The histopathological studies in the liver of rats also supported that cinnamon extract markedly reduced the toxicity of CCl4 and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that cinnamon extract acts as a potent hepatoprotective agent against CCl4 induced hepatotoxicity in rats. PMID:27547174

  9. Rat liver dihydroxyacetone-phosphate acyltransferase : Enzyme characteristics and localization studies

    NARCIS (Netherlands)

    Hardeman, D.; Bosch, H. van den

    1988-01-01

    Peroxisomes were isolated from rat liver by pelleting a light mitochondrial (L) fraction over a 30% (w/v) Metrizamide layer. Peroxisomes were recovered as a loose pellet from the bottom of the tube and the purity of the peroxisomal fraction was calculated to be about 90%. The characteristics of

  10. HETEROGENEITY IN SECRETORY RESPONSES OF RAT-LIVER MACROPHAGES OF DIFFERENT SIZE

    NARCIS (Netherlands)

    HOEDEMAKERS, RMJ; MORSELT, HWM; SCHERPHOF, GL; DAEMEN, T

    1995-01-01

    Four subpopulations of hepatic macrophages, differing in size, were isolated from rat liver. The secretion of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E (PGE) and interleukin-1 (IL-1) by freshly isolated as well as cultured cells was studied after in vitro

  11. 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.

  12. The potential role of combined anti-oxidants against cadmium toxicity on liver of rats.

    Science.gov (United States)

    Koyuturk, Meral; Yanardag, Refiye; Bolkent, Sehnaz; Tunali, Sevim

    2007-08-01

    Cadmium (Cd), a widely distributed toxic trace metal, has been shown to accumulate in liver after long- and short-term exposure. Cd (2 mg/kg/day CdCl2) was intraperitoneally given to rats for eight days. Vitamin C (250 mg/kg/day) + vitamin E (250 mg/kg/day) + sodium selenate (0.25 mg/kg/day) were given to rats by oral means. The animals were treated by anti-oxidants one hour prior to treatment with Cd every day. The degenerative changes were observed in the groups given only Cd and anti-oxidants + Cd. Metallothionein (MT) immunoreactivity increased in cytoplasm of hepatocytes of the rats given Cd when compared with controls. In a number of cells with Cd and anti-oxidants treatment, immunoreactivity increase was more than in the group given Cd only and nuclear MT expression was also detected. Cell proliferation was assessed with proliferating cell nuclear antigen (PCNA) immunohistochemistry. PCNA expressions increased in all groups more than in the controls. Anti-oxidants treatment increased cell proliferation. In the animals administered with Cd, an increase in serum aspartate (AST) and alanine (ALT) aminotransferases, liver glutathione (GSH) and lipid peroxidation (LPO) levels were observed. On the other hand, in the rats treated with anti-oxidants and Cd, serum AST and ALT, liver glutathione and LPO levels decreased. As a result, these results suggest that combined anti-oxidants treatment might be useful in protection of liver against Cd toxicity.

  13. Effect of mancozeb-treated lettuce ( Lactuca sativa ) on wistar rat liver

    African Journals Online (AJOL)

    Because mancozeb, ethylene bis-dithiocarbamate, is mainly used, more than five times, during the growth of lettuce (Lactuca sativa), the aim of the present investigation is to evaluate the potential effect of mancozeb-treated lettuce on the rat liver physiology. Mancozeb-treated lettuce and two doses of mancozeb were ...

  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 anesthetize...

  15. Carnitine biosynthesis. Purification of gamma-butyrobetaine hydroxylase from rat liver

    NARCIS (Netherlands)

    Vaz, F. M.; van Gool, S.; Ofman, R.; IJlst, L.; Wanders, R. J.

    1999-01-01

    gamma-Butyrobetaine hydroxylase catalyse the last step in carnitine biosynthesis, the formation of L-carnitine from gamma-butyrobetaine, a reaction dependent on Fe2+, alpha-ketoglutarate, ascorbate and oxygen. Initial attempts to purify the protein from rat liver showed that gamma-butyrobetaine

  16. The Restriction Fragment Map of Rat-Liver Mitochondrial DNA : A Reconsideration

    NARCIS (Netherlands)

    Pepe, G.; Bakker, H.; Holtrop, M.; Bollen, J.E.; Bruggen, E.F.J. van; Cantatore, P.; Terpstra, P.; Saccone, C.

    1977-01-01

    1. Rat-liver mitochondrial DNA (mtDNA) contains at least 8 cleavage sites for the restriction endonuclease Eco RI, 6 for the restriction endonuclease Hind III, 2 for the restriction endonuclease Bam HI and 11 for the restriction endonuclease Hap II. 2. The physical map of the restriction fragments

  17. 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

  18. S-Adenosylmethionine modulates inducible nitric oxide synthase gene expression in rat liver and isolated hepatocytes.

    Science.gov (United States)

    Majano, P L; García-Monzón, C; García-Trevijano, E R; Corrales, F J; Cámara, J; Ortiz, P; Mato, J M; Avila, M A; Moreno-Otero, R

    2001-12-01

    Hepatocellular availability of S-adenosylmethionine, the principal biological methyl donor, is compromised in situations of liver damage. S-Adenosylmethionine administration alleviates experimental liver injury and increases survival in cirrhotic patients. The mechanisms behind these beneficial effects of S-adenosylmethionine are not completely known. An inflammatory component is common to many of the pathological conditions in which S-adenosylmethionine grants protection to the liver. This notion led us to study the effect of S-adenosylmethionine administration on hepatic nitric oxide synthase-2 induction in response to bacterial lipopolysaccharide and proinflammatory cytokines. The effect of S-adenosylmethionine on nitric oxide synthase-2 expression was assessed in rats challenged with bacterial lipopolysaccharide and in isolated rat hepatocytes treated with proinflammatory cytokines. Interactions between S-adenosylmethionine and cytokines on nuclear factor kappa B activation and nitric oxide synthase-2 promoter transactivation were studied in isolated rat hepatocytes and HepG2 cells, respectively. S-Adenosylmethionine attenuated the induction of nitric oxide synthase-2 in the liver of lipopolysaccharide-treated rats and in cytokine-treated hepatocytes. S-Adenosylmethionine accelerated the resynthesis of inhibitor kappa B alpha, blunted the activation of nuclear factor kappa B and reduced the transactivation of nitric oxide synthase-2 promoter. Our findings indicate that the hepatoprotective actions of S-adenosylmethionine may be mediated in part through the modulation of nitric oxide production.

  19. 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.

  20. Homogeneous distribution of phosphofructokinase in the rat liver acinus: a quantitative histochemical study

    NARCIS (Netherlands)

    Frederiks, W. M.; Marx, F.; van Noorden, C. J.

    1991-01-01

    A quantitative histochemical method was developed for the demonstration in rat liver of the activity of phosphofructokinase, one of the enzymes assumed to be rate-limiting for glycolysis. The procedure was based on the reduction of a tetrazolium salt as final electron acceptor and a multistep

  1. A Para-Canalicular Abscess Resembling an Inflamed Chalazion

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    Diamantis Almaliotis

    2013-01-01

    Full Text Available Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis. When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  2. A para-canalicular abscess resembling an inflamed chalazion.

    Science.gov (United States)

    Almaliotis, Diamantis; Nakos, Elias; Siempis, Thomas; Koletsa, Triantafyllia; Kostopoulos, Ioannis; Chatzipantazi, Maria; Karampatakis, Vasileios

    2013-01-01

    Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis). When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  3. Oftalmomiíase como causa de lesão canalicular Ophthalmomyiasis as a cause of canalicular lesion

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    Fabio P. Saraiva

    2005-02-01

    Full Text Available OBJETIVO: Miíase é a invasão de tecido humano pela larva de uma mosca da ordem Díptera. O envolvimento ocular não é comum. Lesões do aparelho lacrimal geralmente estão associadas a traumas e raramente são devidas a infestações parasitárias. O objetivo deste trabalho é relatar um caso de laceração canalicular causado por larva de Dermatobia hominis. DESCRIÇÃO: Criança do sexo feminino, 8 anos de idade, apresentou-se com celulite pré-septal não responsiva a antibioticoterapia. Foi observada uma larva de D. hominis no saco lacrimal. Realizou-se a extração cirúrgica da larva e observou-se lesão do sistema de drenagem lacrimal. COMENTÁRIOS: A infestação parasitária em via lacrimal é rara. A extração cirúrgica da larva é recomendada como tratamento de escolha. Apesar de incomum, a oftalmomiíase deve ser considerada como um diagnóstico diferencial possível em celulites não responsivas ao tratamento convencional, especialmente em áreas endêmicas. Esta é a primeira descrição de lesão do sistema de drenagem lacrimal por larva de D. hominis.OBJECTIVE: Myiasis is the invasion of human tissues by Diptera larvae. Ocular involvement is uncommon. Trauma is the major cause of lacrimal apparatus lesions. However, it is rarely associated with parasitic infestation. The objective of this paper is to report a case of canalicular laceration caused by Dermatobia hominis larva. DESCRIPTION: An eight-year-old girl presented preseptal cellulitis that was refractive to antibiotics. A Dermatobia hominis larva was observed inside the lacrimal sac. Surgical extraction was performed and laceration of the lacrimal drainage system was noted. COMMENTS: Parasitic infection of the lacrimal apparatus is rare. Surgical extraction is the treatment of choice in such cases. Despite being uncommon, ophthalmomyiasis should be considered as a possible diagnosis when cellulitis is not responsive to antibiotics, especially in endemic areas. This is

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

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    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

  5. Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver

    DEFF Research Database (Denmark)

    Sørensen, M; Jensen, B R; Poulsen, H E

    2001-01-01

    of administration of a Brussels sprouts extract on the expression at the mRNA level and/or catalytic activity in rat liver of three phase I enzymes [cytochrome P450-1A2 (CYP1A2),-2B1/2 (CYP2B1/2) and-2E1 (CYP2E1)] and two phase II enzyme [NADPH:quinone reductase (QR) and glutathione S-transferase pi 7 (GSTpi)], all...... previously suggested to be induced by vegetables. We also examined the activity and/or expression of several important antioxidant enzymes: glutathione peroxidase (GPx), catalase and gamma-glutamyl-cysteine synthetase (GCS) and the activity of the repair enzyme 8-oxoguanine DNA glycosylase (OGG1). QR, GPx...... in the liver. Oral administration of an aqueous Brussels sprouts extract for 4 days was found to induce the expression of GST 1.3-fold (P QR 2.6-fold in rat liver (P

  6. The effect of acute ethanol administration on phosphorylethanolamine uptake and metabolism in rat liver slices.

    Science.gov (United States)

    Corazzi, L; Arienti, G; Tirillini, B; Arienti, U G; Porcellati, G; Orlando, P

    1977-08-01

    Double-labelled phosphorylethanolamine with a [32P]//[14IA1 ratio of 1 was incubated in vitro with rat liver slices prepared from control and ethanol-intoxicated rats, and the radioactivity measured at given time intervals in liver ethanolamine, phosphorylethanolamine, phosphatidylethanolamine and phosphatidylcholine. Evidence is presented that after 10 and 15 minutes phosphorylethanolamine enters the slices as an intact molecule, which is directly converted into lipid forms by the Kennedy's pathways. At longer times a hydrolysis of the ester occurs which lowers considerably the theoretical [32P]/[14C]ratio. Fatty liver slices produced by acute ethanol intoxication uptake from the medium more phosphorylethanolamine than controls, and hydrolyze less efficiently than controls the phosphoric ester to ethanolamine and inorganic phosphate.

  7. Effects of pharmaceutical formulations containing thyme on carbon tetrachloride-induced liver injury in rats.

    Science.gov (United States)

    Rašković, Aleksandar; Pavlović, Nebojša; Kvrgić, Maja; Sudji, Jan; Mitić, Gorana; Čapo, Ivan; Mikov, Momir

    2015-12-18

    Herbal supplements are widely used in the treatment of various liver disases, but some of them may also induce liver injuries. Regarding the infuence of thyme and its constituents on the liver, conflicting results have been reported in the literature. The objective of this study was to examine the influence of two commonly used pharmaceutical formulations containing thyme (Thymus vulgaris L.), tincture and syrup, on carbon tetrachloride-induced acute liver injury in rats. Chemical composition of investigated formulations of thyme was determined by gas chromatography and mass spectrometry. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Liver morphology was characterized by light microscopy using routine hematoxylin and eosin staining. Thymol was found to be predominant active constituent in both tincture and syrup. Investigated thyme preparations exerted antioxidant effects in liver by preventing carbon tetrachloride-induced increase of lipid peroxidation. Furthermore, co-treatment with thyme preparations reversed the activities of oxidative stress-related enzymes xanthine oxidase, catalase, peroxidase, glutathione peroxidase and glutathione reductase, towards normal values in the liver. Hepatotoxicity induced by carbon tetrachloride was reflected by a marked elevation of AST and ALT activities, and histopathologic alterations. Co-administration of thyme tincture resulted in unexpected exacerbation of AST and ALT values in serum, while thyme syrup managed to reduce activites of aminotransferases, in comparison to carbon tetrachloride-treated animals. Despite demonstrated antioxidant activity, mediated through both direct free radical scavenging and activation of antioxidant defense mechanisms, thyme preparations could not ameliorate liver injury in rats. Molecular mechanisms of diverse effects of thyme preparations on chemical

  8. Clearance capacity of rat liver Kupffer, endothelial, and parenchymal cells

    NARCIS (Netherlands)

    Praaning-van Dalen, D.P.; Brouwer, A.; Knook, D.L.

    1981-01-01

    The clearance of five radioactively labeled test substances - polyvinylpyrrolidone, colloidal albumin, antimony sulfur colloid, endotoxin, and heparin - by the reticuloendothelial system was studied after i.v. injection of these substances into rats. The participation of parenchymal, Kupffer, and

  9. Chronic effects of cadmium on kidney, liver, testis, and fertility of male rats.

    Science.gov (United States)

    Saygi, S; Deniz, G; Kutsal, O; Vural, N

    1991-12-01

    Male Wistar rats (n:20), at 5 wk of age, were given cadmium in drinking water (10 mg/L water) for 52 wk; 8 males and 20 female rats, as controls, were given tap water. At the end of 28 and 40 wk, some of the cadmium-treated males and control group male rats were sacrificed for the histopathological examination of testis, kidney, and liver. At the end of 56 wk, histopathological examinations were performed in the same way. Liver, kidney, and testis cadmium levels were also determined by atomic absorption spectrophotometry. All the cadmium-treated male rats showed pathological testicular alterations, and liver and kidney damage after chronic exposure. Cadmium levels were found to be highest in the kidney (1.009 +/- 0.034 microgram/g wet tissue in the infertile group). At the end of the 52-wk period, reproductive capacity of the cadmium-treated rats was investigated and was found to be lost in 39.89% of the animals.

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

    Science.gov (United States)

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

    2010-06-01

    Kisspeptin is a recently discovered hypothalamic peptide which plays an important role in the central control of reproductive functions. We have investigated direct and indirect effects of kisspeptin on the liver oxidative stress in young male rats. Twenty-four rats were divided into four groups (n = 6/group). First group served as control and received saline. Kisspeptin-10 was administered to the animals in the second group (20 nmol/rat/day), for a period of 7 days. Rats were given only one dose gosereline (0.9 mg/rat), a GnRH agonist in the third group. The last group received kisspeptin-10 with gosereline. The activities of catalase, superoxide dismutase (SOD), xanthine oxidase (XO), adenosine deaminase (AD) and level of malondialdehyde were studied in liver tissue. Serum samples were separated for total antioxidant capacity (TAC), total oxidant status (TOS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, blood urea nitrogen (BUN), colesterol, high-density lipoprotein (HDL) and triglyceride. Kisspeptin increased the activities of SOD and catalase (p < 0.05). When compared to the control group, the levels of malondialdehyde, TOS and AST were lower, but levels of BUN, cholesterole, HDL and AD were higher in the other three groups (p < 0.05). In conclusion, our findings suggest that kisspeptin may have antioxidant and thus protective effects on the liver tissue. 2010 John Wiley & Sons, Ltd.

  11. Interactions of gold with cytosolic selenium-containing proteins in rat kidney and liver.

    Science.gov (United States)

    Hu, M L; Viljoen, A J; Tappel, A L

    1988-04-01

    Rats injected with aurothioglucose (ATG) for 5 days were subsequently injected with [75Se]selenious acid and killed after 3 days. Kidney and liver cytosols were chromatographed on Sephadex G-150. 75Se in kidney was associated with high molecular weight (HMW), 85,000 Mr, 26,000 Mr, and 10,000 Mr proteins and with a nonprotein fraction. The elution profile of liver cytosol was similar to that of kidney, but without a 26,000 Mr protein. ATG injection increased the association of 75Se with all fractions of kidney cytosol except the 85,000 Mr fractions, which contained Se-glutathione peroxidase (SeGSHPx) activity; 75Se in liver was increased only in HMW fractions. Unfractionated kidney cytosolic SeGSHPx activity was decreased 14% by ATG injection, but liver enzyme activity was not changed. However, Sephadex G-150 chromatography showed that total and specific activities, respectively, were decreased 28 and 23% in kidney and 25 and 16% in liver. Au coeluted with HMW and 10,000 Mr 73Se-containing kidney proteins; the latter contained 50% of the Au eluted from the column. DEAE Sephacel chromatography of the 10,000 Mr kidney protein showed that both Au and 75Se were tightly associated with metallothionein-like proteins. This study demonstrates the interaction of Au with rat liver and kidney 75Se-containing proteins.

  12. Hepatoprotective effect of aged black garlic on chronic alcohol-induced liver injury in rats.

    Science.gov (United States)

    Kim, Min Hee; Kim, Min Ji; Lee, Jeung Hee; Han, Jang Il; Kim, Jin Hee; Sok, Dai-Eun; Kim, Mee Ree

    2011-01-01

    The hepatoprotective effect of aged black garlic (ABG) against ethanol-induced oxidative liver damage was investigated in adult male Sprague-Dawley rats for 4 weeks. Rats were divided into three groups: a saline (WT) group, an ethanol (ET) group (15 mL/kg of body weight 20% [wt/vol] ethanol), and an ethanol + ABG (ET+ABG) group (ethanol + 100 mg/kg of body weight ABG). ABG administration led to decreased epididymal and total fat pad (P<.05) and liver weights, ameliorated prominent fatty changes around the portal triad, and reduced fat accumulation in liver. ABG caused a significant decrease of the alcohol-induced increases in hepatic activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. Cytochrome P450 2E1 activity was reduced by 55%, whereas the activities of glutathione S-transferase and quinine reductase were increased by 1.5-fold (P<.05) and fourfold (P<.05), respectively, in the ET+ABG group compared with the ET group. ABG treatment significantly decreased the thiobarbituric acid-reactive substances level in liver, heart, and plasma. Glutathione content and the activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase in liver were significantly enhanced. Furthermore, the oxidative damage to blood lymphocyte DNA caused by chronic alcohol ingestion was significantly decreased in the ET+ABG group. In conclusion, ABG has strong antioxidative properties and may be a promising agent for protecting against chronic alcohol-induced liver damage.

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

    Science.gov (United States)

    2013-01-01

    Background Hepatology research has focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Thus, this study evaluated mechanisms of the hepatoprotective activity of Curcuma longa rhizome ethanolic extract (CLRE) on thioacetamide-induced liver cirrhosis in rats. Methods The hepatoprotective effect of CLRE was measured in a rat model of thioacetamide-induced liver cirrhosis over 8 weeks. Hepatic cytochrome P450 2E1 and serum levels of TGF-β1 and TNF-α were evaluated. Oxidative stress was measured by malondialdehyde, urinary 8-hydroxyguanosine and nitrotyrosine levels. The protective activity of CLRE free-radical scavenging mechanisms were evaluated through antioxidant enzymes. Protein expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in animal blood sera was studied and confirmed by immunohistochemistry of Bax, Bcl2 proteins and proliferating cell nuclear antigen. Results Histopathology, immunohistochemistry and liver biochemistry were significantly lower in the Curcuma longa-treated groups compared with controls. CLRE induced apoptosis, inhibited hepatocytes proliferation but had no effect on hepatic CYP2E1 levels. Conclusion The progression of liver cirrhosis could be inhibited by the antioxidant and anti-inflammatory activities of CLRE and the normal status of the liver could be preserved. PMID:23496995

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

    Science.gov (United States)

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

    2011-01-01

    We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer 14C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 ± 0.04, old; 0.59 ± 0.05, young; p acetaminophen across the sinusoidal endothelium (0.034 ± 0.006 mL/s/g, old; 0.048 ± 0.014 mL/s/g, young; p acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. PMID:21300741

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

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    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

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

    Science.gov (United States)

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

    2014-01-01

    The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver.

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

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    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

  18. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver

    NARCIS (Netherlands)

    Beuers, U.; Bilzer, M.; Chittattu, A.; Kullak-Ublick, G. A.; Keppler, D.; Paumgartner, G.; Dombrowski, F.

    2001-01-01

    Ursodeoxycholic acid (UDCA) exerts anticholestatic effects by undefined mechanisms. Previous work suggested that UDCA stimulates biliary exocytosis via Ca(++)- and protein kinase C (PKC)-dependent mechanisms. Therefore, the effect of taurine-conjugated UDCA (TUDCA) was studied in the experimental

  19. Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats.

    Science.gov (United States)

    Zhang, Yang; Luo, Jian-Xing; Hu, Xiao-Yu; Yang, Fang; Zhong, Sen; Lin, Wu

    2016-02-28

    To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats. Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed. D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/β-actin (0.06 ± 0.03, 0.11 ± 0.04 vs 0.25 ± 0.04, P liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 ± 4.91, 25.57 ± 2.94 vs 17.55 ± 2.40, P liver regeneration.

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

    Directory of Open Access Journals (Sweden)

    Xiaxia Cai

    2016-03-01

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

  1. Safety evaluation of an Ayurvedic medicine, Arogyavardhini vati on brain, liver and kidney in rats.

    Science.gov (United States)

    Kumar, Gajendra; Srivastava, Amita; Sharma, S K; Gupta, Y K

    2012-03-06

    Arogyavardhini vati, an Ayurvedic polyherbal formulation has been used for liver and skin disorders in the Ayurvedic system of medicine. However, toxicity due to the presence of heavy metals in this traditional medicine is a matter of concern. To evaluate the safety of Arogyavardhini vati on brain, liver and kidney in rats. Arogyavardhini vati at doses of 50, 250 and 500mg/kg (1, 5 and 10 times of human equivalent dose respectively), mercury chloride (1mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioral parameters were assessed on day 1, 7th, 14th and 28th using Morris water maze, passive avoidance, elevated plus maze and rota rod. Biochemical parameters (acetyl-cholinesterase activity, malondialdehyde, reduced glutathione), histopathology and mercury level in brain, liver, kidney were assessed at the end of the experiment. There was no significant change in behavioral parameters, acetyl-cholinesterase activity, liver function (ALT, AST, ALP and bilirubin) and kidney (serum urea and creatinine) function tests at all doses of Arogyavardhini vati (50, 250 and 500mg/kg) as compared to normal control. However, significant change was observed in mercury chloride treated group. Mercury chloride treated group as well as Arogyavardhini vati treated groups (50, 250 and 500mg/kg) showed increased levels of mercury in brain, liver and kidney as compared to normal control. Histopathological results showed significant cytoarchitectural changes in brain, liver and kidney architecture in mercury chloride treated group. Whereas, normal cytoarchitecture was observed at all doses of Arogyavardhini vati. The finding of the present study suggests that Arogyavardhini vati in the doses equivalent up to 10 times of the human dose administered to rats for 28 days does not have appreciable toxicological effects on brain, liver and kidney. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Dietary protein effects on cadmium and metallothionein accumulation in the liver and kidney of rats

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N.W.; Osborne, T.R.

    1984-03-01

    The relationship of dietary protein to cadmium absorption and tissue deposition was studied in male Sprague-Dawley rats exposed to different levels of cadmium in the drinking water. In animals fed a high-protein or low-protein diet and drinking water containing 25 or 50 ppm cadmium, liver and kidney cadmium and metallothionein were both significantly higher in rats fed the high-protein diet for 2 to 4 months. These differences may possibly be explained by the concentration of cysteine observed between these two diets. When cysteine was added to the low-protein diet to the level observed in the high-protein diet and fed to rats receiving 25 ppm cadmium in the drinking water, significant dietary differences in liver and kidney cadmium and metallothionein were not observed. The importance of dietary protein to cadmium-induced toxicity was also assessed in these studies. The activity of catechol-o-methyltransferase was used as a measure of cadmium-induced toxicity. The activity of this enzyme in the lung, liver and heart was significantly lower in rats fed a low-protein diet than those fed the high-protein diet and 50 ppm cadmium. Metallothionein concentration in the lung and liver from low-protein-fed rats was approximately half the level observed in rats fed the high-protein diet, which suggests a relationship between cadmium-induced toxicity and metallothionein concentrations. These results illustrate the importance of considering dietary protein (and possibly cysteine) when studying cadmium metabolism in experimental animals. 22 references, 6 figures, 6 tables.

  3. Biochemical effects on the liver and kidney of rats administered ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-18

    Aug 18, 2008 ... Chinese herbs. Herbs that contain pyrrolizidine alkaloids, kava, atractylis gummifera, senna alkaloids, cause liver damage (Sickle and Schuppon, 2007) like many synthetic drugs undergoing metabolic activation to form reactive metabolites which are often associated with drug toxicity. It is recognized that ...

  4. 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...... have been investigated. 3. An incubation system where liver slices are incubated in 12-well culture plates was evaluated with respect to metabolism of metronidazole. Optimal viability was observed for a time period of up to 24 h. The Michaelis-Menten parameters for the metabolism of metronidazole......, whereas the intrinsic clearance with respect to formation of the glucuronic acid conjugate was lower in slices compared with hepatocytes. 4. The metabolism of metronidazole in liver slices, in hepatocytes in primary monolayer culture, in hepatocytes incubated in suspension, and in liver microsomes...

  5. Remote or conventional ischemic preconditioning--local liver metabolism in rats studied with microdialysis.

    Science.gov (United States)

    Björnsson, Bergthor; Winbladh, Anders; Bojmar, Linda; Trulsson, Lena M; Olsson, Hans; Sundqvist, Tommy; Gullstrand, Per; Sandström, Per

    2012-07-01

    Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC [759 (84) μM] and the IRI [732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. The effect of aqueous extract of Avicennia marina (Forsk. Vierh. leaves on liver enzymes' activity, oxidative stress parameters and liver histopathology in male diabetic rats

    Directory of Open Access Journals (Sweden)

    Akram Hamzevi

    2017-12-01

    Full Text Available Background: Avicennia marina has antioxidant and anti-diabetic properties. This study was conducted to examine the effect of aqueous extract of A. marina on liver enzymes' activity, oxidative stress parameters and liver histopathology in diabetic rats. Materials and Methods: In this experimental study, 28 male rats were allocated into the equal groups of control, diabetic control and experimental diabetic 1 and 2. The diabetes in diabetic control and experimental diabetic groups was induced using an intraperitoneal injection of 120 mg/kg alloxan. The experimental diabetic groups received the aqueous extract of A. marina (100 and 200 mg/kg, i.p. in alternate days for one month. Sterile distilled water was injected to the animals of control and diabetic control groups. At the end of the treatment period, serum levels of ALT, AST, GGT and ALP were measured. Then, levels of SOD, GST, CAT and MDA were measured in the liver tissue. The liver sections were prepared and examined by an optical microscope. Results: Results showed that administration of the A. marina extract (100 and 300 mg/kg, ip to the diabetic rats significantly decreased the serum levels of liver enzymes and tissue level of MDA. Also, the activity of the liver tissue's antioxidant enzymes was increased (P<0.05. The A. marina extract dose-dependently decreased liver damages in diabetic rats. Conclusion: Administration of the A. marina extract improves liver tissue oxidative stress indices and decreases the serum level of liver enzymes. Also, A. marina extract improves liver tissue injuries induced by diabetes.

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

    Directory of Open Access Journals (Sweden)

    Dinesh Babu Jestadi

    2014-01-01

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

  8. Anti-Inflammatory and Antioxidant Actions of Copaiba Oil Are Related to Liver Cell Modifications in Arthritic Rats.

    Science.gov (United States)

    Castro Ghizoni, Cristiane V; Arssufi Ames, Ana P; Lameira, Osmar A; Bersani Amado, Ciomar A; Sá Nakanishi, Anacharis B; Bracht, Lívia; Marçal Natali, Maria R; Peralta, Rosane M; Bracht, Adelar; Comar, Jurandir F

    2017-10-01

    The present study investigated the action of copaiba oil (Copaifera reticulata) on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis. The later is an experimental autoimmune pathology that shares many features with the human rheumatoid arthritis. Holtzman rats were distributed into the following groups: control (healthy) rats; control rats treated with copaiba oil at the doses of 0.58 and 1.15 g · kg-1 , arthritic rats, and arthritic rats treated with copaiba oil (0.58 and 1.15 g · kg-1 ). The oil was administrated orally once a day during 18 days after arthritis induction. Both doses of copaiba oil improved the paw edema and the dose of 0.58 mg · kg-1 improved the swollen adrenals and lymph nodes besides decreasing the plasmatic myeloperoxidase activity (-30%) of arthritic rats. Copaiba oil (1.15 g · kg-1 ) abolished the increases of protein carbonyl groups and reactive oxygen species in the liver and both doses increased the liver GSH content and the catalase activity in arthritic rats. Copaiba oil (1.15 g · kg-1 ) decreased glycolysis (-65%), glycogenolysis (-58%), and gluconeogenesis (-30%) in the liver of arthritic animals. However, gluconeogenesis was also diminished by the treatment of control rats, which presented lower body weight gain (-45%) and diminished number of hepatocytes per liver area (-20%) associated to higher liver weight (+29%) and increased hepatocyte area (+13%). The results reveal that copaiba oil presented systemic anti-inflammatory and antioxidant actions in arthritic rats. These beneficial effects, however, were counterbalanced by harmful modifications in the liver cell metabolism and morphology of healthy control rats. J. Cell. Biochem. 118: 3409-3423, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Counteraction of oxidative damage in the rat liver by an ancient grain (Kamut brand khorasan wheat).

    Science.gov (United States)

    Benedetti, Serena; Primiterra, Mariangela; Tagliamonte, Maria Chiara; Carnevali, Andrea; Gianotti, Andrea; Bordoni, Alessandra; Canestrari, Franco

    2012-04-01

    We previously demonstrated in rat plasma the antioxidant protective effect of whole-grain bread, particularly when made from Kamut brand khorasan wheat. In the present study, we investigated the effects of the same experimental breads in rat liver using two different bread-making procedures (baker's yeast and sourdough fermentation). Rats were examined in the basal condition and after the administration of doxorubicin, a pro-oxidative agent. The following parameters were measured in liver homogenates: glutathione peroxidase and thioredoxin reductase activities, as antioxidant enzymes containing selenium; glutathione, α-tocopherol and β-carotene, as major non-enzymatic cell antioxidants; malondialdehyde and advanced oxidation protein products, as markers of oxidative damage to lipids and proteins, respectively. A histologic evaluation of liver tissue was also conducted. In agreement with our previous work, we observed a lower oxidative status and a different activity of glutathione peroxidase and thioredoxin reductase in rats fed the whole-grain Kamut khorasan bread than in rats fed the modern whole-grain durum wheat bread. Histologic evaluation of the hepatic tissue showed the onset of inflammation in response to doxorubicin only in rats fed the modern durum wheat bread. Our data confirm that bread made from whole-grain Kamut khorasan protects rats from oxidative stress better than bread made from whole-grain durum wheat. This is consistent with their different antioxidant profiles. The type of wheat used for bread-making appeared to be the main determinant of the observed protective effect. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Characterization of liver changes in ZSF1 rats, an animal model of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Marta Borges-Canha

    Full Text Available Background: The non-alcoholic fatty liver disease is the hepatic counterpart of the metabolic syndrome. ZSF1 rats are a metabolic syndrome animal model in which liver changes have not been described yet. Aim: The characterization of liver histological and innate immunity changes in ZSF1 rats. Methods: Five groups of rats were included (n = 7 each group: healthy Wistar-Kyoto control rats (Ctrl, hypertensive ZSF1 lean (Ln, ZSF1 obese rats with a normal diet (Ob, ZSF1 obese rates with a high-fat diet (Ob-HFD, and ZSF1 obese rats with low-intensity exercise training (Ob-Ex. The animals were sacrificed at 20 weeks of age, their livers were collected for: a measurements of the area of steatosis, fibrosis and inflammation (histomorphological analysis; and b innate immunity (toll-like receptor [TLR] 2, TLR4, peroxisome proliferator-activated receptor γ [PPARγ], toll interacting protein [TOLLIP] and inflammatory marker (tumor necrosis factor-alpha [TNFvs], interleukin 1 [IL-1] expression analysis by real-time PCR. Results: Ob, Ob-HFD and Ob-Ex were significantly heavier than Ln and Ctrl animals. Ob, Ob-HFD and Ob-Ex animals had impaired glucose tolerance and insulin resistance. ZSF1 Ob, Ob-HFD and Ob-Ex presented a higher degree of steatosis (3,5x; p < 0.05 than Ctrl or ZSF1 Ln rats. Steatohepatitis and fibrosis were not observed in any of the groups. No differences in expression were observed between Ctrl, Ln and Ob animals (except for the significantly higher expression of TOLLIP observed in the Ob vs Ln comparison. Ob-HFD and Ob-Ex rats showed increased expression of PPARγ and TOLLIP as compared to other groups. However, both groups also showed increased expression of TLR2 and TLR4. Nevertheless, this did not translate into a differential expression of TNFα or IL-1 in any of the groups. Conclusion: The ZSF1 model is associated with liver steatosis but not with steatohepatitis or a significantly increased expression of innate immunity or

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

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    Mohamad Hafanizam Bin Hassan

    2013-02-01

    Full Text Available Purpose: The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue. Methods: Twenty four male Sprague Dawley rats were allotted randomly to four groups including: control (taking normal diet; low dose (supplemented with 0.01 g/kg/day Nigella sativa; normal dose (supplemented with 0.1 g/kg/day Nigella sativa and high dose (supplemented with 1 g/kg/day Nigella sativa. All of supplements administered in powder form mixed with rats’ pellet for 28 days. To assess liver toxicity, liver enzymes measurement and histological study were done at the end of supplementation. Results: The finding revealed that there was no significant change in serum alanine aminotransferase (ALT and aspartate aminotransferase (AST between treatment groups. Histopathological study showed very minimal and mild changes in fatty degeneration in normal and high doses of Nigella sativa treated group. Inflammation and necrosis were absent. Conclusion: The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg supplemented for a period of 28 days resulted no changes in liver enzymes level and did not cause any toxicity effect on the liver function.

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

    Directory of Open Access Journals (Sweden)

    Eva Koellensperger

    2013-01-01

    Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

  13. Parathyroid hormone-sensitive adenylate cyclase system in plasma membranes of rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, W.F.; Schneider, N.

    1980-12-01

    Purified plasma membranes were prepared from normal rat livers. These membranes were unable to degrade parathyroid hormone (PTH), bovine PTH-(1 to 84) (bPTH-(1 to 84)), or bPTH-(1 to 34). The entire molecule bPTH-(1 to 84) caused a marked activation of adenylate cyclase (cAMP production increased over 5-fold), with half-maximal stimulation at 6.9 x 10/sup -8/ M. The amino-terminal fragment bPTH-(1 to 34) was equipotent but gave a smaller maximal cAMP production. The human (h) amino acid sequence, hPTH-(1 to 34) was only weakly effective at a concentration of 10/sup -5/ M. A similar species specificity was shown with crude rat renal cortical membranes. Of a variety of ligands, only glucagon and 10/sup -3/ M F/sup -/ were cyclase activators in these liver plasma membranes. Binding of (/sup 125/I)iodo-bPTH by these membranes was fairly extensive but showed a saturation of binding only at high hormone concentrations (> 10/sup -6/ M). Clearly, cleavage of the intact molecule PTH-(1 to 84) is not required for activation of the adenylate cyclase system of liver membranes. It appears that two rat tissues, liver and kidney, exhibit some species specificity in cyclase activation, i.e. the hPTH-(1 to 34) (Niall sequence) is inactive.

  14. Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia.

    Science.gov (United States)

    Castro, Márcia B; Ferreira, Bruna K; Cararo, José Henrique; Chipindo, Adália E; Magenis, Marina L; Michels, Monique; Danielski, Lucinéia G; de Oliveira, Marcos R; Ferreira, Gustavo C; Streck, Emilio L; Petronilho, Fabricia; Schuck, Patrícia F

    2016-12-01

    Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 μmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats.

  15. Effect of Platelet-Rich Plasma on CCl4-Induced Chronic Liver Injury in Male Rats

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    Zahra Hesami

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1 mL/kg, i.p. 1 : 1 in olive oil twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5 mL/kg, s.c. two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP.

  16. Protective Effect of Urtica dioica on Liver Injury Induced By Hepatic Ischemia Reperfusion Injury in Rats

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    Alpaslan TERZİ

    2010-05-01

    Full Text Available Background: This study was designed to investigate the effects of Urtica dioica on liverischemia reperfusion injury in rats. Methods: Thirty male Wistar-albino rats were used in this experimental study. Animals weredivided into three groups as sham operated (group 1, control (group 2, and Urtica dioicatreatment group (group 3. Urtica dioica 2ml/kg were administered intraperitoneally beforeischemia and immediately after the reperfusion. The levels of total antioxidant capacity, totalfree sulfidril group, Total oxidant status, Oxidative stress index, and myeloperoxidase in livertissues were measured. The serum levels of ALT, AST and LDH were also measuredResults: Total antioxidant capacity and total free sulfidril group in liver tissue were significantlyhigher in group 3 than in group 2. Oxidative stress index and myeloperoxidase in liver tissuewere significantly lower in group 3 than the group 2. The levels of liver enzymes in treatmentgroup were significantly lower than those in the control group. Histological tissue damage wasmilder in the treatment group than that in the control group.Conclusion: It is concluded that Urtica dioica increase the antioxidant capacity and decreaseoxidative stress and liver enzymes in the hepatic ischemi reperfusion injury of rats.

  17. Hepatoprotective activity of Mentha arvensis Linn. leaves against CCL4 induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Kalpana Patil

    2012-05-01

    Full Text Available Objective: To study the Hepatoprotective activity of ethanol, chloroform and aqueous extracts of Mentha arvensis leaves against CCL4 induced liver damage in rats. Methods: Hepatotoxicity was induced by CCL4 and the biochemical parameters such as serum glutamate pyruvate transminase (sGPT, serum glutamate oxaloacetate transaminase (sGOT, alkaline phosphatase (sALP, serum bilirubin (sB and histopathological changes in liver were studied along with silymarin as standard Hepatoprotective agents. Results: The Phytochemical investigation of the extracts showed presence of flavonoids, steroids, triterpenoids, alkaloids, glycosides, carbohydrates, tannins, phenolic compounds. Treatment of the rats with chloroform, ethanol and aqueous extract with CCL 4 administration caused a significant reduction in the values of sGOT, sGPT, sALP and sB (P<0.01 almost comparable to the silymarin. The Hepatoprotective was confirmed by histopathological examination of the liver tissue of control and treated animals. Conclusions: From the results it can be concluded that Mentha arvensis possesses Hepatoprotective effect against CCL4 induced liver damage in rats.

  18. The para isomer of dinitrobenzene disrupts redox homeostasis in liver and kidney of male wistar rats.

    Science.gov (United States)

    Sangodele, Janet Olayemi; Olaleye, Mary Tolulope; Monsees, Thomas K; Akinmoladun, Afolabi Clement

    2017-07-01

    Para - Dinitrobenzene (p -DNB) is one of the isomers of dinitrobenzene which have been detected as environmental toxicants. Skin irritation and organ toxicities are likely for industrial workers exposed to p -DNB. This study evaluated the effect of sub-chronic exposure of rats to p -DNB on cellular redox balance, hepatic and renal integrity. Forty eight male Wistar rats weighing 160-180 g were administered 50, 75, 1000 and 2000 mg/kg b.wt (body weight) of p -DNB or an equivalent volume of vehicle (control) orally and topically for 14 days. After the period of treatment, the activities of kidney and liver catalase (CAT), alkaline phosphatase (ALP) and superoxide dismutase (SOD) as well as extent of renal and hepatic lipid peroxidation (LPO) were determined. Serum ALP activity and plasma urea concentration were also evaluated. Compared with control animals, p -DNB -administered rats showed decrease in the body and relative kidney and liver weights as well as increased renal and hepatic hydrogen peroxide and lipid peroxidation levels accompanied by decreased superoxide dismutase and catalase activities. However, p -DNB caused a significant increase in plasma urea concentration and serum, liver and kidney ALP activities relative to control. In addition, p -DNB caused periportal infiltration, severe macro vesicular steatosis and hepatic necrosis in the liver. Our findings show that sub-chronic oral and sub-dermal administration of p -DNB may produce hepato-nephrotoxicity through oxidative stress.

  19. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  20. An in vitro method of alcoholic liver injury using precision-cut liver slices from rats

    NARCIS (Netherlands)

    Klassen, Lynell W.; Thiele, Geoffrey M.; Duryee, Michael J.; Schaffert, Courtney S.; DeVeney, Amy L.; Hunter, Carlos D.; Olinga, Peter; Tuma, Dean J.

    2008-01-01

    Alcohol abuse results in liver injury, but investigations into the mechanism(s) for this injury have been hampered by the lack of appropriate in vitro culture models in which to conduct in depth and specific studies. In order to overcome these shortcomings, we have developed the use of precision-cut

  1. Effects of hypophysectomy and GH administration on bovine and human GH binding to rat liver membranes.

    Science.gov (United States)

    Messina, J L; Edén, S; Kostyo, J L

    1985-07-01

    Experiments were conducted to investigate the specific binding of highly purified bovine and human growth hormones (bGH and hGH) to purified liver plasma membranes of male rats at various times after hypophysectomy and after the acute intravenous administration of bGH. Liver membranes prepared from hypophysectomized male rats showed a two- to threefold increase in the specific binding of either [125I]iodo-bGH or [125I]iodo-hGH, when compared with membranes prepared from the livers of age-matched normal male rats. The increase in GH binding was apparent within 3 days after hypophysectomy and persisted for a number of weeks after the operation. The increase in GH binding produced by hypophysectomy appeared to be due to an increase in the number of binding sites present on the membranes. The intravenous injection of 200 micrograms of bGH into hypophysectomized male rats 5-60 min before they were killed markedly reduced the ability of liver membranes prepared from these animals to bind [125I]iodo-bGH specifically. This decrease in GH binding seen after the injection of bGH may have been due to the development of a slowly dissociating hormone-binding site complex, which thereby reduced the number of available binding sites. This conclusion is supported by the finding that bGH, which is bound in vitro to isolated liver membranes, dissociates slowly and incompletely in the presence of an excess of unlabeled hormone. Moreover, the degree to which the bound hormone can dissociate appears to depend on the length of time that association is allowed to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver.

    Science.gov (United States)

    Ferreira, Andréa G K; da Cunha, Aline A; Machado, Fernanda R; Pederzolli, Carolina D; Dalazen, Giovana R; de Assis, Adriano M; Lamers, Marcelo L; dos Santos, Marinilce F; Dutra-Filho, Carlos S; Wyse, Angela T S

    2012-01-01

    The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. Copyright © 2011 Wiley Periodicals, Inc.

  3. Targeting dexamethasone to Kupffer cells: effects on liver inflammation and fibrosis in rats.

    Science.gov (United States)

    Melgert, B N; Olinga, P; Van Der Laan, J M; Weert, B; Cho, J; Schuppan, D; Groothuis, G M; Meijer, D K; Poelstra, K

    2001-10-01

    Kupffer cells (KC) play an important role in the pathogenesis of inflammatory liver diseases leading to fibrosis. Anti-inflammatory drugs are only effective when administered at high doses that may cause side effects. Therefore, dexamethasone coupled to mannosylated albumin (Dexa(5)-Man(10)-HSA) was designed by us to selectively deliver this anti-inflammatory drug to the KC. The effectiveness of Dexa(5)-Man(10)-HSA was studied both in organ cultures and fibrosis induced by bile duct ligation (BDL) in rats. Dexa(5)-Man(10)-HSA accumulated in livers of both healthy and fibrotic rats (67% +/- 5% and 70% +/- 9% of the dose, respectively) and uptake was found almost exclusively in KC. Active dexamethasone was liberated from its carrier, because Dexa(5)-Man(10)-HSA could effectively inhibit nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) release in endotoxin-activated liver slices. In vivo, however, this was associated with increased collagen I and III depositions and enhanced tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression. This was accompanied by a decreased influx of reactive oxygen species (ROS) producing cells in the livers of BDL animals treated with Dexa(5)-Man(10)-HSA as compared with untreated BDL rats. Dexa(5)-Man(10)-HSA treatment also replenished the depleted glycogen stores in hepatocytes of BDL livers. In conclusion, our studies showed selective delivery of dexamethasone to KC with Dexa(5)-Man(10)-HSA. This conjugate reduced intrahepatic ROS in vivo and TNF-alpha production in vitro and prevented glycogen depletion in vivo, indicating effective pharmacologic targeting. Dexa(5)-Man(10)-HSA, however, also accelerated fibrogenesis, which was paralleled by TIMP-1 mRNA induction. Targeting of dexamethasone to KC provides evidence for a dual role of this cell type in fibrogenesis of BDL rats.

  4. Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats

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    Xin Liu

    2017-04-01

    Full Text Available The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1 activity were determined by ELISA assay and liquid chromatography–tandem mass spectrometry (LC–MS/MS analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF were assessed by Western blotting. As a result, bicyclol significantly protected against anti-TB drug-induced liver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic lipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of bicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of HGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant effect on the plasma pharmacokinetics of the anti-TB drug in rats.

  5. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    1981-01-01

    The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

  6. Protective effects of Aristolochia longa and Aquilaria malaccensis against lead induced acute liver injury in rats

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    Derouiche Samir

    2017-09-01

    Full Text Available Objective: To investigate the protective effects of Aristolochia longa (A. longa and Aquilaria malaccensis (A. malaccensis on acute hepatotoxicity induced by lead in female albino rats. Methods: Twenty five (25 apparently healthy female Wistar rats were randomly divided into five groups of five rats in each: control, Pb, Pb + A. longa (Ar, Pb+ A. malaccensis (Aq, and Pb+ A. longa (Ar + A. malaccensis (Aq lead (100 mg/kg b.w. as Pb (C2H3O22 added in their drinking water for 75 days. A. longa (rhizome powder at a dose of 10 g/kg of diet and A. malaccensis (heartwood powder at a dose 10 g/kg of diet were added to the feed during the last 15 days of lead exposed in the animals. Results: Obtained results revealed that lead treatment caused a significant increase in serum GOT, GPT and ALP activities and in liver of MDA level and CAT activity. In contrast, it led to an decrease in the liver GOT, GPT and GST activities and in GSH level in rats. Also, the results clearly showed that lead causes alterations of hepatic tissue in comparison with controls. Our results showed that treatment with A. malaccensis and A. longa a partial correction of the previous parameters. The histological observations confirmed the hepatoprotection results by the biochemical parameters. Conclusions: Results demonstrated beneficial effects of A. longa and A. malaccensis treatment in Pb-induced oxidative stress and tissue damage in liver.

  7. Effects of long-term mildronate treatment on cardiac and liver functions in rats.

    Science.gov (United States)

    Liepinsh, Edgars; Kuka, Janis; Svalbe, Baiba; Vilskersts, Reinis; Skapare, Elina; Cirule, Helena; Pugovics, Osvalds; Kalvinsh, Ivars; Dambrova, Maija

    2009-12-01

    Mildronate is a cardioprotective drug that improves cardiac function during ischaemia and functions by lowering l-carnitine concentration in body tissues and modulating myocardial energy metabolism. The aim of the present study was to characterise cardiovascular function and liver condition after long-term mildronate treatment in rats. In addition, changes in the plasma lipid profile, along with changes in the concentration of mildronate, l-carnitine and gamma-butyrobetaine were monitored in the rat tissues. Wistar rats were perorally treated daily with a mildronate dose of either 100, 200 or 400 mg/kg for 4, 8 or 12 weeks. The l-carnitine-lowering effect of mildronate was dose-dependent. However, the carnitine levels reached a plateau after about four weeks of treatment. During the additional weeks of treatment, the carnitine levels were not considerably changed. The obtained results provide evidence that even a high dose of mildronate does not alter cardiovascular parameters and the function of isolated rat hearts. Furthermore, the histological evaluation of liver tissue cryosections and measurement of biochemical markers of hepatic toxicity showed that all the measured values were within the normal reference range. Our results provide evidence that long-term mildronate administration induces significant changes in carnitine homeostasis, but it is not associated with cardiac impairment or disturbances in liver function.

  8. Renoprotective effect of crocin following liver ischemia/ reperfusion injury in Wistar rats.

    Science.gov (United States)

    Mard, Seyyed Ali; Akbari, Ghaidafeh; Mansouri, Esrafil; Parsanahad, Mahdi

    2017-10-01

    The objectives of the current study were to evaluate the effects of hepatic ischemia/reperfusion (IR) injury on the activity of antioxidant enzymes, biochemical factors, and histopathological changes in rat kidney, and to investigate the effect of crocin on IR-related changes. Thirty-two male Wistar rats were randomly allocated into four groups (n=8). They were sham-operated, IR, crocin pre-treatment, and crocin pretreatment+IR groups. Sham-operated and Crocin pre-treatment groups received normal saline (N/S, 2 ml/day) and crocin (200 mg/kg) for seven consecutive days intraperitoneally (IP), respectively, then rats underwent laparotomy, only. IR and crocin pretreatment+IR groups received N/S and crocin with the same dose, time, and route, respectively, then rats underwent partial (70%) ischemia for 45 min that was followed by reperfusion for 60 min. At the end of the experiment, kidney specimens were taken for histopathological and antioxidant evaluations and also blood samples were obtained for biochemical analysis. The results of the present study showed that crocin pre-treatment significantly increased the activity of antioxidants, decreased the serum levels of liver enzymes and blood urea nitrogen following IR-induced hepatic injury. Crocin also ameliorated kidney's histopathological disturbance beyond IR-induced hepatic injury. Crocin as an antioxidant agent protected renal insult following liver IR injury by increasing the activity of antioxidant enzymes, reducing serum levels of liver enzymes, and improving histopathological changes.

  9. The effect of selenium supplementation on elements distribution in liver of rats subject to strenuous swimming.

    Science.gov (United States)

    Sivrikaya, A; Akil, M; Bicer, M; Kilic, M; Baltaci, A K; Mogulkoc, R

    2013-01-01

    The present study aims to explore how selenium supplementation affects the element distribution in the liver tissue of rats subjected to strenuous swimming exercise. Thirty-two Spraque-Dawley male rats were equally divided into the four groups: Group 1, normal control group. Group 2, selenium-supplemented, non-swimming (0.6 mg/kg/day sodium selenite) group. Group 3, swimming, no supplementation group. Group 4, swimming, selenium-supplemented (0.6 mg/kg/day sodium selenite) group. After one month, the animals were decapitated and liver tissue samples were collected to determine the levels of lead, cobalt, boron, molybdenum, chromium, sulfur, magnesium, sodium, potassium, phosphorus, copper, iron, zinc and selenium. The chromium, molybdenum, iron, sodium and potassium values were higher in the swimming groups, relative to controls. Group 3 had significantly lower lead levels (pselenium and zinc values were obtained in the Group 2 and those of the Group 4 were higher than in the Groups 1 and 3. Group 1 had higher selenium and zinc levels than the Group 3. The results of the present study demonstrated that selenium-supplemented rats subjected to strenuous swimming exercise had distinct elements distribution in liver tissue. Also, selenium supplementation offsets the decrease in zinc levels in rats subjected to vigorous swimming (Tab. 3, Ref. 20).

  10. Hepatoprotective effect of three herbal extracts on aflatoxin B1-intoxicated rat liver.

    Science.gov (United States)

    Shyamal, S; Latha, P G; Suja, S R; Shine, V J; Anuja, G I; Sini, S; Pradeep, S; Shikha, P; Rajasekharan, S

    2010-04-01

    Roots of Ixora coccinea (Rubiaceae), and Rhinacanthus nasuta (Acanthaceae) and whole plants of Spilanthes ciliata (Asteraceae) are extensively used by tribal communities in South India to treat liver diseases. However, the veracity of these tribal claims has not been investigated scientifically using the liver toxin, aflatoxin. This study reports on the protective effects of these three herbal ethanolic extracts on the aflatoxin B1 (AFB1)-intoxicated livers of albino male Wistar rats. Biochemical parameters, including serum hepatic enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase), were studied. Hepatic tissues were processed for assay of reduced glutathione (GSH) and histological alterations. Pre-treatment of the rats with oral administration of the plant ethanolic extracts, Ixora coccinea (IC), Rhinacanthus nasuta (RN), Spilanthes ciliata (SC), prior to AFB1 was found to provide significant protection against toxin-induced liver damage, determined 72 hours after the AFB1 challenge (1.5 mg/kg, intraperitoneally) as evidenced by a significant lowering of the activity of the serum enzymes and enhanced hepatic reduced GSH status. Pathological examination of the liver tissues supported the biochemical findings. The three plant extracts, IC, RN and SC, showed significant antilipid peroxidant effects in vitro. It was concluded that the hepatoprotective effects of the three plant extracts observed in this study might result from their potent antioxidative properties.

  11. Tocotrienols Reverse Cardiovascular, Metabolic and Liver Changes in High Carbohydrate, High Fat Diet-Fed Rats

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    Weng-Yew Wong

    2012-10-01

    Full Text Available Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.

  12. Protective Effects of Hydrolyzed Nucleoproteins from Salmon Milt against Ethanol-Induced Liver Injury in Rats

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    Akiko Kojima-Yuasa

    2016-12-01

    Full Text Available Dietary nucleotides play a role in maintaining the immune responses of both animals and humans. Oral administration of nucleic acids from salmon milt have physiological functions in the cellular metabolism, proliferation, differentiation, and apoptosis of human small intestinal epithelial cells. In this study, we examined the effects of DNA-rich nucleic acids prepared from salmon milt (DNSM on the development of liver fibrosis in an in vivo ethanol-carbon tetrachloride cirrhosis model. Plasma aspartate transaminase and alanine transaminase were significantly less active in the DNSM-treated group than in the ethanol plus carbon tetrachloride (CCl4-treated group. Collagen accumulation in the liver and hepatic necrosis were observed histologically in ethanol plus CCl4-treated rats; however, DNSM-treatment fully protected rats against ethanol plus CCl4-induced liver fibrosis and necrosis. Furthermore, we examined whether DNSM had a preventive effect against alcohol-induced liver injury by regulating the cytochrome p450 2E1 (CYP2E1-mediated oxidative stress pathway in an in vivo model. In this model, CYP2E1 activity in ethanol plus CCl4-treated rats increased significantly, but DNSM-treatment suppressed the enzyme’s activity and reduced intracellular thiobarbituric acid reactive substances (TBARS levels. Furthermore, the hepatocytes treated with 100 mM ethanol induced an increase in cell death and were not restored to the control levels when treated with DNSM, suggesting that digestive products of DNSM are effective for the prevention of alcohol-induced liver injury. Deoxyadenosine suppressed the ethanol-induced increase in cell death and increased the activity of alcohol dehydrogenase. These results suggest that DNSM treatment represents a novel tool for the prevention of alcohol-induced liver injury.

  13. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

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    G.B. Peres

    2014-06-01

    Full Text Available It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old, while 26 age-matched controls received only vehicle. The livers were removed on either the 10th or the 30th day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA of cathepsins B and L was also decreased on the 10th, but not on the 30th day. Sulfatase decreased 30% on the 30th day, while glycosidases did not vary (or presented a transitory and slight decrease. There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.

  14. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

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    Stéphanie Lacotte

    Full Text Available Liver transplantation for hepatocellular carcinoma (HCC results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01, increased liver function tests (p<0.01, the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005, which was related to an increased natural killer (NK cell frequency (p<0.05 and a higher monocyte/macrophage activation level (p<0.01. Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005, and liver monocyte/macrophage activation levels (p<0.01 were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05 and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  15. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Peres, G.B. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Juliano, M.A. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Biofísica, São Paulo, SP, Brasil, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Aguiar, J.A.K.; Michelacci, Y.M. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-05-09

    It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10{sup th} or the 30{sup th} day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10{sup th}, but not on the 30{sup th} day. Sulfatase decreased 30% on the 30{sup th} day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.

  16. 8-Aminoguanine: a base modification produced in rat liver nucleic acids by the hepatocarcinogen 2-nitropropane.

    Science.gov (United States)

    Sodum, R S; Nie, G; Fiala, E S

    1993-01-01

    2-Nitropropane (2-NP), an important industrial chemical and a hepatocarcinogen in rats, had previously been found to produce several modifications of nucleosides in rat liver RNA and DNA that are discernible using HPLC with electrochemical detection. While one of these modifications has been identified as an increase in the levels of 8-oxoguanosine and 8-oxo-2'-deoxyguanosine in RNA and DNA, respectively, the others had not been identified. We now present evidence that a major modification in rat liver nucleic acids due to the administration of 2-NP is the amination of guanine at C8, apparently a completely novel in vivo reaction. 8-Aminoguanosine, isolated from hydrolysates of liver RNA from 2-NP-treated rats, cochromatographed with synthetic or commercially-obtained standard on reverse-phase as well as cation-exchange HPLC, and its UV spectral characteristics at acidic, neutral, and basic pH were identical to those of the standard. Acid hydrolysis produced 8-aminoguanine, which had a retention time and fragmentation pattern identical to that of the standard on gas chromatography-mass spectrometry of the trimethylsilyl derivatives. Evidence for the presence of 8-aminodeoxyguanosine in liver DNA of rats treated with 2-NP was also obtained by cochromatography with synthetic standard on HPLC. Hydroxylamine-O-sulfonic acid was found to react with RNA and DNA to give 8-oxo- and 8-amino-substituted guanines. We propose, as a working hypothesis, that 2-NP may be metabolized to hydroxylamine-O-sulfonate or acetate, which yield the reactive nitrenium ion, NH2+, capable of aminating cellular macromolecules in vivo.

  17. Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver.

    Science.gov (United States)

    Veggi, Luis M; Pretto, Luciana; Ochoa, Elena J; Catania, Viviana A; Luquita, Marcelo G; Taborda, Diego R; Sánchez Pozzi, Enrique J; Ikushiro, Shin-ichi; Coleman, Michael D; Roma, Marcelo G; Mottino, Aldo D

    2008-08-01

    Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on expression/activity of the main DDS phase-II-metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.

  18. Two-step retrograde closed stenting: a novel method for treating canalicular lacerations in Chinese patients.

    Science.gov (United States)

    Bi, Y; Sui, G; Zhou, Q; Heindl, L M; Bock, F; Sun, X; Tang, S; Wang, Z; Cursiefen, C

    2013-11-01

    To evaluate the efficacy of two-step retrograde closed stenting for treating canalicular laceration. methods: Forty-eight consecutive canalicular laceration cases (48 eyes) were randomised and divided into two groups: a one-step group and a two-step group. In the two-step group (23 cases), the first step was performed in the outpatient department and included identifying the medial cut end of the canaliculus and probing under a slit-lamp microscope, followed by a retrograde canalicular stenting assisted by a memory titanium stylet. The second step was canalicular anastomosis, which was performed in the operating room. In the one-step group (25 cases), all of the surgical procedures were performed when preoperative preparations were simultaneously available. The time elapsed from the doctor visit to the treatment was 4.3 ± 2.4 h in the two-step group and 18.8 ± 6.3 h in the one-step group (Ptwo-step group, and 51.4 ± 24.2 min was needed in the one-step group (Ptwo-step group and 5.4 ± 2.2 in the one-step group (Ptwo-step group and nine cases (36%) in the one-step group required other assisted methods to locate the medial cut end (P=0.007). Twenty-one cases (91.3%) in the two-step group and 20 cases (80%) in the one-step group achieved patent lacrimal drainage systems during a 12-month follow-up (P=0.528). The two-step canalicular anastomosis method allows an early search for the medial cut end of the canaliculus and improves the chances of finding it; it is also a quicker, less invasive method for treating canalicular lacerations.

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

    Energy Technology Data Exchange (ETDEWEB)

    Silva, R.N. [Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Bueno, P.G. [Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Avó, L.R.S. [Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Nonaka, K.O.; Selistre-Araújo, H.S. [Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Leal, A.M.O. [Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

    2014-07-25

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

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

    Directory of Open Access Journals (Sweden)

    R.N. Silva

    2014-09-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C and high-fat (HF diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim or a sedentary group (C-Sed and HF-Sed. Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

  1. Effects of six anaesthetic agents on UDP-glucuronic acid and other nucleotides in rat liver.

    Science.gov (United States)

    Christensson, P I; Eriksson, G

    1985-08-01

    Anaesthesia affects the liver nucleotide pool. It was the aim of the present study to examine how anaesthesia for 60 min with pentobarbital, ketamin + diazepam, halothane, enflurane and isoflurane may influence the nucleotide pool in the rat liver, studied with isotachophoresis. It was found that none of the agents gave both safe and reproducible anaesthesia without affecting the nucleotide pools or affecting the experiments in some other way. Halothane and isoflurane were the two best alternatives with respect to both efficiency and safety. Isoflurane may be preferable since it gives a higher energy charge.

  2. Metformin increases liver accumulation of vitamin B12 - An experimental study in rats

    DEFF Research Database (Denmark)

    Greibe, E; Miller, J W; Foutouhi, S H

    2013-01-01

    = 18) were divided into two groups and given daily subcutaneous injections with metformin or saline (control) for three weeks. Following this, the animals received an oral dose of radio-labeled B(12) ((57)[Co]-B(12)), and urine and feces were collected for 24 h. Plasma, bowel content, liver....... Compared with controls, the amount of B(12) in the liver was 36% (p = 0.007) higher in metformin-treated rats, while the B(12) content in the kidney was 34% (p = 0.013) lower. No difference in the total amount of absorbed (57)[Co]-B(12) present in the tissues and organs studied was found, suggesting...

  3. Inhibition of ATP synthesis by fenbufen and its conjugated metabolites in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    Fenbufen is an arylpropionic acid derivative belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs). Even though fenbufen is considered a safe drug, some adverse reactions including hepatic events have been reported. To investigate whether mitochondrial damage could be involved...... in the drug induced liver injury (DILI) by fenbufen, the inhibitory effect of fenbufen and its conjugated metabolites on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria was investigated. Fenbufen glucuronide (F-GlcA), fenbufen-N-acetyl cysteine-thioester (F-NAC) and fenbufen...

  4. Strain-Related Differences on Response of Liver and Kidney Antioxidant Defense System in Two Rat Strains Following Diazinon Exposure

    Directory of Open Access Journals (Sweden)

    Maryam Salehi

    2016-02-01

    Full Text Available Background Diazinon (DZN is one of the most organophosphates that widely used in agriculture and ectoparasiticide formulations. Its extensive use as an effective pesticide was associated with the environmental deleterious effects on biological systems. Objectives The aim of this study was to investigate the potency of DZN to affect serum biochemical parameters and the antioxidant defense system in the liver and kidney of two rat strains. Materials and Methods In this experimental study, 30 female Wistar and 30 female Norway rats were randomly divided into control and DZN groups. DZN group was divided into four subgroups: 25, 50, 100 and 200 mg/kg of DZN administered groups by i.p. injection. The parameters were evaluated after 24 hours. Results At higher doses of DZN, superoxide dismutase, catalase, glutathione S-transferase and lactate dehydrogenase activities and glutathione (GSH and malondialdehyde levels in liver and kidney of Wistar rats were higher than Norway rats. At these concentrations, DZN increased some serum biochemical indices such as liver enzymes activities and levels of urea, uric acid and creatinine in Wistar rat. Conclusions DZN at higher doses alters the oxidant-antioxidant balance in liver and kidney of both rat strains and induces oxidative stress, which is associated with a depletion of GSH and increased lipid peroxidation. However, Wistar rats are found to be more sensitive to the toxicity of DZN compared to Norway rats. In addition, the effect of DZN on liver antioxidant system was more than kidney.

  5. Investigation of Liver Injury of Polygonum multiflorum Thunb. in Rats by Metabolomics and Traditional Approaches

    Science.gov (United States)

    Li, Yun-Xia; Gong, Xiao-Hong; Liu, Mei-Chen; Peng, Cheng; Li, Peng; Wang, Yi-Tao

    2017-01-01

    Liver injury induced by Polygonum multiflorum Thunb. (PM) have been reported since 2006, which aroused widespread concern. However, the toxicity mechanism of PM liver injury remained unclear. In this study, the mechanism of liver injury induced by different doses of PM after long-term administration was investigated in rats by metabolomics and traditional approaches. Rats were randomly divided into control group and PM groups. PM groups were oral administered PM of low (10 g/kg), medium (20 g/kg), high (40 g/kg) dose, while control group was administered distilled water. After 28 days of continuous administration, the serum biochemical indexes in the control and three PM groups were measured and the liver histopathology were analyzed. Also, UPLC-Q-TOF-MS with untargeted metabolomics was performed to identify the possible metabolites and pathway of liver injury caused by PM. Compared with the control group, the serum levels of ALT, AST, ALP, TG, and TBA in middle and high dose PM groups were significantly increased. And the serum contents of T-Bil, D-Bil, TC, TP were significantly decreased. However, there was no significant difference between the low dose group of PM and the control group except serum AST, TG, T-Bil, and D-Bil. Nine biomarkers were identified based on biomarkers analysis. And the pathway analysis indicated that fat metabolism, amino acid metabolism and bile acid metabolism were involved in PM liver injury. Based on the biomarker pathway analysis, PM changed the lipid metabolism, amino acid metabolism and bile acid metabolism and excretion in a dose-dependent manner which was related to the mechanism of liver injury. PMID:29163173

  6. Investigation of Liver Injury of Polygonum multiflorum Thunb. in Rats by Metabolomics and Traditional Approaches

    Directory of Open Access Journals (Sweden)

    Yun-Xia Li

    2017-11-01

    Full Text Available Liver injury induced by Polygonum multiflorum Thunb. (PM have been reported since 2006, which aroused widespread concern. However, the toxicity mechanism of PM liver injury remained unclear. In this study, the mechanism of liver injury induced by different doses of PM after long-term administration was investigated in rats by metabolomics and traditional approaches. Rats were randomly divided into control group and PM groups. PM groups were oral administered PM of low (10 g/kg, medium (20 g/kg, high (40 g/kg dose, while control group was administered distilled water. After 28 days of continuous administration, the serum biochemical indexes in the control and three PM groups were measured and the liver histopathology were analyzed. Also, UPLC-Q-TOF-MS with untargeted metabolomics was performed to identify the possible metabolites and pathway of liver injury caused by PM. Compared with the control group, the serum levels of ALT, AST, ALP, TG, and TBA in middle and high dose PM groups were significantly increased. And the serum contents of T-Bil, D-Bil, TC, TP were significantly decreased. However, there was no significant difference between the low dose group of PM and the control group except serum AST, TG, T-Bil, and D-Bil. Nine biomarkers were identified based on biomarkers analysis. And the pathway analysis indicated that fat metabolism, amino acid metabolism and bile acid metabolism were involved in PM liver injury. Based on the biomarker pathway analysis, PM changed the lipid metabolism, amino acid metabolism and bile acid metabolism and excretion in a dose-dependent manner which was related to the mechanism of liver injury.

  7. Role of mitogen-activated protein kinases in tauroursodeoxycholic acid-induced bile formation in cholestatic rat liver

    NARCIS (Netherlands)

    Denk, Gerald Ulrich; Hohenester, Simon; Wimmer, Ralf; Boehland, Claudia; Rust, Christian; Beuers, Ulrich

    2008-01-01

    Aim: Ursodeoxycholic acid exerts anticholestatic effects in various cholestatic disorders and experimental models of cholestasis. Its taurine conjugate (TUDCA) stimulates bile salt secretion in isolated perfused rat livers (IPRL) under physiological, non-cholestatic conditions, in part by

  8. Cytophotometric analysis of reaction rates of succinate and lactate dehydrogenase activity in rat liver, heart muscle and tracheal epithelium

    NARCIS (Netherlands)

    van Noorden, C. J.; Vogels, I. M.

    1989-01-01

    Reaction rates of succinate and lactate dehydrogenase activity in cryostat sections of rat liver, tracheal epithelium and heart muscle were monitored by continuous measurement of formazan formation by cytophotometry at room temperature. Incubation media contained polyvinyl alcohol as tissue

  9. Comparison of hepatotoxicity and metabolism of butyltin compounds in the liver of mice, rats and guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Shunji; Kashimoto, Takashige; Susa, Nobuyuki; Ishii, Masamitsu; Chiba, Toshikazu [Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Mutoh, Ken-ichiro [Laboratory of Veterinary Anatomy, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Hoshi, Fumio [Laboratory of Veterinary Anatomy, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Suzuki, Takashi [Laboratory of Environmental Health and Toxicology, Kyoto Prefectural University, Hangi-cho, Shimogamo, Sakyo-ku, 606-5822, Kyoto (Japan); Sugiyama, Masayasu [Sugiyama Pharmacy, 1335-1 Shimotama, Tamagawa-cho, 759-3112, Yamaguchi (Japan)

    2003-03-01

    The hepatotoxicity of tributyltin chloride (TBTC) and dibutyltin dichloride (DBTC) was compared among mice, rats and guinea pigs in vivo. Further, the metabolism of these butyltin compounds in the liver was also investigated in these species. The oral administration of TBTC and DBTC to mice induced obvious liver injury, as demonstrated by both serodiagnosis and histopathological diagnosis. The concentrations of TBTC and DBTC that induced hepatotoxicity in mice at 24 h after oral administration were 180 and 60 {mu}mol/kg, respectively. In the case of rats, the liver injury induced by TBTC and DBTC was detected at 24 h by the serodiagnosis, but not by histopathological diagnosis. On the other hand, in guinea pigs, TBTC and DBTC administration did not produce any clear liver injury at 24 h, as evaluated by these two diagnostic methods. Thus, the following ranking was obtained with regard to increasing order of sensitivity to liver injury caused by TBTC and DBTC: mice, rats and guinea pigs. The total butyltin contents in the liver of mice were equivalent at 3 h and 24 h after the administration of TBTC or DBTC; however, the contents in the liver of rats and guinea pigs were relatively lower at 3 h and higher at 24 h than those of mice, although there were no differences between rats and guinea pigs in the total liver butyltin content. Concerning the liver metabolism of these butyltin compounds, the main form of butyltin compounds in these animals treated with TBTC was DBTC within 3 h after oral administration, while the main metabolites at 24 h were different in each species, indicating that the liver metabolism of TBTC might vary by animal type. When the animals were treated with DBTC orally, DBTC was hardly metabolized in the livers of these animals even at 24 h, and the liver levels of DBTC were two times greater in mice and guinea pigs than in rats at 3 h and were lower in mice at 24 h than in rats and guinea pigs. The analysis of cellular distributions of DBTC in

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

    Science.gov (United States)

    Lin, Wen-Chuan; Lin, Wei-Lii

    2006-01-01

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

  11. Dose-dependent emergence of preneoplastic foci in rat livers after exposure to 2-nitropropane.

    Science.gov (United States)

    Denk, B; Filser, J G; Deml, E; Kessler, W; Shen, J; Oesterle, D

    1990-01-01

    Male and female Sprague-Dawley rats, 4-6 days old were exposed for 3 weeks (6 h/day, 5 days/week) to 2-nitropropane vapours of 0, 25, 40, 50, 80 and 125 ppm. One week later polychlorinated biphenyls (Clophen A50, 10 mg/kg body weight) were administered for promotion twice a week for 8 weeks. Thirteen weeks after starting the experiments the logarithms of the numbers of preneoplastic liver foci deficient in adenosine-5'-triphosphatase were found to be linearly related to the exposure concentrations of 2-nitropropane. Male rats exhibited an approximately four times lower foci incidence than females.

  12. Effects of Aqueous Stem Extract of Massularia Acuminata on Some Liver Function Indices of Male Rats

    OpenAIRE

    Musa Toyin Yakubu; Babasoji Percy Omoniwa

    2012-01-01

    Background: Massularia acuminata has been claimed to be used in managingseveral ailments in folk medicine and in some instances substantiated withscientific data. This however has been without recourse to its safety. Therefore,aqueous stem extract of M. acuminata was evaluated for its effects on somefunction indices of the liver of male rats.Methods: Sixty, male rats were grouped into 4 (A, B, C and D) such that Group A(control) was orally administered 1cm3 of distilled water while those in g...

  13. Dietary protein effects on cadmium and metallothionein accumulation in the liver and kidney of rats.

    OpenAIRE

    Revis, N W; Osborne, T R

    1984-01-01

    The relationship of dietary protein to cadmium absorption and tissue deposition was studied in male Sprague-Dawley rats exposed to different levels of cadmium in the drinking water. In animals fed a high-protein or low-protein diet and drinking water containing 25 or 50 ppm cadmium, liver and kidney cadmium and metallothionein were both significantly higher in rats fed the high-protein diet for 2 to 4 months. These differences may possibly be explained by the concentration of cysteine observe...

  14. Expression of isgylation related genes in regenerating rat liver

    Directory of Open Access Journals (Sweden)

    Kuklin A. V.

    2015-10-01

    Full Text Available Our recent studies have revealed the early up-regulated expression of interferon alpha (IFNα in the liver, induced by partial hepatectomy. The role of this cytokine of innate immune response in liver regeneration is still controversial. Aim. To analyze expression of canonical interferon-stimulated genes Ube1l, Ube2l6, Trim25, Usp18 and Isg15 during the liver transition from quiescence to proliferation induced by partial hepatectomy, and acute phase response induced by laparotomy. These genes are responsible for posttranslational modification of proteins by ISGylation. The expression of genes encoding TATA binding protein (TBP and 18S rRNA served as indirect general markers of transcriptional and translational activities. Methods. The abundance of investigated RNAs was assessed in total liver RNA by real time RT–qPCR. Results. Partial hepatecomy induced steady upregulation of the Tbp and 18S rRNA genes expression during 12 hours post-surgery and downregulation or no change in expression of ISGylation-related genes during the first 3 hours followed by slight upregulation at 12 hours. The level of Isg15 transcripts was permanently below that of the control during the prereplicative period. Laparotomy induced a continuous downregulation of Tbp and 18S rRNA expression and early (1–3h upregulation of ISGylation–related transcripts followed by a sharp drop at 6 hours and slight increase/decrease at 12 hours. The changes in the abundance of Ifnα and ISGylation-related mRNAs were oppositely directed at each stage of the response to partial hepatectomy and laparotomy. Conclusion. We suggest that the expression of ISGylation-related genes does not depend on the expression of Ifnα gene after both surgeries. The indirect indices of transcription and translation as well as the expression of ISGylation-relaled genes are principally different in response to partial hepatectomy and laparotomy and argue for the high specificity of innate immune response.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lourdes Sánchez-Sevilla

    2016-10-01

    Full Text Available Abstract Background The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH, by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. Methods This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC, and polyamine levels, were determined. Results Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Conclusions Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased

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

    Science.gov (United States)

    Sánchez-Sevilla, Lourdes; Mendieta-Condado, Edgar; Hernández-Muñoz, Rolando

    2016-10-26

    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. 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. 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. Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased retinoid levels induced by α-tocopherol. Therefore interactions

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Identification and characterization of the 2-enoyl-CoA hydratases involved in peroxisomal beta-oxidation in rat liver.

    OpenAIRE

    Dieuaide-Noubhani, M; Novikov, D.; Vandekerckhove, J.; Van Veldhoven, P P; Mannaerts, G P

    1997-01-01

    In this study we attempted to determine the number of 2-enoyl-CoA hydratases involved in peroxisomal beta-oxidation. We therefore separated peroxisomal proteins from rat liver on several chromatographic columns and measured hydratase activities on the eluates with different substrates. The results indicate that rat liver peroxisomes contain two hydratase activities: (1) a hydratase activity associated with multifunctional protein 1 (MFP-1) (2-enoyl-CoA hydratase/delta 3, delta 2-enoyl-CoA iso...

  20. Clinical characteristics and treatment of blow-out fracture accompanied by canalicular laceration.

    Science.gov (United States)

    Lee, Hwa; Ahn, Jaemoon; Lee, Tae Eun; Lee, Jong Mi; Shin, Hyungho; Chi, Mijung; Park, Minsoo; Baek, Sehyun

    2012-09-01

    Blow-out fracture and canalicular laceration can occur simultaneously as a result of the same trauma. Despite its importance, little research has been conducted to identify clinical characteristics or surgical techniques for repair of a blow-out fracture accompanied by canalicular laceration. The aim of this study was to evaluate the clinical characteristics, the surgical approach, and the outcomes. Thirty-four eyes of 34 patients who underwent simultaneous repair of canalicular laceration using silicone tube intubation and reconstruction of blow-out fracture were included. Medical records were retrospectively reviewed for patient demographics, nature of injury, affected canaliculus, location, and severity of blow-out fracture, associated facial bone fracture, ophthalmic diagnosis, length of follow-up period, and surgical outcome. Mean patient age was 40.0 years (range, 17-71 y). The mean follow-up was 7.3 months. Fist to the orbital area (10 patients, 29.4%) was the most common cause. There were 24 lower canalicular lacerations (70.6%), 6 upper canalicular lacerations (17.6%), and 4 upper and lower canalicular lacerations (11.8%). Isolated medial wall fractures were most common (area A4: 20/34, 58.8%). Fractures involving both the floor and medial wall and maxillo-ethmoidal strut (areas A1, A2, A3, and A4) were the second most common (6/34, 17.6%), and floor and medial wall with intact strut (areas A1, A2, and A4) were injured in 6 patients (17.6%). Pure inferior wall fractures were least frequent (areas A1 and A2: 2/34, 5.9%). The severity of the fracture was severe in most patients except for 1 linear fracture with tissue entrapment and 1 moderate medial wall fracture (32/34, 94.1%). There was lid laceration in 20 patients (58.8%). Nasal bone fracture (5/34, 14.7%) was the most common facial bone fracture. Tubes were removed at a mean of 3.3 months (range, 3-4 mo). In total, 31 patients (91.2%) achieved complete success in canalicular laceration and blow

  1. Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats.

    Science.gov (United States)

    Hamza, Alaaeldin A

    2010-01-01

    This study was carried out to evaluate the effect of Moringa oleifera Lam (Moringa) seed extract on liver fibrosis. Liver fibrosis was induced by the oral administration of 20% carbon tetrachloride (CCl(4)), twice weekly and for 8 weeks. Simultaneously, M.oleifera Lam seed extract (1g/kg) was orally administered daily. The biochemical and histological results showed that Moringa reduced liver damage as well as symptoms of liver fibrosis. The administration of Moringa seed extract decreased the CCl(4)-induced elevation of serum aminotransferase activities and globulin level. The elevations of hepatic hydroxyproline content and myeloperoxidase activity were also reduced by Moringa treatment. Furthermore, the immunohistochemical study showed that Moringa markedly reduced the numbers of smooth muscle alpha-actin-positive cells and the accumulation of collagens I and III in liver. Moringa seed extract showed significant inhibitory effect on 1,1-diphenyl-2-picrylhydrazyl free radical, as well as strong reducing antioxidant power. The activity of superoxide dismutase as well as the content of both malondialdehyde and protein carbonyl, which are oxidative stress markers, were reversed after treatment with Moringa. Finally, these results suggested that Moringa seed extract can act against CCl(4)-induced liver injury and fibrosis in rats by a mechanism related to its antioxidant properties, anti-inflammatory effect and its ability to attenuate the hepatic stellate cells activation. Copyright 2009 Elsevier Ltd. All rights reserved.

  2. Metabonomics study on Polygonum multiflorum induced liver toxicity in rats by GC-MS.

    Science.gov (United States)

    Zhang, Yuan; Wang, Nannan; Zhang, Meiling; Diao, Tingting; Tang, Jingyue; Dai, Mingzhu; Chen, Suhong; Lin, Guanyang

    2015-01-01

    Polygonum multiflorum, a traditional Chinese medicinal herb, is widely used in liver and liver nourishing. Recent years, drug regulatory departments reported that Polygonum multiflorum caused serious adverse reaction in clinic, especially liver injury. In this study, we detected the changes in rat serum and liver tissue metabolites through gas chromatography-mass spectrometry (GC-MS). Mass spectrometry, partial least squares-discriminate analysis (PLS-DA) and other diversified techniques were used to analyze the differences among their metabolites. Compared to the control group, the serum concentrations of L-threonine and serine in water extraction groups increased. The serum concentrations of 9,12-octadecadienoic acid, hexadecanoic acid, oleic acid, D-glucose and octadecanoic acid in alcohol extraction groups increased, while lactic acid decreased to a great extent. For liver tissue, compared to the control group, the concentrations of myo-inositol, oleic acid and cholesterol in water extraction groups increased, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased to a great extent. The concentrations of myo-inositol, phosphoric acid, uridine, oleic acid, cholesterol and butanoic acid in alcohol extraction groups increased to a great extent, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased. The results indicate that Polygonum multiflorum induces the metabolic disorders of energy metabolism, amino acid and lipid metabolism. What's more, liver injury of alcohol extraction group was more serious than group of water extraction.

  3. Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

    Science.gov (United States)

    Burukoglu, Dilek; Baycu, Cengiz; Taplamacioglu, Fulya; Sahin, Erhan; Bektur, Ezgi

    2016-06-01

    Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration. © The Author(s) 2014.

  4. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    Science.gov (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

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

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Olsen, P S

    1990-01-01

    Gastrin has been shown to be an important trophic hormone for the mucosa of the stomach and the proximal intestine. In the present study the effect of gastrin on liver regeneration after partial hepatectomy in rats was investigated. After partial hepatectomy a significant rise in the concentration...... of gastrin in portal venous blood was found six, 12, and 18 hours after 70% hepatectomy. The effect of changes in the endogenous gastrin concentration on the liver regeneration was investigated in rats subjected to antrectomy or to fundectomy. Partial hepatectomy was done three weeks after the primary...... suggests that gastrin has a hepatotrophic effect. Whether this effect is caused by a direct action of gastrin on the hepatocytes or it is an indirect effect mediated by for instance insulin, glucagon or epidermal growth factor has to be further investigated....

  6. Prebiotic and Synbiotic Modifications of Beta Oxidation and Lipogenic Gene Expression after Experimental Hypercholesterolemia in Rat Liver

    Directory of Open Access Journals (Sweden)

    Claudia C. Alves

    2017-10-01

    Full Text Available Background and aims: Non-alcoholic fatty liver disease (NAFLD is characterized by the presence of fat in hepatocytes because of decreased β-oxidation and increased lipogenesis. Prebiotics, probiotics, and synbiotic have modulatory effects on intestinal microbiota and may influence the gut-liver axis. Our aim was to evaluate the effects of prebiotic, probiotics, and synbiotic on liver histopathology and gene expression related to β-oxidation and lipogenesis after hypercholesterolemia.Methods: Wistar male adult rats (n = 40 were submitted to hypercholesterolemic conditions (HPC (60 days. On Day 30 of HPC, rats were subdivided in 5 groups: negative control (NC: without HPC + Gv (distilled water; positive control (PC: with HPC + Gv (distilled water; prebiotic (PRE: HPC + Gv with prebiotic (Fiber FOS®; probiotic (PRO: HPC + Gv with probiotic strains Gv (Probiatop®; and synbiotic (SYN: HPC + Gv with synbiotic (Simbioflora®. All rats were sacrificed on Day 30 post-treatment. Blood was collected to verify total serum cholesterol, and liver tissue was sampled to verify histopathological changes and gene expression. Gene expression related to ß-oxidation (PPAR-α and CPT-1 and lipogenesis (SREBP-1c, FAS and ME was evaluated in liver tissue using RT-qPCR.Results: PC had higher cholesterol levels when compared to NC. PRE and SYN rats had lower cholesterol levels than PC. PC rats showed more histopathological changes than NC rats; PRE and SYN rats showed fewer alterations than PC rats. PPAR-α was expressed at higher levels in SYN and PC rats compared with PRE and PRO rats. CPT-1 expression was similar in all groups. SREBP-1c was expressed at higher levels in PC rats compared with NC rats; levels were lower in SYN rats compared with PRO rats; levels were lower in PRE rats compared with PC and PRO rats. FAS was expressed at lower levels in PRE rats compared with SYN rats. ME expression was lower in PC rats compared with NC rats.Conclusion: Prebiotic and

  7. Experimental liver fibrosis induced in rats receiving high doses of alcohol and alternating between regular and vitamin-depleted diets.

    Science.gov (United States)

    Hirano, H; Hirano, T; Hirata, K; Tamura, M; Yamaura, T; Hamada, T

    1996-07-15

    Liver fibrosis was induced in rats by simulating human alcoholic eating and drinking patterns. Alcohol addiction was established by gradually increasing the ethanol concentration in the drinking water; salts were added at the terminal stage. The hepatocytes of rats receiving alcohol concentrations exceeding 50% (v/v) (similar to vodka) exhibited alcoholic hyaline (Mallory bodies). Alcoholic liver fibrosis was induced by alternating between regular and autoclaved (vitamin-depleted) diets, simulating the irregular eating habits of human alcoholics. In the livers of rats receiving 70% (v/v) ethanol (comparable to absinthe) with 25% saline and fed the alternating diets, pericellular fibrosis was induced. No significant difference in calorie intake between control and alcohol rats was detected except when rats underwent drinking bouts (heavy drinking phase). This indicates that neither a high-fat diet nor a choline-depleted diet is necessary to induce the alcoholic fibrosis seen in human alcoholics.

  8. Anti-oxidative and anti-inflammatory effects of lipoic acid in rat liver

    Directory of Open Access Journals (Sweden)

    Anna Goraca

    2015-03-01

    Full Text Available Introduction: Lipopolysaccharide (LPS is a key inflammatory component of Gram-negative bacteria, which after entering the systemic circulation contributes to the development of septic hepatic failure.Aim: The aim of this study was to evaluate the effects of alpha lipoic acid (LA on oxidative stress parameters and inflammation in endotoxemic rat liver.Material/Methods: Male Wistar rats were divided into 4 groups, each group consisting of 8 animals. Group I received saline and served as a control, Group II received a single dose of LA (60 mg/kg i.v., Group III received lipopolysaccharide (LPS (15 mg/kg i.v., and Group IV received LPS (15 mg/kg i.v. and 30 min later received LA (60 mg/kg i.v.. Five hours after LPS or LA administration, the animals were sacrificed and the liver was isolated for measurements of levels of thiobarbituric acid reactive substances (TBARS, hydrogen peroxide (H2O2, total sulfhydryl groups (-SH, total glutathione (tGSH and reduced glutathione (GSH.Results: Injection of LPS caused a significant increase in liver TBARS and H2O2 levels and a significant decrease in levels of -SH groups, tGSH and GSH. LPS-treated rats also showed an increase in TNF-α and IL-6 levels and edema in the liver. The administration of LA to endotoxemic rats significantly reduced TBARS, H2O2, TNF-α, and IL-6 levels and reduced edema in the liver when compared to the LPS group. This antioxidant also resulted in an increase in -SH groups and tGSH and GSH levels and ameliorated the glutathione redox status when compared to the LPS group.Conclusions: The results indicated that LA administered 30 min following LPS infusion may effectively prevent oxidative stress and inflammation in the liver. Thus LA is a potent antioxidant that can be useful in rebuilding LPS-induced damaged liver tissue.

  9. Citrulline decreases hepatic endotoxin-induced injury in fructose-induced non-alcoholic liver disease: an ex vivo study in the isolated perfused rat liver.

    Science.gov (United States)

    Ouelaa, Wassila; Jegatheesan, Prasanthi; M'bouyou-Boungou, Japhète; Vicente, Christelle; Nakib, Samir; Nubret, Esther; De Bandt, Jean-Pascal

    2017-06-01

    Steatosis can sensitise the liver to various challenges and favour the development of non-alcoholic fatty liver disease (NAFLD). In this context, fructose feeding promotes endotoxin translocation from the gut, contributing to disease progression via an inflammatory process. Citrulline is protective against fructose-induced NAFLD; we hypothesised that this property might be related to its anti-inflammatory and antioxidative action against endotoxin-induced hepatic injuries. This hypothesis was evaluated in a model of perfused liver isolated from NAFLD rats. Male Sprague-Dawley rats (n 30) were fed either a standard rodent chow or a 60 % fructose diet alone, or supplemented with citrulline (1 g/kg per d) for 4 weeks. After an evaluation of their metabolic status, fasted rats received an intraperitoneal injection of lipopolysaccharide (LPS) (2·5 mg/kg). After 1 h, the livers were isolated and perfused for 1 h to study liver function and metabolism, inflammation and oxidative status. In vivo, citrulline significantly decreased dyslipidaemia induced by a high-fructose diet and insulin resistance. In the isolated perfused rat livers, endotoxaemia resulted in higher cytolysis (alanine aminotransferase release) and higher inflammation (Toll-like receptor 4) in livers of fructose-fed rats, and it was prevented by citrulline supplementation. Oxidative stress and antioxidative defences were similar in all three groups. Amino acid exchanges and metabolism (ammonia and urea release) were only slightly different between the three groups. In this context of mild steatosis, our results suggest that fructose-induced NAFLD leads to an increased hepatic sensitivity to LPS-induced inflammation. Citrulline-induced restriction of the inflammatory process may thus contribute to the prevention of NAFLD.

  10. Effect of bone marrow mesenchymal stem cells transplantation on the serum and liver HMGB1 expression in rats with acute liver failure.

    Science.gov (United States)

    Zheng, Sheng; Yang, Juan; Tang, Yingmei; Yang, Jinhui; Shao, Qinghua; Guo, Ling; Liu, Qinghua

    2015-01-01

    This study aimed to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of high mobility group box 1 protein (HMGB1) in the serum and liver of rats with acute liver failure (ALF). Healthy male SD rats were randomly divided into control group, ALF group and BMSCs group. ALF was induced by intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS. In BMSCs group, rats received BMSCs (1.0×10(7)) transplantation via the tail vein at 2 h after ALF induction. Intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS was able to induce ALF in rats. In ALF group, serum ALT and AST increased gradually over time. At 72 h, the serum ALT and AST in BMSCs group were significantly different from those in ALF group. HMGB1 expression in the serum and liver remained at a low level at any time point in control group, but increased significantly in ALF group and BMSCs group. The serum and liver HMGB1 expression increased progressively in ALF group, but reduced gradually in BMSCs group. Significant difference in serum and liver HMGB1 expression was observed between ALF group and BMSCs group at 24 h and 72 h. In addition, there was marked difference in the survival rate among three groups at 24 h (χ (2) =21.098, Pliver function and liver pathology in ALF rats and decrease the serum and liver HMGB1.

  11. The antifibrogenic effect of etanercept on development of liver cirrhosis induced by thioacetamide in rats.

    Science.gov (United States)

    Abdul-Hamid, Manal; Ahmed, Rasha R; Moustafa, Nadia; Nady, Rehab

    2017-01-01

    Liver cirrhosis is an elevating cause of morbidity and mortality worldwide. TNF-α/TNF-R1 signal is implicated in progression of many liver diseases. This study provides histological and ultrastructural view that clarifies the effect of etanercept, a TNF-α inhibitor, on development of thioacetamide (TAA)-induced liver cirrhosis and the accompanied hemosiderosis in rats, highlighting the implication and distribution pattern of hepatic TNF-R1. Sixty male albino rats (Rattus norvegicus) were equally randomized into three groups. Group I served as the control. Liver cirrhosis was triggered in the other two groups by intraperitoneal injection of TAA twice a week for five months. Group II received TAA only, while group III subcutaneously injected with etanercept one hour before TAA, along five months. At the end of the experiment, blood was collected for biochemical analysis and livers were excised for histological, immunohistochemical, and electron microscopical preparations. Rats treated with TAA only developed hepatic cirrhosis accompanied by massive deposition of hemosiderin; strong and widespread expression of hepatic TNF-R1 in sinusoidal endothelial cells (SECs), Kupffer cells (KCs), and many hepatocytes; and frequent appearance of fibrogenic, plasma, and mast cells, at the ultrastructural level. By contrast, administration of etanercept diminished the expression of TNF-R1, attenuated the accumulation of collagen and hemosiderin, and preserved the hepatic histoarchitecture. In conclusion, TNF-α signal via TNF-R1 may be implicated in the mechanism of fibrogenesis and the associated hemosiderosis. Etanercept may provide a promising therapeutic approach not only for attenuating the progression of fibrogenesis, but also for hepatic iron overload-associated disorders.

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

    Science.gov (United States)

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

    2015-07-02

    Fipronil is an insecticide used to control pests in animals and plants that can causes hepatotoxicity in animals and humans, and it is hepatically metabolized to fipronil sulfone by cytochrome P-450. The present study aimed to characterize the effects of fipronil (10-50μM) on energy metabolism in isolated perfused rat livers. In fed animals, there was increased glucose and lactate release from glycogen catabolism, indicating the stimulation of glycogenolysis and glycolysis. In the livers of fasted animals, fipronil inhibited glucose and urea production from exogenous l-alanine, whereas ammonia and lactate production were increased. In addition, fipronil at 50μM concentration inhibited the oxygen uptake and increased the cytosolic NADH/NAD⁺ ratio under glycolytic conditions. The metabolic alterations were found both in livers from normal or proadifen-pretreated rats revealing that fipronil and its reactive metabolites contributed for the observed activity. The effects on oxygen uptake indicated that the possible mechanism of toxicity of fipronil involves impairment on mitochondrial respiratory activity, and therefore, interference with energy metabolism. The inhibitory effects on oxygen uptake observed at the highest concentration of 50μM was abolished by pretreatment of the rats with proadifen indicating that the metabolites of fipronil, including fipronil sulfone, acted predominantly as inhibitors of respiratory chain. The hepatoxicity of both the parent compound and its reactive metabolites was corroborated by the increase in the activity of lactate dehydrogenase in the effluent perfusate in livers from normal or proadifen-pretreated rats. Copyright © 2015. Published by Elsevier Ireland Ltd.

  13. Protective Effect of Ghrelin on Sodium Valproate-induced Liver Injury in Rat

    OpenAIRE

    Sadeghi Niaraki, Mandana; Nabavizadeh, Fatemeh; Vaezi, Gholam H.; Alizadeh, Ali M.; Nahrevanian, Hossein; Moslehi, Azam; Azizian, Saleh

    2013-01-01

    Ghrelin is a peptide that has protective effects on many tissues injury. It has anti-inflammatory and anti-oxidant effects. Sodium valproate is widely used anticonvuisant and anti-depression drug with hepatotoxic side effects. The aim of this study was to evaluated the protective role of ghrelin in liver toxicity due to sodium valproate overdose. Eighteen rats were used in this study and divided in to three groups, containing: control, sodium valproate, and sodium valproate and ghrelin groups...

  14. Protective effect of ghrelin on sodium Valproate-induced liver injury in rat

    OpenAIRE

    Sadeghi, Niaraki; Nabavizadeh, Fatemeh; Vaezi, Gholam; Alizadeh, Ali; Nahrevanian, Hossein; Moslehi, Azam; Azizian, Saleh

    2013-01-01

    Ghrelin is a peptide that has protective effects on many tissues injury. It has anti-inflammatory and anti-oxidant effects. Sodium valproate is widely used anticonvuisant and anti-depression drug with hepatotoxic side effects. The aim of this study was to evaluated the protective role of ghrelin in liver toxicity due to sodium valproate overdose. Eighteen rats were used in this study and divided in to three groups, containing: control, sodium valproate, and sodium valproate and ghrelin groups...

  15. Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs

    NARCIS (Netherlands)

    TSAI, A. C.; THIE, G. M.; Lin, C. R.

    1977-01-01

    The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was

  16. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

    NARCIS (Netherlands)

    Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

  17. Cytotoxicity of retinoic acid, menadione and aflatoxin B1 in rat liver slices using netwell inserts as a culture system

    NARCIS (Netherlands)

    Leeman, W.R.; Gevel, I.A. van de; Rutten, A.A.J.J.L.

    1995-01-01

    Precision-cut rat liver slices were used to develop a new dynamic incubation system in which histomorphology and measurement of the release of lactate dehydrogenase (LDH) and the conversion of MTT were applied to evaluate cytotoxicity. Liver slices, precision-cut using a Krumdieck tissue slicer,

  18. Expression of aquaporin 9 in rat liver and efferent ducts of the male reproductive system after neonatal diethylstilbestrol exposure

    DEFF Research Database (Denmark)

    Wellejus, Anja; Jensen, Henrik E; Loft, Steffen

    2008-01-01

    Aquaporins (AQP) have important solute transport functions in many tissues including the epididymal efferent ducts (ED) and in the liver. We investigated the effect of neonatal exposure to diethylstilbestrol (DES) on AQP9 expressions in the ED and in the liver of rats. DES was administered from d...

  19. Virtual determination of liver and muscle glycogen obtained from fed rats and from 24-hour fasted rats

    Directory of Open Access Journals (Sweden)

    V.M.T.T. Trindidade et al

    2014-08-01

    Full Text Available Introduction: Glycogen is the storage polysaccharide of animals, composed by glucoseresidues forming a branched polymer. The liver glycogen metabolism and hepaticgluconeogenesis are important buffer systems of blood glucose in different physiological orpathological situations, such as, during a fast period. Fasting muscle glycogenolysis alsooccurs, however, the release of glucose into the bloodstream is negligible because themuscle doesn’t have the enzyme glucose-6-P phosphatase, which is present in the liver.Objectives: This panel presents a learning object, mediated by computer, which simulatesthe determination of liver and muscle glycogen obtained from fed rats and from 24-hourfasted rats Materials and Methods: At first, cartoons were planned in order to show themethodology procedures and biochemical fundamentals. The most representative imageswere selected, edited, organized in a scene menu and inserted into an animationdeveloped with the aid of the Adobe ® Flash 8 software. The validation of this object wasperformed by the students of Biochemistry I (Pharmacy-UFRGS from the secondsemester of 2009 until the second semester of 2013. Results and Discussion: Theanalysis of students' answers revealed that 83% of them attributed the excellence rate tothe navigation program, to the display format and to the learning help. Conclusion:Therefore, this learning object can be considered an adequate teaching resource as wellas an innovative support in the construction of theoretical and practical knowledge ofBiochemistry. Support: SEAD-UFRGSAvailable at: http://www.ufrgs.br/gcoeb/obtencaodosagemglicogenio/

  20. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    Science.gov (United States)

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  1. Influence of some aliphatic alcohols on the metabolism of rat liver slices.

    Science.gov (United States)

    Forsander, O A

    1967-10-01

    The influence of some aliphatic alcohols on oxygen uptake, carbon dioxide production, acid formation and lactate and pyruvate concentrations of rat liver slices was studied. At the concentrations used, none of the alcohols was found to influence oxygen uptake. Of the alcohols that are not oxidized by liver alcohol dehydrogenase, methanol increased carbon dioxide production, propan-2-ol decreased it and 2-methylpropan-2-ol was without influence. All the alcohols that are oxidized by the enzyme strongly decreased carbon dioxide production. The alcohols that are not oxidized had no marked effect on the lactate/pyruvate concentration ratio, whereas the other alcohols strongly increased the ratio. A highly significant correlation was found between the effects of the alcohol on pyruvate concentration and carbon dioxide production. It is assumed that the shift in the redox potential inhibits the function of the tricarboxylic acid cycle of the liver.

  2. Proteomic Analysis of Liver Proteins in a Rat Model of Chronic Restraint Stress-Induced Depression

    Directory of Open Access Journals (Sweden)

    Cong Li

    2017-01-01

    Full Text Available Depression is a global mental disorder disease and greatly threatened human health and stress is considered to be one of the important factors that lead to depression. In this study, we used newly developed iTRAQ labeling and high performance liquid chromatography (HPLC and mass spectrum united analysis technology obtained the 2176 accurate proteins. Successively, we used the GO analysis and IPA software to analyze the 98 differentially expressed proteins of liver in depression rats due to chronic restraint stress, showing a map of proteomics analysis of liver proteins from the aspects of related functions, disease and function analysis, canonical pathway analysis, and associated network. This study provide important information for comprehensively understanding the mechanisms of dysfunction or injury in the liver in depression.

  3. A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

    OpenAIRE

    Bayol, Stéphanie A; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

    2010-01-01

    With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow...

  4. Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats.

    Science.gov (United States)

    Mahmoodzadeh, Yavar; Mazani, Mohammad; Rezagholizadeh, Lotfollah

    2017-01-01

    The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE) on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4). 54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups), 4 of them were exposure groups which were respectively administered with 40, 80, and 120 mg/kg of TPE and silymarin for 14 days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120 mg/kg of TPE and silymarin 2, 6, 24, and 48 h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed. Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group. The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4.

  5. Clotrimazole protects the liver against normothermic ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Iannelli, A; de Sousa, G; Zucchini, N; Peyre, L; Gugenheim, J; Rahmani, R

    2009-12-01

    To investigate the possible antiapoptotic prosurvival role of the pregnane X receptor (PXR) in hepatic ischemia-reperfusion injury in rats using clotrimazole (CTZ), a strong PXR transactivator. Male Sprague-Dawley rats were divided into 3 groups of 6 each: sham-treated, control, and CTZ-treated animals. Control and CTZ-treated animals were subjected to 30 minutes of normothermic ischemia of the whole liver followed by 6 hours of reperfusion. The animals were then killed, and the liver was excised and blood samples collected. Clotrimazole induced a significant increase in expression of the CYP3A gene, indicating PXR transactivation, whereas expression of the antiapoptotic Bcl-xL gene was not increased. Serum concentrations of aspartate aminotransaminase and alanine aminotransaminase were lower in CTZ-treated animals than in control animals (difference not significant). Levels of poly(adenosine diphosphate-ribose) polymerase, a caspase-3 substrate, remained significantly higher in the CTZ-treated group compared with controls (P CTZ-treated animals than in controls (P < .05). Clotrimazole-mediated PXR transactivation protects the liver against ischemia-reperfusion apoptosis in rats. Phospho-p 44/42 extracellular signal-regulated kinase 1,2 is activated, whereas gene expression of heat shock proteins 27, 70, and 90 is downregulated by induction of PXR.

  6. Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats.

    Science.gov (United States)

    Oguz, Serhat; Kanter, Mehmet; Erboga, Mustafa; Ibis, Cem

    2013-10-01

    The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL + received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.

  7. 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)

  8. Protective effect of Sida cordata leaf extract against CCl(4) induced acute liver toxicity in rats.

    Science.gov (United States)

    Mistry, Sunil; Dutt, K R; Jena, J

    2013-04-13

    To investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim. Wister albino rats were divided into 6 groups: Group I served as control; Group II served as hepatotoxic (CCl(4) treated) group; Group III, IV and V served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group VI served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies. Obtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl4 induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies. The results of this study strongly indicate the protective effect of SCLE against CCl(4) induced acute liver toxicity in rats and thereby scientifically support its traditional use. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  9. Functional and proliferative effects of repeated low-dose oral administration of furan in rat liver.

    Science.gov (United States)

    Mally, Angela; Graff, Carmen; Schmal, Olga; Moro, Sabrina; Hamberger, Carolin; Schauer, Ute M; Brück, Jens; Ozden, Sibel; Sieber, Max; Steger, Ulrich; Schrenk, Dieter; Hard, Gordon C; Chipman, James Kevin; Dekant, Wolfgang

    2010-11-01

    Furan, a food contaminant formed during heat processing, induces hepatocellular tumors in rodents and high incidences of cholangiocarcinomas in rats even at the lowest dose (2 mg/kg b.w.) administered. Initial estimates suggested that human intake of furan may be as high as 3.5 μg/kg b.w./day, indicating a relatively narrow margin of exposure. The aim of this study was to establish dose-response data for cytotoxicity, regenerative cell proliferation and secondary oxidative DNA damage in livers of male F344 rats treated with furan at doses ≤2 mg/kg b.w. for 28 days. No significant signs of hepatotoxicity other than a mild, dose-dependent increase in serum cholesterol and unconjugated bile acids, and no evidence of oxidative DNA damage were seen. Histopathological alterations and proliferative changes were restricted to subcapsular areas of the left and caudate liver lobes. Although statistically significant effects were only seen at the 2 mg/kg b.w. dose during the course of our study, a ∼two and ∼threefold increase in 5-bromo-2'-deoxyuridine labeling index was observed at 0.1 and 0.5 mg/kg b.w., respectively, suggesting that chronic exposure to doses even below 2 mg/kg b.w. may cause proliferative changes in rat liver and highlighting the need to assess furan carcinogenicity at lower doses.

  10. Successful Transplantation of Reduced Sized Rat Alcoholic Fatty Livers Made Possible by Mobilization of Host Stem Cells

    Science.gov (United States)

    Hisada, Masayuki; Ota, Yoshihiro; Zhang, Xiuying; Cameron, Andrew M; Gao, Bin; Montgomery, Robert A; Williams, George Melville; Sun, Zhaoli

    2015-01-01

    Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for transplantation. Reduced sized (50%) livers or whole livers were transplanted into normal DA recipients, which, in this strain combination, survive indefinitely when the donor has not been fed alcohol. However, none of the rats survived a whole fatty liver transplant while six of seven recipients of reduced sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly increased in reduced size liver grafts compared to whole liver grafts. Lineage-negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the peripheral blood and in allografts after reduced size fatty liver transplantation. In contrast, there were meager increases in cells reactive with anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5 of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with neutralizing antibodies diminished stem cell recruitment and four of five reduced sized fatty liver recipients died. Thus chemokine insuficiency was associated with transplant failure of whole grafts which was overcome by the increased regenerative requirements promoted by the small grafts and mediated by SDF-1 resulting in stem cell influx. PMID:22994609

  11. Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats

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    Sayed M. Mizar

    2015-03-01

    Full Text Available Oxidative stress plays a key role in the pathogenesis of hepatic ischemia/reperfusion (I/R-induced injury, one of the leading causes of liver damage post-surgical intervention, trauma and transplantation. This study aimed to evaluate the protective effect of nebivolol and chrysin against I/R-induced liver injury via their vasodilator and antioxidant effects, respectively. Adult male Wister rats received nebivolol (5 mg/kg and/or chrysin (25 mg/kg by oral gavage daily for one week then subjected to ischemia via clamping the portal triad for 30 min then reperfusion for 30 min. Liver function enzymes, alanine transaminase (ALT and aspartate transaminase (AST, as well as hepatic Myeloperoxidase (MPO, total nitrate (NOx, glutathione (GSH and liver malondialdehyde (MDA were measured at the end of the experiment. Liver tissue damage was examined by histopathology. In addition, the expression levels of nitric oxide synthase (NOS subtypes, endothelial (eNOS and inducible (iNOS in liver samples were assessed by Western blotting and confirmed by immunohistochemical analysis. Both chrysin and nebivolol significantly counteracted I/R-induced oxidative stress and tissue damage biomarkers. The combination of these agents caused additive liver protective effect against I/R-induced damage via the up regulation of nitric oxide expression and the suppression of oxidative stress. Chrysin and nebivolol combination showed a promising protective effect against I/R-induced liver injury, at least in part, via decreasing oxidative stress and increasing nitric oxide levels.

  12. Hepatoprotective Effect of Trigona spp. Bee Propolis against Carbon Tetrachloride-Induced Liver Injury in Rat

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    Rachel Amelia

    2016-06-01

    Full Text Available Background: Oxidative stress reaction can cause liver injury. This process can be prevented by antioxidant activities which can break the destructive chain caused by free radical substances in the liver. Propolis produced by Trigona spp. bee is known to have a high level of antioxidant. The aim of this study was to examine the effect of Trigona spp. bee propolis on liver histological toxicity caused by carbon tetrachloride-induced oxidative stress. Methods:This experimental study was conducted in September 2013 at the Animal Laboratory of Departement of Pharmacology and Therapy, Faculty of Medicine Universitas Padjadjaran. Twenty-four healthy male Wistar rats as objects were adapted for one week and randomly divided into 3 groups. Group I was the control negative, group II was given carbon tetrachloride on day 14, group III was given Trigona spp. bee propolis on day 1-14. On day 14, group III was injected CCl4 intraperitoneally. The quantitative data were statistically analyzed using the one way ANOVA and Tukey test with p value < 0.05. Results: Group I showed the liver contained normal cells, without significant injury of the membrane, round and complete nucleus. The average number of liver cell was 464 ± 9.59281 cells/field; group II underwent necrosis and the average of the cells was 146 ± 7.56885 cells/field; group III showed some normal liver cells, and some necrotic area with the normal liver cells average was 263 ± 14.10860 cells/field. The p-value=0.00. Conclusions: Trigona spp. bee propolis has a hepatoprotective effect against CCl4-induced liver injury histologically.

  13. Antifibrotic activity of hesperidin against dimethylnitrosamine-induced liver fibrosis in rats.

    Science.gov (United States)

    Elshazly, Shimaa M; Mahmoud, Amr A A

    2014-06-01

    Hepatic fibrosis is a significant health problem that may progress to cirrhosis and cancer. It may be caused by viruses or chemicals such as dimethylnitrosamine, which is used as a preservative in processed meats and industrial products. The present study was designed to investigate the antifibrotic effect of hesperidin (100 or 200 mg/kg, a flavanone glycoside with potent anti-inflammatory and antioxidant activities) against liver fibrosis in rats compared to silymarin (100 mg/kg). Liver fibrosis was induced in rats using dimethylnitrosamine (10 mg/kg/day, i.p.) three times per week on alternating days for 4 weeks. After 28 days, tissue and blood samples were collected to assess the protective effect of hesperidin. Dimethylnitrosamine caused liver fibrosis as evidenced by the elevation in the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, as well as hepatic malondialdehyde content, gene expression of inducible nitric oxide synthase, α-smooth muscle actin and caspase-3. In addition, dimethylnitrosamine caused a reduction in serum total protein, albumin and hepatic glutathione content. Treatment with hesperidin (100 or 200 mg/kg) successfully ameliorated the deleterious effects of dimethylnitrosamine on all tested parameters. Our study indicates a novel protective effect of hesperidin against dimethylnitrosamine-induced liver fibrosis. Interestingly, the protection evoked by hesperidin (200 mg/kg) was superior to that of the standard silymarin.

  14. Deregulation of Regulatory T Cells in Acute-on-Chronic Liver Failure: A Rat Model.

    Science.gov (United States)

    Ni, Shunlan; Li, Shanshan; Yang, Naibin; Tang, Xinyue; Zhang, Shengguo; Hu, Danping; Lu, Mingqin

    2017-01-01

    Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months. Then acute liver injury was induced by combined D-galactosamine and lipopolysaccharide. Six time points were examined before or after acute induction. Liver samples were performed with hematoxylin-eosin and Masson staining; circulatory Treg and Th17 cell frequencies were determined using flow cytometry assays; serum levels of alanine aminotransferase, aspartate aminotransferase, interleukin-10 (IL-10), and interferon-γ (IFN-γ) were examined. Results. In group ACLF, both Th17 cell proportion and IFN-γ level presented upgrade firstly and then descend latter tendency; the trends of Treg cell proportion and IL-10 level were observed to gradually decrease and became stable. Conclusion. The Treg cells played an important role in the immunologic mechanism during the process of ACLF. And the function of Treg cells in ACLF was defective.

  15. Comparative Proteomics Provides Insights into Metabolic Responses in Rat Liver to Isolated Soy and Meat Proteins.

    Science.gov (United States)

    Song, Shangxin; Hooiveld, Guido J; Zhang, Wei; Li, Mengjie; Zhao, Fan; Zhu, Jing; Xu, Xinglian; Muller, Michael; Li, Chunbao; Zhou, Guanghong

    2016-04-01

    It has been reported that isolated dietary soy and meat proteins have distinct effects on physiology and liver gene expression, but the impact on protein expression responses are unknown. Because these may differ from gene expression responses, we investigated dietary protein-induced changes in liver proteome. Rats were fed for 1 week semisynthetic diets that differed only regarding protein source; casein (reference) was fully replaced by isolated soy, chicken, fish, or pork protein. Changes in liver proteome were measured by iTRAQ labeling and LC-ESI-MS/MS. A robust set totaling 1437 unique proteins was identified and subjected to differential protein analysis and biological interpretation. Compared with casein, all other protein sources reduced the abundance of proteins involved in fatty acid metabolism and Pparα signaling pathway. All dietary proteins, except chicken, increased oxidoreductive transformation reactions but reduced energy and essential amino acid metabolic pathways. Only soy protein increased the metabolism of sulfur-containing and nonessential amino acids. Soy and fish proteins increased translation and mRNA processing, whereas only chicken protein increased TCA cycle but reduced immune responses. These findings were partially in line with previously reported transcriptome results. This study further shows the distinct effects of soy and meat proteins on liver metabolism in rats.

  16. Down-regulation of MiR-127 facilitates hepatocyte proliferation during rat liver regeneration.

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    Chuanyong Pan

    Full Text Available Liver regeneration (LR after partial hepatectomy (PH involves the proliferation and apoptosis of hepatocytes, and microRNAs have been shown to post-transcriptionally regulate genes involved in the regulation of these processes. To explore the role of miR-127 during LR, the expression patterns of miR-127 and its related proteins were investigated. MiR-127 was introduced into a rat liver cell line to examine its effects on the potential target genes Bcl6 and Setd8, and functional studies were undertaken. We discovered that miR-127 was down-regulated and inversely correlated with the expression of Bcl6 and Setd8 at 24 hours after PH, a time at which hypermethylation of the promoter region of the miR-127 gene was detected. Furthermore, in BRL-3A rat liver cells, we observed that overexpression of miR-127 significantly suppressed cell growth and directly inhibited the expression of Bcl6 and Setd8. The results suggest that down-regulation of miR-127 may be due to the rapid methylation of its promoter during the first 24 h after PH, and this event facilitates hepatocyte proliferation by releasing Bcl6 and Setd8. These findings support a miRNA-mediated negative regulation pattern in LR and implicate an anti-proliferative role for miR-127 in liver cells.

  17. Acute liver damage induced by 2-nitropropane in rats: effect of diphenyl diselenide on antioxidant defenses.

    Science.gov (United States)

    Borges, Lysandro P; Nogueira, Cristina Wayne; Panatieri, Rodrigo B; Rocha, João Batista Teixeira; Zeni, Gilson

    2006-03-25

    The effect of post-treatment with diphenyl diselenide on liver damage induced by 2-nitropropane (2-NP) was examined in male rats. Rats were pre-treated with a single dose of 2-NP (100 mg/kg body weight dissolved in canola oil). Afterward, the animals were post-treated with a dose of diphenyl diselenide (10, 50 or 100 micromol/kg). The parameters that indicate tissue damage such as liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), urea and creatinine were determined. Since the liver damage induced by 2-NP is related to oxidative damage, lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and ascorbic acid level were also evaluated. Diphenyl diselenide (50 and 100 micromol/kg) effectively restored the increase of ALT and AST activities and urea level when compared to the 2-NP group. At the higher dose, diphenyl diselenide decreased GGT activity. Treatment with diphenyl diselenide, at all doses, effectively ameliorated the increase of hepatic and renal lipid peroxidation when compared to 2-NP group. 2-NP reduced CAT activity and neither alter SOD activity nor ascorbic acid level. This study points out the involvement of CAT activity in 2-NP-induced acute liver damage and suggests that the post-treatment with diphenyl diselenide was effective in restoring the hepatic damage induced by 2-NP.

  18. Fe-nitrilotriacetic acid--binding proteins associated with rat liver plasma membranes.

    Science.gov (United States)

    Barisani, D; Wessling-Resnick, M

    1996-10-01

    The uptake of nontransferrin-bound iron by hepatocytes is known to occur and may contribute to the deposition of iron and resulting injury during hemochromatosis. To examine the proteins that may function in the transport of nontransferrin-bound iron, the properties of FeNTA-binding to rat liver basolateral plasma membranes were characterized. The binding of 55FeNTA to purified liver basolateral plasma membranes was measured using a simple centrifugation assay. The binding activity could be solubilized with 0.1% octylglucoside; apparent molecular weight Mapp approximately 210 kd for the binding complex was determined by gel filtration chromatography. Immobilized metal affinity chromatography was used to further purify binding protein(s) from rat liver plasma membranes and at least six polypeptides were identified by silver staining. If associated in a stoichiometric complex, the molecular mass of these proteins would predict a size of approximately 227 kd in fairly close agreement with the gel filtration experiments. The characterization of FeNTA-binding proteins associated with basolateral membranes is the first step towards understanding elements responsible for the uptake of nontransferrin-bound iron by the liver.

  19. Sparse Logistic Regression for Diagnosis of Liver Fibrosis in Rat by Using SCAD-Penalized Likelihood

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    Fang-Rong Yan

    2011-01-01

    Full Text Available The objective of the present study is to find out the quantitative relationship between progression of liver fibrosis and the levels of certain serum markers using mathematic model. We provide the sparse logistic regression by using smoothly clipped absolute deviation (SCAD penalized function to diagnose the liver fibrosis in rats. Not only does it give a sparse solution with high accuracy, it also provides the users with the precise probabilities of classification with the class information. In the simulative case and the experiment case, the proposed method is comparable to the stepwise linear discriminant analysis (SLDA and the sparse logistic regression with least absolute shrinkage and selection operator (LASSO penalty, by using receiver operating characteristic (ROC with bayesian bootstrap estimating area under the curve (AUC diagnostic sensitivity for selected variable. Results show that the new approach provides a good correlation between the serum marker levels and the liver fibrosis induced by thioacetamide (TAA in rats. Meanwhile, this approach might also be used in predicting the development of liver cirrhosis.

  20. Protective Effect of Ghrelin on Sodium Valproate-induced Liver Injury in Rat

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    Sadeghi Niaraki, Mandana

    2013-02-01

    Full Text Available Ghrelin is a peptide that has protective effects on many tissues injury. It has anti-inflammatory and anti-oxidant effects. Sodium valproate is widely used anticonvuisant and anti-depression drug with hepatotoxic side effects. The aim of this study was to evaluated the protective role of ghrelin in liver toxicity due to sodium valproate overdose. Eighteen rats were used in this study and divided in to three groups, containing: control, sodium valproate, and sodium valproate and ghrelin groups. Nitric oxide (NO, prostaglandin E2 (PGE2 and hepatic enzymes AST (aspartate aminotransferase and ALT (alanine aminotransferase, were assessed and histologic study of liver were performed as indicators of liver damage following sodium valproate toxicity. This study showed the ghrelin decreased ALT and AST to the normal level. Our results show that ghrelin significantly increased NO metabolites and decreased PGE2 level comparison with sodium valproate group, but had no significant change compared to the control group. we showed that ghrelin administration inhibited liver injury in rats due to sodium valproate toxicity.

  1. Neoplastic transformation of rat liver epithelial cells is enhanced by non-transferrin-bound iron

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    Messner Donald J

    2008-02-01

    Full Text Available Abstract Background Iron overload is associated with liver toxicity, cirrhosis, and hepatocellular carcinoma in humans. While most iron circulates in blood as transferrin-bound iron, non-transferrin-bound iron (NTBI also becomes elevated and contributes to toxicity in the setting of iron overload. The mechanism for iron-related carcinogenesis is not well understood, in part due to a shortage of suitable experimental models. The primary aim of this study was to investigate NTBI-related hepatic carcinogenesis using T51B rat liver epithelial cells, a non-neoplastic cell line previously developed for carcinogenicity and tumor promotion studies. Methods T51B cells were loaded with iron by repeated addition of ferric ammonium citrate (FAC to the culture medium. Iron internalization was documented by chemical assay, ferritin induction, and loss of calcein fluorescence. Proliferative effects were determined by cell count, toxicity was determined by MTT assay, and neoplastic transformation was assessed by measuring colony formation in soft agar. Cyclin levels were measured by western blot. Results T51B cells readily internalized NTBI given as FAC. Within 1 week of treatment at 200 μM, there were significant but well-tolerated toxic effects including a decrease in cell proliferation (30% decrease, p Conclusion These results establish NTBI as a tumor promoter in T51B rat liver epithelial cells. Changes in cyclin proteins suggest cell cycle disregulation contributes to tumor promotion by NTBI in this liver cell model.

  2. Age and sex dependent changes in liver gene expression during the life cycle of the rat

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    Branham William S

    2010-11-01

    Full Text Available Abstract Background Age- and sex-related susceptibility to adverse drug reactions and disease is a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of hepatic genes expressed at various life cycle stages will impact susceptibility to adverse drug reactions. Understanding the basal liver gene expression patterns is a necessary first step in addressing this hypothesis and will inform our assessments of adverse drug reactions as the liver plays a central role in drug metabolism and biotransformation. Untreated male and female F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age. Liver tissues were collected for histology and gene expression analysis. Whole-genome rat microarrays were used to query global expression profiles. Results An initial list of differentially expressed genes was selected using criteria based upon p-value (p Conclusions These results suggest an underlying role for genes in specific clusters in potentiating age- and sex-related differences in susceptibility to adverse health effects. Furthermore, such a comprehensive picture of life cycle changes in gene expression deepens our understanding and informs the utility of liver gene expression biomarkers.

  3. Autoserum: An Optimal Supplement for Bone Marrow Mesenchymal Stem Cells of Liver-Injured Rats

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    Qinglin Zhang

    2015-01-01

    Full Text Available Mesenchymal stem cells (MSCs are an attractive source for the clinical cell therapy of liver injury. Although the use of adult serum, platelet lysate, or cord blood serum solves some of the problems caused by fetal bovine serum (FBS, the allogeneic immune response, contamination, and donor-to-donor and donor-to-receptor differences still obstruct the application of MSCs. In this study, the influences of autoserum from liver-injured rats (LIRs and allogeneic serum from healthy rats on the isolation and culture of bone marrow MSCs (BMSCs were examined and compared to FBS. The results showed that BMSCs cultured with autoserum or allogeneic serum exhibited better MSC-specific morphology, lower rate of cell senescent, and higher proliferation kinetics than those with FBS. In addition, autoserum promoted the osteogenic differentiation potential of BMSCs as allogeneic serum did. Although there were no significant differences in proliferation activity, immunophenotypic characterization, and differentiation potential between BMSCs cultured with autoserum and those with allogeneic serum, the potential adverse immunological reactions in patients with allogeneic material transplantation must be considered. We therefore believe that the autoserum from liver-injured patients may be a better choice for MSC expansion to meet the needs of liver injury therapy.

  4. Effect of the aqueous extract of Psidium guajava on erythromycin-induced liver damage in rats.

    Science.gov (United States)

    Sambo, N; Garba, S H; Timothy, H

    2009-12-01

    The effect of Psidium guajava extract on erythromycin-induced liver damage in albino rats was investigated using 30 normal rats grouped into six. Group I and II served as the normal and treatment controls that were administered with normal saline and 100 mg/kg body weight of erythromycin stearate daily for 14 days respectively. Rats in group III were administered 450 mg/kg body weight of Psidium guajava only for 7 days while rats in groups IV, V and VI were administered Psidium guajava extract for 7 days and 100mg/kg body weight of erythromycin for 14 days. Histopathological investigation of the liver tissues revealed striking oedema and mild periportal mononuclear cell infiltration of hepatic cords in the liver of rats administered 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract. Pretreatment with 150 mg/kg of Psidium guajava extract showed a slight degree of protection against the induced hepatic injury caused by 100 mg/kg of erythromycin stearate. Biochemical analysis of the serum obtained revealed a significant increase in serum levels of hepatic enzymes measured in the groups administered with 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract compared to the control groups and those pretreated with 150 mg/kg of Psidium guajava extract. This study has shown that the aqueous extract of psidium guajava leaf possesses hepatoprotective property at lower dose and a hepatotoxic property at higher dose but further studies with prolonged duration is recommended.

  5. The effect of ZnO nanoparticles on liver function in rats.

    Science.gov (United States)

    Tang, Hua-Qiao; Xu, Min; Rong, Qian; Jin, Ru-Wen; Liu, Qi-Ji; Li, Ying-Lun

    Zinc oxide (ZnO) is widely incorporated as a food additive in animal diets. In order to optimize the beneficial effects of ZnO and minimize any resultant environmental pollution, ZnO nanoparticles are often used for delivery of the zinc. However, the possible toxic effects of ZnO nanoparticles, including effects on cytochrome P450 (CYP450) enzymes, have not been evaluated. In this study, we investigated the effect of ZnO nanoparticles, in doses used in animal feeds, on CYP450 enzymes, liver and intestinal enzymes, liver and kidney histopathology, and hematologic indices in rats. We found that liver and kidney injury occurred when the concentrations of ZnO nanoparticles in feed were 300-600 mg/kg. Also, liver mRNA expression for constitutive androstane receptor was suppressed and mRNA expression for pregnane X receptor was induced when feed containing ZnO nanoparticles was given at a concentration of 600 mg/kg. Although the expression of mRNA for CYP 2C11 and 3A2 enzymes was induced by ZnO nanoparticles, the activities of CYP 2C11 and 3A2 were suppressed. While liver CYP 1A2 mRNA expression was suppressed, CYP 1A2 activity remained unchanged at all ZnO nanoparticle doses. Therefore, it has been concluded that ZnO nanoparticles, in the doses customarily added to animal feed, changed the indices of hematology and blood chemistry, altered the expression and activity of hepatic CYP enzymes, and induced pathological changes in liver and kidney tissues of rats. These findings suggest that greater attention needs to be paid to the toxic effects of ZnO nanoparticles in animal feed, with the possibility that the doses of ZnO should be reduced.

  6. Effects and mechanisms of Acremoniumterricola milleretal mycelium on liver fibrosis induced by carbon tetrachloride in rats.

    Science.gov (United States)

    Tian, Xiao-Peng; Yin, Yan-Yan; Li, Xia

    2011-01-01

    Acremoniumterricola milleretal mycelium (AMM) is one of the most precious traditional Chinese medicines. It has numerous protective effects on organs, and has been used in Chinese herb prescription to treat refractory diseases. Our preliminary studies demonstrated that AMM had hepatoprotective activity in acute liver injury. We further investigated the effects of AMM on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and explore its possible mechanisms. The animal model was established by injection with 50% CCl(4) subcutaneously in male Sprague-Dawley rats twice a week for eight weeks. Meanwhile, AMM (175, 350 and 700 mg/kg) was administered intragastrically per day until sacrifice. We found that treatment with AMM (175, 350 and 700 mg/kg) decreased CCl(4)-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissues. It also restored the decreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl(4) treatment. Moreover, AMM (350 and 700 mg/kg) decreased the elevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liver injury and the formation of liver fibrosis in rates treated by AMM were improved significantly. Immunoblot analysis showed that AMM (175, 350 and 700 mg/kg) inhibited Smad 2/3 phosphorylation, and elevated inhibitor Smad 7 expression. These results suggested that AMM could protect liver damage and inhibit the progression of hepatic fibrosis induced by CCl(4), and its mechanisms might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.

  7. Aluminum chloride caused liver dysfunction and mitochondrial energy metabolism disorder in rat.

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    Xu, Feibo; Liu, Yanfen; Zhao, Hansong; Yu, Kaiyuan; Song, Miao; Zhu, Yanzhu; Li, Yanfei

    2017-09-01

    Aluminum (Al) is known to exert hepatotoxicity. However, the mechanisms mostly are unclear. Liver is a metabolism organ that maintains the energy level and structural stability of body, mitochondria are the main sites of energy metabolism, thus, we hypothesized that mitochondrial energy metabolism disorder contributes to liver dysfunction in aluminum chloride (AlCl 3 ) treatment rat. To verify the hypothesis, forty male Wistar rats were randomly allocated and orally exposed to 0, 64mg/kg, 128mg/kg and 256mg/kg body weight AlCl 3 in drinking water for 120days, respectively. We found that AlCl 3 exposure reduced the electron transport chain complexes I-V activities and adenosine triphosphate (ATP) level, as well as disturbed mitochondrial DNA transcript, presenting as the inhibited mRNA expressions of NADH dehydrogenase 1, NADH dehydrogenase 2, cytochrome b, cytochrome c oxidase subunit 1, cytochrome c oxidase subunit 3 and ATP synthase 6, indicating that AlCl 3 exposure disturbs the mitochondrial energy metabolism, and it caused an increase in liver enzymes (Aspartate aminotransferase and Alanine aminotransferase) and histopathological lesions. Additionally, we found that reactive oxygen species accumulation and decreased superoxide dismutase activity in mitochondria, and increased 8-Hydroxydeoxyguanosine levels in mitochondrial DNA, demonstrating AlCl 3 exposure promotes mitochondrial oxidative stress, which may be a contributing factor to mitochondrial energy metabolism disorder and liver dysfunction. The study displayed that mitochondria are the potential target of liver damage induced by AlCl 3 , providing considerable direction for the prevention and clinical intervention of liver diseases. Copyright © 2017. Published by Elsevier Inc.

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

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    Hardik Soni

    2014-09-01

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

  9. Gender specific differences in the liver proteome of rats exposed to short term and low-concentration hexabromocyclododecane (HBCD)

    NARCIS (Netherlands)

    Miller, I.; Diepenbroek, C.; Rijntjes, E.; Renaut, J.; Teerds, K.J.; Kwadijk, C.; Cambier, S.; Murk, A.J.; Gutleb, A.C.; Serchi, T.

    2016-01-01

    The influence of short term (7-day) exposure of male rats to the brominated flame retardant hexabromocyclododecane (HBCD) was studied by investigation of the liver proteome, both in euthyroid and hypothyroid rats and by comparing results with general data on animal physiology and thyroid hormone,

  10. Food restriction prevents an age-associated increase in rat liver beta-adrenergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dax, E.M.; Ingram, D.K.; Partilla, J.S.; Gregerman, R.I.

    1989-05-01

    In male Wistar rats fed ad libitum (24% protein, 4.5 Kcal/gm), the (/sup 125/I)iodopindolol binding capacity of the beta-adrenergic receptors in liver of 24-month-old animals is 3-4 times greater than that of 6-month-old counterparts. In rats fed the same diet, on alternate days from weaning, the receptor capacity did not increase significantly between 6 and 24 months (10.20 +/- 0.55 vs 9.20 +/- 0.72 fmol/mg) or between 24 and 30 months. This was not due to acute dietary deprivation, as rats food-restricted for only 2 weeks, at 23.5 months of age, also showed elevated receptor capacities compared to 6-month-old ad libitum fed animals. Moreover, intermittent feeding produced no significant effects among 6-month-old animals, whether restricted since weaning or for two weeks prior to sacrifice. Many biochemical parameters that decrease with aging in rats fed ad libitum are prevented by dietary restriction. Our results demonstrate that a reproducible biochemical process that increases with aging is also prevented with dietary restriction. The age-related, liver beta-receptor increase may be a potentially reliable marker for studying biochemical perturbations that modify life span.

  11. Comparative Effects of Oyster Mushrooms on Lipid Profile, Liver and Kidney Function in Hypercholesterolemic Rats

    Science.gov (United States)

    Alam, Nuhu; Amin, Ruhul; Khan, Asaduzzaman; Ara, Ismot; Shim, Mi Ja; Lee, Min Woong; Lee, U Youn

    2009-01-01

    Comparative effects of oyster mushrooms on plasma and fecal lipid profiles and on liver and kidney function were evaluated in hyper and normocholesterolemic rats. Feeding of hypercholesterolemic rats a 5% powder of oyster mushrooms (Pleurotus ostreatus, P. sajor-caju and P. florida) reduced the plasma total cholesterol level by 37%, 21% and 16%, respectively and reduced the triglyceride level by 45%, 24% and 14%, respectively. LDL/HDL ratio decreased by 64%, 45% and 41% for P. sajor-caju, P. ostreatus and P. florida fed rats, respectively. Mushroom feeding also reduced body weight in hypercholesterolemic rats. However, it had no adverse effect on plasma bilirubin, creatinin and urea nitrogen level. Mushroom feeding also increased the total lipid and cholesterol excretion in the feces. The present study reveals that feeding of 5% oyster mushroom powder does not have detrimental effects on the liver and kidneys rather may provide health benefits for the cardiovascular-related complication by decreasing the atherogenic lipid profiles. PMID:23983505

  12. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats

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    Şule Demir

    2016-01-01

    Full Text Available It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (p0.05. In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD.

  13. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats

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    Demir, Şule; Ünübol, Mustafa; Aypak, Serap Ünübol; İpek, Emrah; Aktaş, Serdar; Ekren, Gamze Sevri; Yılmaz, Murat; Tunca, Recai; Güney, Engin

    2016-01-01

    It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD) pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA) for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (p hypothyroidism-induced group and 102.63 ± 15.51 mg/dL in the control group, with a statistically significant difference between the groups (p = 0.032). The two groups did not differ statistically significantly with respect to visfatin levels (p > 0.05). In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD. PMID:27143968

  14. Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats.

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    Zou, Mi; Arentson, Emily J; Teegarden, Dorothy; Koser, Stephanie L; Onyskow, Laurie; Donkin, Shawn S

    2012-08-01

    Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose (FR) and low-protein (LP) diets are linked to hepatic steatosis and insulin resistance in nonpregnant animals. We hypothesized that dietary FR or LP intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of LP or FR intake on hepatic steatosis and insulin resistance in unmated controls (CTs) and pregnant and lactating rats. Sprague-Dawley rats were fed a CT, or a 63% FR, or an 8% LP diet. Glucose tolerance test at day 17 of the study revealed greater (P Fructose induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated CT rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than an LP diet. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Effect of chronic alcohol drinking on rat liver microsomal nitroreductive metabolism of nifurtimox and benznidazole.

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    de Mecca, M M; Bartel, L C; Castro, J A

    2013-12-01

    Nifurtimox (Nfx) and benznidazole (Bz) have serious toxic side effects. Manufacturers warn about significant adverse effects when simultaneous alcohol consumption is being made, but its mechanism is not known. The levels and toxicity of these drugs are linked to their liver microsomal nitroreduction to reactive metabolites. In this study, we analyzed whether alcohol drinking enhanced those nitroreductive processes. Male and female Sprague-Dawley rats, 5-6 weeks old (125-150 g body weight) were used. They were fed ad libitum for 28 days with Lieber and De Carli control or alcohol regular liquid diets. The rats were separated into two dietary groups: ethanol and control group. Both were pair fed with the respective diet. Their liver microsomes were isolated and the nicotinamide adenine dinucleotide phosphate-dependent nitroreduction of Nfx and Bz were determined. Alcohol drinking significantly induced microsomal nitroreduction of these drugs in male rats (11% for Nfx and 41% for Bz) but not in females. The activity observed in the alcohol-induced male rats was 100% inhibited by diphenyleneiodonium and attributable to P450 reductase. Inductive effects of alcohol drinking on nitroreductive activation of both drugs might be only partially involved in the harmful interactions described.

  16. Effect of “treating liver by nourishing spleen” on gut microbiota in rats with liver fibrosis based on Xiaoyao powder and its separated recipe

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    CHEN Bin

    2016-04-01

    Full Text Available ObjectiveTo investigate the possible mechanism of “treating liver by nourishing spleen” in the treatment of liver fibrosis with reference to the effect of Xiaoyao powder and its separated recipe on gut microbiota and the level of portal endotoxins. MethodsA total of 70 healthy Wistar rats were randomly divided into blank group (10 rats, model group (20 rats, experimental group (20 rats, and control group (20 rats, and tail vein injection of bovine serum albumin was performed for 8 weeks to establish a rat model of immune liver fibrosis. The rats in the experimental group were given Xiaoyao granules by gavage, and those in the control group were given Xiaoyao granules without the spleen-strengthening traditional Chinese medicines Atractylodes macrocephala Koidz., Poria cocos, ginger, and Radix Glycyrrhizae Preparata by gavage. Serum aminotransferases, liver pathology, portal endotoxins, and the enterobacterial repetitive intergenic consensus (ERIC-PCR fingerprint of gut microbiota were observed in each group. The analysis of variance was applied for comparison of continuous data with homogeneity of variance between multiple groups, and the least significant difference t-test was used for further comparison between any two groups; the Tamhane’s method was applied for data with heterogeneity of variance; the Pearson correlation analysis was used for correlation analysis. ResultsCompared with the blank group, the model group showed changes in the diversity and structure of gut microbiota and an increase in the level of portal endotoxins (0.421±0.170 EU/ml vs 0.784±0.180 EU/ml, which showed significant differences between these two groups (P<0.01, and the level of portal endotoxins was positively correlated with collagen area percentage in liver tissue(r=0736,P<001. Compared with the model group, the experimental group had significantly reduced levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and portal

  17. Effects of quinolones on liver microsome cytochrome P450 in rats

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    Yi ZHANG

    2012-11-01

    Full Text Available Objective  To study and compare the effects of fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and pazufloxacin on the enzyme system of liver microsome cytochrome P450 in rat. Methods  Thirty male Wistar rats were equally assigned into five groups: control group, levofloxacin (LV group, gatifloxacin (GT group, moxifloxacin (MX group and pazufloxacin (PZ group. Each drug was consecutively administered by tail vein injection for 7 days in a dosage of 120 mg/(kg•d. Liver microsomes were prepared by differential centrifugation, the concentration of protein in the liver microsome was measured by Lowry method, the content and activity of cy tochrome P450 were detected by spectrophotometric determination, and the results were analyzed by one-way ANOVA. Results  Compared with control group, the weight of liver in MX group and GT group was significantly reduced (P 0.05. Assay of aminopyrine-N-demethylase activity showed that the difference in enzyme activity was statistically significant between the control group and groups LV, GT and MX (P < 0.01. Erythromycin-N-demethylase activity measurement revealed that the enzyme activity was lowered in GT group and slightly elevated in MX group, and the difference was statistically significant compared with that of control group (P < 0.01. Measurement of activity of rat liver microsomal CYP450 enzyme system subfamily showed that the BROD activity increased in LV, MX and PZ groups (P < 0.01, and slightly decreased in GT group as compared with control group (P < 0.05. The PROD activity increased in GT group, but decreased in PZ group (P < 0.01. The EROD activity increased in all the four groups (P < 0.01. Conclusions  The four fluoroquinolones have some effects on the enzyme system of liver microsome cytochrome P450 in rats, but the effects may be different (enhancement or attenuation of the enzymatic activity depending on the enzymes, and the extent of the decrease of effect is in the

  18. Influence of cancer cachexia on drug liver metabolism and renal elimination in rats

    Science.gov (United States)

    Cvan Trobec, Katja; Kerec Kos, Mojca; Trontelj, Jurij; Grabnar, Iztok; Tschirner, Anika; Palus, Sandra; Anker, Stefan D; Springer, Jochen; Lainscak, Mitja

    2015-01-01

    Background Body wasting and cachexia change body composition and organ function, with effects on drug pharmacokinetics. The aim of this study was to investigate how cancer and cancer cachexia modify liver metabolism and renal drug elimination in rats. Methods Nine male Wistar-Han rats received a single oral dose of midazolam and propranolol (markers of hepatic metabolism), and 10 rats received single intravenous dose of iohexol, a marker of glomerular filtration rate. After drug delivery, multiple dried blood samples were obtained within 2 h post-dose to evaluate drug pharmacokinetic profiles. After baseline sampling (D0), rats were injected with tumour cells. Drug application and blood sampling were repeated when rats developed tumours (Day 5—D5), and when rats were severely cachectic (Day 10—D10). Clearance (CL) and volume of distribution (Vd) of drugs were assessed with non-linear mixed effects modelling. Weight and body composition were measured on D0 and D10 and were related to pharmacokinetic parameters. Results All three drugs showed non-significant trend towards increased CL and Vd on D5. On D10, midazolam and propranolol CL and midazolam Vd significantly decreased from baseline (−80.5%, −79.8%, and −72.0%, respectively, P cachexia, which could increase risk of dose-related adverse events. PMID:26136411

  19. Protective effects of Spirulina on the liver function and hyperlipidemia of rats and human

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    Mostafa Mohamed El-Sheekh

    2014-02-01

    Full Text Available In the present study, the effects of Spirulina on subchronic treatments (two weeks of hyperlipidemia and liver function of the rats and humans were investigated. The hyperlipidemia was induced in the rats using 25% of soya bean oil and 25% butter. The butter induced more hyperlipidemia than soya bean oil. Spirulina was used at the concentrations of 0, 2.5, 5.0 and 10 % of diet weight of the rats. The decrease in hyperlipidemia by Spirulina was dependent on its concentration in the diet. In case of human studies, about four g/day of Spirulina was taken via oral administration by Egyptian volunteers patients with hyperlipidemia. Spirulina decreased the levels of hyperlipidemia in these patients. The effects were dependent on the amount and number of administered dose of Sprirulina. The results suggested that the Spirulina treatment could induce marked reduction of aminotransferase through correcting lipid profile and increasing high density lipoprotein.

  20. Changes in serum asymmetric dimethylarginine levels in progression of liver inflammation in an experimental rat model of nonalcoholic fatty liver disease

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    DING Jie

    2016-01-01

    Full Text Available ObjectiveTo investigate the changes in serum asymmetric dimethylarginine (ADMA levels in the progression of liver inflammation in a rat model of nonalcoholic fatty liver disease (NAFLD. MethodsThe rat model of NAFLD was established through high-fat cream by gavage and these rats were considered the experimental group (group M, and the rats in the normal control group (group C were given normal saline by gavage within the same period of time. Liver samples and serum samples were collected from these rats. Serum alanine aminotransferase (ALT and ADMA levels and the content of nitric oxide (NO in liver tissue homogenate were measured at 4, 8, and 12 weeks for group M (M4, M8, and M12 and 12 weeks for group C (C12, and NAFLD activity score (NAS was evaluated for both groups at the same time point. As for the data that were normally distributed and had homogeneity of variance, one-way analysis of variance was applied for comparison between multiple groups, and the least significant difference (LSD t-test was applied for comparison within the same group; as for the data that were normally distributed and had heterogeneity of variance, Kruskal-Wallis H test was applied for comparison between multiple groups. Pearson correlation analysis was applied for correlation analysis. ResultsCompared with the C12 group, the M12 group had significantly increased serum ADMA and ALT levels and content of NO in liver tissue homogenate (P=0.010, P<0.001, and P<0.001, respectively. Serum ADMA level was not significantly correlated with serum ALT level (r=0.195, P=0.228, and was positively correlated with the content of NO in liver tissue homogenate and NAS in rats (r=0.631, P<0.001; r=0.782, P<0.001. ConclusionIn rats with NAFLD, serum ADMA level gradually increases with the progression of liver inflammation, and is positively correlated with the content of NO and NAS. The role of ADMA as a new inflammatory factor for evaluating the grade of chronic liver

  1. Effects of thyroxine and 1-methyl, 2-mercaptoimidazol on phosphoinositides synthesis in rat liver

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    Krasilnikova Oksana A

    2004-12-01

    Full Text Available Abstract Background Phosphoinositides mediate one of the intracellular signal transduction pathways and produce a class of second messengers that are involved in the action of hormones and neurotransmitters on target cells. Thyroid hormones are well known regulators of lipid metabolism and modulators of signal transduction in cells. However, little is known about phosphoinositides cycle regulation by thyroid hormones. The present paper deals with phosphoinositides synthesis de novo and acylation in liver at different thyroid status of rats. Results The experiments were performed in either the rat liver or hepatocytes of 90- and 720-day-old rats. Myo-[3H]inositol, [14C]CH3COONa, [14C]oleic and [3H]arachidonic acids were used to investigate the phosphatidylinositol (PtdIns, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PtdInsP2 synthesis. 1-methyl, 2-mercaptoimidazol-induced hypothyroidism was associated with the decrease of myo-[3H]inositol and [3H]arachidonic acids incorporation into liver phosphoinositides and total phospholipids, respectively. The thyroxine (L-T4 injection to hypothyroid animals increased the hormones contents in blood serum and PtdInsP2 synthesis de novo as well as [3H]arachidonic acids incorporation into the PtdIns and PtdInsP2. Under the hormone action, the [14C]oleic acid incorporation into PtdIns reduced in the liver of hypothyroid animals. A single injection of L-T4 to the euthyroid [14C]CH3COONa-pre-treated animals or addition of the hormone to a culture medium of hepatocytes was accompanied by the rapid prominent increase in the levels of the newly synthesized PtdIns and PtdInsP2 and in the mass of phosphatidic acid in the liver or the cells. Conclusions The data obtained have demonstrated that thyroid hormones are of vital importance in the regulation of arachidonate-containing phosphoinositides metabolism in the liver. The drug-induced malfunction of thyroid gland noticeably changed the

  2. Hepatoprotective effect of Matricaria chamomilla.L in paraquat induced rat liver injury.

    Science.gov (United States)

    Tavakol, H S; Farzad, K; Fariba, M; Abdolkarim, C; Hassan, G; Seyed-Mostafa, H Z; Akram, R

    2015-02-01

    Paraquat (PQ), an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ is known to induce injury via a redox cyclic reaction. The purpose of this study was to investigate the effect of aqueous extract Matricaria chamomilla.L (M. chamomilla) against PQ-induced liver injury in association with its antioxidant activity.The male rats were treated by gastric gavage daily with PQ (5 mg/kg/day) and M. chamomilla (50 mg/kg/day) were administered alone or in combination for 7 days. After treatments, total antioxidant capacity (TAC), total thiol molecules (TTG) levels and catalase (CAT) activity in liver tissue were measured. At the end of the experiment, plasma and lung tissue of the animals was separated. The activity of enzymatic scavengers such as CAT, TAC and TTG were measured in liver homogenate.In this sample, the TAC and TTG were lower in the PQ group as compared with control group. Co-administration of PQ with M. chamomilla extract increased TAC and TTG in liver tissue as compared with PQ group.In conclusion, M. chamomilla as natural antioxidant may be considered beneficial for the protection oxidative liver injury in PQ poisoning. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

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    Hyo Jin Lee

    2015-06-01

    Full Text Available The present study tested the hypothesis that Korean red ginseng (KRG provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON, alcohol control (ET, and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively. Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

  4. PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS.

    Science.gov (United States)

    Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; Khattab, Alshaimaa

    2017-01-01

    Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential.

  5. Metabolomics dataset of PPAR-pan treated rat liver

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    Zsuzsanna Ament

    2016-09-01

    Full Text Available This article contains mass spectrometry (MS data investigating small molecule changes as an effect of a triple peroxisome proliferator-activated receptor (PPAR-pan agonist GW625019 in the liver as described in the manuscript (Ament et al., 2016 [1]. Samples were measured using gas chromatography-mass spectrometry (GC–MS for total fatty acid content, and liquid chromatography-mass spectrometry (LC–MS to measure intact lipids, carnitines and selected aqueous metabolites and eicosanoids. Data files comprise of Excel (Microsoft, WA, USA spreadsheets of identified metabolites and their area ratio values for total fatty acids, carnitines, aqueous metabolites, and eicosanoids where the intensity of the analytes were normalised to the intensity of the internal standard. In the case of open profiling intact lipid data, the Excel file contains area ratio values of retention time and mass to charge ratio pairs; again, the area ratio values were calculated by normalising to the intensity of the internal standard. It should be noted that several metabolic changes are potentially indirect (secondary, tertiary and ensuing changes.

  6. Hydrodynamics-based transfection of rat interleukin-10 gene attenuates porcine serum-induced liver fibrosis in rats by inhibiting the activation of hepatic stellate cells

    Science.gov (United States)

    HUANG, YUE-HONG; CHEN, YUN-XIN; ZHANG, LI-JUAN; CHEN, ZHI-XIN; WANG, XIAO-ZHONG

    2014-01-01

    Liver fibrosis is the common pathological outcome for the majority of chronic liver diseases. Interleukin-10 (IL-10) is a cytokine that downregulates proinflammatory responses and has a modulatory effect on liver fibrogenesis. However, little is known regarding the effect of rat interleukin-10 (rIL-10) gene by hydrodynamics-based transfection (HBT) on liver fibrosis in rats. The aim of this study was to investigate the effect of the rIL-10 gene by HBT on the progression of liver fibrosis induced by porcine serum (PS) in rats and explore its possible mechanism. Plasmid-expressing rIL-10 was transferred into rats by HBT and immunohistochemistry and RT-PCR were used to detect the major organ expressing rIL-10. Liver fibrosis was induced in rats by intraperitoneal administration of PS for 8 weeks. Plasmid pcDNA3-rIL-10 solution was administered weekly by HBT starting at the 5th week. Liver function and hepatic histology were examined. The possible molecular mechanisms of rIL-10 gene therapy were assessed in liver tissue and hepatic stellate cells (HSCs) co-cultured with BRL cells (a hepatocyte line) in vitro. The results showed rIL-10 expression occurred mainly in the liver following rIL-10 gene transfer by HBT. Maintaining a stable expression of rIL-10 in serum was assessed by repeated administration. The rIL-10 gene treatment attenuated liver inflammation and fibrosis in PS-induced fibrotic rats, reduced the deposition of collagen and the expression of α-smooth muscle actin (α-SMA) in fibrotic rats. The in vitro experiment showed that the expression of a-SMA and procollagen type I in HSCs co-cultured with the BRL-transfected rIL-10 gene were significantly decreased. These findings indicate that rIL-10 gene therapy by HBT attenuates PS-induced liver fibrosis in rats and that its mechanism is associated with rIL-10 inhibiting the activation of HSCs and promoting the degeneration of collagen. PMID:24993843

  7. Hydrodynamics-based transfection of rat interleukin-10 gene attenuates porcine serum-induced liver fibrosis in rats by inhibiting the activation of hepatic stellate cells.

    Science.gov (United States)

    Huang, Yue-Hong; Chen, Yun-Xin; Zhang, Li-Juan; Chen, Zhi-Xin; Wang, Xiao-Zhong

    2014-09-01

    Liver fibrosis is the common pathological outcome for the majority of chronic liver diseases. Interleukin-10 (IL-10) is a cytokine that downregulates proinflammatory responses and has a modulatory effect on liver fibrogenesis. However, little is known regarding the effect of rat interleukin‑10 (rIL‑10) gene by hydrodynamics-based transfection (HBT) on liver fibrosis in rats. The aim of this study was to investigate the effect of the rIL-10 gene by HBT on the progression of liver fibrosis induced by porcine serum (PS) in rats and explore its possible mechanism. Plasmid‑expressing rIL-10 was transferred into rats by HBT and immunohistochemistry and RT-PCR were used to detect the major organ expressing rIL-10. Liver fibrosis was induced in rats by intraperitoneal administration of PS for 8 weeks. Plasmid pcDNA3-rIL-10 solution was administered weekly by HBT starting at the 5th week. Liver function and hepatic histology were examined. The possible molecular mechanisms of rIL-10 gene therapy were assessed in liver tissue and hepatic stellate cells (HSCs) co-cultured with BRL cells (a hepatocyte line) in vitro. The results showed rIL-10 expression occurred mainly in the liver following rIL-10 gene transfer by HBT. Maintaining a stable expression of rIL-10 in serum was assessed by repeated administration. The rIL-10 gene treatment attenuated liver inflammation and fibrosis in PS-induced fibrotic rats, reduced the deposition of collagen and the expression of α-smooth muscle actin (α-SMA) in fibrotic rats. The in vitro experiment showed that the expression of a-SMA and procollagen type I in HSCs co-cultured with the BRL‑transfected rIL-10 gene were significantly decreased. These findings indicate that rIL-10 gene therapy by HBT attenuates PS-induced liver fibrosis in rats and that its mechanism is associated with rIL-10 inhibiting the activation of HSCs and promoting the degeneration of collagen.

  8. Study on the effects of blueberry treatment on histone acetylation modification of CCl4-induced liver disease in rats.

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    Zhan, W; Liao, X; Tian, T; Yu, L; Liu, X; Li, B; Liu, J; Han, B; Xie, R J; Ji, Q H; Yang, Q

    2017-02-16

    The objective of this study was to investigate the effects of blueberry treatment on histone acetylation modification of carbon tetrachloride (CCl4)-induced liver disease in rats. Laboratory rats were randomly divided into control, hepatic fibrosis, blueberry treatment, blueberry intervention, and natural recovery groups. Rats in the model groups were treated with CCl4 administered subcutaneously at 4- and 8-week intervals, and then executed. Both the 4- and 8-week treatment groups were treated with blueberry juice for 8 weeks, and then executed after 12 and 16 weeks, respectively. Following the experiment, four liver function and hepatic fibrosis indices were measured. Liver index was calculated, hematoxylin-eosin staining was conducted, and H3K9, H3K14, and H3K18 expressions were evaluated among the nuclear proteins of the liver tissues. No differences in alanine transaminase were noted between the control and intervention groups, but significant differences were detected among the model, treatment, and natural recovery groups (P blueberry treatment, rat liver function and hepatic fibrosis improved, potentially indicating that blueberry components could regulate histone acetylation and improve liver pathologic changes in rats with CCl4-induced disease.

  9. [Effect of artenisiae scopariae and poriae powder on calpain-2 expression in liver tissue from rats with obstructive jaundice].

    Science.gov (United States)

    Cui, Yubao

    2015-05-01

    To explore the eff ect of artenisiae scopariae and poriae powder (ASPD) on calpain-2 expression in liver tissue from rats with obstructive jaundice. The rat model of obstructive jaundice was established. SD rats was divided into the control group, the obstructive jaundice group, the obstructive jaundice model plus ASPD group, the obstructive jaundice model plus saline group. Th e serum levels of TBIL, ALT, AST and other biochemical indexes were detected. The pathological changes of liver tissue were evaluated by HE staining. The calpain-2 mRNA and protein expression in liver was measured by Real-time PCR and immunohistochemistry or Western blot, respectively. The calpain-2 mRNA and protein expression levels were significantly up-regulated in live tissues from the rats with obstructive jaundice in a time-dependent manner. The ASPD could inhibit the calpain-2 expression in rats with obstructive jaundice concomitant with the decreased liver damage and the improved liver function, suggesting that calpain-2 was involved in endoplasmic reticulum stress-mediated cellular apoptosis and the occurrence of obstructive jaundice. ASPD could be used for patients with obstructive jaundice to promote the recovery of liver function after operation and to reduce the incidence of complications, which provide a theoretical basis for the reasonable application of traditional Chinese medicine in the peroperative period.

  10. Transesterification of a series of 12 parabens by liver and small-intestinal microsomes of rats and humans.

    Science.gov (United States)

    Fujino, Chieri; Watanabe, Yoko; Uramaru, Naoto; Kitamura, Shigeyuki

    2014-02-01

    Hydrolytic transformation of parabens (4-hydroxybenzoic acid esters; used as antibacterial agents) to 4-hydroxybenzoic acid and alcohols by tissue microsomes is well-known both in vitro and in vivo. Here, we investigated transesterification reactions of parabens catalyzed by rat and human microsomes, using a series of 12 parabens with C1-C12 alcohol side chains. Transesterification of parabens by rat liver and small-intestinal microsomes occurred in the presence of alcohols in the microsomal incubation mixture. Among the 12 parabens, propylparaben was most effectively transesterified by rat liver microsomes with methanol or ethanol, followed by butylparaben. Relatively low activity was observed with longer-side-chain parabens. In contrast, small-intestinal microsomes exhibited higher activity towards moderately long side-chain parabens, and showed the highest activity toward octylparaben. When parabens were incubated with liver or small-intestinal microsomes in the presence of C1-C12 alcohols, ethanol and decanol were most effectively transferred to parabens by rat liver microsomes and small-intestinal microsomes, respectively. Human liver and small-intestinal microsomes also exhibited significant transesterification activities with different substrate specificities, like rat microsomes. Carboxylesterase isoforms, CES1b and CES1c, and CES2, exhibited significant transesterification activity toward parabens, and showed similar substrate specificity to human liver and small-intestinal microsomes, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Effect of α-lipoic acid on the removal of arsenic from arsenic-loaded isolated liver tissues of rat

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    Noor E-Tabassum

    2006-03-01

    Full Text Available The patient of chronic arsenic toxicity shows oxidative stress. To overcome the oxidative stress, several antioxidants such as beta-carotene, ascorbic acid, α-tocopherol, zinc and selenium had been suggested in the treatment of chronic arsenic toxicity. In the present study universal antioxidant (both water and lipid soluble antioxidant α-lipoic acid was used to examine the effectiveness of reducing the amount of arsenic from arsenic-loaded isolated liver tissues of rat. Isolated liver tissues of Long Evans Norwegian rats were cut into small pieces and incubated first in presence or absence of arsenic and then with different concentrations of α-lipoic acid during the second incubation. α-Lipoic acid decreases the amount of arsenic and malondialdehyde (MDA in liver tissues as well as increases the reduced glutathione (GSH level in dose dependent manner. These results suggest that α-lipoic acid remove arsenic from arsenic-loaded isolated liver tissues of rat.

  12. Effect of alpha-lipoic acid on the removal of arsenic from arsenic-loaded isolated liver tissues of rat

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    Noor-E-Tabassum

    2006-06-01

    Full Text Available The patient of chronic arsenic toxicity shows oxidative stress. To overcome the oxidative stress, several antioxidants such as beta-carotene, ascorbic acid, α-tocopherol, zinc and selenium had been suggested in the treatment of chronic arsenic toxicity. In the present study universal antioxidant (both water and lipid soluble antioxidant α-lipoic acid was used to examine the effectiveness of reducing the amount of arsenic from arsenic-loaded isolated liver tissues of rat. Isolated liver tissues of Long Evans Norwegian rats were cut into small pieces and incubated first in presence or absence of arsenic and then with different concentrations of α-lipoic acid during the second incubation. α-Lipoic acid decreases the amount of arsenic and malondialdehyde (MDA in liver tissues as well as increases the reduced glutathione (GSH level in dose dependent manner. These results suggest that α-lipoic acid remove arsenic from arsenic-loaded isolated liver tissues of rat.

  13. First record of Calodium hepaticum and Taenia taeniaeformis liver infection in wild Norway rats (Rattus norvegicus in Serbia

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    Kataranovski Milena

    2010-01-01

    Full Text Available The nematode Calodium hepaticum and the cestode Taenia taeniaeformis are zoonotic helminths primarly found in the liver of common wild rats. Most reports on these helminth species with cosmopolitan distribution are from Asia, and there is paucity of data for Europe. Wild Norway rats (Rattus norvegicus from urban and suburban habitats of the Belgrade area were examined for the presence of Calodium hepaticum and Taenia taeniaeformis larvae liver infections. The presence of visible cysts and a histomorphology of parasite-related inflammatory liver responses were sought as signs of infection. The total prevalence of infection was 10.9% (C. hepaticum and 29.9% (T. taeniaeformis, with no differences between the sexes. No difference in the annual prevalence of both helminth species was noted. Data obtained in this study provide new information relevant to wild Norway rats as sources of C. hepaticum and T. taeniaeformis liver infection in this geographic area, and, in a wider context, in Europe. .

  14. In vitro detection of fatty liver infiltration in protein-depleted rats using proton nuclear magnetic resonance.

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    Jacobs, D O; Trerotola, S O; Settle, R G; Rolandelli, R H; Wolf, G L; Rombeau, J L

    1985-07-01

    To determine if NMR techniques might be used to detect hepatic steatosis secondary to protein malnutrition, the T1 and T2 relaxation times of liver tissue from rats subjected to long-term protein malnutrition were measured in vitro. The liver tissue from rats fed a protein-deficient rat chow (PD) for 37 days (N = 9) was characterized by increased proportion of fat (P less than 0.001) but decreased water and nitrogen contents (P less than 0.001) relative to controls (N = 9). Mean T1 times were significantly shorter and T2 times significantly longer in liver tissue from protein-depleted animals (P less than 0.001). There was no overlap of T2 times between the protein-depleted and control animals. The consistent changes in T2 that occur with fatty infiltration of the liver should be detectable by current NMR imagers.

  15. Consumption of Coprinus comatus polysaccharide extract causes recovery of alcoholic liver damage in rats.

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    Ozalp, Fatma Ozgul; Canbek, Mediha; Yamac, Mustafa; Kanbak, Gungor; Van Griensven, Leo J L D; Uyanoglu, Mustafa; Senturk, Hakan; Kartkaya, Kazım; Oglakci, Aysegul

    2014-08-01

    Excess use of alcohol is known to be associated with liver diseases such as fatty liver, alcoholic hepatitis, and cirrhosis. Various practices may be applied to prevent or treat the damage caused by chronic alcoholism. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) is a macrofungus that has been reported to aid the recovery of murine livers damaged by benzopyrene. In this study, the possible therapeutic effects of three different doses (50, 100, and 150 mg/kg) of C. comatus polysaccharide (PS) extract were studied in rats subjected to an alcoholic diet. The histological and biochemical results were compared between the control and experimental groups. Modified Lieber-Decarli's calorie-adjusted liquid alcohol diet was given orally for 60 d. In addition to histopathology, alanine transaminase (ALT), aspartate transaminase (AST), mitochondrial membrane integrity, total cytochrome-c oxidase activity (TotalStCox), total mitochondrial cytochrome-c oxidase activity (TotalMtStCox), and caspase-3 values were used as liver parameters, and liver sections from all experimental groups were examined by electron microscopy. Using histopathological assessment, it was observed that there was a decline in liver hepatocyte vacuolization in the treatment group fed 50 mg PS/kg. The TotalStCox and TotalMtStCox values of this group differed from the EtOH control group (p < 0.05). Daily administration of 50 mg/kg of C. comatus PS extract considerably reduced the negative effects of alcohol on liver structure and function.

  16. Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats

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    Aseer, Kanikkai Raja; Kim, Sang Woo; Choi, Myung-Sook; Yun, Jong Won

    2015-01-01

    Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels. PMID:26110898

  17. Protective Effect of Brazilian Propolis against Liver Damage with Cholestasis in Rats Treated with α-Naphthylisothiocyanate

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    Nakamura, Tadashi; Ohta, Yoshiji; Ohashi, Koji; Ikeno, Kumiko; Watanabe, Rie; Tokunaga, Kenji; Harada, Nobuhiro

    2013-01-01

    We examined the protective effect of Brazilian propolis against liver damage with cholestasis in rats treated with α-naphthylisothiocyanate (ANIT) in comparison with that of vitamin E (VE). Rats orally received Brazilian propolis ethanol extract (BPEE) (25, 50, or 100 mg/kg), VE (250 mg/kg) or vehicle at 12 h after intraperitoneal injection of ANIT (75 mg/kg) and were killed 24 h after the injection. Vehicle-treated rats showed liver cell damage and cholestasis, judging from the levels of serum marker enzymes and components. The vehicle group had increased serum total cholesterol, triglyceride, phospholipid, and lipid peroxide levels, increased hepatic lipid peroxide, reduced glutathione, and ascorbic acid levels and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. BPEE (50 mg/kg) administered to ANIT-treated rats prevented liver cell damage and cholestasis and attenuated these serum and hepatic biochemical changes except hepatic ascorbic acid, although administered BPEE (25 or 100 mg/kg) was less effective. VE administered to ANIT-treated rats prevented liver cell damage, but not cholestasis, and attenuated increased serum lipid peroxide level, increased hepatic lipid peroxide level and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. These results indicate that BPEE protects against ANIT-induced liver damage with cholestasis in rats more effectively than VE. PMID:23710219

  18. Exercise counteracts fatty liver disease in rats fed on fructose-rich diet

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    Voltarelli Fabrício A

    2010-10-01

    Full Text Available Abstract Background This study aimed to analyze the effects of exercise at the aerobic/anaerobic transition on the markers of non-alcoholic fatty liver disease (NAFLD, insulin sensitivity and the blood chemistry of rats kept on a fructose-rich diet. Methods We separated 48 Wistar rats into two groups according to diet: a control group (balanced diet AIN-93 G and a fructose-rich diet group (60% fructose. The animals were tested for maximal lactate-steady state (MLSS in order to identify the aerobic/anaerobic metabolic transition during swimming exercises at 28 and 90 days of age. One third of the animals of each group were submitted to swimming training at an intensity equivalent to the individual MLSS for 1 hours/day, 5 days/week from 28 to 120 days (early protocol. Another third were submitted to the training from 90 to 120 days (late protocol, and the others remained sedentary. The main assays performed included an insulin tolerance test (ITT and tests of serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] activities, serum triglyceride concentrations [TG] and liver total lipid concentrations. Results The fructose-fed rats showed decreased insulin sensitivity, and the late-exercise training protocol counteracted this alteration. There was no difference between the groups in levels of serum ALT, whereas AST and liver lipids increased in the fructose-fed sedentary group when compared with the other groups. Serum triglycerides concentrations were higher in the fructose-fed trained groups when compared with the corresponding control group. Conclusions The late-training protocol was effective in restoring insulin sensitivity to acceptable standards. Considering the markers here evaluated, both training protocols were successful in preventing the emergence of non-alcoholic fatty liver status disease.

  19. Modulatory role of Pterocarpus santalinus against alcohol-induced liver oxidative/nitrosative damage in rats.

    Science.gov (United States)

    Bulle, Saradamma; Reddy, Vaddi Damodara; Padmavathi, Pannuru; Maturu, Paramahamsa; N Ch, Varadacharyulu

    2016-10-01

    Pterocarpus santalinus, a traditional medicinal plant has shown protective mechanisms against various complications. The aim of the present study is to evaluate therapeutic efficacy of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced oxidative/nitrosative stress leading to hepatotoxicity. In-vitro studies revealed that PSE possess strong DPPH (1,1-diphenyl-2-picryl hydrazyl) and nitric oxide radical scavenging activity. For in vivo studies male albino Wistar rats were treated with 20% alcohol (5g/kg b.wt/day) and PSE (250mg/kg b.wt/day) for 60days. Results showed that alcohol administration significantly altered plasma lipid profile with marked increase in the levels of plasma transaminases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (γGT). Moreover, lipid peroxides, nitric oxide (NOx) levels in plasma and liver were increased with increased iNOS protein expression in liver was noticed in alcohol administered rats and these levels were significantly brought back close to normal level by PSE administration except iNOS protein expression. Alcohol administration also decreased the content of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-s transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in liver, which were significantly enhanced by administration of PSE. The active compounds pterostilbene, lignan and lupeols present in PSE might have shown protection against alcohol-induced hepatic damage by possibly reducing the rate of lipid peroxidation, NOx levels and increasing the antioxidant defence mechanism in alcohol administered rats. Both biochemical and histopathological results in the alcohol-induced liver damage model emphasize beneficial action of PSE as a hepatoprotective agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats.

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    Mohammed Shaqura

    Full Text Available Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.

  1. Pimpinella anisum L. fruit: Chemical composition and effect on rat model of nonalcoholic fatty liver disease

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    Ali Asadollahpoor

    2017-01-01

    Full Text Available Background: Nonalcoholic fatty liver disease (NAFLD includes a group of chronic liver disorders caused by irregular accumulation of fat in liver tissue. The current study aimed to evaluate chemical composition and the effect of fruit extract and essential oil of Pimpinella anisum in experimental model of NAFLD. Materials and Methods: Sixty rats were randomly divided into ten groups, six in each group. NAFLD was induced in rats using choline-deficient diet for 90 days, followed by 30 days of treatment with 25, 50, 100, and 200 mg/kg/day of hydroethanolic extract (AE as well as 0.125, 0.25, and 0.5 mg/kg/day of essential oil (AO. Blood samples were collected in the final day, and lipid profile, aspartate aminotransferase (AST, alanine aminotransferase (ALT as well as biomarkers of oxidative damage including myeloperoxidase, lipid peroxidation, total thiol molecules, and ferric-reducing ability of plasma were measured. Liver tissue sections of the sacrificed rats were also assessed histologically. Results: AE and AO significantly reversed increase in the plasma levels of total cholesterol, low-density lipoprotein, and triacylglycerol and decrease in high-density lipoprotein level in a dose-dependent manner (P < 0.05. Serum levels of AST and ALT were also significantly modified by treatment with AE and AO (P < 0.05. Biomarkers of oxidative stress were modulated by administration of AE and AO (P < 0.05. Histological assessments also confirmed the effectiveness of treatments by reduced macrovesicular steatohepatitis. Conclusion: It could be concluded that P. anisum fruit extract and essential oil have beneficial effects in the treatment of NAFLD. Further studies are necessary to confirm safety and efficacy of this medicinal plant in clinical setting.

  2. Tissue inhibitor of metalloproteinases-2 (TIMP-2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E2.

    Science.gov (United States)

    Roeb, E; Rose-John, S; Erren, A; Edwards, D R; Matern, S; Graeve, L; Heinrich, P C

    1995-01-02

    To explore the functional role of TIMP-2 in liver, we determined TIMP-2 mRNA levels in primary rat hepatocytes and in total rat liver. Rat hepatocytes constitutively express TIMP-2 mRNA at a low level. Incubation with dexamethasone, prostaglandin E2 and a combination of inflammatory cytokines leads to an up-regulation of TIMP-2 mRNA. In rats in vivo we found a dramatic increase of TIMP-2 expression after intraperitoneal injection of lipopolysaccharide. Compared to our previous findings on TIMP-1 we conclude that TIMP-2 mRNA expression is regulated in a distinct and partially opposite manner. Over-production of TIMP-2 could inhibit the activity of metalloproteinases and thus lead to matrix accumulation. Dysregulation of TIMP-2 synthesis might be involved in the development of liver fibrosis.

  3. Renoprotective effect of crocin following liver ischemia/ reperfusion injury in Wistar rats

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    Seyyed Ali Mard

    2017-10-01

    Full Text Available Objective(s: The objectives of the current study were to evaluate the effects of hepatic ‎ischemia/reperfusion (IR injury on the activity of antioxidant enzymes, biochemical factors, and ‎histopathological changes in rat kidney, and to investigate the effect of crocin on IR-‎related changes. Materials and Methods: Thirty-two male Wistar rats were randomly allocated into four groups (n=8. They were ‎sham-operated, IR, crocin pre-treatment, and crocin pretreatment+IR groups. Sham-operated ‎and Crocin pre-treatment groups received normal saline (N/S, 2 ml/day and crocin (200 mg/kg ‎for seven consecutive days intraperitoneally (IP, respectively, then rats underwent laparotomy, only. ‎IR and crocin pretreatment+IR groups received N/S and crocin with the same dose, time, and route, ‎respectively, then rats underwent partial (70% ischemia for 45 min that was followed by reperfusion ‎for 60 min. At the end of the experiment, kidney specimens were taken for histopathological and ‎antioxidant evaluations and also blood samples were obtained for biochemical analysis. Results: The results of the present study showed that crocin pre-treatment significantly increased ‎the activity of antioxidants, decreased the serum levels of liver enzymes and blood urea nitrogen ‎following IR-induced hepatic injury. Crocin also ameliorated kidney´s histopathological ‎disturbance beyond IR-induced hepatic injury. Conclusion: Crocin as an antioxidant agent protected renal insult following liver IR injury by ‎increasing the activity of antioxidant enzymes, reducing serum levels of liver enzymes, and ‎improving histopathological changes.‎

  4. Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

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    Leone, Angelique; Nie, Alex; Brandon Parker, J.; Sawant, Sharmilee; Piechta, Leigh-Anne; Kelley, Michael F., E-mail: mkelley2@its.jnj.com; Mark Kao, L.; Jim Proctor, S.; Verheyen, Geert; Johnson, Mark D.; Lord, Peter G.; McMillian, Michael K.

    2014-03-15

    Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates. - Highlights: • 28 of 97 drugs gave a positive OS/RM gene expression signature in rat liver. • The specificity of the signature for human idiosyncratic hepatotoxicants was 98%. • The sensitivity of the signature for human idiosyncratic hepatotoxicants was 75%. • The signature can help eliminate hepatotoxicants from drug development.

  5. In vivo proton magnetic resonance spectroscopy of liver metabolites in non-alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons.

    Science.gov (United States)

    Song, Kyu-Ho; Baek, Hyeon-Man; Lee, Do-Wan; Choe, Bo-Young

    2015-10-01

    The aim of this study was to evaluate the transverse relaxation time of methylene resonance as compared to other lipid resonances. The examinations were performed using a 3.0 T scanner with a point-resolved spectroscopy (PRESS) sequence. Lipid relaxation time in a lipid phantom filled with canola oil was estimated with a repetition time (TR) of 6000ms and echo time (TE) of 40-550ms. For in vivo proton magnetic resonance spectroscopy ((1)H-MRS), eight male Sprague-Dawley rats were given free access to a normal-chow (NC) and another eight male Sprague-Dawley rats were given free access to a high-fat (HF) diet. Both groups drank water ad libitum. T2 measurements in the rats' livers were conducted at a fixed TR of 6000ms and TE of 40-220ms. Exponential curve fitting quality was calculated through the coefficients of determination (R(2)). Chemical analyses of the phantom and livers were not performed, but T2 decay curves were acquired. The T2 relaxation time of methylene resonance was estimated as follows: NC rats, 37.1±4.3ms; HF rats, 31.4±1.8ms (p<0.05). The extrapolated M0 values were higher in HF rats than in NC rats (p<0.005). This study of (1)H MRS led to sufficient spectral resolution and signal-to-noise ratio differences to characterize the T2 relaxation times of methylene resonance. (1)H MRS relaxation times may be useful for quantitative characterization of various liver diseases, including fatty liver disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Detection of total parenteral nutrition-induced fatty liver infiltration in the rat by in vitro proton nuclear magnetic resonance.

    Science.gov (United States)

    Jacobs, D O; Settle, R G; Trerotola, S O; Albina, J E; Wolf, G L; Rombeau, J L

    1986-01-01

    In an effort to determine if NMR techniques might be used to detect TPN-induced hepatic steatosis, the NMR spin-lattice (T1) and spin-spin (T2) relaxation times were measured on liver tissue from rats who received one of five dietary regimens: (1) 100% of nonprotein calories as lipid (Fat); (2) a mixture of 50% lipid and 50% glucose nonprotein calories (50/50); (3) 100% of nonprotein calories as glucose (CHO); (4) intravenous saline and standard laboratory rat chow (Saline); and (5) rat chow alone (Oral). The parenteral diets were isonitrogenous and isocaloric. Serum liver function tests were also measured. Animals in the Fat and 50/50 groups had the greatest amounts of liver fat and significantly longer T1 and T2 times (p less than 0.01) than any other group. Furthermore, the correlation of T2 time with liver fat content (r = 0.82) was far superior (p less than 0.001) to that of serum SGPT (r = 0.48) which was the only liver function test which correlated significantly with liver fat content. In a multiple linear regression analysis, T1 and T2 predicted liver fat content with an r value of 0.84 (p less than 0.001). These data suggest that in vivo NMR imaging techniques might be used to detect TPN-induced fatty infiltration of the liver noninvasively.

  7. Pharmacological and antioxidant actions of garlic and.or onion in non-alcoholic fatty liver disease (NAFLD) in rats.

    Science.gov (United States)

    El-Din, Sayed H Seif; Sabra, Abdel-Nasser A; Hammam, Olfat A; Ebeid, Fatma A; El-Lakkany, Naglaa M

    2014-08-01

    Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of fat-induced liver injury, ranging from mild steatosis to cirrhosis and liver failure. This study investigates the hepatoprotective properties of garlic and onion in NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9 groups; normal (I), NAFLD induced with high fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with garlic (IV, V), onion (VI, VII) or the combined garlic+onion (VIII, IX) respectively. A NAFLD rat model was established by feeding the animals with a high-fat diet for 12 wk. These animals were then treated with garlic or/and onion or vehicle for 8 wk (weeks 13-20) and then killed to obtain serum samples and liver tissues. Liver histology, lipids, parameters of oxidative stress, TNF-α and TGF-β were measured. The liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-α, TGF-β and hepatic MDA' were significantly increased (P onion produced a better and significant decrease in liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation versus each one alone. In the same time, NAFLD-induced inflammation was also mitigated via reduction of TNF-α and TGF-β. In addition, these results were better in the group IX versus group VIII.

  8. Impact of dietary oils and fats on lipid peroxidation in liver and blood of albino rats.

    Science.gov (United States)

    Haggag, Mohammad El-Sayed Yassin El-Sayed; Elsanhoty, Rafaat Mohamed; Ramadan, Mohamed Fawzy

    2014-01-01

    To investigate the effects of different dietary fat and oils (differing in their degree of saturation and unsaturation) on lipid peroxidation in liver and blood of rats. The study was conducted on 50 albino rats that were randomly divided into 5 groups of 10 animals. The groups were fed on dietary butter (Group I), margarine (Group II), olive oil (Group III), sunflower oil (Group IV) and corn oil (Group V) for 7 weeks. After 12 h of diet removal, livers were excised and blood was collected to measure malondialdehyde (MDA) levels in the supernatant of liver homogenate and in blood. Blood superoxide dismutase activity (SOD), glutathione peroxidase activity (GPx), serum vitamin E and total antioxidant capacity (TAC) levels were also measured to determine the effects of fats and oils on lipid peroxidation. The results indicated that no significant differences were observed in SOD activity, vitamin E and TAC levels between the five groups. However, there was significant decrease of GPx activity in groups IV and V when compared with other groups. The results indicated that feeding corn oil caused significant increases in liver and blood MDA levels as compared with other oils and fats. There were positive correlations between SOD and GPx, vitamin E and TAC as well as between GPx and TAC (r: 0.743; P<0.001) and between blood MDA and liver MDA (r: 0.897; P<0.001). The results showed also negative correlations between blood MDA on one hand and SOD, GPx, vitamin E and TAC on the other hand. The results demonstrated that feeding oils rich in polyunsaturated fatty acids (PUFA) increases lipid peroxidation significantly and may raise the susceptibility of tissues to free radical oxidative damage. Copyright © 2014 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

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

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    Z.G. Zhao

    2014-02-01

    Full Text Available The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL on lipopolysaccharide (LPS-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1, myeloperoxidase (MPO, and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

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

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    Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J. [Institute of Microcirculation, Hebei North University, Zhangjiakou, China, Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei (China)

    2014-02-17

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na{sup +}-K{sup +}-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na{sup +}-K{sup +}-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na{sup +}-K{sup +}-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  11. Expression of interleukin 6 and apoptosis-related genes in suckling and weaning rat models of hepatectomy and liver regeneration.

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    Coelho, Maria Cecília M; Tannuri, Uenis; Tannuri, Ana Cristina A; Mello, Evandro S; dos Santos, Neide Aparecida S R

    2007-04-01

    The most commonly used model to study the mechanisms of liver regeneration is the adult rat submitted to 70% to 80% hepatectomy. However, there are no studies using newborn or weaning rat models. The process of liver regeneration includes both the hypertrophy and hyperplasia of cells (processes regulated by growth factors and cytokines, mainly interleukin 6 [IL-6]) as well as apoptosis, or programmed cell death (a process regulated mainly by the Bcl-2 family of proteins). Proapoptotic proteins in this family include Bax and Bak. Conversely, Bcl-2 and Bcl-XL are antiapoptotic regulators. Therefore, to expand our understanding of liver regeneration, our study had 2 goals: first, to standardize 2 animal models of hepatectomy and liver regeneration using the newborn suckling and the weaning rat and second, to quantitate the expression levels of IL-6 and several members of the Bcl-2 gene family during the regeneration process. To create the experimental models, newborn suckling rats (age, 5-7 days; weight, 6-10 g) and weaning rats (age, 21-23 days; weight, 30-50 g) underwent 70% hepatectomy. The animals were subsequently sacrificed at days 1, 2, 3, 4, and 7 after hepatectomy, and the remnant liver lobes were harvested for routine histologic examination. Groups of healthy animals not operated on served as controls. For the experimental study, 6 newborn rats and 6 weaning rats underwent hepatectomy. The animals were killed 1 day after liver resection and the remnant livers were harvested to assess gene expression by quantitative reverse transcription-polymerase chain reaction. The hepatectomized groups were compared with control and sham groups. During the creation of the experimental models, 70% of the suckling animals and all the weaning animals survived the hepatectomy. The decreased liver weight was completely restored to control levels by day 7 after hepatectomy. Histologically, the remnant livers of both hepatectomy groups exhibited steatosis, tumefaction of

  12. Insulin Modulates Liver Function in a Type I Diabetes Rat Model

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    Eduardo L. Nolasco

    2015-07-01

    Full Text Available Background/Aims: Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP in rats. Methods: Diabetic (alloxan, 42 mg/kg i.v., 10 days and non-diabetic (control male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a total and differential cell counts in peritoneal lavage (PeL and bronchoalveolar lavage (BAL fluids; (b quantification of tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA; (c total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d biochemical parameters (urea, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP by colorimetric analyses; and (e lung, kidney, and liver morphological analyses (hematoxylin and eosin staining. Results: Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1β, IL-6, IL-10, CINC-1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c., 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels. Conclusion: These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal

  13. 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.

  14. The protective effect of 1alpha, 25-dihydroxyvitamin d3 and metformin on liver in type 2 diabetic rats.

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    Elattar, Samah; Estaphan, Suzanne; Mohamed, Enas A; Elzainy, Ahmed; Naguib, Mary

    2017-10-01

    There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH) 2 D3. Altered 1α,25(OH) 2 D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and 1α,25(OH) 2 D3 supplementation on liver injury in type 2 diabetic rat. Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1α,25(OH) 2 D3 (0.5μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH) 2 D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-α (regulator of lipid metabolism), NF-κB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination. The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1α,25(OH) 2 D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,25(OH) 2 D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings. Our results showed a protective effect of 1α,25(OH) 2 D3 and metformin on liver in diabetic rats as

  15. Sirius red histophotometry and spectrophotometry of sections in the assessment of the collagen content of liver tissue and its application in growing rat liver

    NARCIS (Netherlands)

    James, J.; Bosch, K. S.; Aronson, D. C.; Houtkooper, J. M.

    1990-01-01

    By means of staining with Sirius Red F3BA in a saturated picric acid solution, the collagen contents of rat livers with varying degrees of fibrosis have been measured quantitatively in fixed and sectioned material, using both histophotometry in situ and extraction of bound dye with colorimetric

  16. Disappearance of GFP-positive hepatocytes transplanted into the liver of syngeneic wild-type rats pretreated with retrorsine.

    Science.gov (United States)

    Maeda, Hiromichi; Shigoka, Masatoshi; Wang, Yongchun; Fu, Yingxin; Wesson, Russell N; Lin, Qing; Montgomery, Robert A; Enzan, Hideaki; Sun, Zhaoli

    2014-01-01

    Green fluorescent protein (GFP) is a widely used molecular tag to trace transplanted cells in rodent liver injury models. The differing results from various previously reported studies using GFP could be attributed to the immunogenicity of GFP. Hepatocytes were obtained from GFP-expressing transgenic (Tg) Lewis rats and were transplanted into the livers of wild-type Lewis rats after they had undergone a partial hepatectomy. The proliferation of endogenous hepatocytes in recipient rats was inhibited by pretreatment with retrorsine to enhance the proliferation of the transplanted hepatocytes. Transplantation of wild-type hepatocytes into GFP-Tg rat liver was also performed for comparison. All biopsy specimens taken seven days after transplantation showed engraftment of transplanted hepatocytes, with the numbers of transplanted hepatocytes increasing until day 14. GFP-positive hepatocytes in wild-type rat livers were decreased by day 28 and could not be detected on day 42, whereas the number of wild-type hepatocytes steadily increased in GFP-Tg rat liver. Histological examination showed degenerative change of GFP-positive hepatocytes and the accumulation of infiltrating cells on day 28. PCR analysis for the GFP transgene suggested that transplanted hepatocytes were eliminated rather than being retained along with the loss of GFP expression. Both modification of the immunological response using tacrolimus and bone marrow transplantation prolonged the survival of GFP-positive hepatocytes. In contrast, host immunization with GFP-positive hepatocytes led to complete loss of GFP-positive hepatocytes by day 14. GFP-positive hepatocytes isolated from GFP-Tg Lewis rats did not survive long term in the livers of retrorsine-pretreated wild-type Lewis rats. The mechanism underlying this phenomenon most likely involves an immunological reaction against GFP. The influence of GFP immunogenicity on cell transplantation models should be considered in planning in vivo experiments

  17. Repopulation of the fibrotic/cirrhotic rat liver by transplanted hepatic stem/progenitor cells and mature hepatocytes

    Science.gov (United States)

    Yovchev, Mladen I.; Xue, Yuhua; Shafritz, David A.; Locker, Joseph; Oertel, Michael

    2013-01-01

    Background & Aim Considerable progress has been made in developing anti-fibrotic agents and other strategies to treat liver fibrosis; however, significant long-term restoration of functional liver mass has not yet been achieved. Therefore, we investigated whether transplanted hepatic stem/progenitor cells can effectively repopulate the liver with advanced fibrosis/cirrhosis. Methods Stem/progenitor cells derived from fetal livers or mature hepatocytes from DPPIV+ F344 rats were transplanted into DPPIV− rats with thioacetamide (TAA)-induced fibrosis/cirrhosis; rats were sacrificed 1, 2, or 4 months later. Liver tissues were analyzed by histochemistry, hydroxyproline determination, RT-PCR, and immunohistochemistry. Results After chronic TAA administration, DPPIV− F344 rats exhibited progressive fibrosis, cirrhosis and severe hepatocyte damage. Besides stellate cell activation, increased numbers of stem/progenitor cells (Dlk-1+, AFP+, CD133+, Sox-9+, FoxJ1+) were observed. In conjunction with partial hepatectomy (PH), transplanted stem/progenitor cells engrafted, proliferated competitively compared to host hepatocytes, differentiated into hepatocytic and biliary epithelial cells, and generated new liver mass with extensive long-term liver repopulation (40.8 ± 10.3%). Remarkably, more than 20% liver repopulation was achieved in the absence of PH, associated with reduced fibrogenic activity (e.g., expression of α-SMA, PDGFRβ, desmin, vimentin, TIMP1) and fibrosis (reduced collagen). Furthermore, hepatocytes can also replace liver mass with advanced fibrosis/cirrhosis, but to a lesser extent than FLSPCs. Conclusions This study is a Proof of Principle demonstration that transplanted epithelial stem/progenitor cells can restore injured parenchyma in a liver environment with advanced fibrosis/cirrhosis and exhibit anti-fibrotic effects. PMID:23840008

  18. Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Qiu, Xiang; Gao, Dan-Hong; Xiang, Xiao; Xiong, Yu-Fang; Zhu, Teng-Shi; Liu, Lie-Gang; Sun, Xiu-Fa; Hao, Li-Ping

    2015-07-14

    To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease (NAFLD) and the related underlying mechanism. After 9 d of acclimation to a constant temperature-controlled room (20 °C-22 °C) under 12 h light/dark cycles, male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet (n = 8) or a high-fat diet (HFD) (n = 32) for 10 d. Animals receiving HFD were then randomly divided into 4 groups and administered with 0, 12.5, 25, or 50 mg/kg (body weight) per day of lutein for the next 45 d. At the end of the experiment, the perinephric and abdominal adipose tissues of the rats were isolated and weighed. Additionally, serum and liver lipid metabolic condition parameters were measured, and liver function and insulin resistance state indexes were assessed. Liver samples were collected and stained with hematoxylin eosin and Oil Red O, and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses. Our data showed that after being fed a high-fat diet for 10 d, the rats showed a significant gain in body weight, energy efficiency, and serum total cholesterol (TC) and triglyceride (TG) levels. Lutein supplementation induced fat loss in rats fed a high-fat diet, without influencing body weight or energy efficiency, and decreased serum TC and hepatic TC and TG levels. Moreover, lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content, and also improved insulin sensitivity. Lutein administration also increased the expression of key factors in hepatic insulin signaling, such as insulin receptor substrate-2, phosphatidylinositol 3-kinase, and glucose transporter-2 at the gene and protein levels. Furthermore, high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1, which are associated with

  19. Continuos intravenous infusion of atrial natriuretic peptide (ANP) prevented liver fibrosis in rat.

    Science.gov (United States)

    Ishigaki, Noriko; Yamamoto, Naoki; Jin, Haiyan; Uchida, Kouichi; Terai, Shuji; Sakaida, Isao

    2009-01-16

    The atrial natriuretic peptide (ANP) are used as the acute heart failure treatment in clinical and reported the suppression of fibrosis in the heart, lung recently. The aim of this study was to analyze the suppressive effect of liver fibrosis about ANP. In vitro, rat hepatic stellate cell line (HSC-T6) were treated with ANP. In vivo, Wister rats were injected with dimethylnitrosamine (DMN) twice a week via intra-peritoneal for 4 weeks. ANP group was given by continuance intravenous dosage system used 24h infusion pump for 3 weeks after 1 week of DMN administration. In vitro, ANP suppressed alpha-SMA expression and was inhibited the growth of HSC, and reduced the expression of type 1 procollagen, TIMP-1, -2 expression. In vivo, The ANP group showed lower serum AST, ALT, HA level. Liver fibrosis was suppressed by ANP. ANP also decreased gene expression of type 1 procollagen, TIMP-1, -2 and alpha-SMA, TGF-beta1 expression. Our results showed that continuous ANP infusion has the specific capacity of inhibiting HSC activation and protecting hepatocytes and the useful capacity to suppress the liver fibrosis.

  20. Absence of carcinogenic and anticarcinogenic effects of annatto in the rat liver medium-term assay.

    Science.gov (United States)

    Agner, A R; Barbisan, L F; Scolastici, C; Salvadori, D M F

    2004-10-01

    Annatto (Bixa orellana L.) is a natural food colorant extensively used in many processed foods, especially dairy products. The lower cost of production and the low toxicity, make annatto a very attractive and convenient pigment in substitution to the many synthetic colorants. In the present study we investigate the carcinogenic and anticarcinogenic effects of dietary annatto in Wistar rat liver using the preneoplastic glutathione S-transferase (GST-P) foci and DNA damage biomarkers. Annatto, containing 5% bixin, was administered in the diet at concentrations of 20, 200, and 1000 ppm (0.07; 0.80 and 4.23 bixin/kg body wt/day, respectively), continuously during 2 weeks before, or 8 weeks after DEN treatment (200 mg/kg body wt, i.p.), to evaluate its effect on the liver-carcinogenesis medium-term bioassay. The comet assay was used to investigate the modifying potential of annatto on DEN (20 mg/kg body wt)-induced DNA damage. The results showed that annatto was neither genotoxic nor carcinogenic at the highest concentration tested (1000 ppm). No protective effects were also observed in both GST-P foci development and comet assays. In conclusion, in such experimental conditions, annatto shows no hepatocarcinogenic effect or modifying potential against DEN-induced DNA damage and preneoplastic foci in the rat liver. Copyright 2004 Elsevier Ltd.

  1. An Imaging and Histological Study on Intrahepatic Microvascular Passage of Contrast Materials in Rat Liver

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    Qian Xia

    2017-01-01

    Full Text Available Background. Lipiodol has been applied for decades in transarterial chemoembolization to treat liver malignancies, but its intrahepatic pathway through arterioportal shunt (APS in the liver has not been histologically revealed. This rodent experiment was conducted to provide evidence for the pathway of Lipiodol delivered through the hepatic artery (HA but found in the portal vein (PV and to elucidate the observed unidirectional APS. Methods. Thirty rats were divided into 5 groups receiving systemic or local arterial infusion of red-stained iodized oil (RIO or its hydrosoluble substitute barium sulfate suspension (BSS, or infusion of BSS via the PV, monitored by real-time digital radiography. Histomorphology of serial frozen and paraffin sections was performed and quantified. Results. After HA infusion, RIO and BSS appeared extensively in PV lumens with peribiliary vascular plexus (PVP identified as the responsible anastomotic channel. After PV infusion, BSS appeared predominantly in the PV and surrounding sinusoids and to a much lesser extent in the PVP and HA (P<0.001. Fluid mechanics well explains the one-way-valve phenomenon of APS. Conclusions. Intravascularly injected rat livers provide histomorphologic evidences: (1 the PVP exists in between the HA and PV, which is responsible to the APS of Lipiodol; and (2 the intrahepatic vascular inflow appears HA-PVP-PV unidirectional without a physical one-way valve, which can be postulated by the fluid mechanics.

  2. ISOLATION OF A GOLGI APPARATUS-RICH FRACTION FROM RAT LIVER

    Science.gov (United States)

    Cheetham, R. D.; Morré, D. James; Pannek, Carol; Friend, Daniel S.

    1971-01-01

    The thiamine pyrophosphatase (the en