Journal of Applied Toxicology

Cover image for Vol. 32 Issue 2

February 2012

Volume 32, Issue 2

Pages 81–152

  1. Review

    1. Top of page
    2. Review
    3. Research Articles
    4. Letters to the Editor
    1. Can cytogenetics explain the possible association between exposure to extreme low-frequency magnetic fields and Alzheimer's disease? (pages 81–87)

      Annemarie Maes and Luc Verschaeve

      Version of Record online: 20 SEP 2011 | DOI: 10.1002/jat.1724

      Some epidemiological studies suggested that exposure to extreme low frequency-electromagnetic fields (ELF-EMFs) may be a risk factor for Alzheimer's disease. The disease is characterized by a number of events that partially have a genetic origin. A review is presented on the possible association between exposures to ELF-EMFs and Alzheimer's disease based on indications that these fields may induce genetic changes as those seen in Alzheimer's disease.

  2. Research Articles

    1. Top of page
    2. Review
    3. Research Articles
    4. Letters to the Editor
    1. NMR-based metabonomic approach on the toxicological effects of a Cimicifuga triterpenoid (pages 88–97)

      Cui-Cui He, Yun-Qing Dai, Rong-Rong Hui, Jia Hua, Hong-Juan Chen, Qiao-Yun Luo and Jian-Xin Li

      Version of Record online: 30 MAR 2011 | DOI: 10.1002/jat.1633

      Cimicidol-3-O-β-d-xyloside (CX) is one of the main triterpenoids isolated from a well-known botanical dietary supplement of Cimicifuga extract. The current work is to access the toxicological effects of CX after oral administration over a 7-day period in female SD rats using metabonomic analyses of 1H NMR, together with conventional measurements of blood biochemical parameters. The results indicated that CX has a slight toxicity in liver and kidney and provides reasonable explanation for the clinical hepatotoxicity of Cimicifuga extract.

    2. Malformation spectrum induced by ketoconazole after single administration to pregnant rats during the critical period – comparison with vitamin A-induced malformation spectrum (pages 98–107)

      Hiroshi Mineshima, Tetsuya Fukuta, Emiko Kato, Keiji Uchida, Toyohiko Aoki, Yoshiharu Matsuno and Chisato Mori

      Version of Record online: 11 FEB 2011 | DOI: 10.1002/jat.1636

      Malformations and their sensitive windows induced by ketoconazole (KCZ) were investigated. Pregnant rats were administered a single dose of KCZ by gavage on gestational days 8-15. KCZ-induced malformations included cleft palate, digital anomalies, misshapen limbs and unique discontinuous ribs, and the sensitive window for each was identified. The malformation spectrum was compared with vitamin A palmitate, and the results suggested that the mechanisms of several of the types of KCZ-induced malformation are related to excessive vitamin A.

    3. Effect of structural modifications on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione-induced hepatotoxicity in Fischer 344 rats (pages 108–117)

      Niti N. Patel, Christine M. Crincoli, Douglas M. Frederick, Ruy Tchao and Peter J. Harvison

      Version of Record online: 21 FEB 2011 | DOI: 10.1002/jat.1639

      We conducted a structure–activity relationship study on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)-induced hepatotoxicity in rats. Attachment of a methyl group in the thiazolidinedione (TZD) ring was still associated with liver damage. By contrast, hepatotoxicity was abolished with other TZD ring modifications such as ring opening or removal of either carbonyl group. The toxicity of DCPT analogs was also highly dependent on the nature of the substituents in the phenyl ring. Our results suggest that an intact TZD ring is required for hepatotoxicity.

    4. Regulation of intracellular Ca2+ by reactive oxygen species in osteoblasts treated with antimycin A (pages 118–125)

      Eun Mi Choi

      Version of Record online: 5 MAR 2011 | DOI: 10.1002/jat.1642

      This study evaluated the effects of antimycin A (AMA) on the release of [Ca2+]i, ROS, and bone resorbing factors in osteoblasts. Pretreatment of osteoblasts with trolox and cyclosporin A prevented the AMA-induced increases in [Ca2+]i. BAPTA/AM, dantrolene, and cyclosporine A did not reverse the effect of AMA on ROS release. Trolox prevented the release of RANKL, IL-6, and TNF-a induced by AMA. Moreover, the increased IL-6 and TNF-a release by AMA was markedly reduced by BAPTA/AM and cyclosporin A.

    5. Differential mRNA expression of neuroimmune markers in the hippocampus of infant mice following toluene exposure during brain developmental period (pages 126–134)

      Tin-Tin Win-Shwe, Naoki Kunugita, Yasuhiro Yoshida, Daisuke Nakajima, Shinji Tsukahara and Hidekazu Fujimaki

      Version of Record online: 5 MAR 2011 | DOI: 10.1002/jat.1643

      Toluene, a volatile organic compound with a wide range of industrial applications, can exert neurotoxic and immunotoxic effects. However, the effects of toluene exposure on developmental immunotoxicity in the brain have not yet been characterized. To investigate the susceptible window to toluene exposure during development and the effects of fetal and neonatal toluene exposure on the neuroimmune markers, gestational day (GD) 14 pregnant mice, postnatal day (PND) 2 and PND 8 male offspring were exposed to filtered air (control; 0 ppm)

    6. Investigation of anticholinergic and non-steroidal anti-inflammatory prodrugs which reduce chemically induced skin inflammation (pages 135–141)

      Sherri C. Young, Karine M. Fabio, Mou-Tuan Huang, Jaya Saxena, Meredith P. Harman, Christophe D. Guillon, Anna M. Vetrano, Diane E. Heck, Robert A. Flowers II, Ned D. Heindel and Jeffrey D. Laskin

      Version of Record online: 11 FEB 2011 | DOI: 10.1002/jat.1645

      Presented herein are unique NSAID prodrugs which target inflammation and cholinergic dysfunction. Compounds 1-28 contain NSAIDs linked to choline bioisosteres or to analogs of acetylcholinesterase inhibitors. Many of the prodrugs have activity against 2-chloroethyl ethyl sulfide (CEES), with 5, 18, 22 and 27 reducing inflammation by more than 75%. Compounds 12, 13, 15 and 22 show comparable activity against the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Promising activity in the MEVM is related to rate of NSAID-release, lipophilicity and anticholinesterase activity.

    7. Phthalate esters modulate the differentiation and maturation of mouse peripheral blood mononuclear cell-derived dendritic cells (pages 142–148)

      Tomohiro Ito, Ken-ichiro Inoue, Noriko Nishimura and Hirohisa Takano

      Version of Record online: 28 APR 2011 | DOI: 10.1002/jat.1652

      Phthalate esters are widespread environmental contaminants. The present study sought to investigate whether phthalate esters affect peripheral blood mononuclear cell (PBMC)-derived DCs of NC/Nga mice. DEHP at 10 μM significantly inhibited the expression of DC differentiation and maturation markers, and these effects were partially rescued by treatment with ICI 182,780, an estrogen receptor antagonist. Taken together, these results suggest that DEHP can modulate the differentiation and maturation of mouse PBMC-derived DCs at least partially through activation of the estrogen receptor.

  3. Letters to the Editor

    1. Top of page
    2. Review
    3. Research Articles
    4. Letters to the Editor