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Sample records for copper particle-induced hepatotoxicity

  1. Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: a rapid in vivo screening method for nanotoxicity.

    Science.gov (United States)

    Lei, Ronghui; Wu, Chunqi; Yang, Baohua; Ma, Huazhai; Shi, Chang; Wang, Quanjun; Wang, Qingxiu; Yuan, Ye; Liao, Mingyang

    2008-10-15

    Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using (1)H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid beta-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced

  2. Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid invivo screening method for nanotoxicity

    International Nuclear Information System (INIS)

    Lei Ronghui; Wu Chunqi; Yang Baohua; Ma Huazhai; Shi Chang; Wang Quanjun; Wang Qingxiu; Yuan Ye; Liao Mingyang

    2008-01-01

    Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using 1 H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid β-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by

  3. Assessment of copper nanoparticles (Cu-NPs) and copper (II) oxide (CuO) induced hemato- and hepatotoxicity in Cyprinus carpio

    Science.gov (United States)

    Noureen, Aasma; Jabeen, Farhat; Tabish, Tanveer A.; Yaqub, Sajid; Ali, Muhammad; Shakoor Chaudhry, Abdul

    2018-04-01

    hepatotoxicity in C. carpio of this study.

  4. Hydrazine inhalation hepatotoxicity.

    Science.gov (United States)

    Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

    2007-10-01

    Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management.

  5. Hepatotoxicity of amiodarone

    DEFF Research Database (Denmark)

    Rumessen, J J

    1986-01-01

    of the hepatotoxicity of amiodarone is given. It is concluded that solid evidence exists of hepatic injury due to amiodarone treatment, including steatosis, alterations resembling alcoholic hepatitis, cholestatic hepatitis and micronodular cirrhosis of the liver. Patients receiving amiodarone should be regularly......Amiodarone has proved very effective in the treatment of otherwise resistant cardiac tachyarrhythmias. The use of amiodarone has, however, been limited due to its serious side-effects. A patient with cholestatic hepatitis due to amiodarone treatment is presented below and a review...... screened with respect to hepatic enzyme levels. Therapy should be discontinued on the suspicion of cholestatic injury or hepatomegaly....

  6. Particle induced X-ray emission

    International Nuclear Information System (INIS)

    Cohen, D.D.

    1991-08-01

    The accelerator based ion beam technique of Particle Induced X-ray Emission (PIXE) is discussed in some detail. This report pulls together all major reviews and references over the last ten years and reports on PIXE in vacuum and using external beams. The advantages, limitations, costs and types of studies that may be undertaken using an accelerator based ion beam technique such as PIXE, are also discussed. 25 refs., 7 tabs., 40 figs

  7. Liver inflammation during monocrotaline hepatotoxicity

    International Nuclear Information System (INIS)

    Copple, Bryan L.; Ganey, Patricia E.; Roth, Robert A.

    2003-01-01

    Monocrotaline (MCT) is a pyrrolizidine alkaloid (PA) plant toxin that causes hepatotoxicity in humans and animals. Human exposure occurs from consumption of contaminated grains and herbal teas and medicines. Intraperitoneal injection (i.p.) of 300 mg/kg MCT in rats produced time-dependent hepatic parenchymal cell (HPC) injury beginning at 12 h. At this time, an inflammatory infiltrate consisting of neutrophils (PMNs) appeared in areas of hepatocellular injury, and activation of the coagulation system occurred. PMN accumulation was preceded by up-regulation of the PMN chemokines cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) in the liver. The monocyte chemokine, monocyte chemoattractant protein-1 (MCP-1), was also upregulated. Inhibition of Kupffer cell function with gadolinium chloride (GdCl 3 ) significantly reduced CINC-1 protein in plasma after MCT treatment but had no effect on hepatic PMN accumulation. Since inflammation can contribute to either pathogenesis or resolution of tissue injury, we explored inflammatory factors as a contributor to MCT hepatotoxicity. To test the hypothesis that PMNs contribute to MCT-induced HPC injury, rats were depleted of PMNs with a rabbit anti-PMN serum prior to MCT treatment. Anti-PMN treatment reduced hepatic PMN accumulation by 80% but had no effect on MCT-induced HPC injury or activation of the coagulation system. To test the hypothesis that Kupffer cells and/or tumor necrosis factor-α (TNF-α) are required for MCT-induced HPC injury, rats were treated with either GdCl 3 to inhibit Kupffer cell function or pentoxifylline (PTX) to prevent synthesis of TNF-α. Neither treatment prevented MCT-induced HPC injury. Results from these studies suggest that PMNs, Kupffer cells and TNF-α are not critical mediators of MCT hepatotoxicity. Accordingly, although inflammation occurs in the liver after MCT treatment, it is not required for HPC injury and possibly occurs secondary to

  8. Review article: herbal and dietary supplement hepatotoxicity.

    Science.gov (United States)

    Bunchorntavakul, C; Reddy, K R

    2013-01-01

    Herbal and dietary supplements are commonly used throughout the World. There is a tendency for underreporting their ingestion by patients and the magnitude of their use is underrecognised by Physicians. Herbal hepatotoxicity is not uncommonly encountered, but the precise incidence and manifestations have not been well characterised. To review the epidemiology, presentation and diagnosis of herbal hepatotoxicity. This review will mainly discuss single ingredients and complex mixtures of herbs marketed under a single label. A Medline search was undertaken to identify relevant literature using search terms including 'herbal', 'herbs', 'dietary supplement', 'liver injury', 'hepatitis' and 'hepatotoxicity'. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches. The incidence rates of herbal hepatotoxicity are largely unknown. The clinical presentation and severity can be highly variable, ranging from mild hepatitis to acute hepatic failure requiring transplantation. Scoring systems for the causality assessment of drug-induced liver injury may be helpful, but have not been validated for herbal hepatotoxicity. Hepatotoxicity features of commonly used herbal products, such as Ayurvedic and Chinese herbs, black cohosh, chaparral, germander, greater celandine, green tea, Herbalife, Hydroxycut, kava, pennyroyal, pyrrolizidine alkaloids, skullcap, and usnic acid, have been individually reviewed. Furthermore, clinically significant herb-drug interactions are also discussed. A number of herbal medicinal products are associated with a spectrum of hepatotoxicity events. Advances in the understanding of the pathogenesis and the risks involved are needed to improve herbal medicine safety. © 2012 Blackwell Publishing Ltd.

  9. [Hepatox: database on hepatotoxic drugs].

    Science.gov (United States)

    Quinton, A; Latry, P; Biour, M

    1993-01-01

    Hepatox is a data base on the hepatotoxic drugs file published every year in Gastroentérologie Clinique et Biologique. The program was developed under Omnis 7 for Apple computers, and under Visual Basic Professional Toolkit and Code Base for IBM PC and compatibles computers. The data base includes forms of 866 drugs identified by their approved name and those of their 1,300 corresponding proprietary names in France; drugs are distributed among 104 pharmacological classes. It is possible to have instantaneously access to the card of a drug identified by its approved name. Acceding to a drug identified by its proprietary name gives a list of the approved name of its components; going from a name of this list to the correspondent card of hepatoxicity is immediate. It is easy to extract lists of drugs responsible of a type of hepatic injury, and a table of types of hepatic injuries induced by the drugs of a pharmacological class.

  10. Risk prediction of hepatotoxicity in paracetamol poisoning.

    Science.gov (United States)

    Wong, Anselm; Graudins, Andis

    2017-09-01

    Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment. Similarly, there would be benefit in early identification of those with a low likelihood of developing hepatotoxicity, as this group may be safely treated with an abbreviated acetylcysteine regimen. To review the current literature related to risk prediction tools that can be used to identify patients at increased risk of hepatotoxicity. A systematic literature review was conducted using the search terms: "paracetamol" OR "acetaminophen" AND "overdose" OR "toxicity" OR "risk prediction rules" OR "hepatotoxicity" OR "psi parameter" OR "multiplication product" OR "half-life" OR "prothrombin time" OR "AST/ALT (aspartate transaminase/alanine transaminase)" OR "dose" OR "biomarkers" OR "nomogram". The search was limited to human studies without language restrictions, of Medline (1946 to May 2016), PubMed and EMBASE. Original articles pertaining to the theme were identified from January 1974 to May 2016. Of the 13,975 articles identified, 60 were relevant to the review. Paracetamol treatment nomograms: Paracetamol treatment nomograms have been used for decades to help decide the need for acetylcysteine, but rarely used to determine the risk of hepatotoxicity with treatment. Reported paracetamol dose and concentration: A dose ingestion >12 g or serum paracetamol concentration above the treatment thresholds on the paracetamol nomogram are associated with a greater risk of hepatotoxicity. Paracetamol elimination half

  11. Hepatotoxicity and the present herbal hepatoprotective scenario

    OpenAIRE

    Priyankar Dey; Manas Ranjan Saha; Arnab Sen

    2013-01-01

    Most of the metabolic and physiological processes of our body as well as the detoxification of various drugs and xenobiotic chemicals occur in the liver. During this detoxification process, the reactive chemical intermediates damage the liver severely. There are several commercially available drugs, consumption of which results in idiosyncratic drug reaction mediated hepatotoxicity. Drug induced hepatotoxicity is a burning problem in this regard and several drugs are withdrawn from the market...

  12. Alpha particle induced soft errors in NMOS RAMs: a review

    International Nuclear Information System (INIS)

    Carter, P.M.; Wilkins, B.R.

    1987-01-01

    The paper aims to explain the alpha particle induced soft error phenomenon using the NMOS dynamic random access memory (RAM) as a model. It discusses some of the many techniques experimented with by manufacturers to overcome the problem, and gives a review of the literature covering most aspects of soft errors in dynamic RAMs. Finally, the soft error performance of current dynamic RAM and static RAM products from several manufacturers are compared. (author)

  13. Activation cross-section data for -particle-induced nuclear reactions ...

    Indian Academy of Sciences (India)

    B M ALI

    2018-02-20

    particle-induced nuclear reactions on natural vanadium up to 20 MeV. It should be mentioned that this study represents a part of (a supplement) systematical study of charged particles-induced nuclear reactions. Earlier studies were.

  14. Mitochondrial–Lysosomal Axis in Acetaminophen Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Anna Moles

    2018-05-01

    Full Text Available Acetaminophen (APAP toxicity is the most common cause of acute liver failure and a major indication for liver transplantion in the United States and Europe. Although significant progress has been made in understanding the molecular mechanisms underlying APAP hepatotoxicity, there is still an urgent need to find novel and effective therapies against APAP-induced acute liver failure. Hepatic APAP metabolism results in the production of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI, which under physiological conditions is cleared by its conjugation with glutathione (GSH to prevent its targeting to mitochondria. APAP overdose or GSH limitation leads to mitochondrial NAPQI-protein adducts formation, resulting in oxidative stress, mitochondrial dysfunction, and necrotic cell death. As mitochondria are a major target of APAP hepatotoxicity, mitochondrial quality control and clearance of dysfunctional mitochondria through mitophagy, emerges as an important strategy to limit oxidative stress and the engagement of molecular events leading to cell death. Recent evidence has indicated a lysosomal–mitochondrial cross-talk that regulates APAP hepatotoxicity. Moreover, as lysosomal function is essential for mitophagy, impairment in the fusion of lysosomes with autophagosomes-containing mitochondria may compromise the clearance of dysfunctional mitochondria, resulting in exacerbated APAP hepatotoxicity. This review centers on the role of mitochondria in APAP hepatotoxicity and how the mitochondrial/lysosomal axis can influence APAP-induced liver failure.

  15. [Hepatotoxicity associated with the use of Herbalife].

    Science.gov (United States)

    Jóhannsson, Magnús; Ormarsdóttir, Sif; Olafsson, Sigurdur

    2010-03-01

    Many herbal products are known to be hepatotoxic. In a recent survey in Iceland concerning adverse reactions related to herbal medicines, Herbalife products were implicated in the majority of the reported cases of hepatotoxicity. The clinical presentations of five cases of Herbalife related liver injury during the period of 1999-2008 are analysed. Causality was assessed by using the WHO-UMC system for causality assessment and the RUCAM method. Of the five cases there were four females and one male; median age was 46 years (range 29-78). Herbalife had been used for 1 to 7 months prior to presentation. Four patients presented with a hepatocellular and one with a cholestatic reaction. Median values were for bilirubin 190 micromol/L (range: 26-311; ref. Herbalife products. Hepatotoxicity due to herbal remedies is an important differential diagnosis in the diagnostic work-up of liver injury.

  16. Hepatotoxicity with antituberculosis drugs: the risk factors

    International Nuclear Information System (INIS)

    Mahmood, K.; Samo, A.H.; Jairamani, K.L.; Talib, A.

    2007-01-01

    To assess the severity and frequency of hepatotoxicity caused by different antituberculosis (ATT) drugs and to evaluate whether concurrence of risk factors influence the antituberculosis drug induced hepatotoxicity. This prospective cohort study was conducted in Medical Unit-V and OPD department of Civil Hospital Karachi from July 2004 to July 2005. A total of 339 patients diagnosed of active tuberculosis infection with normal pretreatment liver function were monitored clinically as well as biochemically. Their data were collected on proforma and patients were treated with Isoniazid, Rifampicin and Pyrazinamide. Duration after which derangement in function, if any, occurred and time taken for normalization was noted. Treatment was altered as needed, with exclusion of culprit drug. Finally data was analyzed by SPSS version 10.0. ATT induced hepatotoxicity was seen in 67 (19.76%) out of 339 patients. Females were more affected as compared to males (26.3% vs. 19.7%). BMI (kg/m2) of 91% of diseased group were less than 18.5 (p<0.01) most of them were anemic having low albumin level suggestive of lean body mass. Hepatotoxicity was more severe in AFB smear positive patients. Concomitant use of alcohol, paracetamol and low serum cholesterol were proved as predisposing factors. Isoniazid (37 patients (55.21%), p<0.01) was the main culprit followed by Rifampicin (23 patients, 34.21%) and Pyrazinamide (7 patients, 10.5%). Most of the patients (61%) developed the hepatotoxicity within two weeks of starting antituberculosis therapy with mild to moderate alteration in ALT and AST. ATT-induced hepatitis is significantly more frequent and more severe in patients with hepatotoxicity risk factors. (author)

  17. A facility for low energy charged particle induced reaction studies

    International Nuclear Information System (INIS)

    Vilaithong, T.; Singkarat, S.; Yu, L.D.; Intarasiri, S.; Tippawan, U.

    2000-01-01

    In Chiang Mai, a highly stable low energy ion accelerator (0 - 350 kV) facility is being established. A subnano-second pulsing system will be incorporated into the beam transport line. The detecting system will consist of a time-of-flight charged particle spectrometer and a high resolution gamma-ray system. The new facility will be used in the studies of low energy heavy ion backscattering and charged particle induced cross section measurement in the interests of material characterization and nucleosynthesis. (author)

  18. Enhancement of acetaminophen overdosage-induced hepatotoxicity ...

    African Journals Online (AJOL)

    paracetamol) overdosage-induced hepatotoxicity in three groups of albino Wistar rats. Administration of the minimum toxic dose of paracetamol (150mg/kg body weight) to animals (group II) produced significantly (P≤0.05) higher levels of alanine ...

  19. Analysis of charged particle induced reactions for beam monitor applications

    Energy Technology Data Exchange (ETDEWEB)

    Surendra Babu, K. [IOP, Academia Sinica, Taipe, Taiwan (China); Lee, Young-Ouk [Nuclear Data Evaluation Laboratory, Korea Atomic Energy Research Institute (Korea, Republic of); Mukherjee, S., E-mail: smukherjee_msuphy@yahoo.co.in [Department of Physics, Faculty of Science, M.S. University of Baroda, Vadodara 390 002 (India)

    2012-07-15

    The reaction cross sections for different residual nuclides produced in the charged particle (p, d, {sup 3}He and {alpha}) induced reactions were calculated and compared with the existing experimental data which are important for beam monitoring and medical diagnostic applications. A detailed literature compilation and comparison were made on the available data sets for the above reactions. These calculations were carried out using the statistical model code TALYS up to 100 MeV, which contains Kalbach's latest systematic for the emission of complex particles and complex particle-induced reactions. All optical model calculations were performed by ECIS-03, which is built into TALYS. The level density, optical model potential parameters were adjusted to get the better description of experimental data. Various pre-equilibrium models were used in the present calculations with default parameters.

  20. {alpha}-particle induced reactions on yttrium and terbium

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, S.; Kumar, B.B. [School of Studies in Physics, Vikram University, Ujjain-456010 (India); Rashid, M.H. [Variable Energy Cyclotron Center, 1/AF, Bidhan Nagar, Calcutta (India); Chintalapudi, S.N. [Inter-University Consortium for DAE Facilities, 3/LB, Bidhan Nagar, Calcutta (India)

    1997-05-01

    The stacked foil activation technique has been employed for the investigation of {alpha}-particle induced reactions on the target elements yttrium and terbium up to 50 MeV. Six excitation functions for the ({alpha},xn) type of reactions were studied using high-resolution HPGe {gamma}-ray spectroscopy. A comparison with Blann{close_quote}s geometric dependent hybrid model has been made using the initial exciton number n{sub 0}=4(4p0h) and n{sub 0}=5(5p0h). A broad general agreement is observed between the experimental results and theoretical predictions with an initial exciton number n{sub 0}=4(4p0h). {copyright} {ital 1997} {ital The American Physical Society}

  1. α-particle induced reactions on yttrium and terbium

    International Nuclear Information System (INIS)

    Mukherjee, S.; Kumar, B.B.; Rashid, M.H.; Chintalapudi, S.N.

    1997-01-01

    The stacked foil activation technique has been employed for the investigation of α-particle induced reactions on the target elements yttrium and terbium up to 50 MeV. Six excitation functions for the (α,xn) type of reactions were studied using high-resolution HPGe γ-ray spectroscopy. A comparison with Blann close-quote s geometric dependent hybrid model has been made using the initial exciton number n 0 =4(4p0h) and n 0 =5(5p0h). A broad general agreement is observed between the experimental results and theoretical predictions with an initial exciton number n 0 =4(4p0h). copyright 1997 The American Physical Society

  2. Charged particle induced thermonuclear reaction rates: a compilation for astrophysics

    International Nuclear Information System (INIS)

    Grama, C.

    1999-01-01

    We report on the results of the European network NACRE (Nuclear Astrophysics Compilation of REaction rates). The principal reason for setting up the NACRE network has been the necessity of building up a well-documented and detailed compilation of rates for charged-particle induced reactions on stable targets up to Si and on unstable nuclei of special significance in astrophysics. This work is meant to supersede the only existing compilation of reaction rates issued by Fowler and collaborators. The main goal of NACRE network was the transparency in the procedure of calculating the rates. More specifically this compilation aims at: 1. updating the experimental and theoretical data; 2. distinctly identifying the sources of the data used in rate calculation; 3. evaluating the uncertainties and errors; 4. providing numerically integrated reaction rates; 5. providing reverse reaction rates and analytical approximations of the adopted rates. The cross section data and/or resonance parameters for a total of 86 charged-particle induced reactions are given and the corresponding reaction rates are calculated and given in tabular form. Uncertainties are analyzed and realistic upper and lower bounds of the rates are determined. The compilation is concerned with the reaction rates that are large enough for the target lifetimes shorter than the age of the Universe, taken equal to 15 x 10 9 y. The reaction rates are provided for temperatures lower than T = 10 10 K. In parallel with the rate compilation a cross section data base has been created and located at the site http://pntpm.ulb.ac.be/nacre..htm. (authors)

  3. Applications of particle induced X-ray emission

    International Nuclear Information System (INIS)

    Akselsson, K. R.

    1978-01-01

    In Particle Induced X-ray Emission (PIXE) analysis samples are bombarded by protons or α-particles of a few MeV/u. The induced characteristic x-rays are detected with a x-ray detector e.g. a Si(Li)-detector. The energies of the x-ray peaks are characteristic for the elements in the samples and the intensities of the x-ray transitions are proportional to the abundances of the elements. The research area which first attracted those of us working with PIXE was the study of sources, transport and deposition of airborne particulates. Sources, transport, wet deposition, other applications where PIXE is already known to be competitive are trace elemental analysis of water below the ppb-level and analyses requiring a space resolution of 1-10μ. However, there is still much to do for physicists in developing the full potential of low-energy accelerators as analytical tools in multidisciplinary teams. (JIW)

  4. Investigation of energetic particle induced geodesic acoustic mode

    Science.gov (United States)

    Schneller, Mirjam; Fu, Guoyong; Chavdarovski, Ilija; Wang, Weixing; Lauber, Philipp; Lu, Zhixin

    2017-10-01

    Energetic particles are ubiquitous in present and future tokamaks due to heating systems and fusion reactions. Anisotropy in the distribution function of the energetic particle population is able to excite oscillations from the continuous spectrum of geodesic acoustic modes (GAMs), which cannot be driven by plasma pressure gradients due to their toroidally and nearly poloidally symmetric structures. These oscillations are known as energetic particle-induced geodesic acoustic modes (EGAMs) [G.Y. Fu'08] and have been observed in recent experiments [R. Nazikian'08]. EGAMs are particularly attractive in the framework of turbulence regulation, since they lead to an oscillatory radial electric shear which can potentially saturate the turbulence. For the presented work, the nonlinear gyrokinetic, electrostatic, particle-in-cell code GTS [W.X. Wang'06] has been extended to include an energetic particle population following either bump-on-tail Maxwellian or slowing-down [Stix'76] distribution function. With this new tool, we study growth rate, frequency and mode structure of the EGAM in an ASDEX Upgrade-like scenario. A detailed understanding of EGAM excitation reveals essential for future studies of EGAM interaction with micro-turbulence. Funded by the Max Planck Princeton Research Center. Computational resources of MPCDF and NERSC are greatefully acknowledged.

  5. [Screening of hepatotoxicity fraction of Genkwa Flos and study on UPLC fingerprint of hepatotoxicity fraction].

    Science.gov (United States)

    Yuan, Yang; Geng, Lu-Lu; Zhuang, He-Fei; Meng, Xia; Peng, Ying; Bi, Kai-Shun; Chen, Xiao-Hui

    2013-01-01

    To look for the active fraction of ethanol extract of Genkwa Flos (EGF) induced hepatotoxicity and develop an UPLC fingerprint of the active fraction. Target fraction of EGF induced hepatotoxicity was guided by the serum biochemical and histopathology methods. The UPLC method was applied to establish the chromatographic fingerprint. The separation was achieved on a BEH C18 column (2.1 mm x 50 mm, 1.7 microm) with a mobile phase consisting of acetonitrile and water containing 0.05% phosphate acid running gradient elution. The detection was carried out at 210 nm and the analysis was finished within 10 min. The chloroform phase of EGF could be responsible for the hepatotoxicity of this herb. The common mode of the UPLC fingerprint was set up under the established condition. There were 17 common peaks in fourteen batches of herbs, eight of which were identified, and the similar degrees of the fourteen batches to the common mode were between 0.890-0.999. It is easy to locate the chloroform extraction of EGF with hepatotoxicity. And the UPLC fingerprint was developed for the above fraction, which could provide valuable references for safe and effective clinical use of EGF.

  6. An Evaluation of Hepatotoxicity in Breast Cancer Patients Receiving ...

    African Journals Online (AJOL)

    Background: Hepatic dysfunction in the cancer unit has a significant impact on patient outcomes. The therapeutic application of anthracycline antibiotics are limited by side‑effects mainly myelosuppression, chronic cardiotoxicity, and hepatotoxicity. Aim: To assess the risk of Hepatotoxicity in breast cancer patients receiving ...

  7. Antituberculosis drugs and hepatotoxicity among hospitalized patients in Jos, Nigeria

    Directory of Open Access Journals (Sweden)

    Samson E Isa

    2016-01-01

    Conclusion: Hepatotoxicity due to first-line anti-TBs, whether based on clinical features alone or backed by liver chemistry, is common among hospitalized patients in our environment. Studies to determine the predictors of hepatotoxicity to guide clinical interventions aimed at the prevention or timely identification of cases are needed.

  8. [Constitutional syndrome associated to metformin induced hepatotoxicity].

    Science.gov (United States)

    de la Poza Gómez, Gema; Rivero Fernández, Miguel; Vázquez Romero, Manuel; Angueira Lapeña, Teresa; Arranz de la Mata, Gemma; Boixeda de Miquel, Daniel

    2008-12-01

    Metformin is an oral antidiabetic agent frequently used to manage type II diabetes. This drug produces nonspecific gastrointestinal symptoms in 5-20% of patients and, more rarely, has also been associated with severe adverse effects such as lactic acidosis. Only a few isolated cases of hepatotoxicity due to this drug have been documented. We report the case of an 83-year-old man with constitutional syndrome and hepatic biochemical alterations, which were attributed to metformin after ruling out an oncologic etiology and observing complete clinical and biochemical resolution after withdrawal of the drug.

  9. Possible hepatotoxicity of chronic marijuana usage

    OpenAIRE

    Borini, Paulo; Guimarães, Romeu Cardoso; Borini, Sabrina Bicalho

    2004-01-01

    CONTEXT: Hepatotoxicity is a potential complication from the usage of various illicit drugs, possibly consequent to their liver metabolism, but information on this is scarce in the medical literature. OBJECTIVE: To study the occurrence of clinical and laboratory hepatic alterations in chronic marijuana users, from the use of marijuana on its own or in association with other legal or illicit drugs. TYPE OF STUDY: transversal study SETTING: Hospital Espírita de Marília, Marília, São Paulo, Braz...

  10. Hepatotoxicity of illegal home-made alcohols.

    Science.gov (United States)

    Gökce, Hasan; Akcan, Ramazan; Celikel, Adnan; Zeren, Cem; Ortanca, Ibrahim; Demirkiran, Sumeyra

    2016-10-01

    Alcohol-related hepatotoxicity is not only caused by excessive alcohol consumption but also caused and even accelerated by hepatotoxic ingredients other than ethanol. Concentrations of hepatotoxic substances might be significantly high, particularly in illegally produced home-made alcohols. In this study we aim to analyze the hepatotoxic effects of a home-made alcohol traditionally called "bogma raki" in Turkey. Fifty Wistar albino male rats were used. Five groups were randomly formed with ten animals in each. Besides laboratory diets, groups were fed as follows: Group 1 (control group) distilled water; Group 2 bogma raki with distilled water (%44 (v/v), 9.2 ml/kg/day); Group 3 bogma raki with distilled water (%44 (v/v), 9.2 ml/kg/day)+walnut (10 g/kg/day); Group 4 whisky with distilled water (%40 (v/v), 9.2 ml/kg/day); Group 5 distilled water + walnut (10 g/kg/day), for 28 days. The toxicological analysis of The spirits were analyzed using Hewlett-Packard (Palo Alto, CA) GC/MS system with HP 6890 gas chromatograph, an HP 5972 mass selective detector (MSD) and an HP 6890 automatic liquid sampler GC/MS; the pressure of the carrier gas helium was 6.0 bar and the split value with a ratio of 1:100. The injection unit temperature set to 250 °C and MS quadrupole temperature set to 280 °C. The MS quadrupole detector ionization energy set to 70 eV. The initial column temperature was 60 °C (for 4 min) programmed by 6 °C/min to final temperature 160 °C and kept for 8 min at 160 °C. Utilized whisky and bogma raki samples were analyzed for the amounts of trans-anethole, ethanol, methanol, 1-propanolol, butanol, 2-butanol, 2-methyl-1-propanolol (isobutanol) and 3-methylbutanol (isoamyl alcohol). Histopathological changes in liver tissues were graded as follows; normal = 0 (illegally produced raki sample (%v/v) was as follows: trans-anethole %1.93, ethanol %95.70, 2-methyl-1-propanolol (isobutanol) %0.19, asetic acid %0.25, 3-methylbutanol (isoamyl

  11. Characterization of nuclear physics targets using Rutherford backscattering and particle induced X-ray emission

    International Nuclear Information System (INIS)

    Rubehn, T.; Wozniak, G.J.; Phair, L.; Moretto, L.G.; Yu, K.M.

    1997-01-01

    Rutherford backscattering and particle induced X-ray emission have been utilized to precisely characterize targets used in nuclear fission experiments. The method allows for a fast and non-destructive determination of target thickness, homogeneity and element composition. (orig.)

  12. Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Das S

    2011-06-01

    Full Text Available Suvadra Das, Partha Roy, Runa Ghosh Auddy, Arup MukherjeeDepartment of Chemical Technology, University of Calcutta, Kolkata, West Bengal, IndiaAbstract: Silymarin (Sm is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100® polymer (Rohm Pharma GmbH, Darmstadt, Germany. Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 µmol/g in hepatic tissue due to Smnps.Keywords: silymarin, paracetamol, nanoparticle, glutathione, mouse hepatotoxicity

  13. Possible hepatotoxicity of chronic marijuana usage

    Directory of Open Access Journals (Sweden)

    Paulo Borini

    Full Text Available CONTEXT: Hepatotoxicity is a potential complication from the usage of various illicit drugs, possibly consequent to their liver metabolism, but information on this is scarce in the medical literature. OBJECTIVE: To study the occurrence of clinical and laboratory hepatic alterations in chronic marijuana users, from the use of marijuana on its own or in association with other legal or illicit drugs. TYPE OF STUDY: transversal study SETTING: Hospital Espírita de Marília, Marília, São Paulo, Brazil PARTICIPANTS: The study was made among 123 patients interned in the Hospital Espírita de Marília from October 1996 to December 1998, divided into 3 groups: 26 (21% using only marijuana, 83 (67.5% using marijuana and crack, and 14 (11.4% consuming marijuana and alcohol. PROCEDURES AND MAIN MEASUREMENTS: Patients were examined clinically with special emphasis on types of drugs used, drug intake route, age when consumption began, length and pattern of usage, presence of tattooing, jaundice, hepatomegaly and splenomegaly. Serum determinations of total proteins, albumin, globulin, total and fractions of bilirubin, aspartate (AST and alanine (ALT aminotransferases, alkaline phosphatase (AP, gamma-glutamyltransferase and prothrombin activity were performed. RESULTS: Among users of only marijuana, hepatomegaly was observed in 57.7% and splenomegaly in 73.1%, and slightly elevated AST (42.3%, ALT (34.6% and AP (53.8%. The three groups did not differ significantly in the prevalence of hepatomegaly, splenomegaly and hepatosplenomegaly. The group using both marijuana and alcohol showed the highest prevalence of alterations and highest levels of aminotransferases. Mean AP levels were above normal in all groups. CONCLUSIONS: Chronic marijuana usage, on its own or in association with other drugs, was associated with hepatic morphologic and enzymatic alterations. This indicates that cannabinoids are possible hepatotoxic substances.

  14. Amelioration of lead-induced hepatotoxicity by Allium sativum ...

    African Journals Online (AJOL)

    2010-01-07

    Jan 7, 2010 ... The efficacy of garlic (Allium sativum) to reduce hepatotoxicity induced by ..... fatty acids having double bonds, largely present in the phospholipids of .... disulfide, and diallyl disulfide, possess antioxidant prop- erties and can ...

  15. Hepatotoxic and Nephrotoxic Effects of Petroleum Fumes on Petrol ...

    African Journals Online (AJOL)

    DR SULEIMAN

    Hepatotoxic and Nephrotoxic Effects of Petroleum Fumes on Petrol Attendants in Ibadan, Nigeria. *1A.L. Ogunneye ... inhalation of petrol fumes is associated with adverse effect on the kidney and liver function. ..... neurotoxicity in mice. African ...

  16. Herbal hepatotoxicity: a tabular compilation of reported cases.

    Science.gov (United States)

    Teschke, Rolf; Wolff, Albrecht; Frenzel, Christian; Schulze, Johannes; Eickhoff, Axel

    2012-11-01

    Herbal hepatotoxicity is a field that has rapidly grown over the last few years along with increased use of herbal products worldwide. To summarize the various facets of this disease, we undertook a literature search for herbs, herbal drugs and herbal supplements with reported cases of herbal hepatotoxicity. A selective literature search was performed to identify published case reports, spontaneous case reports, case series and review articles regarding herbal hepatotoxicity. A total of 185 publications were identified and the results compiled. They show 60 different herbs, herbal drugs and herbal supplements with reported potential hepatotoxicity, additional information including synonyms of individual herbs, botanical names and cross references are provided. If known, details are presented for specific ingredients and chemicals in herbal products, and for references with authors that can be matched to each herbal product and to its effect on the liver. Based on stringent causality assessment methods and/or positive re-exposure tests, causality was highly probable or probable for Ayurvedic herbs, Chaparral, Chinese herbal mixture, Germander, Greater Celandine, green tea, few Herbalife products, Jin Bu Huan, Kava, Ma Huang, Mistletoe, Senna, Syo Saiko To and Venencapsan(®). In many other publications, however, causality was not properly evaluated by a liver-specific and for hepatotoxicity-validated causality assessment method such as the scale of CIOMS (Council for International Organizations of Medical Sciences). This compilation presents details of herbal hepatotoxicity, assisting thereby clinical assessment of involved physicians in the future. © 2012 John Wiley & Sons A/S.

  17. Copper hypersensitivity

    DEFF Research Database (Denmark)

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-01-01

    hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common...

  18. Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Ebbesen, Maria S.; Nygaard, Ulrikka; Rosthøj, Susanne

    2017-01-01

    Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine...

  19. Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Nesreen E.M. Mohammed

    2016-11-01

    Conclusion: Amlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.

  20. Herbal Hepatotoxicity: Clinical Characteristics and Listing Compilation

    Directory of Open Access Journals (Sweden)

    Christian Frenzel

    2016-04-01

    Full Text Available Herb induced liver injury (HILI and drug induced liver injury (DILI share the common characteristic of chemical compounds as their causative agents, which were either produced by the plant or synthetic processes. Both, natural and synthetic chemicals are foreign products to the body and need metabolic degradation to be eliminated. During this process, hepatotoxic metabolites may be generated causing liver injury in susceptible patients. There is uncertainty, whether risk factors such as high lipophilicity or high daily and cumulative doses play a pathogenetic role for HILI, as these are under discussion for DILI. It is also often unclear, whether a HILI case has an idiosyncratic or an intrinsic background. Treatment with herbs of Western medicine or traditional Chinese medicine (TCM rarely causes elevated liver tests (LT. However, HILI can develop to acute liver failure requiring liver transplantation in single cases. HILI is a diagnosis of exclusion, because clinical features of HILI are not specific as they are also found in many other liver diseases unrelated to herbal use. In strikingly increased liver tests signifying severe liver injury, herbal use has to be stopped. To establish HILI as the cause of liver damage, RUCAM (Roussel Uclaf Causality Assessment Method is a useful tool. Diagnostic problems may emerge when alternative causes were not carefully excluded and the correct therapy is withheld. Future strategies should focus on RUCAM based causality assessment in suspected HILI cases and more regulatory efforts to provide all herbal medicines and herbal dietary supplements used as medicine with strict regulatory surveillance, considering them as herbal drugs and ascertaining an appropriate risk benefit balance.

  1. A position sensitive parallel plate avalanche fission detector for use in particle induced fission coincidence measurements

    NARCIS (Netherlands)

    Plicht, J. van der

    1980-01-01

    A parallel plate avalanche detector developed for the detection of fission fragments in particle induced fission reactions is described. The active area is 6 × 10 cm2; it is position sensitive in one dimension with a resolution of 2.5 mm. The detector can withstand a count rate of 25000 fission

  2. Qualitative analysis of a powdered diamond sample by particle induced X-ray emission (PIXE)

    International Nuclear Information System (INIS)

    Mabida, C.; Annegarn, H.J.; Renan, M.J.; Sellschop, J.P.F.

    The main purpose of this analysis was to determine whether nickel is present in diamond powder as a trace element. Particle induced X-ray emission (PIXE) showed unambiguously that nickel was present. Due to the convenience of PIXE in multielemental analysis, the investigations also include a number of other trace elements in the sample

  3. 14th International Conference on Particle Induced X-ray Emission ("PIXE 2015")

    Science.gov (United States)

    Przybyłowicz, Wojciech Józef; Pineda-Vargas, Carlos

    2015-11-01

    This special issue of Nuclear Instruments and Methods in Physics Research B contains the proceedings of the 14th International Conference on Particle Induced X-ray Emission ("PIXE 2015") that was held in Somerset West (South Africa) from 25th February to 3rd March 2015.

  4. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

    International Nuclear Information System (INIS)

    Oe, Shinji; Miyagawa, Koichiro; Honma, Yuichi; Harada, Masaru

    2016-01-01

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

  5. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

    Energy Technology Data Exchange (ETDEWEB)

    Oe, Shinji, E-mail: ooes@med.uoeh-u.ac.jp; Miyagawa, Koichiro, E-mail: koichiro@med.uoeh-u.ac.jp; Honma, Yuichi, E-mail: y-homma@med.uoeh-u.ac.jp; Harada, Masaru, E-mail: msrharada@med.uoeh-u.ac.jp

    2016-09-10

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

  6. Hepatotoxic constituents and toxicological mechanism of Xanthium strumarium L. fruits.

    Science.gov (United States)

    Xue, Li-Ming; Zhang, Qiao-Yan; Han, Ping; Jiang, Yi-Ping; Yan, Rong-Di; Wang, Yang; Rahman, Khalid; Jia, Min; Han, Ting; Qin, Lu-Ping

    2014-03-14

    In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This paper is in an attempt to identify the hepatotoxic components in Xanthium strumarium L. fruits (XSF) and interpret the toxicological mechanism induced by XSF. XSF extract was prepared and seven characteristic components were isolated and identified in XSF water extracts. We evaluated their hepatotoxicity effect on cell proliferation and lactate dehydrogenase (LDH) activity in L-02 and BRL liver cell line. An integrated metabonomics study using high-resolution (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy combined with multivariate statistical analysis was undertake to elucidate the hepatotoxicity mechanism induced in rats by XSF. The urine and serum metabolites were measured after treatment of rats with XSF (7.5, 15.0 and 30.0 g/kg/day) for 5 days. The results showed that atractyloside, carboxyatractyloside, 4'-desulphate-atractyloside and XSF induced significant cytotoxic effects in both L-02 and BRL liver cell lines, indicating that atractyloside, carboxyatractyloside, and 4'-desulphate-atractyloside were the toxic components of XSF. When rats were treated with XSF at 30.0 g/kg the hepatotoxicity was reflected in the changes observed in serum biochemical profiles and by the histopathological examination of the liver. The levels of VLDL/LDL, 3-HB, lactate, acetate, acetone and glutamate in serum were increased in this group, while d-glucose, choline and valine were decreased. The elevation in the levels of succinate, citrate, 2-oxo-glutamate, glycine, 3-HB, acetate, lactate, hippurate, dimethylglycine, methylamine, dimethylamine, phenylalanine and tryptophan was observed in urine, in contrast a reduction in the intensities of taurine, d-glucose, N-acetyl-glucoprotein and trimethylamine

  7. Activation of Nrf2 protects against triptolide-induced hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Jia Li

    Full Text Available Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF, has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2 in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN, attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.

  8. Influence of extraction methods on the hepatotoxicity of Azadirachta ...

    African Journals Online (AJOL)

    The influence of extraction methods: Cold aqueous (CA) hot aqueous (HA) and alcoholic extraction (AE) methods on the hepatotoxic effect of Azadirachta indica bark extract (ABC) was investigated using albino rats. A total of forty eight rats were divided into three groups of sixteen rats equally for the extraction methods.

  9. The Effects of Bitter Kola Supplemented Diet on Hepatotoxicity of ...

    African Journals Online (AJOL)

    MICHAEL

    supplemented rat chow and mercury contaminated water, group V animals were ... hepatotoxic effects of the heavy metal indirectly assessed by measurement of the serum levels of alkaline .... III vs V: Group IV vs V.P-values less than 0.05.

  10. Comparative Hepatotoxicity Test of Cadmium and Lead in Rats ...

    African Journals Online (AJOL)

    Background: Adverse environmental impacts include contamination of water, soil, and phytotoxicity from excessive heavy metals dispersed from mines and smelter sites leading to potential risk to human health. This study investigated the comparative hepatotoxicity test of mining pond waters used for domestic purposes in ...

  11. Hepatotoxic and Nephrotoxic Effects of Petroleum Fumes on Petrol ...

    African Journals Online (AJOL)

    The present study was conducted to evaluate the hepatotoxic and nephrotoxic effects of petroleum fumes on male and female petrol attendants. Investigations had been carried out on thirty (30) adult petrol attendants from different filling stations in Ibadan metropolis of Nigeria with ten (10) healthy adults as control. All the ...

  12. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

    Directory of Open Access Journals (Sweden)

    Xinmiao Yan

    2016-03-01

    Full Text Available Pyrrolizidine Alkaloids (PAs are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1 and glutathione peroxidase 1 (GPX1 targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  13. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

    Science.gov (United States)

    Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

    2016-03-07

    Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

  14. Particle induced X-ray emission and complementary nuclear methods for trace element determination; Plenary lecture

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, S A.E. [Lund Univ. (Sweden). Dept. of Nuclear Physics

    1992-03-01

    In this review the state-of-the-art of particle induced X-ray emission (PIXE) methods for the determination of trace elements is described. The developmental work has mostly been carried out in nuclear physics laboratories, where accelerators are available, but now the increased interest has led to the establishment of other dedicated PIXE facilities. The reason for this interest is the versatility, high sensitivity and multi-element capability of PIXE analysis. A further very important advantage is that PIXE can be combined with the microbeam technique, which makes elemental mapping with a spatial resolution of about 1 {mu}m possible. As a technique, PIXE can also be combined with other nuclear reactions such as elastic scattering and particle-induced gamma emission, so that light elements can be determined. The usefulness of PIXE is illustrated by a number of typical applications in biology, medicine, geology, air pollution research, archaeology and the arts. (author).

  15. Particle induced X-ray emission for quantitative trace-element analysis using the Eindhoven cyclotron

    International Nuclear Information System (INIS)

    Kivits, H.

    1980-01-01

    Development of a multi-elemental trace analysis technique using PIXE (Particle Induced X-ray Emission), was started almost five years ago at the Eindhoven University of Technology, in the Cyclotron Applications Group of the Physics Department. The aim of the work presented is to improve the quantitative aspects of trace-element analysis with PIXE, as well as versatility, speed and simplicity. (Auth.)

  16. Influence of resistivity on energetic trapped particle-induced internal kink modes

    International Nuclear Information System (INIS)

    Biglari, H.; Chen, L.

    1986-01-01

    The influence of resistivity on energetic trapped particle-induced internal kink modes, dubbed ''fishbones'' in the literature, is explored. A general dispersion relation, which recovers the ideal theory in its appropriate limit, is derived and analyzed. An important implication of the theory for present generation fusion devices such as the Joint European Torus [Plasma Physics and Controlled Nuclear Fusion Research (IAEA, London, 1984), Vol I, p.11] is that they will be stable to fishbone activity

  17. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Saber, Anne T.; Bornholdt, Jette; Dybdahl, Marianne; Sharma, Anoop K.; Vogel, Ulla; Wallin, Haakan [National Institute of Occupational Health, Copenhagen (Denmark); Loft, Steffen [Copenhagen University, Institute of Public Health, Copenhagen (Denmark)

    2005-03-01

    Particle-induced carcinogenicity is not well understood, but might involve inflammation. The proinflammatory cytokine tumor necrosis factor (TNF) is considered to be an important mediator in inflammation. We investigated its role in particle-induced inflammation and DNA damage in mice with and without TNF signaling. TNF-/- mice and TNF+/+ mice were exposed by inhalation to 20 mg m{sup -3} carbon black (CB), 20 mg m{sup -3} diesel exhaust particles (DEP), or filtered air for 90 min on each of four consecutive days. DEP, but not CB particles, induced infiltration of neutrophilic granulocutes into the lung lining fluid (by the cellular fraction in the bronchoalveolar lavage fluid), and both particle types induced interleukin-6 mRNA in the lung tissue. Surprisingly, TNF-/- mice were intact in these inflammatory responses. There were more DNA strand breaks in the BAL cells of DEP-exposed TNF-/- mice and CB-exposed mice compared with the air-exposed mice. Thus, the CB-induced DNA damage in BAL-cells was independent of neutrophil infiltration. The data indicate that an inflammatory response was not a prerequisite for DNA damage, and TNF was not required for the induction of inflammation by DEP and CB particles. (orig.)

  18. The Possible Efficacy of Artichoke in Fluconazole Related Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hüseyin Kurt

    2014-01-01

    Full Text Available Although fluconazole related hepatotoxicity (FRH is rare, mortal acute hepatic necrosis and jaundice were reported in immunocompromised states such as acquired immunodeficiency syndrome (AIDS and bone marrow transplant (BMT. We present a case of a patient with multiple sclerosis who developed hepatotoxicity with the use of a single 150 mg fluconazole tablet for fungal vaginitis, 10 days after methylprednisolone pulse treatment. Our patient’s alanine aminotransferase (ALT and aspartate aminotransferase (AST levels were decreased, 1200 U/L and 800 U/L, respectively, and bilirubin levels were consistent at 37 mg/dL. Artichoke which has anticholestatic and antioxidant properties was used by our patient. She consumed a 30 mg artichoke leaf extract tea 3 times a day. The bilirubin levels significantly declined at the end of the first week and all liver function tests were normalized within 2 months.

  19. Xenobiotics-induced hepatotoxicity and an influence of HLA typisation

    Directory of Open Access Journals (Sweden)

    Žunić Miodrag

    2014-01-01

    Full Text Available Introduction: The increased reporting of cases of drug-induced liver injuries, reflects the growing number of new agents introduced into clinical practice in the last decades. It should be added to the modernization of industries, and new chemicals which it applied. Drug-induced liver injuries make up a persisting and challenging problem for physicians, health agencies and pharmaceutical firms. Research objectives: The aim of the study is the determination of the most common causes of drug-induced liver injury in our surroundings. We compared the importance of hepatotoxic action of drugs in relation to other noxa in human environment. We determinated the importance of the body sensitivity on the acting agents. We also examined the importance of different drugs in the development of hepatotoxicity, regardless the dose. Materials and methods: We analyzed 52 patients with a diagnosis of hepa-totoxic liver injury (medical history, detailed clinical evaluation of patients, histopathological analysis of the liver, abdominal ultra sound, laboratory determination of standard liver function tests and followed up for 12 months. In the period from 01.04. 2005 to 01.04.2009, in these patients of the Institute of Gastroenterology and Hepatology, Clinical Center of Serbia in Belgrade, we monitored liver functional tests and morphological findings. We used biological markers relevant for the differential diagnosis, monitoring of disease progression and response to therapy. The results of the patients with hepatotoxic liver injury were compared with the values of the findings of the 52 patients in the control group, with the diagnosis of chronic viral hepatitis, hospitalized in the same institution during the same time. Results: The causes of toxic liver damage in our study were following agents, classified into groups: Industrial toxins (8 patients, Food and beverages (9 pts, Antirheumatics and analgesics (6 pts, Antiarrhythmic drugs (4 pts Antilipemic (4 pts

  20. Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity

    International Nuclear Information System (INIS)

    Sawant, Sharmilee P.; Dnyanmote, Ankur V.; Warbritton, Alan; Latendresse, John R.; Mehendale, Harihara M.

    2006-01-01

    Previously, we reported high hepatotoxic sensitivity of type 2 diabetic (DB) rats to three dissimilar hepatotoxicants. Additional work revealed that a normally nonlethal dose of CCl 4 was lethal in DB rats due to inhibited compensatory tissue repair. The present study was conducted to investigate the importance of compensatory tissue repair in determining the final outcome of hepatotoxicity in diabetes, using another structurally and mechanistically dissimilar hepatotoxicant, thioacetamide (TA), to initiate liver injury. A normally nonlethal dose of TA (300 mg/kg, ip), caused 100% mortality in DB rats. Time course studies (0 to 96 h) showed that in the non-DB rats, liver injury initiated by TA as assessed by plasma alanine or aspartate aminotransferase and hepatic necrosis progressed up to 48 h and regressed to normal at 96 h resulting in 100% survival. In the DB rats, liver injury rapidly progressed resulting in progressively deteriorating liver due to rapidly expanding injury, hepatic failure, and 100% mortality between 24 and 48 h post-TA treatment. Covalent binding of 14 C-TA-derived radiolabel to liver tissue did not differ from that observed in the non-DB rats, indicating similar bioactivation-based initiation of hepatotoxicity. S-phase DNA synthesis measured by [ 3 H]-thymidine incorporation, and advancement of cells through the cell division cycle measured by PCNA immunohistochemistry, were substantially inhibited in the DB rats compared to the non-DB rats challenged with TA. Thus, inhibited cell division and compromised tissue repair in the DB rats resulted in progressive expansion of liver injury culminating in mortality. In conclusion, it appears that similar to type 1 diabetes, type 2 diabetes also increases sensitivity to dissimilar hepatotoxicants due to inhibited compensatory tissue repair, suggesting that sensitivity to hepatotoxicity in diabetes occurs in the absence as well as presence of insulin

  1. Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus

    OpenAIRE

    Saxena, Beenam; Sharma, Shiv

    2015-01-01

    Objective: Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. Materials and Methods: Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were ad...

  2. [Hepatotoxicity in healthy infants exposed to nevirapine during pregnancy].

    Science.gov (United States)

    Iveli, Pablo; Noguera-Julian, Antoni; Soler-Palacín, Pere; Martín-Nalda, Andrea; Rovira-Girabal, Núria; Fortuny-Guasch, Clàudia; Figueras-Nadal, Concepció

    2016-01-01

    The use of nevirapine in HIV-infected pregnant women is discouraged due to its potential to cause hepatotoxicity. There is limited information available on the toxicity in non-HIV infected newborn exposed to this drug during pregnancy. The aim of the study is to determine the extent of hepatotoxicity in the newborn exposed to nevirapine and HIV during pregnancy. A cross-sectional, observational, multicenter study was conducted on a cohort of healthy infants born to HIV-infected mothers, in whom the first determination of alanine aminotransferase (ALT), before 6weeks of age, was collected. Patients were allocated to 2groups according to exposure to nevirapine during pregnancy. Hepatotoxicity was rated according to the AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). This study included 160newborns from 159pregnancies (88exposed to nevirapine-based regimens and 71 exposed to protease inhibitors-based therapies). No cases of hepatotoxicity were observed according to the DAIDS Table for Grading. Two cases of ALT above normal values (2.8%; 95%CI: 0.3-9.8%) were observed in patients not exposed to nevirapine, and one case (1.1%; 95%CI: 0.0-6.1%) in the group exposed to nevirapine (P=.585). The lack of differences between groups suggests that highly active antiretroviral treatment regimens including nevirapine administered during pregnancy do not involve a higher risk of liver disease compared to other treatment combinations. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  3. Exacerbation of acetaminophen hepatotoxicity by the anthelmentic drug fenbendazole.

    Science.gov (United States)

    Gardner, Carol R; Mishin, Vladimir; Laskin, Jeffrey D; Laskin, Debra L

    2012-02-01

    Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8-12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administration resulted in centrilobular hepatic necrosis and increases in serum transaminases, which were evident within 12 h. Acetaminophen-induced hepatotoxicity was markedly increased in mice fed the fenbendazole-containing diet, as measured histologically and by significant increases in serum transaminase levels. Moreover, in mice fed the fenbendazole-containing diet, but not the control diet, 63% mortality was observed within 24 h of acetaminophen administration. Fenbendazole by itself had no effect on liver histology or serum transaminases. To determine if exaggerated hepatotoxicity was due to alterations in acetaminophen metabolism, we analyzed sera for the presence of free acetaminophen and acetaminophen-glucuronide. We found that there were no differences in acetaminophen turnover. We also measured cytochrome P450 (cyp) 2e1, cyp3a, and cyp1a2 activity. Whereas fenbendazole had no effect on the activity of cyp2e1 or cyp3a, cyp1a2 was suppressed. A prolonged suppression of hepatic glutathione (GSH) was also observed in acetaminophen-treated mice fed the fenbendazole-containing diet when compared with the control diet. These data demonstrate that fenbendazole exacerbates the hepatotoxicity of acetaminophen, an effect that is related to persistent GSH depletion. These findings are novel and suggest a potential drug-drug interaction that should be considered in experimental protocols evaluating mechanisms of hepatotoxicity in rodent colonies treated with fenbendazole.

  4. Herbalife hepatotoxicity: Evaluation of cases with positive reexposure tests.

    Science.gov (United States)

    Teschke, Rolf; Frenzel, Christian; Schulze, Johannes; Schwarzenboeck, Alexander; Eickhoff, Axel

    2013-07-27

    To analyze the validity of applied test criteria and causality assessment methods in assumed Herbalife hepatotoxicity with positive reexposure tests. We searched the Medline database for suspected cases of Herbalife hepatotoxicity and retrieved 53 cases including eight cases with a positive unintentional reexposure and a high causality level for Herbalife. First, analysis of these eight cases focused on the data quality of the positive reexposure cases, requiring a baseline value of alanine aminotransferase (ALT) Herbalife in these eight cases were probable (n = 1), unlikely (n = 4), and excluded (n = 3). Confounding variables included low data quality, alternative diagnoses, poor exclusion of important other causes, and comedication by drugs and herbs in 6/8 cases. More specifically, problems were evident in some cases regarding temporal association, daily doses, exact start and end dates of product use, actual data of laboratory parameters such as ALT, and exact dechallenge characteristics. Shortcomings included scattered exclusion of hepatitis A-C, cytomegalovirus and Epstein Barr virus infection with only globally presented or lacking parameters. Hepatitis E virus infection was considered in one single patient and found positive, infections by herpes simplex virus and varicella zoster virus were excluded in none. Only one case fulfilled positive reexposure test criteria in initially assumed Herbalife hepatotoxicity, with lower CIOMS based causality gradings for the other cases than hitherto proposed.

  5. TAMH: A Useful In Vitro Model for Assessing Hepatotoxic Mechanisms

    Directory of Open Access Journals (Sweden)

    Madison Davis

    2016-01-01

    Full Text Available In vitro models for hepatotoxicity can be useful tools to predict in vivo responses. In this review, we discuss the use of the transforming growth factor-α transgenic mouse hepatocyte (TAMH cell line, which is an attractive model to study drug-induced liver injury due to its ability to retain a stable phenotype and express drug-metabolizing enzymes. Hepatotoxicity involves damage to the liver and is often associated with chemical exposure. Since the liver is a major site for drug metabolism, drug-induced liver injury is a serious health concern for certain agents. At the molecular level, various mechanisms may protect or harm the liver during drug-induced hepatocellular injury including signaling pathways and endogenous factors (e.g., Bcl-2, GSH, Nrf2, or MAPK. The interplay between these and other pathways in the hepatocyte can change upon drug or drug metabolite exposure leading to intracellular stress and eventually cell death and liver injury. This review focuses on mechanistic studies investigating drug-induced toxicity in the TAMH line and how alterations to hepatotoxic mechanisms in this model relate to the in vivo situation. The agents discussed herein include acetaminophen (APAP, tetrafluoroethylcysteine (TFEC, flutamide, PD0325901, lapatinib, and flupirtine.

  6. Experimental models of hepatotoxicity related to acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

  7. No evidence demonstrating hepatotoxicity associated with hydroxycitric acid

    Institute of Scientific and Technical Information of China (English)

    Sidney J Stohs; Harry G Preuss; Sunny E Ohia; Gilbert R Kaats; Carl L Keen; Lonnie D Williams; George A Burdock

    2009-01-01

    Although a number of cases of hepatotoxicity are associated with the use of Hydroxycut weight management products,it has been alleged that their effects are primarily due to the presence of hydroxycitric acid (HCA,as Super CitriMax) in the formulations.However,while these products contain up to 20 different ingredients,some do not contain HCA.Case studies reported to date have not considered in depth the literature on the numerous animal and human studies that have been conducted on the safety and efficacy of HCA.No HCAassociated hepatotoxicity or treatment-related adverse effects have been reported in these studies,and thus it is premature to make the assumptions presented in the recent case studies regarding Hydroxycut.If it is established in well controlled studies that the use of these formulations with and/or without HCA can result in the occurrence or progression of hepatotoxicity,additional studies should be conducted to characterize the causative factor(s).

  8. Rocuronium is more hepatotoxic than succinylcholine in vitro.

    Science.gov (United States)

    Sauer, Martin; Piel, Ines; Haubner, Cristof; Richter, Georg; Mann, Miriam; Nöldge-Schomburg, Gabriele; Mencke, Thomas

    2017-09-01

    The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. In-vitro study. A basic science laboratory, University Hospital Rostock, Germany. The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured. Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test. Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity. Not suitable.

  9. Histomorphological effects of isoniazid induced hepatotoxicity in male albino mice

    International Nuclear Information System (INIS)

    Humayun, F.; Zareen, N.

    2017-01-01

    To observe the histomorphological changes of isoniazid induced hepatotoxicity in male albino mice. Methodology: This experimental study was carried out at University of Health Sciences, Lahore, Pakistan from January to December 2013. Forty male albino mice selected by simple random technique, were divided into two groups; A-Control, and B-experimental. Group A comprised of 15, while Group B comprised 25 mice. Both the groups were kept under identical conditions and diet. However, experimental group was treated with an additional oral hepatotoxic dose of isoniazid i.e. 100mg/kg bodyweight daily for 30 days. After 30 days, the animals were sacrificed and livers were dissected out. Gross comparison of the organ and stained sections were histologically compared for morphological differences between the groups. Fischer Exact test was used to analyze the qualitative data and a p<0.05 was considered significant. Results: Group A animals showed the normal liver architecture. Whereas, those of Group B showed deranged hepatic histomorphology. Conclusion: Hepatotoxic dose of Isoniazid caused histomorphological alterations in the liver of male albino mice. (author)

  10. Hepatotoxicity induced by methimazole in a previously healthy patient.

    Science.gov (United States)

    Gallelli, Luca; Staltari, Orietta; Palleria, Caterina; De Sarro, Giovambattista; Ferraro, Maria

    2009-09-01

    We report a case of hepatotoxicity induced by methimazole treatment in a patient affected by hyperthyroidism. A 54-year-old man, presented to our observation for palpitations, excessive sweating, weakness, heat intolerance and weight loss. On physical examination, his blood pressure was 140/90 mmHg and heart beat was 100/min regular. He had mild tremors and left exophthalmos. Laboratory test revealed a significant increase in serum thyroid hormone levels with a decrease in thyroid stimulating hormone levels. A diagnosis of hyperthyroidism was made and he began treatment with methimazole (30 mg/day). Fourteen days later, he returned for the development of scleral icterus, followed by dark urine, and abdominal pain in the right upper quadrant. Laboratory examinations and liver biopsy performed a diagnosis of cholestatic hepatitis, secondary to methimazole usage. Methimazole was promptly withdrawn and cholestyramine, ursodeoxycholic acid, and chlorpheniramine were given. After five days, abdominal pain resolved and laboratory parameters returned to normal. Naranjo probability scale indicated a probable relationship between hepatotoxicity and methimazole therapy. In conclusion physicians should be aware the risk of hepatotoxicity related with methimazole.

  11. Hepatotoxic potential of asarones: In vitro evaluation of hepatotoxicity and quantitative determination in herbal products

    Directory of Open Access Journals (Sweden)

    Dhavalkumar Narendrabha Patel

    2015-02-01

    Full Text Available α and β asarones are natural constituents of some aromatic plants, especially species of the genus Acorus. In addition to beneficial properties of asarones, genotoxicity and carcinogenicity are also reported. Due to potential toxic effects of β-asarone, a limit of exposure from herbal products of approximately 2 μg/kg body weight/day has been set temporarily until a full benefit/risk assessment has been carried out by the European Medicines Agency. Therefore, it is important to monitor levels of β-asarone in herbal products. In this study, we developed a simple, rapid and validated GC-MS method for quantitative determination of asarones and applied it in 20 pediatric herbal products after detecting high concentrations of β-asarone in a product suspected to be implicated in hepatotoxicity in a 3 month old infant. Furthermore, targeted toxicological effects were further investigated in human hepatocytes (THLE-2 cells by employing various in vitro assays, with the goal of elucidating possible mechanisms for the observed toxicity. Results showed that some of the products contained as much as 4 to 25 times greater amounts of β-asarone than the recommended levels. In 4 of 10 samples found to contain asarones, the presence of asarones could not be linked to the labeled ingredients, possibly due to poor quality control. Cell-based investigations in THLE2 cells confirmed the cytotoxicity of -asarone (IC50 = 40.0 ± 2.0 µg/mL which was associated with significant lipid peroxidation and glutathione depletion. This observed cytotoxicity effect is likely due to induction of oxidative stress by asarones. Overall, the results of this study ascertained the usability of this GC-MS method for the quantitative determination of asarones from herbal products, and shed light on the importance of controlling the concentration of potentially toxic asarones in herbal products to safeguard consumer safety. Further investigations of the toxicity of asarones are

  12. Copper Test

    Science.gov (United States)

    ... in the arm and/or a 24-hour urine sample is collected. Sometimes a health practitioner performs a liver ... disease , a rare inherited disorder that can lead to excess storage of copper in the liver, brain, and other ...

  13. Fluorine determination in human and animal bones by particle-induced gamma-ray emission

    International Nuclear Information System (INIS)

    Sastri, Chaturvedula S.; Hoffmann, Peter; Ortner, Hugo M.; Iyengar, Venkatesh; Blondiaux, Gilbert; Tessier, Yves; Petri, Hermann; Aras, Namik K.; Zaichick, Vladimir

    2002-01-01

    Fluorine was determined in the iliac crest bones of patients and in ribs collected from postmortem investigations by particle-induced gamma-ray emission based on the 19 F(p,pγ) 19 F reaction, using 20/2.5 MeV protons. The results indicate that for 68% of the human samples the F concentration is in the range 500-1999 μg g -1 . For comparison purposes fluorine was also determined in some animal bones; in some animal tissues lateral profiles of fluorine were measured. (abstract)

  14. Development of a Reference Database for Particle Induced Gamma Ray Emission (PIGE) Spectroscopy

    International Nuclear Information System (INIS)

    2017-09-01

    Ion beam analysis techniques are non-destructive analytical techniques used to identify the composition and structure of surface layers of materials. The applications of these techniques span environmental control, cultural heritage and conservation, materials and fusion technologies. The particle-induced gamma-ray emission (PIGE) spectroscopy technique in particular, is a powerful tool for detecting light elements in certain depths of surface layers. This publication describes the coordinated effort to measure and compile cross section data relevant to PIGE analysis and make these data available to the community of practice through a comprehensive online database.

  15. Pre-equilibrium decay process in alpha particle induced reactions on thulium and tantalum

    International Nuclear Information System (INIS)

    Mohan, Rao, A.V.; Chintalapudi, S.N.

    1994-01-01

    Alpha particle induced reactions on the target elements Thulium and Tantalum were investigated upto 60 MeV using stacked foil activation technique and Ge(Li) gamma ray spectroscopy method. Excitation functions for six reactions of 169 Tm(α,xn); x=1-4 and 181 Ta(α,xn); x=2,4 were studied. The experimental results were compared with the updated version of Hybrid model (ALICE/90) using initial exciton configuration n 0 =4(4pOh). A general agreement was found for all the reactions with this option. (author)

  16. Pre-equilibrium decay process in alpha particle induced reactions on thulium and tantalum

    Energy Technology Data Exchange (ETDEWEB)

    Mohan, Rao, A.V.; Chintalapudi, S.N. (Inter Univ. Consortium for Dept. of atomic Energy Facilities, Calcutta (India))

    1994-01-01

    Alpha particle induced reactions on the target elements Thulium and Tantalum were investigated upto 60 MeV using stacked foil activation technique and Ge(Li) gamma ray spectroscopy method. Excitation functions for six reactions of [sup 169]Tm([alpha],xn); x=1-4 and [sup 181]Ta([alpha],xn); x=2,4 were studied. The experimental results were compared with the updated version of Hybrid model (ALICE/90) using initial exciton configuration n[sub 0]=4(4pOh). A general agreement was found for all the reactions with this option. (author).

  17. Particle induced X-ray emission: a valuable tool for the analysis of metalpoint drawings

    International Nuclear Information System (INIS)

    Duval, A.; Guicharnaud, H.; Dran, J.C.

    2004-01-01

    For several years, we carry out a research on metalpoint drawings, a graphic technique mainly employed by European artists during the 15th and 16th centuries. As a non-destructive and very sensitive analytical technique is required, particle induced X-ray emission (PIXE) analysis with an external beam has been used for this purpose. More than 70 artworks drawn by Italian, Flemish and German artists have been analysed, including leadpoint and silverpoint drawings. Following a short description of the metalpoint technique, the results are compared with the recipes written by Cennino Cennini at the beginning of the 15th century and specific examples are presented

  18. An optimised set-up for total reflection particle induced X-ray emission

    International Nuclear Information System (INIS)

    Kan, J.A. van; Vis, R.D.

    1997-01-01

    MeV proton beams at small angles of incidence (0-35 mrad) are used to analyse trace elements on flat surfaces such as Si wafers or quartz substrates. In these experiments, the particle induced X-ray emission (PIXE) signal is used in a new optimized set-up. This set-up is constructed in such a way that the X-ray detector can reach very large solid angles, larger than 1 sr. Use of these large detector solid angles, combined with the reduction of bremsstrahlung background, affords limits of detection (LOD) of the order of 10 10 at cm -2 using total reflection particle induced X-ray emission (TPIXE). The LODs from earlier TPIXE measurements in a non-optimized set-up are used to estimate LODs in the new TPIXE set-up. Si wafers with low surface concentrations of V, Ni, Cu and Ag are used as standards to calibrate the LODs found with this set-up. The metal concentrations are determined by total reflection X-ray fluorescence (TXRF). The TPIXE measurements are compared with TXRF measurements on the same wafers. (Author)

  19. Charged-particle induced thermonuclear reaction rates: a compilation for astrophysics

    International Nuclear Information System (INIS)

    Grama, Cornelia; Angulo, C.; Arnould, M.

    2000-01-01

    The rapidly growing wealth of nuclear data becomes less and less easily accessible to the astrophysics community. Mastering this volume of information and making it available in an accurate and usable form for incorporation into stellar evolution or nucleosynthesis models become urgent goals of prime necessity. we report on the results of the European network NACRE (Nuclear Astrophysics Compilation of REaction rates). The principal motivation for the setting-up of the NACRE network has been the necessity of building up a well-documented and detailed compilation of rates for charged-particle induced reactions on stable targets up to Si and on unstable nuclei of special significance in astrophysics. This work is meant to supersede the only existing compilation of reaction rates issued by Fowler and collaborators. The cross section data and/or resonance parameters for a total of 86 charged-particle induced reactions are given and the corresponding reaction rates are calculated and given in tabular form. When cross section data are not available in the whole needed range of energies, the theoretical predictions obtained in the framework of the Hauser-Feshbach model is used. Uncertainties are analyzed and realistic upper and lower bounds of the rates are determined. Reverse reaction rates and analytical approximations of the adopted rates are also provided. (authors)

  20. Charged-particle induced thermonuclear reaction rates: a compilation for astrophysics

    International Nuclear Information System (INIS)

    Grama, Cornelia

    1999-01-01

    The rapidly growing wealth of nuclear data becomes less and less easily accessible to the astrophysics community. Mastering this volume of information and making it available in an accurate and usable form for incorporation into stellar evolution or nucleosynthesis models become urgent goals of prime necessity. We report on the results of the European network NACRE (Nuclear Astrophysics Compilation of REaction rates). The principal motivation for the setting-up of the NACRE network has been the necessity of building up a well-documented and detailed compilation of rates for charged -particle induced reactions on stable targets up to Si and on unstable nuclei of special significance in astrophysics. This work is meant to supersede the only existing compilation of reaction rates issued by Fowler and collaborators. The cross section data and/or resonance parameters for a total of 86 charged-particle induced reactions are given and the corresponding reaction rates are calculated and given in tabular form. When cross section data are not available in the whole needed range of energies the theoretical predictions obtained in the framework of the Hauser-Feshbach model are used. Uncertainties are analyzed and realistic upper and lower bounds of the rates are determined. Reverse reaction rates and analytical approximations of the adopted rates are also provided. (author)

  1. Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 (China); Fan, Qiming; Tang, Tingting [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Gu, Dongyun, E-mail: dongyungu@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education of PR China (China); School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030 (China)

    2015-01-01

    Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-κB and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.

  2. Effect of anemia on hepatotoxicity of HAART in HIV patients in Benin ...

    African Journals Online (AJOL)

    Background: Hepatotoxicity is a relevant adverse effect of highly active antiretroviral Treatment owing to its frequency, and it can cause interruption of therapy, hepatitis, and death. There is dearth of information on hepatotoxicity arising from highly active antiretroviral therapy (HAART) in anemic patients. Anemia is the most ...

  3. Herbal hepatotoxicity: suspected cases assessed for alternative causes.

    Science.gov (United States)

    Teschke, Rolf; Schulze, Johannes; Schwarzenboeck, Alexander; Eickhoff, Axel; Frenzel, Christian

    2013-09-01

    Alternative explanations are common in suspected drug-induced liver injury (DILI) and account for up to 47.1% of analyzed cases. This raised the question of whether a similar frequency may prevail in cases of assumed herb-induced liver injury (HILI). We searched the Medline database for the following terms: herbs, herbal drugs, herbal dietary supplements, hepatotoxic herbs, herbal hepatotoxicity, and herb-induced liver injury. Additional terms specifically addressed single herbs and herbal products: black cohosh, Greater Celandine, green tea, Herbalife products, Hydroxycut, kava, and Pelargonium sidoides. We retrieved 23 published case series and regulatory assessments related to hepatotoxicity by herbs and herbal dietary supplements with alternative causes. The 23 publications comprised 573 cases of initially suspected HILI; alternative causes were evident in 278/573 cases (48.5%). Among them were hepatitis by various viruses (9.7%), autoimmune diseases (10.4%), nonalcoholic and alcoholic liver diseases (5.4%), liver injury by comedication (DILI and other HILI) (43.9%), and liver involvement in infectious diseases (4.7%). Biliary and pancreatic diseases were frequent alternative diagnoses (11.5%), raising therapeutic problems if specific treatment is withheld; pre-existing liver diseases including cirrhosis (9.7%) were additional confounding variables. Other diagnoses were rare, but possibly relevant for the individual patient. In 573 cases of initially assumed HILI, 48.5% showed alternative causes unrelated to the initially incriminated herb, herbal drug, or herbal dietary supplement, calling for thorough clinical evaluations and appropriate causality assessments in future cases of suspected HILI.

  4. Potential protective effect of honey against paracetamol-induced hepatotoxicity.

    Science.gov (United States)

    Galal, Reem M; Zaki, Hala F; Seif El-Nasr, Mona M; Agha, Azza M

    2012-11-01

    Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were also evaluated in the rat liver homogenates.  We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta (IL-1β) because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of Il-1β. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in Il-1β and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage.

  5. Incidence and risk of regorafenib-induced hepatotoxicity.

    Science.gov (United States)

    Zhao, Bin; Zhao, Hong

    2017-10-13

    Regorafenib, an oral multi-kinase inhibitor, has been approved for the treatments of several malignancies. Unlike traditional cytotoxic chemotherapeutic agents, regorafenib therapy often induces a distinct profile of adverse events (AEs) including hepatotoxicity. Here we conducted an up-to-date meta-analysis to assess the incidence and risk of regorafenib related hepatic toxicities. PubMed and Embase database were reviewed from inception to June 2017 for relevant trials. Eligible studies include subjects with solid tumors treated with 160 mg of regorafenib daily during the first three week of each four-week cycle, and adequate safety data reporting the elevation of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. Statistical analyses were conducted to calculate the summary incidence and relative risk (RR). A total of 2,213 subjects from 14 trials were included. The incidences of regorafenib-associated all-grade and high-grade hepatotoxicity were: bilirubin elevation: 23% and 5%; AST elevation: 32% and 6%; ALT elevation: 27% and 5%; ALP elevation: 31% and 2%. Regorafenib-treated subjects had a significant increased risk of all-grade (RR = 3.10; 95% CI, 2.22-4.34) and high-grade (RR = 1.74; 95% CI, 1.09-2.80) bilirubin elevation; all-grade (RR = 1.51; 95% CI, 1.13-2.00) and high-grade (RR = 1.79; 95% CI, 1.00-3.22) AST elevation; all-grade (RR = 1.82; 95% CI, 1.25-2.64) and high-grade (RR = 3.07; 95% CI, 1.30-7.22) ALT elevation; and all-grade (RR = 2.11; 95% CI, 1.01-4.40) ALP elevation. Our results suggest that regorafenib is associated with an increased risk of hepatic toxicities. Hepatotoxicity examination at regular intervals should be advised to clinicians.

  6. Antioxidant modulation of nevirapine induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Awodele Olufunsho

    2015-03-01

    Full Text Available HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART. However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day, vitamin C (8 mg/kg/day, vitamin E (5 mg/kg/day and/or NVP (6 mg/kg/day for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (p<0.05 elevation in MDA level observed in the NVP group as compared with control. The results further showed non-significant decreases in the levels of MDA in the NVP plus antioxidant groups, except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E plus C treated groups showed significantly (p<0.05 higher levels of SOD, CAT and GSH. The results also showed statistically significantly (p<0.05 lower levels of ALT and AST in the antioxidant treated groups There was an observed significantly (p<0.05 higher level of TP and urea in the antioxidant treated rats. A significantly (p<0.05 higher white blood cell count was observed in the antioxidant groups. Histopathological assessment of the liver extracted from the rats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.

  7. Hepato-toxic effect of diuron in albino rats.

    Science.gov (United States)

    Agrawal, R C; Kumar, S

    1999-05-01

    Tumour initiating/promoting effect of diuron, a widely used substituted urea herbicide, was studied in rats using liver tumour model. Chronic exposure to diuron at a dose of 250 mg/kg body wt resulted in high mortality and weight loss in treated animals. The animals which received diuron + HCH treatment showed an increase in size and weight of liver as compared to controls. Liver tumours were not observed in any of the treated group whereas some significant histological changes were seen in diuron treated rat liver. Diuron thus has been found to be hepatotoxic albeit neither tumour initiating nor promoting in rat liver tumorigenesis assay system.

  8. Curcumin Attenuates Hepatotoxicity Induced by Zinc Oxide Nanoparticles in Rats

    Directory of Open Access Journals (Sweden)

    Layasadat Khorsandi

    2016-06-01

    Full Text Available Background: Zinc oxide nanoparticles (NZnO are increasingly used in modern life. Most metal nanoparticles have adverse effects on the liver. Aims: To explore the protective action of curcumin (Cur against hepatotoxicity induced by NZnO in rats. Study Design: Animal experimentation. Methods: Control group animals received normal saline, while the Cur group animals were treated with 200 mg/kg of Cur orally for 21 days. NZnO-intoxicated rats received 50 mg/kg of NZnO for 14 days by gavage method. In the NZnO+Cur group, rats were pretreated with Cur for 7 days before NZnO administration. Plasma activities of Alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP were measured as biomarkers of hepatotoxicity. Hepatic levels of malondialdehyde (MDA and superoxide dismutase (SOD and glutathione peroxidase (GPx activities were measured for detection of oxidative stress in liver tissue. Histological changes and apoptosis in liver tissue were studied by using Hematoxylin-eosin staining and the transferase dUTP nick end labeling (TUNEL method. Results: NZnO induced a significant increase in plasma AST (2.8-fold, ALT (2.7-fold and ALP (1.97-fold activity in comparison to the control group (p<0.01. NZnO increased MDA content and reduced SOD and GPx activities. NZnO caused liver damage including centrilobular necrosis and microvesicular steatosis. The percentage of apoptosis in hepatocytes was increased in NZnO-treated rats (p<0.01. Pre-treatment of Cur significantly reduced lipid peroxidation (39%, increased SOD (156% and GPx (26% activities, and attenuated ALT (47%, AST (41% and ALP (30% activities. Pre-treatment with Cur also decreased the histology changes and apoptotic index of hepatocytes (p<0.05. Conclusion: These findings indicate that Cur effectively protects against NZnO-induced hepatotoxicity in rats. However, future studies are required to propose Cur as a potential protective agent against hepatotoxicity

  9. Production of medically useful bromine isotopes via alpha-particle induced nuclear reactions

    Science.gov (United States)

    Breunig, Katharina; Scholten, Bernhard; Spahn, Ingo; Hermanne, Alex; Spellerberg, Stefan; Coenen, Heinz H.; Neumaier, Bernd

    2017-09-01

    The cross sections of α-particle induced reactions on arsenic leading to the formation of 76,77,78Br were measured from their respective thresholds up to 37 MeV. Thin sediments of elemental arsenic powder were irradiated together with Al degrader and Cu monitor foils using the established stacked-foil technique. For determination of the effective α-particle energies and of the effective beam current through the stacks the cross-section ratios of the monitor nuclides 67Ga/66Ga were used. This should help resolve discrepancies in existing literature data. Comparison of the data with the available excitation functions shows some slight energy shifts as well as some differences in curve shapes. The calculated thick target yields indicate, that 77Br can be produced in the energy range Eα = 25 → 17 MeV free of isotopic impurities in quantities sufficient for medical application.

  10. Trace element determination in tomato puree using particle induced X-ray emission and Rutherford backscattering

    International Nuclear Information System (INIS)

    Romero-Davila, E.; Miranda, J.

    2004-01-01

    Particle induced X-ray emission (PIXE) and Rutherford backscattering spectrometry (RBS) were used to determine the concentrations of trace elements in samples of 12 tomato puree brands sold in the Mexican market. While RBS offered information about the main elements present in the matrix, PIXE gave results on trace elements. As a whole, data for 17 elements (C, N, O, Na, Mg, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, and Zn) were obtained. To evaluate the results, a comparison with brands from USA, Japan, Colombia, and Chile was carried out, using tomato purees produced following the domestic technology recipe. Additionally, the results were considered in the light of the Codex Alimentarius and the Mexican standard. It was found that all of the brands fall within the limits established by these standards, being of the same order of magnitude as the foreign brands. (author)

  11. Particle induced x-ray emission (PIXE) measurement of the Cd content in animal tissues

    International Nuclear Information System (INIS)

    Le Huong Quynh; Demeter, I.; Hollos-Nagy, K.; Szoekefalvi-Nagy, Z.

    1989-12-01

    Particle induced x-ray emission (PIXE) measurements were performed on thin samples prepared from different rabbit tissues, using 3 MeV proton beam for inducing x-rays from the animal tissues. This method is very sensitive and very small amounts of trace elements can be detected. Cadmium, one of the most toxic elements which can be concentrated in animal and human tissues due to environmental pollution, was detected with a limit of 0.7 ppm. The trace element concentrations obtained by PIXE were compared to those measured by atomic absorption spectrometry. PIXE method is proposed for routine analysis at the Veterinary and Food Investigating Service, Budapest, Hungary. (D.Gy.) 6 refs.; 3 figs

  12. Detection of halogenated flame retardants in polyurethane foam by particle induced X-ray emission

    International Nuclear Information System (INIS)

    Maley, Adam M.; Falk, Kyle A.; Hoover, Luke; Earlywine, Elly B.; Seymour, Michael D.; DeYoung, Paul A.; Blum, Arlene; Stapleton, Heather M.; Peaslee, Graham F.

    2015-01-01

    A novel application of particle-induced X-ray emission (PIXE) has been developed to detect the presence of chlorinated and brominated flame retardant chemicals in polyurethane foams. Traditional Gas Chromatography–Mass Spectrometry (GC–MS) methods for the detection and identification of halogenated flame retardants in foams require extensive sample preparation and data acquisition time. The elemental analysis of the halogens in polyurethane foam performed by PIXE offers the opportunity to identify the presence of halogenated flame retardants in a fraction of the time and sample preparation cost. Through comparative GC–MS and PIXE analysis of 215 foam samples, excellent agreement between the two methods was obtained. These results suggest that PIXE could be an ideal rapid screening method for the presence of chlorinated and brominated flame retardants in polyurethane foams

  13. Production of medically useful bromine isotopes via alpha-particle induced nuclear reactions

    Directory of Open Access Journals (Sweden)

    Breunig Katharina

    2017-01-01

    Full Text Available The cross sections of α-particle induced reactions on arsenic leading to the formation of 76,77,78Br were measured from their respective thresholds up to 37 MeV. Thin sediments of elemental arsenic powder were irradiated together with Al degrader and Cu monitor foils using the established stacked-foil technique. For determination of the effective α-particle energies and of the effective beam current through the stacks the cross-section ratios of the monitor nuclides 67Ga/66Ga were used. This should help resolve discrepancies in existing literature data. Comparison of the data with the available excitation functions shows some slight energy shifts as well as some differences in curve shapes. The calculated thick target yields indicate, that 77Br can be produced in the energy range Eα = 25 → 17 MeV free of isotopic impurities in quantities sufficient for medical application.

  14. Particle induced x-ray emission studies of some Indian medicinal plants

    International Nuclear Information System (INIS)

    Nomita Devi, K.; Nandakumar Sarma, H.; Kumar, Sanjiv

    2007-01-01

    Medicinal herbs have been used from antiquity by humanity. This paper discusses the elemental composition and concentration of ten Indian medicinal plants investigated by particle induced X-ray emission (PIXE) technique. The accuracy and precision of the technique were assured by analyzing three Certified Standard Reference Materials -cabbage- (GBW 08504, China), wheat flour (NIST-8436) and bovine liver (NIST-1577b). The element K, Ca, Mn, Fe, Cu and Zn were found to be present in all the samples in varying concentrations. No toxic heavy metals such as As, Pb and Hg were detected in the studied plants. The range of the elemental concentrations in dry weight has been found to vary from 4.69x10 4 mg/kg to 1.81 mg/kg in the plants. The results also show that these plants contain elements of vital importance in man's metabolism and that are needed for growth and developments, prevention and heating of diseases. (author)

  15. Quantification of arsenic in activated carbon using particle induced X-ray emission

    International Nuclear Information System (INIS)

    Yadav, Nirbhay N.; Maheswaran, Saravanamuthu; Shutthanandan, Vaithiyalingam; Thevuthasan, Suntharampillai; Ngo, Huu H.; Vigneswaran, Saravanamuth

    2006-01-01

    To date, the trace elemental analysis of solids with inhomogeneous internal structure has been limited, particularly in the case of adsorbents. High-energy ion beam based particle induced X-ray emission (PIXE) is an ideal analytical tool suitable for simultaneous quantification of trace elements with high accuracy. In this study, PIXE was used to quantify arsenic in the adsorbents, granular activated carbon (GAC) and powder activated carbon (PAC). Pelletized and unmodified GAC and PAC samples were analyzed along with powder samples deposited on thin teflon filters. These sample preparation methods resulted in samples of various thicknesses and densities. PIXE measurements taken from these samples were compared to results from neutron activation analysis (NAA) and atomic absorption spectroscopy (AAS). There is a good agreement between the values from the NAA and pelletized PIXE measurements and some AAS measurements

  16. Particle Induced X-ray Emission (PIXE) Approach for the Quantification of Thin Al Films

    International Nuclear Information System (INIS)

    Younes, G; Zahraman, K; Nsouli, B; Soueidan, M; Ferro, G

    2008-01-01

    Particle Induced X-ray Emission (PIXE) has been used as a fast and non-destructive technique for sensitive characterization of ultra thin Al films deposited by evaporation onto Si substrate. In this work the PIXE technique was optimized, using proton beam at different energies and different angles of incidence, for the characterization of ultra thin Al films (few nanometers) deposited onto Si substrate. The PIXE results showed that a proton beam of 300 keV under tilting angle of 80 degree permits an accurate determination of Al with high sensitivity within few minutes of acquisition time and a LOD of less than 0.2 nm. The LOD versus energy and tilting angle will be presented and discussed. (author)

  17. Temperature effects on drift of suspended single-domain particles induced by the Magnus force

    Science.gov (United States)

    Denisov, S. I.; Lyutyy, T. V.; Reva, V. V.; Yermolenko, A. S.

    2018-03-01

    We study the temperature dependence of the drift velocity of single-domain ferromagnetic particles induced by the Magnus force in a dilute suspension. A set of stochastic equations describing the translational and rotational dynamics of particles is derived, and the particle drift velocity that depends on components of the average particle magnetization is introduced. The Fokker-Planck equation for the probability density of magnetization orientations is solved analytically in the limit of strong thermal fluctuations for both the planar rotor and general models. Using these solutions, we calculate the drift velocity and show that the out-of-plane fluctuations of magnetization, which are not accounted for in the planar rotor model, play an important role. In the general case of arbitrary fluctuations, we investigate the temperature dependence of the drift velocity by numerically simulating a set of effective stochastic differential equations for the magnetization dynamics.

  18. Detection of halogenated flame retardants in polyurethane foam by particle induced X-ray emission

    Energy Technology Data Exchange (ETDEWEB)

    Maley, Adam M.; Falk, Kyle A.; Hoover, Luke; Earlywine, Elly B.; Seymour, Michael D. [Department of Chemistry, Hope College, 35 E. 12th Street, Holland, MI 49423 (United States); DeYoung, Paul A. [Department of Physics, Hope College, 27 Graves Place, Holland, MI 49423 (United States); Blum, Arlene [Green Science Policy Institute, Box 5455, Berkeley, CA 94705 (United States); Stapleton, Heather M. [Nicholas School of the Environment, Duke University, LSRC Box 90328, Durham, NC 27708 (United States); Peaslee, Graham F., E-mail: peaslee@hope.edu [Department of Chemistry, Hope College, 35 E. 12th Street, Holland, MI 49423 (United States)

    2015-09-01

    A novel application of particle-induced X-ray emission (PIXE) has been developed to detect the presence of chlorinated and brominated flame retardant chemicals in polyurethane foams. Traditional Gas Chromatography–Mass Spectrometry (GC–MS) methods for the detection and identification of halogenated flame retardants in foams require extensive sample preparation and data acquisition time. The elemental analysis of the halogens in polyurethane foam performed by PIXE offers the opportunity to identify the presence of halogenated flame retardants in a fraction of the time and sample preparation cost. Through comparative GC–MS and PIXE analysis of 215 foam samples, excellent agreement between the two methods was obtained. These results suggest that PIXE could be an ideal rapid screening method for the presence of chlorinated and brominated flame retardants in polyurethane foams.

  19. R-Matrix Codes for Charged-particle Induced Reactionsin the Resolved Resonance Region

    Energy Technology Data Exchange (ETDEWEB)

    Leeb, Helmut [Technical Univ. of Wien, Vienna (Austria); Dimitriou, Paraskevi [Intl Atomic Energy Agency (IAEA), Vienna (Austria); Thompson, Ian J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-01-01

    A Consultant’s Meeting was held at the IAEA Headquarters, from 5 to 7 December 2016, to discuss the status of R-matrix codes currently used in calculations of charged-particle induced reaction cross sections at low energies. The meeting was a follow-up to the R-matrix Codes meeting held in December 2015, and served the purpose of monitoring progress in: the development of a translation code to enable exchange of input/output parameters between the various codes in different formats, fitting procedures and treatment of uncertainties, the evaluation methodology, and finally dissemination. The details of the presentations and technical discussions, as well as additional actions that were proposed to achieve all the goals of the meeting are summarized in this report.

  20. Probiotics protect mice from CoCrMo particles-induced osteolysis

    Directory of Open Access Journals (Sweden)

    Wang Z

    2017-07-01

    Full Text Available Zhenheng Wang,* Kaiwen Xue,* Maosheng Bai, Zhantao Deng, Jingjing Gan, Gang Zhou, Hongbo Qian,* Nirong Bao, Jianning Zhao Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model. In this study, L. casei markedly protected mice from CoCrMo particles (CoPs-induced osteolysis. Osteoclast gene markers and the number of osteoclasts were significantly decreased in L. casei-treated mice. Probiotic treatment decreased the M1-like macrophage phenotype indicated by downregulation of tumor necrosis factor α (TNF-α, interleukin (IL-6 and inducible nitric oxide synthase (iNOS and increased the M2-like macrophage phenotype indicated by upregulation of IL-4, IL-10 and arginase. Collectively, these results indicated that the L. casei treatment modulated the immune status and suppressed wear particle-induced osteolysis in vivo. Thus, probiotic treatment may represent a potential preventive and therapeutic approach to reduced wear debris-induced osteolysis. Keywords: wear particles, gut microbiota, nanotoxicity, macrophage polarization, inflammatory cytokines, aseptic loosening

  1. Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    He, Yi; Zhang, Qing; Shen, Yi; Chen, Xia; Zhou, Feng; Peng, Dan, E-mail: xyeypd@163.com

    2014-07-04

    Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.

  2. Bisphenol A Induces Hepatotoxicity through Oxidative Stress in Rat Model

    Directory of Open Access Journals (Sweden)

    Zeinab K. Hassan

    2012-01-01

    Full Text Available Reactive oxygen species (ROS are cytotoxic agents that lead to significant oxidative damage. Bisphenol A (BPA is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells. Due to limited information concerning the effect of BPA on liver, this study investigates whether BPA causes hepatotoxicity by induction of oxidative stress in liver. Rats were divided into five groups: The first four groups, BPA (0.1, 1, 10, 50 mg/kg/day were administrated orally to rats for four weeks. The fifth group was taken water with vehicle. The final body weights in the 0.1 mg group showed a significant decrease compared to control group. Significant decreased levels of reduced glutathione, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase activity were found in the 50 mg BPA group compared to control groups. High dose of BPA (50 mg/kg significantly increased the biochemical levels of ALT, ALP and total bilirubin. BPA effect on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decrease compared to control. Data from this study demonstrate that BPA generate ROS and reduce the antioxidant gene expression that causes hepatotoxicity.

  3. Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice.

    Science.gov (United States)

    Pan, Qiong; Sun, Yiming; Jin, Qili; Li, Qixiang; Wang, Qing; Liu, Hao; Zhao, Surong

    2016-11-01

    To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. 3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. 3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

  4. Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics.

    Science.gov (United States)

    García-Cortés, Miren; Robles-Díaz, Mercedes; Ortega-Alonso, Aida; Medina-Caliz, Inmaculada; Andrade, Raul J

    2016-04-09

    Dietary supplements (DS) are extensively consumed worldwide despite unproven efficacy. The true incidence of DS-induced liver injury (DSILI) is unknown but is probably under-diagnosed due to the general belief of safety of these products. Reported cases of herbals and DS-induced liver injury are increasing worldwide. The aim of this manuscript is to report a tabular listing with a description of DS associated with hepatotoxicity as well as review the phenotype and severity of DSILI. Natural remedies related to hepatotoxicity can be divided into herbal product-induced liver injury and DS-induced liver injury. In this article, we describe different DS associated with liver injury, some of them manufactured DS containing several ingredients (Herbalife™ products, Hydroxycut™, LipoKinetix™, UCP-1 and OxyELITE™) while others have a single ingredient (green tea extract, linoleic acid, usnic acid, 1,3-Dimethylamylamine, vitamin A, Garcinia cambogia and ma huang). Additional DS containing some of the aforementioned ingredients implicated in liver injury are also covered. We have also included illicit androgenic anabolic steroids for bodybuilding in this work, as they are frequently sold under the denomination of DS despite being conventional drugs.

  5. Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics

    Directory of Open Access Journals (Sweden)

    Miren García-Cortés

    2016-04-01

    Full Text Available Dietary supplements (DS are extensively consumed worldwide despite unproven efficacy. The true incidence of DS-induced liver injury (DSILI is unknown but is probably under-diagnosed due to the general belief of safety of these products. Reported cases of herbals and DS-induced liver injury are increasing worldwide. The aim of this manuscript is to report a tabular listing with a description of DS associated with hepatotoxicity as well as review the phenotype and severity of DSILI. Natural remedies related to hepatotoxicity can be divided into herbal product-induced liver injury and DS-induced liver injury. In this article, we describe different DS associated with liver injury, some of them manufactured DS containing several ingredients (Herbalife™ products, Hydroxycut™, LipoKinetix™, UCP-1 and OxyELITE™ while others have a single ingredient (green tea extract, linoleic acid, usnic acid, 1,3-Dimethylamylamine, vitamin A, Garcinia cambogia and ma huang. Additional DS containing some of the aforementioned ingredients implicated in liver injury are also covered. We have also included illicit androgenic anabolic steroids for bodybuilding in this work, as they are frequently sold under the denomination of DS despite being conventional drugs.

  6. Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions

    Directory of Open Access Journals (Sweden)

    Roy P

    2014-10-01

    Full Text Available Partha Roy,1,2 Suvadra Das,1 Runa Ghosh Auddy,1,3 Arup Mukherjee1,3 1Division of Pharmaceutical and Fine Chemicals Technology, Department of Chemical Technology, University of Calcutta, Kolkata, India; 2Faculty of Technology (Pharmaceutical, Universiti Malaysia, Pahang, Malaysia; 3Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India Abstract: Andrographolide (AG is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7±17.17 nm and ζ-potential +34.4±1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery. Keywords: andrographolide, engineered nanosystems, poly(lactic-co-glycolic acid, cytokine regulation, hepatotoxicity

  7. Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus.

    Science.gov (United States)

    Saxena, Beenam; Sharma, Shiv

    2015-01-01

    Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were administered with 25, 50 and 75 mg/kg body weight blend of sunset yellow, metanil yellow and tartrazine for 30 days. Hepatotoxicity in rats treated with a blend of these food colors was studied by assessing parameters such as serum total protein, serum albumin, serum alkaline phosphatase (ALP) as well as hepatic malondialdehyde (MDA). The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were assessed. Significantly increased concentrations of serum total protein, serum albumin, serum ALP and hepatic MDA and significantly lowered levels of SOD, reduced GSH and CAT in the liver tissue of treated animals were observed when compared with control animals. The alteration in the liver includes necrosis of hepatocytes, infiltration and vacuolation. The result indicates that consumption of food color in diet induces liver tissue damage. The used doses of food color were mostly attributable to hepatocellular damage and drastic alteration in antioxidant defense system.

  8. Bee sting therapy-induced hepatotoxicity: A case report.

    Science.gov (United States)

    Alqutub, Adel Nazmi; Masoodi, Ibrahim; Alsayari, Khalid; Alomair, Ahmed

    2011-10-27

    The use of bee venom as a therapeutic agent for the relief of joint pains dates back to Hippocrates, and references to the treatment can be found in ancient Egyptian and Greek medical writings as well. Also known as apitherapy, the technique is widely used in Eastern Europe, Asia, and South America. The beneficial effects of bee stings can be attributed to mellitinin, an anti-inflammatory agent, known to be hundred times stronger than cortisone. Unfortunately, certain substances in the bee venom trigger allergic reactions which can be life threatening in a sensitized individual. Multiple stings are known to cause hemolysis, kidney injury, hepatotoxicity and myocardial infarction. The toxicity can be immediate or can manifest itself only weeks after the exposure. We describe hepatotoxicity in a 35-year-old female, following bee sting therapy for multiple sclerosis. She presented to our clinic 3 wk after therapy with a history of progressive jaundice. The patient subsequently improved, and has been attending our clinic now for the last 9 mo.

  9. Hepatotoxicity in hyperthyroid patient after consecutive methimazole and propylthiouracil therapies

    Directory of Open Access Journals (Sweden)

    Fernando Gomez-Peralta

    2018-01-01

    Full Text Available Methimazole (MMI and propylthiouracil (PTU are widely used antithyroid drugs (ATD that have been approved for the treatment of hyperthyroidism. Hepatotoxicity may be induced by these drugs, though they exert dissimilar incidence rates of hepatotoxicity and, possibly, with different underlying pathogenic mechanisms. We report the case of a 55-year-old woman with no relevant medical history diagnosed with hyperthyroidism due to Graves’ disease, who developed two episodes of acute hepatitis concurrent with the consecutive administration of two different ATDs, first MMI and then PTU. Given the impossibility of administering ATDs, it was decided to perform a total thyroidectomy because the patient was found to be euthyroid at that point. Pathological anatomy showed diffuse hyperplasia and a papillary thyroid microcarcinoma of 2 mm in diameter. Subsequent clinical check-ups were normal. This case suggests the importance of regular monitoring of liver function for hyperthyroid patients. Due to the potential severity of this side effect, it is recommended to determine baseline liver function prior to initiation of treatment.

  10. Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics

    Science.gov (United States)

    García-Cortés, Miren; Robles-Díaz, Mercedes; Ortega-Alonso, Aida; Medina-Caliz, Inmaculada; Andrade, Raul J.

    2016-01-01

    Dietary supplements (DS) are extensively consumed worldwide despite unproven efficacy. The true incidence of DS-induced liver injury (DSILI) is unknown but is probably under-diagnosed due to the general belief of safety of these products. Reported cases of herbals and DS-induced liver injury are increasing worldwide. The aim of this manuscript is to report a tabular listing with a description of DS associated with hepatotoxicity as well as review the phenotype and severity of DSILI. Natural remedies related to hepatotoxicity can be divided into herbal product-induced liver injury and DS-induced liver injury. In this article, we describe different DS associated with liver injury, some of them manufactured DS containing several ingredients (Herbalife™ products, Hydroxycut™, LipoKinetix™, UCP-1 and OxyELITE™) while others have a single ingredient (green tea extract, linoleic acid, usnic acid, 1,3-Dimethylamylamine, vitamin A, Garcinia cambogia and ma huang). Additional DS containing some of the aforementioned ingredients implicated in liver injury are also covered. We have also included illicit androgenic anabolic steroids for bodybuilding in this work, as they are frequently sold under the denomination of DS despite being conventional drugs. PMID:27070596

  11. Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus

    Science.gov (United States)

    Saxena, Beenam; Sharma, Shiv

    2015-01-01

    Objective: Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. Materials and Methods: Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were administered with 25, 50 and 75 mg/kg body weight blend of sunset yellow, metanil yellow and tartrazine for 30 days. Hepatotoxicity in rats treated with a blend of these food colors was studied by assessing parameters such as serum total protein, serum albumin, serum alkaline phosphatase (ALP) as well as hepatic malondialdehyde (MDA). The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were assessed. Results: Significantly increased concentrations of serum total protein, serum albumin, serum ALP and hepatic MDA and significantly lowered levels of SOD, reduced GSH and CAT in the liver tissue of treated animals were observed when compared with control animals. The alteration in the liver includes necrosis of hepatocytes, infiltration and vacuolation. Conclusion: The result indicates that consumption of food color in diet induces liver tissue damage. The used doses of food color were mostly attributable to hepatocellular damage and drastic alteration in antioxidant defense system. PMID:26862277

  12. Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Pajaree Sriuttha

    2018-01-01

    Full Text Available Background. Nonsteroidal anti-inflammatory drugs (NSAIDs are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review. To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods. Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results. Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2, followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2, and etoricoxib, which ranged from 0.005 to 0.930 (×10−2. Conclusion. Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

  13. Toll-like receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis.

    Science.gov (United States)

    Valladares, Roberto D; Nich, Christophe; Zwingenberger, Stefan; Li, Chenguang; Swank, Katherine R; Gibon, Emmanuel; Rao, Allison J; Yao, Zhenyu; Goodman, Stuart B

    2014-09-01

    Aseptic loosening secondary to particle-associated periprosthetic osteolysis remains a major cause of failure of total joint replacements (TJR) in the mid- and long term. As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade, which results in the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are involved in the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns. Experimentally, polymethylmethacrylate and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle-induced osteolysis remain largely unknown. We hypothesized that TLR-2, -4, and -9 mediated responses play a critical role in the development of PE wear particle-induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE-treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle-induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may represent novel therapeutic targets for prevention of wear particle-induced osteolysis and accompanying TJR failure. © 2013 Wiley Periodicals, Inc.

  14. The quantitative determination of trace elements in giant unicellular plants by particle-induced X-ray emission

    International Nuclear Information System (INIS)

    Navarrete-Dominguez, V.R.; Yoshihara, K.; Tanaka, N.

    1982-01-01

    Particle-induced X-ray emission (PIXE) was applied for the determination of trace elements in biologically interesting materials, giant unicellular plants. It was found that the PIXE method had advantages in multi-element trace analysis of a single cell of the sample plant. (author)

  15. Photon hormesis deactivates alpha-particle induced bystander effects between zebrafish embryos

    International Nuclear Information System (INIS)

    Ng, C.Y.P.; Cheng, S.H.; Yu, K.N.

    2017-01-01

    In the present work, we studied the effects of low-dose X-ray photons on the alpha-particle induced bystander effects between embryos of the zebrafish, Danio rerio. The effects on the naive whole embryos were studied through quantification of apoptotic signals (amounts of cells undergoing apoptosis) at 24 h post fertilization (hpf) using vital dye acridine orange staining, followed by counting the stained cells under a fluorescent microscope. We report data showing that embryos at 5 hpf subjected to a 4.4 mGy alpha-particle irradiation could release a stress signal into the medium, which could induce bystander effect in partnered naive embryos sharing the same medium. We also report that the bystander effect was deactivated when the irradiated embryos were subjected to a concomitant irradiation of 10 or 14 mGy of X-rays, but no such deactivation was achieved if the concomitant X-ray dose dropped to 2.5 or 5 mGy. In the present study, the significant drop in the amount of apoptotic signals on the embryos having received 4.4 mGy alpha particles together X-rays irradiation from 2.5 or 5 mGy to 10 or 14 mGy, together with the deactivation of RIBE with concomitant irradiation of 10 or 14 mGy of X-rays supported the participation of photon hormesis with an onset dose between 5 and 10 mGy, which might lead to removal of aberrant cells through early apoptosis or induction of high-fidelity DNA repair. As we found that photons and alpha particles could have opposite biological effects when these were simultaneously irradiated onto living organisms, these ionizing radiations could be viewed as two different environmental stressors, and the resultant effects could be regarded as multiple stressor effects. The present work presented the first study on a multiple stressor effect which occurred on bystander organisms. In other words, this was a non-targeted multiple stressor effect. The photon hormesis could also explain some failed attempts to observe neutron-induced bystander

  16. Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats

    International Nuclear Information System (INIS)

    Kalender, Yusuf; Yel, Mustafa; Kalender, Suna

    2005-01-01

    Doxorubicin (DXR) is an anthracycline antibiotic, broady used in tumor therapy. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of doxorubicin. Vitamin E (200 IU/kg/week), catechin (200 mg/kg/week), doxorubicin (5 mg/kg/week), doxorubicin + vitamin E (200 IU/kg/week), doxorubicin + catechin (200 mg/kg/week) combinations were given to rats weighing 210-230 g (n = 6/group). Changes in major enzymes participating in free radical metabolism superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSHPx), catalase (CAT) and malondialdehyde (MDA) were evaluated in the livers of all animals. Superoxide dismutase and catalase activity increased in the doxorubicin-treated group compared to control (P 0.05). Electron microscopic studies supported biochemical findings. We conclude that vitamin E and catechin significantly reduce doxorubicin-induced hepatotoxicity in rats

  17. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, L.E.; Dalhoff, K.P.; Poulsen, Henrik E.

    2002-01-01

    . With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1...... was confirmed as the major risk factor in acetaminophen-induced hepatotoxicity and mortality. Chronic alcohol abuse was an independent risk factor that could be counteracted by concomitant acute alcohol ingestion. We suggest that patients with chronic alcoholism and suspected acetaminophen poisoning due......The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were...

  18. Possible hepatotoxic consequence of nevirapine use in juvenile albino rats

    Directory of Open Access Journals (Sweden)

    Elias Adikwu

    2017-08-01

    Full Text Available Context: Nevirapine (NVP is used in human immunodeficiency virus exposed neonates. This could present safety concern due to decreased liver metabolizing enzymes activity and renal clearance in neonates. Aims: To determine the hepatotoxic effect of NVP in juvenile albino rats. Methods: Juvenile albino rats were weighed, divided into groups and treated orally with 4-32 mg/kg/day of NVP for 14 days including a recovery group. The control groups were treated with water (placebo and normal saline (solvent. At the end of NVP treatment, rats were weighed and sacrificed, blood was collected and serum extracted. Serum was analyzed for alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, total bilirubin (TB and conjugated bilirubin (CB. The liver was harvested via dissection, weighed and evaluated for AST, ALT, ALP, superoxide dismutase (SOD, catalase (CAT, glutathione (GSH, malondialdehyde (MDA levels and histological damage. Results: The body, absolute and relative liver weights of rats in NVP treated groups were not significantly different (p>0.05 when compared to placebo. However, serum levels of AST, ALT, ALP, TB and CB were significantly increased (p<0.05 in a dose-dependent manner in NVP-treated groups. Furthermore, liver levels of ALT, ALP, AST and MDA were significantly increased (p<0.05 while SOD, CAT, and GSH were decreased in a dose dependent manner in NVP-treated groups. NVP-treated rats were characterized by varying degrees of hepatic morphological alterations. However, in the recovery group, the effects of NVP were reversed. Conclusions: This study observed dose-dependent and reversible hepatotoxicity in nevirapine- treated juvenile albino rats.

  19. The current state of serum biomarkers of hepatotoxicity.

    Science.gov (United States)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-03-20

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

  20. The current state of serum biomarkers of hepatotoxicity

    International Nuclear Information System (INIS)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-01-01

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

  1. Fructose diet alleviates acetaminophen-induced hepatotoxicity in mice.

    Science.gov (United States)

    Cho, Sungjoon; Tripathi, Ashutosh; Chlipala, George; Green, Stefan; Lee, Hyunwoo; Chang, Eugene B; Jeong, Hyunyoung

    2017-01-01

    Acetaminophen (APAP) is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp) 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet) on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v) fructose in water (or regular water) for 8 weeks, followed by oral administration of APAP. APAP-induced liver injury (determined by serum levels of liver enzymes) was decreased by two-fold in mice pretreated with fructose. Fructose-treated mice exhibited (~1.5 fold) higher basal glutathione levels and (~2 fold) lower basal (mRNA and activity) levels of Cyp1a2 and Cyp2e1, suggesting decreased bioactivation of APAP and increased detoxification of toxic metabolite in fructose-fed mice. Hepatic mRNA expression of heat shock protein 70 was also found increased in fructose-fed mice. Analysis of bacterial 16S rRNA gene amplicons from the cecal samples of vehicle groups showed that the fructose diet altered gut bacterial community, leading to increased α-diversity. The abundance of several bacterial taxa including the genus Anaerostipes was found to be significantly correlated with the levels of hepatic Cyp2e1, Cyp1a2 mRNA, and glutathione. Together, these results suggest that the fructose-supplemented diet decreases APAP-induced liver injury in mice, in part by reducing metabolic activation of APAP and inducing detoxification of toxic metabolites, potentially through altered composition of gut microbiota.

  2. Hepatotoxicity and genotoxicity of gasoline fumes in albino rats

    Directory of Open Access Journals (Sweden)

    Folarin O. Owagboriaye

    2017-09-01

    Full Text Available Toxic effects of gasoline fumes have been reported, but evidence of its hepatotoxicity and genotoxicity are rare. Therefore, this study assesses hepatotoxicity and genotoxicity of gasoline fumes on forty Albino rats randomly assigned to five experimental treatments (T with eight rats per treatment (T1, T2, T3, T4 and T5. T1(Control was housed in a section of experimental animal house free from gasoline fumes while T2, T3, T4 and T5 were exposed to gasoline fumes in exposure chambers for one, three, five and nine hours daily respectively for twelve weeks. Serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and histopathological examination of the liver tissues were used as diagnostic markers to assess liver dysfunction. Genotoxicity test was conducted on the lung tissues using randomly amplified polymorphic DNA fingerprinting polymerase chain reaction (RAPD PCR technique. Significant increase (p < 0.05 in the level of ALT, AST and ALP for T2, T3, T4 and T5 compared to T1 were recorded. Photomicrograph examination of the liver sections of T1 showed hepatic tissue with normal liver cell architecture while that of T2, T3, T4 and T5 revealed degenerative changes in the ultrastructural integrity of the hepatic cells. Genotoxicity test revealed DNA bands at a reducing intensity from T1 to T5. Dendrogram showed DNA damage in the lungs of T3, T4 and T5 were closely similar and the genotoxic impact was more in T3. Frequent exposure to gasoline fumes was observed to induce hepatoxicity and genotoxicity, hence impairing the normal liver function and gene structure.

  3. Fructose diet alleviates acetaminophen-induced hepatotoxicity in mice.

    Directory of Open Access Journals (Sweden)

    Sungjoon Cho

    Full Text Available Acetaminophen (APAP is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v fructose in water (or regular water for 8 weeks, followed by oral administration of APAP. APAP-induced liver injury (determined by serum levels of liver enzymes was decreased by two-fold in mice pretreated with fructose. Fructose-treated mice exhibited (~1.5 fold higher basal glutathione levels and (~2 fold lower basal (mRNA and activity levels of Cyp1a2 and Cyp2e1, suggesting decreased bioactivation of APAP and increased detoxification of toxic metabolite in fructose-fed mice. Hepatic mRNA expression of heat shock protein 70 was also found increased in fructose-fed mice. Analysis of bacterial 16S rRNA gene amplicons from the cecal samples of vehicle groups showed that the fructose diet altered gut bacterial community, leading to increased α-diversity. The abundance of several bacterial taxa including the genus Anaerostipes was found to be significantly correlated with the levels of hepatic Cyp2e1, Cyp1a2 mRNA, and glutathione. Together, these results suggest that the fructose-supplemented diet decreases APAP-induced liver injury in mice, in part by reducing metabolic activation of APAP and inducing detoxification of toxic metabolites, potentially through altered composition of gut microbiota.

  4. Particle-induced bit errors in high performance fiber optic data links for satellite data management

    International Nuclear Information System (INIS)

    Marshall, P.W.; Carts, M.A.; Dale, C.J.; LaBel, K.A.

    1994-01-01

    Experimental test methods and analysis tools are demonstrated to assess particle-induced bit errors on fiber optic link receivers for satellites. Susceptibility to direct ionization from low LET particles is quantified by analyzing proton and helium ion data as a function of particle LET. Existing single event analysis approaches are shown to apply, with appropriate modifications, to the regime of temporally (rather than spatially) distributed bits, even though the sensitivity to single events exceeds conventional memory technologies by orders of magnitude. The cross-section LET dependence follows a Weibull distribution at data rates from 200 to 1,000 Mbps and at various incident optical power levels. The LET threshold for errors is shown, through both experiment and modeling, to be 0 in all cases. The error cross-section exhibits a strong inverse dependence on received optical power in the LET range where most orbital single events would occur, thus indicating that errors can be minimized by operating links with higher incident optical power. Also, an analytic model is described which incorporates the appropriate physical characteristics of the link as well as the optical and receiver electrical characteristics. Results indicate appropriate steps to assure suitable link performance even in severe particle orbits

  5. DCHAIN-SP 2001: High energy particle induced radioactivity calculation code

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Tetsuya; Maekawa, Fujio; Kasugai, Yoshimi; Takada, Hiroshi; Ikeda, Yujiro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Kosako, Kazuaki [Sumitomo Atomic Energy Industries, Ltd., Tokyo (Japan)

    2001-03-01

    For the purpose of contribution to safety design calculations for induced radioactivities in the JAERI/KEK high-intensity proton accelerator project facilities, the DCHAIN-SP which calculates the high energy particle induced radioactivity has been updated to DCHAIN-SP 2001. The following three items were improved: (1) Fission yield data are included to apply the code to experimental facility design for nuclear transmutation of long-lived radioactive waste where fissionable materials are treated. (2) Activation cross section data below 20 MeV are revised. In particular, attentions are paid to cross section data of materials which have close relation to the facilities, i.e., mercury, lead and bismuth, and to tritium production cross sections which are important in terms of safety of the facilities. (3) User-interface for input/output data is sophisticated to perform calculations more efficiently than that in the previous version. Information needed for use of the code is attached in Appendices; the DCHAIN-SP 2001 manual, the procedures of installation and execution of DCHAIN-SP, and sample problems. (author)

  6. Forensic analysis of tempered sheet glass by particle induced X-ray emission (PIXE)

    Energy Technology Data Exchange (ETDEWEB)

    Jisonna, L.J. [Department of Chemistry and Department of Physics, Hope College, Holland, MI 49422-9000 (United States); DeYoung, P.A., E-mail: deyoung@hope.ed [Department of Chemistry and Department of Physics, Hope College, Holland, MI 49422-9000 (United States); Ferens, J.; Hall, C.; Lunderberg, J.M.; Mears, P. [Department of Chemistry and Department of Physics, Hope College, Holland, MI 49422-9000 (United States); Padilla, D. [Department of Physics, San Diego State University, San Diego, CA 92182-1233 (United States); Peaslee, G.F. [Department of Chemistry and Department of Physics, Hope College, Holland, MI 49422-9000 (United States); Sampson, R. [Department of Physics, Columbia University, New York, NY 10027 (United States)

    2011-05-15

    Highlights: {yields} PIXE was found to give the same results for trace elements in glass as ICP. {yields} PIXE can non-destructively determine trace element concentrations in auto glass. {yields} Measured Ca, Fe, Ti, Mn, and Sr in auto glass with PIXE. -- Abstract: The elemental concentrations of five trace elements in tempered sheet glass fragments were determined using particle-induced X-ray emission (PIXE) spectrometry. The trace element concentrations for calcium, iron, manganese, strontium, and titanium are compared to those obtained by inductively-coupled plasma-atomic emission spectrometry (ICP-AES) following complete digestion by hydrofluoric acid. For these five elements, the absolute concentrations obtained by both methods are shown to agree well over a wide range of concentrations. The limits of detection for trace elements are typically lower for the ICP-AES method. However, we show that the concentrations of these five elements can be accurately measured by the PIXE method. Since PIXE is an entirely non-destructive method, there exists a niche for this technique to be used as a complement to the more sensitive ICP-AES technique in the forensic analysis of sheet glass.

  7. Determination of impurities in silicon nitride by particle induced x-ray emission analysis

    International Nuclear Information System (INIS)

    Miyagawa, Yoshiko; Saito, Kazuo; Niwa, Hiroaki; Ishizuka, Toshio; Miyagawa, Soji

    1985-01-01

    A method is presented for quantitative particle induced X-ray emission (PIXE) analysis of impurities in the thick samples of silicon nitride. In the analysis of ceramic materials such as silicon nitride, chemical treatments are required to prepare thin enough samples. However, the chemical treatments are undesirable for the PIXE analysis, because another complications are brought about. Our method does not need any chemical treatments and thick samples can be subjected to the measurements. The determination of impurities were made by on-line use of a personal computer in which standard X-ray intensity data were stored. The method and procedures are as follows: After subtracting a buckground spectrum from an observed PIXE spectrum, the resultant peaks are assigned to individual elements. Then, in order to determine the contents of the impurities, the intensity of each peak is compared with a Gaussian curve which is generated from the standard X-ray intensity data. The latter data were determined theoretically. The results were in satisfactory agreement with those obtained by ICP emission spectrometry. (author)

  8. Applications of particle induced X-ray emission analysis to ambient aerosol studies

    International Nuclear Information System (INIS)

    Lannefors, H.

    1982-01-01

    The characteristics of Particle Induced X-ray Emission (PIXE) analysis in conjunction with different ambient aerosol samplers have been studied. Correction factors have been calculated for homogeneous and inhomogeneous rural and urban aerosol samples. The Nuclepore two stage filter sampler provided the most useful combination of the resolution and particle size fractionation in urban, rural and remote environments. The PIXE-analysis technique in combination with different samplers was employed in aerosol composition studies in rural and remote environments. Particular emphasis was laid on studies of aerosol long range transport. Based on air mass trajectory analysis and aerosol composition measurements the foreign contribution in southern Sweden was estimated to be 70 - 80% for S and Pb but only 30 - 50% for V and Ni. The spatial and temporal extension of a long range transport episode was studied using high time resolution continuous filter samplers in a network in southern Sweden. The variation in the concentration levels of sulphur agreed well with changes in the air mass history. Arctic summer elemental concentration levels as measured during the Swedish YMER-80 icebreaker expedition were typically one order of magnitude lower than Arctic winter levels. The combination of chemical information, optical properties and size distribution data supports the hypothesis of long range transport of air pollution into the Arctic especially during the winter. This takes place during the winter season because the Polar front is further south making conditions for long range transport up to the Arctic more favourable. (Auth.)

  9. Theoretical approach to study the light particles induced production routes of 22Na

    International Nuclear Information System (INIS)

    Eslami, M.; Kakavand, T.; Mirzaii, M.

    2015-01-01

    Highlights: • Excitation function of 22 Na via thirty-three various reactions. • Various theoretical frameworks along with adjustments are employed in the calculations. • The results are given at energy range from the threshold up to 100 MeV. • The results are compared with each other and corresponding experimental data. - Abstract: To create a roadmap for the industrial-scale production of sodium-22, various production routes of this radioisotope involving light charged-particle-induced reactions at the bombarding energy range of threshold to a maximum of 100 MeV have been calculated. The excitation functions are calculated by using various nuclear models. Reaction pre-equilibrium process calculations have been made in the framework of the hybrid and geometry dependent hybrid models using ALICE/ASH code, and in the framework of the exciton model using TALYS-1.4 code. To calculate the compound nucleus evaporation process, both Weisskopf–Ewing and Hauser–Feshbach theories have been employed. The cross sections have also separately been estimated with five different level density models at the whole projectile energies. A comparison with calculations based on the codes, on one hand, and experimental data, on the other hand, is arranged and discussed

  10. The measurement and modeling of alpha-particle-induced charge collection in dynamic memories

    International Nuclear Information System (INIS)

    Oldiges, P.J.

    1989-01-01

    This thesis addresses the problem of α-particle-induced charge collection in high-density dynamic random access memories. A novel technique for the measurement of charge collection in high-density memory cells and bit lines due to α-particle strikes was developed. The technique involves D.C. tests on simple test structures with an α-particle source on the device package as a lid. The advantages of this new measurement technique are: the method allows for in-situ measurements of charge collection on both MOS capacitors and bit lines found in present-day memories; the on-chip measurement technique minimizes errors due to external probes loading the device under test; the measurements can be controlled by a personal computer, with the data being able to be reduced on the same machine. Results obtained using this new measurement technique show that the charge collection is found to depend upon test-structure size and the configuration of its neighbors. Results of two-dimensional simulations of charge flow along the surface of an MOS capacitor from current injection due to an α-particle strike indicate that a spatial potential variation of 0.5V may occur between the point of current injection and capacitor edge for a 1M dRAM capacitor

  11. Composition of Renaissance paint layers: simultaneous particle induced X-ray emission and backscattering spectrometry.

    Science.gov (United States)

    de Viguerie, L; Beck, L; Salomon, J; Pichon, L; Walter, Ph

    2009-10-01

    Particle induced X-ray emission spectroscopy (PIXE) is now routinely used in the field of cultural heritage. Various setups have been developed to investigate the elemental composition of wood/canvas paintings or of cross-section samples. However, it is not possible to obtain information concerning the quantity of organic binder. Backscattering spectrometry (BS) can be a useful complementary method to overcome this limitation. In the case of paint layers, PIXE brings the elemental composition (major elements to traces) and the BS spectrum can give access to the proportion of pigment and binder. With the use of 3 MeV protons for PIXE and BS simultaneously, it was possible to perform quantitative analysis including C and O for which the non-Rutherford cross sections are intense. Furthermore, with the use of the same conditions for PIXE and BS, the experiment time and the potential damage by the ion beam were reduced. The results obtained with the external beam of the Accélérateur Grand Louvre pour l'Analyse Elementaire (AGLAE) facility on various test painting samples and on cross sections from Italian Renaissance masterpieces are shown. Simultaneous combination of PIXE and BS leads to a complete characterization of the paint layers: elemental composition and proportion of the organic binder have been determined and thus provide useful information about ancient oil painting recipes.

  12. A moving target for accelerated charged particle induced X-ray measurement

    International Nuclear Information System (INIS)

    Chuang, L.S.; Shima, K.; Ebihara, H.; Seki, R.; Mikumo, T.

    1980-01-01

    To attain good reproducibility as well as to enable an absolute determination in the measurement of X-ray fluorescences, resulting from bombardment of a heterogeneous sample by accelerated charged particles, a moving-target mechanism incorporating an electronic remote control system has been devised. The system is designed to scan the whole sample area with a chosen constant linear speed, by a fixed particle beam with a cross-sectional area a small fraction of that of the sample. Using 16 MeV protons and 40 MeV oxygen-ion beams, test runs of this system showed that the attempted objectives are attainable with good accuracies: reproducibility of the data for a given target is better than 3%, the linearity of the calibration curve is in good agreement, within the weighing errors of the standard elements and the uncertainty due to beam current fluctuation, with the expected values, and the results of absolute determinations using both metal foils and heterogeneous powder samples are in good agreement with accepted results using different methods. Detailed accounts of the moving-target system, and the test for reproducibility and linearity are presented. An absolute determination of the quantities related to accelerated charged-particle induced X-ray fluorescence (PIXE) using the moving target is presented for samples in different forms. (orig./HP)

  13. Particle-Induced Gamma-ray Emission Spectroscopy Over a Broad Range of Elements

    Science.gov (United States)

    Olds, Hannah; Wilkinson, John; Tighe, Meghanne; McLallen, Walter; McGuire, Patrick

    2017-09-01

    Ion beam analysis is a common application of nuclear physics that allows elemental and isotopic information about materials to be determined from accelerated light ion beams One of the best know ion beam analysis techniques is Particle-Induced Gamma-ray Emission (PIGE) spectroscopy, which can be used ex vacuo to identify the elements of interest in almost any solid target. The energies of the gamma-rays emitted by excited nuclei will be unique to each element and depend on its nuclear structure. For the most sensitivity, the accelerated ions should exceed the Coulomb barrier of the target, but many isotopes are known to be accessible to PIGE even below the Coulomb barrier. To explore the sensitivity of PIGE across the periodic table, PIGE measurements were made on elements with Z = 5, 9, 11-15, 17, 19-35, 37, 42, 44-48, 53, 56, 60, 62, 73, and 74 using 3.4 MeV protons. These measurements will be compared with literature values and be used as a basis for comparison with higher-energy proton beams available at the University of Notre Dame's St. Andre accelerator when it comes online this Fall. The beam normalization technique of using atmospheric argon and its 1459 keV gamma-ray to better estimate the integrated beam on target will also be discussed. Funded by the NSF REU program and the University of Notre Dame.

  14. Boron analysis for neutron capture therapy using particle-induced gamma-ray emission

    International Nuclear Information System (INIS)

    Nakai, Kei; Yamamoto, Yohei; Okamoto, Emiko; Yamamoto, Tetsuya; Yoshida, Fumiyo; Matsumura, Akira; Yamada, Naoto; Kitamura, Akane; Koka, Masashi; Satoh, Takahiro

    2015-01-01

    The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18 μgB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20 min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm. - Highlights: • PIGE was evaluated for measuring blood boron concentration during clinical BNCT. • PIGE detected 18 μgB/mL f-BPA in culture medium. • All measurements of any given sample were taken within 20 min. • Two hours of f-BPA exposure is required to create boron distribution image by PIGE. • Boron on the cell membrane could not be distinguished from boron in the cytoplasm.

  15. Leflunomide for the treatment of rheumatoid arthritis in clinical practice: Incidence and severity of hepatotoxicity

    NARCIS (Netherlands)

    Van Roon, Eric N.; Jansen, Tim L.Th.A.; Houtman, Nella M.; Spoelstra, Piet; Brouwers, Jacobus R.B.J.

    2004-01-01

    Objective: Leflunomide is a novel disease modifying antirheumatic drug (DMARD). Because of reports on possible hepatotoxicity and adaptations in the recommendations for monitoring liver function during leflunomide treatment, we conducted a study to evaluate the incidence and severity of

  16. Predicting Hepatotoxicity of Drug Metabolites Via an Ensemble Approach Based on Support Vector Machine

    Science.gov (United States)

    Lu, Yin; Liu, Lili; Lu, Dong; Cai, Yudong; Zheng, Mingyue; Luo, Xiaomin; Jiang, Hualiang; Chen, Kaixian

    2017-11-20

    Drug-induced liver injury (DILI) is a major cause of drug withdrawal. The chemical properties of the drug, especially drug metabolites, play key roles in DILI. Our goal is to construct a QSAR model to predict drug hepatotoxicity based on drug metabolites. 64 hepatotoxic drug metabolites and 3,339 non-hepatotoxic drug metabolites were gathered from MDL Metabolite Database. Considering the imbalance of the dataset, we randomly split the negative samples and combined each portion with all the positive samples to construct individually balanced datasets for constructing independent classifiers. Then, we adopted an ensemble approach to make prediction based on the results of all individual classifiers and applied the minimum Redundancy Maximum Relevance (mRMR) feature selection method to select the molecular descriptors. Eventually, for the drugs in the external test set, a Bayesian inference method was used to predict the hepatotoxicity of a drug based on its metabolites. The model showed the average balanced accuracy=78.47%, sensitivity =74.17%, and specificity=82.77%. Five molecular descriptors characterizing molecular polarity, intramolecular bonding strength, and molecular frontier orbital energy were obtained. When predicting the hepatotoxicity of a drug based on all its metabolites, the sensitivity, specificity and balanced accuracy were 60.38%, 70.00%, and 65.19%, respectively, indicating that this method is useful for identifying the hepatotoxicity of drugs. We developed an in silico model to predict hepatotoxicity of drug metabolites. Moreover, Bayesian inference was applied to predict the hepatotoxicity of a drug based on its metabolites which brought out valuable high sensitivity and specificity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Risk of hepatotoxicity associated with the use of telithromycin: a signal detection using data mining algorithms.

    Science.gov (United States)

    Chen, Yan; Guo, Jeff J; Healy, Daniel P; Lin, Xiaodong; Patel, Nick C

    2008-12-01

    With the exception of case reports, limited data are available regarding the risk of hepatotoxicity associated with the use of telithromycin. To detect the safety signal regarding the reporting of hepatotoxicity associated with the use of telithromycin using 4 commonly employed data mining algorithms (DMAs). Based on the Adverse Events Reporting System (AERS) database of the Food and Drug Administration, 4 DMAs, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the Gamma Poisson Shrinker (GPS), were applied to examine the association between the reporting of hepatotoxicity and the use of telithromycin. The study period was from the first quarter of 2004 to the second quarter of 2006. The reporting of hepatotoxicity was identified using the preferred terms indexed in the Medical Dictionary for Regulatory Activities. The drug name was used to identify reports regarding the use of telithromycin. A total of 226 reports describing hepatotoxicity associated with the use of telithromycin were recorded in the AERS. A safety problem of telithromycin associated with increased reporting of hepatotoxicity was clearly detected by 4 algorithms as early as 2005, signaling the problem in the first quarter by the ROR and the IC, in the second quarter by the PRR, and in the fourth quarter by the GPS. A safety signal was indicated by the 4 DMAs suggesting an association between the reporting of hepatotoxicity and the use of telithromycin. Given the wide use of telithromycin and serious consequences of hepatotoxicity, clinicians should be cautious when selecting telithromycin for treatment of an infection. In addition, further observational studies are required to evaluate the utility of signal detection systems for early recognition of serious, life-threatening, low-frequency drug-induced adverse events.

  18. Hepatotoxicity evaluation of traditional Chinese medicines using a computational molecular model.

    Science.gov (United States)

    Zhao, Pan; Liu, Bin; Wang, Chunya

    2017-11-01

    Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns. This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity. A quantitative structure-activity relationship (QSAR) analysis was performed based on published data and U.S. Food and Drug Administration's Liver Toxicity Knowledge Base (LTKB). Eleven herbal ingredients with proven liver toxicity in the literature were added into the dataset besides chemicals from LTKB. The finally generated QSAR model yielded a sensitivity of 83.8%, a specificity of 70.1%, and an accuracy of 80.2%. Among the externally tested 20 ingredients from TCMs, 14 hepatotoxic ingredients were all accurately identified by the QSAR model derived from the dataset containing natural hepatotoxins. Adding natural hepatotoxins into the dataset makes the QSAR model more applicable for TCM hepatotoxicity assessment, which provides a right direction in the methodology study for TCM safety evaluation. The generated QSAR model has the practical value to prioritize the hepatotoxicity risk of TCM compounds. Furthermore, an open-access international specialized database on TCM hepatotoxicity should be quickly established.

  19. Development of a Reference Database for Particle-Induced Gamma-ray Emission spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dimitriou, P., E-mail: P.Dimitriou@iaea.org [International Atomic Energy Agency, Wagramerstrasse 5, A-1400 Vienna (Austria); Becker, H.-W. [Ruhr Universität Bochum, Gebäude NT05/130, Postfach 102148, Bochum 44721 (Germany); Bogdanović-Radović, I. [Department of Experimental Physics, Institute Rudjer Boskovic, Bijenicka Cesta 54, 10000 Zagreb (Croatia); Chiari, M. [Istituto Nazionale di Fisica Nucleare, Via Sansone 1, Sesto Fiorentino, 50019 Firenze (Italy); Goncharov, A. [Kharkov Institute of Physics and Technology, National Science Center, Akademicheskaya Str.1, Kharkov 61108 (Ukraine); Jesus, A.P. [Departamento de Física, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa (Portugal); Kakuee, O. [Nuclear Science and Technology Research Institute, End of North Karegar Ave., PO Box 14395-836, Tehran (Iran, Islamic Republic of); Kiss, A.Z. [Institute of Nuclear Research (ATOMKI), Bem ter 18/c, PO Box 51, 4001 Debrecen (Hungary); Lagoyannis, A. [National Center of Scientific Research “Demokritos”, Agia Paraskevi, P.O. Box 60228, 15310 Athens (Greece); Räisänen, J. [Division of Materials Physics, Department of Physics, University of Helsinki, PO Box 43, 00014 University of Helsinki (Finland); Strivay, D. [Institut de Physique Nucleaire, Atomique et de Spectroscopie, Universite de Liège, Sart Tilman, B15 4000 Liège (Belgium); Zucchiatti, A. [Centro de Micro Análisis de Materiales, Universidad Autónoma de Madrid, Faraday 3, Madrid 28049 (Spain)

    2016-03-15

    Particle-Induced Gamma-ray Emission (PIGE) is a powerful analytical technique that exploits the interactions of rapid charged particles with nuclei located near a sample surface to determine the composition and structure of the surface regions of solids by measurement of characteristic prompt γ rays. The potential for depth profiling of this technique has long been recognized, however, the implementation has been limited owing to insufficient knowledge of the physical data and lack of suitable user-friendly computer codes for the applications. Although a considerable body of published data exists in the nuclear physics literature for nuclear reaction cross sections with γ rays in the exit channel, there is no up-to-date, comprehensive compilation specifically dedicated to IBA applications. A number of PIGE cross-section data had already been uploaded to the Ion Beam Analysis Nuclear Data Library (IBANDL) ( (http://www-nds.iaea.org/ibandl)) by members of the IBA community by 2011, however a preliminary survey of this body of unevaluated experimental data has revealed numerous discrepancies beyond the uncertainty limits reported by the authors. Using the resources and coordination provided by the IAEA, a concerted effort to improve the situation was made within the Coordinated Research Project on the Development of a Reference Database for PIGE spectroscopy, from 2011 to 2015. The aim of the CRP was to create a data library for Ion Beam Analysis that contains reliable and usable data on charged particle γ-ray emission cross sections that would be made freely available to the user community. As the CRP has reached its completion, we shall present its main achievements, including the results of nuclear cross-section evaluations and the development of a computer code that will become available to the public allowing for the implementation of a standardless PIGE technique.

  20. Antwerp Copper Plates

    DEFF Research Database (Denmark)

    Wadum, Jørgen

    1999-01-01

    In addition to presenting a short history of copper paintings, topics detail artists’ materials and techniques, as well as aspects of the copper industry, including mining, preparation and trade routes.......In addition to presenting a short history of copper paintings, topics detail artists’ materials and techniques, as well as aspects of the copper industry, including mining, preparation and trade routes....

  1. Copper and Copper Proteins in Parkinson's Disease

    Science.gov (United States)

    Rivera-Mancia, Susana; Diaz-Ruiz, Araceli; Tristan-Lopez, Luis; Rios, Camilo

    2014-01-01

    Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology. PMID:24672633

  2. Separation of copper-64 from copper phthalocyanine

    International Nuclear Information System (INIS)

    Battaglin, R.I.M.

    1979-01-01

    The separation of copper-64 from irradiated copper phthalocyanine by Szilard-Chalmers effect is studied. Two methods of separation are used: one of them is based on the dissolution of the irradiated dry compound in concentrated sulfuric acid following its precipitation in water. In the other one the compound is irradiated with water in paste form following treatment with water and hydrochloric acid. The influence of the crystal form of the copper phthalocyanine on the separation yield of copper-64 is shown. Preliminary tests using the ionic exchange technique for purification and changing of copper-64 sulfate to chloride form are carried out. The specific activity using the spectrophotometric technique, after the determination of the copper concentration in solution of copper-64, is calculated. (Author) [pt

  3. Cross section measurement of alpha particle induced nuclear reactions on natural cadmium up to 52 MeV

    OpenAIRE

    Ditrói, F.; Takács, S.; Haba, H.; Komori, Y.; Aikawa, M.

    2016-01-01

    Cross sections of alpha particle induced nuclear reactions have been measured on thin natural cadmium targets foils in the energy range from 11 to 51.2 MeV. This work was a part of our systematic study on excitation functions of light ion induced nuclear reactions on different target materials. Regarding the cross sections, the alpha induced reactions are not deeply enough investigated. Some of the produced isotopes are of medical interest, others have application in research and industry. Th...

  4. Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong-Ki; Seo, Seung-Jun [Biomedical Engineering and Radiology, School of Medicine, Catholic University of Daegu, Daegu 705-034 (Korea, Republic of); Kim, Ki-Hong [Department of Optometry and Visual Sciences, Catholic University of Daegu, Kyungsan 712-702 (Korea, Republic of); Kim, Tae-Jeong [Applied Chemical Engineering, College of Engineering, Kyungpuk National University, Daegu 702-701 (Korea, Republic of); Chung, Myung-Hwan; Kim, Kye-Ryung [Proton Engineering Frontier Project, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Yang, Tae-Keun, E-mail: jkkim@cu.ac.kr [Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2010-10-22

    Metallic nanoparticles (MNP) are able to release localized x-rays when activated with a high energy proton beam by the particle-induced x-ray emission (PIXE) effect. The exploitation of this phenomenon in the therapeutic irradiation of tumors has been investigated. PIXE-based x-ray emission directed at CT26 tumor cells in vitro, when administered with either gold (average diameter 2 and 13 nm) or iron (average diameter 14 nm) nanoparticles (GNP or SNP), increased with MNP solution concentration over the range of 0.1-2 mg ml{sup -1}. With irradiation by a 45 MeV proton therapy (PT) beam, higher concentrations had a decreased cell survival fraction. An in vivo study in CT26 mouse tumor models with tumor regression assay demonstrated significant tumor dose enhancement, thought to be a result of the PIXE effect when compared to conventional PT without MNP (radiation-only group) using a 45 MeV proton beam (p < 0.02). Those receiving GNP or SNP injection doses of 300 mg kg{sup -1} body weight before proton beam therapy demonstrated 90% or 75% tumor volume reduction (TVR) in 20 days post-PT while the radiation-only group showed only 18% TVR and re-growth of tumor volume after 20 days. Higher complete tumor regression (CTR) was observed in 14-24 days after a single treatment of PT with an average rate of 33-65% for those receiving MNP compared with 25% for the radiation-only group. A lower bound of therapeutic effective MNP concentration range, in vivo, was estimated as 30-79 {mu}g g{sup -1} tissue for both gold and iron nanoparticles. The tumor dose enhancement may compensate for an increase in entrance dose associated with conventional PT when treating large, solid tumors with a spread-out Bragg peak (SOBP) technique. The use of a combined high energy Bragg peak PT with PIXE generated by MNP, or PIXE alone, may result in new treatment options for infiltrative metastatic tumors and other diffuse inflammatory diseases.

  5. Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions

    Science.gov (United States)

    Roy, Partha; Das, Suvadra; Auddy, Runa Ghosh; Mukherjee, Arup

    2014-01-01

    Andrographolide (AG) is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic) acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7±17.17 nm and ζ-potential +34.4±1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery. PMID:25336950

  6. Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity.

    Science.gov (United States)

    Elinav, Eran; Pinsker, Galia; Safadi, Rifaat; Pappo, Orit; Bromberg, Michal; Anis, Emilia; Keinan-Boker, Lital; Broide, Efrat; Ackerman, Zvi; Kaluski, Dorit Nitzan; Lev, Boaz; Shouval, Daniel

    2007-10-01

    Nutritional supplements are frequently considered to be harmless but indiscriminate use of unlabelled ingredients may lead to significant adverse reactions. In 2004, identification of four index cases of acute hepatitis associated with Herbalife intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife products were investigated. Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation. One patient developed sub-fulminant and two fulminant episodes of hepatic failure. Hepatitis resolved in eleven patients, while one patient succumbed to complications following liver transplantation. Three patients resumed consumption of Herbalife products following normalization of liver enzymes, resulting in a second bout of hepatitis. An association between intake of Herbalife products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife products for possible hepatotoxicity. Until then, caution should be exercised by consumers, especially among individuals suffering from underlying liver disease.

  7. Hepatotoxicity Evaluation of Aqueous Extract from Scutia buxifolia

    Directory of Open Access Journals (Sweden)

    Margareth Linde Athayde

    2013-06-01

    Full Text Available Nowadays there is an increase in the number of people taking herbals worldwide. Scutia buxifolia is used for the treatment of hypertension, but little is known about its action on liver. Thirty-two Wistar rats were divided into four groups: control and groups treated during 30 days with 100, 200 and 400 mg of lyophilized aqueous extract of S. buxifolia (SBSB/kg of body weight. This study was planned to explore hepatotoxic effect of SBSB, which was assessed by serum transaminases (ALT and AST. Thiobarbituric acid reactive substances (TBARS levels were determined in liver, along with thiols content (NPSH, catalase (CAT activity and, superoxide dismutase (SOD enzymes. Histopathological studies of liver tissue were performed. Flavonoids and phenolics were quantified in SBSB by high performance liquid chromatography with diode array detection (HPLC/DAD. We did not observe alterations on redox status (TBARS, NPSH, CAT and, SOD in the control and experimental groups. An increase on AST activity was only observed at 200 mg of SBSB, whereas ALT score was not affected by SBSB. Moreover, no morphological alterations were observed on the hepatocytes, matching the analysed biochemical parameters. This way, we conclude that SBSB was not toxic.

  8. Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China.

    Science.gov (United States)

    Yang, Jun; Li, Lin-Fa; Xu, Qin; Zhang, Jun; Weng, Wan-Wen; Zhu, Yang-Jun; Dong, Meng-Jie

    2015-03-01

    Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients. Ninety patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with (131)I from a sample of 8864 patients with hyperthyroidism were studied, and the outcomes were evaluated. The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±standard deviation), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ significantly between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who were treated with (131)I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31). Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. (131)I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.

  9. Toxicogenomic analysis identifies the apoptotic pathway as the main cause of hepatotoxicity induced by tributyltin.

    Science.gov (United States)

    Zhou, Mi; Feng, Mei; Fu, Ling-Ling; Ji, Lin-Dan; Zhao, Jin-Shun; Xu, Jin

    2016-11-01

    Tributyltin (TBT) is one of the most widely used organotin biocides, which has severe endocrine-disrupting effects on marine species and mammals. Given that TBT accumulates at higher levels in the liver than in any other organ, and it acts mainly as a hepatotoxic agent, it is important to clearly delineate the hepatotoxicity of TBT. However, most of the available studies on TBT have focused on observations at the cellular level, while studies at the level of genes and proteins are limited; therefore, the molecular mechanisms of TBT-induced hepatotoxicity remains largely unclear. In the present study, we applied a toxicogenomic approach to investigate the effects of TBT on gene expression in the human normal liver cell line HL7702. Gene expression profiling identified the apoptotic pathway as the major cause of hepatotoxicity induced by TBT. Flow cytometry assays confirmed that medium- and high-dose TBT treatments significantly increased the number of apoptotic cells, and more cells underwent late apoptosis in the high-dose TBT group. The genes encoding heat shock proteins (HSPs), kinases and tumor necrosis factor receptors mediated TBT-induced apoptosis. These findings revealed novel molecular mechanisms of TBT-induced hepatotoxicity, and the current microarray data may also provide clues for future studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Andreas Buness

    Full Text Available Early and accurate pre-clinical and clinical biomarkers of hepatotoxicity facilitate the drug development process and the safety monitoring in clinical studies. We selected eight known model compounds to be administered to male Wistar rats to identify biomarkers of drug induced liver injury (DILI using transcriptomics, metabolite profiling (metabolomics and conventional endpoints. We specifically explored early biomarkers in serum and liver tissue associated with histopathologically evident acute hepatotoxicity. A tailored data analysis strategy was implemented to better differentiate animals with no treatment-related findings in the liver from animals showing evident hepatotoxicity as assessed by histopathological analysis. From the large number of assessed parameters, our data analysis strategy allowed us to identify five metabolites in serum and five in liver tissue, 58 transcripts in liver tissue and seven clinical chemistry markers in serum that were significantly associated with acute hepatotoxicity. The identified markers comprised metabolites such as taurocholic acid and putrescine (measured as sum parameter together with agmatine, classical clinical chemistry markers like AST (aspartate aminotransferase, ALT (alanine aminotransferase, and bilirubin, as well as gene transcripts like Igfbp1 (insulin-like growth factor-binding protein 1 and Egr1 (early growth response protein 1. The response pattern of the identified biomarkers was concordant across all types of parameters and sample matrices. Our results suggest that a combination of several of these biomarkers could significantly improve the robustness and accuracy of an early diagnosis of hepatotoxicity.

  11. Early predictors of severe acetaminophen-induced hepatotoxicity in a paediatric population referred to a tertiary paediatric department

    DEFF Research Database (Denmark)

    Hedeland, Rikke Lindgaard; Andersen, Jesper; Askbo, Natasha Louise Friis

    2014-01-01

    -acetylcysteine treatment on hepatotoxicity and the incidence of nephrotoxicity. METHODS: We carried out a retrospective case study on 25 children aged 11-16 years with severe acetaminophen poisoning. RESULTS: Initial biochemical parameters predicted hepatotoxicity, defined as the maximum levels of the international...

  12. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    Directory of Open Access Journals (Sweden)

    Miriam S. N. Hohmann

    2013-01-01

    Full Text Available 5-Lipoxygenase (5-LO converts arachidonic acid into leukotrienes (LTs and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO-/- mice and background wild type mice were challenged with APAP (0.3–6 g/kg or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10, superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate assay were prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.

  13. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  14. Mechanisms of circadian rhythmicity of carbon tetrachloride hepatotoxicity.

    Science.gov (United States)

    Bruckner, James V; Ramanathan, Raghupathy; Lee, K Monica; Muralidhara, Srinivasa

    2002-01-01

    The toxicity of carbon tetrachloride (CCl(4)) and certain other chemicals varies over a 24-h period. Because the metabolism of some drugs follows a diurnal rhythm, it was decided to investigate whether the hepatic metabolic activation of CCl(4) was rhythmic and coincided in time with maximum susceptibility to CCl(4) hepatotoxicity. A related objective was to test the hypothesis that abstinence from food during the sleep cycle results in lipolysis and formation of acetone, which participates in induction of liver microsomal cytochrome P450IIE1 (CYP2E1), resulting in a diurnal increase in CCl(4) metabolic activation and acute liver injury. Groups of fed and fasted male Sprague-Dawley rats were given a single oral dose of 800 mg of CCl(4)/kg at 2- to 4-h intervals over a 24-h period. Serum enzyme activities, measured 24 h post dosing as indices of acute liver injury, exhibited distinct maxima in both fed and fasted animals dosed with CCl(4) near the beginning of their dark/active cycle. Blood acetone, hepatic CYP2E1 activity, and covalent binding of (14)CCl(4)/metabolites to hepatic microsomal proteins in untreated rats fed ad libitum followed circadian rhythms similar to that of susceptibility to CCl(4). Parallel fluctuations of greater amplitude were seen in rats fasted for 24 h. Hepatic glutathione levels were lowest at the time of greatest susceptibility to CCl(4). Acetone dose-response experiments showed high correlations between blood acetone levels, CYP2E1 induction, and CCl(4)-induced liver injury. Pretreatment with diallyl sulfide suppressed CYP2E1 and abolished the circadian rhythmicity of susceptibility to CCl(4). These findings provide additional support for acetone's physiological role in CYP2E1 induction and for CYP2E1's role in modulating CCl(4) chronotoxicity in rats.

  15. Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity

    International Nuclear Information System (INIS)

    Martinez, Stephanie M.; Bradford, Blair U.; Soldatow, Valerie Y.; Kosyk, Oksana; Sandot, Amelia; Witek, Rafal; Kaiser, Robert; Stewart, Todd; Amaral, Kirsten; Freeman, Kimberly; Black, Chris; LeCluyse, Edward L.; Ferguson, Stephen S.; Rusyn, Ivan

    2010-01-01

    Numerous studies support the fact that a genetically diverse mouse population may be useful as an animal model to understand and predict toxicity in humans. We hypothesized that cultures of hepatocytes obtained from a large panel of inbred mouse strains can produce data indicative of inter-individual differences in in vivo responses to hepato-toxicants. In order to test this hypothesis and establish whether in vitro studies using cultured hepatocytes from genetically distinct mouse strains are feasible, we aimed to determine whether viable cells may be isolated from different mouse inbred strains, evaluate the reproducibility of cell yield, viability and functionality over subsequent isolations, and assess the utility of the model for toxicity screening. Hepatocytes were isolated from 15 strains of mice (A/J, B6C3F1, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, BALB/cByJ, AKR/J, MRL/MpJ, NOD/LtJ, NZW/LacJ, PWD/PhJ and WSB/EiJ males) and cultured for up to 7 days in traditional 2-dimensional culture. Cells from B6C3F1, C57BL/6J, and NOD/LtJ strains were treated with acetaminophen, WY-14,643 or rifampin and concentration-response effects on viability and function were established. Our data suggest that high yield and viability can be achieved across a panel of strains. Cell function and expression of key liver-specific genes of hepatocytes isolated from different strains and cultured under standardized conditions are comparable. Strain-specific responses to toxicant exposure have been observed in cultured hepatocytes and these experiments open new opportunities for further developments of in vitro models of hepatotoxicity in a genetically diverse population.

  16. The hepatotoxicity of multi-walled carbon nanotubes in mice

    Science.gov (United States)

    Ji, Zongfei; Zhang, Danying; Li, Ling; Shen, Xizhong; Deng, Xiaoyong; Dong, Ling; Wu, Minhong; Liu, Yuanfang

    2009-11-01

    The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg-1 by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- α, NF-κB signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.

  17. Hepatoprotective and antioxidant effects of Cuscuta chinensis against acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Yen, Feng-Lin; Wu, Tzu-Hui; Lin, Liang-Tzung; Lin, Chun-Ching

    2007-04-20

    Tu-Si-Zi, the seeds of Cuscuta chinensis Lam. (Convolvulaceae), is a traditional Chinese medicine that is commonly used to nourish and improve the liver and kidney conditions in China and other Asian countries. As oxidative stress promotes the development of acetaminophen (APAP)-induced hepatotoxicity, the aim of the present study was to evaluate and compare the hepatoprotective effect and antioxidant activities of the aqueous and ethanolic extracts of C chinensis on APAP-induced hepatotoxicity in rats. The C chinensis ethanolic extract at an oral dose of both 125 and 250mg/kg showed a significant hepatoprotective effect relatively to the same extent (PCuscuta chinensis can prevent hepatic injuries from APAP-induced hepatotoxicity in rats and this is likely mediated through its antioxidant activities.

  18. Aquatic Life Criteria - Copper

    Science.gov (United States)

    Documents pertain to Aquatic Life Ambient Water Quality criteria for Copper (2007 Freshwater, 2016 Estuarine/marine). These documents contain the safe levels of Copper in water that should protect to the majority of species.

  19. Investigation of electrically-active deep levels in single-crystalline diamond by particle-induced charge transient spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kada, W., E-mail: kada.wataru@gunma-u.ac.jp [Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515 (Japan); Kambayashi, Y.; Ando, Y. [Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515 (Japan); Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan); Onoda, S. [Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan); Umezawa, H.; Mokuno, Y. [National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577 (Japan); Shikata, S. [Kwansei Gakuin Univ., 2-1, Gakuen, Mita, Hyogo 669-1337 (Japan); Makino, T.; Koka, M. [Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan); Hanaizumi, O. [Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515 (Japan); Kamiya, T.; Ohshima, T. [Japan Atomic Energy Agency, Takasaki, Gunma 370-1292 (Japan)

    2016-04-01

    To investigate electrically-active deep levels in high-resistivity single-crystalline diamond, particle-induced charge transient spectroscopy (QTS) techniques were performed using 5.5 MeV alpha particles and 9 MeV carbon focused microprobes. For unintentionally-doped (UID) chemical vapor deposition (CVD) diamond, deep levels with activation energies of 0.35 eV and 0.43 eV were detected which correspond to the activation energy of boron acceptors in diamond. The results suggested that alpha particle and heavy ion induced QTS techniques are the promising candidate for in-situ investigation of deep levels in high-resistivity semiconductors.

  20. Cement analysis by particle-induced prompt photon spectrometry: comparison of the effect of different charged particle beams

    International Nuclear Information System (INIS)

    Gihwala, D.; Peisach, M.

    1985-01-01

    Standard cements were analysed by particle-induced prompt photon spectrometry (PIPPS) using 4,75-MeV protons, 5-MeV 4 He+ ions, and 2-MeV deuterons. Precision and sensitivity attainable were compared. Protons and alpha-particles were comparable for the determination of F, Na, Mg and Si. Protons were preferred for P and Ca, and alpha-particles for the direct determination of O. Sources of interference are discussed with particular reference to delayed gamma-ray emission from deuteron bombardment

  1. Effect of particle-induced displacements on the critical temperature of YBa2Cu3O7-δ

    International Nuclear Information System (INIS)

    Summers, G.P.; Burke, E.A.; Chrisey, D.B.; Nastasi, M.; Tesmer, J.R.

    1989-01-01

    The particle-induced depression of the superconducting critical temperature T c of YBa 2 Cu 3 O 7-δ is shown to be directly proportional, over seven orders of magnitude, to the nonionizing energy deposited in the lattice by primary knock-on atoms displaced by incident electrons, protons, and heavy ions. It is concluded that ΔT c is proportional only to the average number of defects produced and can therefore be predicted for any particle, energy, and fluence from a calculation of the nonionizing energy loss

  2. Copper Bioleaching in Chile

    OpenAIRE

    Juan Carlos Gentina; Fernando Acevedo

    2016-01-01

    Chile has a great tradition of producing and exporting copper. Over the last several decades, it has become the first producer on an international level. Its copper reserves are also the most important on the planet. However, after years of mineral exploitation, the ease of extracting copper oxides and ore copper content has diminished. To keep the production level high, the introduction of new technologies has become necessary. One that has been successful is bioleaching. Chile had the first...

  3. Demystifying Controlling Copper Corrosion

    Science.gov (United States)

    The LCR systematically misses the highest health and corrosion risk sites for copper. Additionally, there are growing concerns for WWTP copper in sludges and discharge levels. There are many corrosion control differences between copper and lead. This talk explains the sometimes c...

  4. Studying effects of Magnolol on alpha-particle induced bystander effects using PADC-film based dishes

    International Nuclear Information System (INIS)

    Wong, T.P.W.; Tse, A.K.W.; Fong, W.F.; Yu, K.N.

    2009-01-01

    Radiation-induced bystander effect refers to the biological response found in cells (called bystander cells) which are not irradiated directly by ionizing radiation but are next to cells irradiated directly by ionizing radiation. In the present paper, the effects of Magnolol, an extract from the bark of Magnolia officinalis which is used as a traditional Chinese medicine, were studied on alpha-particle induced bystander effects. In our experiments, Chinese hamster ovary (CHO) cells were cultured in PADC-film based dishes and were irradiated with low fluences of alpha particles passing through the PADC films. The precise number of cells traversed or missed by alpha particles could be determined by studying the alpha-particle tracks developed on the PADC films upon subsequent chemical etching. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to analyze the biological response of bystander cells in terms of DNA strand breaks. With the pretreatment of Magnolol, the DNA strand breaks in bystander cells were reduced, which showed that the alpha-particle induced bystander effects were suppressed with the presence of Magnolol. Since Magnolol is an antioxidant which can scavenge reactive oxygen species (ROS), our results give support to that ROS play a role in the bystander signal transmission in our experiments.

  5. Studying effects of Magnolol on alpha-particle induced bystander effects using PADC-film based dishes

    Energy Technology Data Exchange (ETDEWEB)

    Wong, T.P.W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Tse, A.K.W.; Fong, W.F. [Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.h [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2009-10-15

    Radiation-induced bystander effect refers to the biological response found in cells (called bystander cells) which are not irradiated directly by ionizing radiation but are next to cells irradiated directly by ionizing radiation. In the present paper, the effects of Magnolol, an extract from the bark of Magnolia officinalis which is used as a traditional Chinese medicine, were studied on alpha-particle induced bystander effects. In our experiments, Chinese hamster ovary (CHO) cells were cultured in PADC-film based dishes and were irradiated with low fluences of alpha particles passing through the PADC films. The precise number of cells traversed or missed by alpha particles could be determined by studying the alpha-particle tracks developed on the PADC films upon subsequent chemical etching. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to analyze the biological response of bystander cells in terms of DNA strand breaks. With the pretreatment of Magnolol, the DNA strand breaks in bystander cells were reduced, which showed that the alpha-particle induced bystander effects were suppressed with the presence of Magnolol. Since Magnolol is an antioxidant which can scavenge reactive oxygen species (ROS), our results give support to that ROS play a role in the bystander signal transmission in our experiments.

  6. STUDIES ON INDUCED HEPATOTOXICITY IN MALE ALBINO RATS (RATTUS NORVEGICUS)

    International Nuclear Information System (INIS)

    ABULYAZID, I.; ABBAS, O.A.; FAYEZ, V.

    2008-01-01

    Levanox, a hepato protective drug, and garlic powder have been considered as safe anti-oxidant agents. The present investigation refers to biochemical and molecular studies to evaluate the protective role of levanox and/or garlic powder toward CCl4-induced toxicity in adult male albino rats. CCl4 intoxication was attempted using a dose of 0.03 ml/kg of rat body weight.Pre-treatment with levanox (one capsule/ kg of rat body weight, each capsule contains 100 mg catechu, 7.5 mg dandelion, 75 mg termiric 2 % curcumin , 17.5 mg silymarin, 100 mg lecithin) was more effective than garlic powder (100mg/kg of rat body weight) in reducing CCl4-induced hepatotoxicity as revealed by its higher potency in reducing elevation of aspartate (AST) and alanine (ALT) aminotransferases in serum. Serum of control rats and those treated with levanox or garlic or CCl4 produced 13 types of proteins, differing in the molecular weight (MW) and densities, while those of levanox + garlic or garlic +CCl4 produced 14 bands differing in the MW and densities. The similarity index at the epigenetic level was also studied using the primers under study. The control sample produced one amplified DNA fragment with Rf of 0.73 and a molecular size (MS) of 67 base pair (bp) . Using the same primers, no amplified DNA fragment with the same MS was produced in the sample taken from levanox + garlic treated group.OPA-2 primer of sequence 5?- AGA TGC AGC C-3? produced one amplified DNA band with MS of 292 bp and Rf of 0.46 . However, the same primer produced one amplified DNA characteristic band with a molecular size of 363 bp and Rf of 0.43 in the sample of levanox + garlic group.In the control sample, OPA-4 primer of sequence 5? - ACG CAC AAC C-3? produced one amplified DNA band of MS of 299 bp and Rf of 0.43. The same primer produced one amplified characteristic DNA band with MS of 363 bp and Rf of 0.43 in the sample of levanox + garlic group.Dual treatment with levanox and garlic powder resulted in a

  7. Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Medine Cumhur Cüre

    2016-10-01

    Full Text Available Background: Cisplatin (Cis is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α. Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. Aims: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. Study Design: Animal experimentation. Methods: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg. In the CIN group, a single dose of infliximab (7 mg/kg was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg was administered. All rats were sacrificed five days after Cis injection. Results: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein than those of the control (278.7±62.1 pg/mg protein, p=0.003 and CIN groups (239.0±64.2 pg/mg protein, p=0.013. The Cis group was found to have high carbonic anhydrase (CA-II and low carbamoyl phosphate synthetase-1 (CPS-1 levels. Aspartate transaminase (AST and alanine transaminase (ALT levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. Conclusion: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and

  8. Evaluation of the zebrafish embryo as an alternative model for hepatotoxicity testing

    NARCIS (Netherlands)

    Driessen, Marja

    2014-01-01

    In this thesis we showed the applicability of the zebrafish embryo as an alternative model for hepatotoxicity testing using analysis of mechanisms through toxicogenomics. By applying a variety of toxicogenomics techniques, we were able to characterize specific responses. NGS revealed that

  9. Lack of Direct Cytotoxicity of Extracellular ATP against Hepatocytes: Role in the Mechanism of Acetaminophen Hepatotoxicity

    NARCIS (Netherlands)

    Xie, Yuchao; Woolbright, Benjamin L.; Kos, Milan; McGill, Mitchell R.; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Jaeschke, Hartmut

    2015-01-01

    Acetaminophen (APAP) hepatotoxicity is a major cause of acute liver failure in many countries. Mechanistic studies in mice and humans have implicated formation of a reactive metabolite, mitochondrial dysfunction and oxidant stress as critical events in the pathophysiology of APAP-induced liver cell

  10. Protective effect of rutin in comparison to silymarin against induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    M. Kasi Reddy

    2017-01-01

    Full Text Available Aim: The aim of this study is to evaluate the hepatoprotective effect of rutin (RTN in comparison to silymarin (SLM against acetaminophen (APAP-induced hepatotoxicity in rats. Materials and Methods: Male Wistar albino rats (n=24 of 3 months age were equally divided into four groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with administration of 500 mg/kg po APAP from day 1-3. Groups 2, 3, and 4 were subsequently administered orally with distilled water, 25 mg/kg of SLM, and 20 mg/kg of RTN, respectively, for 11 days. The mean body weights and biomarkers of hepatotoxicity were estimated on day 0, 4 (confirmation of toxicity, and 15 (at the end of treatment. Hematological parameters were evaluated on day 4 and 15. Antioxidant profile and adenosine triphosphatases (ATPases were assessed at the end of the experiment. Liver tissues were subjected to histopathology and transmission electron microscopy after the sacrifice on day 15. Results: Antioxidant profile, ATPases, and hematological and sero-biochemical parameters were significantly altered, and histopathological changes were noticed in the liver of toxic control group. These changes were reversed in groups 3 and 4 that were administered with SLM and RTN, respectively. Conclusion: The results of the present investigation enunciated that SLM has potent hepatoprotective activity though the RTN was found superior in restoring the pathological alterations in paracetamol-induced hepatotoxicity in Wistar albino rats.

  11. Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro

    NARCIS (Netherlands)

    Hof, Van den W.F.P.M.; Ruiz Aracama, Ainhoa; Summeren, Van Anke; Jennen, D.G.J.; Gaj, Stan; Coonen, M.L.J.; Brauers, Karen; Wodzig, W.K.W.H.; Delft, van J.H.M.; Kleinjans, J.C.S.

    2015-01-01

    In order to improve attrition rates of candidate-drugs there is a need for a better understanding of the mechanisms underlying drug-induced hepatotoxicity. We aim to further unravel the toxicological response of hepatocytes to a prototypical cholestatic compound by integrating transcriptomic and

  12. Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Škop, V.; Trnovská, J.; Oliyarnyk, O.; Marková, I.; Malínská, H.; Kazdová, L.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Kůdela, M.; Pravenec, Michal; Šilhavý, Jan

    2016-01-01

    Roč. 65, č. 6 (2016), s. 891-899 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT14325 Institutional support: RVO:67985823 Keywords : fenofibrate * rosuvastatin * C-reactive protein * transgenic * spontaneously hypertensive rat * inflammation * hepatotoxic Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.461, year: 2016

  13. Advancing Predictive Hepatotoxicity at the Intersection of Experimental, in Silico, and Artificial Intelligence Technologies.

    Science.gov (United States)

    Fraser, Keith; Bruckner, Dylan M; Dordick, Jonathan S

    2018-06-18

    Adverse drug reactions, particularly those that result in drug-induced liver injury (DILI), are a major cause of drug failure in clinical trials and drug withdrawals. Hepatotoxicity-mediated drug attrition occurs despite substantial investments of time and money in developing cellular assays, animal models, and computational models to predict its occurrence in humans. Underperformance in predicting hepatotoxicity associated with drugs and drug candidates has been attributed to existing gaps in our understanding of the mechanisms involved in driving hepatic injury after these compounds perfuse and are metabolized by the liver. Herein we assess in vitro, in vivo (animal), and in silico strategies used to develop predictive DILI models. We address the effectiveness of several two- and three-dimensional in vitro cellular methods that are frequently employed in hepatotoxicity screens and how they can be used to predict DILI in humans. We also explore how humanized animal models can recapitulate human drug metabolic profiles and associated liver injury. Finally, we highlight the maturation of computational methods for predicting hepatotoxicity, the untapped potential of artificial intelligence for improving in silico DILI screens, and how knowledge acquired from these predictions can shape the refinement of experimental methods.

  14. Anti-tuberculosis therapy-induced hepatotoxicity among Ethiopian HIV-positive and negative patients.

    Directory of Open Access Journals (Sweden)

    Getnet Yimer

    2008-03-01

    Full Text Available To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH in HIV positive and HIV negative tuberculosis (TB patients in Ethiopia.In this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1% developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg.Sub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002, concomitant drug intake (p = 0.008, and decrease in CD4 count (p = 0.001. Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk.

  15. Enhancement of the predicted drug hepatotoxicity in gel entrapped hepatocytes within polysulfone-g-poly (ethylene glycol) modified hollow fiber

    International Nuclear Information System (INIS)

    Shen Chong; Zhang Guoliang; Meng Qin

    2010-01-01

    Collagen gel-based 3D cultures of hepatocytes have been proposed for evaluation of drug hepatotoxicity because of their more reliability than traditional monolayer culture. The collagen gel entrapment of hepatocytes in hollow fibers has been proven to well reflect the drug hepatotoxicity in vivo but was limited by adsorption of hydrophobic drugs onto hollow fibers. This study aimed to investigate the impact of hollow fibers on hepatocyte performance and drug hepatotoxicity. Polysulfone-g-poly (ethylene glycol) (PSf-g-PEG) hollow fiber was fabricated and applied for the first time to suppress the drug adsorption. Then, the impact of hollow fibers was evaluated by detecting the hepatotoxicity of eight selected drugs to gel entrapped hepatocytes within PSf and PSf-g-PEG hollow fibers, or without hollow fibers. The hepatocytes in PSf-g-PEG hollow fiber showed the highest sensitivity to drug hepatotoxicity, while those in PSf hollow fiber and cylindrical gel without hollow fiber underestimated the hepatotoxicity due to either drug adsorption or low hepatic functions. Therefore, the 3D culture of gel entrapped hepatocytes within PSf-g-PEG hollow fiber would be a promising tool for investigation of drug hepatotoxicity in vitro.

  16. Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption.

    Directory of Open Access Journals (Sweden)

    An Qin

    Full Text Available Wear particle-induced peri-implant loosening (Aseptic prosthetic loosening is one of the most common causes of total joint arthroplasty. It is well established that extensive bone destruction (osteolysis by osteoclasts is responsible for wear particle-induced peri-implant loosening. Thus, inhibition of osteoclastic bone resorption should prevent wear particle induced osteolysis and may serve as a potential therapeutic avenue for prosthetic loosening. Here, we demonstrate for the first time that saliphenylhalamide, a new V-ATPase inhibitor attenuates wear particle-induced osteolysis in a mouse calvarial model. In vitro biochemical and morphological assays revealed that the inhibition of osteolysis is partially attributed to a disruption in osteoclast acidification and polarization, both a prerequisite for osteoclast bone resorption. Interestingly, the V-ATPase inhibitor also impaired osteoclast differentiation via the inhibition of RANKL-induced NF-κB and ERK signaling pathways. In conclusion, we showed that saliphenylhalamide affected multiple physiological processes including osteoclast differentiation, acidification and polarization, leading to inhibition of osteoclast bone resorption in vitro and wear particle-induced osteolysis in vivo. The results of the study provide proof that the new generation V-ATPase inhibitors, such as saliphenylhalamide, are potential anti-resorptive agents for treatment of peri-implant osteolysis.

  17. Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps

    Science.gov (United States)

    Teschke, Rolf; Eickhoff, Axel

    2015-01-01

    Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI) with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although, herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences) scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality. PMID:25954198

  18. Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps.

    Science.gov (United States)

    Teschke, Rolf; Eickhoff, Axel

    2015-01-01

    Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI) with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although, herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences) scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality.

  19. Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Ana Cecília Montes Gil

    Full Text Available CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART. We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6, A (29, B (78 and C (39. Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN, grade 2 (5.0-9.9 times ULN, grade 3 (10.0-15.0 times ULN and grade 4 (> 15.0 times ULN. To assess hepatotoxicity risk factors, odds ratios (OR and adjusted odds ratios (aOR for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152 patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI, 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85 and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25. No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

  20. Herbal hepatotoxicity in traditional and modern medicine: Actual key issues and new encouraging steps

    Directory of Open Access Journals (Sweden)

    Rolf eTeschke

    2015-04-01

    Full Text Available Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality.

  1. Licochalcone A Upregulates Nrf2 Antioxidant Pathway and Thereby Alleviates Acetaminophen-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hongming Lv

    2018-03-01

    Full Text Available Acetaminophen (APAP overdose-induced fatal hepatotoxicity is majorly characterized by overwhelmingly increased oxidative stress while enhanced nuclear factor-erythroid 2-related factor 2 (Nrf2 is involved in prevention of hepatotoxicity. Although Licochalcone A (Lico A upregulates Nrf2 signaling pathway against oxidative stress-triggered cell injury, whether it could protect from APAP-induced hepatotoxicity by directly inducing Nrf2 activation is still poorly elucidated. This study aims to explore the protective effect of Lico A against APAP-induced hepatotoxicity and its underlying molecular mechanisms. Our findings indicated that Lico A effectively decreased tert-butyl hydroperoxide (t-BHP- and APAP-stimulated cell apoptosis, mitochondrial dysfunction and reactive oxygen species generation and increased various anti-oxidative enzymes expression, which is largely dependent on upregulating Nrf2 nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element promoter activity. Meanwhile, Lico A dramatically protected against APAP-induced acute liver failure by lessening the lethality; alleviating histopathological liver changes; decreasing the alanine transaminase and aspartate aminotransferase levels, malondialdehyde formation, myeloperoxidase level and superoxide dismutase depletion, and increasing the GSH-to-GSSG ratio. Furthermore, Lico A not only significantly modulated apoptosis-related protein by increasing Bcl-2 expression, and decreasing Bax and caspase-3 cleavage expression, but also efficiently alleviated mitochondrial dysfunction by reducing c-jun N-terminal kinase phosphorylation and translocation, inhibiting Bax mitochondrial translocation, apoptosis-inducing factor and cytochrome c release. However, Lico A-inhibited APAP-induced the lethality, histopathological changes, hepatic apoptosis, and mitochondrial dysfunction in WT mice were evidently abrogated in Nrf2-/- mice. These

  2. Excitation function of alpha-particle-induced reactions on {sup nat}Ni from threshold to 44 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Uddin, M.S. [Atomic Energy Research Establishment, Tandem Accelerator Facilities, Institute of Nuclear Science and Technology, Savar, Dhaka (Bangladesh); Kim, K.S.; Nadeem, M.; Kim, G.N. [Kyungpook National University, Department of Physics, Buk-gu, Daegu (Korea, Republic of); Sudar, S. [Debrecen University, Institute of Experimental Physics, Debrecen (Hungary)

    2017-05-15

    Excitation functions of the {sup nat}Ni(α,x){sup 62,63,65}Zn, {sup nat}Ni(α,x){sup 56,57}Ni and {sup nat}Ni(α,x){sup 56,57,58m+g}Co reactions were measured from the respective thresholds to 44MeV using the stacked-foil activation technique. The tests for the beam characterization are described. The radioactivity was measured using HPGe γ-ray detectors. Theoretical calculations on α-particles-induced reactions on {sup nat}Ni were performed using the nuclear model code TALYS-1.8. A few results are new, the others strengthen the database. Our experimental data were compared with results of nuclear model calculations and described the reaction mechanism. (orig.)

  3. Particle-induced X-ray emission: thick-target analysis of inorganic materials in the determination of light elements

    International Nuclear Information System (INIS)

    Perez-Arantegui, J.; Castillo, J.R.; Querre, G.

    1994-01-01

    Particle-induced X-ray emission (PIXE) has been applied to the analysis of inorganic materials to determine some elements with Z < 27: Na, Mg, Al, Si, K, Ca, Ti, Mn and Fe, in thick-target analysis. A PIXE method has been developed for the analysis of geological materials, ceramics and pottery. Work has been carried out with an ion beam analytical system, using a low particle beam energy. Relative sensitivity, detection limits, reproducibility and accuracy of the method were calculated based on the analysis of geological standard materials (river sediments, argillaceous limestone, basalt, diorite and granite). Analysis using PIXE offers a number of advantages, such as short analysis time, multi-elemental and nondestructive determinations, and the results are similar to those obtained with other instrumental techniques of analysis. (Author)

  4. Increased sensitivity in thick-target particle induced X-ray emission analyses using dry ashing for preconcentration

    International Nuclear Information System (INIS)

    Lill, J.-O.; Harju, L.; Saarela, K.-E.; Lindroos, A.; Heselius, S.-J.

    1999-01-01

    The sensitivity in thick-target particle induced X-ray emission (PIXE) analyses of biological materials can be enhanced by dry ashing. The gain depends mainly on the mass reduction factor and the composition of the residual ash. The enhancement factor was 7 for the certified reference material Pine Needles and the limits of detection (LODs) were below 0.2 μg/g for Zn, Cu, Rb and Sr. When ashing biological materials with low ash contents such as wood of pine or spruce (0.3% of dry weight) and honey (0.1% of wet weight) the gain was far greater. The LODs for these materials were 30 ng/g for wood and below 10 ng/g for honey. In addition, the ashed samples were more homogenous and more resistant to changes during the irradiation than the original biological samples. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Development of a PIXE (Particle Induced X-ray Emission) analysis device using an extracted proton beam

    International Nuclear Information System (INIS)

    Saidi, A.

    1989-01-01

    The experimental device described allows the extention of the PIXE (Particle Induced X-ray Emission) method to the analysis, by means of proton beams, of solid or liquid samples, which can not be analyzed under vacuum conditions. The homogeneity of the surfaces to be analysed and elements (in the atmosphere) which absorb X-rays must be taken into account. Liquid samples do not need special care. The results show that: at high energies, the extracted beam sensibility is of the same order of magnitude as those obtained under vacuum; at low energies, the performance under vacuum conditions is better. The particles energy losses, at the exit membrane and in the outer atmosphere, decrease the X-rays production efficiency [fr

  6. Risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/AIDS-coinfected patients under tuberculosis treatment

    OpenAIRE

    Williams Ngouleun; Prosper Cabral Biapa Nya; Anatole Constant Pieme; Phelix Bruno Telefo

    2016-01-01

    Objective/background: Tuberculosis (TB) is a worldwide public health problem. It is a contagious and grave disease caused by Mycobacterium tuberculosis. Current drugs such as isoniazid, pyrazinamide, and rifampicin used for the treatment of tuberculosis are potentially hepatotoxic and can lead to drug hepatitis. In order to improve the follow-up of TB patients in Cameroon, we carried out a study which aimed to evaluate the hepatotoxicity risk factors associated with anti-TB drugs. Methods:...

  7. Unexpected paracetamol (acetaminophen) hepatotoxicity at standard dosage in two older patients: time to rethink 1 g four times daily?

    Science.gov (United States)

    Ging, Patricia; Mikulich, Olga; O'Reilly, Katherine M A

    2016-07-01

    We present two cases of acute hepatotoxicity associated with elevated paracetamol (acetaminophen) levels in older patients. Both patients were receiving a standard European dose of oral paracetamol (2 × 500 mg QDS) with no risk factors for slowed metabolism (weight paracetamol can be hepatotoxic. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Protective effect of the edible brown alga Ecklonia stolonifera on doxorubicin-induced hepatotoxicity in primary rat hepatocytes.

    Science.gov (United States)

    Jung, Hyun Ah; Kim, Jae-I; Choung, Se Young; Choi, Jae Sue

    2014-08-01

    As part of our efforts to isolate anti-hepatotoxic agents from marine natural products, we screened the ability of 14 edible varieties of Korean seaweed to protect against doxorubicin-induced hepatotoxicity in primary rat hepatocytes. Among the crude extracts of two Chlorophyta (Codium fragile and Capsosiphon fulvescens), seven Phaeophyta (Undaria pinnatifida, Sargassum thunbergii, Pelvetia siliquosa, Ishige okamurae, Ecklonia cava, Ecklonia stolonifera and Eisenia bicyclis), five Rhodophyta (Chondrus ocellatus, Gelidium amansii, Gracilaria verrucosa, Symphycladia latiuscula and Porphyra tenera), and the extracts of Ecklonia stolonifera, Ecklonia cava, Eisenia bicyclis and Pelvetia siliquosa exhibited significant protective effects on doxorubicin-induced hepatotoxicity, with half maximal effective concentration (EC50) values of 2.0, 2.5, 3.0 and 15.0 μg/ml, respectively. Since Ecklonia stolonifera exhibits a significant protective potential and is frequently used as foodstuff, we isolated six phlorotannins, including phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofucofuroeckol A (4), dieckol (5) and triphloroethol-A (6). Phlorotannins 2 ∼ 6 exhibited potential protective effects on doxorubicin-induced hepatotoxicity, with corresponding EC50 values of 3.4, 8.3, 4.4, 5.5 and 11.5 μg/ml, respectively. The results clearly demonstrated that the anti-hepatotoxic effects of Ecklonia stolonifera and its isolated phlorotannins are useful for further exploration and development of therapeutic modalities for treatment of hepatotoxicity. © 2014 Royal Pharmaceutical Society.

  9. To Set Up a Logistic Regression Prediction Model for Hepatotoxicity of Chinese Herbal Medicines Based on Traditional Chinese Medicine Theory

    Science.gov (United States)

    Liu, Hongjie; Li, Tianhao; Zhan, Sha; Pan, Meilan; Ma, Zhiguo; Li, Chenghua

    2016-01-01

    Aims. To establish a logistic regression (LR) prediction model for hepatotoxicity of Chinese herbal medicines (HMs) based on traditional Chinese medicine (TCM) theory and to provide a statistical basis for predicting hepatotoxicity of HMs. Methods. The correlations of hepatotoxic and nonhepatotoxic Chinese HMs with four properties, five flavors, and channel tropism were analyzed with chi-square test for two-way unordered categorical data. LR prediction model was established and the accuracy of the prediction by this model was evaluated. Results. The hepatotoxic and nonhepatotoxic Chinese HMs were related with four properties (p 0.05). There were totally 12 variables from four properties and five flavors for the LR. Four variables, warm and neutral of the four properties and pungent and salty of five flavors, were selected to establish the LR prediction model, with the cutoff value being 0.204. Conclusions. Warm and neutral of the four properties and pungent and salty of five flavors were the variables to affect the hepatotoxicity. Based on such results, the established LR prediction model had some predictive power for hepatotoxicity of Chinese HMs. PMID:27656240

  10. Hepatotoxicity associated with microcystin/ Hepatotoxicidade associada à microcistina

    Directory of Open Access Journals (Sweden)

    Ana Paula Frederico Rodrigues Loureiro Bracarense

    2008-08-01

    Full Text Available Urban and industrial discharges, intense agricultural exploitation and fisheries have been causing the eutrophication in both drinking and recreational waters. A frequent consequence of eutrophication in waters is the massive development of cyanobacteria. The occurrence of these blooms induces a severe problem, as Microcystis aeruginosa, the most widespread distributed cyanobacteria, can produce microcystins (MC. Toxic effects of MC have been described in liver, lungs, stomach, and intestine. Deaths in wildlife, livestock and human beings were also associated with MC exposition. MC exposition can occurs directly by ingestion, inhalation, contact, intravenous inoculation of contaminated water (hemodialysis or indirectly, by the consumption of animals, as fish and mollusks, the majors ingestors of cyanobacteria and its toxins. The most toxic MC, an also the most common is microcystin-LR (MC-LR, that has the liver as the main target organ. Microcystin is taken up specifically into the liver by bile acid transporters and, after entering the cytoplasm, inhibit protein phosphatases 1 and 2A, which leads to the increase in protein phosphorylation. This effect has two main consequences: the destruction of cytoskeleton directly causing cytotoxic effects, and deregulation of cell division, leading to tumor-promoting activity. Acute exposition to MC induces severe intrahepatic hemorrhage, necrosis and apoptosis, while chronic exposure can cause hepatic or intestinal neoplasia. It has been documented that MC hepatotoxicity is closely associated with intracellular reactive oxygen species formation. Natural degradation of microcystins depends on the solar radiation and bacteria. If degradation is insufficient, MC will persist in the freshwater food chain. Microcystin contamination of waters is therefore a hazard to human and animal health, so efforts to avoid eutrophication of waters sources are essential, in order to minimize the risks to public health

  11. Copper and silver halates

    CERN Document Server

    Woolley, EM; Salomon, M

    2013-01-01

    Copper and Silver Halates is the third in a series of four volumes on inorganic metal halates. This volume presents critical evaluations and compilations for halate solubilities of the Group II metals. The solubility data included in this volume are those for the five compounds, copper chlorate and iodate, and silver chlorate, bromate and iodate.

  12. Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping.

    Science.gov (United States)

    Solimini, R; Rotolo, M C; Mastrobattista, L; Mortali, C; Minutillo, A; Pichini, S; Pacifici, R; Palmi, I

    2017-03-01

    Anabolic Androgenic Steroids (AAS) abuse and misuse is nowadays a harmful habit involving both professional or recreational athletes, as well as general population. AAS are also frequently present in over-the-counter dietary supplements without being declared in the list of ingredients, leaving consumers unaware of the risks of adverse effects. Indeed, health risks of AAS consumption in pharmaceutical preparations or dietary complements seem still underestimated and under-reported. The variety of complications due to AAS misuse involves cardiovascular, central nervous, musculoskeletal and genitourinary systems of both males and females; psychiatric and behavioral effects, damages to metabolic system, skin and mainly liver. For instance, relevant concern has been raised by the AAS hepatotoxicity including adenoma, hepatocellular carcinoma, cholestasis, and peliosis hepatis. The present review reports the information available on the hepatotoxic effects of AAS use in professional and amateur athletes.

  13. Hibiscus vitifolius (Linn.) root extracts shows potent protective action against anti-tubercular drug induced hepatotoxicity.

    Science.gov (United States)

    Samuel, Anbu Jeba Sunilson John; Mohan, Syam; Chellappan, Dinesh Kumar; Kalusalingam, Anandarajagopal; Ariamuthu, Saraswathi

    2012-05-07

    The roots of Hibiscus vitifolius Linn. (Malvaceae) is used for the treatment of jaundice in the folklore system of medicine in India. This study is an attempt to evaluate the hepatoprotective activity of the roots of Hibiscus vitifolius against anti-tubercular drug induced hepatotoxicity. Hepatotoxicity was induced in albino rats of either sex by oral administration of a combination of three anti-tubercular drugs. Petroleum ether, chloroform, methanol and aqueous extracts of roots of Hibiscus vitifolius (400mg/kg/day) were evaluated for their possible hepatoprotective potential. All the extracts were found to be safe up to a dose of 2000mg/kg. Among the four extracts studied, oral administration of methanol extract of Hibiscus vitifolius at 400mg/kg showed significant difference in all the parameters when compared to control. There was a significant (PHibiscus vitifolius have potent hepatoprotective activity, thereby justifying its ethnopharmacological claim. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Scientific and Regulatory Perspectives in Herbal and Dietary Supplement Associated Hepatotoxicity in the United States

    Directory of Open Access Journals (Sweden)

    Mark I. Avigan

    2016-03-01

    Full Text Available In the United States (US, the risk of hepatotoxicity linked to the widespread use of certain herbal products has gained increased attention among regulatory scientists. Based on current US law, all dietary supplements sold domestically, including botanical supplements, are regulated by the Food and Drug Administration (FDA as a special category of foods. Under this designation, regulatory scientists do not routinely evaluate the efficacy of these products prior to their marketing, despite the content variability and phytochemical complexity that often characterizes them. Nonetheless, there has been notable progress in the development of advanced scientific methods to qualitatively and quantitatively measure ingredients and screen for contaminants and adulterants in botanical products when hepatotoxicity is recognized.

  15. Role of suppressed hepatocellular regeneration and Ca2+ in chlordecone-potentiated CCl4 hepatotoxicity

    International Nuclear Information System (INIS)

    Bell, A.N.

    1987-01-01

    The mechanism by which the chlorinated pesticide chlordecone (CD; Kepone) potentiates CCl 4 -induced hepatotoxicity and lethality was investigated. It was hypothesized that perturbations in Ca 2+ homeostasis, greater than those observed with a low dose of CCl 4 alone, in concert with a suppression of hepatocellular regeneration induced by CD alone or by CD + CCl 4 are responsible, at least in part, for CD-potentiated CCl 4 hepatotoxicity. Ca 2+ homeostasis was evaluated by measuring total cell Ca 2+ and 45 Ca 2+ uptake in viable isolated hepatocyte suspension obtained from normal and CD-pretreated rats receiving CCl 4 in vivo. In the normal rats in vivo CCL challenge did not affect 45 Ca 2+ uptake by viable isolated hepatocytes. In contrast, 45 Ca 2+ uptake was inhibited in viable isolated hepatocytes obtained from rats exposed to CD + CCl 4

  16. Hepatoprotective effect of leaves of aqueous ethanol extract of Cestrum nocturnum against paracetamol-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    M. Imran Qadir

    2014-06-01

    Full Text Available The hepatoprotective activities of Cestrum nocturnum (Queen of Night was evaluated against the paracetamol induced hepatotoxicity in the mice. Aqueous ethanol (30:70 extract of plant was obtained by maceration. Results showed that aqueous ethanol extract of C. nocturnum (250 mg/kg and 500 mg/kg produced significant (p<0.05 hepatoprotective activities against paracetamol induced liver injury in Swiss albino mice. Histopathalogical studied of liver further supported the hepatoprotective effects of C. notrunum. Phyto-chemical screening showed the presence of alkaloids, flavonoids, saponins, terpenes, phenolic compounds, carbohydrates and volatile oils. Most of the flavonoids have hepatoprotective activity. Therefore, the hepatoprotective activity of C. nocturnum may be due to the presence of flavonoids and phenolic components. It was concluded from the present study that aqueous ethanol extract of leaves of C. nocturnum has hepatoprotective activity against the paracetamol-induced hepatotoxicity in albino mice.

  17. Oral Delivery of Curcumin Polymeric Nanoparticles Ameliorates CCl4-Induced Subacute Hepatotoxicity in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Gregory Marslin

    2018-05-01

    Full Text Available Curcumin is the major bioactive compound of Curcuma longa, an important medicinal plant used in traditional herbal formulations since ancient times. In the present study, we report that curcumin nanoparticles (ηCur protects Wistar rats against carbon tetrachloride (CCl4-induced subacute hepatotoxicity. Nanoparticles of sizes less than 220 nm with spherical shape were prepared using PLGA and PVA respectively as polymer and stabilizer. Test animals were injected via intraperitoneal route with 1 mL/kg CCl4 (8% in olive oil twice a week over a period of 8 weeks to induce hepatotoxicity. On the days following the CCl4 injection, test animals were orally administered with either curcumin or its equivalent dose of ηCur. Behavioural observation, biochemical analysis of serum and histopathological examination of liver of the experimental animals indicated that ηCur offer significantly higher hepatoprotection compared to curcumin.

  18. The hepatotoxic potential of a Prudhoe Bay crude oil: effect on mouse liver weight and composition

    International Nuclear Information System (INIS)

    Khan, S.; Irfan, M.; Rahimtula, A.D.

    1987-01-01

    The hepatotoxic properties of a Prudhoe Bay Crude Oil (PBCO) were evaluated in mice. Administration of PBCO (5.0 m1/kg body wt, daily for 2 days) to mice resulted in an increase in (i) liver wet and dry weight, (ii) hepatic total proteins RNA, glycogen and lotal lipids, and (iii) individual lipids such as cholesterol, triglycerides and phospholipids. Hepatic protein biosynthesis, determined in vivo by administration of L-[ 14 C] Leucine was increased in PBCO exposed in mice. The rate of 3 H incorporation from 3 H 2 O was significantly enhanced in liver fatty acids, cholesterol, triglycerides and thus ultimately in total lipids. Also, an increase in 3 H incorporation was noticed in hepatic glycogen after PBCO administration. The results suggest that PBCO may induce hepatotoxicity by altering the intermediary metabolism of biochemical constituents. (author) 39 refs

  19. Trace determination of heavy metal concentrations in fauna, flora and salt samples from Black Sea waters by charged particles - induced X-rays

    International Nuclear Information System (INIS)

    Badica, T.; Ciortea, C.; Dima, S.; Petrovici, A.; Popescu, I.; Serbanescu, O.

    1977-01-01

    Studies were performed on Black Sea pollution by charged particles induced X-rays spectra analysis, using alpha and 16 O beams. Fauna, flora and salt samples were analysed. We found some of the concentrations of pollutant elements to be below the accepted levels. (author)

  20. Potential Role of Activated Nonparenchymal Cells in Acetaminophen-Induced Potentiation of Hepatotoxicity

    Science.gov (United States)

    1991-06-14

    ALT is either being degraded or the activity is inhibited by something in the 133 media. AST activity in cocultures of NPCs and hepatocytes was... Paracetamol Hepatotoxicity: IN VITRO Studies in Isolated Mouse Hepatocytes. Toxicology Letters. 2229: 37-48. Casini, A. M., P. A. Ferrali and M...Acute Liver Necrosis Following Overdose of Paracetamol . British Medical Journal. 2: 497-499. Decker, T., M. L. Lohmann-Matthes, U. Karck, T. Peters

  1. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats

    OpenAIRE

    El-Kott, Attalla Farag; Bin-Meferij, Mashael Mohammed

    2015-01-01

    Background: Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. Objective: To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. Methods: Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. Results: The treatment with Arctium lappa extract reduc...

  2. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate

    OpenAIRE

    Humphreys, Jenny H; Warner, Alexander; Costello, Ruth; Lunt, Mark; Verstappen, Suzanne M M; Dixon, William G

    2017-01-01

    Background Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care. Methods Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were i...

  3. Hypolipidemic Effect of Psidium guajava Leaf Extract Against Hepatotoxicity in Rats.

    Science.gov (United States)

    Vijayakumar, K; Rengarajan, R L; Radhakrishnan, R; Anand, A Vijaya

    2018-01-01

    Plant-based natural extracts cure several diseases in human. However, the extract of Psidium guajava leaf is not yet evaluated on changes of lipid profile in hepatic disease affected rats. The present study was aimed to evaluate the mitigation effect of the ethanolic extract of P. guajava leaf and its isolated quercetin fraction on hepatotoxic rats. Carbon tetrachloride (CCl 4 ) was injected to rats for hepatic disease induction and silymarin drug was used as positive control to compare plant ethanolic extract. The lipid profiles were assessed in both plasma and liver tissue of diseased and control rats. Levels of total cholesterol, triglycerides, free fatty acids, phospholipids, and low-density lipoprotein cholesterol were increased and the level of high-density lipoprotein cholesterol (HDL-C) was decreased in CCl 4 -induced hepatotoxic rats. The treatment of P. guajava (100, 200, and 300 mg/kg, bw) and isolated quercetin fraction (20 mg/kg, bw) doses decreased the elevated levels of all these parameters in diseased rats and restored the normal concentration of HDL-C. The results of the present study concluded that the P. guajava leaf and its isolated quercetin fraction can significantly regulate lipid metabolism in CCl 4 -induced hepatotoxic rats and decrease the disease rate. Psidium guajava leaf extract reduces the hepatotoxicity and disease rate in ratsQuercetin fraction of leaf extract significantly regulates lipid profile in hepatic diseased rats. Abbreviations used: CCl 4 : Carbon tetrachloride; FFA: Free fatty acids; HDL-C: High-density lipoprotein cholesterol; LCAT: Lecithin cholesterol acyltransferase; LDL-C: Low-density lipoprotein cholesterol; PL: Phospholipids; TC: Total cholesterol; TG: Triglycerides; VLDL-C: Very low-density lipoprotein cholesterol.

  4. Acetaminophen hepatotoxicity in mice: Effect of age, frailty and exposure type

    Science.gov (United States)

    Kane, Alice E.; Mitchell, Sarah J.; Mach, John; Huizer-Pajkos, Aniko; McKenzie, Catriona; Jones, Brett; Cogger, Victoria; Le Couteur, David G.; de Cabo, Rafael; Hilmer, Sarah N.

    2018-01-01

    Acetaminophen is a commonly used analgesic that can cause severe hepatotoxicity in overdose. Despite old age and frailty being associated with extensive and long-term utilization of acetaminophen and a high prevalence of adverse drug reactions, there is limited information on the risks of toxicity from acetaminophen in old age and frailty. This study aimed to assess changes in the risk and mechanisms of hepatotoxicity from acute, chronic and sub-acute acetaminophen exposure with old age and frailty in mice. Young and old male C57BL/6 mice were exposed to either acute (300 mg/kg via oral gavage), chronic (100 mg/kg/day in diet for six weeks) or sub-acute (250 mg/kg, t.i.d., for three days) acetaminophen, or saline control. Pre-dosing mice were scored for the mouse clinical frailty index, and after dosing serum and liver tissue were collected for assessment of toxicity and mechanisms. There were no differences with old age or frailty in the degree of hepatotoxicity induced by acute, chronic or subacute acetaminophen exposure as assessed by serum liver enzymes and histology. Age-related changes in the acetaminophen toxicity pathways included increased liver GSH concentrations, increased NQO1 activity and an increased pro- and anti-inflammatory response to acetaminophen in old age. Frailty-related changes included a negative correlation between frailty index and serum protein, albumin and ALP concentrations for some mouse groups. In conclusion, although there were changes in some pathways that would be expected to influence susceptibility to acetaminophen toxicity, there was no overall increase in acetaminophen hepatotoxicity with old age or frailty in mice. PMID:26615879

  5. Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity

    Science.gov (United States)

    Massart, Julie; Begriche, Karima; Moreau, Caroline; Fromenty, Bernard

    2017-01-01

    Background Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Aim The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. Relevance for patients Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening

  6. Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb, Polygonum multiflorum.

    Science.gov (United States)

    Li, Chunyu; Niu, Ming; Bai, Zhaofang; Zhang, Congen; Zhao, Yanling; Li, Ruiyu; Tu, Can; Li, Huifang; Jing, Jing; Meng, Yakun; Ma, Zhijie; Feng, Wuwen; Tang, Jinfa; Zhu, Yun; Li, Jinjie; Shang, Xiaoya; Zou, Zhengsheng; Xiao, Xiaohe; Wang, Jiabo

    2017-06-01

    The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent "knock-out" and "knock-in" strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4'-tetrahydroxy trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization of trans-SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.

  7. The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats

    International Nuclear Information System (INIS)

    Nishiya, Takayoshi; Mori, Kazuhiko; Hattori, Chiharu; Kai, Kiyonori; Kataoka, Hiroko; Masubuchi, Noriko; Jindo, Toshimasa; Manabe, Sunao

    2008-01-01

    To investigate the hepatotoxic potential of tienilic acid in vivo, we administered a single oral dose of tienilic acid to Sprague-Dawley rats and performed general clinicopathological examinations and hepatic gene expression analysis using Affymetrix microarrays. No change in the serum transaminases was noted at up to 1000 mg/kg, although slight elevation of the serum bile acid and bilirubin, and very mild hepatotoxic changes in morphology were observed. In contrast to the marginal clinicopathological changes, marked upregulation of the genes involved in glutathione biosynthesis [glutathione synthetase and glutamate-cysteine ligase (Gcl)], oxidative stress response [heme oxygenase-1 and NAD(P)H dehydrogenase quinone 1] and phase II drug metabolism (glutathione S-transferase and UDP glycosyltransferase 1A6) were noted after 3 or 6 h post-dosing. The hepatic reduced glutathione level decreased at 3-6 h, and then increased at 24 or 48 h, indicating that the upregulation of NF-E2-related factor 2 (Nrf2)-regulated gene and the late increase in hepatic glutathione are protective responses against the oxidative and/or electrophilic stresses caused by tienilic acid. In a subsequent experiment, tienilic acid in combination with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of Gcl caused marked elevation of serum alanine aminotransferase (ALT) with extensive centrilobular hepatocyte necrosis, whereas BSO alone showed no hepatotoxicity. The elevation of ALT by this combination was observed at the same dose levels of tienilic acid as the upregulation of the Nrf2-regulated genes by tienilic acid alone. In conclusion, these results suggest that the impairment of glutathione biosynthesis may play a critical role in the development of tienilic acid hepatotoxicity through extensive oxidative and/or electrophilic stresses

  8. A critical analysis of the hepatotoxicity cases described in the literature related to Herbalife (r products

    Directory of Open Access Journals (Sweden)

    Flávio Ailton Duque Zambrone

    2015-12-01

    Full Text Available Abstract The aim of this study was to assess the hepatotoxicity cases described in the literature, attributed to the consumption of Herbalife(r products, and to determine whether a causal relationship exists between the reported cases of liver injury and the use of these products. A literature search was performed on the PubMed, LILACS and PAHO databases. Seven publications reporting a total of 53 cases of hepatotoxicity linked to the use of Herbalife(r products were retrieved. All of the studies lacked sufficient information to some degree, whether related to patients' history, concomitant use of medication and/or other compounds (including alcohol, observations on interrupted use (dechallenge, results found with markers, viral serology and autoantibodies or observations concerning re-exposure to the products. In addition to these items, the lack of clear information on the type of products evaluated and their respective composition is an important factor to be considered. Furthermore, data quality was also questionable due to the presence of confounding factors, absence of proper exclusion of alternative explanations, and the use of questionable methods for attributing causality. Hence, an association between hepatotoxicity and consumption of these products cannot be proven based on the data collected and rigorous scientific analysis.

  9. The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity.

    Science.gov (United States)

    El-Sherbeeny, Nagla A; Nader, Manar A

    2016-03-01

    The study examined the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, in cyclosporine (CsA)-induced hepatotoxicity. Rats were divided into 4 groups treated for 28 days: control (vehicle), vildagliptin (10 mg/kg, orally), CsA (20 mg/kg, s.c.), and CsA-vildagliptin group. Liver function was assessed by measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), and albumin, and histopathological changes of liver were examined. Oxidative stress markers were evaluated. Assessment of nuclear factor-kappa B (NF-κB) activity in hepatic nuclear extract, serum DPP-4, and expression of Bax and Bcl2 were also done. CsA-induced hepatotoxicity was evidenced by increase in serum levels of AST, ALT, and γGT; a decrease in serum albumin; and a significant alteration in hepatic architecture. Also, significant increase in thiobarbituric acid reactive substance (TBARS) and decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) levels, increased expression Bax proteins with deceased expression of Bcl2, and increased hepatic activity of NF-κB and serum DPP-4 level were observed upon CsA treatment. Vildagliptin significantly improved all altered parameters induced by CsA administration. Vildagliptin has the potential to protect the liver against CsA-induced hepatotoxicity by reducing oxidative stress, DPP-4 activity, apoptosis, and inflammation.

  10. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status.

    Science.gov (United States)

    Ajith, T A; Hema, U; Aswathy, M S

    2007-11-01

    A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (pHepatic lipid peroxidation was enhanced significantly (pofficinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.

  11. Fumonisin B1 hepatotoxicity in mice is attenuated by depletion of Kupffer cells by gadolinium chloride

    International Nuclear Information System (INIS)

    He, Quanren; Kim, Jiyoung; Sharma, Raghubir P.

    2005-01-01

    Fumonisin B 1 (FB 1 ) is a toxic and carcinogenic mycotoxin produced by Fusarium verticillioides found on corn worldwide. The biological effects of FB 1 are attributed to sphingolipid metabolism disruption as a result of ceramide synthase inhibition. Tumor necrosis factor α (TNFα) is an important modulator of FB 1 hepatotoxicity. Kupffer cells are major source of cytokine production in liver. In the present study we investigated the effects of Kupffer cell depletion by gadolinium on FB 1 hepatotoxicity in female BALB/c mice. Mice were given saline or 50 mg/kg of gadolinium chloride once via the tail vein; 16 h later they were treated with subcutaneous injections of vehicle or 2.25 mg/kg/day FB 1 in saline for three successive days. Gadolinium significantly attenuated FB 1 -induced increases in the activities of circulating alanine aminotransferase and aspartate aminotransferase and reduced the FB 1 -induced hepatocyte apoptosis and free sphinganine accumulation in liver. Both gadolinium and FB 1 treatments individually increased the expression of selected cell signal factors; e.g., TNFα, TNF receptor 1, TNF-related apoptosis-inducing ligand, lymphotoxin β, interferon γ, and transforming growth factor β1; gadolinium chloride did not alter FB 1 -induced expression of the above genes. Results indicated that Kupffer cells play a role in FB 1 hepatotoxicity. Decreased FB 1 -induced sphinganine accumulation and increased protective TNFα signaling by gadolinium chloride may in part account for its ameliorating effect on FB 1 liver damage

  12. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats.

    Science.gov (United States)

    Khoza, Star; Moyo, Ishmael; Ncube, Denver

    2017-01-01

    Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels ( p = 0.0017) and AST levels ( p = 0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment ( p terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

  13. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats

    Directory of Open Access Journals (Sweden)

    Star Khoza

    2017-01-01

    Full Text Available Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p=0.0017 and AST levels (p=0.0008 than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p<0.0001. The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

  14. The Ameliorative Effects of L-2-Oxothiazolidine-4-Carboxylate on Acetaminophen-Induced Hepatotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Jun Ho Shin

    2013-03-01

    Full Text Available The aim of the study was to investigate the ameliorative effects and the mechanism of action of L-2-oxothiazolidine-4-carboxylate (OTC on acetaminophen (APAP-induced hepatotoxicity in mice. Mice were randomly divided into six groups: normal control group, APAP only treated group, APAP + 25 mg/kg OTC, APAP + 50 mg/kg OTC, APAP + 100 mg/kg OTC, and APAP + 100 mg/kg N-acetylcysteine (NAC as a reference control group. OTC treatment significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in a dose dependent manner. OTC treatment was markedly increased glutathione (GSH production and glutathione peroxidase (GSH-px activity in a dose dependent manner. The contents of malondialdehyde and 4-hydroxynonenal in liver tissues were significantly decreased by administration of OTC and the inhibitory effect of OTC was similar to that of NAC. Moreover, OTC treatment on APAP-induced hepatotoxicity significantly reduced the formation of nitrotyrosin and terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas of liver tissues in a dose dependent manner. Furthermore, the activity of caspase-3 in liver tissues was reduced by administration of OTC in a dose dependent manner. The ameliorative effects of OTC on APAP-induced liver damage in mice was similar to that of NAC. These results suggest that OTC has ameliorative effects on APAP-induced hepatotoxicity in mice through anti-oxidative stress and anti-apoptotic processes.

  15. Effects of ebselen on radiocontrast media-induced hepatotoxicity in rats.

    Science.gov (United States)

    Basarslan, Fatmagul; Yilmaz, Nigar; Davarci, Isil; Akin, Mustafa; Ozgur, Mustafa; Yilmaz, Cahide; Ulutas, Kemal Turker

    2013-09-01

    Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.

  16. [Nevirapine related hepatotoxicity: the prevalence and risk factors in a cohort of ART naive Han Chinese with AIDS].

    Science.gov (United States)

    Gao, Shi-cheng; Gui, Xi-en; Deng, Li-ping; Zhang, Yong-xi; Yan, Ya-jun; Rong, Yu-ping; Liang, Ke; Yang, Rong-rong

    2010-09-01

    To investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART. 330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted. 267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

  17. Copper carrier protein in copper toxic sheep liver

    Energy Technology Data Exchange (ETDEWEB)

    Harris, A L; Dean, P D.G.

    1973-01-01

    The livers of copper-toxic sheep have been analyzed by gel electrophoresis followed by staining the gels for copper with diethyldithiocarbamate and for protein with amido schwartz. These gels were compared with similar gels obtained from the livers of normal and copper-deficient animals. The copper-toxic livers contained an extra protein band which possessed relatively weakly bound copper. Possible origins of this protein are discussed. 8 references, 1 figure, 2 tables.

  18. COPPER CABLE RECYCLING TECHNOLOGY

    International Nuclear Information System (INIS)

    Chelsea Hubbard

    2001-01-01

    The United States Department of Energy (DOE) continually seeks safer and more cost-effective technologies for use in deactivation and decommissioning (D and D) of nuclear facilities. The Deactivation and Decommissioning Focus Area (DDFA) of the DOE's Office of Science and Technology (OST) sponsors large-scale demonstration and deployment projects (LSDDPs). At these LSDDPs, developers and vendors of improved or innovative technologies showcase products that are potentially beneficial to the DOE's projects and to others in the D and D community. Benefits sought include decreased health and safety risks to personnel and the environment, increased productivity, and decreased costs of operation. The Idaho National Engineering and Environmental Laboratory (INEEL) generated a list of statements defining specific needs and problems where improved technology could be incorporated into ongoing D and D tasks. One such need is to reduce the volume of waste copper wire and cable generated by D and D. Deactivation and decommissioning activities of nuclear facilities generates hundreds of tons of contaminated copper cable, which are sent to radioactive waste disposal sites. The Copper Cable Recycling Technology separates the clean copper from contaminated insulation and dust materials in these cables. The recovered copper can then be reclaimed and, more importantly, landfill disposal volumes can be reduced. The existing baseline technology for disposing radioactively contaminated cables is to package the cables in wooden storage boxes and dispose of the cables in radioactive waste disposal sites. The Copper Cable Recycling Technology is applicable to facility decommissioning projects at many Department of Energy (DOE) nuclear facilities and commercial nuclear power plants undergoing decommissioning activities. The INEEL Copper Cable Recycling Technology Demonstration investigated the effectiveness and efficiency to recycle 13.5 tons of copper cable. To determine the effectiveness

  19. Canine Copper-Associated Hepatitis

    NARCIS (Netherlands)

    Dirksen, Karen; Fieten, Hille

    2017-01-01

    Copper-associated hepatitis is recognized with increasing frequency in dogs. The disease is characterized by centrolobular hepatic copper accumulation, leading to hepatitis and eventually cirrhosis. The only way to establish the diagnosis is by histologic assessment of copper distribution and copper

  20. Posttranslational regulation of copper transporters

    NARCIS (Netherlands)

    van den Berghe, P.V.E.

    2009-01-01

    The transition metal copper is an essential cofactor for many redox-active enzymes, but excessive copper can generate toxic reactive oxygen species. Copper homeostasis is maintained by highly conserved proteins, to balance copper uptake, distribution and export on the systemic and cellular level.

  1. Analysis of α-particle induced incomplete chromosome aberrations, using pan-centro metric and pan-telomeric DNA probes

    International Nuclear Information System (INIS)

    Mestres, M.; Schmid, E.; Stephan, G.; Barrios, L.; Caballin, M. R.; Barquinero, J. F.

    2004-01-01

    The aim of the present study has been the evaluation of the incompleteness of α-particle induced chromosome aberrations by the simultaneous detection of all centromeres and telomeres present in human lymphocytes. For this purpose attached lymphocytes were irradiated at doses of 0.2, 0.5,0.7 and 1 Gy in a ''241Am source. FISH techniques were applied using pan-centromeric and pan-telomeric probes. All abnormal cells were digitalised and analysed using a Cytovision FISH workstation. A total of 378 incomplete chromosomes plus incomplete acentrics was found. Cases with more than 92 telomeres were not detected. The ratio between total incomplete elements and multicentrics was 1.00. The total number of acentric fragments was 822; 57% of then were complete fragments ace (+.+), 26% incomplete fragments ace (+,-), and 17% interstitial fragment ace (-.-). The percentage of incomplete aberrations is higher after high-LET than described for low-LET exposure. The results seem to indicate that compared to low-LET. after α-particle exposure it is more likely to repair the centromere-containing elements. (Author) 30 refs

  2. Trace metal analysis in sea grasses from Mexican Caribbean Coast by particle induced X-ray emission (PIXE)

    International Nuclear Information System (INIS)

    Solis, C.; Issac O, K.; Martinez, A.; Lavoisier, E.; Martinez, M. A.

    2008-01-01

    The growing urban and tourist activity in the Mexican Caribbean coasts has resulted in an increase of chemical substances, metals in particular, discharged to the coastal waters. In order to reach an adequate management and conservation of these marine ecosystems it is necessary to perform an inventory of the actual conditions that reflect the vulnerability and the level of damage. Sea-grasses are considered good biological indicators of heavy metal contamination in marine systems. The goal of this preliminary work is to evaluate the concentrations of trace metals such as Cr, Mn, Fe, Co, Cu, Zn, and Pb in Thalassia testudinum, a very common sea-grass in the Mexican Caribbean Sea. Samples were collected from several locations in the coasts of the Yucatan Peninsula: Holbox, Blanquizal and Punta Allen, areas virtually uninfluenced by anthropogenic activities. Trace elements in different part plants were determined by particle induced X-ray emission (PIXE). This is a very suitable technique since it offers a fast, accurate and multi-element analysis. Also, the analysis by PIXE can be performed directly on powdered leaves without a laborious sample preparation. The trace metal concentration determined in sea-grasses growing in Caribbean generally fall in the range of the lowest valuables reported for sea grasses from the Gulf of Mexico. The results indicate that the studied areas do not present contamination by heavy metals. (Author)

  3. Designing experimental setup and procedures for studying alpha-particle-induced adaptive response in zebrafish embryos in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Choi, V.W.Y.; Lam, R.K.K.; Chong, E.Y.W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Cheng, S.H. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.h [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2010-03-15

    The present work was devoted to designing the experimental setup and the associated procedures for alpha-particle-induced adaptive response in zebrafish embryos in vivo. Thin PADC films with a thickness of 16 mum were fabricated and employed as support substrates for holding dechorionated zebrafish embryos for alpha-particle irradiation from the bottom through the films. Embryos were collected within 15 min when the light photoperiod began, which were then incubated and dechorionated at 4 h post fertilization (hpf). They were then irradiated at 5 hpf by alpha particles using a planar {sup 241}Am source with an activity of 0.1151 muCi for 24 s (priming dose), and subsequently at 10 hpf using the same source for 240 s (challenging dose). The levels of apoptosis in irradiated zebrafish embryos at 24 hpf were quantified through staining with the vital dye acridine orange, followed by counting the stained cells under a florescent microscope. The results revealed the presence of the adaptive response in zebrafish embryos in vivo, and demonstrated the feasibility of the adopted experimental setup and procedures.

  4. PIXE in 1980: Summary of the second international conference on particle induced x-ray emission and its analytical applications

    International Nuclear Information System (INIS)

    Akselsson, K.R.

    1981-01-01

    The Second International Conference on Particle Induced X-ray Emission (PIXE) and its analytical applications was held in Lund, Sweden, June 9-12, 1980. About a hundred papers were presented, including seven invited talks (PIXE and particle scattering, microbeam analysis, applications to aerosols and biological samples). The main impression left by the conference was that both the PIXE method and its applications are in a phase of fast development. Considerable effort has successfully been devoted to optimizing the basic PIXE technique. Also the great advantage of simultaneously getting information about lighter elements and sample mass was reported to have been successfully employed in routine analyses. PIXE, which was initially considered to be a method mainly for thin samples, has also been shown to be competitive for a variety of thick samples. Data from aerosol studies was presented. With the PIXE-method, it is feasible to perform series of measurements over a long period of time, many samples in parallel and/or samples from sites of poor accessibility. However, the advantages of PIXE may be further exploited in aerosol investigations and some promising lines of sampler development were reported. Sample preparation techniques are crucial for applications to biological samples and several laboratories are engaged in such developmental work. However, it was also evident that PIXE is already giving significant contributions to research in biology and medicine

  5. Enhancement of alpha particles-induced cell transformation by oxygen free radicals and tumor necrosis factor released from phagocytes

    International Nuclear Information System (INIS)

    Gong Yifen; Guo Renfeng; Zhu Maoxiang; Shou Jiang; Ge Guixiu; Yang Zhihua; Hieber, L.; Peters, K.; Schippel, C.

    1997-01-01

    To illustrate the role of several endogenous factors released from phagocytes under chronic inflammation in radiation-induced cancer. C 3 T 10 T 1/2 and SHE cells were used as targets, and 238 Pu alpha source was used in alpha irradiation. The enhancement of TF in alpha particles-induced cell transformation by PMA-stimulated human blood and zymosan-stimulated U-937 cells was studied using formation of transformed foci. Transformation frequency (TF) of C 3 H 10 T 1/2 cells exposed to alpha particles of 0.5 Gy increased 2.1 and 2.8 fold by PMA-and PMA-stimulated neutrophils, respectively. TF of irradiated SHE cells at a dose of 0.5 Gy increased 12 fold by the addition of the supernatant of macrophage-like U-937 cell line. It was shown that TF of irradiated SHE cells at above dose increased 8 fold by the supernatant treated with anti-TNF-α could be subcultured continuously in vitro. The cells at 40 th passage and two lines of monoclone cells have the ability to develop malignant tumors in nude mice. The overdose of free radicals and TNF-α released from neutrophils and macrophages have played an important role in low dose radiation-induced cancer

  6. A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose

    Directory of Open Access Journals (Sweden)

    Kalsi SS

    2011-12-01

    Full Text Available Sarbjeet S Kalsi1,2, Paul I Dargan2–4, W Stephen Waring5, David M Wood2–41Emergency Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 2Clinical Toxicology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 3King’s Health Partners, London, UK; 4King’s College London, London, UK; 5York Teaching Hospital NHS Foundation Trust, York, UKAbstract: Paracetamol (acetaminophen poisoning is common throughout the world. The management of nonstaggered (acute paracetamol overdose is based on the plasma paracetamol concentration plotted on a treatment nomogram. In the UK there are two treatment lines on this nomogram, with the lower treatment line used for individuals felt to be at ‘high risk’ of paracetamol-related hepatotoxicity either as a result of induction of cytochrome P450 isoenzymes or reduction of intrahepatic glutathione. In this article we review the risk factors that, in current guidelines, are felt to increase risk due to a reduction in intrahepatic glutathione concentrations. Based on our review of the published literature, we feel that cystic fibrosis, acute viral illness, malnutrition, and eating disorders such as anorexia nervosa are likely to be associated with reduction in intrahepatic glutathione concentrations, and that this risk is likely to be related to malnutrition secondary to the disease. Chronic hepatitis C infection is also associated with reduced glutathione concentrations, although this appears to be independent of any associated malnutrition. Ageing and acute fasting are not associated with an increased risk of paracetamol-related hepatotoxicity due to reductions in glutathione concentrations. Finally, the evidence for HIV infection is inconclusive, particularly as the majority of studies were conducted in the pre-anti-viral treatment (HAART era; however it is likely that patients with symptomatic HIV/AIDS have reduced glutathione concentrations due to associated malnutrition. Although

  7. Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice

    International Nuclear Information System (INIS)

    Gandhi, Adarsh; Guo, Tao; Shah, Pranav; Moorthy, Bhagavatula; Ghose, Romi

    2013-01-01

    Inflammation is a major component of idiosyncratic adverse drug reactions (IADRs). To understand the molecular mechanism of inflammation-mediated IADRs, we determined the role of the Toll-like receptor (TLR) signaling pathway in idiosyncratic hepatotoxicity of the anti-psychotic drug, chlorpromazine (CPZ). Activation of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK). Prolonged activation of JNK leads to cell-death. We hypothesized that activation of TLR2 by lipoteichoic acid (LTA) or TLR4 by lipopolysaccharide (LPS) will augment the hepatotoxicity of CPZ by TIRAP-dependent mechanism involving prolonged activation of JNK. Adult male C57BL/6, TIRAP +/+ and TIRAP −/− mice were pretreated with saline, LPS (2 mg/kg) or LTA (6 mg/kg) for 30 min or 16 h followed by CPZ (5 mg/kg) or saline (vehicle) up to 24 h. We found that treatment of mice with CPZ in presence of LPS or LTA leads to ∼ 3–4 fold increase in serum ALT levels, a marked reduction in hepatic glycogen content, significant induction of serum tumor necrosis factor (TNF) α and prolonged JNK activation, compared to LPS or LTA alone. Similar results were observed in TIRAP +/+ mice, whereas the effects of LPS or LTA on CPZ-induced hepatotoxicity were attenuated in TIRAP −/− mice. For the first time, we show that inflammation-mediated hepatotoxicity of CPZ is dependent on TIRAP, and involves prolonged JNK activation in vivo. Thus, TIRAP-dependent pathways may be targeted to predict and prevent inflammation-mediated IADRs. -- Highlights: ► Inflammation augments the toxicity of an idiosyncratic hepatotoxin chlorpromazine. ► Activation of Toll-like receptors by LPS or LTA induces chlorpromazine toxicity. ► Sustained stress kinase (JNK) activation is associated with chlorpromazine toxicity. ► These studies provide novel mechanistic

  8. The Relation between Hepatotoxicity and the Total Coumarin Intake from Traditional Japanese Medicines Containing Cinnamon Bark.

    Science.gov (United States)

    Iwata, Naohiro; Kainuma, Mosaburo; Kobayashi, Daisuke; Kubota, Toshio; Sugawara, Naoko; Uchida, Aiko; Ozono, Sahoko; Yamamuro, Yuki; Furusyo, Norihiro; Ueda, Koso; Tahara, Eiichi; Shimazoe, Takao

    2016-01-01

    Cinnamon bark is commonly used in traditional Japanese herbal medicines (Kampo medicines). The coumarin contained in cinnamon is known to be hepatotoxic, and a tolerable daily intake (TDI) of 0.1 mg/kg/day, has been quantified and used in Europe to insure safety. Risk assessments for hepatotoxicity by the cinnamon contained in foods have been reported. However, no such assessment of cinnamon bark has been reported and the coumarin content of Kampo medicines derived from cinnamon bark is not yet known. To assess the risk for hepatotoxicity by Kampo medicines, we evaluated the daily coumarin intake of patients who were prescribed Kampo medicines and investigated the relation between hepatotoxicity and the coumarin intake. The clinical data of 129 outpatients (18 male and 111 female, median age 58 years) who had been prescribed keishibukuryogankayokuinin (TJ-125) between April 2008 and March 2013 was retrospectively investigated. Concurrent Kampo medicines and liver function were also surveyed. In addition to TJ-125, the patients took some of the other 32 Kampo preparations and 22 decoctions that include cinnamon bark. The coumarin content of these Kampo medicines was determined by high performance liquid chromatography (HPLC). TJ-125 had the highest daily content of coumarin (5.63 mg/day), calculated from the daily cinnamon bark dosage reported in the information leaflet inserted in each package of Kampo medicine. The coumarin content in 1g cinnamon bark decoction was 3.0 mg. The daily coumarin intake of the patients was 0.113 (0.049-0.541) mg/kg/day, with 98 patients (76.0%) exceeding the TDI. Twenty-three patients had an abnormal change in liver function test value, but no significant difference was found in the incidence of abnormal change between the group consuming less than the TDI value (6/31, 19.4%) and the group consuming equal to or greater than the TDI value (17/98, 17.3%). In addition, no abnormal change related to cinnamon bark was found for individual

  9. Chlorpromazine-induced hepatotoxicity during inflammation is mediated by TIRAP-dependent signaling pathway in mice

    Energy Technology Data Exchange (ETDEWEB)

    Gandhi, Adarsh, E-mail: adarsh.gandhi@nih.gov [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Guo, Tao, E-mail: tguo4@jhu.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Shah, Pranav [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Baylor College of Medicine, Department of Pediatrics, 1102 Bates Avenue, Suite 530, Houston, TX 77030 (United States); Ghose, Romi, E-mail: rghose@uh.edu [University of Houston, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 1441 Moursund Street, Room 517, Houston, TX 77030 (United States)

    2013-02-01

    Inflammation is a major component of idiosyncratic adverse drug reactions (IADRs). To understand the molecular mechanism of inflammation-mediated IADRs, we determined the role of the Toll-like receptor (TLR) signaling pathway in idiosyncratic hepatotoxicity of the anti-psychotic drug, chlorpromazine (CPZ). Activation of TLRs recruits the first adaptor protein, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) to the TIR domain of TLRs leading to the activation of the downstream kinase, c-Jun-N-terminal kinase (JNK). Prolonged activation of JNK leads to cell-death. We hypothesized that activation of TLR2 by lipoteichoic acid (LTA) or TLR4 by lipopolysaccharide (LPS) will augment the hepatotoxicity of CPZ by TIRAP-dependent mechanism involving prolonged activation of JNK. Adult male C57BL/6, TIRAP{sup +/+} and TIRAP{sup −/−} mice were pretreated with saline, LPS (2 mg/kg) or LTA (6 mg/kg) for 30 min or 16 h followed by CPZ (5 mg/kg) or saline (vehicle) up to 24 h. We found that treatment of mice with CPZ in presence of LPS or LTA leads to ∼ 3–4 fold increase in serum ALT levels, a marked reduction in hepatic glycogen content, significant induction of serum tumor necrosis factor (TNF) α and prolonged JNK activation, compared to LPS or LTA alone. Similar results were observed in TIRAP{sup +/+} mice, whereas the effects of LPS or LTA on CPZ-induced hepatotoxicity were attenuated in TIRAP{sup −/−} mice. For the first time, we show that inflammation-mediated hepatotoxicity of CPZ is dependent on TIRAP, and involves prolonged JNK activation in vivo. Thus, TIRAP-dependent pathways may be targeted to predict and prevent inflammation-mediated IADRs. -- Highlights: ► Inflammation augments the toxicity of an idiosyncratic hepatotoxin chlorpromazine. ► Activation of Toll-like receptors by LPS or LTA induces chlorpromazine toxicity. ► Sustained stress kinase (JNK) activation is associated with chlorpromazine toxicity. ► These studies

  10. Fabricating Copper Nanotubes by Electrodeposition

    Science.gov (United States)

    Yang, E. H.; Ramsey, Christopher; Bae, Youngsam; Choi, Daniel

    2009-01-01

    Copper tubes having diameters between about 100 and about 200 nm have been fabricated by electrodeposition of copper into the pores of alumina nanopore membranes. Copper nanotubes are under consideration as alternatives to copper nanorods and nanowires for applications involving thermal and/or electrical contacts, wherein the greater specific areas of nanotubes could afford lower effective thermal and/or electrical resistivities. Heretofore, copper nanorods and nanowires have been fabricated by a combination of electrodeposition and a conventional expensive lithographic process. The present electrodeposition-based process for fabricating copper nanotubes costs less and enables production of copper nanotubes at greater rate.

  11. Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

    Science.gov (United States)

    Wong, Anselm; Sivilotti, Marco L A; Graudins, Andis

    2017-06-01

    The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose. We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ≥1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L. Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L × IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L × IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity.

  12. Micromachining with copper lasers

    Science.gov (United States)

    Knowles, Martyn R. H.; Bell, Andy; Foster-Turner, Gideon; Rutterford, Graham; Chudzicki, J.; Kearsley, Andrew J.

    1997-04-01

    In recent years the copper laser has undergone extensive development and has emerged as a leading and unique laser for micromachining. The copper laser is a high average power (10 - 250 W), high pulse repetition rate (2 - 32 kHz), visible laser (511 nm and 578 nm) that produces high peak power (typically 200 kW), short pulses (30 ns) and very good beam quality (diffraction limited). This unique set of laser parameters results in exceptional micro-machining in a wide variety of materials. Typical examples of the capabilities of the copper laser include the drilling of small holes (10 - 200 micrometer diameter) in materials as diverse as steel, ceramic, diamond and polyimide with micron precision and low taper (less than 1 degree) cutting and profiling of diamond. Application of the copper laser covers the electronic, aerospace, automotive, nuclear, medical and precision engineering industries.

  13. Homogeneous weldings of copper

    International Nuclear Information System (INIS)

    Campurri, C.; Lopez, M.; Fernandez, R.; Osorio, V.

    1995-01-01

    This research explored the metallurgical and mechanical properties of arc welding of copper related with influence of Argon, Helium and mixtures of them. Copper plates of 6 mm thickness were welded with different mixtures of the mentioned gases. The radiography of welded specimens with 100% He and 100% Ar does not show show any porosity. On the other hand, the copper plates welded different gas mixtures presented uniform porosity in the welded zone. The metallographies show recrystallized grain in the heat affected zone, while the welding zone showed a dendritic structure. The results of the tensile strength vary between a maximum of 227 MPa for 100% He and a minimum of 174 MOa for the mixture of 60% He and 40% Ar. For the elongation after fracture the best values, about 36%, were obtained for pure gases. As a main conclusion, we can say that arc welding of copper is possible without loosing the mechanical and metallurgical properties of base metal. 6 refs

  14. copper(II)

    Indian Academy of Sciences (India)

    Unknown

    bis(2,2,6,6-tetramethyl-3,5-heptadionato)copper(II) ... Abstract. Equilibrium concentrations of various condensed and gaseous phases have been thermodyna- ... phere, over a wide range of substrate temperatures and total reactor pressures.

  15. Bacterial Killing by Dry Metallic Copper Surfaces▿

    OpenAIRE

    Santo, Christophe Espírito; Lam, Ee Wen; Elowsky, Christian G.; Quaranta, Davide; Domaille, Dylan W.; Chang, Christopher J.; Grass, Gregor

    2010-01-01

    Metallic copper surfaces rapidly and efficiently kill bacteria. Cells exposed to copper surfaces accumulated large amounts of copper ions, and this copper uptake was faster from dry copper than from moist copper. Cells suffered extensive membrane damage within minutes of exposure to dry copper. Further, cells removed from copper showed loss of cell integrity. Acute contact with metallic copper surfaces did not result in increased mutation rates or DNA lesions. These findings are important fir...

  16. LEP copper accelerating cavities

    CERN Multimedia

    Laurent Guiraud

    1999-01-01

    These copper cavities were used to generate the radio frequency electric field that was used to accelerate electrons and positrons around the 27-km Large Electron-Positron (LEP) collider at CERN, which ran from 1989 to 2000. The copper cavities were gradually replaced from 1996 with new superconducting cavities allowing the collision energy to rise from 90 GeV to 200 GeV by mid-1999.

  17. Copper intoxication in sheep

    Energy Technology Data Exchange (ETDEWEB)

    Gazaryan, V.S.; Sogoyan, I.S.; Agabalov, G.A.; Mesropyan, V.V.

    1966-01-01

    Of 950 sheep fed hay from a vineyard sprayed regularly with copper sulfate, 143 developed clinical copper poisoning and 103 died. The Cu content of the hay was 10.23 mg%, of the liver of dead sheep 17-52 mg%, and of the blood serum of affected sheep 0.86 mg%. The symptoms and the histological findings in kidneys and liver are described.

  18. Copper wire bonding

    CERN Document Server

    Chauhan, Preeti S; Zhong, ZhaoWei; Pecht, Michael G

    2014-01-01

    This critical volume provides an in-depth presentation of copper wire bonding technologies, processes and equipment, along with the economic benefits and risks.  Due to the increasing cost of materials used to make electronic components, the electronics industry has been rapidly moving from high cost gold to significantly lower cost copper as a wire bonding material.  However, copper wire bonding has several process and reliability concerns due to its material properties.  Copper Wire Bonding book lays out the challenges involved in replacing gold with copper as a wire bond material, and includes the bonding process changes—bond force, electric flame off, current and ultrasonic energy optimization, and bonding tools and equipment changes for first and second bond formation.  In addition, the bond–pad metallurgies and the use of bare and palladium-coated copper wires on aluminum are presented, and gold, nickel and palladium surface finishes are discussed.  The book also discusses best practices and re...

  19. Ginger for Prevention of Antituberculosis-induced Gastrointestinal Adverse Reactions Including Hepatotoxicity: A Randomized Pilot Clinical Trial.

    Science.gov (United States)

    Emrani, Zahra; Shojaei, Esphandiar; Khalili, Hossein

    2016-06-01

    In this study, the potential benefits of ginger in preventing antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity have been evaluated in patients with tuberculosis. Patients in the ginger and placebo groups (30 patients in each group) received either 500 mg ginger (Zintoma)(®) or placebo one-half hour before each daily dose of antituberculosis drugs for 4 weeks. Patients' gastrointestinal complaints (nausea, vomiting, dyspepsia, and abdominal pain) and antituberculosis drug-induced hepatotoxicity were recorded during the study period. In this cohort, nausea was the most common antituberculosis drug-induced gastrointestinal adverse reactions. Forty eight (80%) patients experienced nausea. Nausea was more common in the placebo than the ginger group [27 (90%) vs 21 (70%), respectively, p = 0.05]. During the study period, 16 (26.7%) patients experienced antituberculosis drug-induced hepatotoxicity. Patients in the ginger group experienced less, but not statistically significant, antituberculosis drug-induced hepatotoxicity than the placebo group (16.7% vs 36.7%, respectively, p = 0.07). In conclusion, ginger may be a potential option for prevention of antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Element analysis of the eutardigrades Richtersius coronifer and Milnesium cf. asiaticum using Particle Induced X-ray Emission (PIXE

    Directory of Open Access Journals (Sweden)

    Charlotta Nilsson

    2013-05-01

    Full Text Available Semi-terrestrial tardigrades are well-known for their tolerance to a variety of environmental extremes, including desiccation, freezing and radiation. Despite several attempts to reveal the genetic and molecular mechanisms behind the resilience of tardigrades, it is still unknown how these animals are able to maintain the integrity of their cellular components under severe stress. Quantitative or qualitative changes in molecular compounds (e.g., carbohydrates, proteins are expected, and have been the main line of research towards understanding the tolerance of tardigrades. In radiation tolerant bacteria, a tolerance mechanism based on manganese has been proposed. We evaluate this hypothesis in tardigrades and provide the first data on element composition in desiccated and non-desiccated specimens of two eutardigrade species, Richtersius coronifer and Milnesium cf. asiaticum. A focused 2 MeV proton microbeam was utilised to determine the elemental content, distributions and concentrations, using the ion beam analytical technique particle induced X-ray emission (PIXE. The presence of six elements – phosphorus, sulphur, chlorine, potassium, calcium and iron – were confirmed in all tardigrade specimens, at levels up to a few mg g–1. However, manganese was found in less than 10% of the analysed specimens, and in low amounts, thus our study provides no evidence for the manganese hypothesis. We also show that the distributions and/or concentrations of some elements differ between the two species as well as between the dehydrated and hydrated state. In particular, very low levels of iron were found in dehydrated M. cf. asiaticum. Our analysis shows that the PIXE technique is a useful tool for investigating questions on the distribution of elements both in dehydrated and hydrated tardigrades.

  1. Cross section measurement of alpha particle induced nuclear reactions on natural cadmium up to 52MeV.

    Science.gov (United States)

    Ditrói, F; Takács, S; Haba, H; Komori, Y; Aikawa, M

    2016-12-01

    Cross sections of alpha particle induced nuclear reactions have been measured on thin natural cadmium targets foils in the energy range from 11 to 51.2MeV. This work was a part of our systematic study on excitation functions of light ion induced nuclear reactions on different target materials. Regarding the cross sections, the alpha induced reactions are not deeply enough investigated. Some of the produced isotopes are of medical interest, others have application in research and industry. The radioisotope 117m Sn is a very important theranostic (therapeutic + diagnostic) radioisotope, so special care was taken to the results for that isotope. The well-established stacked foil technique followed by gamma-spectrometry with HPGe gamma spectrometers were used. The target and monitor foils in the stack were commercial high purity metal foils. From the irradiated targets 117m Sn, 113 Sn, 110 Sn, 117m,g In, 116m In, 115m In, 114m In, 113m In, 111 In, 110m,g In, 109m In, 108m,g In, 115g Cd and 111m Cd were identified and their excitation functions were derived. The results were compared with the data of the previous measurements from the literature and with the results of the theoretical nuclear reaction model code calculations TALYS 1.8 (TENDL-2015) and EMPIRE 3.2 (Malta). From the cross section curves thick target yields were calculated and compared with the available literature data. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Induction of Mrp3 and Mrp4 transporters during acetaminophen hepatotoxicity is dependent on Nrf2

    International Nuclear Information System (INIS)

    Aleksunes, Lauren M.; Slitt, Angela L.; Maher, Jonathan M.; Augustine, Lisa M.; Goedken, Michael J.; Chan, Jefferson Y.; Cherrington, Nathan J.; Klaassen, Curtis D.; Manautou, Jose E.

    2008-01-01

    The transcription factor NFE2-related factor 2 (Nrf2) mediates detoxification and antioxidant gene transcription following electrophile exposure and oxidative stress. Mice deficient in Nrf2 (Nrf2-null) are highly susceptible to acetaminophen (APAP) hepatotoxicity and exhibit lower basal and inducible expression of cytoprotective genes, including NADPH quinone oxidoreductase 1 (Nqo1) and glutamate cysteine ligase (catalytic subunit, or Gclc). Administration of toxic APAP doses to C57BL/6J mice generates electrophilic stress and subsequently increases levels of hepatic Nqo1, Gclc and the efflux multidrug resistance-associated protein transporters 1-4 (Mrp1-4). It was hypothesized that induction of hepatic Mrp1-4 expression following APAP is Nrf2 dependent. Plasma and livers from wild-type (WT) and Nrf2-null mice were collected 4, 24 and 48 h after APAP. As expected, hepatotoxicity was greater in Nrf2-null compared to WT mice. Gene and protein expression of Mrp1-4 and the Nrf2 targets, Nqo1 and Gclc, was measured. Induction of Nqo1 and Gclc mRNA and protein after APAP was dependent on Nrf2 expression. Similarly, APAP treatment increased hepatic Mrp3 and Mrp4 mRNA and protein in WT, but not Nrf2-null mice. Mrp1 was induced in both genotypes after APAP, suggesting that elevated expression of this transporter was independent of Nrf2. Mrp2 was not induced in either genotype at the mRNA or protein levels. These results show that Nrf2 mediates induction of Mrp3 and Mrp4 after APAP but does not affect Mrp1 or Mrp2. Thus coordinated regulation of detoxification enzymes and transporters by Nrf2 during APAP hepatotoxicity is a mechanism by which hepatocytes may limit intracellular accumulation of potentially toxic chemicals

  3. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate.

    Science.gov (United States)

    Humphreys, Jenny H; Warner, Alexander; Costello, Ruth; Lunt, Mark; Verstappen, Suzanne M M; Dixon, William G

    2017-09-01

    Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care. Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were included. Hepatotoxicity was defined as transaminitis: alanine transaminase or aspartate aminotransferase more than three times the upper limit of normal. Crude rates of transaminitis were calculated per 1000 person-years, categorised by weekly alcohol consumption in units. Cox proportional hazard models tested the association between alcohol consumption and transaminitis univariately, then age and gender adjusted. 11 839 patients were included, with 530 episodes of transaminitis occurring in 47 090 person-years follow-up. Increased weekly alcohol consumption as a continuous variable was associated with increased risk of transaminitis, adjusted HR (95% CI) per unit consumed 1.01 (1.00 to 1.02); consuming between 15 and 21 units was associated with a possible increased risk of hepatotoxicity, while drinking >21 units per week significantly increased rates of transaminitis, adjusted HR (95% CI) 1.85 (1.17 to 2.93). Weekly alcohol consumption of risk of transaminitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Ameliorative effect of vitamin C against hepatotoxicity induced by emamectin benzoate in rats.

    Science.gov (United States)

    Khaldoun Oularbi, H; Richeval, C; Lebaili, N; Zerrouki-Daoudi, N; Baha, M; Djennas, N; Allorge, D

    2017-07-01

    In the present study, we aimed to assess the potential protective effect of ascorbic acid (AA) against emamectin benzoate (EMB)-induced hepatotoxicity. For this purpose, biochemical, histopathological and analytical investigations were performed. Male Wistar rats were distributed into three groups, that is, a control group, an EMB group given 10 mg EMB/kg body weight (BW) by gavage and an EMB + AA group given 10 mg EMB/kg BW and vitamin C intraperitoneally (200 mg/kg). The duration of the treatment was 28 days and the duration of the study was 42 days. There was a statistically significant increase of all hepatic biomarkers, that is, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase activities, and glycemia, in EMB-treated group when compared with the control group. Light microscopic observations revealed variable signs of hepatotoxicity in the EMB group, which were represented by alteration of normal hepatic architecture, inflammatory cell infiltration, hepatocellular steatosis and foci of necrosis at 28 and 42 days post-treatment. However, co-treatment with vitamin C reduced EMB-related liver toxicity and diminished the abnormal biochemical and architectural damage. Emamectin B1a and B1b residues were detectable in all plasma samples of treated rats at 14, 21 and 28 days of treatment. The drug liver tissue concentration was significantly lower in EMB + AA group compared with EMB group at 28 and 42 days. In conclusion, the findings of the present study clearly indicate a significant protective action of vitamin C against EMB hepatotoxicity.

  5. Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Chun-Hung Chiu

    2016-07-01

    Full Text Available Lipopolysaccharide (LPS-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST, a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10 for seven days and then were LPS-challenged (i.p., 5 mg/kg. The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT, glutamic oxaloacetic transaminase (GOT, blood urea nitrogen (BUN, creatinine (CRE, hepatic malondialdehyde (MDA and glutathione peroxidase (GSH-Px, IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS, suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day. Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.

  6. Bees' Honey Attenuation of Metanil-Yellow-Induced Hepatotoxicity in Rats

    OpenAIRE

    Al-Malki, Abdulrahman L.; Sayed, Ahmed Amir Radwan

    2013-01-01

    The present study aims to investigate the protective effect of bees' honey against metanil-yellow-induced hepatotoxicity in rats. Rats were divided into 7 groups: control group; three groups treated with 50, 100, and 200?mg/kg metanil yellow, and three groups treated with metanil yellow plus 2.5?mg ? kg?1 ? day?1 bees' honey for 8 weeks. The obtained data showed that the antioxidant/anti-inflammatory activity of bees' honey reduced the oxidative stress in the liver tissue and downregulated th...

  7. Severe hepatotoxic adverse reaction in a healthy schoolgirl after treatment with flucloxacillin

    Directory of Open Access Journals (Sweden)

    C-J Törnhage

    2009-03-01

    Full Text Available C-J Törnhage1, G Brunlöf2, S M Wallerstedt21Department of Paediatrics, Central Hospital, Skaraborg, Skövde, Sweden; 2Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, SwedenAbstract: This is the first detailed description of a severe hepatotoxic reaction in a previously healthy 9-year-old schoolgirl after ingestion of some flucloxacillin tablets. She was clinically well within one week and alanine aminotransferase in serum was normalized in one month. Follow up for more than one year was normal.Keywords: adverse reaction, children, flucloxacillin, hepatopathy

  8. Hydroxycut hepatotoxicity: A case series and review of liver toxicity from herbal weight loss supplements

    Institute of Scientific and Technical Information of China (English)

    Lily Dare; Jennifer Hewett; Joseph Kartaik Lim

    2008-01-01

    Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxiciLy, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the seLLing of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements,and their individual components which have demonstrated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted.

  9. Ketoconazole hepatotoxicity in a patient treated for environmental illness and systemic candidiasis

    Energy Technology Data Exchange (ETDEWEB)

    Brusko, C.S.; Marten, J.T. (Purdue University School of Pharmacy and Pharmacal Sciences, Lafayette, IN (United States))

    1991-12-01

    Environmental illness, a hypothesized disease caused by exposure to substances such as combustion products, pesticides, food additives, and Candida albicans, is discussed. The case of a patient with environmental illness and systemic candidiasis for six weeks with ketoconazole, liver enzyme concentrations increased. One month after discontinuation of ketoconazole, the liver enzyme concentrations decreased; however, over the next five months, liver enzymes and bilirubin increased. The patient developed encephalopathy and eventually was transferred to a medical center for possible liver transplant. A review of the literature pertaining to ketoconazole hepatotoxicity is also presented.16 references.

  10. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    International Nuclear Information System (INIS)

    Henninger, Christian; Huelsenbeck, Johannes; Huelsenbeck, Stefanie; Grösch, Sabine; Schad, Arno; Lackner, Karl J.; Kaina, Bernd; Fritz, Gerhard

    2012-01-01

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  11. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, Christian [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany); Huelsenbeck, Johannes; Huelsenbeck, Stefanie [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Grösch, Sabine [Institute of Clinical Pharmacology, Johann Wolfgang Goethe University Frankfurt, Theodor Stern Kai 7, D-60590 Frankfurt/Main (Germany); Schad, Arno [Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Lackner, Karl J. [Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Kaina, Bernd [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz (Germany); Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf (Germany)

    2012-05-15

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  12. Copper : recession and recovery

    International Nuclear Information System (INIS)

    Warwick-Ching, T.

    2002-01-01

    In 2002, the world output for copper will fall for the first time in nearly a decade because of financial pressure and voluntary constraints. Cutbacks at copper mines amount to 760,000 tonnes per year. These cutbacks have occurred mostly in the United States which holds the largest share of high cost mines. This paper discussed recent developments in both copper supply and demand. The United States is unique as both a large consumer and producer of copper. At 1.35 million tonnes, US mine output in 2001 was at its lowest since 1987. The cutbacks in mining in general were described in this paper with particular reference to the huge loss of mining and metallurgical activity in the United States during a prolonged period of low prices in the mid 1980s. The author noted that this period was followed by an exceptional decade when much of the industry rebounded. Only 8 mines closed outright in the United States and a handful in Canada since the recession of the 1980s, but that is partly because mines got bigger and there are fewer small mines in North America. There are only 4 electrolytic refineries and 3 smelters still active in the entire United States, of which 2 are operating at a fraction of capacity. It was noted that only the buoyancy of China prevented a much bigger decline in copper demand on a global scale

  13. Accuracy of the paracetamol-aminotransferase product to predict hepatotoxicity in paracetamol overdose treated with a 2-bag acetylcysteine regimen.

    Science.gov (United States)

    Wong, Anselm; Sivilotti, Marco L A; Gunja, Naren; McNulty, Richard; Graudins, Andis

    2018-03-01

    Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol-aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen. We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L). Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase. The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens.

  14. Copper and copper-nickel alloys as zebra mussel antifoulants

    Energy Technology Data Exchange (ETDEWEB)

    Dormon, J.M.; Cottrell, C.M.; Allen, D.G.; Ackerman, J.D.; Spelt, J.K. [Univ. of Toronto, Ontario (Canada)

    1996-04-01

    Copper has been used in the marine environment for decades as cladding on ships and pipes to prevent biofouling by marine mussels (Mytilus edulis L.). This motivated the present investigation into the possibility of using copper to prevent biofouling in freshwater by both zebra mussels and quagga mussels (Dreissena polymorpha and D. bugensis collectively referred to as zebra mussels). Copper and copper alloy sheet proved to be highly effective in preventing biofouling by zebra mussels over a three-year period. Further studies were conducted with copper and copper-nickel mesh (lattice of expanded metal) and screen (woven wire with a smaller hole size), which reduced the amount of copper used. Copper screen was also found to be strongly biofouling-resistant with respect to zebra mussels, while copper mesh reduced zebra mussel biofouling in comparison to controls, but did not prevent it entirely. Preliminary investigations into the mechanism of copper antifouling, using galvanic couples, indicated that the release of copper ions from the surface of the exposed metal into the surrounding water is directly or indirectly responsible for the biofouling resistance of copper.

  15. Electrical conduction in composites containing copper core-copper

    Indian Academy of Sciences (India)

    Composites of nanometre-sized copper core-copper oxide shell with diameters in the range 6.1 to 7.3 nm dispersed in a silica gel were synthesised by a technique comprising reduction followed by oxidation of a suitably chosen precursor gel. The hot pressed gel powders mixed with nanometre-sized copper particles ...

  16. Quantification of particle-induced inflammatory stress response: a novel approach for toxicity testing of earth materials

    Directory of Open Access Journals (Sweden)

    Harrington Andrea D

    2012-04-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are vital regulators of many cellular functions in the body. The intracellular ROS concentration is highly regulated by a balance between pro-oxidants and anti-oxidants. A chronic excess of pro-oxidants leads to elevated ROS concentrations and inflammation, possibly initiating or enhancing disease onset. Mineral-induced generation of ROS, the role of minerals in upregulating cellular ROS, and their role in the development of several occupational diseases are now widely recognized. However, there is no standard protocol to determine changes in ROS production in cells after exposure to mineral dust or earth materials in general. In this study, a new method for determining the degree of cellular toxicity (i.e., cytotoxicity of particles is described that will help bridge the gap in knowledge. Results By measuring the production of ROS and the viability of cells, an inflammatory stress response (ISR indicator is defined. This approach normalizes the ROS upregulation with respect to the number of viable cells at the time of measurement. We conducted experiments on a series of minerals and soils that represent materials that are inert (i.e., glass beads, anatase, and a soil with low trace element content, moderately reactive (i.e., soil with high trace element content, and highly reactive (i.e., pyrite. Inert materials generated the lowest ISR, averaging 350% compared to the control. Acid washed pyrite produced the highest ISR (1,100 fold higher than the control. The measurements conducted as a function of time showed a complex response. Most materials showed an increase in ISR with particle loading. Conclusions The amount of cellularly generated ROS and cell viability combined provide a better understanding of particle-induced oxidative stress. The results indicate that some earth materials may solicit an initial burst of ROS, followed by a second phase in which cell viability decreases and ROS

  17. Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening

    Directory of Open Access Journals (Sweden)

    Mehdi Amirhosseini

    2017-12-01

    Full Text Available Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA. Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change ≥ ±1.5 and adjusted p-value ≤ 0.05 at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL-6, IL-1β, chemokine (C-C motif ligand (CCL2, prostaglandin-endoperoxide synthase (Ptgs2 and leukemia inhibitory factor (LIF showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological

  18. Study of copper fluorination

    International Nuclear Information System (INIS)

    Gillardeau, J.

    1967-02-01

    This report deals with the action of fluorine on copper. Comprehensive descriptions are given of the particular technological methods and of the preparation of the reactants. This fluorination reaction has been studied at medium and low fluorine pressures. A nucleation and growth phenomenon is described. The influence of a pollution of the gas phase on the fluorination process is described. The solid-state reaction between cupric fluoride and cooper has also been studied. A special study has been made of the growth of copper deposits by thermal decomposition of gaseous fluorides. (author) [fr

  19. Brazing copper to dispersion-strengthened copper

    Science.gov (United States)

    Ryding, David G.; Allen, Douglas; Lee, Richard H.

    1996-11-01

    The advanced photon source is a state-of-the-art synchrotron light source that will produce intense x-ray beams, which will allow the study of smaller samples and faster reactions and processes at a greater level of detail than has ben possible to date. The beam is produced by using third- generation insertion devices in a 7-GeV electron/positron storage ring that is 1,104 meters in circumference. The heat load from these intense high-power devices is very high, and certain components must sustain total heat loads of 3 to 15 kW and heat fluxes of 30 W/mm$_2). Because the beams will cycle on and off many times, thermal shock and fatigue will be a problem. High heat flux impinging on a small area causes a large thermal gradient that results in high stress. GlidCop, a dispersion-strengthened copper, is the desired design material because of its high thermal conductivity and superior mechanical properties as compared to copper and its alloys. GlidCop is not amenable to joining by fusion welding, and brazing requires diligence because of high diffusivity. Brazing procedures were developed using optical and scanning electron microscopy.

  20. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospect......Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning...... Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 +/- 1.18 mmol/L vs. 0.68 +/- 0.22 mmol/L, P L vs. 0.59 +/- 0.23 mmol/L, P ...). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than...

  1. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity

    International Nuclear Information System (INIS)

    Beger, Richard D.; Sun, Jinchun; Schnackenberg, Laura K.

    2010-01-01

    Hepatotoxicity and nephrotoxicity are two major reasons that drugs are withdrawn post-market, and hence it is of major concern to both the FDA and pharmaceutical companies. The number of cases of serious adverse effects (SAEs) in marketed drugs has climbed faster than the number of total drug prescriptions issued. In some cases, preclinical animal studies fail to identify the potential toxicity of a new chemical entity (NCE) under development. The current clinical chemistry biomarkers of liver and kidney injury are inadequate in terms of sensitivity and/or specificity, prompting the need to discover new translational specific biomarkers of organ injury. Metabolomics along with genomics and proteomics technologies have the capability of providing translational diagnostic and prognostic biomarkers specific for early stages of liver and kidney injury. Metabolomics has several advantages over the other omics platforms such as ease of sample preparation, data acquisition and use of biofluids collected through minimally invasive procedures in preclinical and clinical studies. The metabolomics platform is reviewed with particular emphasis on applications involving drug-induced hepatotoxicity and nephrotoxicity. Analytical platforms for metabolomics, chemometrics for mining metabolomics data and the applications of the metabolomics technologies are covered in detail with emphasis on recent work in the field.

  2. Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers

    Directory of Open Access Journals (Sweden)

    Zhuoling An

    2018-01-01

    Full Text Available Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically.

  3. Severe hepatotoxicity following ingestion of Herbalife nutritional supplements contaminated with Bacillus subtilis.

    Science.gov (United States)

    Stickel, Felix; Droz, Sara; Patsenker, Eleonora; Bögli-Stuber, Katja; Aebi, Beat; Leib, Stephen L

    2009-01-01

    Nutritional supplements are widely used. Recently, liver injury after consumption of Herbalife preparations was reported but the underlying pathogenesis remained cryptic. Two patients presented with cholestatic hepatitis and pruritus, and cirrhosis, respectively. Viral, alcoholic, metabolic, autoimmune, neoplastic, vascular liver diseases and synthetic drugs as the precipitating causes of liver injury were excluded. However, both patients reported long-term consumption of Herbalife products. All Herbalife products were tested for contamination with drugs, pesticides, heavy metals, and softeners, and examined for microbial contamination according to standard laboratory procedures. Bacteria isolated from the samples were identified as Bacillus subtilis by sequencing the 16S rRNA and gyrB genes. Causality between consumption of Herbalife products and disease according to CIOMS was scored "probable" in both cases. Histology showed cholestatic and lobular/portal hepatitis with cirrhosis in one patient, and biliary fibrosis with ductopenia in the other. No contamination with chemicals or heavy metals was detected, and immunological testing showed no drug hypersensitivity. However, samples of Herbalife products ingested by both patients showed growth of Bacillus subtilis of which culture supernatants showed dose- and time-dependent hepatotoxicity. Two novel incidents of severe hepatic injury following intake of Herbalife products contaminated with Bacillus subtilis emphasize its potential hepatotoxicity.

  4. Therapeutic Effects of Cassia angustifolia in a Cadmium Induced Hepatotoxicity Assay Conducted in Male Albino Rats

    Directory of Open Access Journals (Sweden)

    Muhammad Tahir Haidry

    2016-04-01

    Full Text Available The present study aims to investigate the therapeutic effects of Senna plant (Cassia angustifolia L. in a cadmium-induced hepatotoxicity assay by evaluating the activity of alanine transaminase (ALT, aspartate transaminase (AST, alkaline phosphatase (ALP and total protein (TP in the albino rats’ serum. A total of 30 white albino rats were taken and divided into three groups; each group comprising ten rats. The group A was taken as a control group; group B was given cadmium chloride concentration of 5 mg/kg (body weight for 42 days; and group C was given cadmium chloride 5 mg/kg body weight for first 21 days and then extract of C. angustifolia 100 mg/kg (body weight was given for remaining 21 days. The analysis were performed twice i.e., on 21stst day and 42nd day. Results illustrated that the concentration of cadmium was significantly elevated (P<0.05 at the levels of serum biochemical markers namely ALT, AST, ALP which lowered the protein levels in albino rats. Moreover, treatment with the standard extracts of C. angustifolia observed to reverse the effects of the cadmium significantly (P<0.05. It is concluded that the C. angustifolia had hepatoprotective effects and therapeutic potential against the cadmium-induced hepatotoxicity in albino rats.

  5. Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions

    Directory of Open Access Journals (Sweden)

    Nora Freyer

    2018-03-01

    Full Text Available The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP (p < 0.05 and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP (p < 0.0001, indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP (p < 0.05, suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions.

  6. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    El-Kott, Attalla Farag; Bin-Meferij, Mashael Mohammed

    2015-12-01

    Severe destructive hepatic injuries can be induced by acetaminophen overdose and may lead to acute hepatic failure. To investigate the ameliorative effects of Arctium lappa root extract on acetaminophen-induced hepatotoxicity. Rats were divided into 4 groups: normal control group, Arctium lappa extract group, acetaminophen-injected group, and acetaminophen treated with Arctium lappa extract group. The treatment with Arctium lappa extract reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase in the acetaminophen group when compared with the control group. DNA fragments in the acetaminophen-injected group were also significantly increased (P Arctium lappa treatment (12.97±0.89 nmol/mg) when compared with the acetaminophen-treated-only group (12.97±0.89 nmol/mg). Histopathologic examination revealed that acetaminophen administration produced hepatic cell necrosis, infiltrate of lymphocytes, and vacuolation that were associated with the acetaminophen-treated animal group, but the degree of acetaminophen-induced hepatotoxicity was mediated by treatment with Arctium lappa extract. Arctium lappa can prevent most of the hepatic tissue damage caused by acetaminophen overdose in rats.

  7. [Individualized clinical treatment from the prospective of hepatotoxicity of non-toxic traditional Chinese medicine].

    Science.gov (United States)

    Yang, Nan; Chen, Juan; Hou, Xue-Feng; Song, Jie; Feng, Liang; Jia, Xiao-Bin

    2017-04-01

    Traditional Chinese medicine has a long history in clinical application, and been proved to be safe and effective. In recent years, the toxicity and side-effects caused by the western medicine have been attracted much attention. As a result, increasing people have shifted their attention to traditional Chinese medicine. Nonetheless, due to the natural origin of traditional Chinese medicine and the lack of basic knowledge about them, many people mistakenly consider the absolute safety of traditional Chinese medicine, except for well-known toxic ones, such as arsenic. However, according to the clinical practices and recent studies, great importance shall be attached to the toxicity of non-toxic traditional Chinese medicine, in particular the hepatotoxicity. Relevant studies indicated that the toxicity of non-toxic traditional Chinese medicine is closely correlated with individual gene polymorphism and constitution. By discussing the causes and mechanisms of the hepatotoxicity induced by non-toxic traditional Chinese medicine in clinical practices, we wrote this article with the aim to provide new ideas for individualized clinical therapy of traditional Chinese medicine and give guidance for rational and safe use of traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

  8. The protective effects of vitamin C on hepatotoxicity induced by radiation

    International Nuclear Information System (INIS)

    Ahn, Ki Jung; Park, Sung Kwang; Cho, Heung Lae; Kang, Ki Mun; Chai, Gyu Young; Chung, Duck Wha; Kang, Jin Soon

    2004-01-01

    This study was carried out to determine the protective effects of vitamin C on the hepatotoxicity induced by radiation. The Spraque Dawley rats were randomly divided into 3 groups; the control group, the radiation exposed group, and the radiation and vitamin C-treated group. SOD activity catalase, malondialdehyde and liver enzymes were analyzed to assess the antioxidant effects of vitamin C. The increased level of malondialdehyde and the decreased catalase activity that were induced by radiation were improved after vitamin C but were was no statistical significance among three groups. The superoxide dismutase activity of the liver was increased by vitamin C, but there were no statistically significant differences between the vitamin C-treated group and the non vitamin C-treated group. The level of liver enzymes in sera such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehyrogenase and alkaline phosphatase were remarkably elevated by radiation. The levels of those enzymes were decreased in the vitamin C-treated group and statistical significance was noted for the GPT level (ρ < 0.01). On the electromicrographic findings, the hepatic cell destruction was considerably decreased in the vitamin C-treated group. Vitamin C is thought to be an effective antioxidant against the hepatotoxicity induced by radiation

  9. Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

    Science.gov (United States)

    Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

    2015-03-01

    1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

  10. Moringa oleifera-based diet protects against nickel-induced hepatotoxicity in rats

    Science.gov (United States)

    Stephen Adeyemi, Oluyomi; Sokolayemji Aroge, Cincin; Adewumi Akanji, Musbau

    2017-01-01

    Multiple health-promoting effects have been attributed to the consumption of Moringa oleifera leaves, as part of diet without adequate scientific credence. This study evaluated the effect of M. oleifera-based diets on nickel (Ni) - induced hepatotoxicity in rats. Male rats assigned into six groups were given oral administration of 20 mg/kg body weight nickel sulfate in normal saline and either fed normal diet orM. oleifera-based diets for 21 days. All animals were sacrificed under anesthesia 24 hours after the last treatment. Ni exposure elevated the rat plasma activities of alanine transaminase, aspartate transaminase and alkaline phosphatase significantly. Ni exposure also raised the levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol while depleting the high-density lipoprotein cholesterol concentration. Further, Ni exposure raised rat plasma malondialdehyde but depleted reduced glutathione concentrations. The histopathological presentations revealed inflammation and cellular degeneration caused by Ni exposure. We show evidence thatM. oleifera-based diets protected against Ni-induced hepatotoxicity by improving the rat liver function indices, lipid profile as well as restoring cellular architecture and integrity. Study lends credence to the health-promoting value ofM. oleifera as well as underscores its potential to attenuate hepatic injury. PMID:28808207

  11. Gemfibrozil disrupts lysophosphatidylcholine and bile acid homeostasis via PPARα and its relevance to hepatotoxicity.

    Science.gov (United States)

    Liu, Aiming; Krausz, Kristopher W; Fang, Zhong-Ze; Brocker, Chad; Qu, Aijuan; Gonzalez, Frank J

    2014-04-01

    Gemfibrozil, a ligand of peroxisome proliferator-activated receptor α (PPARα), is one of the most widely prescribed anti-dyslipidemia fibrate drugs. Among the adverse reactions observed with gemfibrozil are alterations in liver function, cholestatic jaundice, and cholelithiasis. However, the mechanisms underlying these toxicities are poorly understood. In this study, wild-type and Ppara-null mice were dosed with a gemfibrozil-containing diet for 14 days. Ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics and traditional approaches were used to assess the mechanism of gemfibrozil-induced hepatotoxicity. Unsupervised multivariate data analysis revealed four lysophosphatidylcholine components in wild-type mice that varied more dramatically than those in Ppara-null mice. Targeted metabolomics revealed taurocholic acid and tauro-α-muricholic acid/tauro-β-muricholic acid were significantly increased in wild-type mice, but not in Ppara-null mice. In addition to the above perturbations in metabolite homeostasis, phenotypic alterations in the liver were identified. Hepatic genes involved in metabolism and transportation of lysophosphatidylcholine and bile acid compounds were differentially regulated between wild-type and Ppara-null mice, in agreement with the observed downstream metabolic alterations. These data suggest that PPARα mediates gemfibrozil-induced hepatotoxicity in part by disrupting phospholipid and bile acid homeostasis.

  12. Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions.

    Science.gov (United States)

    Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Gerstmann, Florian; Storch, Lisa; Damm, Georg; Seehofer, Daniel; Foster Harris, Jennifer; Iyer, Rashi; Schubert, Frank; Zeilinger, Katrin

    2018-03-15

    The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP ( p < 0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions.

  13. The use of cultured hepatocytes to investigate the metabolism of drugs and mechanisms of drug hepatotoxicity.

    Science.gov (United States)

    Gómez-Lechón, M J; Ponsoda, X; Bort, R; Castell, J V

    2001-01-01

    Hepatotoxins can be classified as intrinsic when they exert their effects on all individuals in a dose-dependent manner, and as idiosyncratic when their effects are the consequence of an abnormal metabolism of the drug by susceptible individuals (metabolic idiosyncrasy) or of an immune-mediated injury to hepatocytes (allergic hepatitis). Some xenobiotics are electrophilic, and others are biotransformed by the liver into highly reactive metabolites that are usually more toxic than the parent compound. This activation process is the key to many hepatotoxic phenomena. Mitochondria are a frequent target of hepatotoxic drugs, and the alteration of their function has immediate effects on the energy balance of cells (depletion of ATP). Lipid peroxidation, oxidative stress, alteration of Ca(2+) homeostasis, and covalent binding to cell macromolecules are the molecular mechanisms that are frequently involved in the toxicity of xenobiotics. Against these potential hazards, cells have their own defence mechanisms (for example, glutathione, DNA repair, suicide inactivation). Ultimately, toxicity is the balance between bioactivation and detoxification, which determines whether a reactive metabolite elicits a toxic effect. The ultimate goal of in vitro experiments is to generate the type of scientific information needed to identify compounds that are potentially toxic to man. For this purpose, both the design of the experiments and the interpretation of the results are critical.

  14. Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice.

    Science.gov (United States)

    Sheweita, Salah A; El-Hosseiny, Lobna S; Nashashibi, Munther A

    2016-01-01

    Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP. The data of the present study showed that treatment of male mice with cyclophosphamide (2.5 mg/Kg BW) as repeated dose for 28 consecutive days was found to induce hepatotoxicity through the elevation in the activities of AST, ALT, and ALP. Combined administration of any of these oils with CP to mice partially normalized the altered hepatic biochemical markers caused by CP, whereas administration of fennel, clove or cumin essential oils alone couldn't change liver function indices. Moreover, CP caused histological changes in livers of mice including swelling and dilation in sinusoidal space, inflammation in portal tract and hepatocytes, as well as, hyperplasia in Kuppfer cells. However, co-administration of any of the essential oils with CP alleviated to some extent the changes caused by CP but not as the normal liver. CP was also found to induce free radical levels (measured as thiobarbituric acid reactive substances) and inhibited the activities of superoxide dismutase, glutathione reductase, and catalase as well as activities and protein expressions of both glutathione S-transferase (GSTπ) and glutathione peroxidase. Essential oils restored changes in activities of antioxidant enzymes (SOD, CAT, GR, GST, and GPx) caused by CP to their normal levels compared

  15. Copper and Copper Proteins in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sergio Montes

    2014-01-01

    Full Text Available Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson’s disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson’s disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson’s disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson’s disease and that a mutation in ATP7B could be associated with Parkinson’s disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.

  16. Creative Copper Crests

    Science.gov (United States)

    Knab, Thomas

    2011-01-01

    In this article, the author discusses how to create an art activity that would link the computer-created business cards of fourth-grade students with an upcoming school-wide medieval event. Creating family crests from copper foil would be a great connection, since they, like business cards, are an individual's way to identify themselves to others.…

  17. and copper(II)

    Indian Academy of Sciences (India)

    Unknown

    (II) and copper(II)–zinc(II) complexes. SUBODH KUMAR1, R N PATEL1*, P V KHADIKAR1 and. K B PANDEYA2. 1 Department of Chemistry, APS University, Rewa 486 003, India. 2 CSJM University, Kanpur 208 016, India e-mail: (R N Patel) ...

  18. Reagent conditions of the flotation of copper, copper - molybdenum and copper -zinc ores in foreing countries

    International Nuclear Information System (INIS)

    Nevaeva, L.M.

    1983-01-01

    Reagents-collectors and frothers, used abroad in reagent regimes of flotation of copper, copper-molybdenum and copper zinc ores, have been considered. Xanthogenates, aerofloats, xanthogenformiates, thionocarbamates are mainly used as reagents-collectors. Methylizobutylcarbinol and Daufros are used as reagents-frothers

  19. Hypoxia targeting copper complexes

    International Nuclear Information System (INIS)

    Dearling, J.L.

    1998-11-01

    The importance and incidence of tumour hypoxia, its measurement and current treatments available, including pharmacological and radiopharmacological methods of targeting hypoxia, are discussed. A variety of in vitro and in vivo methods for imposing hypoxia have been developed and are reviewed. Copper, its chemistry, biochemistry and radiochemistry, the potential for use of copper radionuclides and its use to date in this field is considered with particular reference to the thiosemicarbazones. Their biological activity, metal chelation, in vitro and in vivo studies of their radiocopper complexes and the potential for their use as hypoxia targeting radiopharmaceuticals is described. The reduction of the copper(II) complex to copper(l), its pivotal importance in their biological behaviour, and the potential for manipulation of this to effect hypoxia selectivity are described. An in vitro method for assessing the hypoxia selectivity of radiopharmaceuticals is reported. The rapid deoxygenation and high viability of a mammalian cell culture in this system is discussed and factors which may affect the cellular uptake of a radiopharmaceutical are described. The design, synthesis and complexation with copper and radiocopper of a range of bis(thiosemicarbazones) is reported. Synthesis of these compounds is simple giving high yields of pure products. The characteristics of the radiocopper complexes ( 64 Cu) including lipophilicity and redox activity are reported (reduction potentials in the range -0.314 - -0.590 V). High cellular uptakes of the radiocopper complexes of the ligands, in hypoxic and normoxic EMT6 and CHO320 cells, were observed. Extremes of selectivity are shown ranging from the hypoxia selective 64 Cu(II)ATSM to normoxic cell selective 64 Cu(II)GTS. The selectivities observed are compared with the physico chemical characteristics of the complexes. A good correlation exists between selectivity of the complex and its Cu(II)/Cu(I) reduction potential, with hypoxia

  20. Precursors for formation of copper selenide, indium selenide, copper indium diselenide, and/or copper indium gallium diselenide films

    Science.gov (United States)

    Curtis, Calvin J; Miedaner, Alexander; Van Hest, Maikel; Ginley, David S

    2014-11-04

    Liquid-based precursors for formation of Copper Selenide, Indium Selenide, Copper Indium Diselenide, and/or copper Indium Galium Diselenide include copper-organoselenides, particulate copper selenide suspensions, copper selenide ethylene diamine in liquid solvent, nanoparticulate indium selenide suspensions, and indium selenide ethylene diamine coordination compounds in solvent. These liquid-based precursors can be deposited in liquid form onto substrates and treated by rapid thermal processing to form crystalline copper selenide and indium selenide films.

  1. Modulatory effects of dietary inclusion of garlic (Allium sativum) on gentamycin-induced hepatotoxicity and oxidative stress in rats.

    Science.gov (United States)

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Owoloye, Tosin R; Agbebi, Oluwaseun J

    2013-06-01

    To investigate the ameliorative effect of dietary inclusion of garlic (Allium sativum) on gentamycin-induced hepatotoxicity in rats. Adult male rats were randomly divided into four groups with six animals in each group. Groups 1 and 2 were fed basal diet while Groups 3 and 4 were fed diets containing 2% and 4% garlic respectively for 27 d prior to gentamycin administration. Hepatotoxicity was induced by the intraperitoneal administration of gentamycin (100 mg/kg body weight) for 3 d. The liver and plasma were studied for hepatotoxicity and antioxidant indices. Gentamycin induces hepatic damage as revealed by significant (P<0.05) elevation of liver damage marker enzymes (aspartate transaminase and alanine aminotransferase) and reduction in plasma albumin level. Gentamycin also caused a significant (P<0.05) alteration in plasma and liver enzymatic (catalase, glutathione and super oxygen dehydrogenises) and non-enzymatic (glutathione and vitamin C) antioxidant indices with concomitant increase in the malondialdehyde content; however, there was a significant (P<0.05) restoration of the antioxidant status coupled with significant (P<0.05) decrease in the tissues' malondialdehyde content, following consumption of diets containing garlic. These results suggest that dietary inclusion of garlic powder could protect against gentamycin-induced hepatotoxicity, improve antioxidant status and modulate oxidative stress; a function attributed to their phenolic constituents.

  2. Precision-cut liver slices as an ex vivo model to study idiosyncratic hepatotoxicity in mouse and human

    NARCIS (Netherlands)

    Hadi, Mackenzie; Chen, Yixi; Emmen, Harry; Stitzinger, Miranda; Groothuis, Genoveva

    Adverse drug reactions (ADRs) related to hepatotoxicity and drug hypersensitivity are responsible for the top two of toxicity-related drug withdrawals and there are no adequate translational strategies to predict safety. Idiosyncratic adverse drug reactions (IADRs) are ADRs that are rare and

  3. Risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/AIDS-coinfected patients under tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Williams Ngouleun

    2016-01-01

    Conclusion: The results showed that human immunodeficiency virus status and alcohol consumption constitutes aggravating factors for the occurrence of hepatic toxicity. In addition, the consumption of antioxidant foods simultaneously with TB drugs help in reducing the hepatotoxic effects of these drugs.

  4. Relationship Between Structural Alerts in NSAIDs and Idiosyncratic Hepatotoxicity : An Analysis of Spontaneous Report Data from the WHO Database

    NARCIS (Netherlands)

    Jessurun, Naomi; van Puijenbroek, Eugene

    2015-01-01

    BACKGROUND: Idiosyncratic drug reactions such as hepatotoxicity and blood dyscrasias represent one of the major causes of drug withdrawal from the market. According to the reactive metabolite (RM) concept, this may be due to the metabolic activation of structural alerts (SAs), functionalities in the

  5. Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity

    NARCIS (Netherlands)

    Hof, W.F.P.M.; Summeren, van A.; Lommen, A.; Coonen, M.L.J.; Brauers, K.; Herwijnen, van M.; Wodzig, W.K.W.H.; Kleinjans, J.C.S.

    2014-01-01

    The liver is responsible for drug metabolism and drug-induced hepatotoxicity is the most frequent reason for drug withdrawal, indicating that better pre-clinical toxicity tests are needed. In order to bypass animal models for toxicity screening, we exposed primary mouse hepatocytes for exploring the

  6. Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation.

    Science.gov (United States)

    Mahmoud, Ayman M

    2014-09-01

    The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

  7. Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity.

    Science.gov (United States)

    El-Mansy, A A; Mazroa, S A; Hamed, W S; Yaseen, A H; El-Mohandes, E A

    2016-01-01

    The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.

  8. DILI (drug induced liver injury in a 9-month-old infant: a rare case of phenobarbital-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Anna Paola Pinna

    2013-04-01

    Full Text Available Phenobarbital is one of the most commonly prescribed antiepileptic drugs in childhood, but it can rarely cause serious adverse effects, such as hepatotoxicity that includes a broad clinical spectrum (from isolate hypertransaminasemia to acute liver failure. We describe a case of DILI in a 9-month-old infant caused by chronic therapy with phenobarbital.

  9. Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data.

    Science.gov (United States)

    Kim, Marlene Thai; Huang, Ruili; Sedykh, Alexander; Wang, Wenyi; Xia, Menghang; Zhu, Hao

    2016-05-01

    Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program. The ARE-bla computational model and HTS data from a big data source (PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxicity data. Quantitative structure-activity relationship (QSAR) models were developed based on ARE-bla data. The models predicted the potential oxidative stress response for known liver toxicants when no ARE-bla data were available. Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (> 10 million data points). By ranking the in vitro-in vivo correlations (IVIVCs), the most relevant bioassay(s) related to hepatotoxicity were identified. The liver toxicants profile contained the ARE-bla and relevant PubChem assays. Potential toxicophores for well-known toxicants were created by identifying chemical features that existed only in compounds with high IVIVCs. Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources. Kim MT, Huang R, Sedykh A, Wang W, Xia M, Zhu H. 2016. Mechanism profiling of hepatotoxicity caused by oxidative stress using antioxidant response element reporter gene assay models and big data. Environ Health Perspect 124:634-641;

  10. NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure to PCBs and TCDD in rats

    International Nuclear Information System (INIS)

    Lu Chunfeng; Wang Yimei; Sheng Zhiguo; Liu Gang; Fu Ze; Zhao Jing; Zhao Jun; Yan Xianzhong; Zhu Benzhan; Peng Shuangqing

    2010-01-01

    A metabonomic approach using 1 H NMR spectroscopy was adopted to investigate the metabonomic pattern of rat urine after oral administration of environmental endocrine disruptors (EDs) polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) alone or in combination and to explore the possible hepatotoxic mechanisms of combined exposure to PCBs and TCDD. 1 H NMR spectra of urines collected 24 h before and after exposure were analyzed via pattern recognition by using principal component analysis (PCA). Serum biochemistry and liver histopathology indicated significant hepatotoxicity in the rats of the combined group. The PCA scores plots of urinary 1 H NMR data showed that all the treatment groups could be easily distinguished from the control group, so could the PCBs or TCDD group and the combined group. The loadings plots of the PCA revealed remarkable increases in the levels of lactate, glucose, taurine, creatine, and 2-hydroxy-isovaleric acid and reductions in the levels of 2-oxoglutarate, citrate, succinate, hippurate, and trimethylamine-N-oxide in rat urine after exposure. These changes were more striking in the combined group. The changed metabolites may be considered possible biomarker for the hepatotoxicity. The present study demonstrates that combined exposure to PCBs and TCDD induced significant hepatotoxicity in rats, and mitochondrial dysfunction and fatty acid metabolism perturbations might contribute to the hepatotoxicity. There was good conformity between changes in the urine metabonomic pattern and those in serum biochemistry and liver histopathology. These results showed that the NMR-based metabonomic approach may provide a promising technique for the evaluation of the combined toxicity of EDs.

  11. Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events

    Directory of Open Access Journals (Sweden)

    Rankin Elizabeth

    2008-04-01

    Full Text Available Abstract Background Spontaneous reporting systems for adverse drug reactions (ADRs are handicapped by under-reporting and limited detail on individual cases. We report an investigation from a local surveillance for serious adverse drug reactions associated with disease modifying anti-rheumatic drugs that was triggered by the occurrence of liver failure in two of our patients. Methods Serious ADR reports have been solicited from local clinicians by regular postcards over the past seven years. Patients', who had hepatotoxicity on sulfasalazine and met a definition of a serious ADR, were identified. Two clinicians reviewed structured case reports and assessed causality by consensus and by using a causality assessment instrument. The likely frequency of hepatotoxicity with sulfasalazine was estimated by making a series of conservative assumptions. Results Ten cases were identified: eight occurred during surveillance. Eight patients were hospitalised, two in hepatic failure – one died after a liver transplant. All but one event occurred within 6 weeks of treatment. Seven patients had a skin rash, three eosinophilia and one interstitial nephritis. Five patients were of Black British of African or Caribbean descent. Liver enzymes showed a hepatocellular pattern in four cases and a mixed pattern in six. Drug-related hepatotoxicity was judged probable or highly probable in 8 patients. The likely frequency of serious hepatotoxicity with sulfasalazine was estimated at 0.4% of treated patients. Conclusion Serious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important.

  12. Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats

    Directory of Open Access Journals (Sweden)

    Sonam Miglani

    2016-10-01

    Full Text Available Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Liver damage was assessed using biochemical and histological parameters. Administration of goat milk (20 mL/kg along with antitubercular drugs (Group III reversed the levels of serum alanine aminotransferase (82 ± 25.1 vs. 128.8 ± 8.9 units/L and aspartate aminotransferase (174.7 ± 31.5 vs. 296.4 ± 56.4 units/L, p<0.01 compared with antitubercular drug treatment Group II. There was a significant decrease in serum alanine aminotransferase (41.8 ± 4.1 vs. 128.8 ± 8.9 ​ units/L, p<0.01 and aspartate aminotransferase (128.8 ± 8.54 vs. 296.4 ± 56.4 units/L, p<0.001 levels in Group IV (goat milk 40 mL/kg compared with antitubercular drug treatment Group II. Goat milk (20 mL/kg and 40 mL/kg was effective in reversing the rise in malondialdehyde level compared with the antitubercular drug suspension groups (58.5 ± 2 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001 and 69.7 ± 0.78 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001, respectively. Similarly, both doses of milk significantly prevented a fall in superoxide dismutase level (6.23 ± 0.29 vs. 3.1 ± 0.288 units/mL, p<0.001 and 7.8 ± 0.392 vs. 3.1 ± 0.288 units/mL, p<0.001 compared with the group receiving antitubercular drugs alone. Histological examination indicated that goat milk reduced inflammation and necrotic changes in hepatocytes in the treatment groups. The results indicated that goat milk prevented the antitubercular drug-induced hepatotoxicity and is an effective hepatoprotective agent.

  13. Editorial: dose-dependent ZnO particle-induced acute phase response in humans warrants re-evaluation of occupational exposure limits for metal oxides

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Cassee, Flemming R.

    2018-01-01

    in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential...... studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monse et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well...

  14. NACRE II: an update of the NACRE compilation of charged-particle-induced thermonuclear reaction rates for nuclei with mass number A<16

    International Nuclear Information System (INIS)

    Xu, Y.; Takahashi, K.; Goriely, S.; Arnould, M.; Ohta, M.; Utsunomiya, H.

    2013-01-01

    An update of the NACRE compilation [3] is presented. This new compilation, referred to as NACRE II, reports thermonuclear reaction rates for 34 charged-particle induced, two-body exoergic reactions on nuclides with mass number A 6 ≲T⩽10 10 K range. Along with the ‘adopted’ rates, their low and high limits are provided. The new rates are available in electronic form as part of the Brussels Library (BRUSLIB) of nuclear data. The NACRE II rates also supersede the previous NACRE rates in the Nuclear Network Generator (NETGEN) for astrophysics. [ (http://www.astro.ulb.ac.be/databases.html)

  15. Summary report of the first research coordination meeting on development of a reference database for particle-induced gamma ray emission (PIGE) spectroscopy

    International Nuclear Information System (INIS)

    Abriola, D.; Pedro de Jesus, A.

    2011-07-01

    The First Research Coordination Meeting (RCM) of the IAEA Coordinated Research Project (CRP) on 'Development of a Reference Database for Particle-Induced Gamma-ray Emission (PIGE) Spectroscopy' was held at the IAEA, Vienna, from 16-20 May 2011. A summary of the participants' presentations is given as well as background information, objectives and recommendations concerning approach and methodology. The extension of the IBANDL database format to include PIGE data was discussed. The different tasks to achieve the CRP objectives were assigned to participants. A list of priority measurements was produced and the individual sets of measurements assigned to participants. (author)

  16. Summary Report of the 3rd Research Coordination Meeting on Development of a Reference Database for Particle-Induced Gamma ray Emission (PIGE) Spectroscopy

    International Nuclear Information System (INIS)

    Dimitriou, P.; Pedro de Jesus, A.

    2014-05-01

    The Third Research Coordination Meeting (RCM) of the IAEA Coordinated Research Project (CRP) on “Development of a Reference Database for Particle-Induced Gamma-ray Emission (PIGE) Spectroscopy” was held at the IAEA, Vienna, from 7 to 11 April 2014. Participants reviewed the progress made since the previous RCM and agreed upon the work that remains to be done by the end of the CRP. The contents of the final Technical Document were discussed and individual chapters were assigned. The summaries of participants’ presentations as well as the technical discussions and the list of assigned tasks are included in this report. (author)

  17. Improvement in limit of detection in particle induced X-ray emission by means of rise time and pulse shape discrimination

    Energy Technology Data Exchange (ETDEWEB)

    Papp, Tibor E-mail: tibpapp@netscape.nettibpapp@yahoo.ca; Lakatos, Tamas; Nejedly, Zdenek; Campbell, John L

    2002-04-01

    A digital signal processor, based upon high-rate sampling of the preamplifier output, and equipped with rise time and pulse shape discrimination, has been tested in three situations. This processor provided significant improvement of particle induced X-ray emission and X-ray fluorescence detection limits over the state of the art analog processors, depending on the energy and intensity distribution of the X-ray spectra. Additionally it had a superior performance when measurements were performed in an environment of large electronic noise and in large nuclear background environment. It has also improved the reduction of several artifacts in X-ray spectra.

  18. The Effect of Copper

    African Journals Online (AJOL)

    environment, where fishes are found, stuns them ... of earthen ponds are springing up near cocoa ... farm, which posses toxicological risk to farmed ... Veg. oil. 1.0. 1.0. 1.0. 1.0. 1.0. Copper sulphate 0. 1.0. 2.5. 5.0. 7.5. Total ..... Cellulase Production by Wild Strains of Aspergillus Niger, ... Mangrove Area of Lagos, Nigeria.

  19. Copper Pyrimidine based MOFs

    Indian Academy of Sciences (India)

    Synthesized hydrothermally in a 23-mL Teflon lined stainless steel bomb by heating copper(II) 2-pyrazinecarboxylate (31 mg, 0.1 mmol) and tin(II) iodide (75 mg, 0.2 mmol) in 4 mL water at 150±C for 24 h. The reaction vessel was subsequently cooled to 70±C at 1±C/min and held at that temperature for 6 h before returning ...

  20. Attenuation of N-nitrosodimethylamine induced hepatotoxicity by Operculina turpethum in Swiss Albino mice

    Science.gov (United States)

    Sharma, Veena; Singh, Manu

    2014-01-01

    Objective(s): To appraise the antihepatotoxic efficacy of ethanolic extract of Operculum turpethum root on the liver of Swiss albino mice. Materials and Methods: Hepatic fibrosis was induced in adult male albino mice through intraperitoneal administrations of N-nitrosodimethylamine (NDMA) at the concentration of 10 mg/kg body weight. The liver toxicity and therapeutic effect of the plant ethanolic extract was assessed by the analysis of liver marker enzymes and antioxidant enzymes and liver histopathological studies. Results: Hepatotoxicity was manifested by significantly decreased (PNDMA induced toxicity which was also supported by histopathological studies of the liver. Conclusion: O. turpethum manifested therapeutic effects by significantly restoring the enzymatic levels and reducing the hepatic damage in mice. This work intends to aid researchers in the study of natural products which could be useful in the treatment of liver diseases including cancer. PMID:24592311

  1. Effects of α-Melanocortin Enantiomers on Acetaminophen-Induced Hepatotoxicity in CBA Mice

    Directory of Open Access Journals (Sweden)

    Dražen Vikić-Topić

    2009-12-01

    Full Text Available Proteins and peptides in mammals are based exclusively on L-amino acids. Recent investigations show that D-amino acids exhibit physiological effects in vivo, despite of their very small quantities. We have investigated the hepatoprotective effects of the Land D-enantiomers of α-melanocortin peptide (α-MSH. The results showed that peptideenantiomerism is related to the protective effects of melanocortin peptides in vivo. L-α-MSH exhibited potent hepatoprotective effect in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice, while its D-mirror image was inefficient. Furthermore, the antibody to the L-peptide did not recognize the D-structure. The results indicate that the opposite peptide configuration may be used to modulate its function and metabolism in vivo and in vitro.

  2. Hepatotoxicity after liver irradiation in children and adolescents. Results from the RiSK

    Energy Technology Data Exchange (ETDEWEB)

    Roesler, Pascal; Christiansen, Hans [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); Kortmann, Rolf-Dieter [University of Leipzig, Department of Radiotherapy, Leipzig (Germany); Martini, Carmen [University Hospital of Freiburg, Department of Radiotherapy, Freiburg im Breisgau (Germany); Matuschek, Christiane [Heinrich-Heine University of Duesseldorf, Department of Radiotherapy, Medical Faculty, Duesseldorf (Germany); Meyer, Frank [Hospital Augsburg, Department of Radiotherapy, Augsburg (Germany); Ruebe, Christian [University Hospital of Homburg/Saar, Department of Radiotherapy, Homburg/Saar (Germany); Langer, Thorsten [University Hospital of Schleswig-Holstein, Department of Pediatrics, Pediatric Oncology, Campus Luebeck (Germany); Koch, Raphael [University of Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany); Eich, Hans Theodor; Willich, Normann [University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany); Steinmann, Diana [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany)

    2015-05-01

    The aim of this study was to evaluate acute and late radiotherapy-associated hepatotoxicity in consideration of dose-volume effects and liver function in childhood and adolescence. Since 2001, irradiated children and adolescents in Germany have been prospectively documented in the ''Register of Treatment-Associated Late Effects After Radiotherapy of Malignant Diseases in Childhood and Adolescence (RiSK)'' using standardized forms. Toxicity was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Until April 2012, 1,392 children and adolescents from 62 radiotherapy centers were recruited. In all, 216 patients underwent irradiation of the liver (median age 9 years, range 1-18 years, 70 patients with total-body irradiation, TBI). For 75 % of patients without TBI, information on acute toxicity of the liver was available: 24 patients had acute toxicity of grade 1-4 (grade 1, 2, and 4, in 20, 3, and 1 patient, respectively), including five patients receiving simultaneous hepatotoxic chemotherapy. Information on late toxicity was documented in 465 forms from 216 patients, with a median follow-up of 2 years. A maximum grade of toxicity of ≥ 0 occurred in 18 patients over time (with grade 1, 2, and 3 toxicity occurring in 15, 2, and 1 patient, respectively), including three patients (17 %) with TBI. One of them received simultaneous hepatotoxic chemotherapy. In multivariable analysis, volume-dose correlations showed no statistically noticeable effect on acute or chronic toxicity. Only low hepatotoxicity developed in children after irradiation of various abdominal and thoracic tumors. Due to the low radiation doses to the liver (median liver dose = 5 Gy) and the low toxicities that were consecutively observed, dose-volume curves for liver toxicity could not be established. These findings reflect the cautious attitude of radiation oncologists in terms of attributable liver doses in the treatment of the investigated tumor entities. It

  3. Supersonic copper clusters

    International Nuclear Information System (INIS)

    Powers, D.E.; Hansen, S.G.; Geusic, M.E.; Michalopoulos, D.L.; Smalley, R.E.

    1983-01-01

    Copper clusters ranging in size from 1 to 29 atoms have been prepared in a supersonic beam by laser vaporization of a rotating copper target rod within the throat of a pulsed supersonic nozzle using helium for the carrier gas. The clusters were cooled extensively in the supersonic expansion [T(translational) 1 to 4 K, T(rotational) = 4 K, T(vibrational) = 20 to 70 K]. These clusters were detected in the supersonic beam by laser photoionization with time-of-flight mass analysis. Using a number of fixed frequency outputs of an exciplex laser, the threshold behavior of the photoionization cross section was monitored as a function of cluster size.nce two-photon ionization (R2PI) with mass selective detection allowed the detection of five new electronic band systems in the region between 2690 and 3200 A, for each of the three naturally occurring isotopic forms of Cu 2 . In the process of scanning the R2PI spectrum of these new electronic states, the ionization potential of the copper dimer was determined to be 7.894 +- 0.015 eV

  4. Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Dan; Wu, Chun-qi [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Li, Ze-jun [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Guang Dong Pharmaceutical University, Guangzhou 510006 (China); Liu, Yue; Fan, Xing [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Wang, Quan-jun, E-mail: wangquanjunbeijing@163.com [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Ding, Ri-gao, E-mail: dingrigao@nic.bmi.ac.cn [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China)

    2015-04-15

    Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrial respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for hepatotoxicity.

  5. Hepatotoxicity associated with the dietary supplement OxyELITE Pro™ — Hawaii, 2013

    Science.gov (United States)

    Johnston, David I.; Chang, Arthur; Viray, Melissa; Chatham-Stephens, Kevin; He, Hua; Taylor, Ethel; Wong, Linda L.; Schier, Joshua; Martin, Colleen; Fabricant, Daniel; Salter, Monique; Lewis, Lauren; Park, Sarah Y.

    2015-01-01

    Dietary supplements are increasingly marketed to and consumed by the American public for a variety of purported health benefits. On 9 September 2013, the Hawaii Department of Health (HDOH) was notified of a cluster of acute hepatitis and fulminant hepatic failure among individuals with exposure to the dietary supplement OxyELITE Pro™ (OEP). HDOH conducted an outbreak investigation in collaboration with federal partners. Physicians were asked to report cases, defined as individuals with acute onset hepatitis of unknown etiology on or after 1 April 2013, a history of weight-loss/muscle-building dietary supplement use during the 60 days before illness onset, and residence in Hawaii during the period of exposure. Reported cases’ medical records were reviewed, questionnaires were administered, and a product investigation, including chemical analyses and trace back, was conducted. Of 76 reports, 44 (58%) met case definition; of these, 36 (82%) reported OEP exposure during the two months before illness. No other common supplements or exposures were observed. Within the OEP-exposed subset, two patients required liver transplantation, and a third patient died. Excessive product dosing was not reported. No unique lot numbers were identified; there were multiple mainland distribution points, and lot numbers common to cases in Hawaii were also identified in continental states. Product analysis found consumed products were consistent with labeled ingredients; the mechanism of hepatotoxicity was not identified. We report one of the largest statewide outbreaks of dietary supplement-associated hepatotoxicity. The implicated product was OEP. The increasing popularity of dietary supplements raises the potential for additional clusters of dietary supplement-related adverse events. PMID:26538199

  6. Hepatotoxicity associated with the dietary supplement OxyELITE Pro™ - Hawaii, 2013.

    Science.gov (United States)

    Johnston, David I; Chang, Arthur; Viray, Melissa; Chatham-Stephens, Kevin; He, Hua; Taylor, Ethel; Wong, Linda L; Schier, Joshua; Martin, Colleen; Fabricant, Daniel; Salter, Monique; Lewis, Lauren; Park, Sarah Y

    2016-01-01

    Dietary supplements are increasingly marketed to and consumed by the American public for a variety of purported health benefits. On 9 September 2013, the Hawaii Department of Health (HDOH) was notified of a cluster of acute hepatitis and fulminant hepatic failure among individuals with exposure to the dietary supplement OxyELITE Pro™ (OEP). HDOH conducted an outbreak investigation in collaboration with federal partners. Physicians were asked to report cases, defined as individuals with acute onset hepatitis of unknown etiology on or after 1 April 2013, a history of weight-loss/muscle-building dietary supplement use during the 60 days before illness onset, and residence in Hawaii during the period of exposure. Reported cases' medical records were reviewed, questionnaires were administered, and a product investigation, including chemical analyses and traceback, was conducted. Of 76 reports, 44 (58%) met case definition; of these, 36 (82%) reported OEP exposure during the two months before illness. No other common supplements or exposures were observed. Within the OEP-exposed subset, two patients required liver transplantation, and a third patient died. Excessive product dosing was not reported. No unique lot numbers were identified; there were multiple mainland distribution points, and lot numbers common to cases in Hawaii were also identified in continental states. Product analysis found consumed products were consistent with labeled ingredients; the mechanism of hepatotoxicity was not identified. We report one of the largest statewide outbreaks of dietary supplement-associated hepatotoxicity. The implicated product was OEP. The increasing popularity of dietary supplements raises the potential for additional clusters of dietary supplement-related adverse events. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Hepatotoxicity induced by horse ATG and reversed by rabbit ATG: a case report

    Directory of Open Access Journals (Sweden)

    Al-Anazi Khalid A

    2007-06-01

    Full Text Available Abstract Background The use of antilymphocyte agents has improved patient and graft survival in hematopoietic stem cell and solid organ transplantation but has been associated with the development of short-term toxicities as well as long-term complications. Case presentation We report a young female with Fanconi anemia who received antithymocyte globulin as part of the conditioning regimen prior to her planned allogeneic hematopoietic stem cell transplant at King Faisal Specialist Hospital and Research Centre in Riyadh. She developed sudden and severe hepatotoxicity after receiving the first dose of horse antithymocyte globulin, manifested by marked elevation of serum transaminases and mild elevation of serum bilirubin level. Immediately after withdrawal of the offending agent and shifting to the rabbit form of antithymocyte globulin, the gross liver dysfunction started to subside and the hepatic profile results returned to the pre-transplant levels few weeks later. The patient had her allogeneic hematopoietic stem cell transplant as planned without any further hepatic complications. After having a successful allograft, she was discharged from the stem cell transplant unit. During her follow up at the outpatient clinic, the patient remained very well and no major complication was encountered. Conclusion Hepatotoxicity related to the utilization of antithymocyte globulin varies considerably in severity and may be transient or long standing. There may be individual or population based susceptibilities to the development of side effects and these adverse reactions may also vary with the choice of the agent used. Encountering adverse effects with one type of antithymocyte agents should not discourage clinicians from shifting to another type in situations where continuation of the drug is vital.

  8. Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

    International Nuclear Information System (INIS)

    Hu, Dan; Wu, Chun-qi; Li, Ze-jun; Liu, Yue; Fan, Xing; Wang, Quan-jun; Ding, Ri-gao

    2015-01-01

    Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrial respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for hepatotoxicity

  9. Hepatotoxicity of kaurene glycosides from Xanthium strumarium L. fruits in mice.

    Science.gov (United States)

    Wang, Yang; Han, Ting; Xue, Li-Ming; Han, Ping; Zhang, Qiao-Yan; Huang, Bao-Kang; Zhang, Hong; Ming, Qian-Liang; Peng, Wei; Qin, Lu-Ping

    2011-06-01

    The fruit of Xanthium strumarium L. (Cang-Er-Zi) is a traditional Chinese medicine that is used in curing nasal diseases and headache according to the Chinese Pharmacopoeia. However, clinical utilization of Xanthium strumarium is relatively limited because of its toxicity. The present investigation was carried out to evaluate the toxic effects on acute liver injury in mice of the two kaurene glycosides (atractyloside and carbxyatractyloside), which are main toxic constituents isolated from Fructus Xanthii on acute liver injury in mice. Histopathological examinations revealed that there were not obviously visible injury in lungs, heart, spleen, and the central nervous system in the mice by intraperitoneal injection of atractyloside (ATR, at the doses 50,125 and 200 mg/kg) and carbxyatractyloside (CATR, at the doses 50,100 and 150 mg/kg) for 5 days. However, it revealed extensive liver injuries compared with the normal group. In the determination of enzyme levels in serum, intraperitoneal injection of ATR and CATR resulted in significantly elevated serum alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP) activities compared to controls. In the hepatic oxidative stress level, antioxidant-related enzyme activity assays showed that ATR and CATR administration significantly increased hepatic malondialdehyde (MDA) concentration, as well as decreased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) concentration, and this was in good agreement with the results of serum aminotransferase activity and histopathological examinations. Taken together, our results demonstrate that kaurene glycosides induce hepatotoxicity in mice by way of its induction of oxidative stress as lipid peroxidation in liver, which merited further studies. Therefore, these toxic constituents explain, at least in part, the hepatotoxicity of X. strumarium L. in traditional medicine.

  10. Diet Restriction Inhibits Apoptosis and HMGB1 Oxidation and Promotes Inflammatory Cell Recruitment during Acetaminophen Hepatotoxicity

    Science.gov (United States)

    Antoine, Daniel James; Williams, Dominic P; Kipar, Anja; Laverty, Hugh; Park, B Kevin

    2010-01-01

    Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves as a paradigm to elucidate mechanisms, predisposing factors and therapeutic interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity remain controversial. We investigated whether fasting of mice for 24 h can inhibit APAP-induced caspase activation and apoptosis through the depletion of basal ATP. We also investigated in fasted mice the critical role played by inhibition of caspase-dependent cysteine 106 oxidation within high mobility group box-1 protein (HMGB1) released by ATP depletion in dying cells as a mechanism of immune activation. In fed mice treated with APAP, necrosis was the dominant form of hepatocyte death. However, apoptosis was also observed, indicated by K18 cleavage, DNA laddering and procaspase-3 processing. In fasted mice treated with APAP, only necrosis was observed. Inflammatory cell recruitment as a consequence of hepatocyte death was observed only in fasted mice treated with APAP or fed mice cotreated with a caspase inhibitor. Hepatic inflammation was also associated with loss in detection of serum oxidized-HMGB1. A significant role of HMGB1 in the induction of inflammation was confirmed with an HMGB1-neutralizing antibody. The differential response between fasted and fed mice was a consequence of a significant reduction in basal hepatic ATP, which prevented caspase processing, rather than glutathione depletion or altered APAP metabolism. Thus, the inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from fasting promotes an inflammatory response during drug-induced hepatotoxicity/liver pathology. PMID:20811657

  11. Chloroform ingestion causing severe gastrointestinal injury, hepatotoxicity and dermatitis confirmed with plasma chloroform concentrations.

    Science.gov (United States)

    Jayaweera, Dushan; Islam, Shawkat; Gunja, Naren; Cowie, Chris; Broska, James; Poojara, Latesh; Roberts, Michael S; Isbister, Geoffrey K

    2017-02-01

    Poisoning due to chloroform ingestion is rare. The classic features of acute chloroform toxicity include central nervous system (CNS) and respiratory depression, and delayed hepatotoxicity. A 30-year-old female ingested 20-30 mL of 99% chloroform solution, which caused rapid loss of consciousness, transient hypotension and severe respiratory depression requiring endotracheal intubation and ventilation. She was alert by 12 h and extubated 16 h post-overdose. At 38-h post-ingestion, her liver function tests started to rise and she was commenced on intravenous acetylcysteine. Her alanine transaminase (1283 U/L), aspartate transaminase (734 U/L) and international normalized ratio (2.3) peaked 67- to 72-h post-ingestion. She also developed severe abdominal pain, vomiting and diarrhoea. An abdominal CT scan was consistent with severe enterocolitis, and an upper gastrointestinal endoscopy showed erosive oesophagitis, severe erosive gastritis and ulceration. She was treated with opioid analgesia, proton pump inhibitors, sucralfate and total parenteral nutrition. Secretions caused a contact dermatitis of her face and back. Nine days post-ingestion she was able to tolerate food. Her liver function tests normalized and the dermatitis resolved. Chloroform was measured using headspace gas chromatograph mass spectrometry, with a peak concentration of 2.00 μg/mL, 4 h 20 min post-ingestion. The concentration-time data fitted a 1-compartment model with elimination half-life 6.5 h. In addition to early CNS depression and delayed hepatotoxicity, we report severe gastrointestinal injury and dermatitis with chloroform ingestion. Recovery occurred with good supportive care, acetylcysteine and management of gastrointestinal complications.

  12. Deletion of circadian gene Per1 alleviates acute ethanol-induced hepatotoxicity in mice

    International Nuclear Information System (INIS)

    Wang, Tao; Yang, Ping; Zhan, Yibei; Xia, Lin; Hua, Zichun; Zhang, Jianfa

    2013-01-01

    The severity of ethanol-induced liver injury is associated with oxidative stress and lipid accumulation in the liver. Core circadian clock is known to mediate antioxidative enzyme activity and lipid metabolism. However, the link between circadian clock and ethanol-induced hepatotoxicity remains unclear. Here we showed that extents of acute ethanol-induced liver injury and steatosis in mice exhibit circadian variations consistent with hepatic expression of Period (Per) genes. Mice lacking clock gene Per1 displayed less susceptible to ethanol-induced liver injury, as evidenced by lower serum transaminase activity and less severe histopathological changes. Ethanol-induced lipid peroxidation was alleviated in Per1−/− mice. However, Per1 deletion had no effect on antioxidants depletion caused by ethanol administration. Ethanol-induced triglycerides (TG) accumulation in the serum and liver was significantly decreased in Per1−/− mice compared with that in wild-type (WT) mice. Analysis of gene expression in the liver revealed peroxisome proliferators activated receptor-gamma (PPARγ) and its target genes related to TG synthesis are remarkably down-regulated in Per1−/− mice. HepG2 cells were treated with ethanol at 150 mM for 3 days. Per1 overexpression augmented lipid accumulation after treatment with ethanol in HepG2 cells, but had no effect on ethanol-induced oxidative stress. Expression of genes related to lipogenesis, including PPARγ and its target genes, was up-regulated in cells overexpressing Per1. In conclusion, these results indicated that circadian rhythms of ethanol-induced hepatotoxicity are controlled by clock gene Per1, and deletion of Per1 protected mice from ethanol-induced liver injury by decreasing hepatic lipid accumulation

  13. Modulatory Effect of Methanol Extract of Piper guineense in CCl₄-Induced Hepatotoxicity in Male Rats.

    Science.gov (United States)

    Oyinloye, Babatunji Emmanuel; Osunsanmi, Foluso Oluwagbemiga; Ajiboye, Basiru Olaitan; Ojo, Oluwafemi Adeleke; Kappo, Abidemi Paul

    2017-08-24

    This study seeks to investigate the possible protective role of the methanol extract of Piper guineense seeds against CCl₄-induced hepatotoxicity in an animal model. Hepatotoxicity was induced by administering oral doses of CCl₄ (1.2 g/kg bw) three times a week for three weeks. Group 1 (Control) and Group 2 (CCl₄) were left untreated; Piper guineense (PG; 400 mg/kg bw) was administered to Group 3 (T₁) by oral gavage for 14 days prior to the administration of CCl₄ and simultaneously with CCl₄; PG (400 mg/kg bw) was administered simultaneously with CCl₄ in Group 4 (T₂); and Livolin forte (20 mg/kg bw) was administered simultaneously with CCl₄ in Group 5 (T₃), the standard drug group. The administration of CCl₄ induces histopathological alteration in the liver, with concomitant increased activities of serum hepatic marker enzymes associated with increased levels of lipid peroxidation. Similarly, there was decrease in non-enzymatic (reduced glutathione) and enzymatic antioxidants (glutathione S-transferase), superoxide dismutase, and catalase. An elevation in serum triglyceride and total cholesterol levels was noticed along with decreased levels of serum total protein. Treatment with PG 400 mg/kg bw exhibited excellent modulatory activity with respect to the different parameters studied by reversing all the above-mentioned biochemical changes significantly in the experimental animals. These results suggest that PG offered protection comparable to that of Livolin forte with better efficacy when pre-treated with 400 mg/kg bw 14 days prior to CCl₄-exposure.

  14. Role of ascorbic acid supplement in reducing oxidative stress and hepatotoxicity in lead intoxication

    International Nuclear Information System (INIS)

    Farooq, Y.; Hussain, M.M.; Aleem, S.B.

    2013-01-01

    Objective: The present study was conducted to measure the oxidative stress and hepatotoxicity in lead intoxicated sprague dawley rats with and without supplementation of ascorbic acid. Study Design: Randomized Control Trial. Place of Study: Physiology Department, Army Medical College, Rawalpindi. (From Oct 2007 to Sep 2008) Material and Methods: One hundred and five male rats (age, 90-120 days; weight 200 - 250 gm) were divided into three groups each having 35 rats. Rats of group 1 and group 2 were given weekly injections of sodium acetate (10 mg /kg body weight) and lead acetate (10 mg /kg body weight) respectively, whereas rats of group 3 were administered lead acetate(10 mg /kg body weight) through weekly injections and ascorbic acid in drinking water (500 mg/l). After 6 weeks, 4 ml of blood was drawn from each rat by cardiac puncture. The blood was allowed to clot and serum was separated for estimation of serum malondialdehyde (MDA) levels on spectrophotometer; and serum alanine aminotransferase (ALT) levels and aspartate aminotransferase (AST) levels on Merck Micorlab 200. Results: Lead intoxication of rats revealed that serum MDA levels were raised to 7.8 +- 0.48 micro mol/l (control, 3.2 +-0.39 micro mol/l), ALT levels to 76.26 +- 5.88 IU/l (control, 44.1 +- 3.26) and AST levels to 258.06 +- 13.30 IU/l (control, 156.2 +- 4.97). Ascorbic acid supplementation significantly lowered serum MDA levels (3.8 +- 0.34 micro mol/l), ALT levels (52.26 +-4.57 IU/l) and AST levels (188.13 +- 12.91 IU/l). Conclusion: Ascorbic acid supplementation ameliorates lead intoxication probably by reducing the oxidative stress, thus preventing the development of hepatotoxicity, but this amelioration is not equal to the control. (author)

  15. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  16. Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity.

    Science.gov (United States)

    Spruiell, Krisstonia; Gyamfi, Afua A; Yeyeodu, Susan T; Richardson, Ricardo M; Gonzalez, Frank J; Gyamfi, Maxwell A

    2015-09-01

    Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor α, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. U.S. Government work not protected by U.S. copyright.

  17. Hospitalized pediatric antituberculosis drug induced hepatotoxicity: Experience of an Indonesian referral hospital

    Directory of Open Access Journals (Sweden)

    Heda Melinda Nataprawira

    2017-05-01

    Full Text Available Objective: To determine the characteristics and risk factors of pediatric antituberculosis drug induced hepatotoxicity (ADIH in Dr. Hasan Sadikin Hospital, a referral hospital in West Java, Indonesia. Methods: Medical records of hospitalized pediatric ADIH from October 2010 to October 2015 were reviewed retrospectively through computer-based search. Descriptive data were presented as percentage. Analytical case-control study on characteristics of ADIH was conducted using Chi-square and Mann Whitney test. Results: Fifty (3.5% out of 1 424 pediatric TB patients developed ADIH; 20 (40% were boys and 30 (60% girls. More than half were under 5 years old and 33 (66% were malnourished. ADIH occured in 29 (58% cases treated for pulmonary TB, 15 (30% for extrapulmonary TB and 6 (12% for both; 34 cases (68% occured during the intensive phase. We identified hepatic comorbidities including CMV infection [1 (2%] and typhoid [1 (2%], and other diseases treated by hepatotoxic drugs such as chemotherapeutic drugs, antiepileptics, and antiretroviral drugs [9 (18%]. Case-control analysis of 50 ADIH cases and 100 TB controls without ADIH showed that the correlation between gender, age, type of TB, nutritional status and comorbidities to occurence of ADIH was statistically insignificant (P = 0.26, 0.765, 0.495, 0.534 9 and 0.336, respectively. Pediatric ADIH was treated using modified British Thoracic Society guidelines. Conclusions: Pediatric ADIH in our hospital is quite frequent, thus identifying risk factors and development of pediatric guideline is mandatory. Further study is needed to identify other risk factors such as genetic acetylator status.

  18. Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Romi [Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Calcutta 700 019 (India); Saha, Indraneel [Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Calcutta 700 019 (India); Pal, Suman [Microbiology Laboratory, Bose Institute, Kankurgachi, Calcutta 700 054 (India); Bhattacharyya, Arindam [Microbiology Laboratory, Bose Institute, Kankurgachi, Calcutta 700 054 (India); Sa, Gaurisankar [Microbiology Laboratory, Bose Institute, Kankurgachi, Calcutta 700 054 (India); Nag, Tapas C [Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110 020 (India); Das, Tania [Microbiology Laboratory, Bose Institute, Kankurgachi, Calcutta 700 054 (India); Maiti, B R [Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Calcutta 700 019 (India)

    2006-10-03

    Background: There are about 600 million betel quid chewers in the world. Betal quid chewing is one of the major risk factors of hepatocarcinoma, oropharyngeal and esophagus cancers. Arecoline, the main Areca alkaloid of the betel nut is reported to have cytotoxic, genotoxic and mutagenic effects in various cells. It shows strong correlation to the incidence of oral submucosal fibrosis, leukoplakia and oral cancer, and has also been found to impose toxic manifestations in immune, hepatic and other defense systems of the recipient. Aim: The precise molecular mechanisms underlying the toxic effects of arecoline deserve investigation. To clarify the action of arecoline on defense systems, immune, hepatic and detoxification system were studied in mice. Method: Cell count and cell cycle of the splenocytes were studied for evaluating cell immunity. Liver function test (LFT) was followed by assaying different enzyme systems from serum (SGPT, SGOT and ALP) and liver (GST for detoxication enzyme, SOD and catalase for antioxidant enzymes and GSH for non-enzymatic antioxidant) and by ultrastructural studies of hepatocytes. Results: Here we report that arecoline arrested splenic lymphocyte cell cycle at lower concentration with induced apoptosis at higher concentration thereby causing immunosuppression in arecoline recipients. Besides, it resulted in hepatotoxicity in arecoline recipient mice by disrupting the hepatocyte ultrastructure, as judged by liver ultrastructural studies that showed decreased nuclear size, RER with profusely inflated cysternae and abundance of lipid droplets, and by up regulating hepatotoxic marker enzymes (SGOT and SGPT) in serum. Arecoline also caused depression of antioxidants, i.e., superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione-S-transferase (GST) that are known to neutralize reactive oxygen species. Conclusion: All these above-mentioned results led us to conclude that arecoline attacks multiple targets to finally

  19. Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice

    International Nuclear Information System (INIS)

    Dasgupta, Romi; Saha, Indraneel; Pal, Suman; Bhattacharyya, Arindam; Sa, Gaurisankar; Nag, Tapas C.; Das, Tania; Maiti, B.R.

    2006-01-01

    Background: There are about 600 million betel quid chewers in the world. Betal quid chewing is one of the major risk factors of hepatocarcinoma, oropharyngeal and esophagus cancers. Arecoline, the main Areca alkaloid of the betel nut is reported to have cytotoxic, genotoxic and mutagenic effects in various cells. It shows strong correlation to the incidence of oral submucosal fibrosis, leukoplakia and oral cancer, and has also been found to impose toxic manifestations in immune, hepatic and other defense systems of the recipient. Aim: The precise molecular mechanisms underlying the toxic effects of arecoline deserve investigation. To clarify the action of arecoline on defense systems, immune, hepatic and detoxification system were studied in mice. Method: Cell count and cell cycle of the splenocytes were studied for evaluating cell immunity. Liver function test (LFT) was followed by assaying different enzyme systems from serum (SGPT, SGOT and ALP) and liver (GST for detoxication enzyme, SOD and catalase for antioxidant enzymes and GSH for non-enzymatic antioxidant) and by ultrastructural studies of hepatocytes. Results: Here we report that arecoline arrested splenic lymphocyte cell cycle at lower concentration with induced apoptosis at higher concentration thereby causing immunosuppression in arecoline recipients. Besides, it resulted in hepatotoxicity in arecoline recipient mice by disrupting the hepatocyte ultrastructure, as judged by liver ultrastructural studies that showed decreased nuclear size, RER with profusely inflated cysternae and abundance of lipid droplets, and by up regulating hepatotoxic marker enzymes (SGOT and SGPT) in serum. Arecoline also caused depression of antioxidants, i.e., superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione-S-transferase (GST) that are known to neutralize reactive oxygen species. Conclusion: All these above-mentioned results led us to conclude that arecoline attacks multiple targets to finally

  20. Deltamethrin-Induced Hepatotoxicity and Virgin Olive Oil Consumption: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Ali Reza Khalatbary

    2017-11-01

    Full Text Available Background: Deltamethrin (DM is a synthetic pyrethroid insecticide which can lead to pathological effects in mammals through oxidative stress. On the other hand, virgin olive oil (VOO is a rich source of phenolic compounds with antioxidants. The aim of the present study was to determine the protective effects of VOO against DM-induced hepatotoxicity. Methods: Thirty-six mice were randomly separated into 4 groups: vehicle group, VOO group, DM group, and DM plus VOO group. Immunohistochemistry of PARP, COX-2, and caspase-3 with the biochemical analysis of malondialdehyde and total antioxidant capacity levels were performed in the liver samples 5 weeks after gavaging. Statistical analysis was performed using SPSS, version 15. The data were compared between the groups using the Tukey multiple comparison tests and the analysis of the variance. A P value <0.05 was considered significant. Results: The malondialdehyde level in the liver was increased in the DM group (71.18±0.01, whereas it was significantly (P=0.001 decreased after VOO administration in the DM plus VOO group (39.59±2.43. While the total antioxidant capacity level in the liver was decreased in the DM group (3.05±0.05, it was significantly increased (P=0.03 after VOO administration in the DM plus VOO group (3.95±0.04. A greater expression of caspase-3 (P=0.008, COX-2 (P =0.004, and PARP (P 0.006 could be detected in the DM group, while it was significantly (P=0.009 attenuated in the DM plus VOO group. Also, the degeneration of hepatocytes, which was detected in the DM group, was attenuated after VOO consumption. Conclusions: VOO exerted protective effects against DM-induced hepatotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and antioxidative properties.

  1. Deltamethrin-Induced Hepatotoxicity and Virgin Olive Oil Consumption: An Experimental Study.

    Science.gov (United States)

    Khalatbary, Ali Reza; Ghabaee, Davood Nasiry Zarrin; Ahmadvand, Hassan; Amiri, Fereshteh Talebpour; Lehi, Somaieh Tadayoni

    2017-11-01

    Deltamethrin (DM) is a synthetic pyrethroid insecticide which can lead to pathological effects in mammals through oxidative stress. On the other hand, virgin olive oil (VOO) is a rich source of phenolic compounds with antioxidants. The aim of the present study was to determine the protective effects of VOO against DM-induced hepatotoxicity. Thirty-six mice were randomly separated into 4 groups: vehicle group, VOO group, DM group, and DM plus VOO group. Immunohistochemistry of PARP, COX-2, and caspase-3 with the biochemical analysis of malondialdehyde and total antioxidant capacity levels were performed in the liver samples 5 weeks after gavaging. Statistical analysis was performed using SPSS, version 15. The data were compared between the groups using the Tukey multiple comparison tests and the analysis of the variance. A P value group (71.18±0.01), whereas it was significantly (P=0.001) decreased after VOO administration in the DM plus VOO group (39.59±2.43). While the total antioxidant capacity level in the liver was decreased in the DM group (3.05±0.05), it was significantly increased (P=0.03) after VOO administration in the DM plus VOO group (3.95±0.04). A greater expression of caspase-3 (P=0.008), COX-2 (P =0.004), and PARP (P 0.006) could be detected in the DM group, while it was significantly (P=0.009) attenuated in the DM plus VOO group. Also, the degeneration of hepatocytes, which was detected in the DM group, was attenuated after VOO consumption. VOO exerted protective effects against DM-induced hepatotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and antioxidative properties.

  2. Native copper as a natural analogue for copper canisters

    International Nuclear Information System (INIS)

    Marcos, N.

    1989-12-01

    This paper discusses the occurrence of native copper as found in geological formations as a stability analogue of copper canisters that are planned to be used for the disposal of spent nuclear fuel in the Finnish bedrock. A summary of several publications on native copper occurrences is presented. The present geochemical and geohydrological conditions in which copper is met with in its metallic state show that metallic copper is stable in a wide range of temperatures. At low temperatures native copper is found to be stable where groundwater has moderate pH (about 7), low Eh (< +100 mV), and low total dissolved solids, especially chloride. Microscopical and microanalytical studies were carried out on a dozen of rock samples containing native copper. The results reveal that the metal shows no significant alteration. Only the surface of copper grains is locally coated. In the oldest samples there exist small corrosion cracks; the age of the oldest samples is over 1,000 million years. A review of several Finnish groundwater studies suggests that there are places in Finland where the geohydrological conditions are favourable for native copper stability. (orig.)

  3. Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro Zone, South Ethiopia: A cohort study

    Directory of Open Access Journals (Sweden)

    Wondwossen Abera

    2016-01-01

    Conclusion: The incidence of anti-TB-DIH in Dawro Zone was high. The drug responsible for the hepatotoxicity was not known. However, chronic high alcohol intake was associated with the development of anti-TB-DIH.

  4. LIGNOCELLULOSE NANOCOMPOSITE CONTAINING COPPER SULFIDE

    OpenAIRE

    Sanchi Nenkova; Peter Velev; Mirela Dragnevska; Diyana Nikolova; Kiril Dimitrov

    2011-01-01

    Copper sulfide-containing lignocellulose nanocomposites with improved electroconductivity were obtained. Two methods for preparing the copper sulfide lignocellulose nanocomposites were developed. An optimization of the parameters for obtaining of the nanocomposites with respect to obtaining improved electroconductivity, economy, and lower quantities and concentration of copper and sulfur ions in waste waters was conducted. The mechanisms and schemes of delaying and subsequent connection of co...

  5. Copper tolerance in Becium homblei

    Energy Technology Data Exchange (ETDEWEB)

    Reilly, C; Stone, J

    1971-04-09

    Analyses show that Becium homblei has apparently no mechanism for limiting copper uptake. As growth proceeds, the concentration of metal increases in leaves and stems. Much of the copper is bound to structural material of the cells. There is a significant difference between the amount of extractable material in root and leaf tissues. These differences, in conjunction with the extrinsic factor of regular bush fires, were important factors in the evolution of this copper-resistant species of Becium. 9 references.

  6. Mechanical synthesis of copper-carbon nanocomposites: Structural changes, strengthening and thermal stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Nunes, D., E-mail: daniela.nunes@ist.utl.pt [Associacao Euratom/IST, Instituto de Plasmas e Fusao Nuclear - Laboratorio Associado, Instituto Superior Tecnico, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); LNEG, Estrada do Paco do Lumiar, 1649-038 Lisboa (Portugal); ICEMS, Instituto Superior Tecnico, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Livramento, V. [Associacao Euratom/IST, Instituto de Plasmas e Fusao Nuclear - Laboratorio Associado, Instituto Superior Tecnico, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); LNEG, Estrada do Paco do Lumiar, 1649-038 Lisboa (Portugal); Mateus, R. [Associacao Euratom/IST, Instituto de Plasmas e Fusao Nuclear - Laboratorio Associado, Instituto Superior Tecnico, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Correia, J.B. [LNEG, Estrada do Paco do Lumiar, 1649-038 Lisboa (Portugal); Alves, L.C. [ITN, Instituto Tecnologico e Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Vilarigues, M. [Departamento de Conservacao e Restauro e R and D Unit Vidro e da Ceramica Para as Artes, FCT-UNL, Quinta da Torre, 2829-516 Caparica (Portugal); Carvalho, P.A. [ICEMS, Instituto Superior Tecnico, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Departamento de Bioengenharia, Instituto Superior Tecnico, Av. Rovisco Pais, 1049-001 Lisboa (Portugal)

    2011-11-15

    Highlights: {yields} The study characterized Cu-nanodiamond (Cu-nD) and Cu-graphite (Cu-G) composites. {yields} Preservation of nD crystalline structure during high-energy milling was demonstrated. {yields} Higher refinement of matrix in Cu-nD comparing to Cu-G is due to a milling mechanism. {yields} Remarkable thermal stability and microhardness have been achieved in Cu-nD and Cu-G. {yields} Strengthening resulted mainly from grain refinement and second-phase reinforcement. - Abstract: Processing of copper-carbon nanocomposites by mechanical synthesis poses specific challenges as carbon phases are prone to amorphization and exhibit an intrinsically difficult bonding with copper. The present work investigates Cu-nanodiamond (Cu-nD) and Cu-graphite (Cu-G) composites produced by mechanical synthesis and subsequent heat treatments. Transmission electron microscopy observations showed homogeneous particle distributions and intimate bonding between the metallic matrix and the carbon phases. Ring diffraction patterns of chemically extracted carbon phases demonstrated that milled nanodiamond preserved crystallinity, while an essentially amorphous nature could be inferred for milled graphite. Raman spectra confirmed that nanodiamond particles remained essentially unaffected by the mechanical synthesis, whereas the bands of milled graphite were significantly changed into the typical amorphous carbon fingerprint. Particle-induced X-ray emission spectroscopy showed that the total contamination originating from the milling media remained below 0.7 wt.%. The Cu-nanodiamond composite exhibited remarkable microhardness and microstructural thermal stability when compared with pure nanostructured copper.

  7. Mechanical synthesis of copper-carbon nanocomposites: Structural changes, strengthening and thermal stabilization

    International Nuclear Information System (INIS)

    Nunes, D.; Livramento, V.; Mateus, R.; Correia, J.B.; Alves, L.C.; Vilarigues, M.; Carvalho, P.A.

    2011-01-01

    Highlights: → The study characterized Cu-nanodiamond (Cu-nD) and Cu-graphite (Cu-G) composites. → Preservation of nD crystalline structure during high-energy milling was demonstrated. → Higher refinement of matrix in Cu-nD comparing to Cu-G is due to a milling mechanism. → Remarkable thermal stability and microhardness have been achieved in Cu-nD and Cu-G. → Strengthening resulted mainly from grain refinement and second-phase reinforcement. - Abstract: Processing of copper-carbon nanocomposites by mechanical synthesis poses specific challenges as carbon phases are prone to amorphization and exhibit an intrinsically difficult bonding with copper. The present work investigates Cu-nanodiamond (Cu-nD) and Cu-graphite (Cu-G) composites produced by mechanical synthesis and subsequent heat treatments. Transmission electron microscopy observations showed homogeneous particle distributions and intimate bonding between the metallic matrix and the carbon phases. Ring diffraction patterns of chemically extracted carbon phases demonstrated that milled nanodiamond preserved crystallinity, while an essentially amorphous nature could be inferred for milled graphite. Raman spectra confirmed that nanodiamond particles remained essentially unaffected by the mechanical synthesis, whereas the bands of milled graphite were significantly changed into the typical amorphous carbon fingerprint. Particle-induced X-ray emission spectroscopy showed that the total contamination originating from the milling media remained below 0.7 wt.%. The Cu-nanodiamond composite exhibited remarkable microhardness and microstructural thermal stability when compared with pure nanostructured copper.

  8. Copper toxicity in housed lambs

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, A H; Valks, D A; Appleton, M A; Shaw, W B

    1969-09-27

    Copper toxicity among 170 lambs artificially reared indoors at High Mowthorpe NAAS Experimental Husbandry Farm is reported. Although only three lambs were lost it is not unreasonable to suggest that the liver copper levels of the lambs which were slaughtered would have been high and losses could have been much heavier had there been any further copper supplementation. Even a copper level of 20 ppm in lamb concentrates given to lambs reared artificially indoors is dangerous, and intakes of much less than 38 mg per lamb per day can be fatal if given of a prolonged period. 5 references, 1 table.

  9. Copper and copper-nickel-alloys - An overview

    Energy Technology Data Exchange (ETDEWEB)

    Klassert, Anton; Tikana, Ladji [Deutsches Kupferinstitut e.V. Am Bonneshof 5, 40474 Duesseldorf (Germany)

    2004-07-01

    With the increasing level of industrialization the demand for and the number of copper alloys rose in an uninterrupted way. Today, the copper alloys take an important position amongst metallic materials due to the large variety of their technological properties and applications. Nowadays there exist over 3.000 standardized alloys. Copper takes the third place of all metals with a worldwide consumption of over 15 millions tons per year, following only to steel and aluminum. In a modern industrial society we meet copper in all ranges of the life (electro-technology, building and construction industry, mechanical engineering, automotive, chemistry, offshore, marine engineering, medical applications and others.). Copper is the first metal customized by humanity. Its name is attributed to the island Cyprus, which supplied in the antiquity copper to Greece, Rome and the other Mediterranean countries. The Romans called it 'ore from Cyprus' (aes cyprium), later cuprum. Copper deposited occasionally also dapper and could be processed in the recent stone age simply by hammering. Already in early historical time copper alloys with 20 to 50 percent tin was used for the production of mirrors because of their high reflecting power. Although the elementary nickel is an element discovered only recently from a historical perspective, its application in alloys - without any knowledge of the alloy composition - occurred at least throughout the last 2.000 years. The oldest copper-nickel coin originates from the time around 235 B.C.. Only around 1800 AD nickel was isolated as a metallic element. In particular in the sea and offshore technology copper nickel alloys found a broad field of applications in piping systems and for valves and armatures. The excellent combination of characteristics like corrosion resistance, erosion stability and bio-fouling resistance with excellent mechanical strength are at the basis of this success. An experience of many decades supports the use

  10. Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

    International Nuclear Information System (INIS)

    Cosgrove, Benjamin D.; King, Bracken M.; Hasan, Maya A.; Alexopoulos, Leonidas G.; Farazi, Paraskevi A.; Hendriks, Bart S.; Griffith, Linda G.; Sorger, Peter K.; Tidor, Bruce; Xu, Jinghai J.

    2009-01-01

    Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFNγ, IL-1α, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1α, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.

  11. Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Youssef Dgachi

    2016-05-01

    Full Text Available We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 ± 0.03 μM, good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line.

  12. Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro Zone, South Ethiopia: A cohort study

    OpenAIRE

    Wondwossen Abera,; Waqtola Cheneke,; Gemeda Abebe,

    2016-01-01

    Background: Antituberculosis drugs cause hepatotoxicity in some individuals leading to acute liver failure, which results in death. Such phenomena limit the clinical use of drugs, contributing to treatment failure that possibly causes drug resistance. Furthermore, associated risk factors for the development of antituberculosis-drug-induced hepatotoxicity (anti-TB-DIH) are found to be controversial among different study findings. Methods: A prospective cohort study was conducted from May 20...

  13. Spectrographic determination of impurities in copper and copper oxide

    International Nuclear Information System (INIS)

    Sabato, S.F.; Lordello, A.R.

    1990-11-01

    An emission spectrographic method for the determination of Al, Bi, Ca, Cd, Cr, Fe, Ge, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn and Zn in copper and copper oxide is described. Two mixtures (Graphite and ZnO: graphite and GeO sub(2)) were used as buffers. The standard deviation lies around 10%. (author)

  14. Nickel, copper and cobalt coalescence in copper cliff converter slag

    Directory of Open Access Journals (Sweden)

    Wolf A.

    2016-01-01

    Full Text Available The aim of this investigation is to assess the effect of various additives on coalescence of nickel, copper and cobalt from slags generated during nickel extraction. The analyzed fluxes were silica and lime while examined reductants were pig iron, ferrosilicon and copper-silicon compound. Slag was settled at the different holding temperatures for various times in conditions that simulated the industrial environment. The newly formed matte and slag were characterized by their chemical composition and morphology. Silica flux generated higher partition coefficients for nickel and copper than the addition of lime. Additives used as reducing agents had higher valuable metal recovery rates and corresponding partition coefficients than fluxes. Microstructural studies showed that slag formed after adding reductants consisted of primarily fayalite, with some minute traces of magnetite as the secondary phase. Addition of 5 wt% of pig iron, ferrosilicon and copper-silicon alloys favored the formation of a metallized matte which increased Cu, Ni and Co recoveries. Addition of copper-silicon alloys with low silicon content was efficient in copper recovery but coalescence of the other metals was low. Slag treated with the ferrosilicon facilitated the highest cobalt recovery while copper-silicon alloys with silicon content above 10 wt% resulted in high coalescence of nickel and copper, 87 % and 72 % respectively.

  15. Role of copper, zinc, and selenium in uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sarita, P.; Naga Raju, G.J. [Department of Physics, Institute of Technology, GITAM University, Visakhapatnam (India); Bhuloka Reddy, S. [Swami Jnanananda Laboratories for Nuclear Research, Andhra Universily, Visakahpatnam (India)

    2013-07-01

    Full text: The objective of this study was to evaluate the levels of trace elements in blood sera of uterine cervix cancer patients, analyze their alteration with respect to healthy controls, ascertain the role played by them in the initiation, promotion and inhibition of cancer, and identify the best predictors amongst these for disease occurrence and progression. Moreover, the variation of trace elemental content in the sera of cervix cancer patients with the clinical stage of disease and with therapy was also studied. Particle induced X-ray emission (PIXE), a well established method for elemental analysis, was used in this work to identify and quantify trace elements in the blood sera of uterine cervix cancer subjects and healthy control subjects. The PIXE measurements were carried out using 2.5 MeV collimated proton beam from the 3 MV Tandem Pelletron Accelerator at lon Beam Laboratory, Institute of Physics, Bhubaneswar, India. Among all the trace elements identified in this work, statistically significant alterations in serum levels of copper, zinc, and selenium were observed among the various studied groups. The observed alterations are discussed with respect to the possible mechanisms by which these elements might influence the carcinogenic process. (author)

  16. Role of copper, zinc, and selenium in uterine cervical cancer

    International Nuclear Information System (INIS)

    Sarita, P.; Naga Raju, G.J.; Bhuloka Reddy, S.

    2013-01-01

    Full text: The objective of this study was to evaluate the levels of trace elements in blood sera of uterine cervix cancer patients, analyze their alteration with respect to healthy controls, ascertain the role played by them in the initiation, promotion and inhibition of cancer, and identify the best predictors amongst these for disease occurrence and progression. Moreover, the variation of trace elemental content in the sera of cervix cancer patients with the clinical stage of disease and with therapy was also studied. Particle induced X-ray emission (PIXE), a well established method for elemental analysis, was used in this work to identify and quantify trace elements in the blood sera of uterine cervix cancer subjects and healthy control subjects. The PIXE measurements were carried out using 2.5 MeV collimated proton beam from the 3 MV Tandem Pelletron Accelerator at lon Beam Laboratory, Institute of Physics, Bhubaneswar, India. Among all the trace elements identified in this work, statistically significant alterations in serum levels of copper, zinc, and selenium were observed among the various studied groups. The observed alterations are discussed with respect to the possible mechanisms by which these elements might influence the carcinogenic process. (author)

  17. Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, and Antioxidant Agents for Alzheimer′s Disease Therapy

    Directory of Open Access Journals (Sweden)

    Houssem Boulebd

    2016-03-01

    Full Text Available Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-ylethan-1-one (4 is non-hepatotoxic (cell viability assay on HepG2 cells, a selective but moderately potent EeAChE inhibitor (IC50 = 38.7 ± 1.7 μM, and a very potent antioxidant agent on the basis of the ORAC test (2.31 ± 0.29 μmol·Trolox/μmol compound.

  18. Gene expression profiling in the liver of CD-1 mice to characterize the hepatotoxicity of triazole fungicides

    International Nuclear Information System (INIS)

    Goetz, Amber K.; Bao, Wenjun; Ren, Hongzu; Schmid, Judith E.; Tully, Douglas B.; Wood, Carmen; Rockett, John C.; Narotsky, Michael G.; Sun, Guobin; Lambert, Guy R.; Thai, S.-F.; Wolf, Douglas C.; Nesnow, Stephen; Dix, David J.

    2006-01-01

    Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and hypotheses on potential mechanisms of action for this class of chemicals. Adult male CD-1 mice were exposed daily for 14 days to fluconazole, myclobutanil, propiconazole, or triadimefon at three dose levels by oral gavage. Doses were based on previous studies that resulted in liver hypertrophy or hepatotoxicity. All four triazoles caused hepatocyte hypertrophy, and all except triadimefon increased relative liver/body weight ratios at the middle and high dose levels. CYP enzyme activities were also induced by all four triazoles at the middle and high doses as measured by the dealkylations of four alkoxyresorufins, although some differences in substrate specificity were observed. Consistent with this common histopathology and biochemistry, several CYP and xenobiotic metabolizing enzyme (XME) genes were differentially expressed in response to all four (Cyp2d26 and Cyp3a11), or three of the four (Cyp2c40, Cyp2c55, Ces2, Slco1a4) triazoles. Differential expression of numerous other CYP and XME genes discriminated between the various triazoles, consistent with differences in CYP enzyme activities, and indicative of possible differences in mechanisms of hepatotoxicity or dose response. Multiple isoforms of Cyp1a, 2b, 2c, 3a, and other CYP and XME genes regulated by the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) were differentially expressed following triazole exposure. Based on these results, we expanded on our original hypothesis that triazole hepatotoxicity was mediated by CYP induction, to include additional XME genes, many of which are modulated by CAR and PXR

  19. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

    Directory of Open Access Journals (Sweden)

    Alan T Clarke

    Full Text Available Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.

  20. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort

    Science.gov (United States)

    Clarke, Alan T.; Johnson, Paul C. D.; Hall, Gillian C.; Ford, Ian; Mills, Peter R.

    2016-01-01

    Background & Aims Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small. PMID:26983033

  1. Risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/AIDS-coinfected patients under tuberculosis treatment.

    Science.gov (United States)

    Ngouleun, Williams; Biapa Nya, Prosper Cabral; Pieme, Anatole Constant; Telefo, Phelix Bruno

    2016-12-01

    Tuberculosis (TB) is a worldwide public health problem. It is a contagious and grave disease caused by Mycobacterium tuberculosis. Current drugs such as isoniazid, pyrazinamide, and rifampicin used for the treatment of tuberculosis are potentially hepatotoxic and can lead to drug hepatitis. In order to improve the follow-up of TB patients in Cameroon, we carried out a study which aimed to evaluate the hepatotoxicity risk factors associated with anti-TB drugs. The studies were performed on 75 participants who had visited the Loum District Hospital located in the littoral region of Cameroon for their routine consultation. Participants have been selected based on pre-established criteria of inclusion and exclusion. Prior to the informed consent signature, patients were given compelling information about the objective and the result output of the study. They were questioned about antioxidant food and alcohol consumption as well as some clinical signs of hepatotoxicity such as fever, nausea, vomiting, and tiredness. The collected blood was tested for the determination of biochemical markers (transaminases and C-reactive protein) using standard spectrophotometric methods. Biochemical analysis of samples showed a significant increase (pfactors, antioxidant food consumption significantly reduced the liver injury patient percentage for the above parameters, whereas an opposite situation was observed with alcohol consumption between TB-coinfection and TB patients. Regarding the C-reactive protein results, the percentage of positive tests was very high among coinfected patients (40%) compared with the control (15%). The interactions between parameters related to alcohol consumption and intake of antioxidant foods showed a slight decrease in activity compared with interactions without food. The results showed that human immunodeficiency virus status and alcohol consumption constitutes aggravating factors for the occurrence of hepatic toxicity. In addition, the consumption of

  2. Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPARα with clofibrate

    International Nuclear Information System (INIS)

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

    2008-01-01

    The objective was to investigate if the hepatotoxic sensitivity in nonalcoholic steatohepatitic mice to acetaminophen (APAP) is due to downregulation of nuclear receptor PPARα via lower cell division and tissue repair. Male Swiss Webster mice fed methionine and choline deficient diet for 31 days exhibited NASH. On the 32nd day, a marginally toxic dose of APAP (360 mg/kg, ip) yielded 70% mortality in steatohepatitic mice, while all non steatohepatitic mice receiving the same dose survived. 14 C-APAP covalent binding, CYP2E1 protein, and enzyme activity did not differ from the controls, obviating increased APAP bioactivation as the cause of amplified APAP hepatotoxicity. Liver injury progressed only in steatohepatitic livers between 6 and 24 h. Cell division and tissue repair assessed by 3 H-thymidine incorporation and PCNA were inhibited only in the steatohepatitic mice given APAP suggesting that higher sensitivity of NASH liver to APAP-induced hepatotoxicity was due to lower tissue repair. The hypothesis that impeded liver tissue repair in steatohepatitic mice was due to downregulation of PPARα was tested. PPARα was downregulated in NASH. To investigate whether downregulation of PPARα in NASH is the critical mechanism of compromised liver tissue repair, PPARα was induced in steatohepatitic mice with clofibrate (250 mg/kg for 3 days, ip) before injecting APAP. All clofibrate pretreated steatohepatitic mice receiving APAP exhibited lower liver injury, which did not progress and the mice survived. The protection was not due to lower bioactivation of APAP but due to higher liver tissue repair. These findings suggest that inadequate PPARα expression in steatohepatitic mice sensitizes them to APAP hepatotoxicity

  3. Hepatoprotective and Antioxidant activity of Scoparia dulcis Linn, against N Nitrosodiethylamine (DEN) induced Hepatotoxicity in experimental Rats

    OpenAIRE

    Langeswaran K; Jagadeesan A. J; Vijayaprakash S; Balasubramanian M. P

    2012-01-01

    Scoparia dulcis Linn, belongs to the family Scrophulariaceae and have speculated Medicinal properties. In this present investigation, the antioxidant and hepatoprotective activity of the aqueous extracts of Scoparia dulcis was evaluated against N-nitrosodiethylamine (DEN) induced liver cirrhosis in experimental rats. In group III hepatotoxicity induced animals, an oral dose of 500 mg/kg, of the aqueous extracts of Scoparia dulcis exhibited a significant (P

  4. Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic reactive nitrogen formation in mice and in freshly isolated hepatocytes

    Directory of Open Access Journals (Sweden)

    Sudip Banerjee

    Full Text Available The hepatotoxicity of acetaminophen (APAP occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1 inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction. In this work we examined the effect of trifluoperazine (TFP, a calmodulin antagonist that inhibits calcium induced nNOS activation, on APAP hepatotoxicity and reactive nitrogen formation in murine hepatocytes and in vivo. In freshly isolated hepatocytes TFP inhibited APAP induced toxicity, reactive nitrogen formation (NO, GSNO, and 3-nitrotyrosine in protein, reactive oxygen formation (superoxide, loss of mitochondrial membrane potential, decreased ATP production, decreased oxygen consumption rate, and increased NADH accumulation. TFP did not alter APAP induced GSH depletion in the hepatocytes or the formation of APAP protein adducts which indicated that reactive metabolite formation was not inhibited. Since we previously reported that TFP inhibits the hepatotoxicity of APAP in mice without altering hepatic APAP-protein adduct formation, we examined the APAP treated mouse livers for evidence of reactive nitrogen formation. 3-Nitrotyrosine in hepatic proteins and GSNO were significantly increased in APAP treated mouse livers and decreased in the livers of mice treated with APAP plus TFP. These data are consistent with a hypothesis that APAP hepatotoxicity occurs with altered calcium metabolism, activation of nNOS leading to increased reactive nitrogen formation, and mitochondrial dysfunction. Keywords: Acetaminophen, Neuronal nitric oxide, Oxidative stress, Mitochondria

  5. Chemical Diversity Investigation of Hepatotoxic Pyrrolizidine Alkaloids in Qianliguang (Senecio scandens and Related Species by UHPLC-QTOF-MS

    Directory of Open Access Journals (Sweden)

    Lin Zhu

    2015-04-01

    Full Text Available Objective: Qianliguang (Senecio scandens is a common Chinese medicinal herb. Qianliguang-containing herbal proprietary products are registered as over-the-counter remedies in China and exported to Western countries. The presence of hepatotoxic pyrrolizidine alkaloids (PAs has raised concerns about the safety of using Qianliguang and its products. The present study aims at investigation of different types of PAs present in Qianliguang collected from representative locations in China.

  6. A retrospective review of methotrexate-induced hepatotoxicity among patients with psoriasis in a tertiary dermatology center in Malaysia.

    Science.gov (United States)

    Ng, Lim Chui; Lee, Yin Yin; Lee, Chew Kek; Wong, Su-Ming

    2013-01-01

    Methotrexate (MTX) is a common and efficacious systemic agent used for the treatment of moderate to severe psoriasis. Nevertheless, its use is associated with the risk of hepatotoxicity. This study was performed to study the association of MTX dose with regards to hepatotoxicity as evidenced by deranged transaminases. This was a retrospective review of patients with psoriasis on MTX from 2000 to 2009 at the outpatient dermatology clinic, University Malaya Medical Centre (UMMC). We analyzed patients' demography, serial laboratory investigations, liver ultrasounds, and liver biopsies of patients on MTX. Sixty-six of 710 (9.30%) patients with psoriasis were prescribed MTX throughout the 10-year period. Among them 57.6% developed deranged transaminases, with six requiring MTX withdrawal due to hepatotoxicity. The mean cumulative dose of MTX at the detection of liver enzyme derangement was 552.3 ± 596.1 mg. A high proportion of patients on MTX had deranged transaminases. However, the number of serious events was low. We concluded from this study that the use of MTX is relatively safe in patients with moderate to severe psoriasis. © 2013 The International Society of Dermatology.

  7. Suppression of Oncolytic Adenovirus-Mediated Hepatotoxicity by Liver-Specific Inhibition of NF-κB

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    Mitsuhiro Machitani

    2017-12-01

    Full Text Available Telomerase-specific replication-competent adenoviruses (Ads, i.e., TRADs, which possess an E1 gene expression cassette driven by the human telomerase reverse transcriptase promoter, are promising agents for cancer treatment. However, even though oncolytic Ads, including TRAD, are intratumorally administered, they are disseminated from the tumor to systemic circulation, causing concern about oncolytic Ad-mediated hepatotoxicity (due mainly to leaky expression of Ad genes in liver. We reported that inhibition of nuclear factor-κB (NF-κB leads to the suppression of replication-incompetent Ad vector-mediated hepatotoxicity via reduction of the leaky expression of Ad genes in liver. Here, to develop a TRAD with an improved safety profile, we designed a TRAD that carries a liver-specific promoter-driven dominant-negative IκBα (DNIκBα expression cassette (TRAD-DNIκBα. Compared with a conventional TRAD, TRAD-DNIκBα showed hepatocyte-specific inhibition of NF-κB signaling and significantly reduced Ad gene expression and replication in the normal human hepatocyte cell line. TRAD-induced hepatotoxicity was largely suppressed in mice following intravenous administration of TRAD-DNIκBα. However, the replication profiles and oncolytic activities of TRAD-DNIκBα were comparable with those of the conventional TRAD in human non-hepatic tumor cells. These results indicate that oncolytic Ads containing the liver-specific DNIκBα expression cassette have improved safety profiles without inhibiting oncolytic activities.

  8. Strain differences of cadmium-induced hepatotoxicity in Wistar-Imamichi and Fischer 344 rats: involvement of cadmium accumulation

    International Nuclear Information System (INIS)

    Shimada, Hideaki; Takamure, Yasutaka; Shimada, Akinori; Yasutake, Akira; Waalkes, Michael P.; Imamura, Yorishige

    2004-01-01

    We previously reported that Wistar-Imamichi (WI) rats have a strong resistance to cadmium (Cd)-induced lethality compared to other strains such as Fischer 344 (Fischer) rats. The present study was designed to establish biochemical and histological differences in Cd toxicity in WI and Fischer rats, and to clarify the mechanistic basis of these strain differences. A single Cd (4.5 mg/kg, s.c.) treatment caused a significant increase in serum alanine aminotransferase activity, indicative of hepatotoxicity, in Fischer rats, but did not in WI rats. This difference in hepatotoxic response to Cd was supported by pathological analysis. After treatment with Cd at doses of 3.0, 3.5 and 4.5 mg/kg, the hepatic and renal accumulation of Cd was significantly lower in the WI rats than in the Fischer rats, indicating a kinetic mechanism for the observed strain differences in Cd toxicity. Thus, the remarkable resistance to Cd-induced hepatotoxicity in WI rats is associated, at least in part, with a lower tissue accumulation of the metal. Hepatic and renal zinc (Zn) contents after administration were similarly lower in WI than in Fischer rats. When Zn was administered in combination with Cd to Fischer rats, it decreased Cd contents in the liver and kidney, and exhibited a significant protective effect against the toxicity of Cd. We propose the possibility that Zn transporter plays an important role in the strain difference of Cd toxicity in WI and Fischer rats

  9. In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System.

    Science.gov (United States)

    Knöspel, Fanny; Jacobs, Frank; Freyer, Nora; Damm, Georg; De Bondt, An; van den Wyngaert, Ilse; Snoeys, Jan; Monshouwer, Mario; Richter, Marco; Strahl, Nadja; Seehofer, Daniel; Zeilinger, Katrin

    2016-04-16

    Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro.

  10. In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System

    Directory of Open Access Journals (Sweden)

    Fanny Knöspel

    2016-04-01

    Full Text Available Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR, while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro.

  11. Copper: From neurotransmission to neuroproteostasis

    Directory of Open Access Journals (Sweden)

    Carlos M Opazo

    2014-07-01

    Full Text Available Copper is critical for the Central Nervous System (CNS development and function. In particular, different studies have shown the effect of copper at brain synapses, where it inhibits Long Term Potentation (LTP and receptor pharmacology. Paradoxically, according to recent studies copper is required for a normal LTP response. Copper is released at the synaptic cleft, where it blocks glutamate receptors, which explain its blocking effects on excitatory neurotransmission. Our results indicate that copper also enhances neurotransmission through the accumulation of PSD95 protein, which increase the levels of AMPA receptors located at the plasma membrane of the post-synaptic density. Thus, our findings represent a novel mechanism for the action of copper, which may have implications for the neurophysiology and neuropathology of the CNS. These data indicate that synaptic configuration is sensitive to transient changes in transition metal homeostasis. Our results suggest that copper increases GluA1 subunit levels of the AMPA receptor through the anchorage of AMPA receptors to the plasma membrane as a result of PSD-95 accumulation. Here, we will review the role of copper on neurotransmission of CNS neurons. In addition, we will discuss the potential mechanisms by which copper could modulate neuronal proteostasis (neuroproteostasis in the CNS with focus in the Ubiquitin Proteasome System, which is particularly relevant to neurological disorders such Alzheimer’s disease (AD where copper and protein dyshomeostasis may contribute to neurodegeneration. An understanding of these mechanisms may ultimately lead to the development of novel therapeutic approaches to control metal and synaptic alterations observed in AD patients.

  12. Reaction list for charged-particle-induced nuclear reactions: Z = 1 to Z = 98 (H to Cf), July 1973--September 1974

    International Nuclear Information System (INIS)

    McGowan, F.K.; Milner, W.T.

    1975-01-01

    This Reaction List for charged-particle-induced nuclear reactions has been prepared from the journal literature for the period from July 1973 through September 1974. Each published experimental paper is listed under the target nucleus in the nuclear reaction with a brief statement of the type of data in the paper. The nuclear reaction is denoted by A(a,b)B, where the mass of a is greater than or equal to (one nucleon mass). There is no restriction on energy. Nuclear reactions involving mesons in the outgoing channel are not included. Theoretical papers which treat directly with the analysis of nuclear reaction data and results are included in the Reaction List. The cutoff date for literature was September 30, 1974. (U.S.)

  13. Toxicidad hepática por medicamentos antituberculosos Hepatotoxicity induced by antituberculosis drugs

    Directory of Open Access Journals (Sweden)

    Isabel Eugenia Escobar Toledo

    2008-01-01

    Full Text Available

    El fenómeno de la toxicidad hepática inducida por medicamentos cobró relevancia hace algunos años con el estudio de las reacciones adversas a medicamentos. El daño producido en el hígado por un xenobiótico que altera su función es lo que se conoce como toxicidad hepática. La importancia de reconocer y diagnosticar la toxicidad hepática por medicamentos estriba en su gravedad potencial; no en vano es la causa más frecuente por la que la industria farmacéutica retira medicamentos. La tuberculosis es una pandemia que afecta a gran parte de la población mundial y junto con el VIH es una enfermedad cada vez más frecuente en Colombia. Esta enfermedad se puede considerar como una situación especial porque para su tratamiento es preciso suministrar, por largos períodos, medicamentos con potencial tóxico para el hígado.

     

    El objetivo de este artículo es revisar algunos aspectos relacionados con la toxicidad hepática secundaria a medicamentos antituberculosos, tales como: epidemiología, factores de riesgo, mecanismos de toxicidad, manifestaciones clínicas, diagnóstico, tratamiento y seguimiento.

    Hepatotoxicity is the alteration of liver structure and function induced by either drugs or other substances. The importance of its proper diagnosis rests on its potential severity. It is the most frequent reason by which the pharmaceutical industry withdraws its products. Tuberculosis is a pandemic infection affecting a large proportion of the world population. Together with HIV infection it is becoming ever more frequent in Colombia. Tuberculosis poses

  14. Advanced Copper Composites Against Copper-Tolerant Xanthomonas perforans and Tomato Bacterial Spot.

    Science.gov (United States)

    Strayer-Scherer, A; Liao, Y Y; Young, M; Ritchie, L; Vallad, G E; Santra, S; Freeman, J H; Clark, D; Jones, J B; Paret, M L

    2018-02-01

    Bacterial spot, caused by Xanthomonas spp., is a widespread and damaging bacterial disease of tomato (Solanum lycopersicum). For disease management, growers rely on copper bactericides, which are often ineffective due to the presence of copper-tolerant Xanthomonas strains. This study evaluated the antibacterial activity of the new copper composites core-shell copper (CS-Cu), multivalent copper (MV-Cu), and fixed quaternary ammonium copper (FQ-Cu) as potential alternatives to commercially available micron-sized copper bactericides for controlling copper-tolerant Xanthomonas perforans. In vitro, metallic copper from CS-Cu and FQ-Cu at 100 μg/ml killed the copper-tolerant X. perforans strain within 1 h of exposure. In contrast, none of the micron-sized copper rates (100 to 1,000 μg/ml) from Kocide 3000 significantly reduced copper-tolerant X. perforans populations after 48 h of exposure compared with the water control (P copper-based treatments killed the copper-sensitive X. perforans strain within 1 h. Greenhouse studies demonstrated that all copper composites significantly reduced bacterial spot disease severity when compared with copper-mancozeb and water controls (P copper composites significantly reduced disease severity when compared with water controls, using 80% less metallic copper in comparison with copper-mancozeb in field studies (P copper composites have the potential to manage copper-tolerant X. perforans and tomato bacterial spot.

  15. Copper Powder and Chemicals: edited proceedings of a seminar

    Energy Technology Data Exchange (ETDEWEB)

    1980-12-01

    Various papers are presented covering the following topics: Status of Copper Chemical Industry in India, Copper Powder from Industrial Wastes, Manufacture of Copper Hydroxide and High Grade Cement Copper from Low Grade Copper Ore, Manufacture of Copper Sulphate as a By-Product, Hydrometallurgical Treatments of Copper Converter and Smelter Slage for Recovering Copper and other Non-Ferrous Metals, Recovery of Copper from Dilute Solutions, Use of Copper Compounds as Fungicides in India, Copper in Animal Husbandry, and Use of Copper Powder and Chemicals for Marine Applications. The keynote paper given at the Seminar was on Conservation of Copper for Better Use.

  16. Studying preventive effects of Berberisintegerrimaon root on carbon tetrachloride induced hepatotoxicity in broilers

    Directory of Open Access Journals (Sweden)

    mohammadreza mohammadimalayeri

    2013-11-01

    Full Text Available Liver diseases and their economic losses have gained more importancealongside the development of integrated poultry industry. Studies have proved hepatotoxicity induced by carbon tetrachloride as one of the best experimental models of hepatotocicity. Barberries have been used widely in traditional medicine.The purpose of the present study was to evaluaterthe preventive effects of Berberisintegerrima root on carbon tetrachloride induced liver lesions in broilers.For this purpose, 80 day old Ross strain broilers were divided randomly to 8 study groupsconsisting of negative control, positive control which received IP 4ml/kg b.w. carbon tetrachloride twice in 25th and 28thdays , treatment controls consisting of 10,20 and 30 grams of  Berberisintegerrima root per kilogram of diet and treatment groups consisting of 10,20 and 30 gr. Of Berberis root / Kg diet + IPcarbontetrachloride 4ml/Kg b.w. twice in 25th and 28th days.At 29th day, blood samples were collected from animals, then they were sacrificed and their liver samples were fixed in 10% formalin solution. The blood samples were sent to laboratory to measure ALT,AST and ALP activities.Biochemical results didn't show any significant changes of ALT,AST and ALP activities between all study groups (P>0.05. Microscopic results showed significant decrease in pathologic lesions of 20 gr Berberis root /Kg diet treatment group in comparison with the positive control group(P

  17. A three-stage-integrative approach for the identification of potential hepatotoxic compounds from botanical products.

    Science.gov (United States)

    Jin, Yecheng; Zhao, Xiaoping; Zhang, Yufeng; Li, Xiang; Nie, Xiaojing; Wang, Yi; Fan, Xiaohui

    2011-05-01

    With the increasing use of herbal medicines and dietary supplements, intensive concerns about their potential toxicities have been raised. Screening and identifying the toxic compounds from these botanical products composed by hundreds of components have become a critical but challenging problem. In this study, 3 methods, including fraction separation, an in-house-developed fluorescein diacetate-based automatic microscopy screening (FAMS) platform, and liquid chromatography-mass spectrometry-based compounds identification were integrated within the Three-Stage-Integrative (TSI) approach for the identification of potential hepatotoxicants from botanical products. The sensitivity and linear range of FAMS assay was validated and compared with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay by previously reported hepatotoxic compounds. The success of TSI approach was further demonstrated by its application to Fructus aristolochiae. Aristolochic acid IVa and aristolodione were tentatively identified to be potential hepatotoxicants in this plant. These applications suggested that our TSI approach provides an effective tool for identifying potential toxic compounds from botanical products.

  18. Dideoxynucleoside HIV reverse transcriptase inhibitors and drug-related hepatotoxicity: a case report

    Directory of Open Access Journals (Sweden)

    Lapadula Giuseppe

    2007-05-01

    Full Text Available Abstract This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis. A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage.

  19. Hepatotoxic Seafood Poisoning (HSP Due to Microcystins: A Threat from the Ocean?

    Directory of Open Access Journals (Sweden)

    Evangelos Briasoulis

    2013-08-01

    Full Text Available Cyanobacterial blooms are a major and growing problem for freshwater ecosystems worldwide that increasingly concerns public health, with an average of 60% of blooms known to be toxic. The most studied cyanobacterial toxins belong to a family of cyclic heptapeptide hepatotoxins, called microcystins. The microcystins are stable hydrophilic cyclic heptapeptides with a potential to cause cell damage following cellular uptake via organic anion-transporting proteins (OATP. Their intracellular biologic effects presumably involve inhibition of catalytic subunits of protein phosphatases (PP1 and PP2A and glutathione depletion. The microcystins produced by cyanobacteria pose a serious problem to human health, if they contaminate drinking water or food. These toxins are collectively responsible for human fatalities, as well as continued and widespread poisoning of wild and domestic animals. Although intoxications of aquatic organisms by microcystins have been widely documented for freshwater ecosystems, such poisonings in marine environments have only occasionally been reported. Moreover, these poisonings have been attributed to freshwater cyanobacterial species invading seas of lower salinity (e.g., the Baltic or to the discharge of freshwater microcystins into the ocean. However, recent data suggest that microcystins are also being produced in the oceans by a number of cosmopolitan marine species, so that Hepatotoxic Seafood Poisoning (HSP is increasingly recognized as a major health risk that follows consumption of contaminated seafood.

  20. Cuscuta arvensis Beyr "Dodder": In Vivo Hepatoprotective Effects Against Acetaminophen-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Koca-Caliskan, Ufuk; Yilmaz, Ismet; Taslidere, Asli; Yalcin, Funda N; Aka, Ceylan; Sekeroglu, Nazim

    2018-05-02

    Cuscuta arvensis Beyr. is a parasitic plant, and commonly known as "dodder" in Europe, in the United States, and "tu si zi shu" in China. It is one of the preferred spices used in sweet and savory dishes. Also, it is used as a folk medicine for the treatment particularly of liver problems, knee pains, and physiological hepatitis, which occur notably in newborns and their mothers in the southeastern part of Turkey. The purpose of this study was to investigate the hepatoprotective effects and antioxidant activities of aqueous and methanolic extracts of C. arvensis Beyr. on acetaminophen (APAP)-induced acute hepatotoxicity in rats. The results were supported by subsequent histopathological studies. The hepatoprotective activity of both the aqueous and methanolic extracts at an oral dose of 125 and 250 mg/kg was investigated by observing the reduction levels or the activity of alkaline phosphatase, alkaline transaminase, aspartate aminotransferase, blood urine nitrogen, and total bilirubin content. In vivo antioxidant activity was determined by analyzing the serum superoxide dismutase, malondialdehyde, glutathione, and catalase levels. Chromatographic methods were used to isolate biologically active compounds from the extract, and spectroscopic methods were used for structure elucidation. Both the methanolic and aqueous extracts exerted noticable hepatoprotective and antioxidant effects supporting the folkloric usage of dodder. One of the bioactive compounds was kaempferol-3-O-rhamnoside, isolated and identified from the methanolic extract.

  1. Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Yen, Feng-Lin; Wu, Tzu-Hui; Lin, Liang-Tzung; Cham, Thau-Ming; Lin, Chun-Ching

    2008-05-01

    Cuscuta chinensis is a commonly used traditional Chinese medicine to nourish the liver and kidney. Due to the poor water solubility of its major constituents such as flavonoids and lignans, its absorption upon oral administration could be limited. The purpose of the present study was to use the nanosuspension method to prepare C. chinensis nanoparticles (CN), and to compare the hepatoprotective and antioxidant effects of C. chinensis ethanolic extract (CE) and CN on acetaminophen-induced hepatotoxicity in rats. An oral dose of CE at 125 and 250 mg/kg and CN at 25 and 50mg/kg showed a significant hepatoprotective effect relatively to the same extent (P<0.05) by reducing levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. These biochemical assessments were supported by rat hepatic biopsy examinations. In addition, the antioxidant activities of CE and CN both significantly increased superoxide dismutase, catalase, glutathione peroxidase, and reduced malondialdehyde (P<0.05). Moreover, the results also indicated that the hepatoprotective and antioxidant effects of 50 mg/kg CN was effectively better than 125 mg/kg CE (P<0.05), and an oral dose of CN that is five times as less as CE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other water poorly soluble herbal medicines and furthermore to decrease the treatment dosage.

  2. Bees’ Honey Attenuation of Metanil-Yellow-Induced Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Abdulrahman L. Al-Malki

    2013-01-01

    Full Text Available The present study aims to investigate the protective effect of bees’ honey against metanil-yellow-induced hepatotoxicity in rats. Rats were divided into 7 groups: control group; three groups treated with 50, 100, and 200 mg/kg metanil yellow, and three groups treated with metanil yellow plus 2.5 mg·kg-1·day-1 bees’ honey for 8 weeks. The obtained data showed that the antioxidant/anti-inflammatory activity of bees’ honey reduced the oxidative stress in the liver tissue and downregulated the inflammatory markers. In addition, the elevated levels of AGE and the activated NF-κB in the metanil-yellow-treated animals were significantly attenuated. Moreover, the levels of TNF-α and IL-1β were significantly attenuated as a result of bees’ honey administration. Furthermore, the histopathological examination of the liver showed that bees’ honey reduced fatty degeneration, cytoplasmic vacuolization, and necrosis in metanil-yellow-treated rats. In conclusion, the obtained data suggest that bees’ honey has hepatoprotective effect on acute liver injuries induced by metanil-yellow in vivo, and the results suggested that the effect of bees’ honey against metanil yellow-induced liver damage is related to its antioxidant/anti-inflammatory properties which attenuate the activation of NF-κB and its controlled genes like TNF-α and IL-1β.

  3. Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro.

    Science.gov (United States)

    Werbovetz, Karl A; Riccio, Edward S; Furimsky, Anna; Richard, Julian V; He, Shanshan; Iyer, Lalitha; Mirsalis, Jon

    2014-07-01

    N1-Benzylated dihydroquinolin-6-ols and their corresponding esters display exceptional activity against African trypanosomes in vitro, and administration of members of this class of compounds to trypanosome-infected mice results in cures in a first-stage African trypanosomiasis model. Since a quinone imine intermediate has been implicated in the antiparasitic mechanism of action of these compounds, evaluation of the hepatotoxic, mutagenic, and methemoglobin-promoting effects of these agents was performed. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate showed outstanding in vitro selectivity for Trypanosoma brucei compared to the HepG2, Hep3B, Huh7, and PLC5 hepatocyte cell lines. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-(2-methoxybenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate were not mutagenic when screened in the Ames assay, with or without metabolic activation. The latter 2 compounds promoted time- and dose-dependent formation of methemoglobin when incubated in whole human blood, but such levels were below those typically required to produce symptoms of methemoglobinemia in humans. Although compounds capable of quinone imine formation require careful evaluation, these in vitro studies indicate that antitrypanosomal dihydroquinolines merit further study as drug candidates against the neglected tropical disease human African trypanosomiasis. © The Author(s) 2014.

  4. Antioxidant activity of Green tea extract against Isoniazid induced hepatotoxicity in the rats

    Directory of Open Access Journals (Sweden)

    2011-08-01

    Full Text Available Tuberculosis continues to be a common health problem worldwide. Isoniazid, an antibiotic used routinely for tuberculosis chemotherapy is documented to be a potent hepatotoxicant. The aim of the present study was to assess the antioxidant activity of Green tea extract (GTE against Isoniazid induced hepatotoxicity in the rats. Male Wistar rats were randomly assigned into 4 groups of 10 animals each including 1- normal healthy control rats, 2- healthy rats receiving (GTE 3- toxicant control, and 4- toxicant drug+ GTE treatment group. In groups 2 and 4 GTE (1.5%, w/v was given as only source of drinking for 8 weeks. In the midst stage of experiment (4th and 5th weeks, Isonizid (50 mg/kg b.w./day, i.p. was administrated for groups 3 and 4 for a period of 2 weeks. At the end of experiment, product of lipid peroxidation (MDA, activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPX and glutathione reductase (GR were assayed in liver homogenates to evaluate antioxidant activity. Significant differences among the groups were determined by one-way analysis of variance followed by Tukey post-test. Statistical significance was considered at p

  5. Ursodeoxycholic Acid Can Improve Liver Transaminase Quantities in Children with Anticonvulsant Drugs Hepatotoxicity: a Pilot Study.

    Directory of Open Access Journals (Sweden)

    Masoumeh Asgarshirazi

    2015-06-01

    Full Text Available The present study has been directed to investigate Ursodeoxycholic Acid (UDCA effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis. This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.

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

    Science.gov (United States)

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

    2018-03-05

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

  7. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    Directory of Open Access Journals (Sweden)

    T. Scott Devera

    2015-06-01

    Full Text Available Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI, and hepatic alanine aminotransferase (ALT, and aspartate aminotransferase (AST, it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

  8. Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats.

    Science.gov (United States)

    Pari, Leelavinothan; Amali, D Rosalin

    2005-04-30

    Tetrahydrocurcumin (THC) is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of THC and curcumin against chloroquine (CQ) induced hepatotoxicity were studied in female Wistar rats. On single oral administration of CQ (970 mg/kg body weight) the activities of serum marker enzymes namely aspartate transaminase, alanine transaminase and alkaline phosphatase and the levels of bilirubin were significantly increased with significant alterations of lipids in serum and lipidperoxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides in plasma and liver were also elevated in CQ treated rats. The levels of non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) and enzymic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) were also decreased in CQ treated rats. Administration of THC (80 mg/kg body weight) and curcumin (80 mg/kg body weight) for 8 days before and 7 days after single administration of CQ significantly decreased the activities of serum markers and lipids in serum. In addition, the level of TBARS and hydroperoxides were significantly decreased with significant increase in non-enzymic and enzymic antioxidants on treatment with THC and curcumin. The biochemical observation was supplemented by histopathological examination of liver section. The results of the study reveal that THC shows more pronounced protective effect than curcumin against CQ induced toxicity.

  9. Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases.

    Science.gov (United States)

    Acheampong, Paul; Thomas, Simon H L

    2016-10-01

    To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestion (RSPI). Systematic literature review with collation and analysis of individual-level data from reported cases of RSPI associated with liver damage. In 199 cases meeting the selection criteria, severe liver damage (ALT/AST ≥1000 IU l(-1) , liver failure or death) was reported in 186 (93%) cases including 77/78 (99%) children aged ≤6 years. Liver failure occurred in 127 (64%) cases; of these 49 (39%) died. Maximum ingested daily paracetamol doses were above UK recommendations in 143 (72%) patients. US-Australasian thresholds for repeated supratherapeutic ingestions requiring intervention were not met in 71 (36%) cases; of these 35 (49%) developed liver failure and 10 (14%) died. No cases developing liver damage had paracetamol concentration Paracetamol concentrations <20 mg l(-1) with normal serum ALT/AST activity on initial assessment suggests a low risk of subsequent liver damage. These findings are, however, limited by low patient numbers, publication bias and the accuracy of the histories in reported cases. © 2016 The British Pharmacological Society.

  10. Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

    Science.gov (United States)

    Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

    2011-01-01

    AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

  11. Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Surendra K Sharma

    2016-01-01

    Full Text Available Background & objectives: The N-acetyltransferase 2 (NAT2 gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH. Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8% and non-DIH (77.2% patients. However, the genotypic distribution of variant NAT2FNx015/FNx017 amongst slow-acetylator genotypes was significantly higher in DIH (56% group as compared to non-DIH (39% group (odds ratio 2.02; P=0.006. Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

  12. Amelioration of lead induced hepatotoxicity by Allium sativum extracts in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Sharma A

    2010-01-01

    Full Text Available Lead is a blue-gray and highly toxic divalent metal that occurs naturally in the earth crust and isspread throughout the environment by various human activities. The efficacy of garlic (Allium sativumto reduce hepatotoxicity induced by lead nitrate was evaluated experimentally in male mice. Oraltreatment with lead nitrate at a dose of 50 mg/ kg body weight daily for 40 days (1/45 of LD50 induceda significant increase in the levels of hepatic aspartate aminotransferase (AST, alanineaminotransferase (ALT, alkaline phosphatase (ALP, acid phosphatase (ALP, cholesterol, lipidperoxidation (LPO and lead nitrate. In parallel, hepatic protein levels in lead exposed mice weresignificantly depleted. Lead nitrate exposure also produced detrimental effects on the redox status ofthe liver indicated by a significant decline in the levels of liver antioxidants such as superoxidedismutase (SOD, catalase (CAT and glutathione (GSH. After exposure to lead nitrate (50 mg/kgbody weight for 10 days, the animals received aqueous garlic extract (250 mg/ kg body weight and500 mg/ kg body weight and ethanolic garlic extract (100 mg/ kg body weight and 250 mg/ kg bodyweight and partially restored the deranged parameters significantly Histological examination of theliver also revealed pathophysiological changes in lead nitrate exposed group and treatment with garlicimproved liver histology. Our data suggest that garlic is a phytoantioxidant that can counteract thedeleterious effects of lead nitrate.

  13. Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

    Science.gov (United States)

    Adeneye, A A; Benebo, A S

    2007-01-01

    Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (pcholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (pascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed effects.

  14. 21 CFR 73.1647 - Copper powder.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Copper powder. 73.1647 Section 73.1647 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1647 Copper powder. (a) Identity. (1) The color additive copper powder is a very fine free-flowing metallic powder prepared from virgin electrolytic copper. It...

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    NARCIS (Netherlands)

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

    1991-01-01

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

  17. NID Copper Sample Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kouzes, Richard T.; Zhu, Zihua

    2011-09-12

    The current focal point of the nuclear physics program at PNNL is the MAJORANA DEMONSTRATOR, and the follow-on Tonne-Scale experiment, a large array of ultra-low background high-purity germanium detectors, enriched in 76Ge, designed to search for zero-neutrino double-beta decay (0νββ). This experiment requires the use of germanium isotopically enriched in 76Ge. The MAJORANA DEMONSTRATOR is a DOE and NSF funded project with a major science impact. The DEMONSTRATOR will utilize 76Ge from Russia, but for the Tonne-Scale experiment it is hoped that an alternate technology, possibly one under development at Nonlinear Ion Dynamics (NID), will be a viable, US-based, lower-cost source of separated material. Samples of separated material from NID require analysis to determine the isotopic distribution and impurities. DOE is funding NID through an SBIR grant for development of their separation technology for application to the Tonne-Scale experiment. The Environmental Molecular Sciences facility (EMSL), a DOE user facility at PNNL, has the required mass spectroscopy instruments for making isotopic measurements that are essential to the quality assurance for the MAJORANA DEMONSTRATOR and for the development of the future separation technology required for the Tonne-Scale experiment. A sample of isotopically separated copper was provided by NID to PNNL in January 2011 for isotopic analysis as a test of the NID technology. The results of that analysis are reported here. A second sample of isotopically separated copper was provided by NID to PNNL in August 2011 for isotopic analysis as a test of the NID technology. The results of that analysis are also reported here.

  18. Gallium and copper radiopharmaceutical chemistry

    International Nuclear Information System (INIS)

    Green, M.A.

    1991-01-01

    Gallium and copper radionuclides have a long history of use in nuclear medicine. Table 1 presents the nuclear properties of several gallium and copper isotopes that either are used in the routine practice of clinical nuclear medicine or exhibit particular characteristics that might make them useful in diagnostic or therapeutic medicine. This paper will provide some historic perspective along with an overview of some current research directions in gallium and copper radiopharmaceutical chemistry. A more extensive review of gallium radiopharmaceutical chemistry has recently appeared and can be consulted for a more in-depth treatment of this topic

  19. Copper complexes as 'radiation recovery' agents

    International Nuclear Information System (INIS)

    Sorenson, J.R.J.

    1989-01-01

    Copper and its compounds have been used for their remedial effects since the beginning of recorded history. As early as 3000 BC the Egyptians used copper as an antiseptic for healing wounds and to sterilise drinking water; and later, ca 1550 BC, the Ebers Papyrus reports the use of copper acetate, copper sulphate and pulverised metallic copper for the treatment of eye infections. These historical uses of copper and its compounds are particularly interesting in the light of modern evidence concerning the use of certain copper complexes for the treatment of radiation sickness and more recently as an adjunct to radiotherapy for cancer patients. (author)

  20. Unusual Synchronous Methimazole-Induced Agranulocytosis and Severe Hepatotoxicity in Patient with Hyperthyroidism: A Case Report and Review of the Literature

    Science.gov (United States)

    Yang, Jun; Zhang, Jun; Xu, Qin; Sheng, Guo-ping; Weng, Wan-wen; Dong, Meng-jie

    2015-01-01

    Context. To report a patient with hyperthyroidism who developed concurrent occurrence of agranulocytosis and severe hepatotoxicity after taking methimazole (MMI). Case. A 51-year-old Chinese male was diagnosed as hyperthyroidism with normal white blood count and liver function. After 4 weeks' treatment with MMI 20 mg/d, it developed to agranulocytosis and severe cholestatic hepatotoxicity. The patient's symptoms and laboratory abnormalities disappeared after the withdrawal of MMI; his white blood count and liver function recover to normal in 2 weeks and 5 weeks, respectively. 296 MBq dose of 131I was given to the patient 3 weeks after the withdrawal of MMI and his thyroid function was back to normal in 6 months. As we know through literature review, only 5 previous cases reported the synchronous ATD-induced agranulocytosis and severe hepatotoxicity in patients with hyperthyroidism. Methods. Review of the patient's clinical course. Literature review of cases of hyperthyroidism with agranulocytosis and severe hepatotoxicity demonstrated that these complications occurred after taking antithyroid drug (ATD). Conclusions. Patient with hyperthyroidism can have synchronous ATD-induced agranulocytosis and severe hepatotoxicity. This case is extremely rare, but the adverse effects with ATDs is clinically significant. The clinicians need to be careful about this and monitor biochemical of patients who take ATDs. PMID:26060496

  1. Unusual Synchronous Methimazole-Induced Agranulocytosis and Severe Hepatotoxicity in Patient with Hyperthyroidism: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2015-01-01

    Full Text Available Context. To report a patient with hyperthyroidism who developed concurrent occurrence of agranulocytosis and severe hepatotoxicity after taking methimazole (MMI. Case. A 51-year-old Chinese male was diagnosed as hyperthyroidism with normal white blood count and liver function. After 4 weeks’ treatment with MMI 20 mg/d, it developed to agranulocytosis and severe cholestatic hepatotoxicity. The patient’s symptoms and laboratory abnormalities disappeared after the withdrawal of MMI; his white blood count and liver function recover to normal in 2 weeks and 5 weeks, respectively. 296 MBq dose of 131I was given to the patient 3 weeks after the withdrawal of MMI and his thyroid function was back to normal in 6 months. As we know through literature review, only 5 previous cases reported the synchronous ATD-induced agranulocytosis and severe hepatotoxicity in patients with hyperthyroidism. Methods. Review of the patient’s clinical course. Literature review of cases of hyperthyroidism with agranulocytosis and severe hepatotoxicity demonstrated that these complications occurred after taking antithyroid drug (ATD. Conclusions. Patient with hyperthyroidism can have synchronous ATD-induced agranulocytosis and severe hepatotoxicity. This case is extremely rare, but the adverse effects with ATDs is clinically significant. The clinicians need to be careful about this and monitor biochemical of patients who take ATDs.

  2. Copper tailings in stucco mortars

    Directory of Open Access Journals (Sweden)

    Osvaldo Pavez

    Full Text Available Abstract This investigation addressed the evaluation of the use of copper tailings in the construction industry in order to reduce the impact on the environment. The evaluation was performed by a technical comparison between stucco mortars prepared with crushed conventional sand and with copper tailings sand. The best results were achieved with the stucco mortars containing tailings. The tailings presented a fine particles size distribution curve different from that suggested by the standard. The values of compressive strength, retentivity, and adherence in the stucco mortars prepared with copper tailings were much higher than those obtained with crushed sand. According to the results from this study, it can be concluded that the preparation of stucco mortars using copper tailings replacing conventional sand is a technically feasible alternative for the construction industry, presenting the benefit of mitigating the impact of disposal to the environment.

  3. The copper deposits of Michigan

    Science.gov (United States)

    Butler, B.S.; Burbank, W.S.

    1929-01-01

    The copper district of Keweenaw Point, in the northern peninsula of Michigan, is the second largest producer of copper in the world.  The output of the district since 1845 has been more than 7,500,000,000 pounds and showed a rather steady and consistent increase from the beginning of production to the end of the World War in 1918, since which there has been a marked decrease.

  4. Copper atomic-scale transistors.

    Science.gov (United States)

    Xie, Fangqing; Kavalenka, Maryna N; Röger, Moritz; Albrecht, Daniel; Hölscher, Hendrik; Leuthold, Jürgen; Schimmel, Thomas

    2017-01-01

    We investigated copper as a working material for metallic atomic-scale transistors and confirmed that copper atomic-scale transistors can be fabricated and operated electrochemically in a copper electrolyte (CuSO 4 + H 2 SO 4 ) in bi-distilled water under ambient conditions with three microelectrodes (source, drain and gate). The electrochemical switching-on potential of the atomic-scale transistor is below 350 mV, and the switching-off potential is between 0 and -170 mV. The switching-on current is above 1 μA, which is compatible with semiconductor transistor devices. Both sign and amplitude of the voltage applied across the source and drain electrodes ( U bias ) influence the switching rate of the transistor and the copper deposition on the electrodes, and correspondingly shift the electrochemical operation potential. The copper atomic-scale transistors can be switched using a function generator without a computer-controlled feedback switching mechanism. The copper atomic-scale transistors, with only one or two atoms at the narrowest constriction, were realized to switch between 0 and 1 G 0 ( G 0 = 2e 2 /h; with e being the electron charge, and h being Planck's constant) or 2 G 0 by the function generator. The switching rate can reach up to 10 Hz. The copper atomic-scale transistor demonstrates volatile/non-volatile dual functionalities. Such an optimal merging of the logic with memory may open a perspective for processor-in-memory and logic-in-memory architectures, using copper as an alternative working material besides silver for fully metallic atomic-scale transistors.

  5. Atmospheric corrosion effects on copper

    International Nuclear Information System (INIS)

    Franey, J.P.

    1985-01-01

    Studies have been performed on the naturally formed patina on various copper samples. Samples have been obtained from structures at AT and T Bell Laboratories, Murray Hill, NJ (40,2,1 and <1 yr) and the Statue of Liberty (100 yr). The samples show a distinct layering effect, that is, the copper base material shows separate oxide and basic sulfate layers on all samples, indicating that patina is not a homogeneous mixture of oxides and basic sulfates

  6. Chronic copper poisoning in lambs

    Energy Technology Data Exchange (ETDEWEB)

    Ross, D B

    1964-08-08

    This communication presented evidence of the elevation of plasma GOT (glutamic oxaloacetic transaminase or aspartate transaminase) concentration during the development of copper toxicity in some experimental lambs, and also demonstrated that plasma GOT concentration can be used to assess the course of the disease during treatment. A group of Kerry Hill lambs were fed 1 1/2 lb per day of a proprietary concentrate containing 40 parts of copper per million on a dry-matter basis in addition to hay and water ad lib. Data was included for the plasma GOT concentrations of the lambs, bled weekly after weaning from pasture to this diet. There was some variation between the individual lambs, and in one there was no increase in plasma GOT by the 20th week when all the surviving lambs were slaughtered. The concentrations of copper found in the caudate lobe of the liver and in the kidney cortex post mortem were given. The overall findings showed that the liver gave a reliable indication of the copper status of an animal whereas the kidney cortex copper concentration was a better criterion for the diagnosis of copper poisoning and was in agreement with the results of Eden, Todd, and Grocey and Thompson. Observations demonstrated the benefits resulting from the early diagnosis of chronic copper poisoning in lambs, when treatment of affected animals may be commenced before the haemolytic crisis develops. Treatment included reducing the copper intake and dosing with ammonium molybdate and sodium sulfate, and the plasma GOT concentration may be used to assess the rate of recovery. 4 references, 3 tables.

  7. Copper sulphate poisoning in horses

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, M

    1975-01-01

    In the archives of the Clinic for Internal Diseases of Domestic Animals at the Veterinary Faculty of Zagreb University some thirty cases of horse disease diagnosed as copper sulphate poisoning were noted. The data correspond in many respects to the clinical findings of copper sulphate poisoning in other domestic animals. A series of experimental horse poisonings were undertaken in order to determine the toxicity of copper sulphate. The research results are as follows: Horses are sensitive to copper sulphate. Even a single application of 0.125 g/kg body weight in 1% concentration by means of incubation into the stomach causes stomach and gut disturbances and other poisoning symptoms. Poisoning occurs in two types: acute and chronic. The former appears after one to three applications of copper sulphate solution and is characterized by gastroenteritis, haemolysis, jaundice and haemoglobinuria with signs of consecutive damage of kidney, liver and other organs. The disease, from the first application to death lasts for two weeks. Chronic poisoning is caused by ingestion of dry copper sulphate in food (1% solution dried on hay or clover) for two or more months. There are chronic disturbances of stomach and gut and loss of weight, and consecutive (three to four) haemolytic crises similar to those of acute poisoning. From the beginning of poisoning to death six or more months can elapse.

  8. Genome Sequences of Two Copper-Resistant Escherichia coli Strains Isolated from Copper-Fed Pigs

    DEFF Research Database (Denmark)

    Lüthje, Freja L.; Hasman, Henrik; Aarestrup, Frank Møller

    2014-01-01

    The draft genome sequences of two copper-resistant Escherichia coli strains were determined. These had been isolated from copper-fed pigs and contained additional putative operons conferring copper and other metal and metalloid resistances.......The draft genome sequences of two copper-resistant Escherichia coli strains were determined. These had been isolated from copper-fed pigs and contained additional putative operons conferring copper and other metal and metalloid resistances....

  9. Formation of copper-indium-selenide and/or copper-indium-gallium-selenide films from indium selenide and copper selenide precursors

    Science.gov (United States)

    Curtis, Calvin J [Lakewood, CO; Miedaner, Alexander [Boulder, CO; Van Hest, Maikel [Lakewood, CO; Ginley, David S [Evergreen, CO; Nekuda, Jennifer A [Lakewood, CO

    2011-11-15

    Liquid-based indium selenide and copper selenide precursors, including copper-organoselenides, particulate copper selenide suspensions, copper selenide ethylene diamine in liquid solvent, nanoparticulate indium selenide suspensions, and indium selenide ethylene diamine coordination compounds in solvent, are used to form crystalline copper-indium-selenide, and/or copper indium gallium selenide films (66) on substrates (52).

  10. Use of copper radioisotopes in investigating disorders of copper metabolism

    International Nuclear Information System (INIS)

    Camakaris, J.; Voskoboinik, I.; Brooks, H.; Greenough, M.; Smith, S.; Mercer, J.

    1998-01-01

    Full text: Copper is an essential trace element for life as a number of vital enzymes require it. Copper deficiency can lead to neurological disorders, osteoporosis and weakening of arteries. However Cu is also highly toxic and homeostatic mechanisms have evolved to maintain Cu at levels which satisfy requirements but do not cause toxicity. Toxicity is mediated by the oxidative capacity of Cu and its ability to generate toxic free radicals. There are several acquired and inherited diseases due to either Cu toxicity or Cu deficiency. The study of these diseases facilitates identification of genes and proteins involved in copper homeostasis, and this in turn will provide rational therapeutic approaches. Our studies have focused on Menkes disease in humans which is an inherited and usually lethal copper deficiency. Using copper radioisotopes 64 Cu (t 1/2 = 12.8 hr) and 67 Cu (t 1/2 = 61 hr) we have studied the protein which is mutated in Menkes disease. This is a transmembrane copper pump which is responsible for absorption of copper into the body and also functions to pump out excess Cu from cells when Cu is elevated. It is therefore a vital component of normal Cu homeostasis. We have provided the first biochemical evidence that the Menkes protein functions as a P-type ATPase Cu pump (Voskoboinik et al., FEBS Letters, in press) and these data will be discussed. The assay involved pumping of radiocopper into purified membrane vesicles. Furthermore we have transfected normal and mutant Menkes genes into cells and are carrying out structure-function studies. We are also studying the role of amyloid precursor protein (APP) as a Cu transport protein in order to determine how Cu regulates this protein and its cleavage products. These studies will provide vital information on the relationship between Cu and APP and processes which lead to Alzheimers disease

  11. Metallic nickel nano- and fine particles induce JB6 cell apoptosis through a caspase-8/AIF mediated cytochrome c-independent pathway

    Directory of Open Access Journals (Sweden)

    Castranova Vincent

    2009-04-01

    Full Text Available Abstract Background Carcinogenicity of nickel compounds has been well documented. However, the carcinogenic effect of metallic nickel is still unclear. The present study investigates metallic nickel nano- and fine particle-induced apoptosis and the signal pathways involved in this process in JB6 cells. The data obtained from this study will be of benefit for elucidating the pathological and carcinogenic potential of metallic nickel particles. Results Using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, we found that metallic nickel nanoparticles exhibited higher cytotoxicity than fine particles. Both metallic nickel nano- and fine particles induced JB6 cell apoptosis. Metallic nickel nanoparticles produced higher apoptotic induction than fine particles. Western-blot analysis showed an activation of proapoptotic factors including Fas (CD95, Fas-associated protein with death domain (FADD, caspase-8, death receptor 3 (DR3 and BID in apoptotic cells induced by metallic nickel particles. Immunoprecipitation (IP western blot analysis demonstrated the formation of the Fas-related death-inducing signaling complex (DISC in the apoptotic process. Furthermore, lamin A and beta-actin were cleaved. Moreover, we found that apoptosis-inducing factor (AIF was up-regulated and released from mitochondria to cytoplasm. Interestingly, although an up-regulation of cytochrome c was detected in the mitochondria of metallic nickel particle-treated cells, no cytochrome c release from mitochondria to cytoplasm was found. In addition, activation of antiapoptotic factors including phospho-Akt (protein kinase B and Bcl-2 was detected. Further studies demonstrated that metallic nickel particles caused no significant changes in the mitochondrial membrane permeability after 24 h treatment. Conclusion In this study, metallic nickel nanoparticles caused higher cytotoxicity and apoptotic induction than fine particles in JB6 cells. Apoptotic cell death

  12. GARLIC AMELIORATES THE HEPATOTOXIC EFFECT INDUCED BY THIOACETAMIDE IN FEMALE RATS

    International Nuclear Information System (INIS)

    OSMAN, H.F.; TAHA, M.S.

    2008-01-01

    The purpose of this study was to investigate the pretreatment effect of garlic on hepatotoxicity and oxidative stress induced by thioacetamide (TAA) in female albino rats.Sixty female adult albino rats were assigned equally into four groups; control group: animals without treatment, group ?: rats given daily oral dose of 250 mg/ kg garlic for 28 days, group ??: rats injected intraperitonealy by thioacetamide 20 mg ? kg for two weeks and group III: rats given 250 mg / kg garlic orally for 28 day followed by intrapertoneal injection of 20 mg / kg thioacetamide for two weeks. Liver enzymes were evaluated by measurements of AST, ALT and alkaline phosphatase and also trace elements (Cu and Zn) were estimated. Superoxide dismutase, glutathione peroxidase, malondialdehyde and thyroid hormones (T3 and T4) were assessed. Also, histological studies on liver and stomach were carried out. The results indicated that treatment with garlic significantly decreased liver enzymes (AST, ALT and ALP). Cu showed high significant increase in groups treated with garlic and also garlic + TAA, while Zn was increased significantly in TAA group. Superoxide dismutase (SOD) was increased significantly in group I while TAA decreased it significantly. Glutathione peroxidase was decreased significantly in group II while its level in group IV reached near the control value. Similarly, malondialdehyde was decreased significantly in garlic group and garlic ameliorated the thioacetamide effect in garlic + TAA group. The treatment with TAA led to significant increase in T3 and significant decrease in T4 hormones. Garlic ameliorated T3 level to reach the control level. Histologically, pre-treatment with garlic induced a prophylactic activity against the thioacetamide in liver and stomach tissues.According to the obtained results, it could be conclude that garlic treatment may act as antioxidant or pro-oxidant in TAA treated animals besides decreasing the TAA toxic effects on liver enzymes, liver and

  13. Metabolic activation of hepatotoxic drug (benzbromarone) induced mitochondrial membrane permeability transition

    Energy Technology Data Exchange (ETDEWEB)

    Shirakawa, Maho; Sekine, Shuichi; Tanaka, Ayaka [The Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba (Japan); Horie, Toshiharu [Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo (Japan); Ito, Kousei, E-mail: itokousei@chiba-u.jp [The Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba (Japan)

    2015-10-01

    The risk of drug-induced liver injury (DILI) is of great concern to the pharmaceutical industry. It is well-known that metabolic activation of drugs to form toxic metabolites (TMs) is strongly associated with DILI onset. Drug-induced mitochondrial dysfunction is also strongly associated with increased risk of DILI. However, it is difficult to determine the target of TMs associated with exacerbation of DILI because of difficulties in identifying and purifying TMs. In this study, we propose a sequential in vitro assay system to assess TM formation and their ability to induce mitochondrial permeability transition (MPT) in a one-pot process. In this assay system, freshly-isolated rat liver mitochondria were incubated with reaction solutions of 44 test drugs preincubated with liver microsomes in the presence or absence of NADPH; then, NADPH-dependent MPT pore opening was assessed as mitochondrial swelling. In this assay system, several hepatotoxic drugs, including benzbromarone (BBR), significantly induced MPT in a NADPH-dependent manner. We investigated the rationality of using BBR as a model drug, since it showed the most prominent MPT in our assay system. Both the production of a candidate toxic metabolite of BBR (1′,6-(OH){sub 2} BBR) and NADPH-dependent MPT were inhibited by several cytochrome P450 (CYP) inhibitors (clotrimazole and SKF-525A, 100 μM). In summary, this assay system can be used to evaluate comprehensive metabolite-dependent MPT without identification or purification of metabolites. - Highlights: • We constructed a sequential assay system for toxic metabolite induced MPT in one pot. • 14 drugs (e.g. benzbromarone (BBR)) induced toxic metabolite dependent MPT. • Both the production of toxic metabolite and MPT could be inhibited by CYP inhibitors. • This system could evaluate the comprehensive MPT without purification of metabolites.

  14. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  15. Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

    International Nuclear Information System (INIS)

    Xu, Ming-Yuan; Wang, Pan; Sun, Ying-Jian; Wu, Yi-Jun

    2017-01-01

    Pesticides and heavy metals are widespread environmental pollutants. Although the acute toxicity of organophosphorus pesticide chlorpyrifos (CPF) and toxic heavy metal cadmium (Cd) is well characterized, the combined toxicity of CPF and Cd, especially the hepatotoxicity of the two chemicals with long-term exposure at a low dose, remained unclear. In this study, we investigated the toxicity in the liver of rats upon subchronic exposure to CPF and Cd at environmentally relevant doses. Rats were given three different doses (1/135 LD 50 , 1/45 LD 50 and 1/15 LD 50 ) of CPF and Cd as well as their mixtures by oral gavage for 90 days. After treatment, the liver tissues were subjected to histopathological examination and biochemical analysis. Gas chromatography-mass spectrometry (GC–MS) was used to analyze the metabolomic changes in the rat liver upon CPF, Cd and their mixtures treatment. The results showed that CPF and Cd-induced oxidative damage and disrupted energy, amino acid, and fatty acid metabolism in the liver. Eleven biomarkers in liver were identified for CPF-, Cd-, and their mixture-treated rats. Three metabolites, i.e., butanedioic acid, myo-inositol, and urea, were identified as unique biomarkers for the mixture-treated rats. Moreover, we found that Cd could accelerate the metabolism of CPF in the liver when given together to the rats, which may lead to the potential antagonistic interaction between CPF and Cd. In conclusion, our results indicated that even at environmentally relevant doses, CPF and Cd could disrupt the liver metabolism. In addition, the accelerated metabolism of CPF by Cd may lead to their potential antagonistic interaction.

  16. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

    International Nuclear Information System (INIS)

    Liu, Cong; Sekine, Shuichi; Ito, Kousei

    2016-01-01

    Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

  17. Reversal of acetaminophen-generated oxidative stress and concomitant hepatotoxicity by a phytopharmaceutical product

    Directory of Open Access Journals (Sweden)

    Afolabi C. Akinmoladun

    2017-03-01

    Full Text Available The increasing popularity of herbal medicine and the well-established health benefits of phytochemicals have spurred the multiplicity of nutraceutical and phytopharmaceutical products. In this study, Trévo™, a nutraceutical and phytopharmaceutical product, was evaluated for beneficial effects in acetaminophen-induced hepatic toxicity in Wistar rats. Animals received Trévo™ (1.5 mL/kg, 3.0 mL/kg or 4.5 mL/kg orally for 14 days. Hepatotoxicity was induced by the oral administration of acetaminophen (2 g/kg, 24 h prior to sacrifice. Biochemical liver function tests, oxidative stress indicators and histoarchitectural changes were evaluated. Acetaminophen administration occasioned significant increase (P < 0.05 in serum bilirubin level and activities of the aminotransferases, alkaline phosphatase, γ-glutamyltransferase and lactate dehydrogenase accompanied by a significant decrease (P < 0.05 in albumin level as well as histopathological alterations in liver sections. Promotion of hepatic oxidative stress by acetaminophen was revealed by significant (P < 0.05 increase in lipid peroxidation, depletion of reduced glutathione, and decrease in superoxide dismutase and catalase activities. Administration of Trévo™ remarkably ameliorated acetaminophen-induced histopathological alterations and changes in serum and tissue biochemical markers. The protective effect of Trévo™ (4.5 mL/kg was at par with that of Silymarin (25 mg/kg. The present study indicates that Trévo™ has notable salubrious effects.

  18. Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments.

    Directory of Open Access Journals (Sweden)

    Andrew K Smith

    2016-12-01

    Full Text Available Acetaminophen-induced liver injury in mice is a model for drug-induced liver injury in humans. A precondition for improved strategies to disrupt and/or reverse the damage is a credible explanatory mechanism for how toxicity phenomena emerge and converge to cause hepatic necrosis. The Target Phenomenon in mice is that necrosis begins adjacent to the lobule's central vein (CV and progresses outward. An explanatory mechanism remains elusive. Evidence supports that location dependent differences in NAPQI (the reactive metabolite formation within hepatic lobules (NAPQI zonation are necessary and sufficient prerequisites to account for that phenomenon. We call that the NZ-mechanism hypothesis. Challenging that hypothesis in mice is infeasible because 1 influential variables cannot be controlled, and 2 it would require sequential intracellular measurements at different lobular locations within the same mouse. Virtual hepatocytes use independently configured periportal-to-CV gradients to exhibit lobule-location dependent behaviors. Employing NZ-mechanism achieved quantitative validation targets for acetaminophen clearance and metabolism but failed to achieve the Target Phenomenon. We posited that, in order to do so, at least one additional feature must exhibit zonation by decreasing in the CV direction. We instantiated and explored two alternatives: 1 a glutathione depletion threshold diminishes in the CV direction; and 2 ability to repair mitochondrial damage diminishes in the CV direction. Inclusion of one or the other feature into NZ-mechanism failed to achieve the Target Phenomenon. However, inclusion of both features enabled successfully achieving the Target Phenomenon. The merged mechanism provides a multilevel, multiscale causal explanation of key temporal features of acetaminophen hepatotoxicity in mice. We discovered that variants of the merged mechanism provide plausible quantitative explanations for the considerable variation in 24-hour

  19. Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Zenya Saito

    2016-11-01

    Full Text Available Abstract Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST and/or alanine aminotransferase (ALT of more than twice the upper limit of normal (ULN. We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN, moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN, and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN. We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin. Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97. In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046. Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

  20. Ipomoea aquatica Extract Shows Protective Action Against Thioacetamide-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    A. Hamid A. Hadi

    2012-05-01

    Full Text Available In the Indian system of traditional medicine (Ayurveda it is recommended to consume Ipomoea aquatica to mitigate disorders like jaundice. In this study, the protective effects of ethanol extract of I. aquatica against liver damage were evaluated in thioacetamide (TAA-induced chronic hepatotoxicity in rats. There was no sign of toxicity in the acute toxicity study, in which Sprague-Dawley (SD rats were orally fed with I. aquatica (250 and 500 mg/kg for two months along with administration of TAA (i.p injection 200 mg/kg three times a week for two months. The results showed that the treatment of I. aquatica significantly lowered the TAA-induced serum levels of hepatic enzyme markers (ALP, ALT, AST, protein, albumin, bilirubin and prothrombin time. The hepatic content of activities and expressions SOD and CAT that were reduced by TAA were brought back to control levels by the plant extract supplement. Meanwhile, the rise in MDA level in the TAA receiving groups also were significantly reduced by I. aquatica treatment. Histopathology of hepatic tissues by H&E and Masson trichrome stains displayed that I. aquatica has reduced the incidence of liver lesions, including hepatic cells cloudy swelling, infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by TAA in rats. Therefore, the results of this study show that the protective effect of I. aquatica in TAA-induced liver damage might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects. Moreover, it confirms a scientific basis for the traditional use of I. aquatica for the treatment of liver disorders.

  1. Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

    International Nuclear Information System (INIS)

    Xu Jinsheng; Purcell, Wendy M.

    2006-01-01

    The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect the status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity

  2. Mechanism-based biomarker gene sets for glutathione depletion-related hepatotoxicity in rats

    International Nuclear Information System (INIS)

    Gao Weihua; Mizukawa, Yumiko; Nakatsu, Noriyuki; Minowa, Yosuke; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

    2010-01-01

    systems, could be promising biomarkers for preclinical examination of hepatotoxicity.

  3. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  4. Towards non-invasive 3D hepatotoxicity assays with optical coherence phase microscopy

    Science.gov (United States)

    Nelson, Leonard J.; Koulovasilopoulos, Andreas; Treskes, Philipp; Hayes, Peter C.; Plevris, John N.; Bagnaninchi, Pierre O.

    2015-03-01

    Three-dimensional tissue-engineered models are increasingly recognised as more physiologically-relevant than standard 2D cell culture for pre-clinical drug toxicity testing. However, many types of conventional toxicity assays are incompatible with dense 3D tissues. This study investigated the use of optical coherence phase microscopy (OCPM) as a novel approach to assess cell death in 3D tissue culture. For 3D micro-spheroid formation Human hepatic C3A cells were encapsulated in hyaluronic acid gels and cultured in 100μl MEME/10%FBS in 96-well plates. After spheroid formation the 3D liver constructs were exposed to acetaminophen on culture day 8. Acetaminophen hepatotoxicity in 3D cultures was evaluated using standard biochemical assays. An inverted OCPM in common path configuration was developed with a Callisto OCT engine (Thorlabs), centred at 930nm and a custom scanning head. Intensity data were used to perform in-depth microstructural imaging. In addition, phase fluctuations were measured by collecting several successive B scans at the same location, and statistics on the first time derivative of the phase, i.e. time fluctuations, were analysed over the acquisition time interval to retrieve overall cell viability. OCPM intensity (cell cluster size) and phase fluctuation statistics were directly compared with biochemical assays. In this study, we investigated optical coherence phase tomography to assess cell death in a 3d liver model after exposure to a prototypical hepatotoxin, acetaminophen. We showed that OCPM has the potential to assess noninvasively and label-free drug toxicity in 3D tissue models.

  5. Lycopene attenuates dichlorvos-induced oxidative damage and hepatotoxicity in rats.

    Science.gov (United States)

    El-Saad, Am Abu; Ibrahim, M M; Hazani, A A; El-Gaaly, G A

    2016-06-01

    Because of the widespread use of dichlorvos (DDVP) for domestic applications, evaluation of their toxic effects is of major concern to public health. Lycopene may lower oxidative stress by a mechanism that is not fully elucidated. The present study was undertaken to evaluate the protective efficacy of lycopene in terms of normalization of altered biochemical parameters following DDVP treatment in rats. Animals were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were orally treated with lycopene (10 mg kg(-1) body weight (b.w.)), DDVP (1.6 mg kg(-1) b.w.), and DDVP plus lycopene, respectively. Results showed that oral administration of DDVP for 30 days increased the levels of lipid peroxidation markers such as malondialdehyde, 4-hydroxynonanal, and protein carbonyl content in liver. Also, a decrease in levels of vitamin C, vitamin E, and reduced glutathione was detected due to DDVP administration. These were accompanied by a decrease in the activities of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase in the liver tissue. Moreover, DDVP increased the activities of serum transaminases, alkaline phosphatase, lactate dehydrogenase, and lipoxygenase, and the levels of bilirubin, total cholesterol, low-density lipoprotein cholesterol, triglyceride and DNA-protein crosslinks, and 8-hydroxy-2-deoxyguanosine, while decreased the level of high-density lipoprotein cholesterol. Our results provide new insights into the biochemical studies of relation between DDVP hepatotoxicity and lycopene treatment. Administration of lycopene to DDVP-treated rats reverted the status of hepatic markers to near-normal levels. These data suggest that lycopene can protect against the liver damage induced by DDVP. © The Author(s) 2015.

  6. Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice.

    Science.gov (United States)

    Li, Cong; Yi, Li-Tao; Geng, Di; Han, Yuan-Yuan; Weng, Lian-Jin

    2015-05-01

    The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China. The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl4-induced acute liver damage in mice. Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken. Compared with the model group, administration of 400 mg/kg BELE for 7 d in mice significantly decreased the serum ALT (56.25 U/L), AST (297.67 U/L), ALP (188.20 U/L), and TBIL (17.90 mol/L), along with the elevation of TP (64.67 g/L). In addition, BELE (100, 200, and 400 mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67 U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33 nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl4-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation. The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl4, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.

  7. Physiological changes due to hepatotoxicity and the protective role of some medicinal plants

    Directory of Open Access Journals (Sweden)

    Howida S. Abou Seif

    2016-06-01

    Full Text Available The liver is the largest, important organ and the site for essential biochemical reactions in the human body. It has the function to detoxify toxic substances and synthesize useful biomolecules. Therefore, damage to the liver leads to grave consequences. This damage resulted from chronic alcoholic abuse, viral hepatitis or inherited metabolic disease. Liver damage is associated with cellular necrosis, fibrosis, and increase in tissue lipid peroxidation and depletion in tissue glutathione level. Most of the hepatotoxic chemicals damage liver cells mainly by inducing lipid peroxidation and other oxidative damages in the liver. Natural antioxidants are found in many compounds classified as secondary plant metabolites, e.g. polyphenols (phenolic acids and flavonoids and terpenoids (carotenoids, and the consumption of foods that contain these compounds in large quantities seems to play an important role in prophylaxis against many diseases. Herbal medicines derived from plant extracts are being increasingly utilized to treat a wide variety of clinical disease. More attention has been paid to the protective effects of natural antioxidants against drug induced toxicities especially whenever free radical generation is involved. Popularity of herbal remedies is increasing and at least one quarter of patients with liver disease use botanicals. The World Health Organization (WHO estimates that 80 percent of the population of some Asian and African countries presently use herbal medicine for some aspect of primary health care. Some medicinal herbs have proven hepatoprotective potential. Silybum marianum (milk thistle has been used to treat liver diseases since the 16th century. Its major constituents are the flavonoids silibinin, silydianin, silychristin, and isosilibinin, of which silibinin is the biologically most active compound and used for standardization of pharmaceutical products.

  8. APOPTOTIC, HEPATOPROTECTIVE AND ANTIOXIDANT POTENTIAL OF A TRIHERBAL FORMULATION AGAINST D-GALACTOSAMINE HEPATOTOXICITY

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    Onyekachi Ogbonnaya IROANYA

    2016-12-01

    group. The data from this study suggest that GOV possess apoptotic, hepatoprotective and antioxidant activity against D-galactosamine induced hepatotoxicity in rats, thus providing scientific rationale for its use in traditional medicine for the treatment of liver diseases.

  9. Ethephon, an organophosphorous, a Fruit and Vegetable Ripener: Has potential hepatotoxic effects?

    Directory of Open Access Journals (Sweden)

    Pooja Bhadoria

    2018-01-01

    Full Text Available Introduction: In the recent years, ethephon, 2-chloroethylphosphonic acid, is one of the most commonly used plant growth regulators. At present, it is being used on fruits, vegetables, and cereals for promoting pre- and post-harvest ripening. The effect of artificial ripening has become questionable because of various health-related issues. This study was conducted to note the morphology of liver after ethephon administration as it is the site where chemicals undergo first pass metabolism and probably will be affected by ethephon. Materials and Methods: Adult Wistar albino rats were divided into experimental and control groups (10 each. Ethephon was administered at a dose of 200 mg/kg/day by a gavage tube in the experimental rats for 14 days. The animals were sacrificed within 24 h of the last dose; liver was dissected and processed for light microscopy. Hematoxylin and eosin-stained sections were studied using an image-pro express analyzer. The data obtained from control and experimental groups were statistically analyzed. Results: In the experimental rats, the body weight was found to be significantly decreased. The orderly arrangement of hepatocytes was disrupted and was replaced by blood-filled sinusoids. At sites, hepatocytes appeared to be degenerated. Councilman bodies with pyknotic nuclei and inflammatory infiltrations were seen. The population per unit area of the hepatocytes and Kupffer cells was 29.53 ± 10.65 versus 44.18 ± 10.31 and 25.12 ± 4.41versus 13.05 ± 6.5 in experimental and control groups, respectively. The decrease of hepatocytes and increase of Kupffer cells were found to be statistically significant. Conclusions: The observations in the liver are probably indicative of degenerative changes associated with ethephon. Hence, we can conclude that this plant growth regulator, Fruit and Vegetable Ripener, has hepatotoxic potential. General awareness and regarding the use of such plant growth regulators is must to reduce the

  10. Assessment of mitochondrial dysfunction-related, drug-induced hepatotoxicity in primary rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Cong; Sekine, Shuichi, E-mail: ssekine@faculty.chiba-u.jp; Ito, Kousei

    2016-07-01

    Evidence that mitochondrial dysfunction plays a central role in drug-induced liver injury is rapidly accumulating. In contrast to physiological conditions, in which almost all adenosine triphosphate (ATP) in hepatocytes is generated in mitochondria via aerobic respiration, the high glucose content and limited oxygen supply of conventional culture systems force primary hepatocytes to generate most ATP via cytosolic glycolysis. Thus, such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, and are not suitable to identify drugs with mitochondrial liabilities. In this study, primary rat hepatocytes were cultured in galactose-based medium, instead of the conventional glucose-based medium, and in hyperoxia to improve the reliance of energy generation on aerobic respiration. Activation of mitochondria was verified by diminished cellular lactate release and increased oxygen consumption. These conditions improved sensitivity to the mitochondrial complex I inhibitor rotenone. Since oxidative stress is also a general cause of mitochondrial impairment, cells were exposed to test compounds in the presence of transferrin to increase the generation of reactive oxygen species via increased uptake of iron. Finally, 14 compounds with reported mitochondrial liabilities were tested to validate this new drug-induced mitochondrial toxicity assay. Overall, the culture of primary rat hepatocytes in galactose, hyperoxia and transferrin is a useful model for the identification of mitochondrial dysfunction-related drug-induced hepatotoxicity. - Highlights: • Drug-induced mitochondrial toxicity was evaluated using primary rat hepatocytes. • Galactose and hyperoxia could activate OXPHOS in primary rat hepatocytes. • Cells with enhanced OXPHOS exhibit improved sensitivity to mitochondrial toxins. • Transferrin potentiate mitochondrial toxicity via increased ROS production.

  11. NID Copper Sample Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kouzes, Richard T.; Zhu, Zihua

    2011-02-01

    The current focal point of the nuclear physics program at PNNL is the MAJORANA DEMONSTRATOR, and the follow-on Tonne-Scale experiment, a large array of ultra-low background high-purity germanium detectors, enriched in 76Ge, designed to search for zero-neutrino double-beta decay (0νββ). This experiment requires the use of germanium isotopically enriched in 76Ge. The DEMONSTRATOR will utilize 76Ge from Russia, but for the Tonne-Scale experiment it is hoped that an alternate technology under development at Nonlinear Ion Dynamics (NID) will be a viable, US-based, lower-cost source of separated material. Samples of separated material from NID require analysis to determine the isotopic distribution and impurities. The MAJORANA DEMONSTRATOR is a DOE and NSF funded project with a major science impact. DOE is funding NID through an SBIR grant for development of their separation technology for application to the Tonne-Scale experiment. The Environmental Molecular Sciences facility (EMSL), a DOE user facility at PNNL, has the required mass spectroscopy instruments for making these isotopic measurements that are essential to the quality assurance for the MAJORANA DEMONSTRATOR and for the development of the future separation technology required for the Tonne-Scale experiment. A sample of isotopically separated copper was provided by NID to PNNL for isotopic analysis as a test of the NID technology. The results of that analysis are reported here.

  12. NID Copper Sample Analysis

    International Nuclear Information System (INIS)

    Kouzes, Richard T.; Zhu, Zihua

    2011-01-01

    The current focal point of the nuclear physics program at PNNL is the MAJORANA DEMONSTRATOR, and the follow-on Tonne-Scale experiment, a large array of ultra-low background high-purity germanium detectors, enriched in 76 Ge, designed to search for zero-neutrino double-beta decay (0νββ). This experiment requires the use of germanium isotopically enriched in 76 Ge. The DEMONSTRATOR will utilize 76 Ge from Russia, but for the Tonne-Scale experiment it is hoped that an alternate technology under development at Nonlinear Ion Dynamics (NID) will be a viable, US-based, lower-cost source of separated material. Samples of separated material from NID require analysis to determine the isotopic distribution and impurities. The MAJORANA DEMONSTRATOR is a DOE and NSF funded project with a major science impact. DOE is funding NID through an SBIR grant for development of their separation technology for application to the Tonne-Scale experiment. The Environmental Molecular Sciences facility (EMSL), a DOE user facility at PNNL, has the required mass spectroscopy instruments for making these isotopic measurements that are essential to the quality assurance for the MAJORANA DEMONSTRATOR and for the development of the future separation technology required for the Tonne-Scale experiment. A sample of isotopically separated copper was provided by NID to PNNL for isotopic analysis as a test of the NID technology. The results of that analysis are reported here.

  13. Construction and analysis of a human hepatotoxicity database suitable for QSAR modeling using post-market safety data

    International Nuclear Information System (INIS)

    Zhu, Xiao; Kruhlak, Naomi L.

    2014-01-01

    Graphical abstract: - Abstract: Drug-induced liver injury (DILI) is one of the most common drug-induced adverse events (AEs) leading to life-threatening conditions such as acute liver failure. It has also been recognized as the single most common cause of safety-related post-market withdrawals or warnings. Efforts to develop new predictive methods to assess the likelihood of a drug being a hepatotoxicant have been challenging due to the complexity and idiosyncrasy of clinical manifestations of DILI. The FDA adverse event reporting system (AERS) contains post-market data that depict the morbidity of AEs. Here, we developed a scalable approach to construct a hepatotoxicity database using post-market data for the purpose of quantitative structure–activity relationship (QSAR) modeling. A set of 2029 unique and modelable drug entities with 13,555 drug-AE combinations was extracted from the AERS database using 37 hepatotoxicity-related query preferred terms (PTs). In order to determine the optimal classification scheme to partition positive from negative drugs, a manually-curated DILI calibration set composed of 105 negatives and 177 positives was developed based on the published literature. The final classification scheme combines hepatotoxicity-related PT data with supporting information that optimize the predictive performance across the calibration set. Data for other toxicological endpoints related to liver injury such as liver enzyme abnormalities, cholestasis, and bile duct disorders, were also extracted and classified. Collectively, these datasets can be used to generate a battery of QSAR models that assess a drug's potential to cause DILI

  14. Modulation of trabectedin (ET-743) hepatobiliary disposition by multidrug resistance-associated proteins (Mrps) may prevent hepatotoxicity

    International Nuclear Information System (INIS)

    Lee, Jin Kyung; Leslie, Elaine M.; Zamek-Gliszczynski, Maciej J.; Brouwer, Kim L.R.

    2008-01-01

    Trabectedin is a promising anticancer agent, but dose-limiting hepatotoxicity was observed during phase I/II clinical trials. Dexamethasone (DEX) has been shown to significantly reduce trabectedin-mediated hepatotoxicity. The current study was designed to assess the capability of sandwich-cultured primary rat hepatocytes (SCRH) to predict the hepato-protective effect of DEX against trabectedin-mediated cytotoxicity. The role of multidrug resistance-associated protein 2 (Mrp2; Abcc2) in trabectedin hepatic disposition also was examined. In SCRH from wild-type Wistar rats, cytotoxicity was observed after 24-h continuous exposure to trabectedin. SCRH pretreated with additional DEX (1 μM) exhibited a 2- to 3-fold decrease in toxicity at 100 nM and 1000 nM trabectedin. Unexpectedly, toxicity in SCRH from Mrp2-deficient (TR - ) compared to wild-type Wistar rats was markedly reduced. Depletion of glutathione from SCRH using buthionine sulfoximine (BSO) mitigated trabectedin toxicity associated with 100 nM and 1000 nM trabectedin. Western blot analysis demonstrated increased levels of CYP3A1/2 and Mrp2 in SCRH pretreated with DEX; interestingly, Mrp4 expression was increased in SCRH after BSO exposure. Trabectedin biliary recovery in isolated perfused livers from TR - rats was decreased by ∼ 75% compared to wild-type livers. In conclusion, SCRH represent a useful in vitro model to predict the hepatotoxicity of trabectedin observed in vivo. The protection by DEX against trabectedin-mediated cytotoxicity may be attributed, in part, to enhanced Mrp2 biliary excretion and increased metabolism by CYP3A1/2. Decreased trabectedin toxicity in SCRH from TR - rats, and in SCRH pretreated with BSO, may be due to increased basolateral excretion of trabectedin by Mrp3 and/or Mrp4

  15. Herb-Drug Interaction between the Traditional Hepatoprotective Formulation and Sorafenib on Hepatotoxicity, Histopathology and Pharmacokinetics in Rats

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    Chin-Tsung Ting

    2017-06-01

    Full Text Available Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC. In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited information about the herb-drug interactions is available. We hypothesize that the Chinese herbal medicine may exert hepatoprotective effects on the sorafenib-treated group. The aim of this study is to investigate the pharmacokinetic mechanism of drug-drug interactions of sorafenib including interacting with hepatoprotective formulation, Long-Dan-Xie-Gan-Tang formulation (LDXGT and with two cytochrome P450 3A4 (CYP3A4 inhibitors, grapefruit juice and ketoconazole. Liver enzyme levels and histopathology of liver slices were used to evaluate sorafenib-induced hepatotoxicity and the potential hepatoprotective effects of the LDXGT formulation on subjects treated with the combination of sorafenib and the herbal medicine. In this study, a validated HPLC-photodiode array analytical system was developed for the pharmacokinetic study of sorafenib in rats. As the result of the pharmacokinetic data, pretreatment with the LDXGT formulation did not significantly interact with sorafenib compared with sorafenib oral administration alone. Furthermore, grapefruit juice and ketoconazole did not significantly affect sorafenib metabolism. Furthermore, pretreatment with variable, single or repeat doses of the LDXGT formulation did not suppress or exacerbate the sorafenib-induced hepatotoxicity and histopathological alterations. According to these results, the LDXGT formulation is safe, but has no beneficial effects on sorafenib-induced hepatotoxicity. A detailed clinical trial should be performed to further evaluate the efficacy or adverse effects of the LDXGT formulation in combination with sorafenib in humans.

  16. Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo.

    Science.gov (United States)

    Brillant, Nathalie; Elmasry, Mohamed; Burton, Neal C; Rodriguez, Josep Monne; Sharkey, Jack W; Fenwick, Stephen; Poptani, Harish; Kitteringham, Neil R; Goldring, Christopher E; Kipar, Anja; Park, B Kevin; Antoine, Daniel J

    2017-10-01

    The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention. Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to. Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint; r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04). For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration. Copyright © 2017

  17. Fumonisin B{sub 1} hepatotoxicity in mice is attenuated by depletion of Kupffer cells by gadolinium chloride

    Energy Technology Data Exchange (ETDEWEB)

    He, Quanren [Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389 (United States); Kim, Jiyoung [Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389 (United States); Sharma, Raghubir P [Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389 (United States)

    2005-02-01

    Fumonisin B{sub 1} (FB{sub 1}) is a toxic and carcinogenic mycotoxin produced by Fusarium verticillioides found on corn worldwide. The biological effects of FB{sub 1} are attributed to sphingolipid metabolism disruption as a result of ceramide synthase inhibition. Tumor necrosis factor {alpha} (TNF{alpha}) is an important modulator of FB{sub 1} hepatotoxicity. Kupffer cells are major source of cytokine production in liver. In the present study we investigated the effects of Kupffer cell depletion by gadolinium on FB{sub 1} hepatotoxicity in female BALB/c mice. Mice were given saline or 50 mg/kg of gadolinium chloride once via the tail vein; 16 h later they were treated with subcutaneous injections of vehicle or 2.25 mg/kg/day FB{sub 1} in saline for three successive days. Gadolinium significantly attenuated FB{sub 1}-induced increases in the activities of circulating alanine aminotransferase and aspartate aminotransferase and reduced the FB{sub 1}-induced hepatocyte apoptosis and free sphinganine accumulation in liver. Both gadolinium and FB{sub 1} treatments individually increased the expression of selected cell signal factors; e.g., TNF{alpha}, TNF receptor 1, TNF-related apoptosis-inducing ligand, lymphotoxin {beta}, interferon {gamma}, and transforming growth factor {beta}1; gadolinium chloride did not alter FB{sub 1}-induced expression of the above genes. Results indicated that Kupffer cells play a role in FB{sub 1} hepatotoxicity. Decreased FB{sub 1}-induced sphinganine accumulation and increased protective TNF{alpha} signaling by gadolinium chloride may in part account for its ameliorating effect on FB{sub 1} liver damage.

  18. Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis.

    Science.gov (United States)

    Chen, Zhu; Li, Xiang-Pei; Li, Zhi-Jun; Xu, Liang; Li, Xiao-Mei

    2013-03-01

    Combination use of methotrexate (MTX) and leflunomide (LEF) has been proved effective in the treatment of active rheumatoid arthritis (RA). However, previous trials have documented that both are associated with increased incidence of liver toxicity. As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall, total glucosides of paeony (TGP) have been shown to have anti-inflammatory, hepatoprotective and immuno-regulatory activities, without evident toxicity or side effects. In this 24-week, open label, randomized multicenter clinical trial, we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA. A total of 204 patients with active RA (DAS28>3.2) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy (MTX 10 mg/week plus LEF 20 mg/day) with or without TGP for up to 24 weeks by randomization. Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Significantly less frequent hepatotoxicity was observed in patients with TGP than those without (9.5% vs 34.8%, p 1.5 to ≤2 times and >2 to ≤3 times the ULN were lower in TGP group than the control (1.9% vs 10.1%, 2.9% vs 12.4%, p TGP group achieved a European League Against Rheumatism (EULAR) good response or moderate response at 12 weeks, although there is no statistical significance. Similar results were observed at 24 weeks. Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. The Protective Effect of Liquorice Plant Extract on CCl4-Induced Hepatotoxicity in Common Carp (Cyprinus carpio

    Directory of Open Access Journals (Sweden)

    Hassan Malekinejad

    2010-12-01

    Full Text Available The protective effect of liquorice plant extract (LPE on CCl4-induced hepatotoxicity in common carp was evaluated using fifty adult carps. The fish were cultured in a standard environment in terms of water flow rate, oxygen, pH, food and temperature. The fish were assigned into 5 groups (N = 10 as control, sham, and tests. The test groups were pre-treated for 3 h with various concentrations of LPE, 3 days before CCl4 exposure. The control and sham groups received normal saline before and after CCl4 exposure. To induce hepatotoxicity, animals in the sham and test groups were exposed against 100 l L-1 CCl4 for 45 min. The fish in all groups 1 h after CCl4 exposure were anesthetized and the blood samples were collected. Immediately the liver specimens were dissected out and were stored in 10 % formalin for further pathological studies. Determination of serum level of ALP and SGOT revealed that acute form of CCl4 exposure elevated significantly (P < 0.05 the serum level of either tested hepatic marker enzymes. While 3 days pretreatment with LPE prevented from ALP and SGOT enhancement. The pathological evaluation revealed that the CCl4 exposure resulted in a minor pathologic manifestation such as slight congestion, which the LPE pretreated groups showed the remarkable improvement. The anti-oxidant capacity of LPE was assayed by FRAP and DPPH methods. Both provided techniques showed that LPE exerts an excellent anti-oxidant effect. This data suggest that LPE exerts protective effect against CCl4-induced hepatotoxicity. Moreover, the hepatoprotective effect of LPE may attribute to its antioxidant capacity.

  20. A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

    Science.gov (United States)

    Basu, Tapasree; Panja, Sourav; Shendge, Anil Khushalrao; Das, Abhishek; Mandal, Nripendranath

    2018-05-01

    Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation. © 2018 Wiley Periodicals, Inc.

  1. Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals.

    Science.gov (United States)

    Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Saidulu, A; Hayath, Md Sikinder

    2011-10-01

    Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Improving Beneficiation of Copper and Iron from Copper Slag by Modifying the Molten Copper Slag

    Directory of Open Access Journals (Sweden)

    Zhengqi Guo

    2016-04-01

    Full Text Available In the paper, a new technology was developed to improve the beneficiation of copper and iron components from copper slag, by modifying the molten slag to promote the mineralization of valuable minerals and to induce the growth of mineral grains. Various parameters, including binary basicity, dosage of compound additive, modification temperature, cooling rate and the end point temperature of slow cooling were investigated. Meanwhile, optical microscope, scanning electron microscope and energy dispersive spectrometer (SEM-EDS was employed to determine the mineralogy of the modified and unmodified slag, as well as to reveal the mechanisms of enhancing beneficiation. The results show that under the proper conditions, the copper grade of rougher copper concentrate was increased from 6.43% to 11.04%, iron recovery of magnetic separation was increased significantly from 32.40% to 63.26%, and other evaluation indexes were changed slightly, in comparison with unmodified copper slag. Moreover, matte and magnetite grains in the modified slag aggregated together and grew obviously to the mean size of over 50 μm, resulting in an improvement of beneficiation of copper and iron.

  3. Influence of sex and developmental stage on acute hepatotoxic and inflammatory responses to liver procarcinogens in the mouse

    International Nuclear Information System (INIS)

    Hanna, Daniel; Riedmaier, Ariane Emami; Sugamori, Kim S.; Grant, Denis M.

    2016-01-01

    The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development. We also recently observed that female but not male mice exposed postnatally to ABP had slightly increased expression of the antioxidant defense genes Nqo1 and Ggt1, which are regulated by the oxidative stress response protein nuclear factor erythroid 2-related factor 2 (NRF2), while expression of Hmox1 was increased in both sexes. The goal of the present study was therefore to compare selected acute hepatotoxic, inflammatory and oxidative stress defense responses to ABP, DEN, or the prototype hepatotoxicant carbon tetrachloride (CCl 4 ), in male and female mice exposed to these chemicals either postnatally or as adults. Exposure of adult mice to ABP, DEN or CCl 4 produced a 2-fold greater acute elevation in serum levels of the hepatotoxicity biomarker alanine aminotransferase (ALT) in males than in females, while levels of the inflammatory biomarker interleukin-6 (IL-6) showed no sex difference. However, treatment of immature mice with either ABP or DEN using standard tumor-inducing postnatal exposure protocols produced no increase in serum ALT or IL-6 levels in either males or females, while CCl 4 produced a 40-fold ALT elevation but with no sex difference. Basal expression of the NRF2-responsive gene Nqo1 was higher in adult females than in males, but there was no sex difference in basal expression of Ggt1 or Hmox1. Sexually immature animals showed no sex difference in basal

  4. Fentanyl Enhances Hepatotoxicity of Paclitaxel via Inhibition of CYP3A4 and ABCB1 Transport Activity in Mice

    Science.gov (United States)

    Pan, Jia-Hao; Bi, Bing-Tian; Feng, Kun-Yao; Huang, Wan; Zeng, Wei-An

    2015-01-01

    Fentanyl, a potent opioid analgesic that is used to treat cancer pain, is commonly administered with paclitaxel in advanced tumors. However, the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanism of action is not well studied. The purpose of this study was to investigate the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanisms of action. Pharmacokinetic parameters of paclitaxel were tested using reversed phase high-performance liquid chromatography (RP-HPLC). Aspartate transaminase (AST), alanine aminotransferase (ALT), and mouse liver histopathology were examined. Moreover, the cytotoxicity of anti-carcinogens was examined using 1-(4, 5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), and the intracellular accumulation of doxorubicin and rhodamine 123 was detected by flow cytometry. Furthermore, the expression of ABCB1 and the activity of ABCB1 ATPase and CYP3A4 were also examined. In this study, the co-administration of fentanyl and paclitaxel prolonged the half-life (t1/2) of paclitaxel from 1.455 hours to 2.344 hours and decreased the clearance (CL) from 10.997 ml/h to 7.014 ml/h in mice. Fentanyl significantly increased the levels of ALT in mice to 88.2 U/L, which is more than 2-fold higher than the level detected in the control group, and it increased the histological damage in mouse livers. Furthermore, fentanyl enhanced the cytotoxicity of anti-carcinogens that are ABCB1 substrates and increased the accumulation of doxorubicin and rhodamine 123. Additionally, fentanyl stimulated ABCB1 ATPase activity and inhibited CYP3A4 activity in the liver microsomes of mice. Our study indicates that the obvious hepatotoxicity during this co-administration was due to the inhibition of CYP3A4 activity and ABCB1 transport activity. These findings suggested that the accumulation-induced hepatotoxicity of paclitaxel when it is combined with fentanyl should be avoided. PMID:26633878

  5. Analysis of changes in hepatic gene expression in a murine model of tolerance to acetaminophen hepatotoxicity (autoprotection)

    International Nuclear Information System (INIS)

    O'Connor, Meeghan A.; Koza-Taylor, Petra; Campion, Sarah N.; Aleksunes, Lauren M.; Gu, Xinsheng; Enayetallah, Ahmed E.; Lawton, Michael P.; Manautou, José E.

    2014-01-01

    Pretreatment of mice with a low hepatotoxic dose of acetaminophen (APAP) results in resistance to a subsequent, higher dose of APAP. This mouse model, termed APAP autoprotection was used here to identify differentially expressed genes and cellular pathways that could contribute to this development of resistance to hepatotoxicity. Male C57BL/6J mice were pretreated with APAP (400 mg/kg) and then challenged 48 h later with 600 mg APAP/kg. Livers were obtained 4 or 24 h later and total hepatic RNA was isolated and hybridized to Affymetrix Mouse Genome MU430 2 GeneChip. Statistically significant genes were determined and gene expression changes were also interrogated using the Causal Reasoning Engine (CRE). Extensive literature review narrowed our focus to methionine adenosyl transferase-1 alpha (MAT1A), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), flavin-containing monooxygenase 3 (Fmo3) and galectin-3 (Lgals3). Down-regulation of MAT1A could lead to decreases in S-adenosylmethionine (SAMe), which is known to protect against APAP toxicity. Nrf2 activation is expected to play a role in protective adaptation. Up-regulation of Lgals3, one of the genes supporting the Nrf2 hypothesis, can lead to suppression of apoptosis and reduced mitochondrial dysfunction. Fmo3 induction suggests the involvement of an enzyme not known to metabolize APAP in the development of tolerance to APAP toxicity. Subsequent quantitative RT-PCR and immunochemical analysis confirmed the differential expression of some of these genes in the APAP autoprotection model. In conclusion, our genomics strategy identified cellular pathways that might further explain the molecular basis for APAP autoprotection. - Highlights: • Differential expression of genes in mice resistant to acetaminophen hepatotoxicity. • Increased gene expression of Flavin-containing monooxygenase 3 and Galectin-3. • Decrease in MAT1A expression and compensatory hepatocellular regeneration. • Two distinct gene expression

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-03-01

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

  7. Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation

    Directory of Open Access Journals (Sweden)

    Mathavan Sinnakaruppan

    2010-03-01

    Full Text Available Abstract Background Mercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information on in vivo molecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in the in vitro human cell line studies. Results Hepato-transcriptome analysis of mercury-exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations. Conclusion Mercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling

  8. Analysis of changes in hepatic gene expression in a murine model of tolerance to acetaminophen hepatotoxicity (autoprotection)

    Energy Technology Data Exchange (ETDEWEB)

    O' Connor, Meeghan A., E-mail: meeghan.oconnor@boehringer-ingelheim.com [Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-3092 (United States); Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877-0368 (United States); Koza-Taylor, Petra, E-mail: petra.h.koza-taylor@pfizer.com [Pfizer Inc., Groton, CT 06340 (United States); Campion, Sarah N., E-mail: sarah.campion@pfizer.com [Pfizer Inc., Groton, CT 06340 (United States); Aleksunes, Lauren M., E-mail: aleksunes@eohsi.rutgers.edu [Rutgers University, Department of Pharmacology and Toxicology, Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08854 (United States); Gu, Xinsheng, E-mail: xinsheng.gu@uconn.edu [Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-3092 (United States); Enayetallah, Ahmed E., E-mail: ahmed.enayetallah@pfizer.com [Pfizer Inc., Groton, CT 06340 (United States); Lawton, Michael P., E-mail: michael.lawton@pfizer.com [Pfizer Inc., Groton, CT 06340 (United States); Manautou, José E., E-mail: jose.manautou@uconn.edu [Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-3092 (United States)

    2014-01-01

    Pretreatment of mice with a low hepatotoxic dose of acetaminophen (APAP) results in resistance to a subsequent, higher dose of APAP. This mouse model, termed APAP autoprotection was used here to identify differentially expressed genes and cellular pathways that could contribute to this development of resistance to hepatotoxicity. Male C57BL/6J mice were pretreated with APAP (400 mg/kg) and then challenged 48 h later with 600 mg APAP/kg. Livers were obtained 4 or 24 h later and total hepatic RNA was isolated and hybridized to Affymetrix Mouse Genome MU430{sub 2} GeneChip. Statistically significant genes were determined and gene expression changes were also interrogated using the Causal Reasoning Engine (CRE). Extensive literature review narrowed our focus to methionine adenosyl transferase-1 alpha (MAT1A), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), flavin-containing monooxygenase 3 (Fmo3) and galectin-3 (Lgals3). Down-regulation of MAT1A could lead to decreases in S-adenosylmethionine (SAMe), which is known to protect against APAP toxicity. Nrf2 activation is expected to play a role in protective adaptation. Up-regulation of Lgals3, one of the genes supporting the Nrf2 hypothesis, can lead to suppression of apoptosis and reduced mitochondrial dysfunction. Fmo3 induction suggests the involvement of an enzyme not known to metabolize APAP in the development of tolerance to APAP toxicity. Subsequent quantitative RT-PCR and immunochemical analysis confirmed the differential expression of some of these genes in the APAP autoprotection model. In conclusion, our genomics strategy identified cellular pathways that might further explain the molecular basis for APAP autoprotection. - Highlights: • Differential expression of genes in mice resistant to acetaminophen hepatotoxicity. • Increased gene expression of Flavin-containing monooxygenase 3 and Galectin-3. • Decrease in MAT1A expression and compensatory hepatocellular regeneration. • Two distinct gene

  9. Renal cortex copper concentration in acute copper poisoning in calves

    Directory of Open Access Journals (Sweden)

    Luis E. Fazzio

    2012-01-01

    Full Text Available The aim of this study was to estimate the diagnostic value of renal cortex copper (Cu concentration in clinical cases of acute copper poisoning (ACP. A total of 97 calves that died due to subcutaneous copper administration were compiled in eleven farms. At least, one necropsy was conducted on each farm and samples for complementary analysis were taken. The degree of autolysis in each necropsy was evaluated. The cases appeared on extensive grazing calf breeding and intensive feedlot farms, in calves of 60 to 200 kg body weight. Mortality varied from 0.86 to 6.96 %, on the farms studied. The first succumbed calf was found on the farms between 6 and 72 hours after the susbcutaneous Cu administration. As discrepancies regarding the reference value arose, the local value (19.9 parts per million was used, confirming the diagnosis of acute copper poisoning in 93% of the analyzed kidney samples. These results confirm the value of analysis of the cortical kidney Cu concentration for the diagnosis of acute copper poisoning.

  10. Copper metallurgy at the crossroads

    Directory of Open Access Journals (Sweden)

    Habashi F.

    2007-01-01

    Full Text Available Copper technology changed from the vertical to the horizontal furnace and from the roast reaction to converting towards the end of the last century. However, the horizontal furnace proved to be an inefficient and polluting reactor. As a result many attempts were made to replace it. In the past 50 years new successful melting processes were introduced on an industrial scale that were more energy efficient and less polluting. In addition, smelting and converting were conducted in a single reactor in which the concentrate was fed and the raw copper was produced. The standing problem in many countries, however, is marketing 3 tonnes of sulfuric acid per tonne of copper produced as well as emitting large amounts of excess SO2 in the atmosphere. Pressure hydrometallurgy offers the possibility of liberating the copper industry from SO2 problem. Heap leaching technology has become a gigantic operation. Combined with solvent extraction and electrowinning it contributes today to about 20% of copper production and is expected to grow. Pressure leaching offers the possibility of liberating the copper industry from SO2 problem. The technology is over hundred years old. It is applied for leaching a variety of ores and concentrates. Hydrothermal oxidation of sulfide concentrates has the enormous advantage of producing elemental sulfur, hence solving the SO2 and sulfuric acid problems found in smelters. Precipitation of metals such as nickel and cobalt under hydrothermal conditions has been used for over 50 years. It has the advantage of a compact plant but the disadvantage of producing ammonium sulfate as a co-product. In case of copper, however, precipitation takes place without the need of neutralizing the acid, which is a great advantage and could be an excellent substitute for electrowinning which is energy intensive and occupies extensive space. Recent advances in the engineering aspects of pressure equipment design open the door widely for increased

  11. Laboratory verification of the Active Particle-induced X-ray Spectrometer (APXS) on the Chang'e-3 mission

    International Nuclear Information System (INIS)

    Zhang, Guang-Liang; Li, Chun-Lai; Fu, Xiao-Hui; Zhang, Li-Yan; Ban, Cao; Li, Han; Zou, Yong-Liao; Peng, Wen-Xi; Cui, Xing-Zhu; Zhang, Cheng-Mo; Wang, Huan-Yu

    2015-01-01

    In the Chang'e-3 mission, the Active Particle-induced X-ray Spectrometer (APXS) on the Yutu rover is used to analyze the chemical composition of lunar soil and rock samples. APXS data are only valid are only if the sensor head gets close to the target and integration time lasts long enough. Therefore, working distance and integration time are the dominant factors that affect APXS results. This study confirms the ability of APXS to detect elements and investigates the effects of distance and time on the measurements. We make use of a backup APXS instrument to determine the chemical composition of both powder and bulk samples under the conditions of different working distances and integration times. The results indicate that APXS can detect seven major elements, including Mg, Al, Si, K, Ca, Ti and Fe under the condition that the working distance is less than 30 mm and having an integration time of 30 min. The statistical deviation is smaller than 15%. This demonstrates the instrument's ability to detect major elements in the sample. Our measurements also indicate the increase of integration time could reduce the measurement error of peak area, which is useful for detecting the elements Mg, Al and Si. However, an increase in working distance can result in larger errors in measurement, which significantly affects the detection of the element Mg. (paper)

  12. Simultaneous quantification of Li, Ti and O in Lithium titanate by particle induced gamma-ray emission using 8 MeV proton beam

    International Nuclear Information System (INIS)

    Chhillar, Sumit; Acharya, R.; Tripathi, R.; Sodaye, S.; Sudarshan, K.; Pujari, P.K.; Rout, P.C.; Mukherjee, S.K.

    2014-01-01

    Simultaneous quantification of Li, Ti and O in lithium titanate (Li 2 TiO 3 ) is difficult by particle induced gamma-ray emission (PIGE) using low energy (∼4 MeV) proton beam. PIGE method using 8 MeV proton beam at BARC-TIFR pelletron facility was standardized for compositional characterization of sol-gel synthesized Li 2 TiO 3 by determining concentrations of Li, Ti and O simultaneously. Thick targets of samples, synthetic samples and standards were prepared in graphite matrix. Beam current variation was normalized by Rutherford Backscattering Spectrometry (RBS) using a thin gold foil. The gamma-rays of 478, 981 and 6129 keV were measured from 7 Li(p, p'γ) 7 Li, 48 Ti(p, p'γ) 48 Ti and 16 O(p, p'γ) 16 O nuclear reactions for quantification of Li, Ti and O, respectively. The method was validated by determining concentrations of Li, TI and O in a synthetic sample. (author)

  13. An amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis B virus core particles induces a strong and highly cross-reactive antibody response in mice

    International Nuclear Information System (INIS)

    Geldmacher, Astrid; Skrastina, Dace; Petrovskis, Ivars; Borisova, Galina; Berriman, John A.; Roseman, Alan M.; Crowther, R. Anthony; Fischer, Jan; Musema, Shamil; Gelderblom, Hans R.; Lundkvist, Aake; Renhofa, Regina; Ose, Velta; Krueger, Detlev H.; Pumpens, Paul; Ulrich, Rainer

    2004-01-01

    Previously, we have demonstrated that hepatitis B virus (HBV) core particles tolerate the insertion of the amino-terminal 120 amino acids (aa) of the Puumala hantavirus nucleocapsid (N) protein. Here, we demonstrate that the insertion of 120 amino-terminal aa of N proteins from highly virulent Dobrava and Hantaan hantaviruses allows the formation of chimeric core particles. These particles expose the inserted foreign protein segments, at least in part, on their surface. Analysis by electron cryomicroscopy of chimeric particles harbouring the Puumala virus (PUUV) N segment revealed 90% T = 3 and 10% T = 4 shells. A map computed from T = 3 shells shows additional density splaying out from the tips of the spikes producing the effect of an extra shell of density at an outer radius compared with wild-type shells. The inserted Puumala virus N protein segment is flexibly linked to the core spikes and only partially icosahedrally ordered. Immunisation of mice of two different haplotypes (BALB/c and C57BL/6) with chimeric core particles induces a high-titered and highly cross-reactive N-specific antibody response in both mice strains

  14. Elemental and mineralogical study of earth-based pigments using particle induced X-ray emission and X-ray diffraction

    International Nuclear Information System (INIS)

    Nel, P.; Lynch, P.A.; Laird, J.S.; Casey, H.M.; Goodall, L.J.; Ryan, C.G.; Sloggett, R.J.

    2010-01-01

    Artwork and precious artefacts demand non-destructive analytical methodologies for art authentication, attribution and provenance assessment. However, structural and chemical characterisation represents a challenging problem with existing analytical techniques. A recent authentication case based on an Australian Aboriginal artwork, indicate there is substantial benefit in the ability of particle induced X-ray emission (PIXE), coupled with dynamic analysis (DA) to characterise pigments through trace element analysis. However, this information alone is insufficient for characterising the mineralogical residence of trace elements. For this reason a combined methodology based on PIXE and X-ray diffraction (XRD) has been performed to explore the benefits of a more comprehensive data set. Many Aboriginal paintings and artefacts are predominantly earth pigment based. This makes these cultural heritage materials an ideal case study for testing the above combined methodological approach on earth-based pigments. Samples of synthetic and naturally occurring earth-based pigments were obtained from a range of sources, which include Indigenous communities within Australia's Kimberley region. PIXE analyses using a 3 MeV focussed proton beam at the CSIRO nuclear microprobe, as well as laboratory-based XRD was carried out on the above samples. Elemental signature spectra as well as mineralogical data were used to assess issues regarding synthetic and naturally occurring earth pigments with the ultimate aim of establishing provenance.

  15. Investigation of copper nuclei

    International Nuclear Information System (INIS)

    Delfini, M.G.

    1983-01-01

    An extensive study has been performed on copper isotopes in the mass region A=63-66. The results of a precise measurement are presented on the properties of levels of 64 Cu and 66 Cu. They were obtained by bombarding the 63 Cu and 65 Cu nuclei with neutrons. The gamma spectra collected after capture of thermal, 2-keV, 24-keV neutrons have been analysed and combined to give a rather extensive set of precise level energies and gamma transition strengths. From the angular distribution of the gamma rays it is possible to obtain information concerning the angular momentum J of several low-lying states. The level schemes derived from such measurements have been used as a test for calculations in the framework of the shell model. The spectral distributions of eigenstates in 64 Cu for different configuration spaces are presented and discussed. In this study the relative importance of configurations with n holes in the 1f7/2 shell with n up to 16, are investigated. It is found that the results strongly depend on the values of the single-particle energies. The results of the spectral-distribution method were utilized for shell-model calculations. From the information obtained from the spectral analysis it was decided to adopt a configuration space which includes up to one hole in the 1f7/2 shell and up to two particles in the 1g9/2 shell. Further, restrictions on seniority and on the coupling of the two particles in the 1g9/2 orbit have been applied and their effects have been studied. It is found that the calculated excitation energies reproduce the measured values in a satisfactory way, but that some of the electromagnetic properties are less well in agreement with experimental data. (Auth.)

  16. LIGNOCELLULOSE NANOCOMPOSITE CONTAINING COPPER SULFIDE

    Directory of Open Access Journals (Sweden)

    Sanchi Nenkova

    2011-04-01

    Full Text Available Copper sulfide-containing lignocellulose nanocomposites with improved electroconductivity were obtained. Two methods for preparing the copper sulfide lignocellulose nanocomposites were developed. An optimization of the parameters for obtaining of the nanocomposites with respect to obtaining improved electroconductivity, economy, and lower quantities and concentration of copper and sulfur ions in waste waters was conducted. The mechanisms and schemes of delaying and subsequent connection of copper sulfides in the lignocellulosic matrix were investigated. The modification with a system of 2 components: cupric sulfate pentahydrate (CuSO4. 5H2O and sodium thiosulfate pentahydrate (Na2S2O3.5H2O for wood fibers is preferred. Optimal parameters were established for the process: 40 % of the reduction system; hydromodule M=1:6; and ratio of cupric sulfate pentahydrate:sodium thiosulfate pentahydrate = 1:2. The coordinative connection of copper ions with oxygen atoms of cellulose OH groups and aromatic nucleus in lignin macromolecule was observed.

  17. Current trends in copper theft prevention

    Energy Technology Data Exchange (ETDEWEB)

    Mastrofrancesco, A. [Electrical Safety Authority, ON (Canada)

    2009-07-01

    Copper is used in electrical wiring, water and gas piping, currency, and in household items. An increase in the price and demand for copper has made copper theft a profitable venture for some thieves. Copper consumed in North America is typically supplied by recycling. Scrap dealers may pay near-market prices for pure copper wires. However, copper theft poses a serious threat to the safety of utility workers and the public. Power outages caused by copper theft are now affecting grid reliability. This paper examined technologies and techniques used to prevent copper theft as part of a security strategy for utilities. Attempts to steal copper can leave utility substations unsecured and accessible to children. The theft of neutral grounds will cause the local distribution company (LDC) to malfunction and may cause power surges in homes as well as appliance fires. Utilities are now looking at using a hybrid steel and copper alternative to prevent copper theft. Asset identification techniques are also being used to identify the original owners of the copper and more easily prosecute thieves. Automated monitoring techniques are also being used to increase substation security. Utilities are also partnering with law enforcement agencies and pressuring governments to require scrap dealers to record who they buy from. It was concluded that strategies to prevent copper theft should be considered as part of an overall security strategy for utilities. tabs., figs.

  18. Combination therapy with andrographolide and D-penicillamine enhanced therapeutic advantage over monotherapy with D-penicillamine in attenuating fibrogenic response and cell death in the periportal zone of liver in rats during copper toxicosis

    International Nuclear Information System (INIS)

    Roy, Dijendra Nath; Sen, Gargi; Chowdhury, Kaustav Dutta; Biswas, Tuli

    2011-01-01

    Long treatment regime with D-penicillamine is needed before it can exert clinically meaningful benefits in the treatment of copper toxicosis. The consequence of long-term D-penicillamine treatment is associated with numerous side effects. The limitations of D-penicillamine monotherapy prompted us to search for more effective treatment strategies that could decrease the duration of D-penicillamine therapy. The present study was designed to evaluate the therapeutic potential of D-penicillamine in combination with another hepatoprotective drug, andrographolide in treatment of copper toxicosis in rats. D-penicillamine treatment led to the excretion of copper through urine. Addition of andrographolide to D-penicillamine regime appeared to increase protection of liver by increasing the biliary excretion of copper and reduction in cholestatic injury. The early removal of the causative agent copper during combination treatment was the most effective therapeutic intervention that contributed to the early rectification of fibrosis in liver. Combination treatment reduced Kupffer cells accumulation and TNFα production in liver of copper exposed rats. In particular, andrographolide mediated the anti-inflammatory effect by inhibiting the cytokine production. However, another possible mechanism of cytoprotection of andrographolide was decreasing mitochondrial production of superoxide anions that resulted in better restoration of mitochondrial dysfunction during combination therapy than monotherapy. Furthermore, ROS inhibition by combination regimen resulted in significant decline in activation of caspase cascade. Inhibition of caspases attenuated apoptosis of hepatocytes, induced by chronic copper exposure. In summary, this study suggested that added benefit of combination treatment over use of either agent alone in alleviating the hepatotoxicity and fibrosis associated with copper toxicosis.

  19. Mechanochemical reduction of copper sulfide

    DEFF Research Database (Denmark)

    Balaz, P.; Takacs, L.; Jiang, Jianzhong

    2002-01-01

    The mechanochemical reduction of copper sulfide with iron was induced in a Fritsch P-6 planetary mill, using WC vial filled with argon and WC balls. Samples milled for specific intervals were analyzed by XRD and Mossbauer spectroscopy. Most of the reaction takes place during the first 10 min...... of milling and only FeS and Cu are found after 60 min. The main chemical process is accompanied by phase transformations of the sulfide phases as a result of milling. Djurleite partially transformed to chalcocite and a tetragonal copper sulfide phase before reduction. The cubic modification of FeS was formed...... first, transforming to hexagonal during the later stages of the process. The formation of off-stoichiometric phases and the release of some elemental sulfur by copper sulfide are also probable....

  20. Laser sintering of copper nanoparticles

    International Nuclear Information System (INIS)

    Zenou, Michael; Saar, Amir; Ermak, Oleg; Kotler, Zvi

    2014-01-01

    Copper nanoparticle (NP) inks serve as an attractive potential replacement to silver NP inks in functional printing applications. However their tendency to rapidly oxidize has so far limited their wider use. In this work we have studied the conditions for laser sintering of Cu-NP inks in ambient conditions while avoiding oxidation. We have determined the regime for stable, low-resistivity copper (< ×3 bulk resistivity value) generation in terms of laser irradiance and exposure duration and have indicated the limits on fast processing. The role of pre-drying conditions on sintering outcome has also been studied. A method, based on spectral reflectivity measurements, was used for non-contact monitoring of the sintering process evolution. It also indicates preferred spectral regions for sintering. Finally, we illustrated how selective laser sintering can generate high-quality, fine line (<5 µm wide) and dense copper circuits. (paper)

  1. Copper tolerance of Trichoderma species

    Directory of Open Access Journals (Sweden)

    Jovičić-Petrović Jelena

    2014-01-01

    Full Text Available Some Trichoderma strains can persist in ecosystems with high concentrations of heavy metals. The aim of this research was to examine the variability of Trichoderma strains isolated from different ecosystems, based on their morphological properties and restriction analysis of ITS fragments. The fungal growth was tested on potato dextrose agar, amended with Cu(II concentrations ranging from 0.25 to 10 mmol/l, in order to identify copper-resistant strains. The results indicate that some isolated strains of Trichoderma sp. show tolerance to higher copper concentrations. Further research to examine the ability of copper bioaccumulation by tolerant Trichoderma strains is needed. [Projekat Ministarstva nauke Republike Srbije, br. TR 31080 i br. III 43010

  2. Efficacy of free glutathione and niosomal glutathione in the treatment of acetaminophen-induced hepatotoxicity in cats

    Directory of Open Access Journals (Sweden)

    L.A. Denzoin Vulcano

    2013-06-01

    Full Text Available Acetaminophen (APAP administration results in hepatotoxicity and hematotoxicity in cats. The response to three different treatments against APAP poisoning was evaluated. Free glutathione (GSH (200mg/kg, niosomal GSH (14 mg/kg and free amino acids (180 mg/kg of N-acetylcysteine and 280 mg/kg of methionine were administered to cats that were intoxicated with APAP (a single dose of 150 mg/kg, p.o.. Serum concentration of alanine aminotransferase (ALT along with serum, liver and erythrocyte concentration of GSH and methemoglobin percentage were measured before and 4, 24 and 72 hours after APAP administration. Free GSH (200 mg/kg and niosomal GSH (14 mg/kg were effective in reducing hepatotoxicity and hematotoxicity in cats intoxicated with a dose of 150 mg/kg APAP. We conclude that both types of treatments can protect the liver and haemoglobin against oxidative stress in APAP intoxicated cats. Furthermore, our results showed that treatment with niosomal GSH represents an effective therapeutic approach for APAP poisoning.

  3. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

    Science.gov (United States)

    Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

    2016-01-01

    EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

  4. Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice.

    Science.gov (United States)

    Lin, Chun-che; Yin, Mei-chin; Liu, Wen-hu

    2008-11-01

    Alleviative effects of s-allyl cysteine (SAC) and s-ethyl cysteine (SEC) upon methionine and choline deficient (MCD) diet-induced hepatotoxicity in mice were examined. SAC or SEC at 1g/L was added into drinking water for 7 weeks with MCD diet. MCD feeding significantly increased hepatic triglyceride and cholesterol levels, and elevated the activity of glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme, fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (P MCD feeding significantly lowered serum and hepatic glutathione (GSH) levels, increased malondialdehyde (MDA) and oxidized glutathione (GSSG) formation, and suppressed the activity and mRNA expression of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (P MCD feeding significantly enhanced the mRNA expression of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, matrix metalloproteinases-9 (MMP-9) and collagen-alpha1 (P MCD-induced hepatotoxicity.

  5. Determination of the Antiproliferative Activity of New Theobromine Derivatives and Evaluation of Their In Vitro Hepatotoxic Effects.

    Science.gov (United States)

    Georgieva, Maya; Kondeva-Burdina, Magdalena; Mitkov, Javor; Tzankova, Virginia; Momekov, Georgi; Zlatkov, Alexander

    2016-01-01

    A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized. Their anti-proliferative activity against human chronic myelocytic leukemia cell K562, human T-cell leukemia cell SKW-3 and human acute myeloid leukemia HL-60 was evaluated. For the tested compounds a concentrationdependent cytotoxic activity was observed, with 7g outlined as the most active compound within the series. The targed compounds were obtained in yields of 56 to 85% and their structures were elucidated by FTIR, (1)H NMR, (13)C NMR and microanalyses. The compounds purity was proven by elemental analysis and spectral data. In general, the compounds showed low hepatotoxicity on sub-cellular and cellular level. On isolated rat microsomes only 7d showed toxic effect while theobromine, 1-benzyl-theobromine-thioacetic acid (BTTA) and the other new theobromine derivatives were devoid of toxicity. In isolated rat hepatocytes, when compared to theobromine and BTTA, 7f showed lower cytotoxic effects, and 7d exerted higher cytotoxicity. The results indicate 7g as a promising structure for the design of future compounds with low hepatotoxicity and good antiproliferative activity.

  6. The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone

    Directory of Open Access Journals (Sweden)

    D.T. Ito

    2007-03-01

    Full Text Available Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.

  7. Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis.

    Science.gov (United States)

    Luckert, Claudia; Hessel, Stefanie; Lenze, Dido; Lampen, Alfonso

    2015-10-01

    1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 μM of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a |fold change| of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NFκB and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPARα/γ/δ were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload

    International Nuclear Information System (INIS)

    Gross, J.B. Jr.; Myers, B.M.; Kost, L.J.; Kuntz, S.M.; LaRusso, N.F.

    1989-01-01

    We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload

  9. Figurines in Pietrele: Copper Age ideology

    Directory of Open Access Journals (Sweden)

    Svend Hansen

    2011-12-01

    Full Text Available Major trends in figurine production of the copper age settlement of Pietrele (Romania are discussed. The bone figurines are seen as an ideological innovation of the Early Copper Age system in the Eastern Balkans.

  10. Copper tolerance and virulence in bacteria

    Science.gov (United States)

    Ladomersky, Erik; Petris, Michael J.

    2015-01-01

    Copper (Cu) is an essential trace element for all aerobic organisms. It functions as a cofactor in enzymes that catalyze a wide variety of redox reactions due to its ability to cycle between two oxidation states, Cu(I) and Cu(II). This same redox property of copper has the potential to cause toxicity if copper homeostasis is not maintained. Studies suggest that the toxic properties of copper are harnessed by the innate immune system of the host to kill bacteria. To counter such defenses, bacteria rely on copper tolerance genes for virulence within the host. These discoveries suggest bacterial copper intoxication is a component of host nutritional immunity, thus expanding our knowledge of the roles of copper in biology. This review summarizes our current understanding of copper tolerance in bacteria, and the extent to which these pathways contribute to bacterial virulence within the host. PMID:25652326

  11. Human copper transporter 2 is localized in late endosomes and lysosomes and facilitates cellular copper uptake

    NARCIS (Netherlands)

    Berghe, van den P.V.E; Folmer, D.E.; Malingré, H.E.M.; Beurden, van E.; Klomp, A.E.M.; Sluis, van de B.; Merkx, M.; Berger, R.J.; Klomp, L.W.J.

    2007-01-01

    High-affinity cellular copper uptake is mediated by the CTR (copper transporter) 1 family of proteins. The highly homologous hCTR (human CTR) 2 protein has been identified, but its function in copper uptake is currently unknown. To characterize the role of hCTR2 in copper homoeostasis,

  12. Copper nitrate redispersion to arrive at highly active silica-supported copper catalysts

    NARCIS (Netherlands)

    Munnik, P.|info:eu-repo/dai/nl/328228524; Wolters, M.|info:eu-repo/dai/nl/304829560; Gabrielsson, A.; Pollington, S.D.; Headdock, G.; Bitter, J.H.|info:eu-repo/dai/nl/160581435; de Jongh, P.E.|info:eu-repo/dai/nl/186125372; de Jong, K.P.|info:eu-repo/dai/nl/06885580X

    2011-01-01

    In order to obtain copper catalysts with high dispersions at high copper loadings, the gas flow rate and gas composition was varied during calcination of silica gel impregnated with copper nitrate to a loading of 18 wt % of copper. Analysis by X-ray diffraction (XRD), N2O chemisorption, and

  13. Copper and Anesthesia: Clinical Relevance and Management of Copper Related Disorders

    OpenAIRE

    Langley, Adrian; Dameron, Charles T.

    2013-01-01

    Recent research has implicated abnormal copper homeostasis in the underlying pathophysiology of several clinically important disorders, some of which may be encountered by the anesthetist in daily clinical practice. The purpose of this narrative review is to summarize the physiology and pharmacology of copper, the clinical implications of abnormal copper metabolism, and the subsequent influence of altered copper homeostasis on anesthetic management.

  14. 21 CFR 73.1125 - Potassium sodium copper chloropyhllin (chlorophyllin-copper complex).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Potassium sodium copper chloropyhllin (chlorophyllin-copper complex). 73.1125 Section 73.1125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT....1125 Potassium sodium copper chloropyhllin (chlorophyllin-copper complex). (a) Identity. (1) The color...

  15. 21 CFR 73.2125 - Potassium sodium copper chlorophyllin (chlorophyllin-copper complex).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Potassium sodium copper chlorophyllin (chlorophyllin-copper complex). 73.2125 Section 73.2125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... § 73.2125 Potassium sodium copper chlorophyllin (chlorophyllin-copper complex). (a) Identity and...

  16. Particle-induced thermonuclear fusion

    International Nuclear Information System (INIS)

    Salisbury, W.W.

    1980-01-01

    A nuclear fusion process for igniting a nuclear fusion pellet in a manner similar to that proposed for laser beams uses, an array of pulsed high energy combined particle beams, focused to bombard the pellet for isentropically compressing it to a Fermi-degenerate state by thermal blow-off and balanced beam momentum transfer. (author)

  17. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    International Nuclear Information System (INIS)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-01-01

    Dissolution of taurine zinc complex can be increased by solid dispersions (SDs). • Taurine zinc SDs blocked doxorubicin-induced hepatotoxicity and cardiotoxicity. • Taurine zinc SDs can alleviate oxidative stress and dampen JNK phosphorylation. • Taurine zinc SDs increased the expression of UGT, HO-1 at mRNA and protein level. • Taurine zinc SDs revealed greater hepatoprotective effects than silymarin.

  18. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui, E-mail: Donghuixu007@163.com

    2015-11-15

    Dissolution of taurine zinc complex can be increased by solid dispersions (SDs). • Taurine zinc SDs blocked doxorubicin-induced hepatotoxicity and cardiotoxicity. • Taurine zinc SDs can alleviate oxidative stress and dampen JNK phosphorylation. • Taurine zinc SDs increased the expression of UGT, HO-1 at mRNA and protein level. • Taurine zinc SDs revealed greater hepatoprotective effects than silymarin.

  19. Ethephon, an organophosphorus, a fruit and vegetable ripener: Has potential hepatotoxic effects.

    Directory of Open Access Journals (Sweden)

    Pooja Bhadoria

    2015-01-01

    serious hepatotoxic potential. Thus a habit of thorough cleaning and washing of fruits and vegetables, before consumption, should be adopted to prevent the ingestion of this potential hepatotoxin.

  20. Possible Protective Effect of Low-dose Gamma Irradiation and Certain Natural Products on Chemically Induced Hepatotoxicity in Rats

    International Nuclear Information System (INIS)

    Rashed, R.R.A.

    2015-01-01

    Liver, the largest organ in the human body, is a vital organ that performs more than 500 vital metabolic functions. More than a 1000 drugs of the modern pharmacopoeia can induce liver injury with different clinical presentations. In the most severe cases, drug-induced liver injury may require liver transplantation or lead to death of the patient. Acetaminophen (acetyl-para-amino-phenol, paracetamol, APAP) is safe at therapeutic doses, but accidental or intentional overdose can induce severe hepatotoxicity in both humans and experimental animals. APAP-induced hepatotoxicity is dose related and reproducible in animals, and is thus widely used as a model for experimentally induced hepatotoxicity. Many herbs have been used as natural remedies for the prevention and/or treatment of liver diseases. Herbal drugs gained importance and popularity in recent years because of their safety, efficacy and cost effectiveness. Interestingly, exposure to a small dose or dose rate of radiation was reported to induce stress, perturbing homeostasis. Organisms respond adaptively to such disturbances. The mechanisms by which low-dose radiation (LDR) protects the cells or tissue against subsequent radiation- or drug-induced toxicities have been attributed to its stimulation of various protective molecules such as antioxidants and anti apoptotic. In the light of the above mentioned information, this study was constructed in order to investigate the mechanism(s) of the hepato protective effects offered by each of garlic oil (GO), black seed oil (BO) and sesame oil (SO) each alone or combined with low dose total body gamma (γ)-irradiation against APAP-induced hepatotoxicity in male albino Wistar rats. Preliminary pilot studies were performed prior to the main experimental work; in order to select the effective irradiation dose, the hepato protective natural products and the duration of their administration to be used in the main study. To carry out the main study, 96 rats were randomly

  1. Refining processes in the copper casting technology

    OpenAIRE

    Rzadkosz, S.; Kranc, M.; Garbacz-Klempka, A.; Kozana, J.; Piękoś, M.

    2015-01-01

    The paper presents the analysis of technology of copper and alloyed copper destined for power engineering casts. The casts quality was assessed based on microstructure, chemical content analysis and strength properties tests. Characteristic deoxidising (Logas, Cup) and modifying (ODM2, Kupmod2) formulas were used for the copper where high electrical conductivity was required. Chosen examples of alloyed copper with varied Cr and Zr content were studied, and the optimal heat treatment parameter...

  2. 21 CFR 184.1261 - Copper sulfate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Copper sulfate. 184.1261 Section 184.1261 Food and... Substances Affirmed as GRAS § 184.1261 Copper sulfate. (a) Copper sulfate (cupric sulfate, CuSO4·5H2O, CAS... the reaction of sulfuric acid with cupric oxide or with copper metal. (b) The ingredient must be of a...

  3. The Bauschinger Effect in Copper

    DEFF Research Database (Denmark)

    Pedersen, Ole Bøcker; Brown, L .M.; Stobbs, W. M.

    1981-01-01

    A study of the Bauschinger effect in pure copper shows that by comparison with dispersion hardened copper the effect is very small and independent of temperature. This suggests that the obstacles to flow are deformable. A simple composite model based on this principle accounts for the data semi......-quantitatively and also accounts for the stored energy of cold-work. An interesting feature of the model is that it shows very clearly that, although dislocation pile-ups may exist, the flow stress of the composite is entirely due to the resistance to dislocation motion in the tangles of forest dislocations....

  4. Cupriferous peat: embryonic copper ore

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, D C

    1961-07-01

    A Canadian peat was found to contain up to 10% (dry weight) Cu, and a mechanism for Cu accumulation in peat was discussed. Wet chemical techniques and x-ray diffraction were utilized to identify Cu compounds. Copper was organically bound in peat as a chelate complex and did not occur as an oxide, sulfide, or as elemental Cu. Because of the low S content of peat the Cu was assumed to be bound to nitrogen or oxygen-containing components. Copper, having a greater affinity for N, tended to form the more stable Cu-N chelate. The element was concentrated as circulating cupriferous ground waters filtered through the peat.

  5. Tunable synthesis of copper nanotubes

    International Nuclear Information System (INIS)

    Kaniukov, E; Yakimchuk, D; Kozlovsky, A; Shlimas, D; Zdorovets, M; Kadyrzhanov, K

    2016-01-01

    Simple method of tunable synthesis of copper nanotubes based on template synthesis was developed. A comprehensive study of the structural, morphological and electrical characteristics of the obtained nanostructures was carried out. Characterization of structural features was made by methods of scanning electron microscopy, energy dispersive spectroscopy and X-ray diffractometry analysis. Evaluation of wall thickness is made by methods of gas permeability. Electrical conductivity of nanotubes was define in the study of their current-voltage characteristics. The possibility to control of copper nanotubes physical properties by variation of the deposition parameters was shown. (paper)

  6. Electrical conduction in composites containing copper core–copper ...

    Indian Academy of Sciences (India)

    Unknown

    of Mott's small polaron hopping conduction model. ... sample exhibited a metallic conduction confirming the formation of a percolative chain of ..... value of εp. Also the oxide layer formation on the initially unoxidized copper particles will increase the resistivity level of the nanocomposite. This is borne out by results shown in ...

  7. 21 CFR 73.2647 - Copper powder.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Copper powder. 73.2647 Section 73.2647 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2647 Copper powder. (a) Identity and specifications. The color additive copper powder shall conform in identity and specifications to the requirements of § 73...

  8. Contribution to depth profiling by particle induced X-ray emission application to the study of zinc diffusion in AgZn alloy

    International Nuclear Information System (INIS)

    Frontier, J.P.

    1987-08-01

    A contribution of the study of the capacities of Particle Induced X-ray Emission (P.I.X.E.) for depth profiling, in the range of 1 to 10 micrometers and over, is presented here. It is shown that, in a non destructuve way, the concentration profile of a given element can be obtained, in principle, by deconvoluting the X-ray yields of this element, measured in a set of experiments in which the energy of the impinging protons, hence their range, is systematically varied. Direct deconvolution procedure, which leads to the inversion of an ill-conditionned matrix is unsuitable. So we generalized the iterative procedure previously used by Vegh to solve a similar problem. Alternatively we also used a fitting procedure of several parameters which gave us somewhat better than those of the iterative procedure. Both algorithms where applied to a set of X-ray yields induced by protons of energy between 0.45 to 2 MeV, corresponding to the first 6 micrometers of various depletion profiles of zinc in an initially homogeneous Ag-3 at % Zn annealed under vacuum. For investigation of deeper layers, a sectionning technique which consists in analysing thin film hydroxide targets by specific chemistry of tiny turning, was developped with success. Cross-reference of all the obtained profiles was made with electron microprobe determination on transverse section, and with the predictions of the theory of atomic diffusion. In addition, the possibilities of increasing the depth resolution by developping techniques either of controled sanding of the surface, or analysis of the sample is discussed [fr

  9. Use of M-FISH analysis of α-particle-induced chromosome aberrations for the assessment of chromosomal breakpoint distribution and complex aberration formation

    International Nuclear Information System (INIS)

    Anderson, R.M.; Sumption, N.D.; Papworth, D.G.; Goodhead, D.T.

    2003-01-01

    be discussed in the context of how α -particle-induced complex chromosome aberrations may be formed (Anderson et al., (2002) PNAS 99 12167-12172)

  10. Copper nanoparticles in zeolite Y

    NARCIS (Netherlands)

    Seidel, A.; Loos, J.; Boddenberg, B.

    1999-01-01

    CuCl has been dispersed in the supercages of a Y-type zeolite by heating a mechanical salt/host mixture in vacuo. The occluded salt was subsequently reduced to copper metal in a hydrogen atmosphere. Virtually complete reduction of the salt is achieved at 460°C. Under the same conditions,

  11. Effects of copper on mitosis

    Energy Technology Data Exchange (ETDEWEB)

    Kostal, L

    1971-01-01

    The author deals with the effects of copper on mitosis. He found that a Cu concentration of 1 mg per liter is very toxic and strongly inhibits the course of mitosis in Vicia fabia. The effects of 0.5 mg and 0.25 mg Cu concentrations per liter were similar but a much weaker character.

  12. Copper complexes as chemical nucleases

    Indian Academy of Sciences (India)

    Unknown

    anticancer drug famotidine has been shown as a better catalyst than CuCl2 for sulfite ... Effect of addition of bis-chelate copper(II) complexes (dpq, •; phen, ; ..... Reproduction, Development & Genetics for their help in the DNA cleavage studies ...

  13. Copper, lead and zinc production

    International Nuclear Information System (INIS)

    Ayers, J.; Ternan, S.

    2001-01-01

    This chapter provides information on the by-products and residues generated during the production of copper, lead and zinc. The purpose of this chapter is to describe by-products and residues which are generated, how these may be avoided or minimised, and available options for the utilization and management of residues. (author)

  14. on THICKNESS OF COPPER (|) OXIDE

    African Journals Online (AJOL)

    2006-12-20

    Dec 20, 2006 ... known materials to be used as semiconductor devices. The oxide is. Observed to be an attractive starting material for the production of solar cells for low cost terrestrial conversion of solar energy to electricity. Copper (I) oxide is one Of the earliest known photovoltaic materials and the first in which the ...

  15. Lab Tracker and Copper Calculator

    Science.gov (United States)

    ... have to do with factors of asymmetric neurologic development, such as being right or left-handed. The copper is often seen most prominently in the basal ganglia, the area deep within the brain that coordinates movements. The face of the giant ...

  16. Crystallization of copper metaphosphate glass

    Science.gov (United States)

    Bae, Byeong-Soo; Weinberg, Michael C.

    1993-01-01

    The effect of the valence state of copper in copper metaphosphate glass on the crystallization behavior and glass transition temperature has been investigated. The crystallization of copper metaphosphate is initiated from the surface and its main crystalline phase is copper metaphosphate (Cu(PO)3),independent of the (Cu sup 2+)/(Cu(total)). However, the crystal morphology, the relative crystallization rates, and their temperature dependences are affected by the (Cu sup 2+)/(Cu (total)) ratio in the glass. On the other hand, the totally oxidized glass crystallizes from all over the surface. The relative crystallization rate of the reduced glass to the totally oxidized glass is large at low temperature, but small at high temperature. The glass transition temperature of the glass increases as the (Cu sup 2+)/(Cu(total)) ratio is raised. It is also found that the atmosphere used during heat treatment does not influence the crystallization of the reduced glass, except for the formation of a very thin CuO surface layer when heated in air.

  17. COPPER CORROSION AND SOLUBILITY RESEARCH

    Science.gov (United States)

    This poster provides a very cursory summary of TTEB in-house copper research experimental systems, and extramural research projects. The field studies summarized are the Indian Hill (OH) study of the use of orthophosphate for reducing cuprosolvency in a high alkalinity water, an...

  18. Spectroscopic studies of copper enzymes

    International Nuclear Information System (INIS)

    Dooley, D.M.; Moog, R.; Zumft, W.; Koenig, S.H.; Scott, R.A.; Cote, C.E.; McGuirl, M.

    1986-01-01

    Several spectroscopic methods, including absorption, circular dichroism (CD), magnetic CD (MCD), X-ray absorption, resonance Raman, EPR, NMR, and quasi-elastic light-scattering spectroscopy, have been used to probe the structures of copper-containing amine oxidases, nitrite reductase, and nitrous oxide reductase. The basic goals are to determine the copper site structure, electronic properties, and to generate structure-reactivity correlations. Collectively, the results on the amine oxidases permit a detailed model for the Cu(II) sites in these enzymes to be constructed that, in turn, rationalizes the ligand-binding chemistry. Resonance Raman spectra of the phenylhydrazine and 2,4-dinitrophenyl-hydrazine derivatives of bovine plasma amine oxidase and models for its organic cofactor, e.g. pyridoxal, methoxatin, are most consistent with methoxatin being the intrinsic cofactor. The structure of the Cu(I) forms of the amine oxidases have been investigated by X-ray absorption spectroscopy (XAS); the copper coordination geometry is significantly different in the oxidized and reduced forms. Some anomalous properties of the amine oxidases in solution are explicable in terms of their reversible aggregation, which the authors have characterized via light scattering. Nitrite and nitrous oxide reductases display several novel spectral properties. The data suggest that new types of copper sites are present

  19. A Study of Protection of Copper Alloys

    International Nuclear Information System (INIS)

    Kim, E. A.; Kim, S. H.; Kim, C. R.

    1974-01-01

    Volatile treatment of high capacity boiler water with hydrazine and ammonia is studied. Ammonia comes from the decomposition of excess hydrazine injected to treat dissolved oxygen. Ammonia is also injected for the control of pH. To find an effect of such ammonia on the copper alloy, the relations between pH and iron, and ammonia and copper are studied. Since the dependence of corrosion of iron on pH differs from that of copper, a range of pH was selected experimentally to minimize the corrosion rates of both copper and iron. Corrosion rates of various copper alloys are also compared

  20. Electrochemical remediation of copper contaminated clay soils

    Energy Technology Data Exchange (ETDEWEB)

    Korolev, V.A.; Babakina, O.A.; Mitojan, R.A. [Moscow State Univ. (Russian Federation)

    2001-07-01

    The study objective focused on electrochemical remediation copper polluted soils in the presence of adjuvant substances and conditions that are more effective for the treatment. Some of these substances were studied in different researches. Moreover, authors obtained a result of extraction copper rate higher than 90%. In this connection the following problems were set: - Influence organic and inorganic substances on copper mobility in soil under the DC current. - Moisture effect on copper migration in clay. - Electrochemical remediation soils different mineralogical composition. - A washing conditions contribution to electrochemical remediation of soil from copper. - Accuracy rating experimental dates. (orig.)

  1. Tribological properties of copper-based composites with copper coated NbSe2 and CNT

    International Nuclear Information System (INIS)

    Chen, Beibei; Yang, Jin; Zhang, Qing; Huang, Hong; Li, Hongping; Tang, Hua; Li, Changsheng

    2015-01-01

    Graphical abstract: Morphology of copper coated NbSe 2 and CNT; friction coefficient and wear rate of copper-based composites. - Highlights: • NbSe 2 and CNT were coated with copper layers by the means of electroless plating. • The mechanical and tribological properties of copper composites were studied. • The enhancement mechanisms of copper coated NbSe 2 and CNT were proposed. • Copper–copper coated (12 wt.%NbSe 2 –3 wt.%CNT) composite had the best wear resistance. - Abstract: Copper-based composites with copper coated NbSe 2 and/or CNT were fabricated by the powder metallurgy technique. The morphology and phase composition of copper coated NbSe 2 and carbon nanotube (CNT) were observed using high solution transmission electronic microscope (HRTEM), scanning electronic microscope (SEM equipped with EDS) and X-ray diffraction (XRD). The density, hardness, and bending strength of as-prepared copper-based composites were measured, and their tribological properties were investigated using UMT-2 tester. Results indicated that all copper-based composites showed decreased density and bending strength, but increased hardness in comparison with copper matrix. Besides, the incorporation of copper coated NbSe 2 improved the friction-reducing and anti-wear properties of copper matrix. Addition of copper coated CNT greatly enhanced the mechanical and tribological properties. In particular, when the content of copper coated CNT was 3 wt.%, the corresponding composite exhibited the best tribological properties. This was because NbSe 2 was distributed chaotically in matrix, which greatly improved the friction-reducing property of copper, while CNT with superior mechanical strength enhanced the wear resistance by increasing the load-carrying capacity. More importantly, copper layers coated on NbSe 2 and CNT favored the good interfacial combination between fillers and copper matrix showing beneficial effect for the stresses transferring from matrix to fillers

  2. Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans

    International Nuclear Information System (INIS)

    Atienzar, Franck A.; Novik, Eric I.; Gerets, Helga H.; Parekh, Amit; Delatour, Claude; Cardenas, Alvaro; MacDonald, James; Yarmush, Martin L.; Dhalluin, Stéphane

    2014-01-01

    Drug Induced Liver Injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine model along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n = 40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n = 11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n = 14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies. - Highlights: • Importance of species differences in drug development. • Relevance of dog co-culture model for metabolism and toxicology studies. • Hepatotoxicity: higher predictivity of dog co-culture vs HepG2 and human hepatocytes

  3. Computed tomography of the brain, hepatotoxic drugs and high alcohol consumption in male alcoholic patients and a random sample from the general male population

    Energy Technology Data Exchange (ETDEWEB)

    Muetzell, S. (Univ. Hospital of Uppsala (Sweden). Dept. of Family Medicine)

    1992-01-01

    Computed tomography (CT) of the brain was performed in a random sample of a total of 195 men and 211 male alcoholic patients admitted for the first time during a period of two years from the same geographically limited area of Greater Stockholm as the sample. Laboratory tests were performed, including liver and pancreatic tests. Toxicological screening was performed and the consumption of hepatotoxic drugs was also investigated. The groups were then subdivided with respect to alcohol consumption and use of hepatotoxic drugs: group IA, men from the random sample with low or moderate alcohol consumption and no use of hepatotoxic drugs; IB, men from the random sample with low or moderate alcohol consumption with use of hepatotoxic drugs; IIA, alcoholic inpatients with use of alcohol and no drugs; and IIB, alcoholic inpatients with use of alcohol and drugs. Group IIB was found to have a higher incidence of cortical and subcortical changes than group IA. Group IB had a higher incidence of subcortical changes than group IA, and they differed only in drug use. Groups IIN and IIA only differed in drug use, and IIB had a higher incidence of brian damage except for anterior horn index and wide cerebellar sulci indicating vermian atrophy. Significantly higher serum levels of bilirubin, GGT, ASAT, ALAT, CK LD, and amylase were found in IIB. The results indicate that drug use influences the incidence of cortical and subcortical aberrations, except anterior horn index. It is concluded that the groups with alcohol abuse who used hepatotoxic drugs showed a picture of cortical changes (wide transport sulci and clear-cut of high-grade cortical changes) and also of subcortical aberrations, expressed as an increased widening on the third ventricle.

  4. Computed tomography of the brain, hepatotoxic drugs and high alcohol consumption in male alcoholic patients and a random sample from the general male population

    International Nuclear Information System (INIS)

    Muetzell, S.

    1992-01-01

    Computed tomography (CT) of the brain was performed in a random sample of a total of 195 men and 211 male alcoholic patients admitted for the first time during a period of two years from the same geographically limited area of Greater Stockholm as the sample. Laboratory tests were performed, including liver and pancreatic tests. Toxicological screening was performed and the consumption of hepatotoxic drugs was also investigated. The groups were then subdivided with respect to alcohol consumption and use of hepatotoxic drugs: group IA, men from the random sample with low or moderate alcohol consumption and no use of hepatotoxic drugs; IB, men from the random sample with low or moderate alcohol consumption with use of hepatotoxic drugs; IIA, alcoholic inpatients with use of alcohol and no drugs; and IIB, alcoholic inpatients with use of alcohol and drugs. Group IIB was found to have a higher incidence of cortical and subcortical changes than group IA. Group IB had a higher incidence of subcortical changes than group IA, and they differed only in drug use. Groups IIN and IIA only differed in drug use, and IIB had a higher incidence of brian damage except for anterior horn index and wide cerebellar sulci indicating vermian atrophy. Significantly higher serum levels of bilirubin, GGT, ASAT, ALAT, CK LD, and amylase were found in IIB. The results indicate that drug use influences the incidence of cortical and subcortical aberrations, except anterior horn index. It is concluded that the groups with alcohol abuse who used hepatotoxic drugs showed a picture of cortical changes (wide transport sulci and clear-cut of high-grade cortical changes) and also of subcortical aberrations, expressed as an increased widening on the third ventricle

  5. Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans

    Energy Technology Data Exchange (ETDEWEB)

    Atienzar, Franck A., E-mail: franck.atienzar@ucb.com [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium); Novik, Eric I. [H mu rel Corporation, 675 U.S. Highway 1, North Brunswick, NJ 08902 (United States); Gerets, Helga H. [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium); Parekh, Amit [H mu rel Corporation, 675 U.S. Highway 1, North Brunswick, NJ 08902 (United States); Delatour, Claude; Cardenas, Alvaro [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium); MacDonald, James [Chrysalis Pharma Consulting, LLC, 385 Route 24, Suite 1G, Chester, NJ 07930 (United States); Yarmush, Martin L. [Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854 (United States); Dhalluin, Stéphane [UCB Pharma SA, Non-Clinical Development, Chemin du Foriest, 1420 Braine-l' Alleud (Belgium)

    2014-02-15

    Drug Induced Liver Injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine model along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n = 40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n = 11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n = 14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies. - Highlights: • Importance of species differences in drug development. • Relevance of dog co-culture model for metabolism and toxicology studies. • Hepatotoxicity: higher predictivity of dog co-culture vs HepG2 and human hepatocytes.

  6. The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1

    Science.gov (United States)

    Shu, Nan; Hu, Mengyue; Ling, Zhaoli; Liu, Peihua; Wang, Fan; Xu, Ping; Zhong, Zeyu; Sun, Binbin; Zhang, Mian; Li, Feng; Xie, Qiushi; Liu, Xiaodong; Liu, Li

    2016-01-01

    Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation. PMID:27624558

  7. Abrogation of cisplatin-induced hepatotoxicity in mice by xanthorrhizol is related to its effect on the regulation of gene transcription

    International Nuclear Information System (INIS)

    Hwan Kim, Seong; Ok Hong, Kyoung; Chung, Won-Yoon; Kwan Hwang, Jae; Park, Kwang-Kyun

    2004-01-01

    Cisplatin is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because Curcuma xanthorrhiza Roxb. (Zingiberaceae) has been traditionally used to treat liver disorders, the protective effect of xanthorrhizol, which is isolated from C. xanthorrhiza, on cisplatin-induced hepatotoxicity was evaluated in mice. The pretreatment of xanthorrhizol (200 mg/kg/day, po) for 4 days prevented the hepatotoxicity induced by cisplatin (45 mg/kg, ip) with statistical significance. Interestingly, it abrogated cisplatin-induced DNA-binding activity of nuclear factor-kappaB (NF-κB), which consequently affected mRNA expression levels of NF-κB-dependent genes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), even in part. It also attenuated the cisplatin-suppressed DNA-binding activity of activator protein 1 (AP-1). Using differential display reverse transcription-polymerase chain reaction (DDRT-PCR), seven upregulated genes including S100 calcium binding protein A9 (S100A9) mRNA and antigenic determinant for rec-A protein mRNA and five downregulated genes including caseinolytic protease X (ClpX) mRNA and ceruloplasmin (CP) mRNA by cisplatin were identified. Although these mRNA expression patterns were not totally consistent with gel shift patterns, altered expression levels by cisplatin were reversed by the pretreatment of xanthorrhizol. In conclusion, the ability of xanthorrhizol to regulate the DNA-binding activities of transcription factors, NF-κB and AP-1, could be one possible mechanism to elucidate the preventive effect of xanthorrhizol on cisplatin-induced hepatotoxicity. Furthermore, genes identified in this study could be helpful to understand the mechanism of cisplatin-induced hepatotoxicity. Finally, the combination treatment of xanthorrhizol and cisplatin may provide more advantage than single treatment of cisplatin in cancer therapy

  8. Anti-inflammatory effects and hepatotoxicity of Tripterygium-loaded solid lipid nanoparticles on adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Xue, Mei; Jiang, Zhen-zhou; Wu, Tao; Li, Ji; Zhang, Liang; Zhao, Yan; Li, Xue-jun; Zhang, Lu-Yong; Yang, Shu-yu

    2012-08-15

    Tripterygium wilfordii Hook f. (TWHF) has been demonstrated to have anti-inflammatory, immunosuppressive effects and its clinical use was restricted to some extent due to some toxic effects on the digestive, urogenital, and blood circulatory systems, especially the male reproductive system. In the previous study, we had confirmed that TWHF-loaded solid lipid nanoparticles (SLN) have protective effects on male reproductive toxicity in rats. Anti-inflammatory effects and hepatotoxicity of TWHF-SLN remain to be unidentified. The present study was focused on the anti-inflammatory effect of complete Freund's adjuvant-induced arthritis in rats treated with TWHF-SLN as well as the effects of SLN delivery system on decreasing the hepatotoxicity induced by tripterygium. Sixty-four healthy male rats were randomly divided into eight groups with eight rats each. From day 18 after FCA injection, TWHF-SLN group (120, 60, 30 mg/kg) and TWHF group (120, 60, 30 mg/kg) were administered by oral gavage for 24 consecutive days. The control group was with saline and model control group was without any treatment. The volume of the right hind paws was evaluated at 0, 4, 8, 12, 18, 24, 30, 36 and 42 days post-injection of FCA by a home-made connected device. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL) and albumin (ALB) levels were evaluated by an autoanalyzer. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) malondialdehyde (MDA) and xanthine oxidase (XOD) levels were determined using commercial kits. The PG level in sera was examined by double antibody sandwich method. Tissue histopathology was evaluated with hematoxylin and eosin (H&E). The results show that TWHF-SLN can significantly reduce rat paw volume at 60 mg/kg (psystem can enhance the anti-inflammatory activity of TWHF, and meanwhile has a protective effect against TWHF

  9. Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hozeifa M. Hassan

    2018-03-01

    Full Text Available Tuberculosis (TB is one of the oldest infectious diseases that affected humankind and remains one of the world’s deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS potentially enhanced INH toxicity. These enhancing activities ranged between augmenting the inflammatory stress, oxidative stress, alteration of bile acid homeostasis, and CYP2E1 over-expression. Although pre-treatment with dexamethasone (DEX helped overcome both inflammatory and oxidative stress which ended-up in alleviation of LPS augmenting effects, but still minor toxicities were being detected, alongside with CYP2E1 over expression. This finding positively indicated the corner-stone role played by CYP2E1 in the pathogenesis of INH/LPS-induced liver damage. Therefore, we examined whether INH/LPS co-treatment with CYP2E1 inhibitor diallyl sulfide (DAS and DEX can protect against the INH/LPS-induced hepatotoxicity. Our results showed that pre-administration of both DAS and DEX caused significant reduction in serum TBA, TBil, and gamma-glutamyl transferase levels. Furthermore, the histopathological analysis showed that DAS and DEX could effectively reverse the liver lesions seen following INH/LPS treatment and protect against hepatic steatosis as indicated by absence of lipid accumulation. Pre-treatment with DAS alone could not completely block the CYP2E1 protein expression following INH/LPS treatment, as appeared in the immunoblotting and immunohistochemistry results. This is probably due to the fact that the combined enhancement activities of both INH and LPS on CYP2E1 protein expression

  10. Reactivity test between beryllium and copper

    International Nuclear Information System (INIS)

    Kawamura, H.; Kato, M.

    1995-01-01

    Beryllium has been expected for using as plasma facing material on ITER. And, copper alloy has been proposed as heat sink material behind plasma facing components. Therefore, both materials must be joined. However, the elementary process of reaction between beryllium and copper alloy does not clear in detail. For example, other authors reported that beryllium reacted with copper at high temperature, but it was not obvious about the generation of reaction products and increasing of the reaction layer. In the present work, from this point, for clarifying the elementary process of reaction between beryllium and copper, the out-of-pile compatibility tests were conducted with diffusion couples of beryllium and copper which were inserted in the capsule filled with high purity helium gas (6N). Annealing temperatures were 300, 400, 500, 600 and 700 degrees C, and annealing periods were 100, 300 and 1000h. Beryllium specimens were hot pressed beryllium, and copper specimens were OFC (Oxygen Free Copper)

  11. Copper economy in Chlamydomonas: Prioritized allocation and reallocation of copper to respiration vs. photosynthesis

    Science.gov (United States)

    Kropat, Janette; Gallaher, Sean D.; Urzica, Eugen I.; Nakamoto, Stacie S.; Strenkert, Daniela; Tottey, Stephen; Mason, Andrew Z.; Merchant, Sabeeha S.

    2015-01-01

    Inorganic elements, although required only in trace amounts, permit life and primary productivity because of their functions in catalysis. Every organism has a minimal requirement of each metal based on the intracellular abundance of proteins that use inorganic cofactors, but elemental sparing mechanisms can reduce this quota. A well-studied copper-sparing mechanism that operates in microalgae faced with copper deficiency is the replacement of the abundant copper protein plastocyanin with a heme-containing substitute, cytochrome (Cyt) c6. This switch, which is dependent on a copper-sensing transcription factor, copper response regulator 1 (CRR1), dramatically reduces the copper quota. We show here that in a situation of marginal copper availability, copper is preferentially allocated from plastocyanin, whose function is dispensable, to other more critical copper-dependent enzymes like Cyt oxidase and a ferroxidase. In the absence of an extracellular source, copper allocation to Cyt oxidase includes CRR1-dependent proteolysis of plastocyanin and quantitative recycling of the copper cofactor from plastocyanin to Cyt oxidase. Transcriptome profiling identifies a gene encoding a Zn-metalloprotease, as a candidate effecting copper recycling. One reason for the retention of genes encoding both plastocyanin and Cyt c6 in algal and cyanobacterial genomes might be because plastocyanin provides a competitive advantage in copper-depleted environments as a ready source of copper. PMID:25646490

  12. What is the Potential for More Copper Fabrication in Zambia?

    OpenAIRE

    World Bank

    2011-01-01

    The copper fabrication industry lies between: (1) the industry that produces copper (as a commodity metal from mined ores as well as from recycling), and (2) the users of copper in finished products such as electronic goods. Copper fabrication involves the manufacture of products such as copper wire, wire rod, low-voltage cable, and other copper based semi-manufactures. Copper is clearly a...

  13. Accumulation and hyperaccumulation of copper in plants

    Science.gov (United States)

    Adam, V.; Trnkova, L.; Huska, D.; Babula, P.; Kizek, R.

    2009-04-01

    Copper is natural component of our environment. Flow of copper(II) ions in the environment depends on solubility of compounds containing this metal. Mobile ion coming from soil and rocks due to volcanic activity, rains and others are then distributed to water. Bio-availability of copper is substantially lower than its concentration in the aquatic environment. Copper present in the water reacts with other compounds and creates a complex, not available for organisms. The availability of copper varies depending on the environment, but moving around within the range from 5 to 25 % of total copper. Thus copper is stored in the sediments and the rest is transported to the seas and oceans. It is common knowledge that copper is essential element for most living organisms. For this reason this element is actively accumulated in the tissues. The total quantity of copper in soil ranges from 2 to 250 mg / kg, the average concentration is 30 mg / kg. Certain activities related to agriculture (the use of fungicides), possibly with the metallurgical industry and mining, tend to increase the total quantity of copper in the soil. This amount of copper in the soil is a problem particularly for agricultural production of food. The lack of copper causes a decrease in revenue and reduction in quality of production. In Europe, shows the low level of copper in total 18 million hectares of farmland. To remedy this adverse situation is the increasing use of copper fertilizers in agricultural soils. It is known that copper compounds are used in plant protection against various illnesses and pests. Mining of minerals is for the development of human society a key economic activity. An important site where the copper is mined in the Slovakia is nearby Smolníka. Due to long time mining in his area (more than 700 years) there are places with extremely high concentrations of various metals including copper. Besides copper, there are also detected iron, zinc and arsenic. Various plant species

  14. Uptake and internalisation of copper by three marine microalgae: comparison of copper-sensitive and copper-tolerant species.

    Science.gov (United States)

    Levy, Jacqueline L; Angel, Brad M; Stauber, Jennifer L; Poon, Wing L; Simpson, Stuart L; Cheng, Shuk Han; Jolley, Dianne F

    2008-08-29

    Although it has been well established that different species of marine algae have different sensitivities to metals, our understanding of the physiological and biochemical basis for these differences is limited. This study investigated copper adsorption and internalisation in three algal species with differing sensitivities to copper. The diatom Phaeodactylum tricornutum was particularly sensitive to copper, with a 72-h IC50 (concentration of copper to inhibit growth rate by 50%) of 8.0 microg Cu L(-1), compared to the green algae Tetraselmis sp. (72-h IC50 47 microg Cu L(-1)) and Dunaliella tertiolecta (72-h IC50 530 microg Cu L(-1)). At these IC50 concentrations, Tetraselmis sp. had much higher intracellular copper (1.97+/-0.01 x 10(-13)g Cu cell(-1)) than P. tricornutum (0.23+/-0.19 x 10(-13)g Cu cell(-1)) and D. tertiolecta (0.59+/-0.05 x 10(-13)g Cu cell(-1)), suggesting that Tetraselmis sp. effectively detoxifies