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Sample records for rat liver stereology

  1. Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

    PubMed

    Marcos, Ricardo; Correia-Gomes, Carla

    2016-12-01

    Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

  2. Application of quantitative stereology to the evaluation of enzyme-altered foci in rat liver.

    PubMed

    Campbell, H A; Pitot, H C; Potter, V R; Laishes, B A

    1982-02-01

    The mathematical science of quantitative stereology has established relationships for the quantitation of elements in three-dimensional space from observations on two-dimensional planes. This report describes the utilization and importance of such mathematical relationships for the quantitative analysis of focal hepatic lesions in terms relative to the volume of the liver. Three examples are utilized to demonstrate the utility of such calculations in the three-dimensional quantitation of hepatic focal lesions. The first is that of a computer-simulated experiment based on defined hypothetical situations. The simulations demonstrate the applicability of the computations described in this report to the evaluation of two-dimensional data from typical animal experiments. The other two examples are taken from actual experiments and involve the transplantation of hepatic cell populations into the liver suitably prepared hosts and the quantitation of altered foci produced by initiation with diethylnitrosamine-partial hepatectomy followed by promotion with phenobarbital. The quantitation of altered foci by means of a two-dimensional analysis (simple enumeration of focal intersections/area of tissue section) is proportional to the quantitation of foci per volume of liver provided that the mean diameter of the foci for each treatment is sufficiently uniform, as exemplified in the text by the transplantation experiment. When such mean diameters are unequal as in the diethylnitrosamine-phenobarbital experiment described herein, quantitation from three-dimensional analysis gives significantly different results as compared with enumeration of focal intersections on two-dimensional areas. These studies clearly demonstrate that the frequency and size of foci intersections viewed on two-dimensional tissue sections do not necessarily reflect the number of size of foci in the three-dimensional tissue. Only by quantitating the number and size of the foci in relation to the three

  3. Stereology of the pterygopalatine ganglion of the rat.

    PubMed

    Costa, W S; Morais, R; Mandarim-De-Lacerda, C A

    1992-01-01

    The right pterygopalatine ganglia (PG) of 9 male Wistar-strain rats were dissected, embedded in Epon (3 specimens) or paraffin (6 specimens), and prepared for stereological examination under light microscopy. The perikarya were quantitatively characterized, and the ganglionic volume was determined. Stereology is an efficient method for the quantitative evaluation of the perikarya of the PG. The results(expressed as mean +/- standard deviation) were: a) areal fraction occupied by the perikarya = 53.8 +/- 7.4%; b) the perikaryal surface area per volume = 0.101 +/- 0.013 microns-1; c) the number of perikarya per volume x 10(-5) = 5.26 +/- 0.99 microns-3; d) the mean profile area of the perikarya (apk) = 505.93 +/- 78.29 microns 2; e) the mean perikaryal volume (vpk) = 9,179.33 +/- 1,533.52 microns 3; and f) the ganglionic volume = 0.210 +/- 0.127 mm3. The low coefficient of variation the apk and vpk values suggests the presence of only one population of neurons in the PG of the rat. The number of perikarya in the PG is about 11,046 per ganglion. As compared to analogous data in the otic ganglion of the rat, the PG did not show statistically significant stereological differences, but the relatively higher number of neurons found in the PG is probably associated with the higher functional activity of this ganglion.

  4. [Stereological analysis of rat bone tissue after a flight on the Kosmos-1129 biosatellite].

    PubMed

    Prokhonchukov, A A; Peschanskiĭ, V S

    1982-01-01

    Stereological measurements of volume fractions of 53 samples of compact and spongy structures of bones of 15 rats were carried out. The measurements were performed on cortical lamellae, trabecules and lacunae, channels of osteons and matrices of femoral, tibial and fibular bones of rats. Postflight no significant changes were seen in the above parameters as compared to the vivarium controls. During readaptation to I g a slight increase in the volume fraction of spongy bones was noted.

  5. Stereological Analysis of Liver Biopsy Histology Sections as a Reference Standard for Validating Non-Invasive Liver Fat Fraction Measurements by MRI

    PubMed Central

    St. Pierre, Tim G.; House, Michael J.; Bangma, Sander J.; Pang, Wenjie; Bathgate, Andrew; Gan, Eng K.; Ayonrinde, Oyekoya T.; Bhathal, Prithi S.; Clouston, Andrew; Olynyk, John K.; Adams, Leon A.

    2016-01-01

    Background and Aims Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7–8.8)% and 2.4 (95% CI 2.2–2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69–0.93) and 0.990 (95% CI 0.985–0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using HepaFat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF. PMID:27501242

  6. Stereological analysis of cornu ammonis in prenatally stressed rats: a heuristic neurodevelopmental model of schizophrenia

    PubMed Central

    Hosseini-sharifabad, Mohammad; Sabahi, Abdoreza

    2014-01-01

    Objective(s): The hippocampus has been implicated in pathophysiology of schizophrenia. Prenatal stress is a contributing risk factor for a wide variety of neuropsychiatric diseases including schizophrenia. This study examined long-term effects of prenatal restraint stress on the stereological parameters in the Cornu Ammonis (CA) of adult male rats as an animal model of schizophrenia. Materials and Methods: Wistar pregnant dams in experimental group were stressed in a cylindrical Plexiglas restrainer daily for 1 hr during last week of gestation. Controls remained in the animal room and were exposed only to normal animal room conditions. At 2 months of age, the volume of the pyramidal cell layer of the CA, the numerical density and the somal volume of the respective neurons were assessed in the male offspring generated from stressed and control pregnancies. Cavalieri's principle, physical disector and nucleator were applied for stereological analyses. Results: This study showed that prenatal stress significantly decreased the volume of CA3 pyramidal cell layer and the individual somal volume of CA3 pyramidal neurons. However, there were no markedly differences in the numerical density, total number of CA3 pyramidal neurons and stereological parameters in CA1 of prenatally stressed and control animals. Conclusion: These data indicate that prenatal stress exposure induced neuronal changes in the CA3 subfield of hippocampus which are similar to what is observed in schizophrenia. PMID:24847421

  7. Post-natal growth in the rat pineal gland: a stereological study.

    PubMed

    Erbagci, H; Kizilkan, N; Ozbag, D; Erkilic, S; Kervancioglu, P; Canan, S; Gumusburun, E

    2012-10-01

    The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies.

  8. Effects of prolonged alcohol exposure on somatotrophs and corticotrophs in adult rats: Stereological and hormonal study.

    PubMed

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Jurijević, Branka Šošić; Balind, Snežana Raus; Brajković, Gordana; Perčinić-Popovska, Florina; Milošević, Verica

    2016-05-01

    Exposure to alcohol alters many physiological processes, including endocrine status. The present study examined whether prolonged alcohol (A) exposure could modulate selected stereological and hormonal aspects of pituitary somatotrophs (growth hormone-GH cells) and corticotrophs (adrenocorticotropic hormone-ACTH cells) in adult rats. Changes in pituitary gland volume; the volume density, total number and volume of GH and ACTH cells following alcohol exposure were evaluated using a stereological system (newCAST), while peripheral GH and ACTH levels were determined biochemically. Our results demonstrated the reduction (p<0.05) of the volume density (37%) and volume of GH cells (29%) in the group A. Also, there was a tendency for the total number of GH cells to be smaller in the group A. Serum GH level was significantly decreased (p<0.05; 70%) in the group A when compared to control values. Moreover, prolonged alcohol exposure induced declines (p<0.05) in volume density (24%) and volume of ACTH cells (29%). The total number of ACTH cells and ACTH level were higher (p<0.05; 42%) in the group A than in control rats. Collectively, these results indicate that prolonged alcohol exposure leads not only to changes in GH and ACTH hormone levels, but also to alterations of the morphological aspects of GH and ACTH cells within the pituitary.

  9. Sorafenib inhibits liver regeneration in rats

    PubMed Central

    Andersen, Kasper Jarlhelt; Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Sasanuma, Hideki; Nyengaard, Jens Randel; Hamilton-Dutoit, Stephen; Ladekarl, Morten; Mortensen, Frank Viborg

    2013-01-01

    Background Sorafenib is a multikinase inhibitor with antiangiogenic and antiproliferative properties, approved for the treatment of hepatocellular carcinoma. The effect of Sorafenib on liver regeneration in healthy rats was investigated. Methods Sixty Wistar rats received either Sorafenib (group S; 15 mg/kg) or placebo for 14 days prior to resection and until sacrifice. After a 70% partial hepatectomy, the rats were euthanized on post-operative days (POD) 2, 4 or 8. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using stereological methods on sections prepared by systematic uniform random sampling. Results Seven animals (12%) died after surgery. Death rates were similar in treated rats and controls. At hepatectomy, the body weight was significantly lower in group S rats. The liver weight and regeneration rates were lower in group S rats on PODs 2, 4 and 8. Hepatocyte proliferation was significantly lower in group S animals on PODs 2 and 4. Alanine aminotransferase ALAT was significantly higher in the Sorafenib-treated group on PODs 2, 4 and 8. Alkaline phosphatase ALP and bilirubin levels were similar in the two groups, although bilirubin was elevated in group S rats on POD 8. Conclusion In this rat model, Sorafenib did not increase post-hepatectomy mortality, but was associated with a significant impaired liver weight gain, regeneration rates and hepatocyte proliferation. PMID:23461776

  10. Crataegus monogyna aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis: stereological evidences.

    PubMed

    Jalali, Ali Shalizar; Hasanzadeh, Shapour; Malekinejad, Hassan

    2012-01-01

    Cyclophosphamide (CP) is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices) were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.

  11. Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

    PubMed

    Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

    2016-11-09

    Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

  12. Effects of Diabetes on Post-Menopausal Rat Submandibular Glands: A Histopathological and Stereological Examination

    PubMed Central

    Buyuk, Basak; Parlak, Secil Nazife; Keles, Osman Nuri; Can, Ismail; Yetim, Zeliha; Toktay, Erdem; Selli, Jale; Unal, Bunyami

    2015-01-01

    Objective: The menopause in elderly women is a physiological process where ovarian and uterine cycles end. Diabetes means higher blood glucose level that is a metabolic disease and has an increased incidence. The aim of the study was to examine the single or combined effects of menopause and diabetes that causes pathophysiological processes on submandibular gland on ovariectomy and diabetes induced rat models. Materials and Methods: Sprague Dawley twelve weeks old female (n=24) rats were divided randomly into four groups; Healthy control group (n=6), diabetic group (DM, n=6), ovariectomized group (OVX, n=6), post ovariectomy diabetes induced group (DM+OVX, n=6) individually. Histopathological, histochemical and stereological analyses were done in these groups. Results: Significant neutrophil cell infiltrations and myoepithelial cell proliferations, granular duct and seromucous acini damages and changes in the content of especially seromucous acini secretion in DM and/or OVX groups and distinctive interstitial and striated duct damages in post ovariectomy diabetes induced group were detected. Alterations ingranular ducts hypertrophic and in seromucous acini atrophic were determined in DM and/or OVX groups. Conclusion: The results revealed the pathophysiological processes that lead to morphological and functional alterations on the cellular level in submandibular glands. The molecular mechanisms related with pathogenesis of diabetes and menopause need further investigation. PMID:26644770

  13. Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

    PubMed Central

    Rafati, Ali; Hoseini, Leila; Babai, Ali; Noorafshan, Ali; Haghbin, Hossein; Karbalay-Doust, Saied

    2015-01-01

    Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P < 0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P < 0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P < 0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P < 0.03). PMID:26770914

  14. Electroconvulsive stimulation, but not chronic restraint stress, causes structural alterations in adult rat hippocampus--a stereological study.

    PubMed

    Olesen, Mikkel V; Wörtwein, Gitta; Pakkenberg, Bente

    2015-01-01

    The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress induces depression-like behavior, without significantly changing neurogenesis, the total number of neurons or the volume of the hippocampus. Further, electroconvulsive stimulation prevents stress-induced depression-like behavior and increases neurogenesis. The total number of neurons and the granule cell layer volume was not affected by electroconvulsive stimulation.

  15. Comparison of aortic intima and inner media in young adult versus aging rats. Stereology in a polarized system.

    PubMed Central

    Guyton, J. R.; Lindsay, K. L.; Dao, D. T.

    1983-01-01

    Age-related ultrastructural changes in the intima and inner media of rat thoracic aorta were examined by new morphometric techniques. Young adult male rats, 10 weeks old, were compared with 1-year-old male rats. The most marked changes were found in the sub-endothelium, which increased in thickness more than five-fold. Basement-membrane-like and granular material accounted for the bulk of this thickening. Certain other structures were increased sevenfold or more in subendothelium. These structures and the volume fractions they occupied in 1-year-old rats were as follows: banded collagen, 4.3%; mononuclear leukocytes, 4.5%; cystic structures, 3.3%; and fibrillar elastin, 1.0%. Changes were also demonstrated in the fenestrae of and at selected depth levels below the innermost, or alternatively the internal, elastic lamina. Collagen increased strikingly within fenestrae and just below the elastic lamina. This was associated with a 28% increase in the thickness of the elastic lamina and a recession of smooth muscle cytoplasm to a deeper position within the first musculoelastic medial layer. The alterations in subendothelial tissues imply an altered basis for mechanical support for aortic endothelium in aging rats. These results mark the successful application of micro-computer-based stereology to a situation of polarized geometry. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:6846504

  16. Effect of Urtica dioica on morphometric indices of kidney in streptozotocin diabetic rats--a stereological study.

    PubMed

    Golalipour, Mohammad Jafar; Gharravi, Anneh Mohammad; Ghafari, Sorya; Afshar, Mohammad

    2007-11-01

    The aim of the present study was to investigate the effect of Urtica dioica on Morphometric indices of kidney in diabetic rats. Thirty male adult albino wistar rats of 125-175 g divided into control, diabetic and Urtica dioica treatment groups. In treatment Group, diabetic rats received 100 mg kg(-1) daily hydroalcoholic extract of U. dioica intraperitoneally for 4 weeks. After the animals had been sacrified, the kidneys were removed and fixed by formaldehyde, cut horizontally into 1 mm slices and processed, Stained with H and E. Stereological study performed using light microscope and the image projected on a table of olysa software. Cavalieri principle was used to estimate the volume of cortex, medulla and whole kidney. All the grouped data statistically evaluated using Student's t-test, expressed as the Mean +/- SE. Ration of kidney weight/body weight in diabetes (0.51) and diabetes-extract group (0.67) were higher then control group (0.42). Ratio of kidney volume/body weight in diabetes (350) and diabetes-extract group (348) were higher then control group (323). Volume Ratio of cortex/medulla in diabetes-extract group (1.65) was higher then control (1.34) and diabetes group (1.33). Glomerular area and diameter and proximal tubule diameter in diabetes-Extract group was higher than control and diabetes groups. This study revealed that Urtica dioica has no effect on renal morphometric indices in induced diabetic rats.

  17. Stereological study on the number of synapses in the rat spinal dorsal horn with painful diabetic neuropathy induced by streptozotocin.

    PubMed

    Lin, Jing-Yan; Huang, Xiao-Li; Chen, Jing; Yang, Zheng-Wei; Lin, Jing; Huang, San; Peng, Bin

    2017-03-02

    Our previous studies showed that direct injury to the sciatic nerve (chronic constriction injury or axotomy) is associated with a numerical increase in synaptic number in the rat spinal dorsal horn. The aim of this study was to determine whether painful diabetic neuropathy (PDN) was also associated with numerical changes in the synaptic or neuronal numbers in the spinal dorsal horn. Overall, 17 adult SD rats were allocated randomly into the control group (n=5) and the streptozotocin (STZ) group (n=12). STZ was injected intraperitoneally to induce diabetes. In the STZ group, seven rats (STZ-H) showed hyperglycemia (fasting blood glucose >11.1 mM) and the rest of the five rats (STZ-N) did not. Rats were fed and observed for 28 days after hyperglycemia. Two of the seven STZ-H rats died of infection during the observation period. Body weight and paw withdraw threshold (PWT) decreased in the rest of the five STZ-H rats. Twenty-eight days after hyperglycemia, the L5 segment of the spinal cord was removed; paraffin-embedded sections were prepared and stained with Nissl's method and synaptophysin immunohistochemistry, respectively. The optical dissector (a stereological technique) was used to estimate the numbers of neurons and synapses in the spinal dorsal horn. Compared with the control group, the synaptic number and ratio between the numbers of synapses and neurons in the L5 segment of the spinal dorsal horn were increased significantly in the STZ-H rats (P<0.05), whereas the neuronal number did not change significantly (P>0.05). Parameters of STZ-N rats showed no significant changes. In conclusion, PDN, a form of neuropathic pain, is also associated with a synaptic plasticity (numerical increase) in the spinal dorsal horn. This numerical change might be the reason for central sensitization resulting in reduced pain threshold, enhanced responsiveness, and expanded receptive fields associated with PDN. Therefore, our studies indicate that neuropathic pain conditions

  18. Assessment standards: comparing histopathology, digital image analysis, and stereology for early detection of experimental cisplatin-induced kidney injury in rats.

    PubMed

    Shea, Katherine; Stewart, Sharron; Rouse, Rodney

    2014-08-01

    Histopathology generally represents the reference standard for performance evaluation of nonclinical biomarkers used to inform regulatory decision making. This study uses drug-induced nephrotoxicity in rats to evaluate histopathology methods utilized in biomarker performance assessments. Male Sprague-Dawley rats received a single dose of cisplatin (0.5-5.0 mg/kg, intraperitoneally) to produce mild renal injury. Animals were euthanized 72 hr postdose and perfusion fixed. Kidneys were processed for histology and stereology procedures. Kidney injury molecule-1 (Kim-1) was measured in urine and in kidney tissue. Digital slide images were generated and analyzed by pathologists after collaborating on a training set of glass slides and digital images. Image analysis identified immunohistochemistry (IHC)-defined tubular injury. Stereology methods yielded estimations of proximal tubular cell number and volume. Statistical relationships among data sets were determined using correlation coefficients. Receiver operator characteristic (ROC) analyses determined the effect of method on biomarker assessment. Urinary Kim-1 was strongly correlated with digital image analysis and secondarily to histopathology evaluations. Stereology demonstrated weak or no correlation to pathology and urinary Kim-1. In ROC analyses, semiquantitative evaluations determined higher values for urinary Kim-1 performance than did IHC-based qualitative digital analyses. Semiquantitative evaluation as used in this study was most predictive of urinary Kim-1 values.

  19. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves.

    PubMed

    Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E

    2013-12-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function).

  20. Stereological study on the effect of vitamin C in preventing the adverse effects of bisphenol A on rat ovary

    PubMed Central

    Soleimani Mehranjani, Malek; Mansoori, Tayebeh

    2016-01-01

    Background: Bisphenol A (BPA), an environmental pollutant, can generate free radicals which damages the reproductive system. Vitamin C is an antioxidant which may prevent the adverse effects of free radicals. Objective: The aim was to investigate the effect of vitamin C on the ovary tissue in rats treated with BPA. Materials and Methods: In this experimental study, 24 female Wistar rats (200±20 gr) were randomly divided into 4 groups (n=6): control, BPA (60 µg/Kg/day), vitamin C (150 mg/Kg/day) and BPA + vitamin C and orally treated for 20 days. The left ovaries were taken out, fixed for tissue processing and studied using stereological methods. Data were analyzed with SPSS using one-way ANOVA, and the means were considered significantly different at (p<0.05). Results: The total volume of ovary and cortex (p<0.01), medulla (p<0.05), the volume of corpus luteum (p<0.001) and the mean number of antral follicles (p<0.001) significantly reduced in BPA group compared with control, while the number of atretic follicles increased (p<0.05). The volume of oocyte (p<0.01) and its nucleus (p<0.001) in the antral follicles and the thickness of zona pellucida (ZP) in the secondary (p<0.05) and antral (p<0.001) follicles significantly decreased in BPA group compared with controls. The above parameters in the BPA + vitamin C group were compensated to control level. Conclusion: Vitamin C can be used as a potential antioxidant in the case of BPA toxication PMID:27525324

  1. The effects of pomegranate extract on normal adult rat kidney: A stereological study

    PubMed Central

    Mansouri, Esrafil; Basgen, John; Saremy, Sadegh

    2016-01-01

    Pomegranate (Punica granatum L.) has been used widely in the traditional medicine of various civilizations for more than 5000 years. The pomegranate tree has several parts; each part has useful medicinal effects. Previous studies have demonstrated the antibacterial, antioxidant, and anti-inflammatory properties of pomegranate. The aim of the present study was to determine whether administration of pomegranate extract could result in morphometric changes in the kidneys of rats. Eighteen male rats (180-200 g) were divided into three groups that received either: G1, distilled water; G2, 250 mg kg-1 pomegranate extract; and G3, 500 mg kg-1 pomegranate extract via oral gavages daily for eight weeks. At the end of eight weeks, the rats were euthanized and their kidneys were removed and processed for morphometric analyses. In rats received pomegranate extract, the kidney weight, kidney weight/body weight ratio, cortex v/lume and glomerular volume were increased (p < 0.05), while, medulla volume and the number of glomeruli per kidney did not change. No pathological lesions were observed in the kidney. Therefore, pomegranate hydro-alcoholic extract at doses of 250 and 500 (mg kg-1) increased the volume of some parts of the kidney; however, it did not cause any pathological changes in the kidney. PMID:27226880

  2. Age-related changes in rat cerebellar basket cells: a quantitative study using unbiased stereological methods

    PubMed Central

    HENRIQUE, RUI M. F.; ROCHA, EDUARDO; REIS, ALCINDA; MARCOS, RICARDO; OLIVEIRA, MARIA H.; SILVA, MARIA W.; MONTEIRO, ROGÉRIO A. F.

    2001-01-01

    Cortical cerebellar basket cells are stable postmitotic cells; hence, they are liable to endure age-related changes. Since the cerebellum is a vital organ for the postural control, equilibrium and motor coordination, we aimed to determine the quantitative morphological changes in those interneurons with the ageing process, using unbiased techniques. Material from the cerebellar cortex (Crus I and Crus II) was collected from female rats aged 2, 6, 9, 12, 15, 18, 21 and 24 mo (5 animals per each age group), fixed by intracardiac perfusion, and processed for transmission electron microscopy, using conventional techniques. Serial semithin sections were obtained (5 blocks from each rat), enabling the determination of the number-weighted mean nuclear volume (by the nucleator method). On ultrathin sections, 25 cell profiles from each animal were photographed. The volume density of the nucleus, ground substance, mitochondria, Golgi apparatus (Golgi) and dense bodies (DB), and the mean surface density of the rough endoplasmic reticulum (RER) were determined, by point counting, using a morphometric grid. The mean total volumes of the soma and organelles and the mean total surface area of the RER [s̄N (RER)] were then calculated. The results were analysed with 1-way ANOVA; posthoc pairwise comparisons of group means were performed using the Newman-Keuls test. The relation between age and each of the parameters was studied by regression analysis. Significant age-related changes were observed for the mean volumes of the soma, ground substance, Golgi, DB, and s̄N (RER). Positive linear trends were found for the mean volumes of the ground substance, Golgi, and DB; a negative linear trend was found for the s̄N (RER). These results indicate that rat cerebellar basket cells endure important age-related changes. The significant decrease in the s̄N (RER) may be responsible for a reduction in the rate of protein synthesis. Additionally, it may be implicated in a cascade of events

  3. Stereological assessment of vulnerability of immunocytochemically identified striatal and hippocampal neurons after global cerebral ischemia in rats.

    PubMed

    Larsson, E; Lindvall, O; Kokaia, Z

    2001-09-21

    Detailed quantitative analysis of the vulnerability of different hippocampal and striatal neurons to global forebrain ischemia has not previously been performed. Here we have studied the survival of immunocytochemically identified neurons using an unbiased stereological method in rats subjected to global forebrain ischemia for 30 min and sacrificed 48 h, 1 week or 4 weeks thereafter. Within the hippocampal formation, there was extensive, progressive loss of CA1 pyramidal neurons and dentate hilar neuropeptide Y (NPY)-positive interneurons. In contrast, no reduction of the number of CA3 and CA4 pyramidal neurons or hilar parvalbumin-positive interneurons was detected. In the dorsolateral striatum, the insult caused a major loss of projection neurons immunoreactive to dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). The number of parvalbumin-positive striatal interneurons was significantly reduced, while NPY-positive interneurons were resistant. All striatal cholinergic interneurons survived the ischemic insult. At 48 h following the ischemia, the cholinergic interneurons within the lesioned striatum transiently expressed the p75 neurotrophin receptor (p75(NTR)), as shown by double-label immunocytochemistry. Furthermore, there was a significant increase in the number of choline acetyltransferase (ChAT)- and TrkA-immunoreactive interneurons at 4 weeks after the insult. Injections with the cell mitotic division marker BrdU provided no evidence that the elevated cholinergic cell number was due to neurogenesis. Probably, the higher number of ChAT- and TrkA-positive interneurons reflected increased intracellular levels of the corresponding proteins leading to more cells detectable with immunocytochemistry. This study gives the first quantitative description of the vulnerability of defined hippocampal and striatal neurons after global forebrain ischemia. The ischemia-induced increases of p75(NTR), Trk

  4. Effects of prenatal exposure to diclofenac sodium and saline on the optic nerve of 4- and 20-week-old male rats: a stereological and histological study.

    PubMed

    Çolakoğlu, S; Aktaş, A; Raimondo, S; Türkmen, A P; Altunkaynak, B Z; Odacı, E; Geuna, S; Kaplan, S

    2014-02-01

    We investigated the effects of diclofenac sodium (DS) on development of the optic nerve in utero. Pregnant female rats were separated into three groups: control, saline treated and DS treated. Offspring of these animals were divided into 4-week-old and 20-week-old groups. At the end of the 4th and 20th weeks of postnatal life, the animals were sacrificed, and right optic nerves were excised and sectioned for ultrastructural and stereological analyses. We demonstrated that both DS and saline produced structural and morphometric changes in the total axon number and density of axons, but decreased the myelin sheath thickness in male optic nerves. All ultrastructural and morphometric features were well developed in 20-week-old rats. We showed that development of the optic nerve continues during the early postnatal period and that some compensation for exposure to deleterious agents in utero may occur during early postnatal life.

  5. Quantification of rat retinal growth and vascular population changes after single and split doses of proton irradiation: translational study using stereology methods

    NASA Technical Reports Server (NTRS)

    Mao, Xiao W.; Archambeau, John O.; Kubinova, Lucie; Boyle, Soames; Petersen, Georgia; Grove, Roger; Nelson, G. A. (Principal Investigator)

    2003-01-01

    This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (P<0.01) after 28 Gy given in single and split doses and after 20 Gy given as a split dose (P<0.05). Total vessel length in microvessel was significantly shortened at 20 and 28 Gy compared to that of controls (P<0.05). No evident dose recovery was observed in the endothelial populations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.

  6. 17β-estradiol replacement therapy protects myelin sheaths in the white matter of middle-aged female ovariectomized rats: a stereological study.

    PubMed

    Luo, Yanmin; Xiao, Qian; Chao, Fenglei; He, Qi; Lv, Fulin; Zhang, Lei; Gao, Yuan; Qiu, Xuan; Huang, Chunxia; Li, Yongde; Wang, Sanrong; Jiang, Rong; Gu, Hengwei; Tang, Yong

    2016-11-01

    Many studies have shown that estrogen replacement therapy (ERT) can improve cognitive function and affect the structure of the brain, including the white matter, in postmenopausal women. However, it is unclear whether ERT plays an important role in white matter remodeling in postmenopausal women. In the present study, middle-aged (9-12-month-old) female Sprague-Dawley rats were bilaterally ovariectomized (OVX) and randomly allocated to the vehicle treatment (OVX+Veh) group or the 17β-estradiol replacement (OVX+E) group. After 1 month of treatment, spatial learning and memory capacities were assessed using the Morris water maze task. Then, stereological methods were used to quantitatively evaluate white matter volume and myelinated fiber parameters of the white matter in the 2 groups of rats. The results revealed that the mean escape latency of the OVX+E rats in the Morris water maze task was significantly shorter than that of the OVX+Veh rats. The volume density of the myelinated fibers and the volume density and total volume of the myelin sheaths were significantly greater in the OVX+E rats than in the OVX+Veh rats. However, there were no significant differences in white matter volume or in the total length or volume of myelinated fibers in white matter between the 2 groups of rats. Our results showed that 1 month of ERT had significant beneficial effects on spatial learning capacity and on the myelin sheaths and myelinated fibers in the white matter of middle-aged OVX rats.

  7. Introduction to stereology.

    PubMed

    West, Mark J

    2012-08-01

    Just as astrology became astronomy and alchemy became chemistry through the application of mathematics, descriptive anatomy can be expected to become more and more quantitative in nature. This article describes the basics of stereology, which provides meaningful quantitative descriptions of the geometry of three-dimensional (3D) structures from measurements that are made on two-dimensional (2D) images. With precise mathematical descriptions such as those that can be obtained with unbiased stereological techniques, it will be possible to make concise descriptions of the relationships between structure and function, of the dynamics of structure, and to reassert the importance of quantitative morphology as an essential part of the evaluation of biological tissues.

  8. Stereology of the lung.

    PubMed

    Schneider, Jan Philipp; Ochs, Matthias

    2013-01-01

    Many scientific projects require a quantitative assessment of organ, tissue and cell (ultra)structure. Such quantitative (morphometric) data are essential to make statistically valid comparisons between experimental groups. The structures of interest are measured at different microscopic levels. However, measurements in microscopy pose two problems: 1) Only a small fraction of the whole biological system can be analyzed (sampling problem). 2) The analysis is performed on nearly two-dimensional (physical, optical or virtual) sections through the object although the aim is to obtain biologically meaningful three-dimensional data (3D vs 2D problem). These problems are solved by the application of unbiased sampling and measurement tools known as stereology. This chapter gives a brief introduction to the theory and practical application of stereology, using the lung as an example. Stereological tools needed to quantify volume, number and surface area are introduced and examples are given how to estimate total lung volume, volume of lung parenchyma, alveolar surface area and number of alveolar epithelial type II cells per lung.

  9. The quantitative distinction of hyperplasia from hypertrophy in hepatomegaly induced in the rat liver by phenobarbital.

    PubMed

    Carthew, P; Edwards, R E; Nolan, B M

    1998-07-01

    A histological method utilizing the optical dissector principle has been developed for determining the absolute numbers of rat hepatocytes in the liver after treatment with phenobarbital (PB). The optical dissector is a technique derived from the "new stereology" used to measure the number of features, in this case hepatocyte nuclear profiles, that are present in a reference volume of tissue. The method has been applied to distinguish between the hepatomegaly that commonly occurs in rodents after treatment with chemicals, due to an increase in the number of cells caused by cell division (hyperplasia), rather than the size of cells (hypertrophy). In the case of PB treatment, the hepatomegaly was found to be partly due to hypertrophy and partly to hyperplasia after 2 weeks of treatment. While the increase in the absolute number of hepatocytes was not significant after 2 weeks, after 12 weeks of treatment with PB the number of hepatocytes was significantly increased, compared to the controls at that time point. PCNA labeling index measurements of liver hepatocytes confirmed that there was a significant increase in the growth fraction of hepatocytes during PB treatment. The induction of hyperplasia can be associated with an increased risk of eventual liver tumor formation, and the distinction of hyperplasia from hypertrophy, using a purely histological method, for the determination of increases in absolute hepatocyte cell numbers, will be useful in assessing whether treatment-related sustained hyperplasia is occurring in the liver, although this methodology could be applied to any organ.

  10. Chronological protein synthesis in regenerating rat liver.

    PubMed

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

    2015-07-01

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

  11. Intrastriatal injection of botulinum neurotoxin-A is not cytotoxic in rat brain - A histological and stereological analysis.

    PubMed

    Mehlan, Juliane; Brosig, Hans; Schmitt, Oliver; Mix, Eilhard; Wree, Andreas; Hawlitschka, Alexander

    2016-01-01

    Parkinson's disease (PD) is caused by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in a deficiency of dopamine in the striatum and an increased release of acetylcholine by tonically active interneurons. Botulinum neurotoxin-A (BoNT-A) is well known for blocking transmitter release by cholinergic presynaptic terminals. Treating striatal hypercholinism by local application of BoNT-A could be a possible new local therapy option of PD. In previous studies of our group, we analyzed the effect of BoNT-A injection into the CPu of 6-OHDA lesioned hemiparkinsonian rats. Our studies showed that BoNT-A application in hemiparkinson rat model is capable of abolishing apomorphine induced rotations for approximately 3 months. Regularly occurring axonal swellings in the BoNT-A infiltrated striata were also discovered, which we named BoNT-A induced varicosities (BiVs). Résumé: Here we investigated the long-term effect of the injection of 1ng BoNT-A into the right CPu of naive Wistar rats on the number of ChAT-ir interneurons as well as on the numeric density and the volumetric size of the BiVs in the CPu. Significant differences in the number of ChAT-ir neurons between the right BoNT-A treated CPu and the left untreated CPu were not detected up to 12 month post BoNT-A injection. The numeric density of BiVs in the treated CPu reached a maximum 3 months after BoNT-A treatment and decreased afterwards, whereas the volume of single BiVs increased steadily throughout the whole time course of the experiment.

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

    PubMed

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

    2016-02-26

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

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

    PubMed Central

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

    2016-01-01

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

  14. Phenotype of preneoplastic and neoplastic liver lesions during spontaneous liver carcinogenesis of LEC rats.

    PubMed

    Sawaki, M; Enomoto, K; Takahashi, H; Nakajima, Y; Mori, M

    1990-10-01

    The incidence and phenotype of preneoplastic and neoplastic liver lesions appearing in LEC rats after recovery from severe hereditary hepatitis were studied in comparison with the liver lesions appearing in chemical liver carcinogenesis. The livers of 168 rats (90 male, 78 female) were stained for seven histochemical markers at different time periods from the 20th week to the 122nd week of life. Glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and non-specific esterase (ES) were used as negative markers. Gamma-glutamyltransferase (GGT), glutathione S-transferase placental form (GSTP), esterase isozyme L-1 (L1) and alpha-fetoprotein (AFP) were used as positive markers. The study on the incidence of liver lesions in the LEC rats revealed sequential development of liver foci, nodules and hepatocellular carcinomas (HCCs) similar to those seen in chemically induced liver carcinogenesis. These lesions appeared earlier and more frequently in male LEC rats than in female ones, suggesting the importance of hormonal environment in spontaneous HCC development. The histochemical analysis of spontaneous liver lesions in LEC rats showed that GSTP was the most reliable positive marker as previously reported in chemical liver carcinogenesis. There was no essential difference in the expression of the markers in spontaneous and chemically induced liver lesions except for L1, which is considered to be related to xenobiotic metabolism. The results of this study suggest that both spontaneous and chemically induced liver cancer may develop by passing through phenotypically similar preneoplastic processes. In addition, the LEC rat uniquely showed chronic liver damage (hepatocyte death and regeneration) at the promotion stage of carcinogenesis. Such a natural history of HCC development in LEC rats is similar to that of human HCC which is frequently associated with chronic liver damage. Thus, the LEC rat provides a useful model for studying the process and underlying

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

    PubMed

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

    2012-02-01

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

  16. Ideal Experimental Rat Models for Liver Diseases.

    PubMed

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

    2011-05-01

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

  17. Ideal Experimental Rat Models for Liver Diseases

    PubMed Central

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

    2011-01-01

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

  18. Dinucleosidasetetraphosphatase in rat liver and Artemia salina.

    PubMed

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

    1976-06-07

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

  19. Cell Therapy for Liver Disease Using Bioimaging Rats

    PubMed Central

    Haga, Junko; Enosawa, Shin; Kobayashi, Eiji

    2017-01-01

    Advances in stem cell research suggest that cell therapy is a potential alternative to liver transplantation. The use of individualized and minimally invasive cell therapy is desirable to avoid rejection and reduce patient burden. While allo-hepatocyte transplantation has been performed for metabolic hepatic disease, auto-bone marrow transplantation (BMT) has shifted toward mesenchymal stem cells (MSCs) transplantation for liver cirrhosis. In this article, an overview of cell transplantation research for liver disease is provided through our recent rat studies. We have developed various kinds of rat imaging models and have evaluated the effect of cell therapy for liver disease. Bone marrow cells (BMCs) of the Alb-DsRed2 rat were transplanted via the portal vein (PV) in acute and chronic liver damage models. The number of Alb-DsRed2+ albumin-producing cells increased, and the size of the cells increased in the chronic liver damage model as well as in the acute liver damage model. Luciferase transgenic (luc-Tg) rat hepatocytes were transplanted into the hepatectomized LEW rat via the PV. Luminescence intensity lasted for 2 months in the hepatectomized rat. BMCs obtained from green fluorescent protein (GFP) Tg rats were transplanted repeatedly via the PV using an implanted catheter with a port. Repeated BMT via the PV reduced the liver fibrosis. Adipocyte-derived MSCs from the luc-Tg rat were transplanted into the hepatectomized rat model via the PV after ischemic reperfusion. MSCs inhibited hepatocyte apoptosis and promoted liver regeneration. Transplanting the optimal number of cells by an effective and safe way is important for clinical application. Bioimaging rats are a powerful tool for cell transplantation research because it makes observation of the in vivo kinetics of transplanted cells possible. Cell transplantation research using bioimaging rats contributes greatly to evaluating effective methods of cell therapy. PMID:28174669

  20. Importance Rat Liver Morphology and Vasculature in Surgical Research

    PubMed Central

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

    2016-01-01

    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/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. PMID:27911356

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

    PubMed

    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.

  2. ISOLATION OF RAT LIVER PLASMA MEMBRANES

    PubMed Central

    Touster, Oscar; Aronson, N. N.; Dulaney, John T.; Hendrickson, Herman

    1970-01-01

    Nucleotide pyrophosphatase and phosphodiesterase I of rat liver have been found to be localized primarily in cell particulates highly enriched with respect to the most commonly accepted plasma membrane marker, 5'-nucleotidase, and therefore should themselves be assigned a plasma membrane localization. The observation that plasma membranes sediment in isotonic sucrose with both nuclear and microsomal fractions was exploited to obtain plasma membrane preparations from each fraction. Both preparations are similar in chemical and enzymic composition. Moreover, the preparative method developed in this study appears to give the best combination of yield, purity, and reproducibility available. The question of the possible identity of nucleotide pyrophosphatase and phosphodiesterase I is considered, and evidence is presented suggesting that these activities may be manifestations of the same enzyme. PMID:5497542

  3. Iodothyronine Metabolism in Rat Liver Homogenates

    PubMed Central

    Kaplan, Michael M.; Utiger, Robert D.

    1978-01-01

    To investigate mechanisms of extrathyroidal thyroid hormone metabolism, conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) and degradation of 3,3′,5′-triiodothyronine (rT3) were studied in rat liver homogenates. Both reactions were enzymatic. For conversion of T4 to T3, the Km of T4 was 7.7 μM, and the Vmax was 0.13 pmol T3/min per mg protein. For rT3 degradation, the Km of rT3 was 7.5 nM, and the Vmax was 0.36 pmol rT3/min per mg protein. Production of rT3 or degradation of T4 or T3 was not detected under the conditions employed. rT3 was a potent competitive inhibitor of T4 to T3 conversion with a Ki of 4.5 nM; 3,3′-diiodothyronine was a less potent inhibitor of this reaction. T4 was a competitive inhibitor of rT3 degradation with a Ki of 10.2 μM. Agents which inhibited both reactions included propylthiouracil, which appeared to be an allosteric inhibitor, 2,4-dinitrophenol, and iopanoic acid. Sodium diatrizoate had a weak inhibitory effect. No inhibition was found with α-methylparatyrosine, Fe+2, Fe+3, reduced glutathione, β-hydroxybutyrate, or oleic acid. Fasting resulted in inhibition of T4 to T3 conversion and of rT3 degradation by rat liver homogenates which was reversible after refeeding. Serum T4, T3, and thyrotropin concentrations fell during fasting, with no decrease in serum protein binding as assessed by a T3-charcoal uptake. There was no consistent change in serum rT3 concentrations. Dexamethasone had no effect in vitro. In vivo dexamethasone administration resulted in elevated serum rT3 concentrations after 1 day, and after 5 days, in inhibition of T4 to T3 conversion and rT3 degradation without altering serum T4, T3, or thyrotropin concentrations. Endotoxin treatment had no effect of iodothyronine metabolism in liver homogenates. In kidney homogenates the reaction rates and response to propylthiouracil in vitro were similar to those in liver. No significant T4 to T3 conversion or rT3 production or degradation could be detected

  4. Purification and Properties of a Rat Liver Protein That Specifically Inhibits the Proliferation of Nonmalignant Epithelial Cells from Rat Liver

    NASA Astrophysics Data System (ADS)

    McMahon, James B.; Farrelly, James G.; Iype, P. Thomas

    1982-01-01

    An inhibitor of cell proliferation was purified from rat liver by alcohol precipitation, ultrafiltration, and DEAE-cellulose chromatography. The hepatic proliferation inhibitor was shown to be pure by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, analytical isoelectric focusing, and high-performance liquid chromatography. The hepatic proliferation inhibitor was found to have a molecular weight of 26,000 and an isoelectric point of 4.65. This protein inhibited the proliferation of nonmalignant rat liver cells in culture, and removal of the protein reversed the inhibition produced by low doses. It exerted no effect on the proliferation of malignant rat liver cells.

  5. Nucleoside uptake in rat liver parenchymal cells.

    PubMed Central

    Mercader, J; Gomez-Angelats, M; del Santo, B; Casado, F J; Felipe, A; Pastor-Anglada, M

    1996-01-01

    Rat liver parenchymal cells express Na(+)-dependent and Na(+)- independent nucleoside transport activity. The Na(+)-dependent component shows kinetic properties and substrate specificity similar to those reported for plasma membrane vesicles [Ruiz-Montasell, Casado, Felipe and Pastor-Anglada (1992) J. Membr. Biol. 128, 227-233]. This transport activity shows apparent K(m) values for uridine in the range 8-13 microM and a Vmax of 246 pmol of uridine per 3 min per 10(5) cells. Most nucleosides, including the analogue formycin B, cis-inhibit Na(+)-dependent uridine transport, although thymidine and cytidine are poor inhibitors. Inosine and adenosine inhibit Na(+)-dependent uridine uptake in a dose-dependent manner, reaching total inhibition. Guanosine also inhibits Na(+)-dependent uridine uptake, although there is some residual transport activity (35% of the control values) that is resistant to high concentrations of guanosine but may be inhibited by low concentrations of adenosine. The transport activity that is inhibited by high concentrations of thymidine is similar to the guanosine-resistant fraction. These observations are consistent with the presence of at least two Na(+)-dependent transport systems. Na(+)-dependent uridine uptake is sensitive to N-ethylmaleimide treatment, but Na(+)-independent transport is not. Nitrobenzylthioinosine (NBTI) stimulates Na(+)-dependent uridine uptake. The NBTI effect involves a change in Vmax, it is rapid, dose-dependent, does not need preincubation and can be abolished by depleting the Na+ transmembrane electrochemical gradient. Na(+)-independent uridine transport seems to be insensitive to NBTI. Under the same experimental conditions, NBTI effectively blocks most of the Na(+)-independent uridine uptake in hepatoma cells. Thus the stimulatory effect of NBTI on the concentrative nucleoside transporter of liver parenchymal cells cannot be explained by inhibition of nucleoside efflux. PMID:8760370

  6. Effects of early and late adverse experiences on morphological characteristics of Sprague-Dawley rat liver subjected to stress during adulthood

    PubMed Central

    Vásquez, Bélgica; Sandoval, Cristian; Smith, Ricardo Luiz; del Sol, Mariano

    2014-01-01

    The literature indicates that early rupture of the maternal bond and social isolation are variables involved in social and emotional behaviors and in increase in anxiety, particularly in stressful situations. The liver plays a role in the adaptation to stress, yet the possible morphologic changes that its structure can suffer have been studied very little. Therefore, the aim here was to ascertain, through the model of altering the early mother-infant bond and the late social bond through isolation, the effect on the stereologic characteristics of the liver in adult Sprague-Dawley rats subjected to intermittent chronic stress. Twenty-five newborn female rats were used, distributed into 5 groups, under standardized lactation and feeding conditions. The experimental groups were exposed to early (E1), late (E2), and early-late (E3) adverse experiences and then subjected to intermittent chronic stress in adulthood. The liver of each animal was isolated, and the stereologic characteristics of Nv, Vv, and Sv of the hepatocytes were determined. The results from the experimental groups were significantly higher than those obtained in the control groups. The highest values were found in group E3 (Nv = 4.43 ± 0.89 x 105/mm3, Vv = 68.74 ± 2.01%, Sv = 68.78 ± 3.77 mm2/mm3). Considering these results, the hepatic morphology can be affected by exposure to chronic stress; however, when the individuals have been subjected to previous adverse experiences, the changes are more evident. PMID:25197335

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

    PubMed

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

    2002-01-01

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

  8. Stereology techniques in radiation biology

    NASA Technical Reports Server (NTRS)

    Kubinova, Lucie; Mao, XiaoWen; Janacek, Jiri; Archambeau, John O.; Nelson, G. A. (Principal Investigator)

    2003-01-01

    Clinicians involved in conventional radiation therapy are very concerned about the dose-response relationships of normal tissues. Before proceeding to new clinical protocols, radiation biologists involved with conformal proton therapy believe it is necessary to quantify the dose response and tolerance of the organs and tissues that will be irradiated. An important focus is on the vasculature. This presentation reviews the methodology and format of using confocal microscopy and stereological methods to quantify tissue parameters, cell number, tissue volume and surface area, and vessel length using the microvasculature as a model tissue. Stereological methods and their concepts are illustrated using an ongoing study of the dose response of the microvessels in proton-irradiated hemibrain. Methods for estimating the volume of the brain and the brain cortex, the total number of endothelial cells in cortical microvessels, the length of cortical microvessels, and the total surface area of cortical microvessel walls are presented step by step in a way understandable for readers with little mathematical background. It is shown that stereological techniques, based on a sound theoretical basis, are powerful and reliable and have been used successfully.

  9. [Lipogenesis and gluconeogenesis in the liver of irradiated rats].

    PubMed

    Sedlakova, A; Paulikova, E; Diatelinka, I

    1984-01-01

    The incorporation of 14C from [U-14C] glucose and 3H from 3H2O into the total lipids fatty acids and glycogen of the liver incorporation of 3H from 3H2O into blood glucose was studied in rats totally irradiated in a dose of 14.4 Gy. It is shown that in the liver of irradiated rats glucose is accumulated in considerable amounts as glycogen but it is slightly used as a source of carbon for lipid synthesis. The study of 3H incorporation shows that irradiation stimulates glucogenesis, glyconeogenesis and lipogenesis in the liver.

  10. Supercooling Preservation Of The Rat Liver For Transplantation

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Cimica, Velasco . E-mail: vcimica@aecom.yu.edu; Batusic, Danko; Haralanova-Ilieva, Borislava; Chen, Yonglong; Hollemann, Thomas; Pieler, Tomas; Ramadori, Giuliano

    2007-08-31

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

  12. Inflammatory stress potentiates emodin-induced liver injury in rats

    PubMed Central

    Tu, Can; Gao, Dan; Li, Xiao-Fei; Li, Chun-Yu; Li, Rui-Sheng; Zhao, Yan-Ling; Li, Na; Jia, Ge-Liu-Chang; Pang, Jing-Yao; Cui, He-Rong; Ma, Zhi-Jie; Xiao, Xiao-He; Wang, Jia-Bo

    2015-01-01

    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. PMID:26557087

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

    SciTech Connect

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

    1985-03-01

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

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

    PubMed

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

    2016-02-01

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

  15. Stereological study of the capillaries in the thyroid gland after IR laser radiation

    NASA Astrophysics Data System (ADS)

    Perez de Vargas, I.; Vidal, Lourdes; Parrado, C.; Carrillo, F.; Pelaez, A.; Rius, F.

    1994-02-01

    We have planned a stereological ultrastructural study of capillaries in the thyroid gland treated with IR laser radiation and quantified 1 day after the last treatment. Wistar rats, 50 days old, were irradiated with IR laser radiation. The rats were perfused with 2.5 percent glutaraldehyde in 0.1 M phosphate buffer (ph equals 7.4). The pieces obtained after sectioning the thyroid gland were placed immediately into the same fixative. A stereological study of the thyroid capillaries was carried out. This analysis revealed an increase of luminal area in irradiated capillaries.

  16. Impact of Propionic Acid on Liver Damage in Rats

    PubMed Central

    Al- Daihan, Sooad; Shafi Bhat, Ramesa

    2015-01-01

    Propionic acid (PA) is a short chain fatty acid, a common food preservative and metabolic end product of enteric bacteria in the gut. The present study was undertaken to investigate the effect of PA on liver injury in male rats. Male western albino rats were divided into two groups. The first group served as normal control, the second was treated with PA. The activities of serum hepatospecific markers such as aspartate transaminase, alanine transaminase, and alkaline phosphatase were estimated. Antioxidant status in liver tissues was estimated by determining the level of lipid peroxidation and activities of enzymatic and non-enzymatic antioxidants. Sodium and potassium levels were also measured in liver tissue. PA treatment caused significant changes in all hepatospecific markers. Biochemical analysis of liver homogenates from PA-treated rats showed an increase in oxidative stress markers like lipid peroxidation and lactate dehydrogenase, coupled with a decrease in glutathione, vitamin C and glutathione S- transferase. However, PA exposure caused no change in sodium and potassium levels in liver tissue. Our study demonstrated that PA persuade hepatic damage in rats. PMID:26629488

  17. Protective effect of thymoquinone on cholestatic rats with liver injury.

    PubMed

    Kong, L Y; Li, G P; Yang, P; Xi, Z

    2015-10-09

    The aim of this study was to investigate the protective effects of thymoquinone treatment on cholestatic rats with liver injury. Thirty-two Sprague-Dawley rats were divided randomly into four groups: normal control, bile duct ligation model control, low-dose thymoquinone (25 mg/kg), and high-dose thymoquinone (50 mg/kg). Thymoquinone gavage was administered continuously 3 days before bile duct ligation, and saline, at the same volume, was administered to the control group. The rats were sacrificed after 2 weeks of treatment, and the liver tissues were obtained and frozen. The contents of hydroxyproline (HP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the homogenate of the liver tissues were determined to evaluate the changes in hepatic tissue pathology by fibrosis scoring. The HP and MDA levels were significantly lower and the SOD and GPx levels were significantly higher in the thymoquinone-treatment group than the corresponding levels in the model control group, and the differences were statistically significant (P < 0.05) and dose-dependent. The hepatic necrosis areas and hepatic fibrosis scores of the thymoquinone-treatment groups were significantly lower than those of the model group (P < 0.05). Thymoquinone increased the antioxidative capacity of liver and reduced the oxidative stress damage to the liver. Thymoquinone can be used as a liver protectant in patients with cholestasis.

  18. Melatonin protects rat liver against irradiation-induced oxidative injury.

    PubMed

    Koc, Mehmet; Taysi, Seyithan; Buyukokuroglu, Mehmet Emin; Bakan, Nuri

    2003-09-01

    The aim of this study was to investigate the antioxidant roles of different doses of melatonin (5 and 10 mg x kg (-1) ) against gamma-irradiation-caused oxidative damage in liver tissue after total body irradiation (TBI) with a single dose of 6.0 Gy. Fifty adult rats were divided into 5 equal groups, 10 rats each. Groups I and II were injected with 5 and 10 mg x kg (-1) of melatonin, and group III was injected with an isotonic NaCl solution. Group IV was injected with only 5 mg x kg (-1) of melatonin. Group V was reserved as a sham control. Following a 30-min-period, 6.0 Gy TBI was given to groups 1, 2 and 3 in a single fraction. The liver malondialdehyde (MDA) levels, super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured in all groups. TBI resulted in a significant increase in the liver tissue MDA levels and a decrease of SOD and GSH-Px activities. The results demonstrated that the liver tissue MDA levels in irradiated rats that were pretreated with melatonin (5 or 10 mg x kg (-1) ) were significantly decreased, while the SOD and GSH-Px activities were significantly increased. Decreasing the MDA levels by melatonin was dose dependent, but the liver tissue SOD and GSH activities were not. The data obtained in this study suggest that melatonin administration prior to irradiation may prevent liver damage by irradiation.

  19. Cyanide-induced injury to the isolated perfused rat liver.

    PubMed

    Younes, M; Strubelt, O

    1988-11-01

    In order to study the events that follow cyanide-induced inhibition of oxidative metabolism and produce cellular injury, isolated, haemoglobin-free perfused rat livers from fasted rats were exposed to KCN (100 mg/l). KCN reduced the oxygen consumption of the livers by about 80%. Hepatotoxicity was evident by a marked release of enzymes (LDH, SDH) and of glutathione (mainly GSSG) into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. Cyanide-induced hepatotoxicity could be prevented completely by feeding the rats before preparing the liver as well as by addition of fructose to the perfusate of fasted livers. Both treatments resulted in an increased energy supply from anaerobic glycolysis as evidenced by a large release of lactate + pyruvate into the perfusate. The toxic actions of cyanide were markedly attenuated by deferrioxamine as well as by allopurinol. These antitoxic actions occurred without changes in anaerobic glycolysis. Omission of calcium from the perfusate, however, did not influence cyanide toxicity. Thus, energy supply from anaerobic glycolysis seems to be sufficient for the basic functions of the liver to occur, when oxidative metabolism is inhibited by cyanide. The effects of deferrioxamine and allopurinol indicate the involvement of radical intermediates and/or Fe2+ in cyanide-induced cellular toxicity. An influx of calcium from the extracellular to the intracellular space is not involved in cyanide-induced hepatocellular injury.

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

    PubMed

    Gu, Ke; Lai, Song-Tao; Ma, Ning-Yi; Zhao, Jian-Dong; Ren, Zhi-Gang; Wang, Jian; Liu, Jin; Jiang, Guo-Liang

    2011-01-01

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

  1. Supercooling preservation and transplantation of the rat liver.

    PubMed

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

    2015-03-01

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

  2. Effects of hypergravity on rat liver regeneration

    NASA Technical Reports Server (NTRS)

    Feller, D. D.

    1982-01-01

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

  3. Caffeine Induction of Sulfotransferases in Rat Liver and Intestine

    PubMed Central

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

    2011-01-01

    Sulfotransferases (SULTs) are important phase II drug-metabolizing enzymes. SULTs regulation by hormones and other endogenous molecules is relatively well understood, while xenobiotic induction of SULTs is not well studied. Caffeine is one of the most widely consumed psychoactive substances. However, SULTs regulation by caffeine has not been reported. In this report, male and female rats were treated with different oral doses of caffeine (2, 10, 50 mg/kg/day) for 7 days. Western blot and real-time RT-PCR were used to investigate the changes of SULT protein and mRNA expression following the caffeine treatment. Caffeine induced both rat aryl sulfotransferase (rSULT1A1, AST-IV) and rat hydroxysteroid sulfotransferase (rSULT2A1, STa) in the liver and intestine of female rats in a dose-dependent manner. Caffeine induction of rSULT1A1 and rSULT2A1 in the female rat intestine was much stronger than that in the liver. Although caffeine induced rSULT1A1 significantly in the male rat liver, it did not significantly induce rSULT2A1. In male rat intestine, caffeine significantly induced rSULT2A1. The different SULTs induction patterns in male and female rats suggest that the regulation of rat SULTs by caffeine may be affected by different hormone secretion patterns and levels. Our results suggest that consumption of caffeine can induce drug metabolizing SULTs in drug detoxification tissues. PMID:21721019

  4. Creatine supplementation and oxidative stress in rat liver

    PubMed Central

    2013-01-01

    Background The objective of this study was to determine the effects of creatine supplementation on liver biomarkers of oxidative stress in exercise-trained rats. Methods Forty 90-day-old adult male Wistar rats were assigned to four groups for the eight-week experiment. Control group (C) rats received a balanced control diet; creatine control group (CCr) rats received a balanced diet supplemented with 2% creatine; trained group (T) rats received a balanced diet and intense exercise training equivalent to the maximal lactate steady state phase; and supplemented-trained (TCr) rats were given a balanced diet supplemented with 2% creatine and subjected to intense exercise training equivalent to the maximal lactate steady state phase. At the end of the experimental period, concentrations of creatine, hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS) were measured as well as the enzyme activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-GPx) and catalase (CAT). Liver tissue levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were also determined. Results Hepatic creatine levels were highest in the CCr and TCr groups with increased concentration of H2O2 observed in the T and TCr animal groups. SOD activity was decreased in the TCr group. GSH-GPx activity was increased in the T and TCr groups while CAT was elevated in the CCr and TCr groups. GSH, GGS and the GSH/GSSG ratio did not differ between all animal subsets. Conclusions Our results demonstrate that creatine supplementation acts in an additive manner to physical training to raise antioxidant enzymes in rat liver. However, because markers of liver oxidative stress were unchanged, this finding may also indicate that training-induced oxidative stress cannot be ameliorated by creatine supplementation. PMID:24325803

  5. Antifibrotic effect of heparin on liver fibrosis model in rats

    PubMed Central

    Shah, Binita; Shah, Gaurang

    2012-01-01

    AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl4) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups. CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis. PMID:23494756

  6. Amino acid uptake by liver of genetically obese Zucker rats.

    PubMed Central

    Ruiz, B; Felipe, A; Casado, J; Pastor-Anglada, M

    1991-01-01

    Alanine and glutamine uptake by the liver of 50-52-day-old genetically obese Zucker rats and their lean littermates has been studied. The net uptake in vivo of L-alanine is 2-fold higher in the obese animals. No significant change in L-glutamine net balance was found. We also studied the Na(+)-dependent uptake of L-alanine and L-glutamine into plasma-membrane vesicles isolated from either obese- or lean-rat livers. Vmax. values of both L-alanine and L-glutamine transport were 2-fold higher in those preparations from obese rats. No change in Km was observed. As suggested by inhibition studies, this seemed to be mediated by an enhancement of the activities of systems A, ASC and N. We conclude that the liver of the obese Zucker rat is extremely efficient in taking up neutral amino acids from the afferent blood, which results in an enhanced net uptake of L-alanine in vivo. The changes in transport activities at the plasma-membrane level might contribute to increase amino acid disposal by liver, probably for lipogenic purposes, as recently reported by Terrettaz & Jeanrenaud [Biochem. J. (1990) 270, 803-807]. PMID:1684102

  7. IN VITRO METABOLISM OF PYRETHROIDS IN RAT LIVER MICROSOMES

    EPA Science Inventory


    IN VITRO METABOLISM OF PYRETHROIDS IN RAT LIVER MICROSOMES

    SJ Godin1, RA Harrison2 MF. Hughes 2, MJ DeVito2; 1Curriculum In Toxicology, UNC-CH, Chapel Hill NC, USA; 2ETD, NHEERL, ORD, US EPA, RTP, NC, 27711, USA.

    Pyrethroids are neurotoxic pesticides that bin...

  8. Aluminium toxicity in the rat liver and brain

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Ohashi, H.; Nagai, H.; Kakimi, S.; Ishikawa, A.; Kobayashi, K.; Ogawa, Y.; Ishii, K.

    1993-04-01

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

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

    PubMed Central

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

    2016-01-01

    Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL. PMID:27556445

  10. Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis.

    PubMed

    Demirbilek, Savaş; Tas, Erkan; Gurunluoglu, Kubilay; Akin, Melih; Aksoy, Rauf T; Emre, Memet H; Aydin, Nasuhi E; Ay, Selma; Ozatay, Nilufer

    2007-02-01

    Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n=10) or BDL (n=20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P<0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P<0.001). All of these changes were significantly attenuated (P<0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.

  11. Electrophoretically unique amylases in rat livers: phylogenic and ontogenic study on the mammalian liver.

    PubMed

    Koyama, Iwao; Komine, Shin-Ichi; Hokari, Shigeru; Matsunaga, Toshiyuki; Nakamura, Koh-Ich; Komoda, Tsugikazu

    2002-09-01

    Liver amylase activity in rodents was assayed with Blue Starch as substrate, and found to be higher than in humans or pigs. Based on the result of concanavalin A affinity chromatography, we found that the sugar moieties of amylase molecules increased in parallel with amylase activity in the tested mammals. However, the amounts of amylase proteins determined by Western bloting with anti-human salivary-type antibody as the probe, were similar to the levels in mammalian livers. Moreover, a similar expression of amylase mRNA was also detected in the mammalian livers by a reverse transcriptional-polymerase chain reaction using primers specific for the human salivary and/or pancreatic amylase complementary DNA (cDNA) sequences. The amylase was detected at the catalytic activity, protein molecule and mRNA levels in rat liver at all ages from fetus to adult. Salivary-type liver amylase activity increased up to one week after birth, and was maintained at the adult level thereafter. However, based on the results of the electrophoretic mobility test, livers with accelerated amylase activity, e.g., at 2-4 weeks after birth or during liver regeneration after partial hepatectomy, were also found to express an amylase electrophoretical identical to pancreatic-type amylase in addition to salivary-type activity. These results suggest that the liver may express an etopic amylase in a certain condition.

  12. Desialation of transferrin by rat liver endothelium.

    PubMed Central

    Irie, S; Kishimoto, T; Tavassoli, M

    1988-01-01

    To examine the role of liver endothelium in desialation of transferrin (TF), pulse-chase studies were done by incubation of either 3H (sialic acid labeled)-, or 125I, or 59Fe (protein core labeled)-TF with fractionated liver endothelium. While 125I or 59Fe labels were externalized after initial binding and internalization, a large proportion of 3H label was internalized and remained within the cell. When the supernatant of these experiments was studied by isoelectricfocusing and Ricinus communis agglutinin (RCA120) affinity chromatography, generation of asialotransferrin was noted by both techniques. Incubation of liver endothelium with double-labeled TF (sialic acids with 3H and protein core with 125I or 59Fe) led initially to a concordant uptake of the two labels, which were then dissociated and 3H was retained by the cell. These findings indicate desialation of TF by liver endothelium. The significance of these findings in the pathogenesis of hepatic siderosis is discussed. PMID:3165384

  13. Borax counteracts genotoxicity of aluminum in rat liver.

    PubMed

    Turkez, Hasan; Geyikoğlu, Fatime; Tatar, Abdulgani

    2013-10-01

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

  14. Pyogenic liver abscess: contrast-enhanced MR imaging in rats.

    PubMed

    Weissleder, R; Saini, S; Stark, D D; Elizondo, G; Compton, C; Wittenberg, J; Ferrucci, J T

    1988-01-01

    MR imaging was used to evaluate experimentally induced pyogenic liver abscesses in an animal model. Rats were examined before and after IV administration of either gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), ferrite particles, or both contrast agents together. Pyogenic liver abscesses appeared hypointense on T1-weighted images and hyperintense on T2-weighted images. Bolus administration of Gd-DTPA using a fast spin-echo sequence with repetition time of 250 msec and echo time of 20 msec (SE 250/20) showed transient selective enhancement of normal hepatic tissue and increased lesion conspicuity, quantitatively assessed by the contrast-to-noise ratio, which increased from -35.7 to -59.0. Delayed leakage of Gd-DTPA into the abscess center partially obscured small lesions at 30-60 min. Ferrite particles reduced the signal intensity of normal liver, and the abscess then appeared homogenously hyperintense. Applying the SE 500/32 sequence, the contrast-to-noise ratio increased from -1.2 to +74.0. Coordinated administration of both contrast agents showed a further increase in contrast to +94.0, with a hyperintense abscess rim surrounded by hypointense liver. Gd-DTPA increases abscess-liver contrast by rim enhancement of the abscess wall, and ferrite increases the abscess-liver contrast by selectively decreasing the signal intensity of surrounding normal liver. As a result of increased contrast-to-noise ratio, both contrast agents, alone or in combination, increase the conspicuity of hepatic abscesses.

  15. Mitochondrial development in liver of foetal and newborn rats

    PubMed Central

    Jakovcic, S.; Haddock, J.; Getz, G. S.; Rabinowitz, M.; Swift, H.

    1971-01-01

    The development of the inner mitochondrial membrane in foetal and neonatal rat liver was studied by following three parameters: (1) the activity of several respiratory enzymes in homogenates and purified mitochondria, (2) the spectrophotometric determination of cytochrome content in the mitochondria and (3) the cardiolipin content in both homogenates and purified mitochondria. Respiratory-enzyme activities of homogenates of foetal liver were one-quarter to one-twentieth of those of homogenates of adult liver, and the enzyme specific activities in purified mitochondria from foetal liver were one-half to one-eighth of those in mitochondria from adult liver. The cardiolipin content of liver homogenates increased approximately twofold during the development period, but there was no significant change in the cardiolipin content of purified mitochondria. It is concluded that cell mitochondrial content approximately doubles in the immediate postnatal period. There was no evidence for an increase in the relative amount of cristae protein in mitochondria during this period to account for increases in mitochondrial enzyme specific activity, since cardiolipin and cytochrome concentrations remained unchanged and electron micrographs revealed no differences. The cause of the lower respiratory-enzyme specific activity in foetal liver mitochondria is unclear. Qualitative differences in respiratory units in foetal and mature animals are suggested. ImagesPLATE 1PLATE 2 PMID:4330092

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

    PubMed

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

    2016-01-01

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

  17. Morphological changes in the liver of rats intoxicated with methanol.

    PubMed

    Kasacka, I; Skrzydlewska, E

    1999-01-01

    On the basis of morphological examinations in light and electron microscope, the evaluation of methanol influence on the liver of rats was conducted. The examination was carried out in the group of 36 rats that were given a single dose of methanol (1.5 g/kg b.w.) into the stomach through a gastric tube. The liver was taken from rats under the ether anaesthesia after 6, 12, and 24 hours as well as after 2, 5, and 7 days of methanol administration. Results showed that methanol intoxication caused visible changes in the examined organ. Only 6 h after intoxication, lobular peripheral hepatocytes presented characteristic features of vacuolar degradation persisting up to 48 h. Since the second day of intoxication, many cells with double nuclei were found more frequently than in controls. Single hepatocytes or small hepatocytic clusters with the features of deliquescent necrosis could be seen after 5 and 7 days of examination. All animals intoxicated with methanol showed distinct weakness of glycogen reaction. The loss of glycogen resources was highest at 24 h after methanol administration. The results indicate, that methanol causes morphological changes in the rat liver and that intensification of these changes depends on the time after intoxication.

  18. Uptake of Free Choline by Isolated Perfused Rat Liver

    NASA Astrophysics Data System (ADS)

    Zeisel, Steven H.; Story, David L.; Wurtman, Richard J.; Brunengraber, Henri

    1980-08-01

    The uptake of free choline by isolated perfused rat liver was characterized. A saturable uptake mechanism [Ka=0.17± 0.07 mM (SD); Vmax=0.84± 0.16\\ μ mol/min × g dry weight] and a nonsaturable mechanism (through which uptake is proportional to choline concentration in the perfusate) were identified. Most of the choline transported into hepatocytes was converted to betaine, phosphorylcholine, or lecithin. Free choline also accumulated within the intracellular space, suggesting that choline oxidase activity does not always limit choline's uptake by the liver.

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

    PubMed

    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.

  20. Oxidative metabolism of cinnarizine in rat liver microsomes.

    PubMed

    Kariya, S; Isozaki, S; Narimatsu, S; Suzuki, T

    1992-10-06

    The oxidative metabolism of cinnarizine (CZ) [1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine] to 1-(diphenylmethyl)piperazine (M-1), 1-(diphenylmethyl)-4-[3-(4'-hydroxyphenyl)-2-propenyl]piperazine (M-2), benzophenone (M-3) and 1-[4'-hydroxyphenyl)-phenylmethyl]-4-(3- phenyl-2-propenyl)piperazine (M-4) has been studied in rat liver microsomes. In Wistar rats, kinetic analysis revealed sex differences (male > female) in the Km values for formation of all the metabolites and the Vmax values for the formation of M-1, M-3 and M-4. The reactions required NADPH, and were inhibited by carbon monoxide and SKF 525-A. Only M-2 formation was suppressed by sparteine or metoprolol, and was significantly lower in female Dark Agouti rats than in Wistar rats of both sexes. The results suggest that CZ is oxidized by cytochrome P450, and M-2 formation is related to debrisoquine/sparteine-type polymorphic drug oxidation.

  1. Characterization and subcellular distribution of somatogenic receptor in rat liver

    SciTech Connect

    Husman, B.; Andersson, G.; Norstedt, G.; Gustafsson, J.A.

    1985-06-01

    Binding of (/sup 125/I)iodobovine GH ((/sup 125/I)iodo-bGH) to rat liver microsomes and Golgi/endosomal fractions isolated from male and female rats has been characterized. Binding of bGH to a pure somatogenic site was suggested by the finding that 50% inhibition of (/sup 125/I)iodo-bGH binding required 5-130 ng bGH, rGH, or hGH/incubation, while around 500 ng rat PRL/incubation were needed to obtain the same effect. Binding of (/sup 125/I)iodo-bGH to microsomes and Golgi/endosomes was time, temperature, and protein dependent. Maximal specific binding occurred at 15-16 and 15-20 h at 22 C in Golgi and microsomal membranes, respectively. Subcellular distribution studies demonstrated in the Golgi/endosomal fractions compared to the total particulate fraction, while residual microsomes devoid of Golgi/endosomal-derived components were approximately 2-fold enriched. Low levels of somatogenic receptors were detected in lysosome-enriched fractions. Removal of endogenous ligand by treating Golgi/endosomal membranes with 3M MgCl/sub 2/ increased specific binding of bGH about 2- to 3-fold. These results indicate that approximately 50% of specific somatogenic binding sites in the low density fractions represent internalized ligand-receptor complexes. The level of rat liver somatogenic receptors did not show a pronounced sex differentiation; however, an endocrine dependence of somatogenic receptor levels is suggested by the finding that livers from rats in the late stages of pregnancy had a level of somatogenic receptors exceeding that of nonpregnant rats.

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

    PubMed

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

    1979-01-01

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

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

    PubMed

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

    1992-05-01

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

  4. Citrate synthesis in intact rat-liver mitochondria is irreversible.

    PubMed

    Greksák, M; Lopes-Cardozo, M; van den Bergh, S G

    1982-02-01

    Rat-liver mitochondria were incubated with [1,5-14C]citrate in the presence of fluorocitrate to block its oxidation in the Krebs cycle. The reaction products were analysed enzymatically and by anion-exchange chromatography. Incorporation of 14C into acetyl-L-carnitine or ketone bodies via a backward action of citrate synthase was not observed. The optimal rate of citrate synthesis from pyruvate and malate in the presence of fluorocitrate was 15 nmol . mg-1 min-1. In the absence of fluorocitrate, but in the presence of malonate, citrate was oxidized to succinate at a rate of 4 nmol . mg-1 . min-1. We conclude that the synthesis of citrate by intact rat liver mitochondria is an irreversible process. The possible mechanism underlying this phenomenon and the consequence for metabolic regulation are discussed.

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

    PubMed

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

    2011-05-01

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

  6. Determination of boron distribution in rat's brain, kidney and liver.

    PubMed

    Pazirandeh, Ali; Jameie, Behnam; Zargar, Maysam

    2009-07-01

    To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney.

  7. Isolation and characterization of endosomes from rat liver

    SciTech Connect

    Kennedy, G.C.

    1987-01-01

    Three fractions of rat liver endosomes, called 50 Kg Light, 50 Kg Heavy, and 150 Kg have been isolated on 16% Percoll gradients. The 50 Kg Heavy fraction accumulates ligand as a function of time after injection, using either /sup 125/I-asialoorosomucoid (/sup 125/I-ASOR) or /sup 125/I-immunoglobulin A (/sup 125/I-IgA) as ligands. A pulse-chase protocol was also used to study the kinetics of ligand entry into the endosomal compartments. A double-label, 3,3'-diaminobenzidine (DAB)-induced density shift protocol was used to study the internalization of two ligands with different destinations in the hepatocyte. Rats were injected intraportally with /sup 125/I-ASOR-HRP and /sup 131/I-IgA and the liver was fractionated at various times post-injection. The three ligand-containing endosomal fractions were isolated and each subjected to the DAB shift procedure. This treatment causes organelles containing /sup 125/I-ASOR-HRP and another ligand occupying the same compartment to shift to a higher density. Thus, information on whether the /sup 131/I-IgA is colocalized or segregated from the /sup 125/I-ASOR-HRP can be obtained. The authors have used an instantaneous pulse, temperature shift protocol to study the heterogeneity of these three endosomal fractions isolated from rat liver.

  8. Metabolism of circulating renin by liver and kidney of rats

    SciTech Connect

    Kim, S.; Iwao, H.; Nakamura, N.; Ikemoto, F.; Yamamoto, K.; Mizuhira, V.; Yokofujita, J.

    1987-01-01

    Rat renal renin, highly purified and labeled with /sup 125/I, was intravenously given to conscious rats, to study the fate of the circulating renin. Rat antirenin antiserum was used to identify the labeled renin. The disappearance of (/sup 125/I)-renin from the plasma showed two exponential components and the metabolic clearance rate was 11.4 +/- 1.0 ml/min/kg. Both 70% hepatectomy and bilateral nephrectomy decreased the clearance rate by about 50%. (/sup 125/I)-renin accumulated mainly in the liver and kidney, and high performance liquid chromatography (HPLC) analysis indicated the degradation of (/sup 125/I)-renin by these organs. Biliary excretion of (/sup 125/I)-renin was negligible and urinary excretion accounted for 2% of the injected dose. Light- and electron-microscopic autoradiography indicated that (/sup 125/I)-renin is taken up mainly by Kupffer cells and proximal convoluted tubular cells in the liver and kidney, respectively, and thereafter distributes to the lysosomes. In conclusion, both the liver and kidney are responsible for the clearance of circulating renin.

  9. Partial purification of benzene hydroxylase activity from rat liver mitoplasts

    SciTech Connect

    Karaszkiewicz, J.W.; Snyder, R.; Kalf, G.F.

    1986-05-01

    Benzene is a hemopoietic toxin and a carcinogen which causes aplastic anemia and leukemia in humans and leukemia and certain solid tumors in rodents. Bioactivation of benzene is required for toxicity and, presumably, carcinogenicity. The authors have demonstrated that rat liver mitochondria, stripped of outer membrane to avoid microsomal contamination (mitoplasts), metabolize benzene in an NADPH-dependent reaction to compounds capable of covalently binding to mitochondrial DNA. They report here on the partial purification of a benzene hydroxylase activity from rat liver mitoplasts which converts benzene to phenol and which appears to be a cytochrome P-450. The activity is solubilized with 0.4% sodium cholate and further purified by a 5-15% polyethylene glycol (PEG) fractionation. The production of (/sup 3/H)phenol from (/sup 3/H)benzene by the 5-15% PEG fraction requires an NADPH-generating system and is completely dependent on the addition of exogenous bovine adrenodoxin. Although benzene hydroxylase activity has been demonstrated in rat liver microsomes, adrenodoxin has no effect on the activity of microsomal cytochromes P-450, providing evidence that our activity is indeed of mitochondrial origin.

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

    SciTech Connect

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

    1986-03-05

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

  11. Metastatic hemangiosarcoma of the liver in a young rat

    PubMed Central

    Tanaka, Makoto; Miyoshi, Seiji; Sawamoto, Osamu

    2016-01-01

    Spontaneous hemangiosarcoma is generally uncommon in rats. Furthermore, there are only a few case reports in young rats. This report describes a spontaneous hemangiosarcoma in a young 7-week-old rat. At necropsy, no remarkable changes were noted in any organs including the liver. Histopathologically, multifocal small tumors were located mainly in the perilobular region of the liver. The tumors comprised polygonal to short spindle-shaped cells that showed cellular atypia and local infiltration. In the foci, there were blood-filled spaces lined by spindle-shaped cells. Reticular fibers, which were loosely connected together and formed an irregular network within the foci, were noticed with Azan and silver stain. Immunohistochemistry revealed that tumor cells expressed vascular endothelial cell markers: von willebrand factor and CD34, respectively. These features indicate that the tumor originated from vascular endothelial cells. Although the primary lesion was uncertain, the foci were all small and multicentrically located mainly in the perilobular region, indicating that the liver lesion likely formed by hematogenic metastasis. Taken together, we diagnosed this case as a metastatic hemangiosarcoma. PMID:28190928

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

    PubMed Central

    Praet, Marleen; De Hemptinne, Bernard

    1999-01-01

    In the rat model of heterotopic auxiliary liver transplantation (HALTx), the opinion varies on whether and how the recipient's native liver should be handicapped. To avoid atrophy of the transplanted organ, in this study, two different handicaps were evaluated and their effects on post-operative animal survival and liver biology are described. With a sole portacaval shunt (group 1) all rats survived longer than 3 months. An additional handicap of the liver with either a 68% partial hepatectomy (68% PH) (group 2), or both a 68% PH and a common bile duct ligation (CBDL) (group 3) led to a 100% mortality within 2 days after surgery. When an auxiliary liver was transplanted to the rats handicapped with a 68% PH (group 4), serum Bilirubin and ALAT values were significantly lower than those handicapped with both a 68% PH and a CBDL (group 5). Autopsy and histology of the long-term survivors revealed the atrophy of the engrafted livers and the regeneration of the native livers in group 4, whereas it showed the opposite in group 5. Thus the various manipulations of the native liver do influence differently the post-transplant animal survival, serum liver biochemistry and the outcome of the engrafted liver in this rat model of HALTx. PMID:10468113

  13. Histopathological effects of anthrax lethal factor on rat liver.

    PubMed

    Altunkaynak, Berrin Zuhal; Ozbek, Elvan

    2015-01-01

    Bacillus anthracis, the causative agent of anthrax, has become an increasingly important scientific topic due to its potential role in bioterrorism. The lethal toxin (LT) of B. anthracis consists of lethal factor (LF) and a protective antigen (PA). This study investigated whether only lethal factor was efficient as a hepatotoxin in the absence of the PA. To achieve this aim, LF (100 µg/kg body weight, dissolved in sterile distilled water) or distilled water vehicle were intraperitoneally injected once into adult rats. At 24 h post-injection, the hosts were euthanized and their livers removed and tissue samples examined under light and electron microscopes. As a result of LF application, hepatic injury - including cytoplasmic and nuclear damage in hepatocytes, sinusoidal dilatation, and hepatocellular lysis - became apparent. Further, light microscopic analyses of liver sections from the LF-injected rats revealed ballooning degeneration and cytoplasmic loss within hepatocytes, as well as peri-sinusoidal inflammation. Additionally, an increase in the numbers of Kupffer cells was evident. Common vascular injuries were also found in the liver samples; these injuries caused hypoxia and pathological changes. In addition, some cytoplasmic and nuclear changes were detected within the liver ultrastructure. The results of these studies allow one to suggest that LF could be an effective toxicant alone and that PA might act in situ to modify the effect of this agent (or the reverse situation wherein LF modifies effects of PA) such that lethality results.

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

    SciTech Connect

    Kovalenko, V.M.; Bagnyukova, T.V.; Sergienko, O.V.; Bondarenko, L.B.; Shayakhmetova, G.M.; Matvienko, A.V.; Pogribny, I.P.

    2007-12-15

    Drug-induced liver injury, including drug-induced hepatotoxicity during the treatment of tuberculosis infection, is a major health problem with increasingly significant challenges to modern hepatology. Therefore, the assessment and monitoring of the hepatotoxicity of antituberculosis drugs for prevention of liver injury are great concerns during disease treatment. The recently emerged data showing the ability of toxicants, including pharmaceutical agents, to alter cellular epigenetic status, open a unique opportunity for early detection of drug hepatotoxicity. Here we report that treatment of male Wistar rats with antituberculosis drug pyrazinamide at doses of 250, 500 or 1000 mg/kg/day body weight for 45 days leads to an early and sustained decrease in cytosine DNA methylation, progressive hypomethylation of long interspersed nucleotide elements (LINE-1), and aberrant promoter hypermethylation of placental form glutathione-S-transferase (GSTP) and p16{sup INK4A} genes in livers of pyrazinamide-treated rats, while serum levels of bilirubin and activity of aminotransferases changed modestly. The early occurrence of these epigenetic alterations and their association with progression of liver injury specific pathological changes indicate that alterations in DNA methylation may be useful predictive markers for the assessment of drug hepatotoxicity.

  15. CHARACTERIZATION OF RAT LIVER SUBCELLULAR MEMBRANES

    PubMed Central

    DeHeer, David H.; Olson, Merle S.; Pinckard, R. Neal

    1974-01-01

    The induction of acute hepatocellular necrosis in rats resulted in the production of complement fixing, IgM autoantibodies directed toward inner and outer mitochondrial membranes, microsomal membrane, lysosomal membrane, nuclear membrane, cytosol, but not to plasma membrane. Utilizing selective absorption procedures it was demonstrated that each subcellular membrane fraction possessed unique autoantigenic activity with little or no cross-reactivity between the various membrane fractions. It is proposed that the development of membrane-specific autoantibodies may provide an immunological marker useful in the differential characterization of various subcellular membranes. PMID:4813214

  16. Molecular responses of radiation-induced liver damage in rats.

    PubMed

    Cheng, Wei; Xiao, Lei; Ainiwaer, Aimudula; Wang, Yunlian; Wu, Ge; Mao, Rui; Yang, Ying; Bao, Yongxing

    2015-04-01

    The aim of the present study was to investigate the molecular responses involved in radiation‑induced liver damage (RILD). Sprague‑Dawley rats (6‑weeks‑old) were irradiated once at a dose of 20 Gy to the right upper quadrant of the abdomen. The rats were then sacrificed 3 days and 1, 2, 4, 8 and 12 weeks after irradiation and rats, which were not exposed to irradiation were used as controls. Weight measurements and blood was obtained from the rats and liver tissues were collected for histological and apoptotic analysis. Immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis were performed to measure the expression levels of mRNAs and proteins, respectively. The serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were increased significantly in the RILD rats. Histological investigation revealed the proliferation of collagen and the formation of fibrotic tissue 12 weeks after irradiation. Apoptotic cells were observed predominantly 2 and 4 weeks after irradiation. The immunohistochemistry, RT‑qPCR and western blot analysis all revealed the same pattern of changes in the expression levels of the molecules assessed. The expression levels of transforming growth factor‑β1 (TGF‑β1), nuclear factor (NF)‑κB65, mothers against decapentaplegic homolog 3 (Smad3) and Smad7 and connective tissue growth factor were increased during the recovery period following irradiation up to 12 weeks. The expression levels of tumor necrosis factor‑α, Smad7 and Smad4 were only increased during the early phase (first 4 weeks) of recovery following irradiation. In the RILD rat model, the molecular responses indicated that the TGF‑β1/Smads and NF‑κB65 signaling pathways are involved in the mechanism of RILD recovery.

  17. Stereology and morphometry of lung tissue.

    PubMed

    Mühlfeld, Christian; Knudsen, Lars; Ochs, Matthias

    2013-01-01

    This chapter deals with the stereological quantification of structural characteristics of the lung. The aim of design-based stereological methods is the unbiased and efficient estimation of structural features without making any assumptions on the underlying nature of the biological sample. The methods are based on rigorous sampling of location and orientation, the application of appropriate test systems, and the controlling of the precision of the estimates. Here, we describe the workflow from the fixation of the lung over the processing of the tissue samples to gaining estimates on the structural properties of the lung. Specifically, this chapter deals with methods for estimating the reference volume, sampling location, and sampling orientation, estimating volumes and surface areas of alveolar compartments, estimating total alveolar number, performing stereology at light and electron microscopic level, and dealing with technical problems such as tissue shrinkage. The procedures are illustrated using a worked example from the authors' own laboratory.

  18. Therapeutic effect of Zijin capsule in liver fibrosis in rats

    PubMed Central

    Cai, Da-Yong; Zhao, Gang; Chen, Jia-Chun; Ye, Gan-Mei; Bing, Fei-Hong; Fan, Bu-Wu

    1998-01-01

    AIM: To confirm the therapeutic effect of Zijin capsule on liver fibrosis in rat model. METHODS: Model group: Bovine serum albumin (BSA) Freund’s incomplete adjuvant 0.5 mL was injected subdermally at d1 d15 d22 d29 and d36 for primary sensitization. Seven days after the fifth injection, BSA antibody in the serum was detected by double agar diffusion method. Normal saline of 0.4 mL was injected through cauda vein to BSA antibody-positive rat twice a week for fifteen times. Traditional Chinese medicine (TCM) decoction group and Zijin capsule group: In the attack injection period, Chinese medicinal decoction or Zijin capsule was given ig, the others were the same as in the model group. NS was used in the control group. The collagen content of rat liver was determined by Bergman’s method and expressed as x- ± s. The liver pathological changes were divided into four grades and expressed as the avarage of the total rank sum. RESULTS: The collagen content (mg/g) of the liver in the control group (7.2 ± 1.9) was significantly lower than that in the other groups; it was higher in the model group (31.7 ± 16.6) than that in the two therapeutic groups; and lower in Zijin capsule group (9.7 ± 2.8) than that in the TCM decoction group (11.5 ± 5.3). The pathological changes were more aggravated in the model group (37.4) than those in the two therapeutic groups; and more severe in the TCM decoction group (30.2) than in the Zijin capsule group (22.9). CONCLUSION: The therapeutic effect of Zijin capsule on the model was confirmed. PMID:11819291

  19. Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats

    PubMed Central

    Cupertino, Marli C; Costa, Kyvia L C; Santos, Daiane C M; Novaes, Rômulo D; Condessa, Suellen S; Neves, Ana C; Oliveira, Juraci A; Matta, Sérgio L P

    2013-01-01

    Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis. PMID:24020407

  20. Influx of Thyroid Hormones into Rat Liver In Vivo

    PubMed Central

    Pardridge, William M.; Mietus, Lawrence J.

    1980-01-01

    The transport of [125I]thyroxine (T4) and [125I]triiodothyronine (T3) into liver was investigated with a tissue sampling-portal vein injection technique in the anesthetized rat. The method allows the investigation of the effects of plasma proteins in human serum on the unidirectional influx of T4 or T3 into liver cells. The percent extraction of unidirectional clearance of T3 and T4 was 77±2% and 43±2%, respectively, after portal injection of a bolus of Ringer's solution. Cell membrane transport of T4 or T3 was nonsaturable because 50-μM concentrations of unlabeled hormone had no effect on transport. The addition of bovine albumin in concentrations of 1, 5, or 10 g/100 ml bound >98% of T4 or T3 in vitro, but had no significant effect on T3 or T4 transport in vivo. Conversely, 10% rabbit antisera specific for T3 or T4, completely abolished the intracellular distribution of thyroid hormone into liver. In the presence of rat serum, which contains albumin and thyroid hormone binding pre-albumin (TBPA), 18 and 81% of total plasma T4 and T3, respectively, were available for transport in vivo. The fraction of hormone available for transport in the presence of normal human serum, which contains albumin, TBPA, and thyroid hormone binding globulin (TBG) was 11% for T4 and 72% for T3. The fraction of hormone transported into liver after injection of serum obtained from pregnant or birth control pilltreated volunteers was 4% for T4 (but this was not significantly different from zero) and 54% for T3. These data suggest: (a) The mechanism by which T4 and T3 traverse the liver cell membrane is probably free diffusion. (b) Albumin-bound T4 or T3 is freely cleared by liver, ∼50% of TBG-bound T3 is transported, but little, if any, of TBPA-bound T4 or TBG-bound T4 is cleared by liver cells. (c) Although the albumin-bound fraction of T4 greatly exceeds the free (dialyzable) moiety, the two fractions are both inversely related to the existing TBA or TBG level; therefore, in vitro

  1. Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats.

    PubMed

    Casey, Carol A; McVicker, Benita L; Donohue, Terrence M; McFarland, Melinda A; Wiegert, Robert L; Nanji, Amin A

    2004-01-01

    It has been demonstrated that the oral administration of ethanol (Lieber-DeCarli liquid diet) to rats results in a decreased expression and content of the asialoglycoprotein receptor (ASGP-R) in the resultant fatty liver. In the present study, we wanted to determine whether the extent of impaired receptor content was correlated with the severity of liver pathology by using the intragastric feeding model. When ASGP-R protein and mRNA levels were measured in animals infused with ethanol or dextrose in the presence of fish oil (FO) or medium-chain triglyceride as the source of fat, more significant impairments to the ASGP-R were observed in the FO-ethanol group compared with the medium-chain triglyceride-ethanol group. Furthermore, only the FO-ethanol group showed pathological liver changes. These results demonstrate that a correlation exists between the progression of alcohol-associated liver injury, as defined by the severity of liver pathology, and an ethanol-induced decline in ASGP-R content.

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

    PubMed

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

    2001-02-15

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

  3. Proteomic analysis of liver mitochondria from rats with nonalcoholic steatohepatitis

    PubMed Central

    Li, Lin; Lu, De-Zhao; Li, You-Ming; Zhang, Xue-Qun; Zhou, Xin-Xin; Jin, Xi

    2014-01-01

    AIM: To explore mitochondrial dysfunction in nonalcoholic steatohepatitis (NASH) by analyzing the proteome of liver mitochondria from a NASH model. METHODS: The NASH rat model was established by feeding rats a fat-rich diet for 24 wk and was confirmed using hematoxylin and eosin staining of liver tissue and by changes in the levels of serum alanine transaminase, aspartate aminotransferase, triglyceride, total cholesterol and other markers. Liver mitochondria from each group were isolated using differential centrifugation. The mitochondrial samples were lyzed, purified and further analyzed using two-dimensional electrophoresis combined with matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Bioinformatic analyses of assigned gene ontology and biological pathway was used to study functional enrichments in the abundant proteomic data. RESULTS: Eight up-regulated and sixteen down-regulated proteins were identified that showed greater than 1.5-fold differences between the controls and the NASH group. These dysregulated proteins were predicted to be involved in different metabolic processes including fatty acid β-oxidation processes, lipid metabolic processes, cell-cycle arrest, cell polarity maintenance, and adenosine triphosphate/sex hormone metabolic processes. Novel proteins that may be involved in NASH pathogenesis including the trifunctional enzyme Hadha, thyroxine, prohibitin, aldehyde dehydrogenase ALDH1L2, UDP-glucuronosyltransferase 2B31, and carbamoyl-phosphate synthase were identified using bioinformatics tools. The decreased expression of Hadha in NASH liver was verified by Western blotting, which was used as a complementary technique to confirm the proteomic results. CONCLUSION: This novel report on the liver mitochondrial proteome of a NASH model may provide a reservoir of information on the pathogenesis and treatment of NASH. PMID:24782632

  4. Differential Sympathetic Vasomotor Activation Induced by Liver Cirrhosis in Rats

    PubMed Central

    Bergamaschi, Cássia T.; Campos, Ruy R.

    2016-01-01

    We tested the hypothesis that there is a topographical sympathetic activation in rats submitted to experimental cirrhosis. Baseline renal (rSNA) and splanchnic (sSNA) sympathetic nerve activities were evaluated in anesthetized rats. In addition, we evaluated main arterial pressure (MAP), heart rate (HR), and baroreceptor reflex sensitivity (BRS). Cirrhotic Wistar rats were obtained by bile duct ligation (BDL). MAP and HR were measured in conscious rats, and cardiac BRS was assessed by changes in blood pressure induced by increasing doses of phenylephrine or sodium nitroprusside. The BRS and baseline for the control of sSNA and rSNA were also evaluated in urethane-anesthetized rats. Cirrhotic rats had increased baseline sSNA (BDL, 102 vs control, 58 spikes/s; p<0.05), but no baseline changes in the rSNA compared to controls. These data were accompanied by increased splanchnic BRS (p<0.05) and decreased cardiac (p<0.05) and renal BRS (p<0.05). Furthermore, BDL rats had reduced basal MAP (BDL, 93 vs control, 101 mmHg; p<0.05) accompanied by increased HR (BDL, 378 vs control, 356; p<0.05). Our data have shown topographical sympathetic activation in rats submitted to experimental cirrhosis. The BDL group had increased baseline sSNA, independent of dysfunction in the BRS and no changes in baseline rSNA. However, an impairment of rSNA and HR control by arterial baroreceptor was noted. We suggest that arterial baroreceptor impairment of rSNA and HR is an early marker of cardiovascular dysfunction related to liver cirrhosis and probably a major mechanism leading to sympathoexcitation in decompensated phase. PMID:27055088

  5. STEREO: a program on a PC-Windows 95 platform for recording and evaluating quantitative stereologic investigations of multistage hepatocarcinogenesis in rodents.

    PubMed

    Xu, Y H; Dragan, Y P; Campbell, H A; Pitot, H C

    1998-04-01

    The most common organ site of neoplasms induced by carcinogenic chemicals in the rodent bioassay is the liver. The development of cancer in rodent liver is a multistage process involving sequentially the stages of initiation, promotion, and progression. During the stages of promotion and progression, numerous lesions termed altered hepatic foci (AHF) develop. STEREO was developed for the purpose of efficient and accurate quantitation of AHF and related lesions in experimental and test rodents. The system utilized is equipped with a microcomputer (IBM-compatible PC running Windows 95) and a Summagraphics MICROGRID or SummaSketch tablet digitizer. The program records information from digitization of single or serial sections obtained randomly from rat liver tissue. With this information and the methods of quantitative stereology, both the number and volume percentage fraction of AHF in liver are calculated in three dimensions. The recorded data files can be printed graphically or in the format of tabular numerical data. The results of stereologic calculations are stored on floppy disks and can be sorted into different categories and analyzed or displayed with the use of statistics and graphic functions built into the overall program. Results may also be exported into Microsoft Excel for use at a later time. Any IBM-compatible PC capable of utilizing Windows 95 and MS Office can be used with STEREO, which offers inexpensive, easily operated software to obtain three-dimensional information from sections of two dimensions for the identification and relative potency of initiators, promoters, and progressors, and for the establishment of information potentially useful in developing estimations of risk for human cancer.

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

    PubMed

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

    2011-08-01

    Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, p<0.05) and a damage of the respiratory function. In diabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V(3) and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

  7. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats.

    PubMed

    Zhou, Ji Yin; Zhou, Shi Wen; Zhang, Ke Bin; Tang, Jian Lin; Guang, Li Xia; Ying, Yi; Xu, Ying; Zhang, Le; Li, Dan Dan

    2008-06-01

    Berberine is one of the main alkaloids of Rhizoma coptidis which has been used as a folk medicine to treat diabetes mellitus for more than 1400 years in China. To investigate the chronic effect of berberine on diabetic hyperlipidemic rats, fasted rats were intraperitoneally injected 35 mg/kg streptozotocin. Diabetic rats were admitted after 2 weeks and given a high-carbohydrate/high-fat diet to induce hyperlipidemia. The rats were divided into 7 groups at the end of week 16: normal and diabetic rats received no drug, 5 treatment groups were administered with either 75, 150, 300 mg/kg berberine, 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone per day for 16 weeks, respectively. The blood glucose, hemoglobin A1c, lipid metabolic parameters and hepatic glycogen and triglyceride were measured, and histopathology and peroxisome proliferator-activated receptors (PPARs) alpha/delta/gamma expression of liver were determined by hematoxylin eosin and immunohistochemical staining. Berberine reduced diabetic rats' body weight, liver weight and liver to body weight ratio. Berberine restored the increased blood glucose, hemoglobin A1c, total cholesterol, triglyceride, low density lipoprotein-cholesterol, apolipoprotein B and the decreased high density lipoprotein-cholesterol, apolipoprotein AI levels in diabetic rats to near the control ones. Berberine alleviated the pathological progression of liver and reverted the increased hepatic glycogen and triglyceride to near the control levels. Berberine increased PPARalpha/delta expression and reduced PPARgamma expression in liver of diabetic rat to near the control ones. Berberine improved glucolipid metabolism both in blood and liver in diabetic rats possibly through modulating the metabolic related PPARalpha/delta/gamma protein expression in liver.

  8. Effects of IR laser radiation in thyroid follicular cells: fine structural and stereological study

    NASA Astrophysics Data System (ADS)

    Vidal, Lourdes; Perez de Vargas, I.; Ruiz, C.; Parrado, C.; Pelaez, A.

    1993-06-01

    We have examined the results obtained from the stereological ultraestructural study of follicular cells in thyroid glands treated with IR laser (904 nm). We studied 40 wistar rats exposed to radiation with doses of 46,80 J/cm2. They were sacrificed 1 and 180 days after the treatment. A stereological study of the volume and surface density was made in mitochondria, rER. Gogi complex and cytoplasmic granules. In the rats sacrificed 1 day after exposure to laser radiation, the thyrocited showed minimal morphological changes. In the rats sacrificed after a long period (180 days) the thyrocites showed a significant increase of volume and surface densities of rER, that may mean decreased capacity of the cells to synthesize thyroglobulin. Volume and surface densities of the citoplasmic granules experienced a significant increase.

  9. Hepatoprotective Activity of Heptoplus on Isoniazid and Rifampicin Induced Liver Damage in Rats

    PubMed Central

    Sankar, M.; Rajkumar, Johanna; Sridhar, Dorai

    2015-01-01

    The present study is designed to evaluate the efficacy of heptoplus a polyherbal formulation as an oral supplementary agent for isoniazid and rifampicin induced hepatotoxicity in rats. 50 and 100 mg/kg of heptoplus supplement were fed orally to the rats along with isoniazid and rifampicin and compared to rats treated with 100 mg/kg Liv 52 standard drug. Rats treated with isoniazid and rifampicin suffered from severe oxidative stress by the virtue of free radicals induced lipid per oxidation. As a result abnormal index of serum biochemical markers for liver function and increased liver lysosomal enzymes activity was observed. However rats nourished with 100 mg/kg of heptoplus and Liv 52 protected the liver from oxidative damage by maintaining normal antioxidant profile status and restored normal serum liver biochemical markers. Increased liver lysosomal enzymes activity is prevented in the rats supplemented with heptoplus and Liv 52. Histopathological analysis also revealed severe vascular changes and lobular necrosis in the treatment of isoniazid and rifampicin. Heptoplus (100 mg/kg) and Liv 52 supplemented rats liver apparently revealed normal architecture of liver. This study confirms that heptoplus has liver protective activity against Isoniazid and Rifampicin induced liver injury in rats, in par with Liv 52. PMID:26798170

  10. Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats.

    PubMed

    Kawai, Hiroshi; Kudo, Naomi; Kawashima, Yoichi; Mitsumoto, Atsushi

    2009-02-01

    Estimation of liver damage is important in the pathophysiological and toxicological study of liver disease. As a novel, non-invasive marker of liver damage, we studied the efficacy of urine bile acids (UBA) in a rat model of liver disease. Thioacetamide (TAA)-treated rats were used in this study. Single intraperitoneal administration of high-dose TAA induces severe damage to the liver, and thus is used as a model of acute hepatitis. Continuous administration of low-dose TAA yields mild damage to the liver, and induces cirrhosis and hepatic tumors. In this study, it was found that both acute and chronic administration of TAA was associated with a dose-dependent elevation of UBA. The elevation of UBA content correlated with the alteration of blood biochemical indicators, and UBA screening showed a remarkable ability to distinguish liver-damaged rats from healthy rats. In particular, UBA analysis was found to have high sensitivity, specificity, and positive predictive value for the screening of rats with abnormal serum alkaline phosphatase (ALP) activity due to chronic liver damage, which was confirmed to include cholestasis and subsequent cirrhosis by liver histological analysis. In conclusion, we demonstrated that measurement of UBA is a simple, non-invasive and effective method for the screening of cholestasis in TAA-treated rats. We suggest that UBA analysis may have potent applicability for monitoring the progress of liver damage in animal models of chronic liver disease, such as cirrhosis and hepatic encephalopathy.

  11. Deiodination of thyroid hormones by the perfused rat liver

    PubMed Central

    Hillier, A. P.

    1972-01-01

    1. An investigation has been made into the deiodination of thyroid hormones by the perfused rat liver. The hormones were labelled with 125I in the phenolic ring and the rate of deiodination was estimated by measuring the release of radio-iodide into the perfusate. 2. At tracer concentrations, 0·98% of the liver thyroxine is deiodinated/5 min. The deiodination of tri-iodothyronine is considerably faster, 3·3%/5 min. 3. Deiodination is very sensitive to changes in temperature. 4. The reaction shows saturation kinetics typical of many enzymes, the reciprocal of the rate of deiodination being proportional to the reciprocal of the hormone concentration in the tissue. The maximum rate of deiodination of each hormone is about 1·5 μg/min for a whole liver preparation weighing 16 g. 5. Tri-iodothyronine inhibits thyroxine deiodination and vice versa, suggesting that a single enzyme is responsible for both reactions. 6. Propyl thiouracil (PTU) at high concentrations inhibits the deiodination of both hormones. 7. An abnormally high rate of deiodination is associated with the actual injection of hormone into the preparation. This suggests that only the free (unbound) hormone in the tissue is directly available to the deiodinating enzyme. 8. About half of the whole body deiodination of thyroxine is relatively insensitive to PTU. It is suggested that most of this type of deiodination is performed in the liver and that the process is one of inactivation. PMID:5033472

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

    PubMed

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

    1997-10-01

    We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased

  13. The Metabolism and Toxicity of Menthofuran in Rat Liver Slices and in Rats

    PubMed Central

    Khojasteh, S. Cyrus; Oishi, Shimako; Nelson, Sidney D.

    2010-01-01

    Menthofuran is a monoterpene present in mint plants that is oxidized by mammalian cytochrome P450 (CYP)1 to hepatotoxic metabolites. Evidence has been presented that p-cresol and other unusual oxidative products are metabolites of menthofuran in rats, and that p-cresol may be responsible in part for the hepatotoxicity caused by menthofuran (Madyastha and Raj, Drug Metabolism and Disposition 20, 295–301, 1992). In the present study, several oxidative metabolites of menthofuran were characterized in rat and human liver microsomes, and in rat liver slices exposed to cytotoxic concentrations of menthofuran. Metabolites that were identified were monohydroxylation products of the furanyl and cyclohexyl groups, mintlactones and hydroxymintlactones, a reactive γ-ketoenal, and a glutathione conjugate. A similar spectrum of metabolites was found in urine 24 hr after the administration of hepatotoxic doses of menthofuran to rats. In no case was p-cresol (or any of the other reported unusual oxidative metabolites of menthofuran) detected above background concentrations that were well below concentrations of p-cresol that cause cytotoxicity in rat liver slices. Thus, the major metabolites responsible for the hepatotoxic effects of menthofuran appear to be a γ-ketoenal and/or epoxides formed by oxidation of the furan ring. PMID:20945912

  14. Partial purification and properties of rat liver glutaminase.

    PubMed Central

    Patel, M; McGivan, J D

    1984-01-01

    The mitochondrial enzyme phosphate-dependent glutaminase was partially purified from rat liver. The enzyme had Mr 290 000 as judged by chromatography on Sephacryl S-300. After sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the preparation, glutaminase was tentatively identified with a peptide of Mr 73 500. The concentration-dependence on glutamine was highly sigmoidal, with half-maximum velocity at 22 mM-glutamine. Half-maximum activity was obtained with 5 mM-phosphate. The enzyme required ammonia as an obligatory activator, in agreement with previous reports on intact and sonicated mitochondria. These findings further differentiate liver glutaminase from the phosphate-dependent glutaminase present in kidney and several other tissues. Images Fig. 2. PMID:6743288

  15. Glycerophosphate-dependent hydrogen peroxide production by rat liver mitochondria.

    PubMed

    Jesina, P; Kholová, D; Bolehovská, R; Cervinková, Z; Drahota, Z; Houstek, J

    2004-01-01

    We studied the extent to which hormonally-induced mitochondrial glycerophosphate dehydrogenase (mGPDH) activity contributes to the supply of reducing equivalents to the mitochondrial respiratory chain in the rat liver. The activity of glycerophosphate oxidase was compared with those of NADH oxidase and/or succinate oxidase. It was found that triiodothyronine-activated mGPDH represents almost the same capacity for the saturation of the respiratory chain as Complex II. Furthermore, the increase of mGPDH activity induced by triiodothyronine correlated with an increase of capacity for glycerophosphate-dependent hydrogen peroxide production. As a result of hormonal treatment, a 3-fold increase in glycerophosphate-dependent hydrogen peroxide production by liver mitochondria was detected by polarographic and luminometric measurements.

  16. Lactoferrin Enhanced Apoptosis and Protected Against Thioacetamide-Induced Liver Fibrosis in Rats

    PubMed Central

    Hessin, Alyaa; Hegazy, Rehab; Hassan, Azza; Yassin, Nemat; Kenawy, Sanaa

    2015-01-01

    BACKGROUND: Liver fibrosis is the common pathologic consequence of all chronic liver diseases. AIM: Lactoferrin (Lf) was investigated for its possible hepatoprotective effect against thioacetamide (TAA)-induced liver fibrosis rat model. MATERIAL AND METHODS: Rats received TAA (200 mg/kg/biweekly, ip) for four successive weeks. Lf (200 mg/kg/day, p.o.) or vehicle (VHC) was administered for one month before and another month during TAA injection. Body weight and mortality rate were assessed during the month of TAA-intoxication. Thereafter, serum and liver tissues were analyzed for liver function, oxidative, fibrotic and apoptotic markers. RESULTS: Lf conserved rats against TAA-induced body weight-loss and mortality. Preservation of serum albumin, alkaline phosphatase and total bilirubin levels was also observed. Lf also protected rats against TAA-induced decrease in reduced glutathione and increase in malondialdehyde liver contents. Normal liver contents of hydroxyproline, nuclear factor kappa B and alpha fetoprotein; as markers of fibrosis; were increased with TAA and conserved with Lf-TAA. Lf maintained the normal architecture of the liver and immunohistochemical findings revealed increase in apoptotic bodies compared to TAA that favored necrosis. CONCLUSION: In conclusion, Lf improved liver function, reduced oxidative stress and liver fibrosis, and enhanced apoptosis in rats with liver fibrosis, suggesting it to have useful therapeutic potential in patients with liver fibrosis. PMID:27275221

  17. Assay-specific genotoxicity of N-nitrosodibenzylamine to the rat liver in vivo

    SciTech Connect

    Schmezer, P.; Pool, B.L. ); Lefevre, P.A.; Callander, R.D.; Tinwell, H.; Ashby, J. ); Ratpan, F. )

    1990-01-01

    N-Nitrosodibenzylamine (NDBzA) is mutagenic to Salmonella typhimurium and induces DNA strand breaks in isolated rat hepatocytes, yet it is reported to be non-carcinogenic to the rat. Here the authors report that it is inactive in both the rat and mouse bone marrow micronucleus assays and in a rat liver autoradiographic assay for unscheduled DNA synthesis. It is, however, clearly active as a micronucleus-inducing agent and mitogen in the rat liver and is capable of inducing single-strand breaks in the DNA of rat liver. The origin and implications of this curious conflict of in vivo genotoxicity data are discussed. Irrespective of that discussion, it is concluded that NDBzA is genotoxic to the rat liver in vivo.

  18. Integrated stereological and biochemical studies on hepatocytic membranes. I.V. Heterogeneous distribution of marker enzymes on endoplasmic reticulum membranes in fractions

    PubMed Central

    1980-01-01

    The purpose of the study was to consider quantitatively the relationships between the surface area of the endoplasmic reticulum (ER) and constituent marker enzyme activities, as they occur in fractions collected from rat liver homogenates. The ER surface area was estimated in five membrane-containing fractions by use of a combined cytochemical-stereological technique (5), while, at the same time, ER marker enzymes were assayed biochemically. Fraction/homogenate recoveries for the ER enzymes averaged 100%, total membrane surface area 98%, and ER surface area 96%. Relative specific activities, which compare the relative amounts of ER marker enzyme activities to the relative ER surface area in the membrane-containing fractions, indicate variable distributions for glucose-6-phosphatase and NADPH cytochrome c reductase, but not for esterase. PMID:6248565

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

    PubMed Central

    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

  20. Excision of apurinic sites from DNA with enzymes isolated from rat-liver chromatin.

    PubMed

    Goffin, C; Verly, W G

    1982-10-01

    Apurinic sites were excised from phi X174 RF DNA with two enzymes isolated from rat liver chromatin: an apurinic/apyrimidinic endodeoxyribonuclease and a 5'-3'-exonuclease; the resulting gap was filled with DNA polymerase beta also prepared from rat liver chromatin and the repair was fully terminated with T4 ligase.

  1. Protein F-induced immune tolerance in liver transplantation in rats.

    PubMed

    Zhuang, Jianbin; Wang, Yijun; Du, Zhi; Wang, Sumei

    2014-05-01

    Liver-specific protein F is commonly used in liver transplantation studies for its allograft immunogenicity. The objective of this study was to investigate immune tolerance induced by protein F in liver transplantation in rats. Healthy inbred male Wistar and Sprague-Dawley (SD) rats were used in this study. The transplant recipient rats were randomly divided into three groups. The SD rats transplanted with liver tissues from SD rats or Wistar rats were defined as intragraft control group (Group A) or acute reaction group (Group B), respectively. The SD rats that received thymic administration of 4 mg protein F 1 week prior to transplantation with livers from Wistar rats were defined as protein F interference group (Group C). Kamada's two-cuff technique was utilized in the liver transplantation surgeries. The postoperative general condition, transplantation survival time, pathological examination, and serum IFN-γ level (quantified by ELISA) were recorded and compared to evaluate the immune response and outcomes in the recipient rats after liver transplantation. Group A rats exhibited good postoperative condition and prolonged survival (median survival time was 92 days). In contrast, Group B rats lost body weight rapidly after liver transplantation, and died starting at day 12 (median survival time was 15 days). Compared to Group B, Group C rats showed significantly longer survival (medium survival time was 71 days). Our findings indicate that protein F is an important transplantation antigen with allograft immunogenicity, which could successfully induce immune tolerance in liver transplantation.

  2. Abate Cytochrome C induced apoptosome to protect donor liver against ischemia reperfusion injury on rat liver transplantation model

    PubMed Central

    Zhuang, Zhuonan; Lian, Peilong; Wu, Xiaojuan; Shi, Baoxu; Zhuang, Maoyou; Zhou, Ruiling; Zhao, Rui; Zhao, Zhen; Guo, Sen; Ji, Zhipeng; Xu, Kesen

    2016-01-01

    Objective: Aim of this study is to protect donor liver against ischemia-reperfusion injury by abating Cytochrome C induced apoptosome on rat model. Methods: A total of 25 clean SD inbred male rats were used in this research. The rats in ischemia-reperfusion injury group (I/R group, n=5) were under liver transplantation operation; rats in dichloroacetate diisopropylamine group (DADA group, n=5) were treated DADA before liver transplantation; control group (Ctrl group, n=5); other 10 rats were used to offer donor livers. Results: In DADA therapy group, Cytochrome C expression in donor hepatocellular cytoplasm was detected lower than that in I/R group. And the Cytochrome C induced apoptosome was also decreased in according to the lower expressions of Apaf-1 and Caspase3. Low level of cleaved PARP expression revealed less apoptosis in liver tissue. The morphology of donor liver mitochondria in DADA group was observed to be slightly edema but less than I/R group after operation 12 h. The liver function indexes of ALT and AST in serum were tested, and the results in DADA group showed it is significantly lower than I/R group after operation 12 h. The inflammation indexes of IL-6 and TNF-α expressions in DADA group were significantly lower than that in I/R group after operation 24 h. Conclusion: The dichloroacetate diisopropylamine treatment could protect the hepatocellular mitochondria in case of the spillage of Cytochrome C induced apoptosome, and protect the liver against ischemia-reperfusion injury. Thus, it may be a method to promote the recovery of donor liver function after transplantation. PMID:27186297

  3. Evaluation of methylmercury biotransformation using rat liver slices.

    PubMed

    Yasutake, A; Hirayama, K

    2001-09-01

    To examine the demethylation reaction of methylmercury (MeHg) in rat liver, slices prepared from MeHg-treated rats were incubated in L-15 medium under 95% O2/5% CO2 atmosphere. During the incubation, the amount of inorganic Hg in the slices markedly increased in a time-dependent manner, although the concentration of total Hg remained unchanged. Since the C-Hg bond in MeHg was demonstrated to be cleaved by the action of some reactive oxygen species, the effects on MeHg demethylation of several reagents that could modify reactive oxygen production were examined in the present system. Methylviologen was found to be an effective enhancer of the demethylation reaction with only a minor effect on lipid peroxidation. On the other hand, ferrous ion added to the medium showed no effect on demethylation in the presence or absence of methylviologen, although lipid peroxide levels were increased significantly by ferrous ion. Similarly, deferoxamine mesylate, which effectively suppressed the increase in lipid peroxide levels, also had no effect on demethylation. Furthermore, hydroxy radical scavengers, such as mannitol and dimethylsulfoxide, had no effect on inorganic Hg production. Rotenone, an inhibitor of complex I in the mitochondrial electron transport system, increased levels of both inorganic Hg and lipid peroxide. However, other inhibitors, such as antimycin A, myxothiazole and NaCN, significantly suppressed the demethylation reaction. Cell fractionation of the MeHg-treated rat liver revealed that the ratio of inorganic Hg to total Hg was highest in the mitochondrial fraction. Furthermore, superoxide anion could degrade MeHg in an organic solvent but not in water. These results suggested that the demethylation of MeHg by the liver slice would proceed with the aid of superoxide anion produced in the electron transfer system at the hydrophobic mitochondrial inner membrane. Furthermore, the involvement of hydroxy radicals, which have been demonstrated to be effective in

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

    PubMed Central

    Solmaz, Ali; Gülçiçek, Osman Bilgin; Erçetin, Candaş; Yiğitbaş, Hakan; Yavuz, Erkan; Arıcı, Sinan; Erzik, Can; Zengi, Oğuzhan; Demirtürk, Pelin; Çelik, Atilla; Çelebi, Fatih

    2016-01-01

    Obstructive jaundice (OJ) can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8), control (n = 8), and nesfatin (n = 8). After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114). Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032). Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75). DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects. PMID:27524109

  5. [Tissue stereological analysis of myocardial atrophy during hypokinesia].

    PubMed

    Nepomniashchikh, G I; Tumanov, V P; Kolesnikova, L V; Nepomniashchikh, L M

    1984-06-01

    The myocardium of Wistar rats which were in a state of hypokinesia for 5, 15 and 30 days was assayed morphologically. Morphometric and stereological methods were used to measure the diameter of cardiomyocytes, the volume and surface densities of muscle fibers and interstitial connective tissue. Myocardial atrophy (absolute heart weight loss, reduction in the cardiomyocyte diameter) was shown to develop in the course of hypokinesia. Informational analysis revealed the increased enthropy and relative enthropy as well as reduction of excess myocardial tissue. Long-term immobilization also resulted in an increase of the relative volume density of the stroma, collagenization of the interstitial connective tissue, and marked tendency toward diminution of the surface-volume ratio of the capillaries.

  6. Catabolism of amino acids in livers from cafeteria-fed rats.

    PubMed

    de Castro Ghizoni, Cristiane Vizioli; Gasparin, Fabiana Rodrigues Silva; Júnior, Antonio Sueiti Maeda; Carreño, Fernando Olinto; Constantin, Rodrigo Polimeni; Bracht, Adelar; Ishii Iwamoto, Emy Luiza; Constantin, Jorgete

    2013-01-01

    Most studies using a hypercaloric diet to induce obesity have focused on the metabolism of fat and carbohydrates. Less concern has been given to the metabolism of amino acids, despite evidence of modifications in nitrogen metabolism during obesity. The aim of this study was to evaluate amino acid metabolism in livers from cafeteria diet-induced obese rats. Blood parameters were analysed, and histological sections of livers were stained with Sudan III. The enzymatic activities of some enzymes were determined in liver homogenates. Gluconeogenesis, ureagenesis, and oxygen consumption were evaluated in rat livers perfused with glutamine, alanine, or ammonium chloride. Compared to control rats, cafeteria-fed rats demonstrated higher levels of triacylglycerol and glucose in the blood and greater accumulation of fat in livers. Gluconeogenesis and urea production in livers perfused with glutamine and alanine at higher concentrations showed a substantial reduction in cafeteria-fed rats. However, no significant difference was observed among groups perfused with ammonium chloride. The activities of the enzymes alanine aminotransferase, glutaminase, and aspartate aminotransferase in the livers were reduced in cafeteria-fed rats. Taken together, these data are consistent with the hypothesis that livers from cafeteria diet-induced obese rats exhibit a limitation in their maximal capacity to metabolise glutamine and alanine to glucose, ammonia, and urea, not because of an impairment in gluconeogenesis and/or ureagenesis, but rather due to a depression in the activities of enzymes that catalyse the initial steps of amino acid metabolism.

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

    PubMed

    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

  8. Rhinacanthus nasutus Improves the Levels of Liver Carbohydrate, Protein, Glycogen, and Liver Markers in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Visweswara Rao, Pasupuleti; Madhavi, K.; Dhananjaya Naidu, M.; Gan, Siew Hua

    2013-01-01

    The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200 mg/kg/day while glibenclamide was administered at 50 mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state. PMID:24204387

  9. Amelioration of Liver Injury by Continuously Targeted Intervention against TNFRp55 in Rats with Acute-on-Chronic Liver Failure

    PubMed Central

    Bao, Shishan; Tabassam, Fazal; Cai, Wei; Xiang, Xiaogang; Zhao, Gangde; Wu, Haiqing; Gao, Ting; Li, Hai; Xie, Qing

    2013-01-01

    Background Acute-on-chronic liver failure (ACLF) is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor)/TNFR (tumor necrosis factor receptor) 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc]) prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55) pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF. Methodology Chronic liver disease (liver fibrosis/cirrhosis) was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA), and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN)/lipopolysaccharide (LPS) i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations. Principal Findings Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL)-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA). This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats. Conclusions sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value. PMID:23874752

  10. Properties of aldehyde dehydrogenas from chemically-induced rat hepatomas and normal rat liver.

    PubMed

    Lindahl, R

    1980-01-01

    The subcellular distribution and properties of four aldehyde dehydrogenase isozymes (I-IV) identified in 2-acetylaminofluorene-induced rat hepatomas and three aldehyde dehydrogenase (I-III) identified in normal rat liver are compared. In normal liver, mitochondria (50%) and microsomes (27%) possess the majority of the aldehyde dehydrogenase (AlDH), with cytosol possessing little activity. Isozymes I-III can be identified in both fractions and can be differentiated on the basis of substrate and coenzyme specificity, substrate Km, inhibition by disulfiram and anti-hepatoma aldehyde dehydrogenase sera, and/or isoelectric point. Hepatomas possess considerable cytosolic AlDH (20%), in addition to mitochondrial (23%) and microsomal (35%) activity. Although isozymes I-III are present in tumor mitochondria and microsomes, little isozyme I or II is found in cytosol. Hepatoma cytosolic AlDH is composed (50%) of a hepatoma-specific isozyme (IV), differing in several properties from isozymes I-III; the remainder of the tumor cytosolic activity is due to isozyme III (48%). The data indicate that expression of the tumor-specific aldehyde dehydrogenase phenotype requires both qualitative and quantitative changes involving cytosolic and microsomal aldehyde dehydrogenase. The qualitative change requires the derepression of a gene for an aldehyde dehydrogenase expressed in normal liver only following exposure to potentially harmful xenobiotics. The quantitative change involves both an increase in activity and change in subcellular location of a basal, normal liver AlDH isozyme.

  11. A brief update on lung stereology.

    PubMed

    Ochs, Matthias

    2006-06-01

    Lung stereology has a long and successful tradition. From mice to men, the application of new stereological methods at several levels (alveoli, parenchymal cells, organelles, proteins) has led to new insights into normal lung architecture, parenchymal remodelling in emphysema-like pathology, alveolar type II cell hyperplasia and hypertrophy and intracellular surfactant alterations as well as distribution of surfactant proteins. The Euler number of the network of alveolar openings, estimated using physical disectors at the light microscopic level, is an unbiased and direct estimate of alveolar number. Surfactant-producing alveolar type II cells can be counted and sampled for local size estimation with physical disectors at a high magnification light microscopic level. The number of their surfactant storage organelles, lamellar bodies, can be estimated using physical disectors at the EM level. By immunoelectron microscopy, surfactant protein distribution can be analysed with the relative labelling index. Together with the well-established classical stereological methods, these design-based methods now allow for a complete quantitative phenotype analysis in lung development and disease, including the structural characterization of gene-manipulated mice, at the light and electron microscopic level.

  12. Perfluorononanoic acid disturbed the metabolism of lipid in the liver of streptozotocin-induced diabetic rats.

    PubMed

    Fang, Xuemei; Gao, Guizhen; Zhang, Xingtao; Wang, Haichao

    2015-01-01

    Most studies on the liver toxicity of perfluorinated compounds (PFCs) are focused on healthy individuals, whereas the effects of PFCs on individuals with diabetes mellitus have not been fully characterized. This study aimed to investigate the acute exposure of perfluorononanoic acid (PFNA) on the metabolism of lipid in the liver of streptozotocin-induced diabetic rats. Male diabetic rats were orally dosed by gavage for 7 days with 0, 0.2, 1 and 5 mg/kg/day PFNA. The contents of lipid, the activities of enzyme, the expressions of protein in the liver and the serum parameters were detected. The results indicate that dose-dependent accumulation of triglyceride and total cholesterol occurred in the livers of diabetic rats after PFNA treatment. PFNA increased the activities of lipid synthetase, fatty acid synthease, glucose-6-phosphate dehydrogenase and decreased the activity of lipolytic enzyme, hepatic lipase, in the liver of diabetic rats. The changes of the isocitrate dehydrogenase, malicenzyme and lipoprotein lipase were not obvious. The expressions of protein related to lipid homeostasis, liver X receptor α and apolipoprotein E, were decreased after PFNA administration. Exposure to PFNA also increased the activity of serum alanine aminotransferase in diabetic rats. In conclusion, this study discloses that exposure to PFNA impacts on enzymes and proteins related to liver lipid metabolism and lead to obvious accumulation of lipid in the liver of diabetic rats, which may be responsible for hepatotoxicity of this compound in individuals with diabetes mellitus.

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

    PubMed

    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).

  14. Decreased immunoreactivity of visfatin in the pancreas and liver of rats with renovascular hypertension.

    PubMed

    Piotrowska, Ż; Janiuk, I; Lewandowska, A; Kasacka, I

    2016-01-01

    Hypertension is one of the major endocrine and metabolic disorders, in which visfatin plays a significant role. The objective of this study was to evaluate the immunoreactivity of visfatin in pancreas and liver of “two kidney, one clip” (2K1C) renovascular hypertension model in rats. The studies were carried out on the pancreas and liver of rats. After a 6-week period of the renal artery clipping procedure, 2K1C rats developed a stable hypertension. Paraffin sections were stained with hematoxylin and eosin (for general histological examination) and processed for immunolocalization of visfatin. The intensity of immunohistochemical reaction was measured using Nikon NIS-Elements Advanced Research software. The hypertension significantly weakened the immunohistochemical reaction exhibiting visfatin in the pancreas and liver of hypertensive rats, compared to control animals. The changes induced by hypertension in the visfatin-containing cells in the pancreas and liver of the rats are discussed and needs further study.

  15. Effects of dehydroepiandrosterone and carnitine treatment on rat liver.

    PubMed

    Battelli, D; Bellei, M; Kneer, N; Contri, M B; Ronchetti, I P; Bobyleva, V; Lardy, H A

    1994-08-01

    It is well established that DHEA treatment is associated in the rat to an increase in fatty acids metabolism. This condition would require levels of L-carnitine much higher than those physiologically present in the liver. The possibility thus exist that during DHEA treatment the concentration of L-carnitine may become a limiting factor for fatty acids oxidation and therefore responsible of some of the effects observed after administration of the hormone. The present experiments were designed to test this hypothesis. The results show that the increase in the levels of peroxisomal enzymes induced in hepatocytes by DHEA, is greatly reduced by parallel administration of L-carnitine. Furthermore, L-carnitine administration counteracts the effect of DHEA on mitochondrial structure. On the contrary, carnitine has no significant effect on the reduction in weight gain observed upon short- or long-term treatment with DHEA.

  16. Interaction of rat liver glucocorticoid receptor with sodium tungstate.

    PubMed

    Murakami, N; Healy, S P; Moudgil, V K

    1982-06-15

    Effects of sodium tungstate on various properties of rat liver glucocorticoid receptor were examined at pH7 and pH 8. At pH 7, [3H]triamcinolone acetonide binding in rat liver cytosol preparations was completely blocked in the presence of 10--20 mM-sodium tungstate at 4 degrees C, whereas at 37 degrees C a 30 min incubation of cytosol receptor preparation with 1 mM-sodium tungstate reduced the loss of unoccupied receptor by 50%. At pH 8.0, tungstate presence during the 37 degrees C incubation maintained the steroid-binding capacity of unoccupied glucocorticoid receptor at control (4 degrees C) levels. In addition, heat-activation of cytosolic glucocorticoid-receptor complex was blocked by 1 mM- and 10 mM-sodium tungstate at pH 7 and pH 8 respectively. The DNA-cellulose binding by activated receptor was also inhibited completely and irreversibly by 5 mM-tungstate at pH 7, whereas at pH 8 no significant effect was observed with up to 20 mM-tungstate. The entire DNA-cellulose-bound glucocorticoid-receptor complex from control samples could be extracted by incubation with 1 mM- and 20 mM-tungstate at pH 7 and pH 8 respectively, and appeared to sediment as a 4.3--4.6 S molecule, both in 0.01 M- and 0.3 M-KCl-containing sucrose gradients. Tungstate effects are, therefore, pH-dependent and appear to involve an interaction with both the non-activated and the activated forms of the glucocorticoid receptor.

  17. [Effects of manganese, zircon and lithium alone on rat liver lipid peroxidation].

    PubMed

    Li, S; Long, S

    2001-05-01

    Lipid peroxide (LPO) in rat liver was detected by malondiadehyde (MDA) colorimetry. The effect of manganese, zircon and lithium alone on lipid peroxidation in rat liver was also studied. The results showed that manganese and zircon at the doses of (9.862-1.972) x 10(-4) and (0.1972-9.862) x 10(-5) nmol/L respectively decreased LPO in rat liver(P < 0.01). Lithium inhibited lipid peroxidation at the dose of (19.72-1.972) x 10(-4) nmol/L, and induced lipid peroxidation at higher concentration.

  18. Pterostilbene inhibits dimethylnitrosamine-induced liver fibrosis in rats.

    PubMed

    Lee, Ming-Fen; Liu, Min-Lung; Cheng, An-Chin; Tsai, Mei-Ling; Ho, Chi-Tang; Liou, Wen-Shiung; Pan, Min-Hsiung

    2013-06-01

    Pterostilbene, found in grapes and berries, exhibits pleiotropic effects, including anti-inflammatory, antioxidant, and anti-proliferative activities. This study was conducted to investigate the effect of pterostilbene on liver fibrosis and the potential underlying mechanism for such effect. Sprague-Dawley rats were intraperitoneally given dimethyl n-nitrosamine (DMN) (10mg/kg) 3 days per week for 4 weeks. Pterostilbene (10 or 20mg/kg) was administered by oral gavage daily. Liver function, morphology, histochemistry, and fibrotic parameters were examined. Pterostilbene supplementation alleviated the DMN-induced changes in the serum levels of alanine transaminase and aspartate transaminase (p<0.05). Fibrotic status and the activation of hepatic stellate cells were improved upon pterostilbene supplementation as evidenced by histopathological examination as well as the expression of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase 2 (MMP2). These data demonstrated that pterostilbene exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-β1/Smad signaling.

  19. Burn trauma disrupts circadian rhythms in rat liver

    PubMed Central

    Rao, Rohit; Yang, Qian; Orman, Mehmet A; Berthiaume, Francois; Ierapetritou, Marianthi G; Androulakis, Ioannis P

    2016-01-01

    Circadian rhythms play an important role in maintaining homeostasis and solid organ function. The purpose of this study is to assess the implications of burn injury in rats on the underlying circadian patterns of gene expression in liver. Circadian-regulated genes and burn-induced genes were identified by applying consensus clustering methodology to temporally differentially expressed probe sets obtained from burn and sham-burn data sets. Of the liver specific genes which we hypothesize that exhibit circadian rhythmicity, 88% are not differentially expressed following the burn injury. Specifically, the vast majority of the circadian regulated-genes representing central carbon and nitrogen metabolism are “up-regulated” after the burn injury, indicating the onset of hypermetabolism. In addition, cell-cell junction and membrane structure related genes showing rhythmic behavior in the control group were not differentially expressed across time in the burn group, which could be an indication of hepatic damage due to the burn. Finally, the suppression of the immune function related genes is observed in the postburn phase, implying the severe “immunosuppression”. Our results demonstrated that the short term response (24-h post injury) manifests a loss of circadian variability possibly compromising the host in terms of subsequent challenges. PMID:27335693

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

    PubMed

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

    2014-08-01

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

  1. Interaction of human lactoferrin with the rat liver

    SciTech Connect

    Debanne, M.T.; Regoeczi, E.; Sweeney, G.D.; Krestynski, F.

    1985-04-01

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

  2. Glutamine as a major nitrogen carrier to the liver in suckling rat pups.

    PubMed Central

    Casado, J; Felipe, A; Pastor-Anglada, M; Remesar, X

    1988-01-01

    We measured the amino acid concentrations in the afferent and efferent vessels of the liver in anaesthetized fed adult rats and in fed suckling rat pups. A much higher content of glutamine in the portal vein and the aorta than in hepatic veins suggests that this amino acid is actively taken up by the liver of fed suckling rat pups, conversely to what is found in adult rats. In an attempt to characterize further the mechanism(s) contributing to this enhanced glutamine uptake, we monitored the time course of 1 mM-glutamine transport into plasma-membrane vesicles purified from the livers of either adult or suckling rats. The concentrative Na+-dependent uptake of glutamine was lower in those vesicles obtained from pups than in those obtained from adult rats. Glutaminase and glutamine synthetase activities in livers from both experimental groups were also measured. Glutaminase and glutamine synthetase activities in suckling rats were about 3-fold higher and 2-fold lower respectively than those in adult rats. It is concluded that glutamine is a main nitrogen carrier to the liver in fed suckling rats. A high availability of this amino acid and an enzyme imbalance between glutamine-synthesizing and -degrading activities may account for the net uptake found in vivo. PMID:2906242

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

    PubMed

    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.

  4. Selenium regulates gene expression for estrogen sulfotransferase and alpha 2U-globulin in rat liver.

    PubMed

    Yang, Q; Christensen, M J

    1998-03-01

    Dietary intake of the essential trace element selenium (Se) regulates expression of genes for selenoproteins and certain non-Se-containing proteins. However, these proteins do not account for all of Se's biological effects. The objective of this work was to identify additional genes whose expression is regulated by Se. Identification of these genes may reveal new functions for Se or define mechanisms for its biological effects. Weanling male Sprague-Dawley rats were fed a Torula yeast-based Se-deficient basal diet or the same diet supplemented with 0.5 mg Se/kg diet as sodium selenite for 13 weeks. Total RNA was used as template for RNA fingerprinting. Two differentially expressed cDNA fragments were identified and cloned. The first had 99% nucleotide identity with rat liver estrogen sulfotransferase (EST) isoform-6. The second had 99% nucleotide sequence identity with rat liver alpha 2u-globulin. The mRNA levels for both were markedly reduced in Se deficiency. Laser densitometry showed that EST mRNA in Se deficiency was 7.3% of that in Se-adequate rat liver. The level of alpha 2u-globulin mRNA in Se-deficient rat liver was only 12.6% of that in Se-adequate rat liver. These results indicate that dietary Se may play a role in steroid hormone metabolism in rat liver.

  5. Exercise training attenuates anaphylactic venoconstriction in rat perfused liver, but does not affect anaphylactic hypotension in conscious rats.

    PubMed

    Cui, Sen; Shibamoto, Toshishige; Zhang, Wei; Kurata, Yasutaka; Kashimura, Osamu; Miyamae, Shunichi

    2010-09-01

    1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (P(pv)) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (R(pre) and R(post), respectively). In conscious rats, systemic arterial pressure (SAP) and P(pv) were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in R(pre) and R(post), respectively. The anaphylaxis-induced increase in R(pre) was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester (100 micromol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in R(pre). In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in

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

    PubMed

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

    2004-12-01

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

  7. The protective effect of resveratrol on dimethylnitrosamine-induced liver fibrosis in rats.

    PubMed

    Hong, Sang-Won; Jung, Kyung Hee; Zheng, Hong-Mei; Lee, Hee-Seung; Suh, Jun-Kyu; Park, In-Suh; Lee, Don-Haeng; Hong, Soon-Sun

    2010-04-01

    Oxidative stress in liver injury is a major pathogenetic factor in progress of liver fibrosis. Resveratrol, a representative antioxidant derived from grapes, has been reported to show widespread pharmacological properties. In this study, we investigated the protective effects of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were treated with resveratrol daily by oral gavage for seven days after a single intraperitoneal injection of DMN (40 mg/kg). Resveratrol remarkably recovered body and liver weight loss due to DMN-induced liver fibrosis. Liver histology showed that resveratrol alleviated the infiltration of inflammatory cells and fibrosis of liver tissue. Resveratrol decreased the level of malondialdehyde and increased the levels of glutathione peroxidase and superoxide dismutase. Also, resveratrol significantly inhibited the mRNA expression of inflammatory mediators including inducible nitric oxide, tumor necrosis factor-alpha and interleukin-1beta. In addition, resveratrol showed not only reduced mRNA expression of fibrosis-related genes such as transforming growth factor beta 1, collagen type I, and alpha-smooth muscle actin, but also a significant decrease of hydroxyproline in rats with DMN-induced liver fibrosis. Our results suggest that resveratrol could be used to treat liver injury and fibrosis and be useful in preventing the development of liver fibrosis and cirrhosis.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. Increased metallothionein content in rat liver induced by x irradiation and exposure to high oxygen tension

    SciTech Connect

    Shiraishi, N.; Aono, K.; Utsumi, K.

    1983-08-01

    X irradiation and exposure to high oxygen tension are known to induce lipid peroxidation. The effects of these stresses on hepatic content of metallothionein, which may be involved in the regulation of zinc and copper metabolism, have been studied. The amount of metallothionein in rat liver was increased 11-fold by a high dose of X irradiation (1000 R). Increased metallothionein content (about 15 times) was also observed in liver of rats exposed to high oxygen tension for 3 days.

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

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

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

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

    PubMed

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

    1996-01-01

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

  12. Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney.

    PubMed

    Akbari, Mohsen; Goodarzi, Nader; Tavafi, Majid

    2017-03-01

    The functions of the mammalian kidney are closely related to its structure. This suggests that renal function can be completely characterized by accurate knowledge of its quantitative morphological features. The aim of this study was to investigate the histomorphometric features of the kidney using design-based and unbiased stereological methods in the Persian squirrel (Sciurus anomalus), which is the only representative of the Sciuridae family in the Middle East. The left kidneys of five animals were examined. Total volume of the kidney, cortex, and medulla were determined to be 960.75 ± 87.4, 754.31 ± 77.09 and 206.1 ± 16.89 mm(3), respectively. The glomerular number was 32844.03 ± 1069.19, and the total glomerular volume was estimated to be 36.7 ± 1.45 mm(3). The volume and length of the proximal convoluted tubule were estimated at 585.67 ± 60.7 mm(3) and 328.8 ± 14.8 m, respectively, with both values being greater than those reported in the rat kidney. The volume and length of the distal convoluted tubule were calculated at 122.34 ± 7.38 mm(3) and 234.4 ± 17.45 m, respectively, which are also greater than those reported in the rat kidney. Despite the comparable body weight, the total number and mean individual volume of glomeruli in the Persian squirrel kidney were greater than those in the rat kidney. Overall, the stereological variables of the kidneys elucidated in this study are exclusive to the Persian squirrel. Our findings, together with future renal physiological data, will contribute to a better understanding of the renal structure-function relationship in the Persian squirrel.

  13. Estrogen Accelerates Cell Proliferation through Estrogen Receptor α during Rat Liver Regeneration after Partial Hepatectomy

    PubMed Central

    Batmunkh, Baatarsuren; Choijookhuu, Narantsog; Srisowanna, Naparee; Byambatsogt, Uugantsetseg; Synn Oo, Phyu; Noor Ali, Mohmand; Yamaguchi, Yuya; Hishikawa, Yoshitaka

    2017-01-01

    Although estrogen is implicated in the regulation of cell growth and differentiation in many organs, the exact mechanism for liver regeneration is not completely understood. We investigated the effect of estrogen on liver regeneration in male and female Wistar rats after 70% partial hepatectomy (PHx) and performed immunohistochemistry, western blotting and Southwestern histochemistry. 17β-estradiol (E2) and ICI 182,780 were injected into male rats on the day before PHx. The proliferating cell nuclear antigen (PCNA) labeling index reached a maximum at 48 hr after PHx in males, and at 36 hr in females and E2-treated male rats. Estrogen receptor α (ERα) was expressed in zones 1 and 2 in male rats, but was found in all zones in female rats. Interestingly, ERα was not detected at 6–12 hr after PHx but was found at 24–168 hr in male rats. However, ERα expression was found at all sampling time-points in female and E2-treated male rats. The activity of estrogen responsive element binding proteins was detected from 12 hr after PHx in male rats but was found from 6 hr in female and E2-treated male rats. ERα was co-expressed with PCNA during liver regeneration. These results indicate that estrogen may play an important role in liver regeneration through ERα. PMID:28386149

  14. Spontaneous long-term acceptance of RT-1-incompatible liver allografts in inbred rats. Analysis of the immune status.

    PubMed

    Houssin, D; Charpentier, B; Gugenheim, J; Baudot, P; Tamisier, D; Lang, P; Gigou, M; Bismuth, H

    1983-12-01

    In several combinations of inbred rats, liver allografts are spontaneously tolerated, and after a few weeks liver tolerant rats are in a state of donor-specific transplantation tolerance. In vivo and in vitro experiments were conducted to analyze the immunological status of LEW or BN rats with spontaneously tolerated (LEW X BN) F1 liver allografts several months after transplantation. Acute rejection of secondary donor-specific heart allografts retransplanted from liver-tolerant rats to normal syngeneic hosts suggests that the state of tolerance in liver-tolerant rats is related to an active modification of the immune system of the rat and not to a reduced immunogenicity of the graft. No cytotoxic antibodies or cells were found in liver-tolerant rats. Reactivity in mixed lymphocyte culture was normal or slightly reduced. Arguments for the presence of splenic suppressor cells were found in LEW tolerant rats using a local graft-versus-host assay, but these could not be found in BN rats, or when attempting to transfer or to break the tolerance state. A nonspecific humoral blocking factor was found in vitro in liver-tolerant rats but transfer of serum from liver-tolerant rats to normal syngeneic hosts did not permit a significant prolongation of donor-specific heart allografts. These results suggest that more than one mechanism may be involved at the maintenance phase of liver allograft tolerance.

  15. PPAR{alpha} agonists up-regulate organic cation transporters in rat liver cells

    SciTech Connect

    Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus . E-mail: klaus.eder@landw.uni-halle.de

    2006-11-24

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

  16. Ginkgo biloba extract reverses CCl4 –induced liver fibrosis in rats

    PubMed Central

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

    2004-01-01

    AIM: To study the reversing effect of Ginkgo biloba extract (GbE) on established liver fibrosis in rats. METHODS: Following confirmation of CCl4-induced liver fibrosis, GbE or saline was administrated to the rats for 4 weeks. The remaining rats received neither CCl4 nor GbE as normal control. The four groups were compared in terms of serum enzymes, tissue damage, expression of αSMA and tissue inhibitor-1 of metalloproteinase (TIMP-1) and metalloproteinase-1 (MMP-1). RESULTS: Compared with saline-treated group, liver fibrosis rats treated with GbE had decreased serum total bilirubin (P < 0.01) and aminotransferase levels (P < 0.01) and increased levels of serum albumin (P < 0.01). Microscopic studies revealed that the livers of rats receiving GbE showed allieviation in fibrosis (P < 0.05) as well as expression of αSMA (P<0.01). The liver collagen and reticulum contents were lower in rats treated with GbE than saline-treated group (P < 0.01). RT-PCR revealed that the level of TIMP-1 decreased while the level of MMP-1 increased in GbE group. CONCLUSION: Administration of GbE improved CCl4–induced liver fibrosis. It is possibly attributed to its effect of inhibiting the expression of TIMP-1 and promoting the apoptosis of hepatic stellate cells. PMID:15052689

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

    PubMed

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

    2014-07-01

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

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

    SciTech Connect

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

    1988-01-01

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

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

    SciTech Connect

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

    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

  20. Protective Effects of Norursodeoxycholic Acid Versus Ursodeoxycholic Acid on Thioacetamide-induced Rat Liver Fibrosis

    PubMed Central

    Buko, Vyacheslav U.; Lukivskaya, Oxana Y.; Naruta, Elena E.; Belonovskaya, Elena B.; Tauschel, Horst-Dietmar

    2014-01-01

    Background/objectives Effects of norursodeoxycholic acid (norUDCA) and ursodeoxycholic acid (UDCA) on liver fibrosis progression and liver fibrosis reversal in thioacetamide (TAA)-treated rats were studied. Methods Advanced liver fibrosis was induced by TAA treatment (200 mg/kg, i.p.) for 12 weeks. In the second experiment resolution of liver fibrosis was assessed after 8 weeks of TAA withdrawal. During 8 last weeks of each trial, fibrotic rats were daily administered with UDCA (80 mg/kg) and norUDCA (equimolar to 80 mg/kg of UDCA) by oral gavage. Liver fibrosis was assessed by Sirius red staining, liver hydroxyproline and serum fibrosis markers determination. Results The TAA treatment resulted in advanced fibrosis and increase in liver hydroxyproline content and serum fibrosis markers. These signs of fibrosis were less pronounced in rats after TAA withdrawal. Treatment with of norUDCA significantly decreased the total and relative liver hydroxyproline contents in rats with fibrosis reversal, whereas UDCA did not change these parameters. Both compounds decreased serum TGFβ and type IV collagen contents, whereas other serum markers did not differ from the placebo group. In the fibrosis progression model the square of connective tissue was decreased by norUDCA. Serum type IV collagen and procollagen III-NT contents in these experiments were lowered by both UDCA and norUDCA, whereas rest of serum fibrosis markers were diminished only by norUDCA. Conclusions Both norUDCA and UDCA showed therapeutic and prophylactic antifibrotic effect in rats with TAA-induced liver fibrosis. For most of tested parameters norUDCA was more effective than UDCA, especially in the experiment with liver fibrosis regression. PMID:25755576

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

    SciTech Connect

    Lanza-Jacoby, S.; Tabares, A. )

    1990-04-01

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

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

    PubMed

    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.

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

    EPA Science Inventory

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

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

    PubMed

    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.

  5. Regulation of phosphatidylcholine synthesis in rat liver endoplasmic reticulum.

    PubMed Central

    Sribney, M; Knowles, C L; Lyman, E M

    1976-01-01

    The biosynthesis of phosphatidylcholine in rat liver microsomal preparations catalysed by CDP-choline-1,2-diacylglycerol cholinephosphotransferase (EC 2.7.8.2) was inhibited by a combination of ATP and CoA or ATP and pantetheine. ATP alone at high concentrations (20 mM) inhibits phosphatidylcholine formation to the extent of 70%. In the presence of 0.1 mM-CoA, ATP (2 mM) inhibits to the extent of 80% and in the presence of 1 mM-pantetheine to the extent of 90%. ADP and other nucleotide triphosphates in combination with either CoA or pantetheine are only 10-30% as effective in inhibiting phosphatidylcholine synthesis. AMP(CH2)PP [adenosine 5'-(alphabeta-methylene)triphosphate] together with CoA inhibits to the extent of 59% and with pantetheine by 48%. AMP-P(CH2)P [adenosine 5'-(betagamma-methylene)triphosphate] together with either CoA or pantetheine had no significant effect on phosphatidylcholine formation. Other closely related derivatives of pantothenic acid were without effect either alone or in the presence of ATP, as were thiol compounds such as cysteine, homocysteine, cysteamine, dithiothreitol and glutathione. Several mechanisms by which this inhibition might take place were ruled out and it is concluded that ATP together with either CoA or pantetheine interacts reversibly with phosphatidylcholine synthetase to cause temporarily the inhibition of phosphatidylcholine formation. PMID:182154

  6. Molecular cloning and expression of rat liver aminopeptidase B.

    PubMed

    Fukasawa, K M; Fukasawa, K; Kanai, M; Fujii, S; Harada, M

    1996-11-29

    We isolated, by immunological screening of a Uni-ZAP XR cDNA library constructed from rat liver mRNAs, a cDNA clone with 2212 base pairs encoding aminopeptidase B (EC 3.4.11.6). The open reading frame encodes a 649-amino acid protein with a theoretical molecular mass of 72,545 Da and bears the consensus sequence of the zinc metalloexopeptidases, indicating that the enzyme belongs to this family, which includes aminopeptidase A, aminopeptidase N, and leukotriene-A4 hydrolase. Escherichia coli SOLR cells infected with the pBluescript phagemid excised from the Uni-ZAP XR vector containing the aminopeptidase B cDNA had a high L-arginyl-beta-naphthylamidase activity. The recombinant protein was purified to homogeneity from the recombinant E. coli extracts. The enzyme had Cl--dependent aminopeptidase activity specifically restricted to the Arg and Lys derivatives and contained 1 mol of zinc per mol of the enzyme.

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

    PubMed Central

    Burns, S P; 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 from glucose synthesized periportally, was increased in the presence of fructose. During fructose infusion there was a small decrease in cell pH periportally, but acidification of up to 0.5 pH units perivenously. The evidence suggests that in situ the apparent direct conversion of fructose into lactate represents, to a substantial extent, the result of periportal conversion of fructose into glucose and the subsequent uptake and glycolysis to lactate in the perivenous zone of some of that glucose. (31)P NMR spectroscopy showed that the cellular concentration of phosphomonoesters changes very little periportally during fructose infusion, but there was an approximate twofold increase perivenously, presumably due to the accumulation of fructose 1-phosphate. It may be inferred that fructokinase activity is expressed throughout the hepatic lobule. PMID:10880353

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

    PubMed

    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.

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

    PubMed

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

    2016-09-01

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

  10. Ameliorated effects of green tea extract on lead induced liver toxicity in rats.

    PubMed

    Mehana, E E; Meki, Abdel Raheim M A; Fazili, Khalid Majid

    2012-05-01

    In the present study, the effect of green tea extract (GTE) on lead induced toxicity was studied in Sprague-Dawley rats. Four groups of rats were used in the study. Lead and GTE was given orally to the rats with drinking water for 8 weeks. Lead concentration in the digested tissues of liver was detected using atomic absorption spectroscopy. The activities of glutathione-S-transferase (GST) and superoxide dismutase (SOD) were used as markers to evaluate the anti oxidant status of tissues. Lead exposure was found to attenuate the antioxidant potential of liver, which was however augmented when supplemented with green tea extract. Liver enzymes ALT, AST and ALP and serum protein determinations indicated the protective effects of green tea extract. Histopathological studies of liver revealed that supplementation of green tea extract resulted in mild degeneration and congestion of the blood vessels and an enhanced regenerative capacity.

  11. Comparison of cell-surface glycoproteins of rat hepatomas and embryonic rat liver.

    PubMed Central

    van Beek, W. P.; Emmelot, P.; Homburg, C.

    1977-01-01

    Cell-surface glycoprotein of 3 rat hepatoma strains and late-embryonic liver was metabolically labelled in vivo with [3H]- or [14C]-fucose. Trypsinization of the cells and exhaustive pronase digestion of combined hepatoma-liver trypsinates followed by gel filtration over Sephadex-Biogel mixtures, yielded elution profiles that contained more early-eluting (high-mol.-wt.) glycopeptides for hepatomas than for liver. At least 3 factors were identified which acted to augment the fraction of early-eluting tumour glycopeptides: (a) increase of neuraminidase-sensitive sialic acid, (b) increase of neuraminidase-insensitive sialic acid that was sensitive to mild HCl hydrolysis, and (c) presence of sugar sulphate groups contributing to a restricted extent, relative to possible unknown factor(s). Whether (a), (b) or (c) operated depended on the hepatoma strain or its mode of growth. Notwithstanding these differences in the nature of the increase in early-eluting glycopeptides, the increase itself appears not to be due to growth per se, nor to an embryonic expression, but rather may serve as a marker of tumourigenicity. PMID:199223

  12. Comparison of the effects of difenacoum and brodifacoum on the ultrastructure of rat liver cells.

    PubMed

    Gül, Nursel; Yiğit, Nuri; Saygılı, Fulya; Demirel, Ebru; Geniş, Ceren

    2016-09-01

    We used transmission electron microscopy to examine the cytotoxic effects of the second-generation anticoagulant rodenticides difenacoum and brodifacoum on rat liver. A single dose of difenacoum or brodifacoum was administered to rats by gastric gavage and liver samples were taken after 24 h, four days or seven days. In the livers of rats treated with difenacoum for 24 h, hepatocytes typically showed increased numbers of lysosomes, as well as enlargement of both the perinuclear space and the cisternae of the rough endoplasmic reticulum (RER), while sinusoids were irregularly shaped and contained Kupffer cells. Similar irregularities occurred in brodifacoum-treated rats at the same time point, but additionally increased numbers of vacuoles, damaged mitochondrial cristae, and clumping of chromatin were observed in hepatocytes, and hemolysed erythrocytes were noted in the sinusoids. Comparable findings were made in each group of rats after four days. After seven days of difenacoum treatment, hepatocytes suffered loss of cytoplasmic material and mitochondrial shrinkage, while RER cisternae became discontinuous. In contrast, exposure to brodifacoum for seven days caused the formation of numerous vacuoles and lipid droplets, disordered mitochondrial morphology, chromatin clumping and invagination of the nuclear envelope in hepatocytes. Sinusoids in the livers of rodenticide-treated rats contained an accumulation of dense material, lipid droplets, cells with pycnotic nuclei and hemolysed erythrocytes. Overall, our results show that brodifacoum causes more severe effects in liver cells than difenacoum. Thus our microscopic data along with additional biochemical assays point to a severe effect of rodenticide on vertebrates.

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

    PubMed

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

    2016-02-26

    The aim of this study was to explore the therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats. Rats were fed high-fat fodder to establish a rat fatty liver model, and were then fed different concentrations of Pleurotus eryngii cellulose for six weeks. Lipitor was used as a positive control. Measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and total triglyceride (TG); the activity of malondialdehyde (MDA), superoxide dismutase (SOD), hepatic lipase (HL), and lipoprotein lipase; and liver histopathological changes. Successfully established rat fatty liver model after feeding high-fat fodder for one week. A diet of P. eryngii cellulose for six weeks significantly reduced ALT, AST, TC, and TG levels in rat serum (P < 0.01); TC and AST levels in P. eryngii cellulose high-dose group and Lipitor group were not significantly different from those of the control (P > 0.05). SOD activity increased significantly, while MDA and HL activity decreased (P < 0.05); fatty degeneration and fat accumulation both decreased in hepatic tissue. Hepatic protection of P. eryngii cellulose showed dose-related effect. P. eryngii cellulose can affect lipid metabolism, having therapeutic effects on fatty liver in rats.

  14. Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats

    SciTech Connect

    Iwai, M.; Shimazu, T.

    1988-01-01

    The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCL/sub 4/) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine amino-transferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VHM) in CCl/sub 4/-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VHM stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl/sub 4/ injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve, possibly by affecting liver metabolism more than the blood flow change to the liver.

  15. Alleviation of dimethylnitrosamine-induced liver injury and fibrosis by betaine supplementation in rats.

    PubMed

    Kim, Sang K; Seo, Jung M; Chae, Yu R; Jung, Young S; Park, Jae H; Kim, Young C

    2009-02-12

    Previous studies suggested that betaine intake might antagonize the induction of oxidative stress-mediated acute liver injury through regulation of the sulfur-amino acid metabolism. In this study we examined the protective effects of betaine on chronic liver injury and fibrosis induced by dimethylnitrosamine (DMN). Male rats were supplemented with betaine (1%, w/v) in drinking water from 2 weeks prior to the initiation of DMN treatment (10mg/(kg day), i.p., 3 days/week, for 1, 2, or 4 weeks) until sacrifice. Induction of liver injury was determined by quantifying serum alanine aminotransferase, aspartate aminotransferase activities, bilirubin levels, hepatic xenobiotic-metabolizing capacity, histopathological changes and 4-hydroxyproline levels. Development of oxidative injury was estimated by malondialdehyde (MDA) levels and total oxyradical scavenging capacity (TOSC) of liver and serum toward hydroxyl, peroxyl radicals, and peroxynitrite. Progressive changes in the parameters of liver injury and fibrosis were evident in the rats challenged with DMN. Elevation of MDA levels in liver was significant before the onset of a change in any parameters determined in this study. Betaine supplementation markedly attenuated the induction of hepatotoxicity and fibrosis by DMN. Elevation of MDA and the reduction of TOSC were also depressed significantly. Development of liver injury corresponded well with the induction of oxidative stress in rats treated with DMN, both of which are inhibited effectively by betaine supplementation. It is suggested that betaine may protect liver from fibrogenesis by maintaining the cellular antioxidant capacity.

  16. Bacterial translocation aggravates CCl4-induced liver cirrhosis by regulating CD4+ T cells in rats

    PubMed Central

    Shi, Haiyan; Lv, Longxian; Cao, Hongcui; Lu, Haifeng; Zhou, Ning; Yang, Jiezuan; Jiang, Haiyin; Dong, Huihui; Hu, Xinjun; Yu, Wei; Jiang, Xiawei; Zheng, Beiwen; Li, Lanjuan

    2017-01-01

    Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3+CD4+CD25+Foxp3+), Th17 (CD3+CD4+IL-17+), and Th1 (CD3+CD4+IFN-γ+) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl4. We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT. We found that BT may cause increase of Treg cells in the proximal small intestine and decrease of Th17 cells in the whole intestine and blood in cirrhotic rats. It may also aggravate the CCl4-induced decrease in Th1 cells in the whole intestine, liver, caecum, and blood and the CCl4-induced increase in Th17 cells in the liver and Tregs in the distal small intestine, colon, and liver. Our data suggest that BT may aggravate liver injury and decrease liver function via an interaction with CD4+ T Cells. The results of this study may be helpful for the development of new treatments for liver cirrhosis. PMID:28134306

  17. Effects of Fluoride on DNA Damage and Caspase-Mediated Apoptosis in the Liver of Rats.

    PubMed

    Song, Guo Hua; Huang, Fu Bing; Gao, Ji Ping; Liu, Mao Lin; Pang, Wen Biao; Li, Wei bin; Yan, Xiao Yan; Huo, Mei Jun; Yang, Xia

    2015-08-01

    Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver. In this study, we investigated liver histopathology, DNA damage, apoptosis, and the mRNA and protein expressions of caspase-3 and -9 in the rat livers by administering varying concentrations of fluoride (0, 50, 100, 200 mg/L ) for 120 days. The results showed fluoride-induced morphological changes and significantly increased apoptosis and DNA damage in rats exposed to fluoride, especially in response to higher doses. The immunohistochemical and qRT-PCR results indicated that caspase-3, caspase-9 protein positive expression and mRNA relative expression enhanced with increasing NaF concentration. In summary, our findings suggest that chronic exposure to fluoride causes damages to liver histopathology and leads to liver apoptosis through caspase-mediated pathways.

  18. The effects of ultraviolet C radiation on the ultrastructure of the liver cells of mole rats.

    PubMed

    Tekın, Saban; Türker, Hüseyin; Güven, Turan; Yel, Mustafa

    2016-01-01

    The aim of this study was to elucidate the ultrastructural changes in the liver cells of mole rats (Spalax leucodon) exposed to ultraviolet radiation (UVR). Thirteen mole rats used in this study were caught from nature. They were divided into four groups. The first group was separated as a control and was not given any radiation. The rest were exposed to ultraviolet C (UVC) radiation for 7, 14, and 21 days. The electron microscopic examinations revealed that significant ultrastructural changes occurred in the liver tissue. These changes were the reduction in cytoplasmic organelles, dilatation in rough endoplasmic reticulum, impairment of nucleus membrane, and broadened and vacuolated mitochondria in the cytoplasm. Also, UVC radiation caused significant changes in liver enzymes of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gama-glutamiltransferase values. After long-term exposure to radiation, some excessive ultrastructural changes occurred. These results indicated that longer exposure to UVR would cause more ultrastructural effects on the liver cells and liver enzymes.

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

    PubMed

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

    2016-03-01

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

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

    PubMed

    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.

  1. Exposure to industrial wideband noise increases connective tissue in the rat liver.

    PubMed

    Oliveira, Maria João R; Freitas, Diamantino; Carvalho, António P O; Guimarães, Laura; Pinto, Ana; Águas, Artur P

    2012-01-01

    Rats were daily exposed (eight hours/day) for a period of four weeks to the same high-intensity wideband noise that was recorded before in a large textile plant. Histologic observation of liver sections of the rats was used to perform quantitative comparison of hepatic connective tissue (dyed by Masson trichromic staining) between the noise-exposed and control animals. For that, we have photographed at random centrolobular areas of stained rat liver sections. We found that noise exposure resulted in significant enhancement in the area of collagen-rich connective tissue present in the centrolobular domain of the rat liver. Our data strengthen previous evidence showing that fibrotic transformation is a systemic effect of chronic exposure of rodents and humans to industrial wideband noise.

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

    PubMed

    Liu, Weihui; You, Nan; Dou, Kefeng

    2012-01-01

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

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

    PubMed

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

    2011-02-01

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

  4. Matrine protects sinusoidal endothelial cells from cold ischemia and reperfusion injury in rat orthotopic liver transplantation.

    PubMed

    Zhu, Xinhua; Qiu, Yudong; Shi, Mingke; Ding, Yitao

    2003-01-01

    The effect of matrine on cold ischemia and reperfusion injury of sinusoidal endothelial cells (SEC) was investigated in rats using an orthotopic liver transplantation (OLT) model. Syngeneic Sprague-Dawley (SD) rats were randomly assigned to 4 groups of 32 rats: untreated group (controls), low-dose treated group, high-dose treated group, and sham operation group (normals). After 5 hr of preservation in Ringer's solution, orthotopic implantation of the donor liver was performed. At 1, 2, 4, and 24 hr after reperfusion, 6 rats from each group were killed to collect blood and to excise the median hepatic lobe; the other 8 rats were observed to assess the 1-wk survival rate post-transplantation. All transplant recipients in the untreated group (controls) died within 48 hr, mostly between 10 to 20 hr. Matrine treatment increased the 1-wk survival rate to 75% in both treated groups. Plasma levels of hyaluronic acid (HA) at 1, 2, and 4 hr post-implantation were decreased significantly by matrine treatment. The immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in rat liver decreased significantly in both treated groups, and the pathological changes of SEC were ameliorated. Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). Hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were improved by matrine administration. In conclusion, matrine can protect SEC from cold ischemia and reperfusion injury after rat orthotopic liver transplantation.

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

    PubMed Central

    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

  6. Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.

    PubMed

    Mazzucco, María Belén; Fornes, Daiana; Capobianco, Evangelina; Higa, Romina; Jawerbaum, Alicia; White, Verónica

    2016-01-01

    We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

  7. Growth of alveoli during postnatal development in humans based on stereological estimation.

    PubMed

    Herring, Matt J; Putney, Lei F; Wyatt, Gregory; Finkbeiner, Walter E; Hyde, Dallas M

    2014-08-15

    Alveolarization in humans and nonhuman primates begins during prenatal development. Advances in stereological counting techniques allow accurate assessment of alveolar number; however, these techniques have not been applied to the developing human lung. Based on the recent American Thoracic Society guidelines for stereology, lungs from human autopsies, ages 2 mo to 15 yr, were fractionated and isometric uniform randomly sampled to count the number of alveoli. The number of alveoli was compared with age, weight, and height as well as growth between right and left lungs. The number of alveoli in the human lung increased exponentially during the first 2 yr of life but continued to increase albeit at a reduced rate through adolescence. Alveolar numbers also correlated with the indirect radial alveolar count technique. Growth curves for human alveolarization were compared using historical data of nonhuman primates and rats. The alveolar growth rate in nonhuman primates was nearly identical to the human growth curve. Rats were significantly different, showing a more pronounced exponential growth during the first 20 days of life. This evidence indicates that the human lung may be more plastic than originally thought, with alveolarization occurring well into adolescence. The first 20 days of life in rats implies a growth curve that may relate more to prenatal growth in humans. The data suggest that nonhuman primates are a better laboratory model for studies of human postnatal lung growth than rats.

  8. Alkaline ribonuclease and phosphodiesterase activity in rat liver plasma membranes

    PubMed Central

    Prospero, Terence D.; Burge, Malcolm L. E.; Norris, Kenneth A.; Hinton, Richard H.; Reid, Eric

    1973-01-01

    The ribonuclease and phosphodiesterase activities of rat liver plasma membranes, purified from the crude nuclear fraction by centrifugation in an A-XII zonal rotor and flotation, were examined and compared. The plasma membrane is responsible for between 65 and 90% of the phosphodiesterase activity of the cell and between 25 and 30% of the particulate ribonuclease activity measured at pH8.7 in the presence of 7.5mm-MgCl2. Both enzymes were most active between pH8.5 and 8.9. Close to the pH optimum, both enzymes were more active in Tris buffer than in Bicine or glycine buffer. Both plasma-membrane phosphodiesterase and ribonuclease were strongly activated by Mg2+, there being at least a 12-fold difference between the activity in the presence of Mg2+ and of EDTA. There is, however, a difference in the response of the enzymes to Mg2+ and EDTA in that the phosphodiesterase is fully activated by 1.0mm-MgCl2 and fully inhibited by 1.0mm-EDTA, whereas the ribonuclease requires 7.5mm-MgCl2 for full activation and 5mm-EDTA for full inhibition. Density-gradient centrifugation has indicated that on solubilization in Triton X-100 most of the ribonuclease activity is released into a small fragment of the same size as that containing the phosphodiesterase activity. The relationship between the two activities is discussed in view of these results. PMID:4353377

  9. Dietary-regulation of catabolic disposal of 4-hydroxynonenal analogs in rat liver

    PubMed Central

    Li, Qingling; Tomcik, Kristyen; Zhang, Shenghui; Puchowicz, Michelle A; Zhang, Guo-Fang

    2012-01-01

    Our previous work in perfused rat livers has demonstrated that 4-hydroxynonenal (HNE) is catabolized predominantly via beta oxidation. Therefore, we hypothesized that perturbations of beta oxidation, such as diet-altered fatty acid oxidation activity, could lead to changes in HNE levels. To test our hypothesis, we (i) developed a simple and sensitive GC/MS method combined with mass isotopomer analysis to measure HNE and HNE analogs, 4-oxononenal (ONE) and 1,4-dihydroxynonene (DHN), and (ii) investigated the effects of four diets (standard, low fat, ketogenic, and high fat mix diets) on HNE, ONE, and DHN concentrations in rat livers. Our results showed that livers from rats fed ketogenic diet or high fat mix diet had high ω-6 polyunsaturated fatty acid concentrations and markers of oxidative stress. However, high concentrations of HNE (1.6 ± 0.5 nmol/g) and ONE (0.9 ± 0.2 nmol/g) were only found in livers from rats fed the high fat mix diet. Livers from rats fed the ketogenic diet had low HNE (0.8 ± 0.1 nmol/g) and ONE (0.4 ± 0.07 nmol/g), similar to rats fed the standard diet. A possible explanation is that the predominant pathway of HNE catabolism (i.e. beta oxidation) is activated in the liver by the ketogenic diet. This is consistent with a 10 fold decrease in malonyl-CoA in livers from rats fed a ketogenic diet compared to a standard diet. The accelerated catabolism of HNE lowers HNE and HNE analog concentrations in livers from rats fed the ketogenic diet. On the other hand, rats fed the high fat mix diet had high rates of lipid synthesis and low rates of fatty acid oxidation, resulting in the slowing down of the catabolic disposal of HNE and HNE analogs. Thus, decreased HNE catabolism by a high fat mix diet induces high concentrations of HNE and HNE analogs. The results of the present work suggested a potential causal relationship to metabolic syndrome induced by western diets (i.e. high fat mix), as well as the effects of the ketogenic diet on the

  10. Dietary regulation of catabolic disposal of 4-hydroxynonenal analogs in rat liver.

    PubMed

    Li, Qingling; Tomcik, Kristyen; Zhang, Shenghui; Puchowicz, Michelle A; Zhang, Guo-Fang

    2012-03-15

    Our previous work in perfused rat livers has demonstrated that 4-hydroxynonenal (HNE) is catabolized predominantly via β oxidation. Therefore, we hypothesized that perturbations in β oxidation, such as diet-altered fatty acid oxidation activity, could lead to changes in HNE levels. To test our hypothesis, we (i) developed a simple and sensitive GC/MS method combined with mass isotopomer analysis to measure HNE and HNE analogs, 4-oxononenal (ONE) and 1,4-dihydroxynonene (DHN), and (ii) investigated the effects of four diets (standard, low-fat, ketogenic, and high-fat mix) on HNE, ONE, and DHN concentrations in rat livers. Our results showed that livers from rats fed the ketogenic diet or high-fat mix diet had high ω-6 polyunsaturated fatty acid concentrations and markers of oxidative stress. However, high concentrations of HNE (1.6 ± 0.5 nmol/g) and ONE (0.9 ± 0.2 nmol/g) were found only in livers from rats fed the high-fat mix diet. Livers from rats fed the ketogenic diet had low HNE (0.8 ± 0.1 nmol/g) and ONE (0.4 ± 0.07 nmol/g), similar to rats fed the standard diet. A possible explanation is that the predominant pathway of HNE catabolism (i.e., β oxidation) is activated in the liver by the ketogenic diet. This is consistent with a 10-fold decrease in malonyl-CoA in livers from rats fed a ketogenic diet compared to a standard diet. The accelerated catabolism of HNE lowers HNE and HNE analog concentrations in livers from rats fed the ketogenic diet. On the other hand, rats fed the high-fat mix diet had high rates of lipid synthesis and low rates of fatty acid oxidation, resulting in the slowing down of the catabolic disposal of HNE and HNE analogs. Thus, decreased HNE catabolism from a high-fat mix diet induces high concentrations of HNE and HNE analogs. The results of this work suggest a potential causal relationship to metabolic syndrome induced by Western diets (i.e., high-fat mix), as well as the effects of a ketogenic diet on the catabolism of lipid

  11. A review of recent developments and applications of morphometry/stereology in lung research.

    PubMed

    Mühlfeld, Christian; Hegermann, Jan; Wrede, Christoph; Ochs, Matthias

    2015-09-15

    Design-based stereology is the gold standard of morphometry in lung research. Here, we analyze the current use of morphometric and stereological methods in lung research and provide an overview on recent methodological developments and biological observations made by the use of stereology. Based on this analysis we hope to provide useful recommendations for a good stereological practice to further the use of advanced and unbiased stereological methods.

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

    PubMed

    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.

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

    PubMed Central

    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

  14. Protective effect of black tea on integral membrane proteins in rat liver.

    PubMed

    Szachowicz-Petelska, Barbara; Skrzydlewska, Elżbieta; Figaszewski, Zbigniew

    2013-01-01

    Ethanol intoxication is accompanied by oxidative stress formation. Consequently, it leads to disturbances in cellular metabolism that can alter the structure and function of cell membrane components. Black tea displays antioxidant properties, protects membrane phospholipids and may protect integral membrane proteins. In the present study, we examined whether black tea induces changes in the liver integral membrane proteins of 12-months old rats chronically intoxicated with ethanol. To estimate qualitatively and quantitatively the levels of the liver integral membrane proteins, the proteins were selectively hydrolyzed by trypsin, the obtained peptides were resolved by HPLC and the levels of specific amino acids within the individual peptides were determined. All of the obtained peptides contained phenylalanine (Phe), cysteine (Cys) and lysine (Lys). Compared to the control group, rats in the ethanol intoxication group showed decreased liver levels of integral membrane proteins as well as fewer trypsin-hydrolyzed peptides and amino acids in the hydrolyzed peptides. Administration of black tea to ethanol-intoxicated rats partially protected proteins against the structural changes caused by ethanol. Black tea prevented decreases in the levels of cysteine (in about 90% of cases), lysine (in about 60% of cases), phenylalanine (in about 70% of cases) and examined peptides (in about 60% of cases). The liver protein level was higher (by about 18%) in rats who received black tea and ethanol than in those who received ethanol alone. In conclusion, black tea partially protects the composition and level of rat liver cell integral membrane proteins against changes caused by ethanol intoxication.

  15. Chenodeoxycholic Acid Derivative HS-1200 Inhibits Hepatocarcinogenesis and Improves Liver Function in Diethylnitrosamine-Exposed Rats by Downregulating MTH1

    PubMed Central

    Zhao, Qi; Liu, Hui; Qi, Jianni

    2017-01-01

    Aim. To investigate the effects of HS-1200 on liver tumorigenesis and liver function in a diethylnitrosamine- (DEN-) induced hepatocellular carcinoma (HCC) rat model. Methods. Rats were randomly assigned into five groups: control, HS-1200, HCC, HCC + low dose HS-1200, and HCC + high dose HS-1200 groups. Rat HCC model was established by intraperitoneal injection of DEN. And rats were given HS-1200 by daily oral gavage. After 20 weeks, we examined animal body weight, liver weight, liver pathological changes, serum levels of AST, ALT, and AFP, and mutT homologue gene 1 (MTH1) in liver tissue. Results. Oral gavage of HS-1200 significantly increased animal body weight and decreased liver weight as well as liver coefficient in HCC rats (P < 0.05 versus HCC group). Moreover, oral administration of HS-1200 suppressed tumorigenesis, attenuated pathological changes in liver tissues, and decreased serum levels of AST, ALT, and AFP in HCC rats (P < 0.05 versus HCC group). In addition, the mRNA level of MTH1 was upregulated in the liver tissues of HCC rats (P < 0.05 versus control group), which was reversed by HS-1200 treatment in a dose-dependent manner (P < 0.05 versus HCC group). Conclusions. HS-1200 inhibits hepatocarcinogenesis and improves liver function maybe by inducing downregulation of MTH1. PMID:28261604

  16. Expression and localization of rat NBC4c in liver and renal uroepithelium.

    PubMed

    Abuladze, Natalia; Pushkin, Alexander; Tatishchev, Sergei; Newman, Debra; Sassani, Pakan; Kurtz, Ira

    2004-09-01

    Previous studies provided functional evidence for electrogenic Na(+)-HCO(3)(-) cotransport in hepatocytes and in intrahepatic bile duct cholangiocytes. The molecular identity of the transporters mediating electrogenic sodium-bicarbonate cotransport in the liver is currently unknown. Of the known electrogenic Na(+)-HCO(3)(-) cotransporters (NBC1 and NBC4), we previously showed that NBC4 mRNA is highly expressed in the liver. In the present study, we performed RT-PCR, immunoblotting, and immunohistochemistry to characterize the expression pattern of NBC4 in rat liver and kidney. For immunodetection, a polyclonal antibody against rat NBC4 was generated and affinity purified. Of the known human NBC4 variants, only the rat NBC4c ortholog was detected by RT-PCR in rat liver, and the molecular mass of the NBC4c protein was approximately 145 kDa. NBC4c protein was expressed in hepatocytes and in the cholangiocytes lining the intrahepatic bile ducts. In hepatocytes, NBC4c was localized to the basolateral plasma membrane, whereas intrahepatic cholangiocytes stained apically. The NBC1 electrogenic sodium cotransporter variants kNBC1 and pNBC1 were not detected by immunoblotting and immunohistochemistry in rat liver. The pattern of localization of NBC4c in the liver suggests that the cotransporter plays a role in mediating Na(+)-HCO(3)(-) cotransport in hepatocytes and intrahepatic cholangiocytes. Unlike the liver, the rat kidney expressed electrogenic sodium-bicarbonate cotransporter proteins kNBC1 and NBC4c. In kidney, NBC4c also had a molecular mass of approximately 145 kDa and was immunolocalized to uroepithelial cells lining the renal pelvis, where the cotransporter may play an important role in protecting the renal parenchyma from alterations in urine pH.

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

    PubMed

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

    2015-11-01

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

  18. Iron promotes DEN initiated GST-P foci in rat liver.

    PubMed

    Carthew, P; Nolan, B M; Smith, A G; Edwards, R E

    1997-03-01

    Diethylnitrosamine (DEN) was administered to rats as a single dose, which is known not to give rise to liver tumours without subsequent promotion. Iron dextran (Fe/Dex) was then administered parenterally to the animals, to induce iron overload. At 3 and 6 months after the final Fe/Dex treatments, livers were examined quantitatively for the numbers of the placental form of glutathione-S-transferase (GST-P) expressing foci, the area occupied by these foci and their size distribution. The results demonstrate that iron not only increased the number of foci after DEN initiation in the rat liver, but that the area occupied by these lesions increased significantly between 3 and 6 months after initiation. There is no evidence that iron increased the number of GST-P expressing foci present in rats not exposed to DEN. This indicates that iron did not act as an initiator in this rodent model of liver cancer. The increase in the area of the liver occupied by the foci in iron and DEN treated rats was due to an increase in the size of the foci, as well as to an increase in the number of foci. This is the first demonstration that iron can act as a promoter of DEN initiated hepatocytes. It also demonstrates that fibrogenesis is not an absolute requirement for the promotion, by iron, of liver foci in the rat, and that this could also be the case for iron overload in man. Iron may also act as a promoter of already initiated hepatocytes in the development of human liver cancer, as it does in the rat.

  19. Near-Infrared Fluorescence Imaging of Liver Metastases in Rats using Indocyanine Green

    PubMed Central

    van der Vorst, Joost R.; Hutteman, Merlijn; Mieog, Sven D.; de Rooij, Karien E.; Kaijzel, Eric L.; Löwik, Clemens W.G.M.; Putter, Hein; Kuppen, Peter J.K.; Frangioni, John V.; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.

    2011-01-01

    Background Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is a promising technique to obtain real-time assessment of the extent and number of colorectal liver metastases during surgery. The current study aims to optimize dosage and timing of ICG administration. Materials and methods Liver tumors were induced in 18 male WAG/Rij rats by subcapsular inoculation of CC531 rat colorectal cancer cells into three distinct liver lobes. Rats were divided in 2 groups: imaging after 24 and 48 hours or 72 and 96 hours after intravenous ICG administration. In each time group, rats were allocated to three dose groups: 0.04, 0.08, or 0.16 mg ICG. Intraoperative imaging and ex vivo measurements were performed using Mini-FLARE™ and confirmed by fluorescence microscopy. Fluorescence intensity was quantified using the Mini-FLARE software and the difference between tumor signal and liver signal (tumor-to-liver ratio; TLR) was calculated. Results In all 18 rats, all colorectal liver metastases (N = 34), some as small as 1.2 mm, were identified using ICG and the Mini-FLARE™ imaging system. Average tumor-to-liver ratio (TLR) over all groups was 3.0 ± 1.2. TLR was significantly higher in the 72 h time group compared to other time points. ICG dose did not significantly influence TLR, but a trend was found favoring the 0.08 mg dose group. Fluorescence microscopy demonstrated a clear fluorescent rim around the tumor. Conclusions This study demonstrates that colorectal cancer liver metastases can be clearly identified during surgery using ICG and the Mini-FLARE™ imaging system, with optimal timing of 72 h post-injection and an optimal dose of 0.08 mg (0.25 mg/kg) ICG. NIR fluorescence imaging has the potential to improve intraoperative detection of micrometastases and thus the completeness of resection. PMID:21396660

  20. Is hydrogen peroxide involved in the benzyl viologen-mediated in-vivo inactivation of rat liver glutamine synthetase?

    PubMed Central

    Muriana, F. J.; Ruiz-Gutierrez, V.; Relimpio, A. M.

    1993-01-01

    After benzyl viologen administration to rats, a decrease in the rat liver glutamine synthetase activity was observed. An increase in the rat liver catalase activity was found concomitantly. In combination with the catalase inhibitor aminotriazole, benzyl viologen again diminished, but markedly, the rat liver glutamine synthetase activity. Moreover, partially purified glutamine synthetase from rat liver underwent rapid inactivation upon aerobic incubation with NAD(P)H and benzyl viologen. This inactivation was prevented by catalase, which suggests that the NAD(P)H/BV2+/O2-dependent system has a role in H2O2 production. Our results suggest that H2O2 is involved in the benzyl viologen-mediated in-vivo inactivation of the rat liver glutamine synthetase. In contrast, benzyl viologen alone or in combination with aminotriazole produced a significant increase of brain glutamine synthetase. PMID:8098954

  1. The involvement of reactive oxygen species in hypoxic injury to rat liver.

    PubMed

    Younes, M; Strubelt, O

    1988-03-01

    Isolated perfused livers from fasted, but not from fed rats showed hepatotoxic responses when subjected to 30 min of hypoxia followed by 60 min of reoxygenation. Toxicity was evident by a release of glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. This indicates, that the liver is resistant to hypoxic injury as long as glycogen is present to maintain anaerobic ATP-synthesis. This is substantiated by the fact that addition of fructose--but not glucose--to the medium resulted in a protection of the liver against hypoxic injury concomitant with its degradation to lactate + pyruvate. Superoxide dismutase, catalase, desferrioxamine and allopurinol prevented hypoxic liver injury suggesting a substantial role of reactive oxygen species formed via the xanthine oxidase reaction in mediating hypoxic liver injury.

  2. Effect of chronic carbon monoxide exposure on experimental alcoholic liver injury in rats

    SciTech Connect

    Nanji, A.A. ); Jui, L.T.; French, S.W. )

    1989-01-01

    Two groups of experimental animals with pair-fed controls were studied to evaluate the effect of chronic carbon monoxide (CO) exposure on progression of experimental alcoholic liver injury. Eight pairs of male Wistar rats were continuously infused liquid diet and ethanol or isocaloric dextrose for four months. Four pairs were also exposed to CO. Liver damage was followed monthly by serum ALT and morphologic assessment of liver biopsy. Serum levels of ALT were significantly higher in the CO-ethanol group compared to other groups. Electron microscopy revealed a greater degree of cell necrosis in the CO exposed group which explained the significantly higher ALT activity in these animals. Both experimental groups had significantly greater liver damage than controls. Carboxyhemoglobin levels were not different in the ethanol-fed and control group. Our results show that chronic CO exposure enhances liver cell necrosis in ethanol-fed rats thereby lending support to the hypothesis that ethanol and hypoxia enhance cellular disruption in the liver which could be important in the pathogenesis of alcoholic liver disease in rats.

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

    PubMed Central

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

    2016-01-01

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

  4. Methanobactin reverses acute liver failure in a rat model of Wilson disease

    PubMed Central

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K.; Schirmacher, Peter; DiSpirito, Alan A.; Bandow, Nathan; Baral, Bipin S.; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P.; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A.; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H.J.; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz

    2016-01-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration– and European Medicines Agency–approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  5. Thyroid status alters structure of VLDL secreted by perfused rat liver.

    PubMed

    Schroeder, F; Keyes, W G; Wilcox, H G; Heimberg, M

    1982-01-01

    The interaction of thyroid status and oleic acid infusion rate on the thermal behavior of the very low density lipoprotein (VLDL) secreted by isolated perfused rat liver was examined. The livers were infused at 37 degrees C with oleate at rates of 0, 83, 166, or 332 mumoles/hr for 4 hours and VLDL was isolated from the perfusate at 12 degrees C. The lipid composition of the VLDL secreted by the perfused liver from hyperthyroid animals was dramatically different from controls at all infusion rates of oleate. Significant changes in the ratio of [phospholipid + cholesterol]/[triglyceride] and in fatty composition of secreted triglycerides occurred. Differential scanning calorimetry of the intact VLDL and extracted triglycerides secreted by euthyroid rats suggested the existence of four thermotropic endothermic transitions centered at -20.5, -14.0, -3.0, and 9.0 degrees C. Both the total enthalpies and the temperatures at which the phase alterations occurred in the triglyceride fraction from VLDL secreted by livers from euthyroid rats were highly dependent on the rate of infusion of oleate. Pretreatment of the rats with triiodothyronine and infusion of 332 mumoles oleate/hr abolished in the intact VLDL the temperature transitions centered at -20.8 and at 10.5 degrees C and decreased the total enthalpy from 8.13 to 38.5 cal/gm. Livers from rats pretreated with propylthiouracil and infused with oleate at 332 mumoles/hr secreted VLDL in which only one transition centered at -5.0 degrees C remained. The total enthalpy was unaffected. At all rates of infusion of oleate, the phase behavior of the intact VLDL or triglycerides extracted from the VLDL was altered by prior treatment of the rats with triiodothyronine or propylthiouracil. The thyroid state of the rat profoundly affected the thermal properties of the VLDL secreted by the perfused liver infused with the unsaturated fatty acid oleate.

  6. Metabolism of hyperpolarized [1‐13C]pyruvate through alternate pathways in rat liver

    PubMed Central

    Moreno, Karlos X.; Wang, Jian‐Xiong; Fidelino, Leila; Merritt, Matthew E.; Sherry, A. Dean; Malloy, Craig R.

    2016-01-01

    The source of hyperpolarized (HP) [13C]bicarbonate in the liver during metabolism of HP [1‐13C]pyruvate is uncertain and likely changes with physiology. Multiple processes including decarboxylation through pyruvate dehydrogenase or pyruvate carboxylase followed by subsequent decarboxylation via phosphoenolpyruvate carboxykinase (gluconeogenesis) could play a role. Here we tested which metabolic fate of pyruvate contributed to the appearance of HP [13C]bicarbonate during metabolism of HP [1‐13C]pyruvate by the liver in rats after 21 h of fasting compared to rats with free access to food. The 13C NMR of HP [13C]bicarbonate was observed in the liver of fed rats, but not in fasted rats where pyruvate carboxylation and gluconeogenesis was active. To further explore the relative fluxes through pyruvate carboxylase versus pyruvate dehydrogenase in the liver under typical conditions of hyperpolarization studies, separate parallel experiments were performed with rats given non‐hyperpolarized [2,3‐13C]pyruvate. 13C NMR analysis of glutamate isolated from the liver of rats revealed that flux from injected pyruvate through pyruvate dehydrogenase was dominant under fed conditions whereas flux through pyruvate carboxylase dominated under fasted conditions. The NMR signal of HP [13C]bicarbonate does not parallel pyruvate carboxylase activity followed by subsequent decarboxylation reaction leading to glucose production. In the liver of healthy well‐fed rats, the appearance of HP [13C]bicarbonate exclusively reflects decarboxylation of HP [1‐13C]pyruvate via pyruvate dehydrogenase. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd. PMID:26836042

  7. Metabolism of hyperpolarized [1-(13)C]pyruvate through alternate pathways in rat liver.

    PubMed

    Jin, Eunsook S; Moreno, Karlos X; Wang, Jian-Xiong; Fidelino, Leila; Merritt, Matthew E; Sherry, A Dean; Malloy, Craig R

    2016-04-01

    The source of hyperpolarized (HP) [(13)C]bicarbonate in the liver during metabolism of HP [1-(13)C]pyruvate is uncertain and likely changes with physiology. Multiple processes including decarboxylation through pyruvate dehydrogenase or pyruvate carboxylase followed by subsequent decarboxylation via phosphoenolpyruvate carboxykinase (gluconeogenesis) could play a role. Here we tested which metabolic fate of pyruvate contributed to the appearance of HP [(13)C]bicarbonate during metabolism of HP [1-(13)C]pyruvate by the liver in rats after 21 h of fasting compared to rats with free access to food. The (13)C NMR of HP [(13)C]bicarbonate was observed in the liver of fed rats, but not in fasted rats where pyruvate carboxylation and gluconeogenesis was active. To further explore the relative fluxes through pyruvate carboxylase versus pyruvate dehydrogenase in the liver under typical conditions of hyperpolarization studies, separate parallel experiments were performed with rats given non-hyperpolarized [2,3-(13)C]pyruvate. (13)C NMR analysis of glutamate isolated from the liver of rats revealed that flux from injected pyruvate through pyruvate dehydrogenase was dominant under fed conditions whereas flux through pyruvate carboxylase dominated under fasted conditions. The NMR signal of HP [(13)C]bicarbonate does not parallel pyruvate carboxylase activity followed by subsequent decarboxylation reaction leading to glucose production. In the liver of healthy well-fed rats, the appearance of HP [(13)C]bicarbonate exclusively reflects decarboxylation of HP [1-(13)C]pyruvate via pyruvate dehydrogenase.

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

    PubMed Central

    Marfà, Santiago; Morales-Ruiz, Manuel; Oró, Denise; Ribera, Jordi; Fernández-Varo, Guillermo; Jiménez, Wladimiro

    2016-01-01

    ABSTRACT At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1) were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis. PMID:27230648

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

    SciTech Connect

    Price, Roger J.; Walters, David G.; Finch, John M.; Gabriel, Karl L.; Capen, Charles C.; Osimitz, Thomas G. . E-mail: tom@sciencestrategies.com; Lake, Brian G.

    2007-01-15

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

  10. Studies on responsiveness of hepatoma cells to catecholamines. II. Comparison of beta-adrenergic responsiveness of rat ascites hepatoma cells with cultured normal rat liver cells.

    PubMed

    Miyamoto, K; Matsunaga, T; Takemoto, N; Sanae, F; Koshiura, R

    1985-05-01

    The pharmacological properties of beta-adrenoceptors in rat ascites hepatoma cells were compared with those in normal rat liver cells which were cultured for 24 hr after collagenase digestion. Adenylate cyclases in the homogenates of cultured normal rat liver cells and rat ascites hepatoma cells, AH44, AH66, AH109A, AH130 and AH7974, were all activated by isoproterenol or NaF to different degrees. The enzyme in rat liver cells was activated by several beta 2-agonists but those in all hepatoma cells hardly responded. Furthermore, salbutamol, a beta 2-partial agonist, antagonized the cyclase activation by isoproterenol in AH130 cells. The Kact value of isoproterenol for the activation of adenylate cyclase in AH130 cells was smaller than that in rat liver cells. A comparison of the Ki values of beta-antagonists for the inhibition of isoproterenol-stimulated cyclase activity shows that while the Ki values of propranolol and butoxamine in AH130 cells were similar to those in rat liver cells, a significant difference was observed in the values for beta 1-selective antagonists between AH130 cells and rat liver cells. The Ki values of metoprolol and atenolol for AH130 cells were 137- and 90-fold lower, respectively, than for normal rat liver cells. From these findings, it is strongly suggested that beta-adrenoceptors in rat ascites hepatoma cells including AH130 cells have similar properties to the mammalian beta 1-receptor.

  11. Nonalcoholic Fatty Liver Disease Progression in Rats is Accelerated by Splenic Regulation of Liver PTEN/AKT

    PubMed Central

    Wang, Ziming; Li, Naishu; Wang, Biao; Lin, Jianhua

    2015-01-01

    Background/Aim: The spleen has been reported to participate in the development of nonalcoholic fatty liver disease (NAFLD), but the mechanism has not been fully characterized. This study aims to elucidate how the spleen affects the development of NAFLD in a rat model. Materials and Methods: Following either splenectomy or sham operation, male Sprague–Dawley (SD) rats were fed a high-fat diet to drive the development of NAFLD; animals fed a normal diet were used as controls. Two months after surgery, livers and blood samples were collected. Serum lipids were measured; liver histology, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene expression, and the ratio of pAkt/Akt were determined. Results: Splenectomy increased serum lipids, except triglyceride (TG) and high-density lipoprotein (HDL), in animals fed either a high-fat or normal diet. Furthermore, splenectomy significantly accelerated hepatic steatosis. Western blot analysis and real-time polymerase chain reaction showed splenectomy induced significant downregulation of PTEN expression and a high ratio of pAkt/Akt in the livers. Conclusions: The spleen appears to play a role in the development of NAFLD, via a mechanism involving downregulation of hepatic PTEN expression. PMID:26228367

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

    PubMed Central

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

    2015-01-01

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

  13. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    PubMed

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity.

  14. Examination of serum class I antigen in liver-transplanted rats.

    PubMed Central

    Sumimoto, R; Shinomiya, T

    1991-01-01

    We examined the appearance of donor (DA) type class I antigen in the serum of rats that had received isogeneic (DA----DA) or allogeneic (DA----PVG, DA----BN, DA----LEW) liver transplants with or without cyclosporin A treatment, using two-site enzyme immunoassay. We also tested the serum titre of class I antigen in the normal DA rats with either 70% hepatectomy or cyclosporin A treatment, in order to clarify the relationship between the fluctuation in the serum titre of class I antigen in the recipient and the outcome of the transplanted liver graft. The suppression of liver graft rejection by cyclosporin A treatment significantly lowered the serum level of donor liver-derived class I antigen as compared with that of the recipient without cyclosporin A for a certain period. However, there was almost no correlation between the intensity of rejection of the liver graft and the serum level type class I among these allogeneic rejection and non-rejection liver transplantation combinations. The amount of donor-type class I antigen in the recipient's serum is dependent on whether the grafted liver is severely damaged following partial hepatectomy, whether the liver has associated biliary complications or ischaemic damage, or whether the liver has had absolute residual parenchymal cell volume or function following liver rejection. Our results suggest that the appearance of donor type class I antigen following liver transplantation is dependent on many factors, and therefore the titre of serum class 1 antigen may not always be a decisive indicator of liver graft rejection. PMID:2070555

  15. Effect of cold preservation on lymphocyte adherence in the perfused rat liver.

    PubMed

    Clavien, P A; Morgan, G R; Sanabria, J R; Petrunka, C; Levy, G A; Robert, P; Harvey, C; Strasberg, S M

    1991-09-01

    A study was designed to determine if cold preservation induces an increase in lymphocyte adherence to liver sinusoids on reperfusion. Rat livers were stored at 1 degree C in University of Wisconsin solution for 45 min, 8 hr, or 30 hr, and then reperfused for 90 min at 37 degrees C in an isolated perfused rat liver apparatus. Just prior to reperfusion, isogeneic rat lymphocytes prepared on a Ficoll-Paque gradient were added to the perfusate. In some studies lymphocytes were labeled with a fluorescent lipophilic membrane marker. There was no change in the number of circulating lymphocytes in an anhepatic circuit. When livers were present in the circuit, lymphocytes were lost from the perfusate into the liver in all studies, with the most rapid decrease occurring within 10 min of reperfusion. The length of preservation had a marked and statistically significant effect on the rate of disappearance of lymphocytes from the perfusate. Reduction by 50% of the number of lymphocytes infused did not affect the results when expressed as percent lymphocytes remaining in perfusate. To exclude the possibility that the loss of lymphocytes into the liver was due to a damaged subpopulation of lymphocytes, two livers stored 3 for 45 min were put into the circuit in sequence. The percent reduction in cells due to exposure to a second liver was not significantly different from that observed when cells were exposed only to a single liver. Histological studies showed fluorescence-labeled lymphocytes adherent in sinusoids, and the number of labeled cells was directly related to the length of preservation. Cold preservation induces an increase in lymphocyte adherence in the reperfused liver, which might be important in graft malfunction and rejection.

  16. Practical application of stereological methods in experimental kidney animal models.

    PubMed

    Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora

    The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies.

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

    PubMed Central

    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

  18. Insulin and diet-induced changes in the ubiquitin-modified proteome of rat liver

    PubMed Central

    Shtein, Harrison C.; Nguyen, Thinh Q.; Suryana, Eurwin; Poronnik, Philip; Cooney, Gregory J.; Saunders, Darren N.

    2017-01-01

    Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions. KEGG pathway analysis of these proteins identified enrichment of metabolic pathways, TCA cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and carbon metabolism, with similar pathways altered by diet and insulin resistance. Thus, the rat liver ubiquitome is sensitive to diet and insulin stimulation and this is perturbed in insulin resistance. PMID:28329008

  19. Study on Biological Effects of La(3+) on Rat Liver Mitochondria by Microcalorimetric and Spectroscopic Methods.

    PubMed

    Wu, Man; Gao, Jia-Ling; Feng, Zhi-Jiang; Liu, Wen; Zhang, Ye-Zhong; Liu, Yi; Dai, Jie

    2015-09-01

    The effects of lanthanum on heat production of mitochondria isolated from Wistar rat liver were investigated with microcalorimetry; simultaneously, the effects on mitochondrial swelling and membrane potential (Δψ) were determined by spectroscopic methods. La(3+) showed only inhibitory action on mitochondrial energy turnover with IC50 being 55.8 μmol L(-1). In the spectroscopic experiments, La(3+), like Ca(2+), induced rat liver mitochondrial swelling and decreased membrane potential (Δψ), which was inhibited by the specific permeability transition inhibitor, cyclosporine A (CsA). The induction ability of La(3+) was stronger than that of Ca(2+). These results demonstrated that La(3+) had some biotoxicity effect on mitochondria; the effects of La(3+) and Ca(2+) on rat liver mitochondrial membrane permeability transition (MPT) are different, and La represents toxic action rather than Ca analogy.

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

    PubMed

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

    2017-01-09

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  1. Effect of Tridax procumbens (Linn.) on bile duct ligation-induced liver fibrosis in rats.

    PubMed

    Joshi, P P; Patil, S D; Silawat, N; Deshmukh, P T

    2011-12-01

    The present study was undertaken to clarify whether methanolic extract of Tridax procumbens prevents liver fibrosis in rat. The hepatic fibrosis was induced by 28 days of bile duct ligation in rats. The 4-week treatment with Tridex procumbens reduced the serum aspartate aminotransferase (U L⁻¹), glutamate pyruvate transaminase (U L⁻¹), alkaline phosphatase (IU L⁻¹), lactate dehydrogenase (IU L⁻¹), total bilirubin (mg dL⁻¹), direct bilirubin (mg dL⁻¹) and hydroxyproline (mg gm⁻¹) content in liver and improved the histological appearance of liver section. The results of this study led us to conclude that T. procumbens can reduce the degree of hepatocellular damage and may become antifibrotic agent for liver fibrosis.

  2. Protective effects of Flos lonicera extract on acute liver injury by dimethylnitrosamine-induced in rats.

    PubMed

    Teng, Yang; Sun, Chang Hai; Li, Guangzhi; Sun, Guangchen; Nomachi, Yui; Yokota, Junko; Yoshioka, Saburo; Gang, Jinbo; Jiao, Shuqing; Zhang, Yu; Miyamura, Mitsuhiko

    2010-07-01

    The aim of this study is to investigate effects of Flos lonicera extract (FLE) on acute liver injury model rats which induced by 35 mg/kg dimethylnitrosamine (DMN). Model rats were divided into hepatic injury control group (administrated with water), FLE group (administrated with FLE) and silymarin group (administrated with silymarin which is hepatotherapeutic drug) as positive control. They were examined including ALT, AST, ALP, gamma-GT, ALB and TP levels in serum, and MDA, GPx levels in liver tissue. In addition, pathologic changes, particularly fibrosis, were examined by Azan staining. The results revealed that the ALT, AST, ALP, gamma-GT, MDA GPx and liver fibrosis degree in the LJE group were lower than the silymarin group and control group, ALB and TP were higher than the silymarin group and control group. These results suggested that LJE may help in inhibiting of acute liver injury greater than silymarin.

  3. Hepatoprotective effect of rooibos tea (Aspalathus linearis) on CCl4-induced liver damage in rats.

    PubMed

    Ulicná, O; Greksák, M; Vancová, O; Zlatos, L; Galbavý, S; Bozek, P; Nakano, M

    2003-01-01

    Hepatoprotective properties of rooibos tea (Aspalathus linearis) were investigated in a rat model of liver injury induced by carbon tetrachloride (CCl(4)). Rooibos tea, like N-acetyl-L-cysteine which was used for the comparison, showed histological regression of steatosis and cirrhosis in the liver tissue with a significant inhibition of the increase of liver tissue concentrations of malondialdehyde, triacylglycerols and cholesterol. Simultaneously, rooibos tea significantly suppressed mainly the increase in plasma activities of aminotransferases (ALT, AST), alkaline phosphatase and billirubin concentrations, which are considered as markers of liver functional state. The antifibrotic effect in the experimental model of hepatic cirrhosis of rats suggests the use of rooibos tea as a plant hepatoprotector in the diet of patients with hepatopathies.

  4. Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - I. Nucleotide composition of RNAs from the liver and tumor tissues of rats.

    PubMed

    Ratkiewicz, A; Galasinski, W

    1976-01-01

    The characteristics of the ribonucleic acids of Guerin tumor was the subject of this work. The effect of tumor development on the structure of the ribonucleic acids in the liver of tumor bearing rats was studied. Some differences of nucleotide compositions in RNAs isolated from subcellular fractions of liver of control and tumor bearing rats and of cancer tissue were observed. The nucleotide compositions of cancer nuclear RNA is distinctly different from liver RNA. The changes in primary structure of liver RNAs due by development of tumor in rats may be result of metabolic peculiarities of these RNAs.

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

    SciTech Connect

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

    2011-09-01

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

  6. Silymarin’s Protective Effects and Possible Mechanisms on Alcoholic Fatty Liver for Rats

    PubMed Central

    Zhang, Wei; Hong, Rutao; Tian, Tulei

    2013-01-01

    Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin’s protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat’s alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-κB (NF-κB), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-κB p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-κB. PMID:24244810

  7. Purification of rat liver particulate neutral ribonuclease and comparison of properties with pancreas and serum ribonucleases.

    PubMed Central

    Bartholeyns, J; Baudhuin, P

    1977-01-01

    Rat liver particulate neutral ribonuclease (EC 3.1.4.22) was extensively purified (up to 40000-fold). It is shown to be an endonuclease, specific for pyrimidine bases, hydrolysing 5'-phosphate ester bonds. The enzyme specificity, Km, pH optimum, stability in acid medium and thermal stability at high temperature are the same as those of rat pancreatic and serum ribonucleases. Like pancreatic and serum neutral ribonucleases, the hepatic enzyme is sensitive to the liver natural inhibitor. This inhibitor was purified 8000-fold; its association with ribonuclease follows zero-order kinetics. These identical properties for ribonuclease of rat liver, pancreas and serum support the hypothesis [Bartholeyns, Peeters-Joris & Baudhuin (1975) Eur. J. Biochem. 60, 385-393] of an extrahepatic origin for the liver enzyme, the plasma ribonuclease of pancreatic origin being taken up by endocytosis in the liver. Neutral ribonuclease activity was detected in all rat organs investigated; its distribution among tissues is different from the distribution of the natural ribonuclear inhibitor. PMID:19011

  8. Memantine effects on liver and adrenal gland of rats exposed to cold stress

    PubMed Central

    2011-01-01

    Background Memantine attenuates heart stress due cold stress, however, no study focused its effects on liver and adrenal gland. We evaluated its effects on lipid depletion in adrenal gland and glycogen depletion in liver of rats exposed to cold stress. Methods Male rats divided into 4 groups: 1)Control (CON); 2)Memantine (MEM); 3)Induced cold stress (IH) and; 4)Induced cold stress memantine (IHF). Memantine were administrated by gavage (20 mg/kg/day) during eight days. Cold stress were performed during 4 hours once at - 8°C. Lipid and glycogen depletion were presented as its intensity levels. Results Rats exposed to cold stress presented the highest glycogen (p < 0.001) and lipid depletion (p < 0.001) in liver and adrenal gland, respectively. We noted that memantine significantly reduced lipid depletion in adrenal gland and glycogen depletion in liver. Conclusion Memantine prevented glycogen depletion in liver and lipid depletion in adrenal gland of rats under a cold stress condition. PMID:21255456

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

    PubMed

    Montenegro-Miranda, Paula S; Pañeda, Astrid; ten Bloemendaal, Lysbeth; Duijst, Suzanne; de Waart, Dirk R; Gonzalez- Aseguinolaza, Gloria; Aseguinolaza, Gloria Gonzalez; Bosma, Piter J

    2013-01-01

    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.

  10. Methylene blue attenuates acute liver injury induced by paraquat in rats.

    PubMed

    Chen, Jun-Liang; Dai, Li; Zhang, Peng; Chen, Wei; Cai, Gao-Shan; Qi, Xiao-Wei; Hu, Ming-Zhu; Du, Bin; Pang, Qing-Feng

    2015-09-01

    Paraquat (PQ) poisoning often leads to severe oxidative liver injury. Recent studies have reported that methylene blue (MB) can prevent oxidative stress-induced diseases. This study tested the hypothesis that MB treatment reduced acute liver injury induced by PQ in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: (1) normal group, (2) MB group (2mg/kg i.p.), (3) PQ group (35 mg/kg i.p.) and (4) PQ+MB group (MB 2mg/kg i.p. administrated 2h after PQ). We evaluated the changes of liver histopathology, serum liver enzymatic activities, oxidative stress, heme oxygenase-1 expression, and mitochondrial permeability transition. The rats were injected with PQ produced liver injury, evidenced by histological changes and elevated serum alkaline phosphatase and alanine transaminase levels; PQ also led to oxidative stress, an increase of malondialdehyde content and mitochondrial permeability transition pore opening. Pathological damage and all of the above mentioned markers were reversed in the animals treated with MB than in those who received PQ alone. Meanwhile, MB significantly increased the contents of superoxide dismutase, adenosine triphosphate and the expression of heme oxygenase-1. In conclusion, MB had a protective effect against PQ-induced hepatic damage in rats. The mechanisms of the protection seem to be the inhibition of mitochondrial permeability transition opening and the increase of heme oxygenase-1 expression.

  11. Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis.

    PubMed

    Song, E; Chen, J; Ouyang, N; Wang, M; Exton, M S; Heemann, U

    2001-05-04

    Metastasis of colorectal carcinomas rarely occurs in cirrhotic livers. Our study investigated the influence of activated Kupffer cells from cirrhotic rat livers on hepatic colonization and FasR-mediated apoptosis of colon cancer cells. A rat colon cancer cell line, RCN-9, was used to inoculate rat livers. Treatment with conditioned media of Kupffer cells isolated from CCl(4)-induced cirrhotic rat livers (cirrhotic KCM) significantly reduced the incidence of hepatic colonization of RCN-9 cells. In vitro cytotoxicity of Kupffer cells and tumour infiltrating lymphocytes (TILs) on RCN-9 cells was evaluated using [(3)H]-release assay. RCN-9 cells were resistant to cytotoxicity mediated by cirrhotic Kupffer cells, but were sensitized to TIL-mediated killing after treatment with cirrhotic KCM. The specific killing induced by TILs was FasR-mediated, as it was inhibited by ZB4, an antagonistic anti-FasR antibody. In agreement, cirrhotic KCM increased recombinant Fas ligand-induced apoptosis of RCN-9 cells, and up-regulated FasR expression on RCN-9 cells as evaluated by RT-PCR and flow cytometry. These findings suggest that Kupffer cells in cirrhotic livers sensitize metastatic colon cancer cells to FasR-mediated apoptosis by up-regulating the receptors, which thus prepare them to be eliminated by infiltrating lymphocytes.

  12. Repeated-dose liver micronucleus test of 4,4'-methylenedianiline using young adult rats.

    PubMed

    Sanada, Hisakazu; Koyama, Naomi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    Liver micronucleus (MN) tests using partial hepatectomized rats or juvenile rats have been shown to be useful for the detection of hepatic carcinogens. Moreover, Narumi et al. established the repeated-dose liver MN test using young adult rats for integration into general toxicity. In the present study, in order to examine the usefulness of the repeated-dose liver MN test, we investigated MN induction with a 14 or 28 day treatment protocol using young adult rats treated with 4,4′-methylenedianiline (MDA), a known hepatic carcinogen. MDA dose-dependently induced micronuclei in hepatocytes in 14- and 28-day repeated-dose tests. However, although statistically significant increases in micronuclei were observed in bone marrow cells at two dose levels in the 14-day study, there was no dose response and no increases in micronuclei in the 28-day study. These results indicate that the evaluation of genotoxic effects using hepatocytes is effective in cases where chromosomal aberrations are not clearly detectable in bone marrow cells. Moreover, the repeated-dose liver MN test allows evaluation at a dose below the maximum tolerable dose, which is required for the conventional MN test because micronucleated hepatocytes accumulate. The repeated-dose liver MN test employed in the present study can be integrated into the spectrum of general toxicity tests without further procedural modifications.

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

    PubMed

    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 < 0.001) than control-fed rats and gained less weight (p < 0.001). DHEA feeding caused significant decreases (p < 0.001) in the serum levels of IGF-1 and IGFBP-3 and significantly increased (p < 0.001) serum levels of 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.

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

    PubMed

    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.

  15. Characterization of CC-531 as a Rat Model of Colorectal Liver Metastases

    PubMed Central

    White, Sarah Beth; Procissi, Daniele; Chen, Jeane; Gogineni, Venkateswara Rao; Tyler, Patrick; Yang, Yihe; Omary, Reed A.; Larson, Andrew C.

    2016-01-01

    Purpose Surgical resection of colorectal liver metastases is not achievable in more than 70% of the cases. Although the liver directed therapies have become a part of the stand of care, lack of a preclinical model impedes the assessment of toxicity and therapeutic benefits attributed several candidate drugs or treatment regimens that can be designed. In the present study we aim develop and characterize a rat colorectal liver metastasis model. Materials and Methods Growth characteristics of CC-531 cells were determined in vitro followed by subcapsular liver implantation in syngeneic WAG/Rij rats. Tumor growth progression was followed over 3 weeks by ultrasound (US) and magnetic resonance imaging (MRI). Growth characteristics were also assessed by histopathology and immunohistochemistry in harvested tumor tissues. Results The doubling time of CC-531 cells was found be under 24hrs and all the implanted rats grew tumors. US imaging showed hypoechoic masses and MRI showed contrast enhancement representing complex tumor microenvironments. Hematoxylin and Eosin staining confirmed tumor growth and uniform CD31 staining in tumor confirmed even vessel density. Conclusion CC-531 can be used as a metastatic rat tumor colorectal liver metastases model with well-defined characteristics that can be readily followed by imaging whilst having a therapeutic window for interventions. PMID:27171151

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

    PubMed

    Ronis, Martin J J; Baumgardner, January N; Sharma, Neha; Vantrease, Jamie; Ferguson, Matthew; Tong, Yudong; Wu, Xianli; Cleves, Mario A; Badger, Thomas M

    2013-02-01

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by non-alcoholic fatty liver disease (NAFLD) leading to non-alcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been shown to protect against steatosis and alcoholic liver injury. The current study was designed to determine if a similar beneficial effect of MCT occurs in a rat model of NAFLD. Groups of male rats were isocalorically overfed diets containing 10%, 35% or 70% total energy as corn oil or a 70% fat diet in which corn oil was replaced with increasing concentrations of saturated fat (18:82, beef tallow:MCT oil) from 20% to 65% for 21 days using total enteral nutrition (TEN). As dietary content of corn oil increased, hepatic steatosis and serum alanine amino transferases were elevated (P < 0.05). This was accompanied by greater expression of cytochrome P450 enzyme CYP2E1 (P < 0.05) and higher concentrations of polyunsaturated 18:2 and 20:4 fatty acids (FA) in the hepatic lipid fractions (P < 0.05). Keeping the total dietary fat at 70%, but increasing the proportion of MCT-enriched saturated fat resulted in a dose-dependent reduction in steatosis and necrosis without affecting CYP2E1 induction. There was no incorporation of C8-C10 FAs into liver lipids, but increasing the ratio of MCT to corn oil: reduced liver lipid 18:2 and 20:4 concentrations; reduced membrane susceptibility to radical attack; stimulated FA β- and ω-oxidation as a result of activation of peroxisomal proliferator activated receptor (PPAR)α, and appeared to increase mitochondrial respiration through complex III. These data suggest that replacing unsaturated fats like corn oil with MCT oil in the diet could be utilized as a potential treatment for NAFLD.

  17. Rat liver microsomal lipid peroxidation produced during the oxidative metabolism of ethacrynic acid.

    PubMed

    Yamamoto, K; Masubuchi, Y; Narimatsu, S; Kobayashi, S; Horie, T

    2001-04-01

    Thiobarbituric acid reactive substances (TBARS) were produced in rat liver microsomal suspension incubated with ethacrynic acid (loop diuretic drug) and NADPH. Two oxidative metabolites of ethacrynic acid with dicarboxylic acid and hydroxylated ethyl group, respectively, were formed in the reaction mixture. The oxidative metabolism of ethacrynic acid was inhibited by cytochrome P450 inhibitors. The formation of TBARS was remarkably depressed by inhibitors like diethyldithiocarbamate and disulfiram. These results indicate that lipid peroxidation occurred in rat liver microsomes through the oxidative metabolism of ethacrynic acid.

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

    NASA Technical Reports Server (NTRS)

    Hillyard, L. A.; Entenman, C.

    1973-01-01

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

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

    SciTech Connect

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

    2006-04-01

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

  20. RNA interference against discoidin domain receptor 2 ameliorates alcoholic liver disease in rats.

    PubMed

    Luo, Zheng; Liu, Huimin; Sun, Xiaomeng; Guo, Rong; Cui, Ruibing; Ma, Xiangxing; Yan, Ming

    2013-01-01

    Discoidin domain receptor 2 (DDR2) is involved in fibrotic disease. However, the exact pathogenic implications of the receptor in early alcoholic liver disease are still controversial. We constructed plasmid vectors encoding short-hairpin RNA against DDR2 to investigate its role in alcoholic liver disease in an immortalized rat hepatic stellate cell line, HSC-T6, and in rats by MTT, RT-PCR and western blot analyses; immunohistochemistry and electron microscopy. Alcohol-induced upregulation of DDR2 was associated with the expression of matrix metalloproteinase 2, the transforming growth factor β1 signaling pathway and tissue inhibitor of metalloproteinase 1; collagen deposition; and extracellular matrix remodeling. Inhibition of DDR2 decreased HSC-T6 cell proliferation and liver injury in rats with 10-week-induced alcoholic liver disease. DDR2 may have an important role in the pathogenesis of early-stage alcoholic liver disease. Silencing DDR2 may be effective in preventing early-stage alcoholic liver disease.

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

    SciTech Connect

    Shchelkunova, T.A.; Rozen, V.B.; Smirnov, A.N.

    1986-01-01

    Model experiments were conducted to study the effect of a highly purified preparation of specific estrogen-binding protein (SEBP) on the intensity of estradiol and testosterone metabolism under the influence of enzymes in liver homogenate from female rats, not containing SEBP. The liver of mature female rats was homogenized in two volumes of 50 mM Tris-HCl buffer, pH 7.5, containing 600 mg% of glucose. The tritium-steroid was preincubated for 15 min at 0-4 C with 0-4 microg of the preparation of SEBP (200 microl). A standard preparation of partially purified SEBP was obtained from liver cystosol of mature male rats; affinity chromatography on estradiolagarose was used. It is shown that SEBP can really take part in regulation of the dynamics of sex steroids in the liver. E/sub 1/ did not affect the metabolic rate of H 3-E/sub 2/ by liver homogenate from females, but caused marked acceleration of H 3-E/sub 2/ metabolism by male liver homogenate.

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

    PubMed

    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.

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

    PubMed Central

    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

  4. Estrogen- and progestin-receptor complexes and their interaction with rat liver cell nuclei during ontogenesis

    SciTech Connect

    Konoplya, E.F.; Luksha, G.L.; Savateev, S.K.; Naumov, A.D.

    1986-11-10

    Steroid-receptor complexes (SRC) of estrogens and progestins have been isolated from the rat liver and purified 1500-2000-fold. Both in the state of the initial cytosol and purified 2000-fold, the SRC were characterized by gel filtration on Sephadex G-100 and by DEAE-cellulose chromatography. The purified SRC from the rat liver were used for binding to isolated liver cell nuclei from rats of different ages (1.5 months, 6 months, 12 months, 24 months). The maximum binding of SRC of progestins and estrogens from the rat liver is observed with homologous nuclei of 1.5-month-old rats. With age the binding of SRC by the nuclei decreases progressively and reaches a minimum by 24 months. The detected differences in the binding of SRC by the nuclei of cells of animals of different ages, in their opinion, may lie at the basis of changes in the functioning of the organism under the influence of hormones at different stages of ontogenesis.

  5. PASS-Predicted Hepatoprotective Activity of Caesalpinia sappan in Thioacetamide-Induced Liver Fibrosis in Rats

    PubMed Central

    Kadir, Farkaad A.; Kassim, Normadiah M.; Abdulla, Mahmood Ameen; Ahmadipour, Fatemeh; Yehye, Wageeh A.

    2014-01-01

    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. PMID:24701154

  6. Mitochondrial respiration in muscle and liver from cold-acclimated hypothyroid rats.

    PubMed

    Zaninovich, Angel A; Rebagliati, Ines; Raices, Marcela; Ricci, Conrado; Hagmuller, Karl

    2003-10-01

    The effects of long-term cold exposure on muscle and liver mitochondrial oxygen consumption in hypothyroid and normal rats were examined. Thyroid ablation was performed after 8-wk acclimation to 4 degrees C. Hypothyroid and normal controls remained in the cold for an additional 8 wk. At the end of 16-wk cold exposure, all hypothyroid rats were alive and normothermic and had normal body weight. At ambient temperature (24 degrees C), thyroid ablation induced a 65% fall in muscle mitochondrial oxygen consumption, which was reversed by thyroxine but not by norepinephrine administration. After cold acclimation was reached, suppression of thyroid function reduced muscle mitochondrial respiration by 30%, but the hypothyroid values remained about threefold higher than those in hypothyroid muscle in the warm. Blockade of beta- and alpha1-adrenergic receptors in both hypothyroid and normal rats produced hypothermia in vivo and a fall in muscle, liver, and brown adipose tissue mitochondria respiration in vitro. In normal rats, cold acclimation enhanced muscle respiration by 35%, in liver 18%, and in brown adipose tissue 450% over values in the warm. The results demonstrate that thyroid hormones, in the presence of norepinephrine, are major determinants of thermogenic activity in muscle and liver of cold-acclimated rats. After thyroid ablation, cold-induced nonshivering thermogenesis replaced 3,5,3'-triiodothyronine-induced thermogenesis, and normal body temperature was maintained.

  7. STEREOLOGICAL ANALYSIS OF MAMMALIAN SKELETAL MUSCLE

    PubMed Central

    Eisenberg, Brenda R.; Kuda, Aileen M.; Peter, James B.

    1974-01-01

    A quantitative analysis of the volumes, surface areas, and dimensions of the ultrastructural components in the soleus muscle fibers of the guinea pig was made by using point counting methods of stereology. Muscle fibers have structural orientation (anisotropy) and have spatial gradients of the structures within the fiber; therefore the standard stereological methods were modified where necessary. The entire analysis was repeated at two section orientations to test the modifications and identical results obtained from both. The volume of lipid droplets was 0.20 ± 0.06% (mean ± standard error, n = 5 animals) and the nuclei volume was 0.86 ± 0.20% of the fiber volume. The total mitochondrial volume was 4.85 ± 0.66% of the fiber volume with about one-third being found in an annulus within 1 µm of the sarcolemma. The mitochondrial volume in the remaining core of the fiber was 3.6 ± 0.4%. The T system has a volume of 0.14 ± 0.01% and a surface area of 0.064 ± 0.005 µm2/µm3 of the fiber volume. The surface area of the sarcolemma is 0.116 ± 0.013 µm2/µm3 which is twice the T system surface area. The volume of the entire sarcoplasmic reticulum is 3.52 ± 0.33% and the surface area is 0.97 ± 0.09 µm2/µm3. The sarcoplasmic reticulum is composed of the terminal cisternae whose volume is 1.04 ± 0.19% and surface area is 0.24 ± 0.05 µm2/µm3. The tubules of the sarcoplasmic reticulum in the I band and A band have volumes of 1.97 ± 0.24% and 0.51 ± 0.08%, and the surface areas of the I and A band reticulum are 0.56 ± 0.07 µm2/µm3 and 0.16 ± 0.04 µm2/µm3, respectively. The Z line width, myofibril and fiber diameters were measured. PMID:4824293

  8. Pharmacokinetics and therapeutic effects of oltipraz after consecutive or intermittent oral administration in rats with liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Bae, Soo K; Lee, Shin J; Kim, Taekrho; Kim, Jin W; Lee, Inchul; Kim, Sang G; Lee, Myung G

    2006-05-01

    Pharmacokinetics and therapeutic effects of oltipraz were evaluated after consecutive (once per day at 30 mg/kg/day for 7 and 14 days) or intermittent (once per week at 100 mg/kg/week for 1-3 weeks) oral administration to rats with liver cirrhosis induced by dimethylnitrosamine. The AUC of oltipraz was significantly greater in cirrhotic rats than controls (890 compared with 270 microg . min/mL) due to impaired liver function in cirrhotic rats. However, the AUC values after consecutive 7 (421 compared with 753 microg . min/mL) and 14 (309 compared with 821 microg . min/mL) days oral administration of oltipraz in cirrhotic rats were significantly smaller than those in respective vehicle-treated cirrhotic rats. Moreover, the AUC values after intermittent 2 and 3 weeks in cirrhotic rats were also significantly smaller than that in 1 week vehicle-treated cirrhotic rats (2370 and 1690 compared with 4760 microg . min/mL). This could be due to induction of CYP isozymes and considerably greater numbers of normal liver cells in cirrhotic rats by oral administration of oltipraz. Improved liver function by oltipraz in cirrhotic rats was proved by liver microscopy; livers are free of significant fibrosis, although evidence of bridging necrosis is still present in many rats.

  9. Histopathological changes in liver, kidney and muscles of pesticides exposed malnourished and diabetic rats.

    PubMed

    Benjamin, Nidhi; Kushwah, Ameeta; Sharma, R K; Katiyar, A K

    2006-03-01

    Histopathological changes were observed in liver, kidney and muscles of normal, protein-malnourished, diabetic as well as both protein-malnourished and diabetic albino rats when exposed to a mixture of monocrotophos, hexachlorocyclohexane and endosulfan at varying intervals. The examination revealed hepatotoxic, nephrotoxic and muscular necrotic effects in pesticides exposed rats. Toxicity was aggravated in protein-malnourished and diabetic animals and more so, if the animals were both diabetic and protein-malnourished.

  10. Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in rats.

    PubMed

    Xu, X-F; Zhang, J

    2013-01-01

    To determine the effect of saturated hydrogen saline on lipopolysaccharide (LPS)-induced acute liver dysfunction, rats were divided into control, LPS, and LPS plus saturated hydrogen saline (LPS+H(2)) groups. Treatment with saturated hydrogen saline prolonged the median survival time and reduced liver dysfunction. Moreover, saturated hydrogen saline significantly reduced pathological alterations in liver tissues, the number of ballooned hepatocytes, serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, and myeloperoxidase (MPO) and malondialdehyde (MDA) levels in liver tissues (P<0.05). Cell apoptosis was detected in liver tissues after LPS treatment, and attenuated by saturated hydrogen saline treatment. Saturated hydrogen saline also decreased phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated Jun kinase (p-JNK), nuclear factor-kappa B (NF-kappaB), and second mitochondria-derived activator of caspase (Smac) levels, and increased p38 activation (P<0.05). Thus, saturated hydrogen saline may attenuate LPS-induced acute liver dysfunction in rats, possibly by reducing inflammation and cell apoptosis. Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to saturated hydrogen saline-mediated liver protection.

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

    NASA Technical Reports Server (NTRS)

    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.

  12. Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

    PubMed

    Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

    2014-11-01

    The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

  13. Simple steatosis sensitizes cholestatic rats to liver injury and dysregulates bile salt synthesis and transport

    PubMed Central

    Lionarons, Daniël A.; Heger, Michal; van Golen, Rowan F.; Alles, Lindy K.; van der Mark, Vincent A.; Kloek, Jaap J.; de Waart, Dirk R.; Marsman, Hendrik A.; Rusch, Henny; Verheij, Joanne; Beuers, Ulrich; Paulusma, Coen C.; van Gulik, Thomas M.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. It is uncertain if simple steatosis, the initial and prevailing form of NAFLD, sensitizes the liver to cholestasis. Here, we compared the effects of obstructive cholestasis in rats with a normal liver versus rats with simple steatosis induced by a methionine/choline-deficient diet. We found that plasma liver enzymes were higher and hepatic neutrophil influx, inflammation, and fibrosis were more pronounced in animals with combined steatosis and cholestasis compared to cholestasis alone. Circulating bile salt levels were markedly increased and hepatic bile salt composition shifted from hydrophilic tauro-β-muricholate to hydrophobic taurocholate. This shift was cytotoxic for HepG2 hepatoma cells. Gene expression analysis revealed induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1), and modulation of the hepatic bile salt transport system. In conclusion, simple steatosis sensitizes the liver to cholestatic injury, inflammation, and fibrosis in part due to a cytotoxic shift in bile salt composition. Plasma bile salt levels were elevated, linked to dysregulation of bile salt synthesis and enhanced trafficking of bile salts from the liver to the systemic circulation. PMID:27535001

  14. Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats

    PubMed Central

    Urbanowicz, W; Sogni, P; Moreau, R; Tazi, K A; Barriere, E; Poirel, O; Martin, A; Guimont, M C; Cazals-Hatem, D; Lebrec, D

    2004-01-01

    Background/aims: Lipopolysaccharide (LPS) induces liver injury which is associated with upregulated endothelin (ET)-1 production. The aim of this study was to investigate the effects of tezosentan, a non-selective ETA and ETB receptor antagonist, in LPS challenged rats with cirrhosis. Methods: Rats with cirrhosis received LPS and then tezosentan or placebo one hour later. Four hours after LPS administration, rats were killed to measure serum transaminase activity and plasma tumour necrosis factor α (TNF-α) levels. Hepatic inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), a marker of neutrophil infiltration, and cyclooxygenase (COX)-2 expression were also measured. Results: LPS administration significantly decreased arterial pressure and significantly increased plasma endothelin levels. Following LPS and tezosentan administration, serum aspartate aminotransferase and alanine aminotransferase activities were similar to those in the control group while they were increased by more than 700% with LPS alone. Plasma TNF-α levels were significantly lower in rats receiving LPS and tezosentan (182 (38) pg/ml) compared with those receiving LPS alone (821 (212) pg/ml). Tezosentan significantly decreased hepatic MPO activity and hepatic neutrophils but had no effect on LPS induced iNOS or COX-2. Survival rate was significantly higher in rats receiving LPS plus tezosentan (80%) than in rats receiving LPS alone (50%). Conclusion: In LPS challenged cirrhotic rats, tezosentan administration prevents LPS induced liver injury by decreasing intrahepatic neutrophil infiltration. In addition, tezosentan increases survival in these rats. PMID:15542526

  15. Bioimaging of DsRed fluorescence in the transgenic rat liver

    NASA Astrophysics Data System (ADS)

    Arao, Yukitomo; Hakamata, Yoji; Igarashi, Yuka; Sato, Yuki; Murakami, Takashi; Kobayashi, Eiji

    2006-02-01

    We developed the Alb-DsRed2 transgenic (Tg) rat designed with liver-specific expression of the red fluorescent protein, DsRed2. Herein, we report high expression of DsRed2 in neonate liver of both sexes, although they were sexually dimorphic and exhibited a male-specific pattern in adult rats. In an effort to examine the expression in each animal under development, we employed an in vivo Bio-imaging system to quantitatively estimate hepatic DsRed2 expression levels. The temporal profiles pertaining to DsRed expression were similar in male and female Tg rats until 28 days old. The levels in both sexes decreased gradually following birth, and were not detectable at 21 days. Subsequently, expression in males increased again at 35 days and was maintained at a persistently high level thereafter. On the other hand, expression in females disappeared steadily. Although hepatic DsRed expression levels in gonadectomized Tg rats was not significantly different, DsRed expression in hypophysectomized female Tg rats appeared dramatically 72 hr following operation. Hepatocytes were collected from adult Tg rats and cultured in conditioning medium. DsRed expression in female hepatocytes could be detected 72 hr following culturing. These results suggest that hepatic DsRed expression in female rats is regulated in vivo by the pituitary. This report is shows use of Alb-DsRed2 Tg rats in conjunction with a novel bio-imaging system represents a powerful experimental system.

  16. Hepatoprotective and antioxidant effect of tender coconut water on carbon tetrachloride induced liver injury in rats.

    PubMed

    Loki, Anthony Loperito; Rajamohan, T

    2003-10-01

    Hepatoprotective and antioxidant effects of tender coconut water (TCW) were investigated in carbon tetrachloride (CCl4)-intoxicated female rats. Liver damage was evidenced by the increased levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and decreased levels of serum proteins and by histopathological studies in CCl4-intoxicated rats. Increased lipid peroxidation was evidenced by elevated levels of thiobarbituric acid reactive substance (TBARS) viz, malondialdehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD), and also by significant decrease in antioxidant enzymes activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx) and glutathione reductase (GR) and also reduced glutathione (GSH) content in liver. On the other hand, CCl4-intoxicated rats treated with TCW retained almost normal levels of these constituents. Decreased activities of antioxidant enzymes in CCl4-intoxicated rats and their reversal of antioxidant enzyme activities in TCW treated rats, shows the effectiveness of TCW in combating CCl4-induced oxidative stress. Hepatoprotective effect of TCW is also evidenced from the histopathological studies of liver, which did not show any fatty infiltration or necrosis, as observed in CCl4-intoxicated rats.

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

    PubMed

    Liu, Wei-hui; Li, Ren; Dou, Ke-feng

    2011-03-01

    Although the stem cells are commonly isolated by FACS or MACS, they are very expensive and these is no specific marker for liver stem/progentior cells (LSPCs). This paper applied a convenient and efficient method to enrich LSPCs. The fetal liver cells (FLCs) were firstly enriched by Percoll discontinuous gradient centrifugation (PDGC) from the rat fetal liver. Then the FLCs in culture were purified to be homogeneous in size by differential trypsinization and differential adherence (DTDA). Flow cytometric analysis revealed more than half of the purified FLCs expressed alternative markers of LSPCs (CD117, c-Met, Sca-1, CD90, CD49f and CD133). In other words, the purified FLCs were heterogeneous. Therefore, they were sequentially layered into six fractions by Percoll continuous gradient centrifugation (PCGC). Both CD133 and CD49f expressed decreasingly from fraction 1 to 6. In fraction 1 and 2, about 85% FLCs expressed CD133, which were revealed to be LSPCs by high expressions of AFP and CK-19, low expressions of G-6-P and ALB. To conclude, the purity of CD133(+) LSPCs enriched by combination of PDGC, DTDA and PCGC is close to that obtained by MACS. This study will greatly contribute to two important biological aspects: liver stem cells isolation and liver cell therapy.

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2014-09-01

    We investigated the feasibility of using 3-D ultrasound Nakagami imaging to detect the early stages of liver fibrosis in rats. Fibrosis was induced in livers of rats (n = 60) by intraperitoneal injection of 0.5% dimethylnitrosamine (DMN). Group 1 was the control group, and rats in groups 2-6 received DMN injections for 1-5 weeks, respectively. Each rat was sacrificed to perform 3-D ultrasound scanning of the liver in vitro using a single-element transducer of 6.5 MHz. The 3-D raw data acquired at a sampling rate of 50 MHz were used to construct 3-D Nakagami images. The liver specimen was further used for histologic analysis with hematoxylin and eosin and Masson staining to score the degree of liver fibrosis. The results indicate that the Metavir scores of the hematoxylin and eosin-stained sections in Groups 1-4 were 0 (defined as early liver fibrosis in this study), and those in groups 5 and 6 ranged from 1 to 2 and 2 to 3, respectively. To quantify the degree of early liver fibrosis, the histologic sections with Masson stain were analyzed to calculate the number of fiber-related blue pixels. The number of blue pixels increased from (2.36 ± 0.79) × 10(4) (group 1) to (7.68 ± 2.62) × 10(4) (group 4) after DMN injections for 3 weeks, indicating that early stages of liver fibrosis were successfully induced in rats. The Nakagami parameter increased from 0.36 ± 0.02 (group 1) to 0.55 ± 0.03 (group 4), with increasing numbers of blue pixels in the Masson-stained sections (p-value < 0.05, t-test). We concluded that 3-D Nakagami imaging has potential in the early detection of liver fibrosis in rats and may serve as an image-based pathologic model to visually track fibrosis formation and growth.

  20. Ex vivo study of acoustic radiation force impulse imaging elastography for evaluation of rat liver with steatosis.

    PubMed

    Guo, Yanrong; Dong, Changfeng; Lin, Haoming; Zhang, Xinyu; Wen, Huiying; Shen, Yuanyuan; Wang, Tianfu; Chen, Siping; Liu, Yingxia; Chen, Xin

    2017-02-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in developed countries. Accurate, noninvasive tests for diagnosing NAFLD are urgently needed. The goals of this study were to evaluate the utility of acoustic radiation force impulse (ARFI) elastography for determining the severity grade of steatosis in rat livers, and to investigate the changes in various histologic and biochemical characteristics. Steatosis was induced in the livers of 57 rats by gavage feeding of a high fat emulsion; 12 rats received a standard diet only and served as controls. Liver mechanics were measured ex vivo using shear wave velocity (SWV) induced by acoustic radiation force. The measured mean values of liver SWV ranged from 1.33 to 3.85m/s for different grades of steatosis. The area under the receiver operative characteristic curve (⩾S1) was equal to 0.82 (95% CI=0.69, 0.96) between the steatosis group and the normal group, and the optimal cutoff value was 2.59 with sensitivity of 88% and specificity of 76%. However, there are no significant differences in SWV measurements between the steatosis grades. SWV values did not correlate with the early grade of inflammation. In conclusion, ARFI elastography is a promising method for differentiating normal rat liver from rat liver with steatosis, but it cannot reliably predict the grade of steatosis in rat livers. The early grade of inflammation activity did not significantly affect the SWV measurements.

  1. Antifibrotic effect of edaravone in rat liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Tanaka, Hiroto; Ueda, Hiroki; Fukuchi, Hiroko; Ichinose, Masakazu

    2009-09-01

    Edaravone (EDA), a newly synthesized free radical scavenger, has shown excellent results in the treatment of stroke. An overproduction of reactive oxygen species (ROS) causing oxidative DNA damage has been accounted as a major factor causing liver injury and fibrosis. Therefore, we examined its effect of EDA in rat model of liver cirrhosis induced by dimethylnitrosamine (DMN). Ten rats (DMN-group) were injected intraperitoneally with DMN (10 microg/g body weight) alone and another ten rats (EDA-group) were injected intraperitoneally with EDA (10 mg/kg body weight) 2 h after being injected with DMN. Both groups underwent their injection regimen three times a week for 4 weeks, after which the rats were sacrificed and their liver tissue sections were stained with Azan-Mallory for quantitative analyses of fibrosis development, using soft imaging and a previously published scoring system. Additionally, these sections were immunohistochemically stained using an antibody against alpha-smooth muscle actin (alpha-SMA). The total-bililubin in the EDA-group was found to be lower than that in the DMN-group. Quantitive analysis of liver fibrosis showed that the fibrotic area of the EDA-group was significantly smaller than that of the DMN-group. Additionally, the number of alpha-SMA positive cells in the EDA-group were significantly lower than that in the DMN-group. This study showed that EDA reduces liver fibrosis in a rat of cirrhosis induced by DMN. These data suggest that the reduction of liver fibrosis by EDA may be induced by the suppression of activated hepatic stellate cells.

  2. Effect of Oenanthe Javanica Extract on Antioxidant Enzyme in the Rat Liver

    PubMed Central

    Lee, Choong-Hyun; Park, Joon-Ha; Cho, Jeong-Hwi; Kim, In-Hye; Ahn, Ji-Hyeon; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Bae, Eun Joo; Kang, Il-Jun; Won, Moo-Ho; Kim, Jong-Dai

    2015-01-01

    Background: Oenanthe javanica (O. javanica) has been known to have high antioxidant properties via scavenging reactive oxygen species. We examined the effect of O. javanica extract (OJE) on antioxidant enzymes in the rat liver. Methods: We examined the effect of the OJE on copper, zinc-superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPx) in the rat liver using immunohistochemistry and western blot analysis. Sprague-Dawley rats were randomly assigned to three groups; (1) normal diet fed group (normal-group), (2) diet containing ascorbic acid (AA)-fed group (AA-group) as a positive control, (3) diet containing OJE-fed group (OJE-group). Results: In this study, no histopathological finding in the rat liver was found in all the experimental groups. Numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells and their protein levels were significantly increased in the AA-fed group compared with those in the normal-group. On the other hand, in the OJE-group, numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells in the liver were significantly increased by about 190%, 478%, 685%, and 346%, respectively, compared with those in the AA-group. In addition, protein levels of SOD1, SOD2, CAT, and GPx in the OJE-group were also significantly much higher than those in the AA-group. Conclusion: OJE significantly increased expressions of SOD1 and SOD2, CAT, and GPx in the liver cells of the rat, and these suggests that significant enhancements of endogenous enzymatic antioxidants by OJE might be a legitimate strategy for decreasing oxidative stresses in the liver. PMID:26063368

  3. Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique

    NASA Astrophysics Data System (ADS)

    Lin, Jian; Lu, Fake; Zheng, Wei; Xu, Shuoyu; Tai, Dean; Yu, Hanry; Huang, Zhiwei

    2011-11-01

    We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for label-free monitoring of the progression of liver steatosis and fibrosis generated in a bile duct ligation (BDL) rat model. Among the 21 adult rats used in this study, 18 rats were performed with BDL surgery and sacrificed each week from weeks 1 to 6 (n = 3 per week), respectively; whereas 3 rats as control were sacrificed at week 0. Colocalized imaging of the aggregated hepatic fats, collagen fibrils, and hepatocyte morphologies in liver tissue is realized by using the integrated CARS, SHG, and TPEF technique. The results show that there are significant accumulations of hepatic lipid droplets and collagen fibrils associated with severe hepatocyte necrosis in BDL rat liver as compared to a normal liver tissue. The volume of normal hepatocytes keeps decreasing and the fiber collagen content in BDL rat liver follows a growing trend until week 6; whereas the hepatic fat content reaches a maximum in week 4 and then appears to stop growing in week 6, indicating that liver steatosis and fibrosis induced in a BDL rat liver model may develop at different rates. This work demonstrates that the integrated CARS and multiphoton microscopy imaging technique has the potential to provide an effective means for early diagnosis and detection of liver steatosis and fibrosis without labeling.

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

    PubMed

    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.

  5. Stereological analyses of the whole human pancreas

    PubMed Central

    Poudel, Ananta; Fowler, Jonas L.; Zielinski, Mark C.; Kilimnik, German; Hara, Manami

    2016-01-01

    The large size of human tissues requires a practical stereological approach to perform a comprehensive analysis of the whole organ. We have developed a method to quantitatively analyze the whole human pancreas, as one of the challenging organs to study, in which endocrine cells form various sizes of islets that are scattered unevenly throughout the exocrine pancreas. Furthermore, the human pancreas possesses intrinsic characteristics of intra-individual variability, i.e. regional differences in endocrine cell/islet distribution, and marked inter-individual heterogeneity regardless of age, sex and disease conditions including obesity and diabetes. The method is built based on large-scale image capture, computer-assisted unbiased image analysis and quantification, and further mathematical analyses, using widely-used software such as Fiji/ImageJ and MATLAB. The present study includes detailed protocols of every procedure as well as all the custom-written computer scripts, which can be modified according to specific experimental plans and specimens of interest. PMID:27658965

  6. Upregulation of cytochromes P450 2B in rat liver by orphenadrine

    PubMed Central

    Murray, Michael; Fiala-Beer, Eva; Sutton, Dylan

    2003-01-01

    The alkylamine drug orphenadrine (ORPH) is an inducer and inhibitor of the microsomal cytochrome P450 (CYP) system in mammals. This study evaluated the selectivity of CYP induction by ORPH in rat liver. Immunoblot analysis indicated that ORPH was a selective inducer of the phenobarbitone (PB)-inducible CYP2B in rat liver. CYP2B protein was increased to ∼14-fold of levels in untreated rat liver. By comparison PB increased CYP2B expression 40-fold. Corresponding increases in the activity of CYP2B-dependent androstenedione 16β-hydroxylation were measured in microsomes from ORPH and PB-induced rats. Northern analysis indicated that CYP2B1/2 mRNA was increased in ORPH-induced rat liver. Consistent with this finding, ORPH was found to activate a PB-responsive enhancer module in constitutive androstane receptor (CAR)-transfected Hep G2 cells. Other alkylamines like troleandomycin impair CYP turnover. We tested whether ORPH induction of CYP2B may include a post-translational component. In PB-pretreated animals ORPH administration delayed the loss of CYP2B after PB withdrawal, but no evidence for altered turnover was found. These studies establish ORPH as a selective inducer of CYP2B in rat liver. Induction appears to be mediated pretranslationally by CAR activation of CYP2B gene transcription. Post-translational stabilisation by an ORPH metabolite does not elicit induction. Induction of CYP2B may influence pharmacokinetic interactions involving ORPH. PMID:12813002

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

    PubMed Central

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

    2016-01-01

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

  8. Effect of hyperthyroidism and hypothyroidism on lipid and carbohydrate metabolism of the perfused rat liver.

    PubMed Central

    Laker, M E; Mayes, P A

    1981-01-01

    1. Liver from hyper- and hypo-thyroid male fed rats were perfused with whole blood and their metabolism was compared with euthyroid controls. 2. Hyperthyroid livers produced more bile than controls and hypothyroid livers produced less. 3. Glucose output by all livers was similar; glycogen declined only during perfusion of hyperthyroid livers. Lactate uptake increased in hyperthyroid but decreased in hypothyroid livers. These results may be explained by changes in oxidation of carbohydrate rather than in gluconeogenesis. 4. Secretion of triacylglycerol was decreased in hyperthyroid and not changed significantly in hypothyroid livers. 5. Fractional extraction of infused [1-14C]oleate was unaltered. Hyperthyroid livers oxidized more oleate to CO2 and ketone bodies, esterified less and incorporated less into lipoproteins of d less than 1.006. Hypothyroid livers oxidized and esterified oleate to the same extent as controls; their decreased O2 consumption was due to diminished oxidation of other (non-lipid) substrates; 14C-labelled ketone-body formation was increased, but at the expense of 14CO2 production. 6. Lipogenesis (measured with 3H2O) was unaltered in hyperthyroid but was decreased in hypothyroid livers. Incorporation of 3H and 14C into triacylglycerol relative to phospholipid decreased in hyperthyroid and increased in hypothyroid livers. Cholesterol synthesis was similar in all perfusions. 7. During oleate infusion, the cytosolic redox state, as indicated by the perfusate [lactate]/[pyruvate] ratio, was decreased in hyperthyroid and increased in hypothyroid livers. No change in [3-hydroxybutyrate]/[acetoacetate] was detected. 8. The importance of relating the concentration of plasma non-esterified fatty acids to the interpretation of metabolic data obtained under differing thyroid status is emphasized. PMID:7306071

  9. Vanadate-induced toxicity towards isolated perfused rat livers: the role of lipid peroxidation.

    PubMed

    Younes, M; Strubelt, O

    1991-02-11

    The toxic potential of sodium orthovanadate towards isolated perfused rat livers was investigated at a dose of 2 mmol/l. In livers from fasted rats, vanadate led to a release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH] and mitochondrial (glutamate dehydrogenase (GLDH] enzymes, an accumulation of calcium in the liver, a marked depletion of hepatic glutathione and an enhanced release of it into the perfusate, as well as an augmented formation and release of thiobarbituric acid-reactive material by the liver. Furthermore, a marked inhibition of oxygen consumption was observed. Vanadate-induced vasoconstriction resulted in a progressive decrease in perfusate flow rate. Control experiments with similarly reduced flow rates led to a comparable reduction in oxygen consumption. GPT and LDH release and hepatic glutathione depletion were also evident, though to a lesser extent than in the presence of vanadate, but no increase in GLDH release, in tissue calcium content or TBA-reactive material in the liver or the perfusate were observed. Thus, indirect toxic effects due to a reduced flow rate contribute only partly to vanadate hepatotoxicity and do not affect mitochondrial integrity. Omission of calcium from the perfusate did not prevent hepatotoxic responses to vanadate, although less calcium was present in the treated livers than in the control organs, indicating that calcium influx is not involved in vanadate-induced hepatotoxicity in the intact organ, in contrast to isolated hepatocytes. Feeding the animals, resulting in an activation of anaerobic energy conservation reactions, strongly attenuated vanadate hepatotoxicity indicating that the energetic status of the liver is the main target of vanadate. Superoxide dismutase did not affect the hepatotoxic responses of livers from fasted rats towards vanadate, while allopurinol and deferrioxamine inhibited lipid peroxidation and hepatotoxicity due to vanadate. The strong correlation

  10. Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats.

    PubMed

    Keshavarzian, A; Choudhary, S; Holmes, E W; Yong, S; Banan, A; Jakate, S; Fields, J Z

    2001-11-01

    Only 30% of alcoholics develop liver disease (ALD) suggesting that additional factors are needed. Endotoxin is one such factor, but its etiology is unclear. Since the gut is the main source of endotoxin, we sought to determine whether an increase in intestinal permeability (leaky gut) is required for alcohol-induced endotoxemia and liver injury and whether the gut leakiness is preventable. For 10 weeks, rats received by gavage increasing alcohol doses (to 8 g/kg/day) and either oats (10 g/kg) or chow b.i.d. Intestinal permeability was then assessed by urinary excretion of lactulose and mannitol. Liver injury was evaluated histologically, biochemically (liver fat content), and by serum aminotransferase. Alcohol caused gut leakiness that was associated with both endotoxemia and liver injury. Oats prevented these changes. We conclude that chronic gavage of alcohol in rats is a simple experimental model that mimics key aspects of ALD, including endotoxemia and liver injury, and can be useful to study possible mechanisms of endotoxemia in ALD. Since preventing the gut leakiness by oats also prevented the endotoxemia and ameliorated liver damage in rat, our results suggest that alcohol-induced gut leakiness 1) may cause alcohol-induced endotoxemia and liver injury and 2) may be the critical cofactor in the 30% of alcoholics who develop ALD. Further studies are needed to determine whether ALD in humans can be prevented by preventing alcohol-induced gut leakiness, studies that should lead to the development of useful therapeutic agents for the prevention of ALD.

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

    SciTech Connect

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

    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. Regulation of the Conversion of Thyroxine to Triiodothyronine in the Perfused Rat Liver

    PubMed Central

    Jennings, Anthony S.; Ferguson, Duncan C.; Utiger, Robert D.

    1979-01-01

    This study was undertaken to determine what factors control the conversion of thyroxine (T4) to triiodothyronine (T3) in rat liver under conditions approximating those found in vivo. Conversion of T4 to T3 was studied in the isolated perfused rat liver, a preparation in which the cellular and structural integrity is maintained and that can perform most of the physiologic functions of the liver. The perfused liver readily extracted T4 from perfusion medium and converted it to T3. Production of T3 by the perfused liver was a function of the size of the liver, the uptake of T4 by the liver, and the presence of T4-5′-deiodinase activity. Production of T3 was increased by increasing the uptake of T4 by liver, which could be accomplished by increasing the liver size, by increasing the perfusate T4 concentration, or by decreasing the perfusate albumin concentration. These changes occurred without altering the conversion of T4 to T3. The liver had a large capacity for extracting T4 and for T4-5′-deiodination to T3, which was not saturated at a T4 concentration of 60 μg/dl. Production of T3 was decreased by inhibiting hepatic T4-5′-deiodinase with propylthiouracil, which decreased T3 production by decreasing the conversion of T4 to T3. Propylthiouracil did not alter hepatic T4 uptake. Fasting resulted in a progressive decrease in hepatic T4 uptake to 42% of control levels by the 3rd d of fasting; this was accompanied by a proportionate decrease in T3 production. The rate of conversion of T4 to T3 did not change during fasting. When T4 uptake in 2-d-fasted rat livers was raised to levels found in fed rats by increasing the perfusate T4 concentration from 10 to 30 μg/dl, T3 production returned to normal. Again, no change in the rate of conversion of T4 to T3 was observed. These results indicate that the decreased hepatic T3 production during fasting primarily results from decreased hepatic uptake of T4, rather than from changes in T4-5′-deiodinase activity. Thus

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

    PubMed Central

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

    2015-01-01

    Background: The regenerating gene (Reg), encoding lectin-related protein, was originally isolated from a rat regenerating pancreatic islets. Interleukin-22 (IL-22), a recently identified cytokine, is produced by Th 17 cells and natural killer cells. Both of them have been shown to play an important role in controlling tissue repair. But, it is unclear whether the IL-22/Reg axis is involved in liver regeneration and the improvement of liver function in a rat model of acute liver injury. Aims: We investigated the expression levels of Reg proteins after IL-22 stimulation in a rat model of acute liver injury, and estimated the effects of Reg proteins ameliorating acute liver injury. Methods: Western blot was used to measure the expressions of Reg I, Reg III, Reg IV proteins after treatment with recombinant lentivirus IL-22. At the same time, the expression levels of TB, ALT, AST, endotoxin (ETM), superoxide dismutase (SOD), malondialdehyde (MDA) were detected by related reagents. Results: In a rat model of acute liver injury, the expression levels of Reg I, Reg III, Reg IV proteins were increased after treatment with IL-22 recombinant lentivirus compared with treatment with lentivirus-empty vector, especially, Reg IV protein expression. Meanwhile, treatment with IL-22 recombinant lentivirus reduced serum levels of TB, ALT, AST, ETM, and decreased MAD levels in rat liver tissues, but increased SOD levels in rat liver tissues. Conclusion: IL-22 stimulation enhanced the expressions of Reg proteins in liver cell, especially, Reg IV protein, and ameliorated liver injury in a rat model of acute liver injury. Reg protein, especially Reg IV protein, might act as a biological mediator of immune cell-derived IL-22 in the recovering mechanism of liver injury. PMID:25785121

  14. Morphological and biochemical assessment of the liver response to excess dietary copper in Fischer 344 rats.

    PubMed

    Aburto, E M; Cribb, A E; Fuentealba, I C; Ikede, B O; Kibenge, F S; Markham, F

    2001-04-01

    The aim of this study was to determine the amount of excess dietary copper (Cu) necessary to experimentally induce liver lesions characteristic of Cu-associated disease in Fischer 344 rats. Male weanling Fischer 344 rats of uniform age were divided into 6 groups (n = 5) and fed a rodent diet containing 18 (control), 750, 1000, 1250, 1500, and 2000 microg/g Cu added as CuSO4. Rats were euthanized after 3 months on the experimental diets and their livers processed for histology, histochemistry, Cu analysis (by atomic absorption spectrophotometry), and quantification of malondialdehyde (MDA) by the thiobarbituric acid reaction. Hepatic Cu levels were significantly higher (P < 0.01) in rats receiving over 1000 microg/g Cu compared to the controls (means for each diet: control = 4.8 microg/g, 750 microg/g Cu = 39.6 microg/g, 1000 microg/g Cu = 111.2 microg/g, 1250 microg/g Cu = 389 microg/g, 1500 microg/g Cu = 509.4 microg/g, and 2000 microg/g Cu = 766 microg/g). Histological lesions increased gradually according to the level of dietary Cu. Significant morphologic changes (necrosis, portal inflammation, hyaline remnants) and reduced growth rate occurred in rats receiving over 1250 microg/g Cu. However, no significant differences were found for MDA levels between groups. The present study demonstrates that compared to other species, very high levels of excess dietary Cu are needed to induce significant liver injury in Fischer 344 rats. Increased MDA content was not detected in rats with morphologic evidence of liver damage, suggesting that lipid peroxidation may not play a major role in this model of Cu toxicity.

  15. Membrane binding sites for plasma lipoproteins on endosomes from rat liver.

    PubMed Central

    Jaeckle, S; Brady, S E; Havel, R J

    1989-01-01

    Highly purified endosomal membranes from rat liver, enriched in receptors for a number of macromolecules taken up into hepatocytes via the coated pit/endosome/lysosome pathway [including the receptor for low density lipoproteins (LDL)], were used to characterize binding sites for lipoproteins containing apolipoprotein E. In endosomal membranes from livers of estradiol-treated rats, in which LDL receptors are induced manyfold, two high-affinity binding sites were found for two apolipoprotein E-rich lipoproteins: very low density beta-lipoproteins (beta-VLDL) from cholesterol-fed rabbits and rat chylomicron remnants. One of these sites, binding to which is inhibited by 30 mM EDTA, appears identical to the LDL receptor by ligand and immunoblotting and other characteristics. The other site, highly resistant to EDTA, does not bind LDL. Binding to the EDTA-resistant site, however, is readily inhibited by heparin (as is the LDL receptor) and also by antisera prepared against rat or bovine LDL receptor. The distribution of the EDTA-resistant site among early endosomes, late endosomes, and endosome-derived receptor-recycling membranes is similar to that of the LDL receptor and other recycling receptors. The LDL receptor was present in endosomal membranes from livers of untreated rats at about 10% of the level found in membranes from estradiol-treated rats, but the EDTA-resistant site was barely detectable. No saturable binding of beta-VLDL that could not be inhibited by antisera to the LDL receptor could be detected in endosomal membranes from livers of either untreated or estradiol-treated rats. The EDTA-resistant site may be a modified form of the LDL receptor that recognizes apolipoprotein E but not the B apolipoprotein of LDL. Alternatively, it may be a distinct receptor sharing immunological determinants with the LDL receptor, specialized for the endocytosis of certain lipoproteins containing apolipoprotein E, including chylomicron remnants. Images PMID:2538819

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

    PubMed

    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.

  17. Increased iron deposition in rat liver fibrosis induced by a high-dose injection of dimethylnitrosamine.

    PubMed

    Guo, Limei; Enzan, Hideaki; Hayashi, Yoshihiro; Miyazaki, Eriko; Jin, Yulan; Toi, Makoto; Kuroda, Naoto; Hiroi, Makoto

    2006-12-01

    Using a developed rat model of hepatic necrosis and subsequent fibrosis induced by a high-dose intraperitoneal injection of dimethylnitrosamine (DMN), we studied iron deposition and expression of transforming growth factor-beta(1) (TGF-beta(1)) during the development of persistent liver fibrosis. Rats were sacrificed at several timepoints from 6 h to 10 months post-injection and the livers were examined for iron content and distribution, and for expression of alpha-smooth muscle actin, ED-1, TGF-beta(1), and collagen (alpha(2))I. Morphologic evidence of acute submassive hemorrhagic necrosis peaked at 36 h; on day 3 the residual parenchyma contained activated hepatic stellate cells (HSCs) and necrotic areas contained numerous macrophages; and on day 5, necrotic tissues and erythrocytes had been phagocytosed and macrophages contained abundant iron deposits. From days 7 to 10, iron-laden macrophages and activated HSCs (myofibroblasts) populated the fibrous septa in parallel. From week 2 to month 10, closely arranged macrophages and myofibroblasts were found in central-to-central bridging fibrotic tissue. TGF-beta(1) was strongly detected in both macrophages and HSCs during development of liver fibrosis. Our data suggest that increased iron deposition may be involved in the initiation and perpetuation of rat liver fibrosis. Iron-laden macrophages may influence HSCs through the action of TGF-beta(1) in DMN-induced liver fibrosis.

  18. Beneficial effects of fluvastatin on liver microcirculation and regeneration after massive hepatectomy in rats.

    PubMed

    Tokunaga, Takuya; Ikegami, Toru; Yoshizumi, Tomoharu; Imura, Satoru; Morine, Yuji; Shinohara, Hisamitsu; Shimada, Mitsuo

    2008-11-01

    Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (alpha-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells.

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

    SciTech Connect

    Hirayama, H.; Xu, X.; Pang, K.S. )

    1989-08-01

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

  20. Effect of zinc supplementation on type 2 diabetes parameters and liver metallothionein expressions in Wistar rats.

    PubMed

    Wang, Xue; Li, Hongyan; Fan, Zhe; Liu, Ya

    2012-12-01

    Zinc is a trace metal and acts as an active component of various enzymes. Zinc deficiency has been suggested to be associated with the development of diabetes. The present study investigated the role of zinc supplementation on prevention of diabetic conditions. A double-disease model mimicking hyperlipidemia and type 2 diabetes was created by applying high-fat diet and streptozotocin (STZ) to Wistar rats. We demonstrated that zinc supplementation improved symptoms of diabetes such as polydipsia and increased serum level of high-density lipoprotein cholesterol, indicating that zinc supplementation has a potential beneficial effect on diabetic conditions. The level of maldondialdehyde (MDA), an oxidative stress marker, was reduced in liver by zinc supplementation in high fat-fed rats with or without STZ injection. Meanwhile, we observed an increase in the expression of metallothioneins (MTs) in liver of rats treated with zinc. This suggests that the induction of MTs in liver, which has been shown to be important in scavenging free radicals, could be one of the underlying mechanisms of zinc supplementation on reducing MDA levels in liver. Finally, we found that zinc levels in liver were increased while there was no change in serum zinc levels, indicating that local zinc level might be a critical factor for the induction of MTs. Also, the level of MTs could potentially be an index of zinc bioavailability. Taken together, these results suggest that both zinc and MT could play an important role in balancing nutrition and metabolism to prevent diabetic development.

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

    PubMed

    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 (CCl4)-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl4 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 CCl4-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 CCl4 -induced liver damage in rats.

  2. Low G preconditioning reduces liver injury induced by high +Gz exposure in rats

    PubMed Central

    Shi, Bin; Feng, Zhi-Qiang; Li, Wen-Bing; Zhang, Hong-Yi

    2015-01-01

    AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats. METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na+-K+-ATPase were determined in hepatic tissue. RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na+-K+-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation. CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats. PMID:26074692

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

    PubMed

    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.

  4. Erythropoietin administration increases splenic erythroferrone protein content and liver TMPRSS6 protein content in rats.

    PubMed

    Gurieva, Iuliia; Frýdlová, Jana; Rychtarčíková, Zuzana; Vokurka, Martin; Truksa, Jaroslav; Krijt, Jan

    2017-02-28

    Erythroferrone (ERFE) and TMPRSS6 are important proteins in the regulation of iron metabolism. The objective of the study was to examine splenic ERFE and liver TMPRSS6 synthesis in rats treated with a combination of iron and erythropoietin (EPO). EPO was administered to female Wistar rats at 600U/day for four days, iron-pretreated rats received 150mg of iron before EPO treatment. Content of ERFE and TMPRSS6 proteins was determined by commercial antibodies. Iron pretreatment prevented the EPO-induced decrease in hepcidin expression. Content of phosphorylated SMAD 1,5,8 proteins was decreased in the liver by both EPO and iron plus EPO treatment. Fam132b expression in the spleen was increased both by EPO and iron plus EPO treatments; these treatments also significantly induced splenic Fam132a expression. ERFE protein content in the spleen was increased both by EPO and iron plus EPO to a similar extent. EPO administration increased TMPRSS6 content in the plasma membrane-enriched fraction of liver homogenate; in iron-pretreated rats, this increase was abolished. The results confirm that iron pretreatment prevents the EPO-induced decrease in liver Hamp expression. This effect probably occurs despite high circulating ERFE levels, since EPO-induced ERFE protein synthesis is not influenced by iron pretreatment.

  5. Activation of ras oncogene in aflatoxin-induced rat liver carcinogenesis.

    PubMed Central

    Sinha, S; Webber, C; Marshall, C J; Knowles, M A; Proctor, A; Barrass, N C; Neal, G E

    1988-01-01

    The presence of activated transforming genes was investigated in four primary aflatoxin-induced rat liver tumors in male Fischer rats, in two cell lines generated from such tumors, in an epithelial liver-derived nontransformed cell line, and in the latter cell line after transformation by aflatoxin B1 in vitro. When DNA extracted from these sources was transfected into NIH 3T3 cells, negative results were obtained from focus assays. Cotransfection of these DNA samples with a gene for resistance to G418, followed by selection for resistance to that antibiotic, and tumorigenicity testing in nude mice demonstrated DNA-mediated transfer of the neoplastic phenotype in all cases except for DNA from the nontransformed cell line. DNA extracted from these primary nude mouse tumors used in a secondary round of transfection with NIH 3T3 cells gave positive results in focus assays, which were conserved through succeeding rounds of transfection. By use of appropriate radiolabeled probes, activated ras oncogenes were detected in all samples. N-ras activation was detected in three of the primary rat liver tumors and both hepatoma cell lines. Ki-ras activation was detected in one primary rat liver tumor, and Ha-ras activation was detected in the cell line transformed in vitro with activated aflatoxin B1. The activated Ki-ras oncogene was further characterized by use of synthetic oligonucleotide probes and was shown to contain a G----A transition at the second nucleotide in codon 12. Images PMID:3287372

  6. Increased in vitro phosphorylation of rat liver nucleolar proteins following triiodothyronine administration.

    PubMed

    Fugassa, E; Gallo, G; Pertica, M

    1976-11-15

    It has been shown that triiodothyronine (Ta) administration to thyroidectomized rats induces an increase in the in vitro net 32P uptake into liver nucleolar proteins. Such an increase depends on a stimulation of the nucleolus-associated protein kinase activity and not on a lower dephosphorylation rate.

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

    EPA Science Inventory

    Chloral hydrate decreases gap junction communication in rat liver epithelial cells

    Gap junction communication (GJC) is involved in controlling cell proliferation and differentiation. Connexins (Cx) that make up these junctions are composed of a closely related group of m...

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

    PubMed Central

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

    PubMed

    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.

  10. ESTIMATING CHLOROFORM BIOTRANSFORMATION IN F-344 RAT LIVER USING IN VITRO TECHNIQUES AND PHARMACOKINETIC MODELING

    EPA Science Inventory

    ESTIMATING CHLOROFORM BIOTRANSFORMATION IN F-344 RAT LIVER USING IN VITRO TECHNIQUES AND PHARMACOKINETIC MODELING

    Linskey, C.F.1, Harrison, R.A.2., Zhao, G.3., Barton, H.A., Lipscomb, J.C4., and Evans, M.V2., 1UNC, ESE, Chapel Hill, NC ; 2USEPA, ORD, NHEERL, RTP, NC; 3 UN...

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

    EPA Science Inventory

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

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

    PubMed Central

    Wong, Wei-Lun; Abdulla, Mahmood Ameen; Chua, Kek-Heng; Kuppusamy, Umah Rani; Tan, Yee-Shin; Sabaratnam, Vikineswary

    2012-01-01

    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. PMID:22649470

  13. Tissue inhibitor of metalloproteinase-1 and -2 RNA expression in rat and human liver fibrosis.

    PubMed Central

    Herbst, H.; Wege, T.; Milani, S.; Pellegrini, G.; Orzechowski, H. D.; Bechstein, W. O.; Neuhaus, P.; Gressner, A. M.; Schuppan, D.

    1997-01-01

    The remodeling of extracellular matrix during chronic liver disease may partially be attributed to altered activity of matrix metalloproteinases and their tissue inhibitors (TIMPs). Expression of TIMP-1 and -2 was studied by in situ hybridization combined with immunohistochemistry in rat (acute and chronic carbon tetrachloride intoxication and secondary biliary fibrosis) and human livers and on isolated rat hepatic stellate cells. TIMP-1 and -2 transcripts appeared in rat livers within 1 to 3 hours after intoxication, pointing to a role in the protection against accidental activation of matrix metalloproteinases, and were present at high levels in all fibrotic rat and human livers predominantly in stellate cells. TIMP-2 RNA distribution largely matched with previously reported patterns of matrix metalloproteinase-2 (72-kd gelatinase) expression, suggesting generation of a TIMP-2/matrix metalloproteinase-2 complex (large inhibitor of metalloproteinases). Isolated stellate cells expressed TIMP-1 and -2 RNA. Addition of transforming growth factor-beta 1 enhanced TIMP-1 and matrix metalloproteinase-2 RNA levels in vitro, whereas TIMP-2-specific signals were reduced, likely to result in a stoichiometric excess of matrix-metalloproteinase-2 over TIMP-2. In the context of previous demonstrations of transforming growth factor-beta 1 and matrix metalloproteinase-2 in vivo, these patterns suggest an intrahepatic environment permitting only limited matrix degradation, ultimately resulting in redistribution of extracellular matrix with relative accumulation of collagen type 1. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:9137090

  14. Messenger RNA patterns in rat liver nuclei before and after treat-ment with growth hormone.

    PubMed

    Drews, J; Brawerman, G

    1967-06-09

    Like cortisol, growth hormone enhances RNA synthesis in rat liver nuclei. However, DNA-RNA hybridization experiments show that the application of growth hormone does not stimulate the formation of new species of messenger RNA. The latter phenomenon was observed after treatment with cortisol.

  15. Tetramethylpyrazine attenuates carbon tetrachloride-caused liver injury and fibrogenesis and reduces hepatic angiogenesis in rats.

    PubMed

    Zhao, Shifeng; Zhang, Zili; Qian, Linnan; Lin, Qiuyi; Zhang, Chenxi; Shao, Jiangjuan; Zhang, Feng; Zheng, Shizhong

    2017-02-01

    Liver fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with abnormalities of angiogenesis in the liver. Capillarization of liver sinusoidal endothelial cell (LSEC) is the pivotal event during liver angiogenesis. In the current study, we sought to investigate the effect of tetramethylpyrazine (TMP) on carbon tetrachloride (CCl4)-induced liver injury and fibrosis in rats, and to further examine the molecular mechanisms of TMP-induced anti-angiogenic effect. We found that TMP significantly ameliorated histopathological feature of liver fibrosis characterized by decreased collagen deposition, hepatocyte apoptosis, and expression of biochemical indicators, such as aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Moreover, TMP appeared to play an essential role in controlling pathological angiogenesis. In addition, TMP attenuated angiogenesis by downregulation of vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGF-R2), platelet-derived growth factor-BB (PDGF-BB), and platelet-derived growth factor-β receptor (PDGF-βR), four important factors transmitting pro-angiogenic pathways. Besides, TMP inhibited LSEC capillarization in CCl4-induced liver fibrotic model with the morphological features of increasing sinusoidal fenestrae. Importantly, we found that disruption of angiogenesis is required for TMP to inhibit hepatocyte apoptosis in rats. Treatment with TMP significantly inhibited the expression of Bax, and up-regulated Bcl-2 expression. Interestingly, treatment with angiogenesis-inducer AngII dramatically eliminated the effect of TMP on Bax/Bcl-2 axis. Overall, these results provide novel perspectives to reveal the protective effect of TMP on liver, opening up the possibility of using TMP based anti-angiogenic drugs for the liver diseases.

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

    SciTech Connect

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

    1987-06-01

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

  17. Comparative studies of effects of dehydroepiandrosterone on rat and chicken liver.

    PubMed

    Bobyleva, V; Kneer, N; Bellei, M; Battelli, D; Muscatello, U; Lardy, H

    1993-01-01

    1. An attempt to identify the cause of decrease of gain in body weight during dehydroepiandrosterone (DHEA) treatment was made comparing the effects of hormone treatment on chickens and rats. 2. Chickens treated with DHEA for 7-10 days do not change their weight gain with respect to controls although their mitochondrial respiration and peroxisomal catalase (index of peroxisomal mass) were increased. 3. Liver cytosolic malic enzyme and sn-glycerol-3-phosphate dehydrogenase were depressed in chickens treated with DHEA in comparison with activities in untreated controls. DHEA treatment did not increase the activity of mitochondrial sn-glycerol 3-phosphate dehydrogenase. 4. In contrast to rat liver cytosolic sn-glycerol-3-phosphate dehydrogenase this enzyme in chicken liver was inactive with NADPH.

  18. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.

  19. Molecular cloning of cDNA for rat liver gap junction protein

    PubMed Central

    1986-01-01

    An affinity-purified antibody directed against the 27-kD protein associated with isolated rat liver gap junctions was produced. Light and electron microscopic immunocytochemistry showed that this antigen was localized specifically to the cytoplasmic surfaces of gap junctions. The antibody was used to select cDNA from a rat liver library in the expression vector lambda gt11. The largest cDNA selected contained 1,494 bp and coded for a protein with a calculated molecular mass of 32,007 daltons. Northern blot analysis indicated that brain, kidney, and stomach express an mRNA with similar size and homology to that expressed in liver, but that heart and lens express differently sized, less homologous mRNA. PMID:3013898

  20. Effect of insulin and glucose on the activity of insulin-degrading enzymes in rat liver.

    PubMed

    Jurcovicová, J; Németh, S; Vigas, M

    1977-09-01

    The degradation of insulin by insulin protease and glutathion-insulin transhydrogenase (glutathioneproteindisulphide oxidoreductase--EC 1.8.4.2, GIT) was measured in rat liver either after replacing food and water by 15% glucose solution, or after daily insulin administration 8 U daily for 3 days or after fasting. The breakdown of radioiodinated insulin was followed by measuring the increase of TCA soluble radioactivity during incubation of cell fractions with 125I insulin at 37 degrees C. The highest GIT activity was observed in liver microsomes of rats after glucose feeding and after insulin administration, whereas enzyme activity of fasted animals did not essentially differ from corresponding values of normally fed controls. The insulin protease in cytosol of liver cells remained unchanged after these procedures. The important role of GIT in insulin degradation seems to be conclusively demonstrated.

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

    PubMed Central

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

    1980-01-01

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

  2. Saikokeishito Extract Exerts a Therapeutic Effect on alpha-Naphthylisothiocyanate-Induced Liver Injury in Rats through Attenuation of Enhanced Neutrophil Infiltration and Oxidative Stress in the Liver Tissue.

    PubMed

    Ohta, Yoshiji; Kongo-Nishimura, Mutsumi; Hayashi, Takahiro; Kitagawa, Akira; Matsura, Tatsuya; Yamada, Kazuo

    2007-01-01

    We examined whether Saikokeishito extract (TJ-10), a traditional Japanese herbal medicine, exerts a therapeutic effect on alpha-naphthylisothiocyanate (ANIT)-induced liver injury in rats through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. In rats treated once with ANIT (75 mg/kg, i.p.), liver injury with cholestasis occurred 24 h after treatment and progressed at 48 h. When ANIT-treated rats orally received TJ-10 (0.26, 1.3 or 2.6 g/kg) at 24 h after the treatment, progressive liver injury with cholestasis was significantly attenuated at 48 h after the treatment at the dose of 1.3 or 2.6 g/kg. At 24 h after ANIT treatment, increases in hepatic lipid peroxide and reduced glutathione contents and myeloperoxidase activity occurred with decreases in hepatic superoxide dismutase and glutathione reductase activities. At 48 h after ANIT treatment, these changes except for reduced glutathione were enhanced with decreases in catalase, Se-glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. TJ-10 (1.3 or 2.6 g/kg) post-administered to ANIT-treated rats attenuated these changes found at 48 h after the treatment significantly. These results indicate that TJ-10 exerts a therapeutic effect on ANIT-induced liver injury in rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue.

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-02-01

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

  5. Hepatoprotective effects of zingerone on carbon tetrachloride- and dimethylnitrosamine-induced liver injuries in rats.

    PubMed

    Cheong, Kyoung Ook; Shin, Dong-Su; Bak, Jeonghyeon; Lee, Changyong; Kim, Kyung Wook; Je, Nam Kyung; Chung, Hae Young; Yoon, Sik; Moon, Jeon-Ok

    2016-02-01

    In this study, we investigated the hepatoprotective and anti-fibrotic effects of zingerone, one of the active components of ginger, against carbon tetrachloride (CCl4)- and dimethylnitrosamine (DMN)-induced liver injuries in rats, respectively. Oral administration of zingerone (10 mg/kg) reduced CCl4-induced abnormalities in liver histology, serum alanine aminotransferase and aspartate aminotransferase levels, and liver malondialdehyde levels. Zingerone treatment attenuated CCl4-induced increases in inflammatory mediators, including tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase mRNA levels. Western blot analysis showed that zingerone suppressed activation of nuclear factor-kappa B (NF-κB) p65 and phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinases (MAPKs). Liver fibrosis induced by DMN (10 mg/kg, intraperitoneally) was ameliorated by administration of zingerone (10 and 20 mg/kg, orally). Zingerone treatment reduced DMN-induced elevation of hydroxyproline content and hepatic stellate cell activation. In conclusion, zingerone showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream MAPKs. Moreover, zingerone had hepatoprotective and anti-fibrotic effects against DMN-induced liver injury suggesting its usefulness in the prevention of liver inflammation and the development of hepatic fibrosis.

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

    PubMed Central

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

    2013-01-01

    Background. Researchers focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Objectives. Evaluating the hepatoprotective activity of Boesenbergia rotunda (BR) rhizome ethanolic extract on thioacetamide-induced liver cirrhosis in rats. Methods. Male Sprague-Dawley rats were intraperitoneally injected with 200 mg/kg TAA 3 times/week and daily oral administration of 250 mg/kg, 500 mg/kg of BR extract, and 50 mg/kg of the reference drug Silymarin for 8 weeks. At the end of the experiment, Masson's trichrome staining was used to measure the degree of liver fibrosis. Hepatic antioxidant enzymes (CAT and GPx), nitrotyrosine, cytochrome (P450 2E1), matrix metalloproteinase (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), and urinary 8-hydroxyguanosine were measured. Serum levels of transforming growth factor TGF-β1, nuclear transcription factor NF-κB, proinflammatory cytokine IL-6, and caspase-3 were evaluated. Serum protein expression and immunohistochemistry of proapoptotic Bax and antiapoptotic Bcl-2 proteins were measured and confirmed by immunohistochemistry of Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA). Results. BR treatment improved liver histopathology, immunohistochemistry, and biochemistry, triggered apoptosis, and inhibited cytokines, extracellular matrix proteins, and hepatocytes proliferation. Conclusion. Liver cirrhosis progression can be inhibited by the antioxidant and anti-inflammatory activities of BR ethanolic extract while preserving the normal liver status. PMID:23997791

  7. In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake.

    PubMed

    Boveris, A; Llesuy, S; Azzalis, L A; Giavarotti, L; Simon, K A; Junqueira, V B; Porta, E A; Videla, L A; Lissi, E A

    1997-09-19

    The influence of acute ethanol administration on the oxidative stress status of rat brain and liver was assessed by in situ spontaneous organ chemiluminescence (CL). Brain and liver CL was significantly increased after acute ethanol administration to fed rats, a response that is time-dependent and evidenced at doses higher than 1 g/kg. Ethanol-induced CL development is faster in liver compared with brain probably due to the greater ethanol metabolic capacity of the liver, whereas the net enhancement in brain light emission at 3 h after ethanol treatment is higher than that of the liver, which could reflect the greater susceptibility of brain to oxidative stress. The effect of ethanol on brain and liver CL seems to be mediated by acetaldehyde, due to its abolishment by the alcohol dehydrogenase inhibitor 4-methylpyrazole and exacerbation by the aldehyde dehydrogenase inhibitor disulfiram. In brain, these findings were observed in the absence of changes in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. However, the content of brain glutathione was significantly decreased by 31%, by ethanol, thus establishing an enhanced oxidative stress in this tissue.

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

    PubMed Central

    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

  9. Procedure for Decellularization of Rat Livers in an Oscillating-pressure Perfusion Device.

    PubMed

    Hillebrandt, Karl; Polenz, Dietrich; Butter, Antje; Tang, Peter; Reutzel-Selke, Anja; Andreou, Andreas; Napierala, Hendrik; Raschzok, Nathanael; Pratschke, Johann; Sauer, Igor M; Struecker, Benjamin

    2015-08-10

    Decellularization and recellularization of parenchymal organs may enable the generation of functional organs in vitro, and several protocols for rodent liver decellularization have already been published. We aimed to improve the decellularization process by construction of a proprietary perfusion device enabling selective perfusion via the portal vein and/or the hepatic artery. Furthermore, we sought to perform perfusion under oscillating surrounding pressure conditions to improve the homogeneity of decellularization. The homogeneity of perfusion decellularization has been an underestimated factor to date. During decellularization, areas within the organ that are poorly perfused may still contain cells, whereas the extracellular matrix (ECM) in well-perfused areas may already be affected by alkaline detergents. Oscillating pressure changes can mimic the intraabdominal pressure changes that occur during respiration to optimize microperfusion inside the liver. In the study presented here, decellularized rat liver matrices were analyzed by histological staining, DNA content analysis and corrosion casting. Perfusion via the hepatic artery showed more homogenous results than portal venous perfusion did. The application of oscillating pressure conditions improved the effectiveness of perfusion decellularization. Livers perfused via the hepatic artery and under oscillating pressure conditions showed the best results. The presented techniques for liver harvesting, cannulation and perfusion using our proprietary device enable sophisticated perfusion set-ups to improve decellularization and recellularization experiments in rat livers.

  10. Schisandra chinensis Prevents Alcohol-Induced Fatty Liver Disease in Rats

    PubMed Central

    Park, Hyoung Joon; Lee, Soo-Jung; Song, Yuno; Jang, Sun-Hee; Ko, Yeoung-Gyu; Kang, Suk Nam; Chung, Byung Yeoup; Kim, Hong-Duck; Kim, Gon-Sup

    2014-01-01

    Abstract Schisandra chinensis (SC), a traditional herbal medicine, has been prescribed for patients suffering from various liver diseases, including hepatic cancer, hypercholesterolemia, and CCl4-induced liver injury. We investigated whether SC extract has a protective effect on alcohol-induced fatty liver and studied its underlying mechanisms. Rats were fed with ethanol by intragastric administration every day for 5 weeks to induce alcoholic fatty liver. Ethanol treatment resulted in a significant increase in alanine aminotransferase, aspartate aminotransferase, and hepatic triglyceride (TG) levels and caused fatty degeneration of liver. Ethanol administration also elevated serum TG and total cholesterol (TC) and decreased high-density lipoprotein (HDL) cholesterol levels. However, after administration of ethanol plus SC extracts, the ethanol-induced elevation in liver TC and TG levels was reversed. Elevation in serum TG was not observed after treatment with SC. Moreover, compared with the ethanol-fed group, the rats administered ethanol along with SC extracts for 5 weeks showed attenuated fatty degeneration and an altered lipid profile with decreased serum TC and TG, and increased HDL cholesterol levels. Chronic ethanol consumption did not affect peroxisome proliferator-activated receptor γ (PPARγ) levels, but it decreased PPARα and phospho-AMP-activated protein kinase (AMPK) levels in the liver. However, SC prevented the ethanol-induced decrease in PPARα expression and induced a significant decrease in sterol regulatory element-binding protein-1 expression and increase in phospho-AMPK expression in rats with alcoholic fatty liver. SC administration resulted in a significant decrease in intracellular lipid accumulation in hepatocytes along with a decrease in serum TG levels, and it reversed fatty liver to normal conditions, as measured by biochemical and histological analyses. Our results indicate that the protective effect of SC is accompanied by a

  11. Gold nanoparticles induce DNA damage in the blood and liver of rats

    NASA Astrophysics Data System (ADS)

    Cardoso, Eria; Londero, Eduardo; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rohr, Paula; da Silva, Luciano; Andrade, Vanessa M.; da Silva Paula, Marcos Marques

    2014-11-01

    The potential of gold nanoparticles (GNPs) for use in different biological applications has led to a strong interest in the study of their possible deleterious effects in biological systems and how these effects may be mitigated. This study was undertaken to investigate the effects of the acute and chronic administration of GNPs with mean diameters of 10 and 30 nm on deoxyribonucleic acid (DNA) damage in the blood and liver of adult rats. For the acute administration, Wistar adult rats received a single intraperitoneal injection of either GNPs or a saline solution. For the chronic administration, Wistar adult rats received a daily single injection of the same GNPs or saline solution for 28 days. Twenty-four hours after either the single (acute) or final injection (chronic), the rats were euthanised by decapitation, and the blood and liver were isolated for the evaluation of DNA damage. In this study, we demonstrated that the acute and chronic administration of GNPs 10 and 30 nm in size increased the frequency of DNA damage and the damage index in the blood and liver of adult rats. These findings suggest that the DNA damage may be caused by oxidative stress, which occurred regardless of the type of administration and GNP size.

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

    SciTech Connect

    Albornoz, L.; Jones, J.M.; Crutchfield, C.; Veech, R.L. Univ. of Arkansas Medical Sciences, Little Rock )

    1991-03-11

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

  13. A rat liver foci promotion study with 50-Hz magnetic fields.

    PubMed

    Rannug, A; Holmberg, B; Mild, K H

    1993-08-01

    To investigate the possible tumor-promoting effect of magnetic fields (MF), we have performed two liver foci bioassays in rats which were exposed to MF at four flux density levels (0.5 microT, 5 microT, 0.05 mT, and 0.5 mT). The MF were generated in exposure equipment consisting of copper coils surrounding racks with animal cages and giving homogenous horizontal 50-Hz magnetic fields. Rats previously submitted to partial hepatectomy and diethylnitrosamine treatment were exposed to MF for 12 weeks. Exposed and control rats were kept in separate rooms. As a positive control phenobarbital (PB) was administered for 12 weeks. The number, area, and volume of foci expressing gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST-p) were evaluated. The body weight gains and relative liver weights of MF-exposed rats were not different as compared to control rats. There was a slight increase in GGT-staining foci, but not in GST-p-staining foci, in the groups exposed to flux densities of 0.5 microT and 0.05 mT compared to the control group in the first experiment. The number of both GGT- and GST-p-staining foci in the livers of all MF-exposed groups were, however, within the control range when the results of the two experiments were considered together.

  14. Proinflammatory Liver and Antiinflammatory Intestinal Mediators Involved in Portal Hypertensive Rats

    PubMed Central

    Aller, Maria Angeles; Vara, Elena; Garcia, Cruz; Palma, Maria Dolores; Arias, Jorge L.; Nava, Maria Paz; Arias, Jaime

    2005-01-01

    Proinflammatory (TNF-α, IL-1β, and NO) and antiinflammatory (IL-10, CO) levels were assayed in serum, liver, and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n = 11) and one group with a triple stenosing ligation of the portal vein (n = 23) after 28 days of evolution. In one subgroup of portal hypertensive rats, portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF-α, IL-1β, and IL-10 were quantified in liver and ileum by enzyme-linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL-10 (0.30 ± 0.12 versus 0.14 ± 0.02 pmol/mg protein; P < .01) is associated with a liver production of both proinflammatory mediators (TNF-α: 2 ± 0.21 versus 1.32 ± 0.60 pmol/mg protein; P < .05, IL-1β: 19.17 ± 2.87 versus 5.96 ± 1.84 pmol/mg protein; P = .005, and NO: 132.10 ± 34.72 versus 61.05 ± 8.30 nmol/mL; P = .005) and an antiinflammatory mediator (CO: 6.49 ± 2.99 versus 3.03 ± 1.59 pmol/mL; P = .005). In short-term prehepatic portal hypertension a gut-liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications, could be proposed. PMID:16030393

  15. Endogenous carbon monoxide downregulates hepatic cystathionine-γ-lyase in rats with liver cirrhosis

    PubMed Central

    GUO, SHI-BIN; DUAN, ZHI-JUN; WANG, QIU-MING; ZHOU, QIN; LI, QING; SUN, XIAO-YU

    2015-01-01

    The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) pathway in cirrhotic rat livers. The rats were allocated at random into four groups: Sham, cirrhosis, cobalt protoporphyrin (CoPP) and zinc protoporphyrin IX (ZnPP). The expression of hepatic CSE mRNA was evaluated using a quantitative polymerase chain reaction, while CSE protein expression was determined using immunohistochemical analysis. Hematoxylin and eosin staining was performed for the histological evaluation of liver fibrosis. The levels of H2S, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and carboxyhemoglobin (COHb) in the arterial blood were determined, in addition to the portal vein pressure. The mRNA and protein expression levels of hepatic CSE and the serum levels of H2S were significantly decreased in the cirrhosis group compared with those in the sham group (P<0.05). Compared with the cirrhosis group, rats in the ZnPP group had significantly lower levels of serum ALT, AST and TBIL, arterial COHb and hepatic fibrosis, while hepatic CSE expression and the production of H2S were significantly increased (P<0.05). The CoPP group exhibited decreased hepatic CSE expression and H2S production, but aggravated hepatic function and fibrosis (P<0.05). In conclusion, the H2S/CSE pathway is involved in the formation of liver cirrhosis and serves a crucial function in protecting liver cells against the progression of liver fibrosis. Endogenous CO downregulates hepatic CSE mRNA and protein expression and the production of H2S in rats with liver cirrhosis. PMID:26668593

  16. Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

    PubMed

    Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

    2014-08-01

    Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups

  17. Non-alcoholic steatohepatitis and preneoplastic lesions develop in the liver of obese and hypertensive rats: suppressing effects of EGCG on the development of liver lesions.

    PubMed

    Kochi, Takahiro; Shimizu, Masahito; Terakura, Daishi; Baba, Atsushi; Ohno, Tomohiko; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2014-01-01

    Non-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of glutathione S-transferase placental form (GST-P)-positive (GST-P(+)) foci, a hepatic preneoplastic lesion, in SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP-ZF) obese and hypertensive rats. Male 7-week-old SHRSP-ZF rats and control non-obese and normotensive WKY rats were fed a high fat diet and received intraperitoneal injections of carbon tetrachloride twice a week for 8weeks. The rats were also provided tap water containing 0.1% EGCG during the experiment. SHRSP-ZF rats presented with obesity, insulin resistance, dyslipidemia, an imbalance of adipokines in the serum, and hepatic steatosis. The development of GST-P(+) foci and liver fibrosis was markedly accelerated in SHRSP-ZF rats compared to that in control rats. Additionally, in SHRSP-ZF rats, RAS was activated and inflammation and oxidative stress were induced. Administration of EGCG, however, inhibited the development of hepatic premalignant lesions by improving liver fibrosis, inhibiting RAS activation, and attenuating inflammation and oxidative stress in SHRSP-ZF rats. In conclusion, obese and hypertensive SHRSP-ZF rats treated with a high fat diet and carbon tetrachloride displayed the histopathological and pathophysiological characteristics of NASH and developed GST-P(+) foci hepatic premalignant lesions, suggesting the model might be useful for the evaluation of NASH-related liver tumorigenesis. EGCG might also be able to prevent NASH-related liver fibrosis and tumorigenesis.

  18. Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats.

    PubMed

    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 < .05) blood glucose at 10 (75.6 mg/dL vs 64.0 ± 4.8 mg/dL) minutes and 20 (72.4 mg/dL vs 58.6 ± 4.0 mg/dL) minutes after glucose dose and greater area under the curve (4302.3 mg∙dL(-1)∙min(-1) vs 3763.4 ± 263.6 mg∙dL(-1)∙min(-1)) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < .05) livers (9.3%, 7.1% body weight vs 4.8% ± 0.2% body weight) and elevated (P < .05) liver triacylglycerol (216.0, 130.0 mg/g vs 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. 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.

  19. Agaricus blazei Murill extract abrogates CCl4-induced liver injury in rats.

    PubMed

    Wu, Ming-Fang; Hsu, Yu-Ming; Tang, Ming-Chu; Chen, Hsueh-Chin; Chung, Jing-Gung; Lu, Hsu-Feng; Lin, Jing-Pin; Tang, Nou-Ying; Yeh, Chun; Yeh, Ming-Yang

    2011-01-01

    Agaricus blazei Murill (ABM) is enriched with polysaccharides, lipids, vitamins, fibers and minerals. Many studies have shown that ABM possesses immune-enhancing and anti-tumor effects. However, little is known about its protective effects on liver function. We employed carbon tetrachloride (CCl(4)) to induce hepatic fibrosis in a rat model to examine the protective effects of ABM on the liver in this study. The experiments included non-treatment control, CCl(4)-only control, and treatment with 200 mg and 2,000 mg of ABM extracts (per kilogram rat weight). All groups other than the non-treatment control were treated with intraperitoneal injections of CCl(4) twice a week. Experimental and control rats were tube-fed with experimental ABM extracts or double-distilled water, respectively, on the remaining four days each week. The whole experimental protocol lasted 8 weeks; blood and liver samples were collected for biochemical and tissue histochemical analysis. Plasma alanine aminotransferase and aspartate aminotransferase, and the activities of the anti-oxidative enzymes glutathione peroxidase, superoxide dismutase and catalase in the liver were measured. We found that high-dose ABM treatment reduced hepatic necrosis and fibrosis caused by CCl(4) in comparison with the CCl(4) control group. ALT and AST activities in the sera collected from ABM-treated rats were lower than those in the CCl(4) control rats. These results suggested that ABM extract was capable of either enhancing liver recovering from CCl(4) damage or attenuating CCl(4) toxicity. Results of anti-oxidative enzyme activity analysis showed no apparent differences among ABM-treated groups and CCl(4) control groups, indicating that removal of free radicals does not explain the protective/recovery effects observed in this study.

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

    PubMed Central

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

    2014-01-01

    The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements’ bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver. PMID:24403828

  1. Effects of Antrodia camphorata on alcohol clearance and antifibrosis in livers of rats continuously fed alcohol.

    PubMed

    Wu, Min-Tze; Tzang, Bor-Show; Chang, Yuan-Yen; Chiu, Chih-Hsien; Kang, Wen-Yu; Huang, Chia-Hsin; Chen, Yi-Chen

    2011-04-27

    Alcoholic fatty liver disease (AFLD) is the result of an excessive or chronic consumption of alcohol. Nine male Wistar rats per group were randomly assigned to one of the following drinking treatments: a 20% (w/w) alcohol solution (ALC); a 20% (w/w) alcohol solution cotreated with 0.25 g silymarin/kg BW/day; or a 20% (w/w) alcohol solution cotreated with 0.025 g Niuchangchih ( Antrodia camphorata )/kg BW/day for 4 weeks. Rats with cotreatments of silymarin or Niuchangchih had smaller (p < 0.05) relative liver size, less (p < 0.05) liver lipid accumulation, and lower (p < 0.05) liver damage indices [aspartate aminotransferase (AST) and alkaline phosphatase (ALP) values]. In the regulation of alcohol metabolism, the lower serum alcohol level was observed only in alcohol-fed rats supplemented with Niuchangchih. Meanwhile, cotreatment of silymarin or Niuchangchih increased (p < 0.05) CAT and ALDH activities but did not (p > 0.05) affect ADH and CYP2E1 expressions, which accelerate alcohol metabolism in the body. Additionally, neither silymarin nor Niuchangchih (p > 0.05) influenced serum/hepatic MMP-2 activities and NF-κB, AP1, and α-SMA gene expressions, but serum/hepatic MMP-9 activities and TNF-α, KLF-6, and TGF-β1 gene expressions of alcohol-fed rats were down-regulated (p < 0.05) by silymarin or Niuchangchih, which also could explain the lower liver damage observed in rats chronically fed alcohol.

  2. Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats.

    PubMed

    Kubota, Masatoshi; Watanabe, Reiko; Yamaguchi, Miki; Hosojima, Michihiro; Saito, Akihiko; Fujii, Mikio; Fujimura, Shinobu; Kadowaki, Motoni

    2016-10-01

    We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P<0·05). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P<0·01). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P<0·05), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl-β-d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P<0·01). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P<0·01). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.

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

    PubMed

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

    2014-02-01

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

  4. Induction of fatty acid synthesis by pravastatin sodium in rat liver and primary hepatocytes.

    PubMed

    Fujioka, T; Tsujita, Y; Shimotsu, H

    1997-06-11

    We examined the effect of pravastatin sodium (pravastatin), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on fatty acid synthesis in rat liver. The repeated administration of pravastatin to rats at 250 mg/kg for 7 days led to a 2.8-fold increase in fatty acid synthesis in the liver. The diurnal change of fatty acid synthesis was not affected by the treatment. Hepatic fatty acid synthase activity was increased 3.2-fold, while acetyl-CoA carboxylase activity was not changed by the repeated administration of pravastatin. In rat hepatocytes, the incubation with 2 microg/ml pravastatin for 24 h increased fatty acid synthase activity 1.5-fold, as well as HMG-CoA reductase activity 2.8-fold. These results suggest that HMG-CoA reductase inhibitors might increase fatty acid synthesis in vivo through the induction of hepatic fatty acid synthase.

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

    PubMed

    Nemeth, S; Tigranian, R A

    1983-01-01

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

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

    PubMed

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

    1988-03-01

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

  7. Troxerutin protects the isolated perfused rat liver from a possible lipid peroxidation by coumarin.

    PubMed

    Adam, B S; Pentz, R; Siegers, C P; Strubelt, O; Tegtmeier, M

    2005-01-01

    For more than 40 years coumarin has been successfully used in the therapy of chronic venous insufficiency (CVI). The occurrence of liver injuries is rather rare and happens predominantly when doses are administered which are significantly higher than necessary for therapeutical use. Such effects caused by high coumarin concentrations are reproducible in in vivo experiments in mice or rats and HepG2-cells. In order to characterize the mechanism of liver injuries, the isolated perfused rat liver has been chosen as model. Since liver injuries are quite rare, if coumarin is used in co-medication with troxerutin, a possible protective influence of this flavonoid has been investigated. In concentrations higher than 4 mmol/l, coumarin alone is effective in the isolated perfused rat liver. Then the release of the enzymes alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increases and there is a measurable reduction of perfusion flow, oxygen consumption and rate of bile secretion. Additionally, the concentrations of hepatic adenosine triphosphate (ATP) and oxidized and total glutathione (GSSG/GSH) decrease. In the livers of fasting animals, coumarin doubles the concentration of hepatic malondialdehyde (MDA). This effect cannot be detected if troxerutin is added. In general, troxerutin reduces the concentration of all coumarin-metabolites in the perfusate and bile and changes the ratio of the main metabolites, coumarin: 3-hydroxycoumarin: 7-hydroxycoumarin. An analysis of the metabolic steps also shows that the amount of coumarin eliminated via faeces does not stem from absorbed coumarin, because the amount of orally applied coumarin detectable in the bile is less than 1%. The study demonstrates that troxerutin has hepatoprotective properties and thus protects the liver from a possible lipid peroxidation caused by coumarin. However, it is necessary to point out that these adverse effects caused by coumarin can be detected only in very high concentrations

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

    SciTech Connect

    Elferink, M.G.L. Olinga, P.; Draaisma, A.L.; Merema, M.T.; Bauerschmidt, S.; Polman, J.; Schoonen, W.G.; Groothuis, G.M.M.

    2008-06-15

    The microarray technology, developed for the simultaneous analysis of a large number of genes, may be useful for the detection of toxicity in an early stage of the development of new drugs. The effect of different hepatotoxins was analyzed at the gene expression level in the rat liver both in vivo and in vitro. As in vitro model system the precision-cut liver slice model was used, in which all liver cell types are present in their natural architecture. This is important since drug-induced toxicity often is a multi-cellular process involving not only hepatocytes but also other cell types such as Kupffer and stellate cells. As model toxic compounds lipopolysaccharide (LPS, inducing inflammation), paracetamol (necrosis), carbon tetrachloride (CCl{sub 4}, fibrosis and necrosis) and gliotoxin (apoptosis) were used. The aim of this study was to validate the rat liver slice system as in vitro model system for drug-induced toxicity studies. The results of the microarray studies show that the in vitro profiles of gene expression cluster per compound and incubation time, and when analyzed in a commercial gene expression database, can predict the toxicity and pathology observed in vivo. Each toxic compound induces a specific pattern of gene expression changes. In addition, some common genes were up- or down-regulated with all toxic compounds. These data show that the rat liver slice system can be an appropriate tool for the prediction of multi-cellular liver toxicity. The same experiments and analyses are currently performed for the prediction of human specific toxicity using human liver slices.

  9. Erythropoietin reduces ischemia-reperfusion injury after liver transplantation in rats.

    PubMed

    Schmeding, Maximilian; Hunold, Gerhard; Ariyakhagorn, Veravoorn; Rademacher, Sebastian; Boas-Knoop, Sabine; Lippert, Steffen; Neuhaus, Peter; Neumann, Ulf P

    2009-07-01

    Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. One-hundred-and-twenty Wistar rats were used: 60 recipients received liver transplantation following donor organ treatment (60 donors) with either 1000 IU rHuEpo or saline injection (controls) into portal veins (cold ischemia 18 h, University of Wisconsin (UW) solution). Recipients were allocated to two groups, which either received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Animals were sacrificed at defined time-points (2, 4.5, 24, 48 h and 7 days postoperatively) for analysis of liver enzymes, histology [hematoxylin-eosin (HE) staining, periodic acid Schiff staining (PAS)], immunostaining [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Hypoxyprobe] and real-time polymerase chain reaction (RT-PCR) of cytokine mRNA (IL-1, IL-6). Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) values were significantly reduced among the epo-treated animals 24 and 48 h after liver transplantation (LT). The TUNEL and Hypoxyprobe analyses as well as necrotic index evaluation displayed significant reduction of apoptosis and necrosis in rHuEpo-treated graft livers. Erythropoietin reduces ischemia-reperfusion injury after orthotopic liver transplantation in rats.

  10. In vivo quantitation of the rat liver's ability to eliminate endotoxin from portal vein blood

    SciTech Connect

    Yamaguchi, Y.; Yamaguchi, K.; Babb, J.L.; Gans, H.

    1982-12-01

    The in vivo uptake of endotoxin by the liver from portal vein blood was assessed during a single passage through the liver. /sup 51/Cr labeled and unlabeled endotoxin were infused in different amounts into the femoral vein of three groups of lead-sensitized rats: a nonoperated, a sham-operated, and a surgically created reversed Eck fistula (REF) group. Whereas in the former two the infused endotoxin encounters the lung as the first filter organ, the liver performs this function in the latter experimental model. The mortality rates observed in control and sham-operated, lead-sensitized rats were found to correlate closely and reproducibly to the degree of endotoxemia. This assay was then applied to determine the amount of endotoxin eliminated by the liver by establishing, in the REF rat, the amounts of endotoxin that escaped hepatic clearance. The capacity of the liver to eliminate endotoxin from portal vein blood during a single passage increases as the portal vein endotoxin level rises; it approaches a maximum, suggesting that endotoxin's interaction with the Kupffer cells conforms to classical saturation kinetics. A Lineweaver-Burk plot prepared from these data indicates that the maximal in vivo capacity of the liver to remove endotoxin from portal vein blood approximates 1.5 micrograms/gm liver/hr. Data obtained with the use of radiolabeled endotoxin corroborate the information obtained with the bioassay technique. Endotoxin eliminated by the Kupffer cells in these quantities is slowly disintegrated; 4 hr after termination of the endotoxin infusion, less than 4% of the radiolabel is found in the urine and none in the bile. These observations indicate that the Kupffer cell's functional capacity to sequester and detoxify endotoxin is extensive and far exceeds the requirements imposed by physiological and most pathological conditions.

  11. Phosphatidic acid metabolism in rat liver cell nuclei.

    PubMed

    Gaveglio, Virginia L; Pasquaré, Susana J; Giusto, Norma M

    2013-04-02

    The aim of the present research was to analyze the pathways for phosphatidic acid metabolism in purified nuclei from liver. Lipid phosphate phosphatase, diacylglycerol lipase, monoacylglycerol lipase and PA-phospholipase type A activities were detected. The presence of lysophosphatidic acid significantly reduced DAG production while sphingosine 1-phoshate and ceramide 1-phosphate reduced MAG formation from PA. Using different enzymatic modulators (detergents and ions) an increase in the PA metabolism by phospholipase type A was observed. Our findings evidence an active PA metabolism in purified liver nuclei which generates important lipid second messengers, and which could thus be involved in nuclear processes such as gene transcription.

  12. Impairment of the liver insulin receptor autoactivation cascade at full-term pregnancy in the rat.

    PubMed

    Martinez, C; Molero, J C; Ruiz, P; Del Arco, A; Andres, A; Carrascosa, J M

    1995-10-15

    Partially purified liver insulin receptors from full-term pregnant rats show decreased autophosphorylation rates if compared with receptors from virgins. We studied the molecular mechanism of this phenomenon, looking at possible structural and functional changes of several domains. The ATP-binding domain seems to be unaltered in receptors from pregnant rats since Km for ATP was similar to that observed in virgins. In contrast, the Vmax. is decreased some 45%, suggesting changes in the kinase domain. Truncation of a fragment of 10 kDa from the C-terminal tail does not normalize the kinase activity in receptors from pregnant rats, suggesting that this domain is not involved in the inhibitory regulation. Treatment with alkaline phosphatase increases the [32P]Pi incorporation into receptors from pregnant rats; however, the autophosphorylation remains lower than that observed in virgin rats. Tryptic phosphopeptide maps of phosphorylated receptors show that the same phosphopeptides are present in receptors from virgin and pregnant rats. However, the progression through the autoactivation cascade in the kinase domain is impaired in receptors from pregnant rats. Differences in the cleavage by trypsin at the two alternative sites in the kinase domain were observed, indicating possible structural changes in receptors from pregnant rats that could be related to the impairment of the autoactivation cascade. Integrity of the alpha- and beta-subunits, as well as differential expression of the two receptor isotypes, were shown to be unaltered. We conclude that (1) the decreased autophosphorylation rate of the liver insulin receptor from pregnant rats is associated with the impairment of its autoactivation cascade, probably as a consequence of the basal Ser/Thr phosphorylation; and (2) the inhibition of the autoactivation cascade does not account for the overall inhibition of autophosphorylation observed in receptors from pregnant rats.

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

    PubMed

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

    2015-11-01

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

  14. Liver volume, as assessed by four ultrasonic crystals arranged to form a tetrahedron, decreases during anaphylactic shock in anesthetized rats.

    PubMed

    Takano, Hiromichi; Shibamoto, Toshishige; Zhang, Wei; Kurata, Yasutaka

    2010-12-01

    We determined the hepatic volume change in anaphylactic hypotension by using four ultrasonic crystals in anesthetized rats. The hepatic volume was measured with four ultrasonic crystals arranged to form a tetrahedron on the liver surface. Before in vivo experiments, using isolated perfused rat liver preparations, we compared the measured liver volume changes with the whole-liver weight changes during hepatic blood flow rate changes and venoconstriction induced by norepinephrine. The measured relative change of the tetrahedron volume (V[utc]; percentage changes of the initial volume) was closely correlated with the liver weight change (W; percentage changes of the initial liver weight): V(utc) = 0.85W - 4.11 (r² = 0.67). Then, we measured the liver weight and the tetrahedron volume during hepatic anaphylaxis in isolated perfused liver excised from the rats sensitized with ovalbumin. An injection of the antigen into the perfusate caused anaphylactic venoconstriction, liver weight loss (1.1 ± 0.3 g; 9% ± 1%), and the tetrahedron volume reduction (12% ± 4%). Finally, we measured the liver volume change during anaphylactic hypotension in anesthetized ovalbumin-sensitized rats. When the antigen was i.v. injected into anesthetized rats, along with systemic hypotension and hepatic venoconstriction, the liver tetrahedron volume decreased by 6% ± 2% from baseline. In conclusion, we established a method to measure the hepatic volume by using four ultrasonic crystals forming a tetrahedron. Using this ultrasonic crystal method, we demonstrated that liver volume decreases during anaphylactic hypotension in anesthetized rats.

  15. Dietary effects of bitter gourd oil on blood and liver lipids of rats.

    PubMed

    Noguchi, R; Yasui, Y; Suzuki, R; Hosokawa, M; Fukunaga, K; Miyashita, K

    2001-12-15

    Bitter gourd is widely used as an edible plant in Asia. In this study, we evaluated the effects of bitter gourd oil (BGO) on the blood and liver lipids of rats. Three groups of rats were given a basal diet (AIN-93G) containing 7% fat by weight. The dietary fat consisted of soybean oil (control), soybean oil + BGO (6.5:0.5, w/w; 0.5% BGO), or soybean oil + BGO (5:2, w/w; 2.0% BGO). This fat treatment gave 3.4 and 15.4% of cis(c)9,trans(t)11,t13-18:3 in the dietary fat of 0.5 and 2.0% BGO, respectively. Fatty acid analysis showed the occurrence of c9,t11-18:2 in the liver of rats fed BGO diets, whereas this conjugated linoleic acid (CLA) isomer was not detected in the liver of rats fed the control diet. Furthermore, dietary BGO decreased the concentration of 18:2n-6 and increased the concentration of 22:6n-3. The formation of the CLA isomer in the liver lipids of rats fed BGO diets could be explained by either of the following two metabolic pathways, namely, enzymatic biohydrogenation of c9,t11,t13-18:3 or enzymatic isomerization of c9,c12-18:2. The BGO diets had significantly reduced free cholesterol levels with a trend toward an increase in HDL cholesterol, but there was no significant change in the total cholesterol. The dietary BGO also affected the level of plasma hydroperoxides. A slight but significant increase in hydroperoxides was found in the rats fed 2.0% BGO. This may be attributed to the lower oxidative stability of c9,t11,t13-18:3 in BGO.

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

    PubMed

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

    2016-04-12

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

  17. Lycium barbarum polysaccharides protect rat liver from non-alcoholic steatohepatitis-induced injury

    PubMed Central

    Xiao, J; Liong, E C; Ching, Y P; Chang, R C C; Fung, M L; Xu, A M; So, K F; Tipoe, G L

    2013-01-01

    Background: Lycium barbarum polysaccharides (LBPs) are antioxidant and neuroprotective derivative from Wolfberry. However, whether LBP has a protective effect in non-alcoholic steatohepatitis (NASH)-induced hepatic injury is still unknown. Objective: We aimed to study the possible hepatoprotective effects and mechanisms of LBP on a diet-induced NASH rat model. Methods and Design: In this study, female rats were fed a high-fat diet to induce NASH with or without an oral 1 mg kg−1 LBP feeding daily for 8 weeks. After 8 weeks, blood serum and liver samples from each rat were subjected to histological analysis, biochemical and molecular measurements. Results: Compared with control rats, NASH rats showed typical NASH features including an increase in liver injury, lipid content, fibrosis, oxidative stress, inflammation and apoptosis. In contrast, NASH+LBP-co-treated rats showed (1) improved histology and free fatty acid levels; (2) re-balance of lipid metabolism; (3) reduction in profibrogenic factors through the TGF-β/SMAD pathway; (4) improved oxidative stress through cytochrome P450 2E1-dependent pathway; (5) reduction in hepatic pro-inflammatory mediators and chemokines production; and (6) amelioration of hepatic apoptosis through the p53-dependent intrinsic and extrinsic pathways. The preventive effects of LBP were partly modulated through the PI3K/Akt/FoxO1, LKB1/AMPK, JNK/c-Jun and MEK/ERK pathways and the downregulation of transcription factors in the liver, such as nuclear factor-κB and activator protein-1. Conclusion: LBP is a novel hepatoprotective agent against NASH caused by abnormal liver metabolic functions. PMID:23877747

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

    PubMed Central

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

    2016-01-01

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

  19. Cognitive flexibility but not cognitive coordination is affected in rats with toxic liver failure.

    PubMed

    Wesierska, Malgorzata; Klinowska, Hanna D; Adamska, Iwona; Fresko, Inez; Sadowska, Joanna; Albrecht, Jan

    2006-07-15

    Hepatic encephalopathy (HE), a consequence of liver damage, is associated with cognitive deficits. In this study, behavioral activity, non-associative learning, associative memory, cognitive coordination and flexibility were investigated in rats with subclinical HE evoked by thioacetamide treatment. Non-associative learning was studied in the open field (OF) set up in 12 HE and 8 saline-injected control rats (C). Memory was examined in spatial place avoidance tasks in 10 HE and 10 C rats. The Room+ Arena- task involved the selection of distal room stimuli from irrelevant arena stimuli (i.e. intramaze cues and/or self-motion information), which engages processes of cognitive coordination. Following the Room+ Arena- training, cognitive flexibility of rats was tested in the Arena+ place avoidance condition, which demands the previously ignored stimuli from arena. In the OF test HE and control rats behaved similar. They displayed high activity in the first block of each session and this pattern was stable. In both groups of rats darkness enhanced locomotor activity in comparison to light only in the first block. The HE and C rats avoided the to-be-avoided place in the Room+ Arena- task, whereas only HE rats were affected in the Arena+ task. In conclusion, these results demonstrate cognitive inflexibility in HE rats. We suggest that (1) the behavioral changes in the TAA model are typical of subclinical HE and (2) test for cognitive flexibility may be modified towards a routine use in patients with subclinical HE.

  20. The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

    PubMed

    Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

    2016-01-01

    We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity.

  1. Mechanistic study on liver tumor promoting effects of flutamide in rats.

    PubMed

    Tawfeeq, Mohammad Monir; Hayashi, Hitomi; Shimamoto, Keisuke; Suzuki, Kazuhiko; Shibutani, Makoto; Inokuma, Hisashi; Mitsumori, Kunitoshi

    2012-03-01

    Flutamide (FLU), a nonsteroidal anti-androgen, is used for the treatment of prostate cancer but is also a cytochrome P450 (CYP) 1A inducer. Some CYP1A inducers are known to exert hepatocellular tumor-promoting activities in rodents, and reactive oxygen species (ROS) produced by CYP1A1 induction via a metabolism of FLU is probably involved in the liver tumor promotion. In the present study, to clarify the possible liver tumor promoting effect of FLU, a two-stage liver carcinogenesis assay was performed using male F344 rats. Rats received an intraperitoneal (ip) injection of 200 mg/kg body weight of N-diethylnitrosamine (DEN) and fed a diet containing 0, 0.1 or 0.2% FLU for 6 weeks. After 2 weeks of DEN treatment, all rats were subjected to two-thirds partial hepatectomy. Animals were killed 8 weeks after ip injection of DEN. Immunohistochemically, the number and area of glutathione S-transferase placental form (GST-P)-positive foci significantly increased in the liver of rats given 0.2% FLU as compared with the control. Ki-67-positive cell ratio also increased in rats given FLU at both concentrations. ROS generation in the microsomal fraction and production of thiobarbituric acid-reactive substance [TBARS] and 8-hydroxy-2'-deoxyguanosine (8-OHdG) content in the liver did not increase in any of the FLU-treated groups. The results of microarray and real-time RT-PCR revealed that phase 1 drug-metabolizing enzymes such as CYP1A1, Ugt1a61 and Nqo1 and phase II drug-metabolizing enzymes such as Yc2, Akr1b7, Akr1b8, Akr1b10, Aldh1a1, Gpx2 and Me1 were up-regulated in rats treated with FLU. In addition, the MAPK pathway family-related genes such as Prkcα, Mek1, Rafb, Myc, Mek2, Raf1 and Egfr were also up-regulated in FLU-treated groups. The results of the present study indicate that FLU is a CYP1A inducer but does not cause any production of microsomal ROS in the liver and suggest that microsomal ROS is not involved in the liver tumor promoting effect of FLU.

  2. Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat.

    PubMed Central

    Dejong, C H; Deutz, N E; Soeters, P B

    1993-01-01

    Renal glutamine uptake and subsequent urinary ammonia excretion could be an important alternative pathway of ammonia disposal from the body during liver failure (diminished urea synthesis), but this pathway has received little attention. Therefore, we investigated renal glutamine and ammonia metabolism in midly hyperammonemic, portacaval shunted rats and severely hyperammonemic rats with acute liver ischemia compared to their respective controls, to investigate whether renal ammonia disposal from the body is enhanced during hyperammonemia and to explore the limits of the pathway. Renal fluxes, urinary excretion, and renal tissue concentrations of amino acids and ammonia were measured 24 h after portacaval shunting, and 2, 4, and 6 h after liver ischemia induction and in the appropriate controls. Arterial ammonia increased to 247 +/- 22 microM after portacaval shunting compared to controls (51 +/- 8 microM) (P < 0.001) and increased to 934 +/- 54 microM during liver ischemia (P < 0.001). Arterial glutamine increased to 697 +/- 93 microM after portacaval shunting compared to controls (513 +/- 40 microM) (P < 0.01) and further increased to 3781 +/- 248 microM during liver ischemia (P < 0.001). In contrast to controls, in portacaval shunted rats the kidney net disposed ammonia from the body by diminishing renal venous ammonia release (from 267 +/- 33 to -49 +/- 59 nmol/100 g body wt per min) and enhancing urinary ammonia excretion from 113 +/- 24 to 305 +/- 52 nmol/100 g body wt per min (both P < 0.01). Renal glutamine uptake diminished in portacaval shunted rats compared to controls (-107 +/- 33 vs. -322 +/- 41 nmol/100 g body wt per min) (P < 0.01). However, during liver ischemia, net renal ammonia disposal from the body did not further increase (294 +/- 88 vs. 144 +/- 101 nmol/100 g body wt per min during portacaval shunting versus liver ischemia). Renal glutamine uptake was comparable in both hyperammonemic models. These results indicate that the rat kidney plays

  3. Quantitative Estimation of the Amount of Fibrosis in the Rat Liver Using Fractal Dimension of the Shape of Power Spectrum

    NASA Astrophysics Data System (ADS)

    Kikuchi, Tsuneo; Nakazawa, Toshihiro; Furukawa, Tetsuo; Higuchi, Toshiyuki; Maruyama, Yukio; Sato, Sojun

    1995-05-01

    This paper describes the quantitative measurement of the amount of fibrosis in the rat liver using the fractal dimension of the shape of power spectrum. The shape of the power spectrum of the scattered echo from biotissues is strongly affected by its internal structure. The fractal dimension, which is one of the important parameters of the fractal theory, is useful to express the complexity of shape of figures such as the power spectrum. From in vitro experiments using rat liver, it was found that this method can be used to quantitatively measure the amount of fibrosis in the liver, and has the possibility for use in the diagnosis of human liver cirrhosis.

  4. Dynamic expression of extracellular signal-regulated kinase in rat liver tissue during hepatic fibrogenesis

    PubMed Central

    Zhang, Xiao-Lan; Liu, Jin-Ming; Yang, Chang-Chun; Zheng, Yi-Lin; Liu, Li; Wang, Zhan-Kui; Jiang, Hui-Qing

    2006-01-01

    AIM: To investigate whether extracellular signal-regulated kinase 1 (ERK1) is activated and associated with hepatic stellate cell (HSC) proliferation in fibrotic rat liver tissue. METHODS: Rat hepatic fibrosis was induced by bile duct ligation (BDL). Histopathological changes were evaluated by hematoxylin and eosin staining, and Masson’s trichrome method. ERK1 mRNA in rat liver tissue was determined by reverse transcription-polymerase chain reaction, while the distribution of ERK1 was assessed by immunohistochemistry. ERK1 protein was detected by Western blotting analysis. The number of activated HSCs was quantified after alpha smooth muscle actin (α-SMA) staining. RESULTS: With the development of hepatic fibrosis, the positive staining cells of α-SMA increased obviously, and mainly resided in the portal ducts. Fiber septa and perisinuses were accompanied with proliferating bile ducts. The positive staining areas of the rat livers in model groups 1-4 wk after ligation of common bile duct (12.88% ± 2.63%, 22.65% ± 2.16%, 27.45% ± 1.86%, 35.25% ± 2.34%, respectively) were significantly larger than those in the control group (5.88% ± 1.46%, P < 0.01). With the development of hepatic fibrosis, the positive cells of ERK1 increased a lot, and were mainly distributed in portal ducts, fiber septa around the bile ducts, vascular endothelial cells and perisinusoidal cells. Western blotting analysis displayed that the expression of ERK1 and ERK2 protein was up-regulated during the model course, and its level was the highest 4 wk after operation, being 3.9-fold and 7.2-fold higher in fibrotic rat liver than in controls. ERK1 mRNA was expressed in normal rat livers as well, which was up-regulated two days after BDL and reached the highest 4 wk after BDL. The expression of ERK1 was positively correlated with α-SMA expression (r = 0.958,P < 0.05). CONCLUSION: The expression of ERK1 protein and mRNA is greatly increased in fibrotic rat liver tissues, which may play a

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

    PubMed

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

    2017-03-21

    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. This article is protected by copyright. All rights reserved.

  6. Maternal high-fat-diet programs rat offspring liver fatty acid metabolism.

    PubMed

    Seet, Emily L; Yee, Jennifer K; Jellyman, Juanita K; Han, Guang; Ross, Michael G; Desai, Mina

    2015-06-01

    In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD-1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD-1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD-1 protein abundance and alters the liver C16 desaturase pathway.

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

    PubMed Central

    Mei, Nan; Guo, Lei; Liu, Ruqing; Fuscoe, James C; Chen, Tao

    2007-01-01

    Background Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats. Results Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a P-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail. Conclusion The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks

  8. Successful 20-hour rat liver preservation with chlorpromazine in sodium lactobionate sucrose solution.

    PubMed

    Tokunaga, Y; Wicomb, W N; Concepcion, W; Nakazato, P; Collins, G M; Esquivel, C O

    1991-07-01

    We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing through the portal vein at the time of transplantation were 145 +/- 20 IU/L (mean +/- SEM) in the controls, 525 +/- 78 IU/L in UW, 492 +/- 44 IU/L in SLS, 290 +/- 39 IU/L in SLS + chlorpromazine, 1 mg/L, 290 +/- 11 IU/L in SLS + chlorpromazine, 10 mg/L. The values for the SLS + chlorpromazine were significantly lower than for SLS and UW (p less than 0.05). The pH of the effluent was 7.10 +/- 0.10 in controls, 6.42 +/- 0.12 in UW, 6.64 +/- 0.18 in SLS, and 7.07 +/- 0.02 in SLS + chlorpromazine, 1 mg/L and 10 mg/L. The pH drop was significantly greater in the groups without chlorpromazine (p less than 0.01). This study shows that superior rat liver preservation was achieved with a simplified lactobionate solution containing sodium as the principal cation, sucrose in place of raffinose, and omitting the colloid and several of the other UW components. The addition of low concentrations of chlorpromazine further enhanced the effectiveness of this solution, without the need for donor pretreatment.

  9. Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

    PubMed Central

    Reichen, J; Egger, B; Ohara, N; Zeltner, T B; Zysset, T; Zimmermann, A

    1988-01-01

    We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver. PMID:3198765

  10. SIMPLE MACHINE PERFUSION SIGNIFICANTLY ENHANCES HEPATOCYTE YIELDS OF ISCHEMIC AND FRESH RAT LIVERS.

    PubMed

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3 hour room temperature (20±2°C) machine perfusion protocol to treat non-premedicated livers exposed to 1 hour of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers, and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Further, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized.

  11. Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers

    PubMed Central

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E.; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L.; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3-h room temperature (20 ± 2°C) machine perfusion protocol to treat nonpremedicated livers exposed to 1 h of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated, and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Furthermore, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized. PMID:25431743

  12. Kava feeding in rats does not cause liver injury nor enhance galactosamine-induced hepatitis.

    PubMed

    DiSilvestro, Robert A; Zhang, Wenyi; DiSilvestro, David J

    2007-07-01

    Kava, like a number of herbals, has been associated with causing liver damage based on limited evidence. In contrast, the present study found that in rats, 3 mo feedings of two types of kava extracts (an acetone extract and an ethanol extract of the Samoan kava cultivar Ava Laau) at three different doses (31.25, 62.5 and 133 mg/kg diet) produced no liver injury based on serum markers of liver damage (sorbitol dehydrogenase activities, bile acid concentrations, and beta-glucuronidase activities) and serum lipid peroxide readings. In fact, for some measurements and some kava doses, the injury marker readings were below control values. Moreover, for these same parameters, kava feeding did not enhance the effects of the hepatotoxin galacatosamine (500 mg/kg ip); some kava doses even showed modest protection against liver injury. Liver histology analysis showed no signs of kava causing or enhancing liver injury. Thus, this study does not support the concept that kava produces or aggravates liver injury.

  13. IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver transplantation

    PubMed Central

    Mosbah, I B; Zaouali, M A; Martel, C; Bjaoui, M; Abdennebi, H B; Hotter, G; Brenner, C; Roselló-Catafau, J

    2012-01-01

    Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality. PMID:22402603

  14. Induction of rat liver tumor using the Sleeping Beauty transposon and electroporation.

    PubMed

    Park, June-Shine; Kim, Bae-Hwan; Park, Sung Goo; Jung, Sun Young; Lee, Do Hee; Son, Woo-Chan

    2013-05-10

    The Sleeping Beauty (SB) transposon system has been receiving much attention as a gene transfer method of choice since it allows permanent gene expression after insertion into the host chromosome. However, low transposition frequency in higher eukaryotes limits its use in commonly-used mammalian species. Researchers have therefore attempted to modify gene delivery and expression to overcome this limitation. In mouse liver, tumor induction using SB introduced by the hydrodynamic method has been successfully accomplished. Liver tumor in rat models using SB could also be of great use; however, dose of DNA, injection volume, rate of injection and achieving back pressure limit the use of the hydrodynamics-based gene delivery. In the present study, we combined the electroporation, a relatively simple and easy gene delivery method, with the SB transposon system and as a result successfully induced tumor in rat liver by directly injecting the c-Myc, HRAS and shp53 genes. The tumor phenotype was determined as a sarcomatoid carcinoma. To our knowledge, this is the first demonstration of induction of tumor in the rat liver using the electroporation-enhanced SB transposon system.

  15. Effects of twelve months ethanol feeding on rat liver metabolic activity.

    PubMed

    Biewald, J; Bromme, H J; Nilius, R; Langner, J

    1999-03-01

    Thirty male Wistar rats were fed with 15% ethanol (V/V) for one year. Thirty other male animals were the control group. To determine the possible metabolic disturbances caused by chronic ethanol feeding in blood we measured in blood metabolic parameters, and in a liver perfusion assay the hepatic insulin clearance and hepatic urea production in these animals. Between the ethanol-fed and the control animals there were significant differences in the following parameters: blood insulin concentration (47 vs. 2 microU/ml) and activities of amino acid transferases in liver homogenates at the end of the perfusion experiments (ASAT, 5950 vs. 70; ALAT, 3632 vs. 93 U/l). The other parameters were still normal in the ethanol-fed animals. Thus in these experiments after 12 months of 15% (V/V) ethanol feeding the rats still showed only a state of beginning metabolic disturbances in the liver. The results are discussed under consideration of the formation of acetaldehyde protein adducts in all rat organs investigated, namely, liver, kidney, heart and skeleton muscle, gut and spleen.

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

    PubMed

    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.

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

    PubMed Central

    Deming, Li; Ziwei, Li; Xueqiang, Guo; Cunshuan, Xu

    2015-01-01

    Epidermal growth factor (EGF) is an important factor for healing after tissue damage in diverse experimental models. It plays an important role in liver regeneration (LR). The objective of this experiment is to investigate the methylation variation of 10 CpG sites in the Egf promoter region and their relevance to Egf expression during rat liver regenera- tion. As a follow up of our previous study, rat liver tissue was collected after rat 2/3 partial hepatectomy (PH) during the re-organization phase (from days 14 to days 28). Liver DNA was extracted and modified by sodium bisulfate. The methylation status of 10 CpG sites in Egf promoter region was determined using bisulfite sequencing polymerase chain reaction (PCR), as BSP method. The results showed that 3 (sites 3, 4 and 9) out of 10 CpG sites have strikingly methylation changes during the re-organization phase compared to the regeneration phase (from 2 hours to 168 hours, P=0.002, 0.048 and 0.018, respectively). Our results showed that methylation modification of CpGs in the Egf promoter region could be restored to the status before PH operation and changes of methylation didn’t affect Egf mRNA expression during the re-organization phase. PMID:26464832

  18. Identification of homeobox genes expressed during the process of rat liver regeneration after partial hapatectomy

    SciTech Connect

    Mizuta, Ikuko; Ogasawara, Naotake; Yoshikawa, Hiroshi; Sakoyama, Yasuhiko

    1996-02-01

    Homeobox (HBox) genes are well-known to be involved in development and differentiation. To ascertain a role of HBox genes in the process of liver regeneration, we identified HBox genes expressed at various times after partial hepatectomy in rats (at 0 hr, 1 hr, 2 days, and 4 days) by using reverse transcription-polymerase chain reaction (RT-PCR), cloning, and sequencing techniques. By the competitive RT-PCR method using generic primers, expression levels of HBox genes in regenerating livers were estimated at as low as only 0.4-2% of that in 14-day embryonic liver; however, we identified multiple HBox genes at different stages. Comparing sets of HBox genes identified at different stages, we could find two candidates of stage specifically expressed HBox genes (one rat caudal-related gene, RCdx-3, stimulated at 1 hr, and one rat Hox gene, RHoxB5, repressed after hepatectomy) and continuous expression of five Hox genes (RHoxAl, A4, A5, B2, and B3) before and after hepatectomy. These HBox genes are considered to correlate with the process of liver regeneration. 36 refs., 6 figs., 2 tabs.

  19. Ex vivo expansion of circulating CD34+ cells enhances the regenerative effect on rat liver cirrhosis

    PubMed Central

    Nakamura, Toru; Koga, Hironori; Iwamoto, Hideki; Tsutsumi, Victor; Imamura, Yasuko; Naitou, Masako; Masuda, Atsutaka; Ikezono, Yu; Abe, Mitsuhiko; Wada, Fumitaka; Sakaue, Takahiko; Ueno, Takato; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Asahara, Takayuki; Torimura, Takuji

    2016-01-01

    Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34+ cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34+ cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34+ cells were injected via the spleen. After 7 days, CD34+ cells were effectively expanded in a serum-free culture medium. Expanded CD34+ cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34+ cells increased compared with nonexpanded CD34+ cells. Expanded CD34+ cell transplantation reduced liver fibrosis, with a decrease of αSMA+ cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34+ cells over non-expanded CD34+ cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34+ cells and aggravated liver fibrosis. These findings suggest that expanded CD34+ cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. PMID:27162932

  20. Effect of Alocasia indica Tuber Extract on Reducing Hepatotoxicity and Liver Apoptosis in Alcohol Intoxicated Rats

    PubMed Central

    Bhattacharya, Koushik; Mukherjee, Soumya

    2014-01-01

    The possible protective role of ethanolic extract of A. indica tuber (EEAIT) in hepatotoxicity and apoptosis of liver caused by alcohol in rats was investigated. Treatment of rats with alcohol (3 g ethanol per kg body weight per day for 15 days intraperitoneally) produced marked elevation of liver biomarkers such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT), and total bilirubin levels which were reduced by EEAIT in a dose-dependent manner. Furthermore, EEAIT improved antioxidant status (MDA, NO, and GSH) and preserved hepatic cell architecture. Simultaneous supplementation with EEAIT significantly restored hepatic catalase (CAT) and superoxide dismutase (SOD) activity levels towards normal. The studies with biochemical markers were strongly supported by the histopathological evaluation of the liver tissue. EEAIT also attenuated apoptosis and necrosis features of liver cell found in immunohistochemical evaluation. HPLC analysis of the extract showed the presence of three major peaks of which peak 2 (RT: 33.33 min) contains the highest area (%) and UV spectrum analysis identified it as flavonoids. It is therefore suggested that EEAIT can provide a definite protective effect against chronic hepatic injury caused by alcohol in rats, which may mainly be associated with its antioxidative effect. PMID:24977149

  1. Effect of Alocasia indica tuber extract on reducing hepatotoxicity and liver apoptosis in alcohol intoxicated rats.

    PubMed

    Pal, Swagata; Bhattacharjee, Ankita; Mukherjee, Sandip; Bhattacharya, Koushik; Mukherjee, Soumya; Khowala, Suman

    2014-01-01

    The possible protective role of ethanolic extract of A. indica tuber (EEAIT) in hepatotoxicity and apoptosis of liver caused by alcohol in rats was investigated. Treatment of rats with alcohol (3 g ethanol per kg body weight per day for 15 days intraperitoneally) produced marked elevation of liver biomarkers such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT), and total bilirubin levels which were reduced by EEAIT in a dose-dependent manner. Furthermore, EEAIT improved antioxidant status (MDA, NO, and GSH) and preserved hepatic cell architecture. Simultaneous supplementation with EEAIT significantly restored hepatic catalase (CAT) and superoxide dismutase (SOD) activity levels towards normal. The studies with biochemical markers were strongly supported by the histopathological evaluation of the liver tissue. EEAIT also attenuated apoptosis and necrosis features of liver cell found in immunohistochemical evaluation. HPLC analysis of the extract showed the presence of three major peaks of which peak 2 (RT: 33.33 min) contains the highest area (%) and UV spectrum analysis identified it as flavonoids. It is therefore suggested that EEAIT can provide a definite protective effect against chronic hepatic injury caused by alcohol in rats, which may mainly be associated with its antioxidative effect.

  2. Evaluation of 2-year-old intrasplenic fetal liver tissue transplants in rats.

    PubMed

    Lupp, Amelie; Danz, Manfred; Müller, Dieter

    2003-01-01

    Liver cell transplantation into host organs like the spleen may possibly provide a temporary relief after extensive liver resection or severe liver disease or may enable treatment of an enzyme deficiency. With time, however, dedifferentiation or malignant transformation of the ectopically transplanted cells may be possible. Thus, in the present study syngenic fetal liver tissue suspensions were transplanted into the spleen of adult male rats and evaluated 2 years thereafter in comparison to orthotopic livers for histopathological changes and (as markers for preneoplastic transformation) for cytochrome P450 (P450) and glutathione S-transferase (GST) isoform expression. Because inducibility of P450 and GST isoforms may be changed in preneoplastic foci, prior to sacrifice animals were additionally treated either with beta-naphthoflavone, phenobarbital, dexamethasone, or the respective solvent. In the 2-year-old grafts more than 70% of the spleen mass was occupied by the transplant. The transplanted hepatocytes were arranged in cord-like structures. Also few bile ducts were present. Morphologically, no signs of malignancy were visible. With all rats, transplant recipients as well as controls, however, discrete nodular structures were seen in the livers. Due to age, both livers and transplants displayed only a low P450 2B1 and 3A2 and GST class alpha and mu isoform expression. No immunostaining for P450 1A1 was visible. At both sites, beta-naphthoflavone, phenobarbital, or dexamethasone treatment enhanced P450 1A1, P450 2B1 and 3A2, or P450 3A2 expression, respectively. No immunostaining for GST class pi isoforms was seen in the transplants. The livers of both transplant recipients and control rats, however, displayed GST pi-positive foci, corresponding to the nodular structures seen histomorphologically. Compared to the surrounding tissue, these foci also exhibited a more pronounced staining for GST class alpha and mu isoforms and a stronger inducibility of the P450 1A

  3. Activated neutrophils injure the isolated, perfused rat liver by an oxygen radical-dependent mechanism.

    PubMed Central

    Dahm, L. J.; Schultze, A. E.; Roth, R. A.

    1991-01-01

    Under certain circumstances, segmented neutrophils (PMNs) injure extrahepatic tissue by releasing toxic oxygen species and degradative enzymes. The authors used an isolated, perfused rat liver preparation to determine whether PMNs might injure the liver. Livers from fasted rats were perfused with Krebs-Ringer bicarbonate buffer (pH 7.4) containing 3% bovine serum albumin (BSA) in a recirculating system. Rat peritoneal PMNs (4 x 10(8] or vehicle (Hank's balanced salt solution [HBSS], pH 7.35) were added, and liver injury was assessed 90 minutes later by release of alanine aminotransferase (ALT) into the perfusion medium and histopathologic analysis of liver sections. Perfusion of livers receiving only HBSS for 90 minutes resulted in a small increase in ALT activity in the perfusion medium but did not significantly alter histologic features of liver sections. Addition of unstimulated PMNs did not increase further the ALT activity and, with the exception of vascular neutrophilia, did not significantly change the histomorphology compared with controls. When PMNs activated with a combination of phorbol myristate acetate (PMA, 31 ng/ml) and lithocholate (100 mumol/l [micromolar]) were added to the perfusion system, however, livers released greater amounts of ALT than those perfused with PMA, lithocholate, and HBSS. Activated PMNs caused a transient reduction in flow of perfusion medium that lasted approximately 5 to 15 minutes. Liver sections had multifocal to coalescing foci of moderate to severe, acute hepatocellular necrosis associated with the areas of intense sinusoidal neutrophilia. In addition a second type of lesion was observed and was characterized by triangular foci of necrosis located adjacent to periportal regions of sinusoids or portal veins containing neutrophilic thrombi. These lesions were void of PMNs and were consistent with infarcts. A combination of superoxide dismutase and catalase added to the perfusion medium (500 U/ml each) prevented the

  4. Modifying influence of swine-serum-induced liver fibrosis on development of preneoplastic lesions in rat liver.

    PubMed

    Wada, S; Kato, T; Mutai, M; Ozaki, K; Yamaguchi, S; Kim, D J; Baba-Toriyama, H; Asamoto, M; Ito, N; Tsuda, H

    1996-03-01

    Modifying effects of fibrosis or a cirrhotic state, caused by treatment with swine serum (SS), on the induction of preneoplastic focal lesions were assessed in a rat medium-term liver bioassay model for the detection of environmental carcinogens, in which the test compound is administered during the promotion phase after initiation with diethylnitrosamine. In experiment I, repeated intraperitoneal administration of SS concomitantly with the hepatopromoting agent deoxycholic acid (DCA) or phenobarbital (PB) resulted in a cirrhotic state and a significant increase in the number or size of preneoplastic glutathione S-transferase placental form (GST-P)-positive liver cell foci as compared to the corresponding DCA or PB alone groups. In experiment II, SS was given prior to commencement of the same medium-term bioassay system, in which a known hepatopromoting agent, DCA, 17-alpha-ethynylestradiol, or 2-acetylaminofluorene, was applied. In this case, the liver did not show obvious cirrhotic change and, rather than any enhancement, slight inhibition of promotion occurred. The results indicate that a coexisting, but not a pre-existing, cirrhotic condition acts to increase growth pressure on GST-P+ preneoplastic foci, and suggest that concomitant administration of SS with the promoting agent could be applied to improve the sensitivity of the assay protocol.

  5. Stereological characterization of dry alpine snow for microwave remote sensing

    NASA Technical Reports Server (NTRS)

    Davis, Robert E.; Dozier, Jeff

    1989-01-01

    A persistent problem in investigations of electromagnetic properties of snow, from reflectance at visible wavelengths to emission and backscattering in the microwave, has been the proper characterization of the snow's physical properties. It is suggested that the granular and laminar structure of snow can be measured in its aggregated state by stereology performed on sections prepared from snow specimens, and that these kinds of measurements can be incorporated into models of the electromagnetic properties. With careful sampling, anisotropy in the snow microstructure at various scales can be quantified. It is shown how stereological parameters can be averaged over orientation and optical depth for radiative transfer modeling.

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

    PubMed Central

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

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved. PMID:25075578

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

    PubMed

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

    2014-09-01

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

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

    PubMed

    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.

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

    PubMed Central

    SOBRAL, Felipe Antonio; DAGA, Henrique; RASERA, Henrique Nogueira; PINHEIRO, Matheus da Rocha; CELLA, Igor Furlan; MORAIS, Igor Henrique; MARQUES, Luciana de Oliveira; COLLAÇO, Luiz Martins

    2016-01-01

    ABSTRACT Background: Different lesions may affect the liver resulting in harmful stimuli. Some therapeutic procedures to treat those injuries depend on liver regeneration to increase functional capacity of this organ. Aim: Evaluate the effects of tranexamic acid on liver regeneration after partial hepatectomy in rats. Method: 40 rats (Rattus norvegicus albinus, Rodentia mammalia) of Wistar-UP lineage were randomly divided into two groups named control (CT) and tranexamic acid (ATX), with 20 rats in each. Both groups were subdivided, according to liver regeneration time of 32 h or seven days after the rats had been operated. The organ regeneration was evaluated through weight and histology, stained with HE and PCNA. Results: The average animal weight of ATX and CT 7 days groups before surgery were 411.2 g and 432.7 g, and 371.3 g and 392.9 g after the regeneration time, respectively. The average number of mitotic cells stained with HE for the ATX and CT 7 days groups were 33.7 and 32.6 mitosis, and 14.5 and 14.9 for the ATX and CT 32 h groups, respectively. When stained with proliferating cell nuclear antigen, the numbers of mitotic cells counted were 849.7 for the ATX 7 days, 301.8 for the CT 7 days groups, 814.2 for the ATX 32 hand 848.1 for the CT 32 h groups. Conclusion: Tranexamic acid was effective in liver regeneration, but in longer period after partial hepatectomy. PMID:27438036

  10. Reversal of chemical-induced liver fibrosis in Wistar rats by puerarin.

    PubMed

    Zhang, Shuihua; Ji, Guang; Liu, Jianwen

    2006-07-01

    Puerarin is a major isoflavonoid compound isolated from Pueraria lobata, an edible vine used widely for various medicinal purposes. It has been used for centuries in China to counteract alcohol intoxication. However, the effects of puerarin on chemical-induced liver fibrosis have not been reported. In the present study, we investigated the effects of puerarin on liver fibrosis in Wistar rats induced by alcohol plus carbon tetrachloride administration. Liver fibrosis was produced in rats by treatment with a mixture (50% alcohol, 8 g/kg per day; corn oil, 2 g/kg per day; pyrazole, 24 mg/kg per day; ig) once a day and by intraperitoneal injection of 0.25 ml/kg of a 25% solution of carbon tetrachloride in olive oil twice a week for 8 weeks. After 8 weeks, treatment with puerarin (0.4 and 0.8 g/kg ig, daily for 4 weeks) was conducted to examine its therapeutic effects. At the same time, the model group and treatment group continued to receive the chemical mixture, while the control group received saline instead of the chemical mixture. Upon pathological examination, the puerarin-treated rats significantly reversed the symptoms of liver fibrosis and other hepatic lesions. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as indexes of hepatic cell disruption, were reduced with puerarin treatment, whereas no significant effect was discovered in the levels of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities. A significant increase in apoptosis of activated hepatic stellate cell (HSC) was found by flow cytometric analysis of the hepatic tissues. And the expression of bcl-2 mRNA was down-regulated after puerarin administration. Consequently, all these results showed that puerarin could effectively reverse chemical-induced liver fibrosis in experimental rats, via the recovery of hepatic injury as well as the induction of apoptosis in activated HSC.

  11. Protective effects of garcinol on dimethylnitrosamine-induced liver fibrosis in rats.

    PubMed

    Hung, Wei-Lun; Tsai, Mei-Ling; Sun, Pei-Pei; Tsai, Chen-Yu; Yang, Chin-Chou; Ho, Chi-Tang; Cheng, An-Chin; Pan, Min-Hsiung

    2014-11-01

    Garcinol, a polyisoprenylated benzophenone derivative, mainly isolated from Garcinia indica fruit rind, has been suggested to exhibit many biological benefits including antioxidative, anti-inflammatory, and anti-tumor activities. The aim of this study is to evaluate the protective effects of garcinol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. The administration of DMN for six consecutive weeks resulted in the decrease of body weights, the elevation of serum aminotransferases, as well as histological lesions in livers. However, oral administration of garcinol remarkably inhibited the elevation of aspartate transaminase (AST) and relieved liver damage induced by DMN. Furthermore, our results revealed that garcinol not only effectively reduced the accumulation of extracellular matrix (ECM) components but also inhibited the expression of α-smooth muscle actin (α-SMA) in livers. The expression of transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad 2 and Smad 3 were also suppressed by garcinol supplementation. In conclusion, our current study suggested that garcinol exerted hepatoprotective and anti-fibrotic effects against DMN-induced liver injury in rats.

  12. Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced rat liver injury

    PubMed Central

    Liang, Bo; Guo, Xiao-Ling; Jin, Jing; Ma, Yong-Chun; Feng, Zheng-Quan

    2015-01-01

    AIM: To investigate anti-apoptotic effects of glycyrrhizic acid (GA) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury and its contributing factors. METHODS: Liver fibrosis was induced by administration of CCl4 for 8 wk. Pathological changes in the liver of rats were examined by hematoxylin-eosin staining. Collagen fibers were detected by Sirius red staining. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of cleaved caspase-3, Bax, α-SMA, connective tissue growth factor (CTGF), matrix metalloproteinase (MMP) 2 and MMP9 proteins were evaluated by western blot analysis, and α-SMA mRNA, collagen type I and III mRNA were estimated by real-time PCR. RESULTS: Treatment with GA significantly improved the pathological changes in the liver and markedly decreased the positive area of Sirius red compared with rats in the CCl4-treated group. TUNEL assay showed that GA significantly reduced the number of TUNEL-positive cells compared with the CCl4-treated group. The expression levels of cleaved caspase-3, Bax, α-SMA, CTGF, MMP2 and MMP9 proteins, and α-SMA mRNA, collagen type I and III mRNA were also significantly reduced by GA compared with the CCl4-treated group (P < 0.05). CONCLUSION: GA treatment can ameliorate CCl4-induced liver fibrosis by inhibiting hepatocyte apoptosis and hepatic stellate cell activation. PMID:25954100

  13. Ameliorating effect of Allium Sativum on high-fat diet induced fatty liver in albino rats

    PubMed Central

    Qamar, Aisha; Usmani, Ambreen; Waqar, Humera; Siddiqui, Asma; Kumar, Hemant

    2016-01-01

    Objective: To assess the hepatoprotective effect provided by fresh garlic on fatty liver induced by high-fat diet. Methods: This experimental study was carried out at BMSI, JPMC from October to November 2008. Thirty adult albino rats, 200-240 gram weight, were divided into three groups. Group A received control diet, Group B received high-fat diet (20 mg butter/100 gm diet) and Group C received high-fat diet with fresh garlic (20 mg butter with 6 gm fresh garlic/100 gm diet). The groups were further divided on the basis of duration of treatment, four weeks and eight weeks respectively. The rats were sacrificed, liver removed, weighed and relative liver weight calculated. Hepatic tissue was processed and tissue slides stained with haematoxylin and eosin. Results: There was significant increase in relative liver weight in group B animals as compared to the control animals, which decreased significantly in group C. Haematoxylin and eosin stained sections revealed ballooned hepatocytes having vesicular appearance with pyknotic nuclei in high-fat group which were preserved to a great extent in group C animals. Conclusion: This study has shown that use of fresh garlic along with high-fat diet prevents its damaging effects on liver to a great extent. PMID:27182249

  14. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

    PubMed

    Tanvir, E M; Afroz, R; Chowdhury, Maz; Gan, S H; Karim, N; Islam, M N; Khalil, M I

    2016-09-01

    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.

  15. Butyrate Protects Rat Liver against Total Hepatic Ischemia Reperfusion Injury with Bowel Congestion

    PubMed Central

    Wang, Qingbao; Wang, Fangrui; Ma, Zhenyu; Qiao, Yingli

    2014-01-01

    Hepatic ischemia/reperfusion (I/R) injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation. PMID:25171217

  16. Anzer honey prevents N-ethylmaleimide-induced liver damage in rats.

    PubMed

    Korkmaz, Asli; Kolankaya, Dürdane

    2009-07-01

    N-ethylmaleimide (NEM) is a sulphydryl blocker which impairs the sulphydryl dependent antioxidant system (mainly glutathione) in the body by alkylating endogenous sulphydryls. This study was designed to investigate the effects of Anzer honey on NEM-induced liver injury in rats. Thirty female Wistar albino rats were divided equally into three groups. Group 1: control; Group 2: NEM; Group 3: Anzer honey+NEM. NEM (0.075mg kg(-1)) was given to both group 2 and 3 administered subcutaneously (s.c.) for 30 days. The animals in the Anzer honey+NEM group were treated with Anzer honey at a dose of 0.275g kg(-1), (p.o.) at 1h prior to every NEM injection. At the end of the 30 day treatment period, liver samples were taken for determination of the glutathione levels and histological examination. NEM treatment alone caused a significant reduction of the liver glutathione levels in group 2. Furthermore, NEM treatment caused congestion and mononuclear cell infiltration in the liver when compared to the control group. In group 3, Anzer honey treatment reversed all the changes in glutathione level, as well as histopathological alterations, normally induced by NEM. The findings imply that depletion of glutathione concentration plays a causal role in NEM-induced liver injury, and that the hepatoprotective effect of Anzer honey may be mediated through sulfhydryl-sensitive processes. They further imply that it may also possess antioxidant properties.

  17. Specificity of procaine and ester hydrolysis by human, minipig, and rat skin and liver.

    PubMed

    Jewell, Christopher; Ackermann, Chrisita; Payne, N Ann; Fate, Gwendolyn; Voorman, Richard; Williams, Faith M

    2007-11-01

    The capacity of human, minipig, and rat skin and liver subcellular fractions to hydrolyze the anesthetic ester procaine was compared with carboxylesterase substrates 4-methylumbelliferyl-acetate, phenylvalerate, and para-nitrophenylacetate and the arylesterase substrate phenylacetate. Rates of procaine hydrolysis by minipig and human skin microsomal and cytosolic fractions were similar, with rat displaying higher activity. Loperamide inhibited procaine hydrolysis by human skin, suggesting involvement of human carboxylesterase hCE2. The esterase activity and inhibition profiles in the skin were similar for minipig and human, whereas rat had a higher capacity to metabolize esters and a different inhibition profile. Minipig and human liver and skin esterase activity was inhibited principally by paraoxon and bis-nitrophenyl phosphate, classical carboxylesterase inhibitors. Rat skin and liver esterase activity was inhibited additionally by phenylmethylsulfonyl fluoride and the arylesterase inhibitor mercuric chloride, indicating a different esterase profile. These results have highlighted the potential of skin to hydrolyze procaine following topical application, which possibly limits its pharmacological effect. Skin from minipig used as an animal model for assessing transdermal drug preparations had similar capacity to hydrolyze esters to human skin.

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

    NASA Technical Reports Server (NTRS)

    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.

  19. Effect of zinc deficiency of expression of specific mRNAs in rat liver

    SciTech Connect

    Chen, S.J.; Kimball, S.R.; Leure-duPree, A.E.; Jefferson, L.S. )

    1991-03-15

    Retinol is released from the liver bound to a specific transport protein, retinol binding protein (RBP), which binds to transthyretin (TTR) to transport retinol to the retinal pigment epithelium for use in the visual cycle. The synthesis of RBP as well as the transport of vitamin A from the liver is especially sensitive to zinc deficiency (ZD). Impaired hepatic synthesis of RBP has been reported in zinc-deficient rats. In the present study, the effect of ZD on the expression of mRNAs in the liver was examined by isolating total RNA from control, pair-fed, and zinc-deficient rats and translating the RNA in a messenger-dependent reticulocyte lysate. The radiolabeled translation products were analyzed by two-dimensional gel electrophoresis followed by autoradiography. The amounts of 12 of the approximately 200 radiolabeled translation products which could be distinguished were found to be altered in zinc-deficient compare to control samples. To investigate the expression of a specific mRNA, a cDNA to TTR was employed to probe the RNA samples. Slot blot analysis revealed that TTR mRNA was reduced to 57 {plus minus} 14% of the control in pair-fed rats to 29 {plus minus} 19% of control in zinc-deficient rats. The decrease in TTR mRNA is consistent with the observation that serum TTR is decreased during zinc deficiency caused by cirrhosis.

  20. Betaine treatment decreased oxidative stress, inflammation, and stellate cell activation in rats with alcoholic liver fibrosis.

    PubMed

    Bingül, İlknur; Başaran-Küçükgergin, Canan; Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-07-01

    The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-β1 (TGF-β1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-β protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.

  1. Functional abnormalities of sinusoidal endothelial cells in rats with acute liver rejection.

    PubMed

    Yokoi, Y; Nakamura, S; Muro, H; Baba, S

    1994-01-01

    The purpose of this study was to determine the changes of hepatic sinusoidal endothelial cell (SEC) function in acute liver rejection with respect to receptor-mediated endocytosis. Orthotopic rat liver transplantation was performed in Lewis rats grafted with DA livers and in Lewis rats grafted with Lewis livers as rejectors and controls, respectively. Animals were killed at 1, 3, 5, 7, and 10 days after the operation. Fc receptors (FcRs) were histochemically stained on frozen liver sections by applying peroxidase-antiperoxidase IgG complex as a ligand, and the FcR activity, i.e., capacity of binding the ligands represented by the FcR staining intensity, was semiquantitatively analyzed as an indicator of SEC function. The serum level of hyaluronic acid, which is specifically cleared from the circulation by receptor-mediated SEC endocytosis, was also assayed, along with the total serum bilirubin. Three days after the operation, the SECs of rejectors showed a significantly weaker FcR staining intensity of about half the value of that seen in the controls (P < 0.05), and staining disappeared after 5 days (P < 0.01). The decrease of FcR staining intensity, i.e., FcR activity, showed a correlation with elevation of the serum hyaluronic acid level (r = -0.77; P < 0.001). Histological evidence of endothelialitis and a significant elevation of total serum bilirubin (P < 0.01) were also present at 3 and 5 days, respectively. These results suggest that impairment of the endocytic function of SECs occurs at an earlier phase of acute liver rejection when compared with development of abnormalities of traditional indicators. Determination of receptor-mediated SEC endocytic functions may thus provide useful information for the early diagnosis of acute rejection.

  2. Cyclosporine a augments P-glycoprotein expression in the regenerating rat liver.

    PubMed

    Daoudaki, Maria; Fouzas, Ioannis; Stapf, Verena; Ekmekcioglu, Cem; Imvrios, George; Andoniadis, Antonios; Demetriadou, Aphrodite; Thalhammer, Theresia

    2003-03-01

    In the liver, the multidrug resistance (MDR) protein P-glycoprotein (P-gp) is physiologically expressed at the bile canalicular membrane, where it participates in the biliary excretion of various lipophilic drugs and xenobiotics. Previous studies showed that the immunosuppressive agent cyclosporine A (CsA) modulates P-gp and exerts a hepatotrophic influence in the regenerating liver. Hepatocytes isolated from regenerating rat liver, after 2/3 partial hepatectomy (PH 2/3), were used as an in vivo experimental model of cells with high proliferating activity in order to investigate whether CsA influences cellular levels of P-gp in those cells. Male Wistar rats were treated with CsA (20 mg/kg body weight) for 4 d preoperatively and 1 d postoperatively, and regenerating hepatocytes were isolated by collagenase perfusion 12, 24 and 48 h after PH 2/3. Flow cytometry and Western blotting studies with the monoclonal antibodies C494 and C219 showed that after PH 2/3, cellular levels of P-gp were initially suppressed, 12 h after PH 2/3, by 23%, but were significantly elevated thereafter, 24 and 48 h after PH 2/3 by 28% and 73%, respectively. In CsA pretreated animals, P-gp levels were increased even in normal hepatocytes by 34%, and an additional augmentation was seen in hepatocytes from 24 and 48 h regenerating livers (60% and 56%, respectively). In summary, we demonstrate for the first time that CsA has an additive effect on the expression of P-glycoprotein during liver regeneration in the rat. Therefore, induction of P-gp might also be considered in patients receiving CsA after liver transplantation for hepatocellular carcinoma and chemotherapy as an adjuvant treatment for the prevention of tumor recurrence.

  3. Carcinogenicity of by-products of disinfection in mouse and rat liver

    SciTech Connect

    Herren-Freund, S.L.; Pereira, M.A.

    1986-11-01

    By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of ..gamma..-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylene, and N-Cl piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform either had no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-days-old Swiss mice initiated with ethylnitrosourea (ENU). ENU at 5 and 20 ..mu..g/g caused a dose-dependent increase in liver tumors. In male mice, chloroform inhibited both spontaneous and ENU-induced liver tumors. When administered in the drinking water, chloroform inhibited, whereas phenobarbital promoted, hepatocarcinogenesis in mice.

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

    PubMed Central

    Kojima-Yuasa, Akiko; Goto, Mayu; Yoshikawa, Eri; Morita, Yuri; Sekiguchi, Hirotaka; Sutoh, Keita; Usumi, Koji; Matsui-Yuasa, Isao

    2016-01-01

    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. PMID:27999369

  5. Corrections by melatonin of liver mitochondrial disorders under diabetes and acute intoxication in rats.

    PubMed

    Cheshchevik, Vitali T; Dremza, Iosif K; Lapshina, Elena A; Zabrodskaya, Svetlana V; Kujawa, Jolanta; Zavodnik, Ilya B

    2011-08-01

    The aim of the present work was to investigate the mechanisms of oxidative damage of the liver mitochondria under diabetes and intoxication in rats as well as to evaluate the possibility of corrections of mitochondrial disorders by pharmacological doses of melatonin. The experimental (30 days) streptozotocin-induced diabetes mellitus caused a significant damage of the respiratory activity in rat liver mitochondria. In the case of succinate as a respiratory substrate, the ADP-stimulated respiration rate V₃ considerably decreased (by 25%, p < 0·05) as well as the acceptor control ratio (ACR) V₃/V₂ markedly diminished (by 25%, p < 0·01). We observed a decrease of the ADP-stimulated respiration rate V₃ by 35% (p < 0·05), with glutamate as substrate. In this case, ACR also decreased (by 20%, p < 0·05). Surprisingly, the phosphorylation coefficient ADP/O did not change under diabetic liver damage. Acute rat carbon tetrachloride-induced intoxication resulted in considerable decrease of the phosphorylation coefficient because of uncoupling of the oxidation and phosphorylation processes in the liver mitochondria. The melatonin administration during diabetes (10 mg·kg⁻¹ body weight, 30 days, daily) showed a considerable protective effect on the liver mitochondrial function, reversing the decreased respiration rate V₃ and the diminished ACR to the control values both for succinate-dependent respiration and for glutamate-dependent respiration. The melatonin administration to intoxicated animals (10 mg·kg⁻¹ body weight, three times) partially increased the rate of succinate-dependent respiration coupled with phosphorylation. The impairment of mitochondrial respiratory plays a key role in the development of liver injury under diabetes and intoxication. Melatonin might be considered as an effector that regulates the mitochondrial function under diabetes.

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

    SciTech Connect

    Angelico, M.; Alvaro, D.; Cantafora, A.; Masella, R.; Gaudio, E.; Gandin, C.; Ginanni Corradini, S.; Ariosto, F.; Riggio, O.; Capocaccia, L. )

    1991-07-01

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

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

    PubMed

    Kojima-Yuasa, Akiko; Goto, Mayu; Yoshikawa, Eri; Morita, Yuri; Sekiguchi, Hirotaka; Sutoh, Keita; Usumi, Koji; Matsui-Yuasa, Isao

    2016-12-19

    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.

  8. Rat liver regeneration following ablation with irreversible electroporation

    PubMed Central

    Bruinsma, Bote G.; Jaramillo, Maria; Yarmush, Martin L.

    2016-01-01

    During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naïve extracellular matrix is decellularized in vivo with completely preserved extracellular architecture. PMID:26819842

  9. Rat liver regeneration following ablation with irreversible electroporation.

    PubMed

    Golberg, Alexander; Bruinsma, Bote G; Jaramillo, Maria; Yarmush, Martin L; Uygun, Basak E

    2016-01-01

    During the past decade, irreversible electroporation (IRE) ablation has emerged as a promising tool for the treatment of multiple diseases including hepatic cancer. However, the mechanisms behind the tissue regeneration following IRE ablation have not been investigated. Our results indicate that IRE treatment immediately kills the cells at the treatment site preserving the extracellular architecture, in effect causing in vivo decellularization. Over the course of 4 weeks, progenitor cell differentiation, through YAP and notch pathways, together with hepatocyte expansion led to almost complete regeneration of the ablated liver leading to the formation of hepatocyte like cells at the ablated zone. We did not observe significant scarring or tumor formation at the regenerated areas 6 months post IRE. Our study suggests a new model to study the regeneration of liver when the naïve extracellular matrix is decellularized in vivo with completely preserved extracellular architecture.

  10. Preventive Effect of Carvacrol Against Oxidative Damage in Aged Rat Liver.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    2016-11-21

    The present study was designed to investigate the changes in activities of antioxidant enzymes and lipid peroxidation level in the liver of 2, 10 and 20 months old rats, and to see whether these changes are restored to those of the two month old rats after carvacrol treatment. Male rats of 2, 10, and 20 months (n = 10 for each group) were used for all the experiments. The aged rats (10 and 20 months old) were given carvacrol (15 mg/day per body weight) for 30 days. Control animals received an equal volume of vehicle. After the treatment, livers were removed for estimation of superoxide dismutase-SOD, glutathione-S-transferase-GST, catalase-CAT activities and lipid peroxidation level. The present findings determined that normal aging was associated with a significant decrease in the activities of antioxidant enzymes (SOD; 11.87 ± 0.6 (2 months old) vs 7.56 ± 0.1 (20 months old); P < 0.001) in liver, as well as an increase in lipid peroxidation level (MDA; 0.15 ± 0.01 (2 months old) vs 0.41 ± 0.01 (20 months old); P < 0.001) in aged rats. Also, the results of this study indicated that carvacrol treatment increased the activities of the antioxidant enzymes in 20 months old animals versus the aged matched control group (SOD; 9.87 ± 0.4; P < 0.01). Furthermore, carvacrol decreased lipid peroxidation content in 10 and 20 months old animals compared with the aged matched control (MDA; 9.87 ± 0.4; P < 0.001). Our data shows that carvacrol could be a candidate to inhibit the development of age-induced liver damage through inhibition of oxidative stress and also increasing antioxidant defenses.

  11. Effect of galangin supplementation on oxidative damage and inflammatory changes in fructose-fed rat liver.

    PubMed

    Sivakumar, Allur Subramaniyan; Anuradha, Carani Venkatraman

    2011-09-05

    The study examined the effects of galangin (GA) on oxidative stress, inflammatory cytokine levels and nuclear factor-kappa B (NF-κB) activation in fructose-fed rat liver. Adult male albino Wistar rats were divided into 4 groups. Groups 1 and 4 received the control diet containing starch as the source of carbohydrate while groups 2 and 3 were fed a diet containing fructose. Groups 3 and 4 additionally received GA (100μg/kg, p.o) from the 15th day. At the end of 60 days, the levels of plasma glucose, insulin and triglycerides, insulin sensitivity indices and oxidative stress markers in the liver were determined. Cytokines of interest were assayed by ELISA and RT-PCR and NF-κB p65 nuclear translocation by Western blot and RT-PCR. Compared to control diet-fed animals, fructose-fed animals developed hyperglycemia, hyperinsulinemia, hypertriglyceridemia and insulin resistance (IR) (all p<0.01). GA prevented the rise in plasma glucose, insulin and triglycerides and improved insulin sensitivity. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in plasma and the mRNA and protein levels of TNF-α and transforming growth factor-β1(TGF-β(1)) in liver were significantly higher in fructose-fed rats than control rats. However, treatment with GA downregulated the expression of these cytokines. Translocation of NF-κB into the nucleus was also increased in fructose diet-fed animals, which was prevented by GA. These results suggest that GA prevents oxidative damage and has a downregulatory effect on the inflammatory pathway in liver of fructose-fed rats.

  12. Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats.

    PubMed

    Jatobá, Carlos André Nunes; de Rezende, Adriana Augusto; de Paiva Rodrigues, Sarah Jane; de Almeida Câmara, Maria Margareth; das Graças Almeida, Maria; Freire-Neto, Francisco; da Rocha, Luiz Reginaldo Menezes; da Medeiros, Aldo Cunha; Brandão-Neto, José; de Carvalho Formiga, Maria Célia; de Azevedo, Italo Medeiros; de Oliveira Ramos, Ana Maria

    2008-04-01

    Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.

  13. Persistence and accumulation of micronucleated hepatocytes in liver of rats after repeated administration of diethylnitrosamine.

    PubMed

    Narumi, Kazunori; Ashizawa, Koji; Fujiishi, Yohei; Tochinai, Ryota; Okada, Emiko; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Hamada, Shuichi; Kaneko, Kimiyuki; Ohyama, Wakako

    2013-08-15

    A repeat-dose micronucleus assay in adult rat liver was recently developed [Mutat. Res. 747 (2012) 234-239]. This assay demonstrated a high detectability of hepatocarcinogens at relatively low doses, as indicated by dose-dependent micronucleus induction. Because the adult rat liver is known to have a long life-span, this desirable property of the assay will be an advantage in detecting micronucleated hepatocytes (MNHEPs) that have persisted for long periods in the liver following repeated dosing. However, no data directly supporting the underlying mechanisms have been published to date. In the present study, we verified the mechanisms by means of pulse-labeling of micronucleated hepatocytes with the thymidine analog 5-ethynyl-2'-deoxyuridine (EdU). The rodent hepatocarcinogen diethylnitrosamine (DEN) was repeatedly administered orally to male Crl:CD (SD) rats (6 weeks old) for up to 2 weeks, and EdU was injected intraperitoneally on days 1, 7, or 14. Hepatocytes were isolated by use of a non-perfusion technique at 24h, 1 week, or 2 weeks after EdU injection and analyzed for EdU incorporation and micronucleus formation. The results of our study confirmed that MNHEPs labeled with EdU on the first day of DEN administration persisted until 2 weeks post-administration in the rat livers. However, the frequency of MHNEPs among EdU-labeled hepatocytes decreased over time. In addition, the number of terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL)-positive cells in the liver tissue increased, suggesting selective removal of micronucleated cells. Theoretical calculation of the cumulative MNHEP frequency on each of the days on which DEN was administered, taking into account the rate of loss, came out closer to the actual value observed in the liver micronucleus test. Taken together, these results indicate that although micronucleated cells induced in rat livers by administration of the genotoxic hepatocarcinogen DEN undergo selective removal, they

  14. Hepatoprotective activity of Peganum harmala against ethanol-induced liver damages in rats.

    PubMed

    Bourogaa, Ezzeddine; Jarraya, Raoudha Mezghani; Damak, Mohamed; Elfeki, Abdelfattah

    2015-05-01

    In this study, we investigated the protective effects of Peganum harmala seeds extract (CPH) against chronic ethanol treatment. Hepatotoxicity was induced in male Wistar rats by administrating ethanol 35% (4 g/kg/day) for 6 weeks. CPH was co-administered with ethanol, by intraperitonial (IP) injection, at a dose of 10 mg/kg bw/day. Control rats were injected by saline solution (NaCl 9‰). Chronic ethanol administration intensified lipid peroxidation monitored by an increase of TBARS level in liver. Ethanol treatment caused also a drastic alteration in antioxidant defence system; hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. A co-administration of CPH during ethanol treatment inhibited lipid peroxidation and improved antioxidants activities. However, treatment with P. harmala extract protects efficiently the hepatic function of alcoholic rats by the considerable decrease of aminotransferase contents in serum of ethanol-treated rats.

  15. An improved stereologic method for three-dimensional estimation of particle size distribution from observations in two dimensions and its application.

    PubMed

    Xu, Yi-Hua; Pitot, Henry C

    2003-09-01

    Single enzyme-altered hepatocytes; altered hepatic foci (AHF); and nodular lesions have been implicated, respectively in the processes of initiation, promotion, and progression in rodent hepatocarcinogenesis. Qualitative and quantitative analyses of such lesions have been utilized both to identify and to determine the potency of initiating, promoting, and progressor agents in rodent liver. Of a number of possible parameters determined in the study of such lesions, estimation of the number of foci or nodules in the liver is very important. The method of Saltykov has been used for estimating the number of AHF in rat liver. However, in practice, the Saltykov calculation has at least two weak points: (a) the size class range is limited to 12, which in many instances is too narrow to cover the range of AHF data obtained; and (b) under some conditions, the Saltykov equation generates negative values in several size classes, an obvious impossibility in the real world. In order to overcome these limitations in the Saltykov calculations, a study of the particle size distribution in a wide-range, polydispersed sphere system was performed. A stereologic method, termed the 25F Association method, was developed from this study. This method offers 25 association factors that are derived from the frequency of different-sized transections obtained from transecting a spherical particle, thus expanding the size class range to be analyzed up to 25, which is sufficiently wide to encompass all rat AHF found in most cases. This method exhibits greater flexibility, which allows adjustments to be made within the calculation process when NA((k,k)), the net number of transections from the same size spheres, was found to be a negative value, which is not possible in real situations. The reliability of the 25F Association method was tested thoroughly by computer simulation in both monodispersed and polydispersed sphere systems. The test results were compared with the original Saltykov method

  16. Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

    PubMed Central

    Burk, Raymond F.; Lawrence, Richard A.; Lane, James M.

    1980-01-01

    Paraquat and diquat facilitate formation of superoxide anion in biological systems, and lipid peroxidation has been postulated to be their mechanism of toxicity. Paraquat has been shown to be more toxic to selenium-deficient mice than to controls, presumably as the result of decreased activity of the selenoenzyme glutathione peroxidase. The present study was designed to measure lipid peroxidation and to assess toxicity in control and selenium-deficient rats given paraquat and diquat. Lipid peroxidation was measured by determining ethane production rates of intact animals; toxicity was assessed by survival and by histological and serum enzyme evidence of liver and kidney necrosis. Paraquat and diquat were both much more toxic to selenium-deficient rats than to control rats. Diquat (19.5 μmol/kg) caused rapid and massive liver and kidney necrosis and very high ethane production rates in selenium-deficient rats. The effect of paraquat (78 μmol/kg) was similar to that of diquat but was not as severe. Acutely lethal doses of paraquat (390 μmol/kg) and diquat (230 μmol/kg) in control rats caused very little ethane production and no evidence of liver necrosis. These findings suggest that paraquat and diquat exert their acute toxicity largely through lipid peroxidation in selenium-deficient rats. Selenium deficiency had no effect on superoxide dismutase activity in erythrocytes or in 105,000 g supernate of liver or kidney. Glutathione peroxidase, which represents the only well-characterized biochemical function of selenium in animals, was dissociated from the protective effect of selenium against diquat-induced lipid peroxidation and toxicity by a time-course study in which selenium-deficient rats were injected with 50 μg of selenium and later given diquat (19.5 μmol/kg). Within 10 h, the selenium injection provided significant protection against diquat-induced lipid peroxidation and mortality even though this treatment resulted in no rise in glutathione peroxidase

  17. Interaction of Lens culinaris lectin, concanavalin A, Ricinus communis agglutinin and wheat germ agglutinin with the cell surface of normal and transformed rat liver cells.

    PubMed

    Roth, J; Neupert, G; Thoss, K

    1975-01-01

    The observation of BOREK et al. (1973) on nonagglutinability of transformed rat liver cells by Lens culinaris lectin and our ultrastructural findings of a greater mobility of the Lens culinaris lectin receptors on transformed rat liver cells as compared to normal rat liver cells (ROTH 1975) initiated the present agglutination experiments on liver cells with lectins. For agglutination assay the microhemadsorption technique after FURMANSKI et al. (1973) was used with exception of several tests on EDTA-detached cells. The transformed rat liver cells exhibited, in contrast to the findings of BOREK et al. (1973), a positive microhemadsorption with Lens culinaris lectin as well as with Concanavalin A, Ricinus communis lectin and wheat germ agglutinin whereas the normal rat liver cells became positive only after a brief trypsin treatment. The significance of the difference in agglutinability of rat liver cells with Lens culinaris lectin and the other lectins used is discussed with regard to the cell-cell interaction mediated by lectins.

  18. Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

    PubMed Central

    2013-01-01

    It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. PMID:23442260

  19. Swim training increases glucose output from liver perfused in situ with glucagon in fed and fasted rats.

    PubMed

    Drouin, Réjean; Robert, Geneviève; Milot, Martin; Massicotte, Denis; Péronnet, François; Lavoie, Carole

    2004-08-01

    The effect of endurance swim training (3 hours per day, 5 days/week, for 10 weeks) on hepatic glucose production (HGP) in liver perfused in situ for 60 minutes with glucagon and insulin was studied in Sprague-Dawley rats. The experiments were performed in fed rats and in rats fasted for 24 hours, but with lactate (8 mmol/L) added to the perfusion medium. Liver glycogen content was significantly lower in fasted than fed rats (fasted untrained and trained: 14 +/- 4 and 11 +/- 3 micromol glycosyl U/g of liver wet weight (WW); fed untrained and trained: 205 +/- 11 and 231 +/- 11 micromol glycosyl U/g of liver WW; not significantly different in trained and untrained rats). Glucagon increased HGP in the 4 experimental groups, but the increases were more rapid and pronounced in trained than in untrained rats in both fed and fasted states. HGP values (area under the curve [AUC] in micromol/g of liver WW) were significantly higher in trained fed (112.1 +/- 7.1 v 85.9 +/- 12.2 in untrained rats) than in trained fasted rats (50.8 +/- 4.4 v 34.7 +/- 3.6 in untrained rats). When compared with untrained rats, the total amount of glucose released by the liver in response to glucagon in trained rats was approximately 30% higher in the fed state and approximately 45% larger in the fasted state. These results indicate that endurance training increases the response of both glycogenolysis and gluconeogenesis to glucagon.

  20. Enhanced liver tumor promotion activity in rats subjected to combined administration of phenobarbital and orphenadrine.

    PubMed

    Morita, Reiko; Yafune, Atsunori; Shiraki, Ayako; Itahashi, Megu; Akane, Hirotoshi; Nakane, Fumiyuki; Suzuki, Kazuhiko; Shibutani, Makoto; Mitsumori, Kunitoshi

    2013-01-01

    Phenobarbital (PB) and orphenadrine (ORPH) are cytochrome P450 (CYP) 2B inducers and have liver tumor-promoting effects in rats. In this study, we performed a rat two-stage liver carcinogenesis bioassay to examine the tumor-promoting effect of PB and ORPH co-administration. Twelve male rats per group were given an intraperitoneal injection of N-diethylnitrosamine (DEN) for initiation. Two-week after DEN administration, rats were given PB (60 or 120 ppm in drinking water), ORPH (750 or 1,500 ppm in diet) or 60 ppm PB+750 ppm ORPH for 6-week. One-week after the PB/ORPH treatment, all rats were subjected to two-thirds partial hepatectomy. To evaluate the effect of the combined administration, we used two statistical models: a heteroadditive model and an isoadditive model. In the heteroadditive model, the net values of the number and area of glutathione S-transferase placental form (GST-P) positive foci, Cyp2b1/2, Gstm3 and Gpx2 mRNA levels, microsomal reactive oxygen species (ROS) production and thiobarbituric acid-reactive substances level in the PB+ORPH group were significantly higher than the sum of the net values of those in the Low PB and Low ORPH groups. In the isoadditive model, the average values of the area of GST-P positive foci and PCNA positive hepatocyte ratio and Gstm3 mRNA level in the PB+ORPH group were significantly higher than the average values of those in the High PB and High ORPH groups. These results suggest that PB and ORPH co-administration causes synergistic effects in liver tumor-promoting activity in rats resulting from oxidative stress due to enhanced microsomal ROS production.

  1. Effect of dietary lipid, carnitine and exercise on lipid profile in rat blood, liver and muscle.

    PubMed

    Karanth, Jyothsna; Jeevaratnam, K

    2009-09-01

    Aim of this study was to investigate the influence of physical exercise on effects of the daily intake of vegetarian diet of either vegetable hydrogenated fat (HF) or peanut oil (PO) with or without carnitine on the lipid profile. Eight groups of male Wistar rats were fed HF-diet (4 groups) or PO-diet (4 groups), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. Plasma triglycerides (TG), total cholesterol (TC), HDL-cholesterol, free fatty acids (FFA), liver and thigh muscle glycogen, total fat (TF), TG, TC and FFA were analyzed. HF-fed rats showed significantly increased plasma TC, VLDL+LDL-cholesterol and TG compared to PO-fed rats, wherein a lowered plasma TC, TG levels in all the groups with significantly increased liver cholesterol and decreased muscle cholesterol was observed. Physical exercise of moderate intensity reduced plasma TC and TG accompanied by significantly reduced tissue TG and cholesterol while FFA and glycogen increased in all the groups. The influence of exercise was less pronounced in carnitine supplemented rats since carnitine could significantly reduce TG in plasma and tissues of sedentary rats. Results from the present study showed that the intake of HF diet significantly increased the plasma and tissue lipid profile and MUFA-rich diet or carnitine supplementation and/or exercise may ameliorate the deleterious effects of HF.

  2. Induction of rat kidney gluconeogenesis during acute liver intoxication by carbon tetrachloride.

    PubMed Central

    Faus, M J; Lupiáñez, A; Vargas, A; Sánchez-Medina, F

    1978-01-01

    1. Glucose production from L-lactate was completely inhibited 24h after carbon tetrachloride treatment in liver from 48h-starved rats. The activities of phosphoenolpyruvate carboxykinase, fructose diphosphatase and glucose 6-phosphatase were decreased by this treatment in fed and starved rats, whereas lactate dehydrogenase activity was only decreased in fed animals. 2. The production of glucose by renal cortical slices from fed rats previously treated with carbon tetrachloride was enhanced when L-lactate, pyruvate and glutamine but not fructose were used as glucose precursors. Renal phosphoenolpyruvate carboxykinase activity was increased in this condition. 3. This increase was counteracted by cycloheximide or actinomycin D, suggesting that the effect was due to the synthesis de novo of the enzyme. 4. The pattern of hepatic gluconeogenic metabolites in treated animals was characterized by an increase in lactate, pyruvate, malate and citrate as well as a decrease in glucose 6-phosphate, suggesting an impairment of liver gluconeogenesis in vivo. 5. In contrast, the profile of renal metabolites suggested that gluconeogenesis was operative in the treated rats, as indicated by the marked increase in the content of phosphoenolpyruvate, 2-phosphoglycerate, 3-phosphoglycerate and glucose 6-phosphate. 6. It is postulated that renal gluconeogenesis could contribute to the maintenance of glycaemia in carbon tetrachloride-treated rats. PMID:708398

  3. Activities of xenobiotic metabolizing enzymes in rat placenta and liver in vitro.

    PubMed

    Fabian, Eric; Wang, Xinyi; Engel, Franziska; Li, Hequn; Landsiedel, Robert; van Ravenzwaay, Bennard

    2016-06-01

    In order to assess whether the placental metabolism of xenobiotic compounds should be taken into consideration for physiologically-based toxicokinetic (PBTK) modelling, the activities of seven phase I and phase II enzymes have been quantified in the 18-day placenta of untreated Wistar rats. To determine their relative contribution, these activities were compared to those of untreated adult male rat liver, using commonly accepted assays. The enzymes comprised cytochrome P450 (CYP), flavin-containing monooxygenase (FMO), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), esterase, UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST). In contrast to liver, no activities were measurable for 7-ethylresorufin-O-dealkylase (CYP1A), 7-pentylresorufin-O-dealkylase (CYP2B), 7-benzylresorufin-O-dealkylase (CYP2B, 2C and 3 A), UGT1, UGT2 and GST in placenta, indicating that the placental activity of these enzymes was well below their hepatic activity. Low activities in placenta were determined for FMO (4%), and esterase (8%), whereas the activity of placental ADH and ALDH accounted for 35% and 40% of the hepatic activities, respectively. In support of the negligible placental CYP activity, testosterone and six model azole fungicides, which were readily metabolized by rat hepatic microsomes, failed to exhibit any metabolic turnover with rat placental microsomes. Hence, with the possible exception of ADH and ALDH, the activities of xenobiotic-metabolizing enzymes in rat placenta are too low to warrant consideration in PBTK modelling.

  4. Sorghum-based alcoholic beverage, Burukutu, perturbs the redox status of the liver of male rats

    PubMed Central

    Ajiboye, Taofeek O; Iliasu, Ganiyat A; Ojewuyi, Oluwayemisi B; Abdulazeez, Azeemat T; Muhammed, Aisha O; Kolawole, Fausat L

    2014-01-01

    The redox status of male rat liver following 28 days consumption of Burukutu was investigated. Twenty rats were randomized into four groups with five rats each. Burukutu consumption at 0.78 g/kg alcohol produced no significant change in the activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). However, 3.71 and 7.43 g/kg dosages resulted in significant decrease in the activities of ALP, ALT and AST with corresponding increase in serum. The activity of cytochrome P450(CYP 2E1) increased significantly in the liver of rats following consumption of Burukutu at all doses investigated. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase decreased significantly (P < 0.05) in rats treat with 0.78 g/kg, 3.41 and 7.43 g/kg Burukutu. There was a significant increase in the level of glutathione disulfide (GSSG) with reduction in the levels of glutathione reduced (GSH) and GSH:GSSG. The levels of oxidative stress biomarkers, malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and percentage DNA fragmentation, increased significantly (P < 0.05). It is evident from the alterations in the activities of the hepatocellular enzymes, antioxidant enzymes and oxidative stress biomarkers that Burukutu mediated its toxicity through the depletion of the antioxidant enzymes. PMID:25473518

  5. Protective Effect of Curcumin against the Liver Toxicity Caused by Propanil in Rats

    PubMed Central

    Otuechere, Chiagoziem A.; Abarikwu, Sunny O.; Olateju, Victoria I.; Animashaun, Azeezat L.; Kale, Oluwafemi E.

    2014-01-01

    We investigated the protective effects of curcumin on propanil-induced alterations in biochemical indices in blood and liver of male Wistar rats. The study consisted of four treatment groups, with six animals each, designated as control, propanil (20mg/kg), curcumin(50 mg/kg), and curcumin (50 mg/kg) + propanil (20 mg/kg). Rats were administered their respective doses orally, every other day, for 28 days. Propanil administration elicited significant (P < 0.001) increases in plasma aspartate aminotransferase and alkaline phosphatase activities, by 24% and 56%, respectively, compared to the control. Treatment with propanil elevated bilirubin, creatinine, and total cholesterol levels in rats, but these were not significant relative to controls. Administration of propanil to rats significantly (P < 0.001) increased lipid peroxidation levels. However, catalase activity, vitamin C, and reduced glutathione levels were significantly reduced. Exposure to propanil did not produce any significant changes in packed cell volume, neutrophils, and leukocyte counts. The supplementation of curcumin attenuated the adverse effects of propanil intoxication by reducing lipid peroxidation levels and restored the levels of serum enzymes and reduced glutathione. The present study showed that propanil increased oxidative stress and altered some biochemical parameters in the rats but curcumin could afford some protection to attenuate propanil-induced toxicity in the liver. PMID:27437486

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

    PubMed

    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.

  7. Therapeutic effect of transplanting magnetically labeled bone marrow stromal stem cells in a liver injury rat model with 70%-hepatectomy

    PubMed Central

    Chen, Xiao-Wu; Zhu, Da-Jian; Ju, Yong-Le; Zhou, Shu-Feng

    2012-01-01

    Summary Background There are only few reports about the use of bone marrow stromal stem cells (BMSCs) for the treatment of traumatic liver injury. This study aimed to study the therapeutic effect of fluorescence-labeled BMSCs administered to rats subject to traumatic liver injury. Material/Methods Male SD rats with a 70% resection of the liver were injected with feridex-labeled BMSCs which could be induced to functional hepatocytes in vitro. Liver function was assayed and the liver scanned by 1.5-T MRI at 12 hrs and on days 1, 3, 5, 7, and 14 post-operation. The pathological changes of liver sections were monitored. Results The serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin in the transplantation group were significantly lower than the control group. The MRI showed rats of the transplantation group had an oval low signal area at 12 hr after operation; the low signal range gradually expanded and the signal intensity gradually decreased over 14 days after operation. The low signal range in the control group disappeared 12 hr after the operation. After Prussian blue staining, rats of the transplantation group contained blue granules with no significant hypertrophy or edema in hepatocytes, while the control group showed no blue granules with significant hypertrophy and edema. Conclusions The BMSCs transplanted into the injured rat liver gradually migrate to the surrounding liver tissue and partially repair the liver surgical injury in rats. BMSCs may represent an effective therapeutic approach for acute liver injury. PMID:23018343

  8. Histochemical and histoenzymatic liver changes in Guérin tumour-grafted rats.

    PubMed

    Bădescu, A; Cotuţiu, C; Mârza, D

    1981-01-01

    In order to follow up the morphological changes of the rat liver as a reaction to the tumour graft, three groups of Guérin tumour-grafted animals were used: a first control group, a second one treated with leucotrophine (LT) and a third one treated with LT and thiamine diphosphate (TDP). The tumour-grafted rats showed hepatic changes affecting mainly the organelles involved in cellular respiration and synthesis, as well as some morphological changes of Kupffer cells expressing an increased endocytosis. The protection by immunostimuli determined the diminution of histochemical and histoenzymatic changes both in hepatocytes and Kupffer cells.

  9. Purification and characterization of lead-induced zinc thionein in the liver of rats

    SciTech Connect

    Arizono, K.; Ito, T.; Ota, S.; Ariyoshi, T.

    1985-08-01

    Metallothioneins are involved in homeostasis of essential metals, but its exact biological function remains obscure. Recently it was observed that the administration of lead increased zinc content in the low molecular-weight protein fraction in the rat hepatic 105000x g soluble fraction by using Sephadex G-75 gel filtration, and that this fraction contained only zinc, not lead, as metal. Therefore, the authors have investigated the effects of some drugs on this zinc contained low molecular-weight protein (zinc binding protein, Zn-BP), and further isolated and purified the ZN-BP from liver of rats treated with lead.

  10. Mutagenicity of the potent rat hepatocarcinogen 6BT to the liver of transgenic (lacI) rats: consideration of a reduced mutation assay protocol.

    PubMed

    Lefevre, P A; Tinwell, H; Ashby, J

    1997-01-01

    6-(p-dimethylaminophenylazo)benzothiazole (6BT) is an unusually potent rat hepatocarcinogen, producing large malignant liver tumours after only 2-3 months of dietary administration in a riboflavin-deficient diet. This azocarcinogen has been evaluated in a Big Blue F344 transgenic rat (lacI) gene mutation assay. In a reproduction of the early stages of the carcinogenesis bioassay of this agent, rats were maintained on a riboflavin-deficient diet and were given 10 consecutive daily doses of 6BT (10 mg/kg) by oral gavage. The animals were killed and the livers examined 11 days after the final dose. The livers of 6BT-treated rats showed evidence of hepatocellular hypertrophy in centrolobular areas, with some indication of an increased incidence of mitotic figures. An approximately 10-fold increase in the mutation frequency of DNA isolated from an aliquot of the combined liver homogenates of 6BT-treated rats was observed over that obtained from an equivalent aliquot from control animals. Examination of DNA samples isolated from the livers of individual animals confirmed that 6BT was mutagenic in Big Blue rat livers. These data extend the sensitivity of this transgenic assay to include azo hepatocarcinogens. The determination of mutation frequencies using pooled tissue samples represented a major resource-saving adaptation of the assay protocol in the present study; the general advantages and disadvantages of this practice are discussed.

  11. Oncostatin M gene therapy attenuates liver damage induced by dimethylnitrosamine in rats.

    PubMed

    Hamada, Tetsuhiro; Sato, Ayuko; Hirano, Tadamichi; Yamamoto, Takashi; Son, Gakuhei; Onodera, Masayuki; Torii, Ikuko; Nishigami, Takashi; Tanaka, Minoru; Miyajima, Atsushi; Nishiguchi, Shuhei; Fujimoto, Jiro; Tsujimura, Tohru

    2007-09-01

    To assess the usefulness of oncostatin M (osm) gene therapy in liver regeneration, we examined whether the introduction of OSM cDNA enhances the regeneration of livers damaged by dimethylnitrosamine (DMN) in rats. Repeated injection of OSM cDNA enclosed in hemagglutinating virus of Japan envelope into the spleen resulted in the exclusive expression of OSM protein in Kupffer cells of the liver, which was accompanied by increases in body weight, liver weight, and serum albumin levels and the reduction of serum liver injury parameters (bilirubin, aspartate aminotransferase, and alanine aminotransferase) and a serum fibrosis parameter (hyaluronic acid). Histological examination showed that osm gene therapy reduced centrilobular necrosis and inflammatory cell infiltration and augmented hepatocyte proliferation. The apoptosis of hepatocytes and fibrosis were suppressed by osm gene therapy. Time-course studies on osm gene therapy before or after DMN treatment showed that this therapy was effective not only in enhancing regeneration of hepatocytes damaged by DMN but in preventing hepatic cytotoxicity caused by subsequent treatment with DMN. These results indicate that OSM is a key mediator for proliferation and anti-apoptosis of hepatocytes and suggest that osm gene therapy is useful, as preventive and curative means, for the treatment of patients with liver damage.

  12. Protective role of erdosteine on vancomycin-induced oxidative stress in rat liver.

    PubMed

    Sahin, Mehmet; Cam, Hakan; Olgar, Seref; Tunc, Sevket Ercan; Arslan, Cagatay; Uz, Efkan; Yilmaz, H Ramazan

    2006-10-01

    Drug-induced liver toxicity is a common cause of liver injury. This study was designed to elucidate whether high dose vancomycin (VCM) induces oxidative stress in liver and to investigate the protective effects of erdosteine, an expectorant agent. Twenty-two young Wistar rats were divided into three groups as follows: control group, VCM, and VCM plus erdosteine. VCM was administered intraperitoneally in the dosage of 200 mg/kg twice daily for 7 days. Erdosteine was administered orally administered once a day at a dose of 10 mg/kg body weight. The activities of antioxidant enzymes such as superoxide dismutase and catalase as well as the concentration of malondialdehyde, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the liver. VCM administration increased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities. Erdosteine co-administration with VCM injections caused significantly decreased malondialdehyde levels (p < 0.001), superoxide dismutase (p < 0.01) and catalase (p < 0.001) activities in liver tissue when compared with VCM alone. It can be concluded that erdosteine may prevent VCM-induced oxidative changes in liver by reducing reactive oxygen species.

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

    PubMed

    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.

  14. Participation of cysteine and cystine in inactivation of tyrosine aminotransferase in rat liver homogenates.

    PubMed Central

    Buckley, W T; Milligan, L P

    1978-01-01

    1. Inactivation of tyrosine aminotransferase was studied in rat liver homogenates. Under an O2 atmosphere with cysteine added, inactivation was rapid after a lag period of approx. 1h, whereas a N2 atmosphere extended the lag period to approx. 3h. 2. Replacement of cysteine with cystine resulted in rapid inactivation both aerobically and anaerobically. 3. Removal of the particulate fraction by centrifuging rat liver homogenates at 13,000g for 9min resulted in an aerobic lag period of 0.5h in the presence of cystine and approx. 3h in the presence of cysteine. 4. It is proposed that the stimulatory effect of cysteine on tyrosine aminotransferase inactivation occurs largely as a result of oxidation to cystine, which appears to be a more directly effective agent. PMID:33669

  15. Inhibition effects of some metal ions on the rat liver 6-phosphogluconate dehydrogenase

    NASA Astrophysics Data System (ADS)

    Adem, Şevki; Kayhan, Naciye

    2016-04-01

    6-phosphogluconate dehydrogenase is an enzyme in the pentose phosphate path. The main functions of the pathway are the manufacture of the reduced coenzyme NADPH and the formation of ribose 5-phosphate for nucleic acid synthesis and nucleotide. Both NADPH and ribose 5-phosphate involve a critical biochemical process. Metals have been recognized as important toxic agents for living for a long time. It has been considered that they lead to in the emergence of many diseases. To evaluate whether metals is effect towards rat liver 6PGD, we apply various concentrations of metals and enzyme inhibition was analyzed using enzyme activity assays. The IC50 values of Pb+2, Cr+3, Co+2, Ni+2, Cd+2, and Va+2, metals on rat liver 6PGD were calculated as 138,138, 169, 214, 280, and 350 µM, respectively.

  16. Effect of pesticides on cell survival in liver and brain rat tissues.

    PubMed

    Astiz, Mariana; de Alaniz, María J T; Marra, Carlos Alberto

    2009-10-01

    Pesticides are the main environmental factor associated with the etiology of human neurodegenerative disorders such as Parkinson's disease. Our laboratory has previously demonstrated that the treatment of rats with low doses of dimethoate, zineb or glyphosate alone or in combination induces oxidative stress (OS) in liver and brain. The aim of the present work was to investigate if the pesticide-induced OS was able to affect brain and liver cell survival. The treatment of Wistar rats with the pesticides (i.p. 1/250 LD50, three times a week for 5 weeks) caused loss of mitochondrial transmembrane potential and cardiolipin content, especially in substantia nigra (SN), with a concomitant increase of fatty acid peroxidation. The activation of calpain apoptotic cascade (instead of the caspase-dependent pathway) would be responsible for the DNA fragmentation pattern observed. Thus, these results may contribute to understand the effect(s) of chronic and simultaneous exposure to pesticides on cell survival.

  17. [Calcium transport in endoplasmic reticulum of the rat liver during lipid peroxidation].

    PubMed

    Gubskiĭ, Iu I; Kurskiĭ, M D; Zadorina, O V; Fedorov, A N; Briuzgina, T S; Iurzhenko, N N

    1990-01-01

    Some parameters of calcium transport in rat liver microsomes under conditions of lipoperoxidation activation modelled by antioxidant deficiency (AOD) were studied. This process was shown to be associated with a sharp stimulation of NADPH- and ascorbate-dependent lipid peroxidation in hepatocyte endoplasmic reticulum. The activation of lipid peroxidation was accompanied by disturbances in the kinetic properties of Ca2(+)-ATPase. This was paralleled with a considerable decrease of the ATP-dependent 45Ca-accumulation, increase in the passive permeability of microsomal vesicles for Ca2+ and Ca2+ elevation in the microsomal fraction. The AOD-induced diminution of the Ca2(+)-pump efficiency was slightly prevented by injections of rats with the antioxidants, alpha-tocopherol acetate and ionol which enable Ca2+ compartmentation correction in liver cytosol and membrane fractions.

  18. Biochemical changes in rat liver after 18.5 days of spaceflight (41566)

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

    The effect of weightlessness on liver metabolism was investigated using tissue from rats flown in earth orbit for 18.5 days on the Soviet Cosmos 936 biosatellite and the changes in the activities of 28 carbohydrate and lipid enzymes were determined. The activities of two enzymes, palmitoyl-CoA desaturase and lactate dehydrogenase, increased, while the activities of five, glycogen phosphorylase, 6-phosphogluconate dehydrogenase, both acyltransferases which act on alpha-glycerolphosphate and diglycerides, and and aconitate hydratase decreased. The other enzyme activities were found to be unchanged. In addition, increased levels of liver glycogen and palmitoleate were detected which probably resulted from the lowered glycogen phosphorylase and increased palmitoyl-CoA desaturase activities, respectively, in those animals that experienced weightlessness. All of the changes observed in the rats after 18.5 days of spaceflight disappear by 25 days after the flight.

  19. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    NASA Technical Reports Server (NTRS)

    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.

  20. Coffee and caffeine protect against liver injury induced by thioacetamide in male Wistar rats.

    PubMed

    Furtado, Kelly S; Prado, Monize G; Aguiar E Silva, Marco A; Dias, Marcos C; Rivelli, Diogo P; Rodrigues, Maria A M; Barbisan, Luis F

    2012-11-01

    Coffee intake has been inversely related to the incidence of liver diseases, although there are controversies on whether these beneficial effects on human health are because of caffeine or other specific components in this popular beverage. Thus, this study evaluated the protective effects of coffee or caffeine intake on liver injury induced by repeated thioacetamide (TAA) administration in male Wistar rats. Rats were randomized into five groups: one untreated group (G1) and four groups (G2-G5) treated with the hepatotoxicant TAA (200 mg/kg b.w., i.p.) twice a week for 8 weeks. Concomitantly, rats received tap water (G1 and G2), conventional coffee (G3), decaffeinated coffee (G4) or 0.1% caffeine (G5). After 8 weeks of treatment, rats were killed and blood and liver samples were collected. Conventional and decaffeinated coffee and caffeine intake significantly reduced serum levels of alanine aminotransferase (ALT) (p < 0.001) and oxidized glutathione (p < 0.05), fibrosis/inflammation scores (p < 0.001), collagen volume fraction (p < 0.01) and transforming growth factor β-1 (TGF-β1) protein expression (p ≤ 0.001) in the liver from TAA-treated groups. In addition, conventional coffee and caffeine intake significantly reduced proliferating cellular nuclear antigen (PCNA) S-phase indexes (p < 0.001), but only conventional coffee reduced cleaved caspase-3 indexes (p < 0.001), active metalloproteinase 2 (p ≤ 0.004) and the number of glutathione S-transferase placental form (GST-P)-positive preneoplastic lesions (p < 0.05) in the liver from TAA-treated groups. In conclusion, conventional coffee and 0.1% caffeine intake presented better beneficial effects than decaffeinated coffee against liver injury induced by TAA in male Wistar rats.

  1. Effect of conjugated linoleic acid (CLA) on lipid profile and liver histology in laboratory rats fed high-fructose diet.

    PubMed

    Kostogrys, Renata B; Pisulewski, Paweł M

    2010-11-01

    The objective of the study was to assess the effect of CLA on serum lipid profile, plasma malondialdehyde and liver histology in Wistar rats fed high-fructose diet. Eighteen rats were randomly assigned to three experimental groups and fed for the next 21 days. The experimental diets were: I, Control; II, Fructose (63.2% of fructose); and III, CLA+Fructose (1% CLA and 63.2% of fructose). The experimental treatments had no effect on body weight of the rats. The LDL+VLDL cholesterol, TG and liver weight were significantly increased in animals fed Fructose. MDA concentrations were significantly increased in rats fed Fructose diet but CLA+Fructose diet had no effect on this marker. In the same line, the histological examination of the livers showed a series of morphological alterations, notably hepatic steatosis in animals fed high-fructose diet. No signs of the steatosis in rats fed CLA+Fructose diet were observed. In conclusion, CLA in high-fructose diet, decreases serum LDL+VLDL and TG and plasma MDA concentrations as well as liver weight and liver cholesterol, thus opposing the effects of high-fructose diet and showing a potential antiatherogenic effect. Similarly, dietary CLA fed at 1% level (w/w) in high-fructose diet, prevented steatosis observed histologically in livers of rats fed high-fructose diets.

  2. Ultrastructural features of Glisson's capsule and the overlying mesothelium in rat, monkey and pike liver.

    PubMed

    Chapman, G B; Eagles, D A

    2007-10-01

    Samples from the liver of a male rat (Sprague-Dawley), a monkey (Macacus rhesus), and a longnose gar pike (Lepisosteus osseus) were studied in a transmission electron microscope to provide cytological and histological information about structures previously poorly documented in the literature. Glisson's capsule consisted of dense, irregular connective tissue of typical Type-I collagen fibrils. The capsule was formed by a single stratum of fibroblasts in the rat and in the pike, but by one or two strata of fibroblasts in the monkey. In the rat, but not in the monkey or pike, fibroblast processes interdigitated with processes from the hepatocytes. In the pike, fibroblast processes extended toward both mesothelium and hepatocytes. In some areas of the rat and pike, mesothelial cells had desmosomal connections and microvillous projections into the peritoneal cavity. Marginated heterochromatin was more abundant in the rat and monkey. The mesothelium was discontinuous in the rat and monkey but, in areas of discontinuity, the capsular surface was covered by a basal lamina, often barely perceptible beneath mesothelial cells of the rat and monkey, but prominent in the pike. In the pike, the mesothelium had numerous pinocytotic vesicles on both peritoneal and capsular surfaces.

  3. Protective effect of rosuvastatin treatment by regulating oxidized low-density lipoprotein expression in a rat model of liver fibrosis.

    PubMed

    Yu, Shuiping; Zhou, Xueling; Hou, Bingzong; Tang, Bo; Li, Jian; Zhang, Baimeng

    2016-09-01

    The present study aimed to evaluate the protective effect of rosuvastatin treatment on the mechanism of oxidized low-density lipoprotein (Ox-LDL) in rats with liver fibrosis. In total, 72 male Sprague-Dawley rats were divided into 3 groups: 24 in the control group (A), 24 in the obstructive jaundice models group (B) and 24 in the rosuvastatin group (C). Each group was further divided into four subgroups for assessment at different time-points. The obstructive jaundice models were established and rosuvastatin was administered by gavage. Liver fibrosis indicators, Ox-LDL, malonaldehyde (MDA) and superoxide dismutase (SOD), were measured and liver pathological changes were observed at weeks 1, 2, 3 and 4 after model induction. In groups B and C, the rat models were successfully established, and there were significant changes in the expression of Ox-LDL and the three liver fibrosis indicators when compared to group A (P<0.01). However, the expression of Ox-LDL and the three liver fibrosis indicators in group C were decreased compared with group B (P<0.05), while SOD increased (P<0.05) and MDA decreased (P<0.05). The three liver fibrosis indicators were different in comparison to group B (P<0.05). Thus, there appeared to be an association between the expression of Ox-LDL and liver fibrosis. Treatment with rosuvastatin could regulate the expression of Ox-LDL and improve liver fibrosis in rat models with obstructive jaundice.

  4. DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion

    SciTech Connect

    Rabes, H.M.; Kerler, R.; Wilhelm, R.

    1983-01-01

    Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of (/sup 14/C)N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O6-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O6-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.

  5. Involvement of the H+/organic cation antiporter in nicotine transport in rat liver.

    PubMed

    Tega, Yuma; Akanuma, Shin-Ichi; Kubo, Yoshiyuki; Hosoya, Ken-Ichi

    2015-01-01

    Nicotine is an addictive alkaloid in cigarette smoke and is responsible for tobacco dependence. It is important to consider the blood-to-liver transport of nicotine to understand the nicotine elimination from the body because most of the nicotine is converted to inactive metabolites by cytochrome P450 localized in the endoplasmic reticulum of the hepatocytes. In this study, the blood-to-liver transport of nicotine was investigated by means of an in vivo portal vein injection technique in rats, and the in vitro uptake by freshly isolated rat hepatocytes was used to clarify its mechanism. The results obtained showed that the in vivo blood-to-liver transport of [(3)H]nicotine was significantly inhibited by 50 mM nicotine and pyrilamine, suggesting involvement of a carrier-mediated transport process in the blood-to-liver transport of nicotine. The in vitro uptake study using freshly isolated rat hepatocytes showed a time- and concentration-dependent uptake of [(3)H]nicotine with a Km value of 141 µM, and the uptake was increased under alkaline extracellular conditions. In addition, intracellular acidification caused an increase in [(3)H]nicotine uptake, suggesting that the influx transport of nicotine is driven by an oppositely directed H(+) gradient in hepatocytes. Moreover, [(3)H]nicotine uptake was strongly inhibited in the presence of cationic drugs, such as pyrilamine, whereas only weak inhibitory effects were shown by substrates of typical organic cation transporters, such as tetraethylammonium, 1-methyl-4-phenylpyridinium, choline, and l-carnitine. In conclusion, a carrier-mediated system controlling the blood-to-liver transport of nicotine appears to be present on the sinusoidal membrane of hepatocytes. The pattern of inhibition and ion dependence is suggestive of an H(+)/organic cation antiporter-mediated nicotine transport system.

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

    PubMed Central

    Chae, Hyun-Jung; Yim, Jung-Eun; Kim, Kyung-Ah

    2014-01-01

    As well-being foods pursuing healthy life are becoming popular, interest in Rubus coreanus Miquel (RCM) fruit, a type of Korean blackberry, is increasing due to its medicinal actions including protecting the liver, brightening the eyes, and alleviating diabetes. This study was carried out to evaluate the hepatoprotective effects of RCM concentrates on liver injuries induced by carbon tetrachloride (CCl4) in rats. RCM, produced in June ~ July 2008 at Chunbook, Gochang (South Korea), was finely mashed. The seeds were removed and the juices were condensed. Thirty-two Sprague-Dawley rats were divided into four groups according to treatment: normal (eight rats), CCl4, 1% RCM, and 2% RCM. Experimental diets were provided to the experimental animals for 4 weeks. We measure total cholesterol, high density lipoprotein-cholesterol (HDL-C), aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) levels. Part of the livers was isolated for histopathological evaluation, and analyzed for lipid peroxide (TBARS), superoxide dismutase (SOD) and liver proteins. The activities of serum AST, ALT, and ALP were elevated following CCl4 administration. Levels of hepatic TBARS were also significantly increased in the CCl4 groups. However, hepatic TBARS levels and the activities of serum enzymes were markedly reduced by supplementation with the RCM concentrates (P < 0.05). Hepatic SOD activity increased in the RCM concentrates group versus CCl4 groups. Histopathological examination revealed massive necrosis in the centrilobular area and degenerative changes caused by CCl4 were ameliorated by dietary supplementation with RCM concentrates. These results suggest that RCM concentrates have hepatoprotective effects and may improve the symptoms of liver injuries. PMID:24611104

  7. Protective Effects of Ecklonia stolonifera Extract on Ethanol-Induced Fatty Liver in Rats

    PubMed Central

    Bang, Chae-Young; Byun, Jae-Hyuk; Choi, Hye-Kyung; Choi, Jae-Sue; Choung, Se-Young

    2016-01-01

    Chronic alcohol consumption causes alcoholic liver disease, which is associated with the initiation of dysregulated lipid metabolism. Recent evidences suggest that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver disease. Ecklonia stolonifera (ES), a perennial brown marine alga that belongs to the family Laminariaceae, is rich in phlorotannins. Many studies have indicated that ES has extensive pharmacological effects, such as antioxidative, hepatoprotective, and antiinflammatory effects. However, only a few studies have investigated the protective effect of ES in alcoholic fatty liver. Male Sprague-Dawley rats were randomly divided into normal diet (ND) (fed a normal diet for 10 weeks) and ethanol diet (ED) groups. Rats in the ED group were fed a Lieber-DeCarli liquid diet (containing 5% ethanol) for 10 weeks and administered ES extract (50, 100, or 200 mg/kg/day), silymarin (100 mg/kg/day), or no treatment for 4 weeks. Each treatment group comprised of eight rats. The supplementation with ES resulted in decreased serum levels of triglycerides (TGs), total cholesterol, alanine aminotransferase, and aspartate aminotransferase. In addition, there were decreases in hepatic lipid and malondialdehyde levels. Changes in liver histology, as analyzed by Oil Red O staining, showed that the ES treatment suppressed adipogenesis. In addition, the ES treatment increased the expression of fatty acid oxidation-related genes (e.g., PPAR-α and CPT-1) but decreased the expression of SREBP 1, which is a TG synthesis-related gene. These results suggest that ES extract may be useful in preventing fatty acid oxidation and reducing lipogenesis in ethanol-induced fatty liver. PMID:27795452

  8. Macrophages mediate colon carcinoma cell adhesion in the rat liver after exposure to lipopolysaccharide

    PubMed Central

    Gül, Nuray; Grewal, Simran; Bögels, Marijn; van der Bij, Gerben J.; Koppes, Malika M.A.; Oosterling, Steven J.; Fluitsma, Donna M.; Hoeben, Kees A.; Beelen, Robert H. J.; van Egmond, Marjolein

    2012-01-01

    The surgical resection of primary colorectal cancer is associated with an enhanced risk of liver metastases. Moreover, bacterial translocation or anastomic leakage during resection has been shown to correlate with a poor long-term surgical outcome, suggesting that bacterial products may contribute to the formation of metastases. Driven by these premises, we investigated the role of the bacterial product lipopolysaccharide (LPS) in the generation of liver metastases. Intraperitoneal injection of LPS led to enhanced tumor-cell adhesion to the rat liver as early as 1.5 h post-administration. Furthermore, a rapid loss of the expression of the tight junction protein zonula occludens-1 (ZO-1) was observed, suggesting that LPS disrupts the integrity of the microvasculature. LPS addition to endothelial-macrophage co-cultures damaged endothelial monolayers and caused the formation of intercellular gaps, which was accompanied by increased tumor-cell adhesion. These results suggest that macrophages are involved in the endothelial damage resulting from exposure to LPS. Interestingly, the expression levels of of ZO-1 were not affected by LPS treatment in rats in which liver macrophages had been depleted as well as in rats that had been treated with a reactive oxygen species (ROS) scavenger. In both settings, decreased tumor-cell adhesion was observed. Taken together, our findings indicate that LPS induces ROS release by macrophages, resulting in the damage of the vascular lining of the liver and hence allowing increased tumor-cell adherence. Thus, peri-operative treatments that prevent the activation of macrophages and—as a consequence—limit endothelial damage and tumor-cell adhesion may significantly improve the long-term outcome of cancer patients undergoing surgical tumor resection. PMID:23264898

  9. Dose-Dependent Effect of Deltamethrin in Testis, Liver, and Kidney of Wistar Rats

    PubMed Central

    Sharma, Poonam; Singh, Rambir; Jan, Mysra

    2014-01-01

    Objectives: Deltamethrin is a synthetic pyrethroid insecticide used worldwide in agriculture, household pest control, protection of foodstuff, and disease vector control. Although initially thought to be least toxic, a number of recent reports showed its toxic effects in mammalian and non-mammalian animal species. The current study was performed to assess the dose-dependent deltamethrin toxicity on testes, liver, and kidney of male Wistar rats. Materials and Methods: Twenty-four rats were divided in four groups of 6 each. Group A served as normal control. Group B, C, and D were administered with different doses (2 or 3 or 6 mg/kg corresponding to 1/30th or 1/20th or 1/10th of LD50, respectively) of deltamethrin for 28 days. Results: Deltamethrin exposure caused a significant reduction in weight of reproductive organs, decrease in sperm count, sperm motility, serum testosterone (T), follicle stimulating hormones (FSH), and luteinizing hormones (LH) in testis. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) were decreased in testis, liver and kidney of exposed rats. Deltamethrin exposure significantly increased sperm abnormalities in testis. Significant increase in lipid peroxidation (LPO) level was observed in testis, liver and kidney. Deltamethrin also caused histological alterations in testes, liver, and kidney. Conclusions: The results indicated that deltamethrin at a dose of 6 mg/kg exerts significant harmful effects on testes, liver and kidney as compare to 2 mg and 3 mg/kg. The study concluded that the system toxicity induced by deltamethrin was dose dependent. PMID:25253921

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

    PubMed

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

    2014-06-01

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

  11. The interaction of glycolysis, gluconeogenesis and the tricarboxylic acid cycle in rat liver in vivo

    PubMed Central

    Heath, D. F.; Threlfall, C. J.

    1968-01-01

    1. The equations derived by Heath (1968) were applied to data from experiments on rats in four metabolic states: fed, post-absorptive, starved and 2hr. after an eventually lethal injury. T