Journal of Applied Toxicology

Cover image for Vol. 32 Issue 10

October 2012

Volume 32, Issue 10

Pages 751–866

  1. Review Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. You have full text access to this OnlineOpen article
      Hypothesis Holiday sudden cardiac death: food and alcohol inhibition of SULT1A enzymes as a precipitant (pages 751–755)

      Ken Eagle

      Version of Record online: 8 JUN 2012 | DOI: 10.1002/jat.2764

      This article reviews the data supporting the existence of a holiday cardiac death phenomenon, the involvement of catecholamines and the normal modes of human catecholamine deactivation. Further evidence is reviewed that supports a hypothesized mechanism whereby critical SULT1A catecholamine deactivation enzymes can in some patients be inhibited by naturally-occurring phenols and polyphenols in foods and alcohols. If deactivation is inhibited by holiday consumption excesses, holiday stress or excitement could lead to a buildup of catecholamines that can cause fatal arrhythmias.

    2. The genetic toxicity of methylphenidate: a review of the current literature (pages 756–764)

      Suzanne M. Morris, Dayton M. Petibone, Wei-Jiun Lin, James J. Chen, Benedetto Vitiello, Kristine L. Witt and Donald R. Mattison

      Version of Record online: 15 FEB 2012 | DOI: 10.1002/jat.2721

      The symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) are effectively treated with methylphenidate (MPH). In 2005, reported increases in cytogenetic damage in the lymphocytes of MPH-treated pediatric patients caused world-wide concern. Numerous studies were initiated to verify or refute the findings. As reviewed in this communication, neither the laboratory animal nor human subject studies found an increase in MPH-induced genetic damage. The subsequent studies do not support the initial hypothesis that MPH treatment increases the risk of genetic damage in ADHD patients.

    3. Evolution of approaches in conducting total diet studies (pages 765–776)

      A. Betsy, V. Sudershan Rao and K. Polasa

      Version of Record online: 19 MAR 2012 | DOI: 10.1002/jat.2718

      Total diet studies (TDS) are the most cost-effective surveillance tools for exposure assessment of various chemicals. Introduced in 1961 by FDA, TDS have evolved to encompass many developing countries along with the developed ones. This article describes the various changes undergone by TDS in many countries to emerge as an accurate approach to risk assessment.

  2. Research Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Visual analogue scales: how can we interpret them in experimental studies of irritation in the eyes, nose, throat and airways? (pages 777–782)

      Lena Ernstgård and Matteo Bottai

      Version of Record online: 5 APR 2011 | DOI: 10.1002/jat.1681

      The aim of this study was to investigate if visual analogue scales of objective symptoms could be validated against objective measurements in exposure studies of chemical vapours in humans. This validation comprises the results of symptom ratings of irritation and objective measurements of effects of the eye, nose, and throat from studies of 9 different chemicals. The results support that there is a relationship between subjective symptoms and objective measures regarding eye and nose irritation at low chemical exposure levels.

    2. Selection of scFv phages specific for chloramphenicol acetyl transferase (CAT), as alternatives for antibodies in CAT detection assays (pages 783–789)

      Bieke Van Dorst, Jaytry Mehta, Elsa Rouah-Martin, Jelke Backeljau, Wim De Coen, Dominique Eeckhout, Geert De Jaeger, Ronny Blust and Johan Robbens

      Version of Record online: 18 APR 2011 | DOI: 10.1002/jat.1685

      Chloramphenicol acetyl transferase (CAT) is frequently used as a reporter protein in mammalian reporter gene assays. Although CAT can be measured by different detection systems, like enzymatic and immune assays, there is still need for a cost-effective and fast detection system. Therefore, in this study scFv phages were selected with affinity for CAT, which can be used as a fast, cheap and animal-friendly alternative for capturing antibodies in a highly sensitive detection test to measure CAT concentrations in reporter gene assays.

    3. Dark cell change of the cerebellar Purkinje cells induced by terbutaline under transient disruption of the blood–brain barrier in adult rats: morphological evaluation (pages 790–795)

      Naoaki Yamada, Satoshi Sasaki, Hiroyuki Ishii, Junko Sato, Takeshi Kanno, Yumi Wako and Minoru Tsuchitani

      Version of Record online: 25 MAY 2011 | DOI: 10.1002/jat.1690

      This study aimed to establish a cerebellar degeneration animal model and to characterize the dark cell change of Purkinje cells. Dark-stained Purkinje cells and prominent Bergmann glial cells were observed. Ultrastructurally, the Bergmann glial process showed swelling, and large lamella bodies were observed close to the dendritic spines. These findings may suggest that terbutaline induced a failure of Bergmann glial cell and resulted in dark cell degeneration of the Purkinje cells due to glutamate excitotoxicity.

    4. Protective effects of salecan against carbon tetrachloride-induced acute liver injury in mice (pages 796–803)

      Peng Chen, Zhongqiu Wang, Liyan Zeng, Shiming Wang, Wei Dong, Aiqun Jia, Chun Cai and Jianfa Zhang

      Version of Record online: 4 JUL 2011 | DOI: 10.1002/jat.1694

      Carbon tetrachloride (CCl4) is a well-established model for screening hepato-protective drugs. The aim of the present study was to evaluate the potential protective effects of a novel soluble β-Glucan salecan on acute liver injury induced by CCl4 in mice and to further explore the underlying mechanisms. Our data presented herein provide evidence that salecan played the hepatoprotective effect against CCl4 induced acute liver injury through attenuating oxidative stress at early stage and accelerating hepatocytes proliferation during later stage.

    5. Caffeine induction of sulfotransferases in rat liver and intestine (pages 804–809)

      Tianyan Zhou, Yue Chen, Chaoqun Huang and Guangping Chen

      Version of Record online: 1 JUL 2011 | DOI: 10.1002/jat.1698

      Our results suggest that consumption of caffeine can induce drug-metabolizing SULTs, rat aryl sulfotransferase (rSULT1A1, AST-IV) and rat hydroxysteroid sulfotransferase (rSULT2A1, STa), in drug detoxification tissues, liver and intestine. Induction of SULTs in intestine was stronger than that in liver. The induction pattern of rat SULTs by caffeine was also gender-dependent.

    6. Nandrolone androgenic hormone presents genotoxic effects in different cells of mice (pages 810–814)

      Carolina Almeida do Carmo, Álvaro Luiz Martini Gonçalves, Daisy Maria Fávero Salvadori and Edson Luis Maistro

      Version of Record online: 30 JUN 2011 | DOI: 10.1002/jat.1701

      Nandrolone is an androgenic–anabolic steroid (AAS) with diverse medical applications but taken indiscriminately by some to rapidly increase muscle mass. The aim of this study was to evaluate the genotoxic and clastogenic potential of nandrolone (deca-durabolin®) in vivo in different cells of mice, using the comet assay and micronucleus test, respectively. The animals received subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg−1 body weight). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE–NCE ratio).

    7. Involvement of Th2 cytokines in the mouse model of flutamide-induced acute liver injury (pages 815–822)

      Satonori Higuchi, Masanori Kobayashi, Azusa Yano, Koichi Tsuneyama, Tatsuki Fukami, Miki Nakajima and Tsuyoshi Yokoi

      Version of Record online: 7 JUL 2011 | DOI: 10.1002/jat.1706

      Drug-induced liver injury is a growing concern for pharmaceutical companies and patients because numerous drugs have been linked to hepatotoxicity and it is the most common reason for a drug to be withdrawn. Flutamide rarely causes liver dysfunction in humans, and immune allergic reactions have been suggested in some cases. In this study, we investigated the mechanisms of flutamide-induced liver injury in BALB/c mice.

    8. Th2 cytokine-mediated methimazole-induced acute liver injury in mice (pages 823–833)

      Masanori Kobayashi, Satonori Higuchi, Mika Ide, Satomi Nishikawa, Tatsuki Fukami, Miki Nakajima and Tsuyoshi Yokoi

      Version of Record online: 9 MAR 2012 | DOI: 10.1002/jat.2731

      Methimazole (MTZ) induced liver injury and increased plasma IL-4 level and hepatic mRNA expression levels of helper T cells (Th2 cells) related factors in mice. These changes were markedly enhanced by pre-treatment of L-buthionine sulfoximine, an inhibitor of GSH synthesis. Neutralization of IL-4 using a monoclonal anti-mouse IL-4 antibody suppressed the hepatotoxic effect of MTZ. Th2 cytokine-mediated immune responses are involved in the MTZ-induced acute liver injury in mice.

    9. Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates (pages 834–842)

      Dingsheng Wen, Aiming Liu, Feng Chen, Julin Yang and Renke Dai

      Version of Record online: 29 JUN 2012 | DOI: 10.1002/jat.2755

      The risk of compounds causing bradycardia in transgenic zebrafish expressing green fluorescent protein (GFP) exclusively in myocardium correlated well with that causing QT prolongation and hERG K+ current blockage in established models. The relationship between logP values and the risk of QT prolongation in this model was proposed, and non-sensitivity to antibacterial agents was revealed. The present transgenic zebrafish model is high throughput used to screen QT prolongation-related cardio toxicity of drug candidates.

    10. The point of transition on the dose-effect curve as a reference point in the evaluation of in vitro toxicity data (pages 843–849)

      Salomon Sand, Joakim Ringblom, Helen Håkansson and Mattias Öberg

      Version of Record online: 25 JUN 2012 | DOI: 10.1002/jat.2757

      A new reference point (BMDT) that represents the dose where the slope of the dose-effect curve changes the most in the low-dose region is described. It offers an objective geometrical definition of a reference point in the low-dose region. It is shown that the interpretation of the in vitro results, as potency and rank orders, may depend on the choice and definition of the reference point (BMDT, EC10 or EC50).

    11. Corn oil as a vehicle in drug development exerts a dose-dependent effect on gene expression profiles in rat thymus (pages 850–857)

      Xing-Chao Geng, Bo Li, Liang Zhang, Ying Song, Zhi Lin, Ying-Qi Zhang and Jun-Zhi Wang

      Version of Record online: 4 JUL 2012 | DOI: 10.1002/jat.2773

      Corn oil (CO) exerts a dose-dependent effect on gene expression profiles in rat. 10 ml/kg CO caused 458 dysregulated genes in rat thymus. Transcription levels of genes related to CO treatment were confirmed by qRT-PCR. Altered gene functions included immune response, organics response, et al. 2 ml/kg/day might be more appropriate for CO gavage as a vehicle in genomics study.

    12. Predictive model for L-type channel inhibition: multichannel block in QT prolongation risk assessment (pages 858–866)

      Barbara Wiśniowska, Aleksander Mendyk, Kamil Fijorek, Anna Glinka and Sebastian Polak

      Version of Record online: 3 JUL 2012 | DOI: 10.1002/jat.2784

      The human ether-à-go-go-related gene (hERG) block is regarded as a marker of proarrhythmic risk. However, some concerns have been raised about its specificity. One of the possible sources of the problem is drug interaction with multiple cardiac channels.

      The aim of this study was to develop a model for CaL-channel inhibition and also the assessment of drug–multichannel interaction effects on the QTc interval. The performed simulations showed that the evaluation of the multichannel interaction of drugs makes the proarrhythmic risk assessment more reliable.