Journal of Applied Toxicology

Cover image for Vol. 33 Issue 2

February 2013

Volume 33, Issue 2

Pages 78–156

  1. Review Article

    1. Top of page
    2. Review Article
    3. Research Articles
    1. Silver nanoparticle-induced oxidative stress, genotoxicity and apoptosis in cultured cells and animal tissues (pages 78–89)

      Soohee Kim and Doug-Young Ryu

      Article first published online: 31 AUG 2012 | DOI: 10.1002/jat.2792

      Silver nanoparticles (AgNPs) have emerged as an important class of nanomaterials for a wide range of applications. However, the unique properties of AgNPs could potentially lead to unexpected hazards to human and environmental health. In this study, a number of previous studies are summarized that demonstrate oxidative stress-, genotoxicity- and apoptosis-related changes brought about by AgNPs. The physicochemical properties of AgNPs that are involved in encouraging such changes are also discussed.

  2. Research Articles

    1. Top of page
    2. Review Article
    3. Research Articles
    1. Ovarian disorders in immature rats after postnatal exposure to environmental polycyclic aromatic hydrocarbons (pages 90–99)

      Vladimír Kummer, Jarmila Mašková, Zdeněk Zralý and Martin Faldyna

      Article first published online: 22 AUG 2011 | DOI: 10.1002/jat.1714

      Neonates were injected (days 1–14) with benzo(a)pyrene, benz(a)anthracene or benzo(k)fluoranthene and killed on day 23. Exposure to benzo(a)pyrene or benz(a)anthracene increased the number of nonatretic antral follicles and the thecal layer thickness. Disturbed primordial oocytes were only observed after exposure to benzo(a)pyrene. Alterations in ovarian ERβ expression were detected. The response of the ovaries to estradiol in rats exposed to PAHs was suppressed. The study showed that postnatal exposure to PAHs disturbed development of the ovaries and caused ovarian dysfunction.

    2. Direct and metabolism-dependent cytochrome P450 inhibition assays for evaluating drug–drug interactions (pages 100–108)

      Kye Sook Lee and Sang Kyum Kim

      Article first published online: 14 SEP 2011 | DOI: 10.1002/jat.1720

      We developed methods for evaluating inhibitory potential of eight human cytochrome P450 isoforms using substrate cocktail, human liver microsomes and liquid chromatography/tandem mass spectrometry. Our methods can distinguish between a direct inhibition and a metabolism-dependent inhibition (MDI) based on shift of IC50 values following preincubation with tested compound and NADPH. These CYP inhibition assays are considered to be useful tools for evaluating both direct inhibition and MDI at an early stage of the drug discovery and development process.

    3. Polycyclic aromatic hydrocarbons within airborne particulate matter (PM2.5) produced DNA bulky stable adducts in a human lung cell coculture model (pages 109–119)

      Imane Abbas, Guillaume Garçon, Françoise Saint-Georges, Véronique Andre, Pierre Gosset, Sylvain Billet, Jérémie Le Goff, Anthony Verdin, Philippe Mulliez, François Sichel and Pirouz Shirali

      Article first published online: 13 SEP 2011 | DOI: 10.1002/jat.1722

      The metabolic activation of polycyclic aromatic hydrocarbons (PAH) within air pollution particulate matter (PM2.5) and PAH-DNA bulky stable adducts in human alveolar macrophage (AM) and/or human lung epithelial L132 cells in mono- and/or in cocultures were studied. Taken together, our relevant results support the exertion of genotoxicity of highly reactive PAH-derived metabolites produced within human AM not only in primary target human AM, but also in secondary target L132 cells.

    4. Palytoxin causes nonoxidative necrotic damage to PC12 cells in culture (pages 120–124)

      Takefumi Sagara, Naoyoshi Nishibori, Mari Itoh, Kyoji Morita and Song Her

      Article first published online: 12 SEP 2011 | DOI: 10.1002/jat.1728

      The direct effect of palytoxin (PTX) on PC12 cells was examined as a model experiment for investigating its neurotoxic action. PTX reduced the cell viability, and this reduction was not significantly altered by antioxidants. PTX failed to cause the chromatin condensation and the DNA fragmentation, while caused the positive staining of the cell cytoplasm with propidium iodide and the release of lactate dehydrogenase into the medium. PTX may disrupt the plasma membranes, causing the non-oxidative necrotic cell death.

    5. Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish (pages 125–133)

      June Choi, Gi Jung Im, Jiwon Chang, Sung Won Chae, Seung Hoon Lee, Soon-Young Kwon, Ah-Young Chung, Hae-Chul Park and Hak Hyun Jung

      Article first published online: 6 DEC 2011 | DOI: 10.1002/jat.1729

      Apocynin, which is used as a specific NADPH oxidase inhibitor, has a preventive effect for intracellular ROS generation. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Apocynin has antioxidative effects and prevents cisplatin induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish.

    6. Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy (pages 134–141)

      Ritu Tyagi, Poonam Rana, Mamta Gupta, Ahmad Raza Khan, Deepak Bhatnagar, P. J. S. Bhalla, Shubhra Chaturvedi, Rajendra P Tripathi and Subash Khushu

      Article first published online: 16 SEP 2011 | DOI: 10.1002/jat.1730

      An integrated metabonomic approach, based on high-resolution 1H NMR spectroscopy, was applied to find acute biochemical effects of NiCl2 on renal tissues of rats. The metabolite changes corresponding to nickel exposure are related to amino acids, osmolytes and energy metabolites. Differential responses were observed in 1H NMR spectra of these metabolites with exposure to low and high doses of NiCl2. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal toxicity.

    7. Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood (pages 142–150)

      Greicy M. M. Conterato, Rachel P. Bulcão, Rocheli Sobieski, Angela M. Moro, Mariele F. Charão, Fernando A. de Freitas, Fernanda L. de Almeida, Ana P. L. Moreira, Miguel Roehrs, Raquel Tonello, Bruno L. Batista, Denise Grotto, Fernando Barbosa Jr, Solange C. Garcia and Tatiana Emanuelli

      Article first published online: 9 SEP 2011 | DOI: 10.1002/jat.1731

      The relationship of blood lead level (BLL) and blood cadmium level (BCL) with hematological and oxidative stress parameters was evaluated in exposed workers (50 painters and 23 battery workers) and control subjects (36). The changes in oxidative stress and hematological parameters were distinctively associated with either BLL or BCL. Thioredoxin reductase activity was not changed in the exposed workers. However, biochemical and hematological changes at low BLLs underlie the necessity of reevaluating the recommended health-based limits in occupational exposure to this metal.

    8. In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100) (pages 151–156)

      Diego Di Felipe Ávila Alcântara, Helem Ferreira Ribeiro, Plínio Cerqueira dos Santos Cardoso, Taíssa Maíra Thomaz Araújo, Rommel Rodriguez Burbano, Adriana Costa Guimarães, André Salim Khayat and Marcelo de Oliveira Bahia

      Article first published online: 23 SEP 2011 | DOI: 10.1002/jat.1734

      We conducted a cytotoxic and genotoxic study in PG100 cell line and human lymphocytes after treatment with artemether. Using MTT assay, comet assay and ethidium bromide/acridine orange viability staining, we showed that artemether has a cytotoxic effect and induces necrosis in the PG100 gastric cancer cell line. However, its use as a possible antineoplastic drug is not recommended, since the cytotoxic effects were more consistent in human lymphocytes.

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