Journal of Applied Toxicology

Cover image for Vol. 31 Issue 7

October 2011

Volume 31, Issue 7

Pages 599–706

  1. Review

    1. Top of page
    2. Review
    3. Research Articles
    4. Short Communications
    5. Erratum
    1. Preclinical risk assessment of drug-induced hypo- and hyperprolactinemia (pages 599–607)

      Adam Hargreaves and Johannes Harleman

      Article first published online: 2 SEP 2011 | DOI: 10.1002/jat.1723

      Drug-induced changes in prolactin signaling may obscure interpretation of preclinical toxicological endpoints. However, with informed consideration, classic hallmarks of hypo-/hyperprolactinemia can be recognized in short- and long-term rodent bioassays. Findings can be supported and expanded with additional in vivo and in vitro datasets. When taken together with human epidemiological evidence pertaining to the consequences of drug-induced hypo-/hyperprolactinemia, such findings permit both an analysis of human relevance and an assessment of human risk.

  2. Research Articles

    1. Top of page
    2. Review
    3. Research Articles
    4. Short Communications
    5. Erratum
    1. Application of dosimetry systems and cytogenetic status of the child population exposed to diagnostic X-rays by use of the cytokinesis-block micronucleus cytome assay (pages 608–617)

      Goran Gajski, Đurđica Milković, Mária Ranogajec-Komor, Saveta Miljanić and Vera Garaj-Vrhovac

      Article first published online: 19 NOV 2010 | DOI: 10.1002/jat.1603

      In the present study we used micronucleus assay for the assessment of chromosomal damage in children exposed to diagnostic X-rays. It was shown that, after diagnostic X-rays, the mean total number of micronucleus assay parameters was significantly higher. Those data suggest that even diagnostic X-ray exposure may induce DNA damaging effect in exposed children, indicating that immense care should be given in both minimizing and optimizing radiation exposure.

    2. Fluoride-induced genotoxicity in mouse bone marrow cells: effect of buthionine sulfoximine and N-acetyl- l-cysteine (pages 618–625)

      Santosh Podder, Ansuman Chattopadhyay, Shelley Bhattacharya, Manas Ranjan Ray and Anindita Chakraborty

      Article first published online: 10 DEC 2010 | DOI: 10.1002/jat.1605

      To understand the mechanism of sodium fluoride (NaF) induced genotoxicity NaF was injected intra-peritoneally in normal, buthionine sulfoximine (BSO) or N-acetyl-L-cysteine (NAC) treated mice. Bone marrow cells were collected at the same divisional cycle and processed for analysis of cell cycle, induction of apoptosis and chromosomal aberrations (CAs). BSO-treatment prior to injection of 2.5 to 7.5 mg NaF kg−1 body weight was found to increase the frequency of CAs significantly whereas they were reduced by NAC pre-treatment.

    3. Toxicological responses of Cyprinus carpio exposed to the herbicide penoxsulam in rice field conditions (pages 626–632)

      Roberta Cattaneo, Bárbara Clasen, Vania Lucia Loro, Charlene Cavalheiro de Menezes, Bibiana Moraes, Adriana Santi, Candida Toni, Luis Antonio de Avila and Renato Zanella

      Article first published online: 28 DEC 2010 | DOI: 10.1002/jat.1606

      Cyprinus carpio were exposed to penoxsulam in field conditions during 7, 21 and 72 days. The acetylcholinesterase activity in the brain was increased after 7 days and reduced after 21 and 72 days. Muscle AChE was reduced after 72 days. TBARS and GST showed variations during experimental periods. Liver Catalase was reduced at 21 days. Liver protein carbonyl showed reduction and increasing during exposure. This study shows long-term effects of penoxsulam at environmentally relevant concentrations on toxicological parameters of fish.

    4. In vivo genotoxicity assessment of nerolidol (pages 633–639)

      Fernanda Pículo, Ceci Guiraldeli Macedo, Sérgio Faloni de Andrade and Edson Luis Maistro

      Article first published online: 19 NOV 2010 | DOI: 10.1002/jat.1607

      Nerolidol is a sesquiterpenoid component of essential oil used as a flavor and aroma enhancer. The objective of this study was to evaluate the ability of a single nerolidol treatment to induce DNA damage in peripheral blood and liver cells of mice and micronuclei in polychromatic erythrocytes (PCEs) of bone marrow cells of the same animals. The doses used in the experiments were 250, 500 and 2000 mg/kg, administered by gavage. For the comet assay, peripheral blood cells were collected 4 and 24 h after the treatments and liver cells 24 h after. Bone marrow cells were collected 24 h after the treatments to the micronucleus test. The results showed that nerolidol induced weak levels of dose-related DNA damage in both types of cells analyzed, and enhanced the average number of micronucleated cells in the two high doses tested.

    5. New aspects of the Slug Mucosal Irritation assay: predicting nasal stinging, itching and burning sensations (pages 640–648)

      Joke Lenoir, Els Adriaens and Jean-Paul Remon

      Article first published online: 6 DEC 2010 | DOI: 10.1002/jat.1610

      The objective of this study was to evaluate the mucosal tolerance of several marketed nasal formulations using the slug Arion lusitanicus. None of the tested formulations resulted in tissue damage, however a clear effect on the mucus production of the slugs was observed, due to the active ingredient, the presence of benzalkonium chloride as a preservative or the hyperosmolality of the formulation. The new 1-day protocol of the Slug Mucosal Irritation assay is a good tool to predict nasal clinical discomfort.

    6. Determination of fentanyl, metabolite and analogs in urine by GC/MS (pages 649–654)

      Sabina Strano-Rossi, Iván Álvarez, María Jesús Tabernero, Pamela Cabarcos, Purificación Fernández and Ana María Bermejo

      Article first published online: 6 DEC 2010 | DOI: 10.1002/jat.1613

      A sensitive method for determining alfentanyl, sufentanyl, fentanyl (and its major metabolite norfentanyl) in urine is described. The method was fully validated and applied to real samples from subjects who had received therapeutic doses of fentanyl, and to a subject whose death was attributed to fentanyl overdose.

    7. Toxicological characterization of N-methyl-N-nitrosourea-induced cataract in rats by LC/MS-based metabonomic analysis (pages 655–662)

      Yuko Miyazono, Kazuo Harada, Koji Sugiyama, Motonobu Ueno, Mikinori Torii, Ikuo Kato, Hideyuki Matsuura and Kazumasa Hirata

      Article first published online: 7 JAN 2011 | DOI: 10.1002/jat.1615

      We conducted a toxicological characterization of MNU-induced cataract in rats by LC/MS-based metabonomic analysis. The principal component analysis of lens samples of the control and MNU-treated groups revealed that the metabolite profiles of lens differed from each other, and several lens metabolites, such as lots of α-amino acids or gluthathione, decreased after MNU treatment. Metabonomic analysis enabled identification of new marker candidates for cataract and provided a better understanding of the mechanism related to MNU-induced cataract.

    8. Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy (pages 663–670)

      Ritu Tyagi, Poonam Rana, Ahmad Raza Khan, Deepak Bhatnagar, M Memita Devi, Shubhra Chaturvedi, Rajendra P. Tripathi and Subash Khushu

      Article first published online: 7 JAN 2011 | DOI: 10.1002/jat.1617

      An NMR spectroscopy-based study was conducted for identification of metabolite markers for thallium toxicity. Urine samples were collected from mice at several time points post injection of low and high doses of Tl2SO4. Spectral analysis showed dose-dependent alterations in various metabolites involved in gut flora, membrane metabolite, energy and protein metabolism The present study shows the great potential of NMR-based metabonomics in mapping metabolic response and for identification of potential markers for Tl toxicity.

    9. A possible mechanism for hepatotoxicity induced by BIRB-796, an orally active p38 mitogen-activated protein kinase inhibitor (pages 671–677)

      Shunsuke Iwano, Yoshiji Asaoka, Hideo Akiyama, Satoko Takizawa, Hitoshi Nobumasa, Hisashi Hashimoto and Yohei Miyamoto

      Article first published online: 16 FEB 2011 | DOI: 10.1002/jat.1622

      The mechanism responsible for the hepatotoxicity of BIRB-796 has yet to be elucidated. In the present study, we performed a toxicogenomic analysis using a highly sensitive DNA chip, 3D-Gene™ Mouse Oligo chip 24k, and the glutathione-trapping method with mouse and human liver microsomes. The production of this reactive metabolite in the liver may be one of the causes of BIRB-796's hepatotoxicity.

    10. Effect of leukotriene receptor antagonists on lung fibrosis in rats (pages 678–684)

      Olfat G. Shaker and Doaa A. Sourour

      Article first published online: 5 MAR 2011 | DOI: 10.1002/jat.1625

      The effects of montelukast, prednisone and their combination in a rat model of bleomycin-induced lung fibrosis were compared. Rats treated with either Montelukast or with both montelukast & prednisone showed reduction in collagen deposition & lung hydroxyproline content. There is reduction in the mean area percent of α-SMA in montelukast and montelukast & prednisone treated groups compared with bleomycin group. Montelukast may be therapeutically effective for inhibiting further progression of lung fibrosis through inhibition of α-SMA positive myofibroblasts.

    11. Cell damage through pentose phosphate pathway in fetus fibroblast cells exposed to methyl mercury (pages 685–689)

      Jamileh Salar Amoli, Abbas Barin, Mina Ebrahimi-Rad and Parisa Sadighara

      Article first published online: 24 MAR 2011 | DOI: 10.1002/jat.1628

      Methylmercury (MeHg) is a global pollutant that causes malformations. There has been no direct evidence for the effect of MeHg on pentose phosphate pathway (PPP). In embryonic development, PPP is much more active. This pathway produces ribose for DNA/RNA production. It is possible that one of teratogenicity mechanisms of MeHg is through PPP. The fetus fibroblast cells were incubated with different concentrations of MeHg (0.1–100 μm). A dose–response dependence was observed in MTT assay.

    12. Nrf2/HO-1 pathway activation by manganese is associated with reactive oxygen species and ubiquitin–proteasome pathway, not MAPKs signaling (pages 690–697)

      Huangyuan Li, Siying Wu, Nian Shi, Shuangqing Lian and Wei Lin

      Article first published online: 7 MAR 2011 | DOI: 10.1002/jat.1654

      Recent studies suggest that the activation of Nrf2 is induced by manganese. However, possible pathway of Nrf2 activation by manganese is still not clear. A link between reactive oxygen species (ROS), proteasomes or MAPKs and Nrf2/HO-1 induction in manganese-treated PC12 cells was determined by the use of various agents or pharmacological inhibitors. Here, we report for the first time that Nrf2/HO-1 activation by manganese in PC12 cells is associated with ROS generation and the ubiquitin-proteasome pathway, but not MAPKs signaling.

    13. Bisphenol A decreases atrial contractility involving NO-dependent G-cyclase signaling pathway (pages 698–702)

      Jayanti Pant, Pratibha Ranjan and Shripad B. Deshpande

      Article first published online: 23 FEB 2011 | DOI: 10.1002/jat.1647

      Effect of bisphenol-A (BPA), a toxic chemical present in plastics, on spontaneously beating rat right atria was examined. BPA (0.1-100 microM) reduced rate and force of atrial contractions (> 90% decrease at 100 microM). BPA-induced changes were not blocked by its solvent or by atropine. However, NOS inhibitor or G-cyclase inhibitor blocked the BPA induced changes in rate and force. Nitroglycerine (NO-donor) decreased the rate and force of atrial contractions. Therefore, BPA decreases atrial contractility by involving NO-G-cyclase signaling mechanisms.

  3. Short Communications

    1. Top of page
    2. Review
    3. Research Articles
    4. Short Communications
    5. Erratum
    1. Reduction in fluoride-induced genotoxicity in mouse bone marrow cells after substituting high fluoride-containing water with safe drinking water (pages 703–705)

      Santosh Podder, Ansuman Chattopadhyay and Shelley Bhattacharya

      Article first published online: 5 MAR 2011 | DOI: 10.1002/jat.1644

      Treatment of mice with 15 mg l−1 sodium fluoride for 30 days increased the number of cell death, chromosomal aberrations and ‘cells with chromatid breaks’ compared with control. The present study was intended to determine whether the genotoxicity could be reduced by safe drinking water. A significant fall in last two parameters after safe water treatment in mice was observed. This observation suggests that fluoride induced genotoxicity could be reduced by substituting high fluoride containing water with safe drinking water.

  4. Erratum

    1. Top of page
    2. Review
    3. Research Articles
    4. Short Communications
    5. Erratum
    1. Protective actions of des-aspartate-angiotensin I in mice model of CEES-induced lung intoxication (page 706)

      Eugene Teck-Leong Ng, Meng-Kwoon Sim and Weng-Keong Loke

      Article first published online: 24 OCT 2011 | DOI: 10.1002/jat.1755

      This article corrects:

      Protective actions of des-aspartate-angiotensin I in mice model of CEES-induced lung intoxication

      Vol. 31, Issue 6, 568–578, Article first published online: 9 NOV 2010