Journal of Applied Toxicology

Cover image for Vol. 35 Issue 3

March 2015

Volume 35, Issue 3

Pages 229–326

  1. Obituary

    1. Top of page
    2. Obituary
    3. Research Articles
    1. Memorial address to Dr Tohru Inoue (page 229)

      Yoko Hirabayashi

      Article first published online: 21 JAN 2015 | DOI: 10.1002/jat.3101

  2. Research Articles

    1. Top of page
    2. Obituary
    3. Research Articles
    1. Experimentally induced, synergistic late effects of a single dose of radiation and aging: significance in LKS fraction as compared with mature blood cells (pages 230–240)

      Yoko Hirabayashi, Isao Tsuboi, Kei Nakachi, Yoichiro Kusunoki and Tohru Inoue

      Article first published online: 21 NOV 2014 | DOI: 10.1002/jat.3088

      The number of murine mature blood cells recovered within 6 weeks after 2-Gy whole-body irradiation, whereas in the case of the undifferentiated hematopoietic stem/progenitor cell compartment, their numerical recovery was significantly delayed. In the case of 21-month-old mice with radiation exposure, Ccnd1, PiK3r1, and Fyn were overexpressed solely in the undifferentiated hematopoietic stem/progenitor cell compartment. Because Ccnd1and PiK3r1 upregulated by aging were further upregulated by single-dose radiation, the prolonged effects of radiation seem to modify the xenobiotic processes during aging.

    2. Cardiotoxicity evaluation of anthracyclines in zebrafish (Danio rerio) (pages 241–252)

      Ying Han, Jing-pu Zhang, Jian-qin Qian and Chang-qin Hu

      Article first published online: 22 MAY 2014 | DOI: 10.1002/jat.3007

      Drug-induced cardiotoxicity is a leading factor for drug withdrawals, and limits drug efficacy and clinical use. Therefore, new alternative animal models and methods for drug safety evaluation have been given great attention. Anthracyclines (ANTs) are widely prescribed anticancer agents that have a cumulative dose relationship with cardiotoxicity. We performed experiments to study the toxicity of ANTs in early developing zebrafish embryos, especially their effects on the heart. LC50 values for daunorubicin, pirarubicin, doxorubicin (DOX), epirubicin and DOX-liposome at 72 h post-fertilization were 122.7 μM, 111.9 μM, 31.2 μM, 108.3 μM and 55.8 μM, respectively.

    3. Endocrine disruption effects of p,p′-DDE on juvenile zebrafish (pages 253–260)

      Marta Sofia Monteiro, Maria Pavlaki, Augusto Faustino, Alexandra Rêma, Mariana Franchi, Letícia Gediel, Susana Loureiro, Inês Domingues, Jaime Rendón von Osten and Amadeu Mortágua Velho Maia Soares

      Article first published online: 15 MAY 2014 | DOI: 10.1002/jat.3014

      Potential endocrine effects of p,p'-DDE, the major metabolite of the insecticide DDT, were investigated in zebrafish during gonad differentiation. Juveniles were exposed to sub-lethal concentrations during 14 days and maintained in control water for further 4 months. An increase in vtg production was observed in exposed juveniles. Female gonads presented histopathological changes, which might impair their successful reproduction. These results demonstrate the ability of p,p'-DDE to cause endocrine disruption during gonad differentiation of zebrafish.

    4. Developmental toxicity assay using high content screening of zebrafish embryos (pages 261–272)

      Susan Lantz-McPeak, Xiaoqing Guo, Elvis Cuevas, Melanie Dumas, Glenn D. Newport, Syed F. Ali, Merle G. Paule and Jyotshna Kanungo

      Article first published online: 28 MAY 2014 | DOI: 10.1002/jat.3029

      High content assay quantifies developmental toxicity in zebrafish embryos.

    5. Protective role of L-ascorbic acid, N-acetylcysteine and apocynin on neomycin-induced hair cell loss in Zebrafish (pages 273–279)

      Chia-Yen Wu, Han-Jung Lee, Chi-Fang Liu, Mallikarjuna Korivi, Hwei-Hsien Chen and Ming-Huan Chan

      Article first published online: 4 AUG 2014 | DOI: 10.1002/jat.3043

      Hair cells are sensitive to the therapeutic drugs, like aminoglycosides which cause hearing loss. Co-administration with L-ascorbic acid, NAC, and apocynin protected neomycin-induced hair cell loss within the neuromasts in zebrafish. These compounds reduced ROS production in neuromasts exposed to neomycin, but did not influence the uptake of neomycin into hair cells. Data implies that prevention of hair cell damage against neomycin by L-ascorbic acid, NAC, and apocynin might be associated with inhibition of ROS production, but not neomycin uptake.

    6. A representative retinoid X receptor antagonist UVI3003 induced teratogenesis in zebrafish embryos (pages 280–286)

      Liang Zheng, Ting Xu, Daoji Li and Junliang Zhou

      Article first published online: 3 SEP 2014 | DOI: 10.1002/jat.3051

      Retinoid X receptor (RXR) interfering activity has been detected in different water resources. To study RXR disruptor-induced toxicological effects on vertebrates, embryos of zebrafish (Danio rerio) were exposed to a representative RXR antagonist UVI3003. Results showed that the teratogenic index (LC50/EC50) of UVI3003 was as high as 5.4. UVI3003 induced multiple malformations of embryos, including deformed fins, reduced brains, small jaws, bent tails and edema in hearts, the degree of which became more severe with increasing exposure concentration.

    7. Perturbation of cytosolic calcium by 2-aminoethoxydiphenyl borate and caffeine affects zebrafish myofibril alignment (pages 287–294)

      Hsin-Ju Wu, Tsorng-Harn Fong, Shen-Liang Chen, Jen-Cheng Wei, I-Jong Wang, Chi-Chung Wen, Chao-Yuan Chang, Xing-Guang Chen, Wei-Yu Chen, Hui-Min Chen, Juin-Lin Horng, Yun-Hsin Wang and Yau-Hung Chen

      Article first published online: 4 SEP 2014 | DOI: 10.1002/jat.3057

      The objective of the current study was to investigate the correlation of cytosolic calcium levels and myofibril alignments during zebrafish embryogenesis. We exposed 2-aminoethoxydiphenyl borate and caffeine to zebrafish embryos to disturb the cytosolic calcium levels. Our data show that (1) both enhanced and reduced of cytosolic calcium led to mis-alignment of myofibrils; (2) reduction of cytosolic calcium increases myod expression; and (3) electron density is affected by intracellular calcium reduction. In conclusion, we proposed that cytosolic calcium is important for myofibrils alignment.

    8. Tween-80 and impurity induce anaphylactoid reaction in zebrafish (pages 295–301)

      Rui Yang, Qiao-Cong Lao, Hang-Ping Yu, Yong Zhang, Hong-Cui Liu, Lin Luan, Hui-Min Sun and Chun-Qi Li

      Article first published online: 27 OCT 2014 | DOI: 10.1002/jat.3069

      This study developed a microplate-based quantitative in vivo zebrafish assay for assessing anaphylactoid reaction. We assessed 10 batches of Tween-80 and 3 Tween-80 impurities (ethylene glycol, 2-chloroethanol and hydrogen peroxide) in this model and found that 3 batches of Tween-80 and one Tween-80 impurity hydrogen peroxide (H2O2) induced anaphylactoid reaction in zebrafish. H2O2 residue in combination with oxidized fatty acid residues in Tween-80 samples, but not Tween-80 itself, may induce anaphylactoid reaction.

    9. Characterization of Oryzias latipes glucocorticoid receptors and their unique response to progestins (pages 302–309)

      Shinichi Miyagawa, Anke Lange, Saki Tohyama, Yukiko Ogino, Takeshi Mizutani, Tohru Kobayashi, Norihisa Tatarazako, Charles R. Tyler and Taisen Iguchi

      Article first published online: 23 JUL 2014 | DOI: 10.1002/jat.3020

      We here report the molecular characterization of medaka (Oryzias latipes) corticosteroid receptors (GRs), and show that GR2 is most likely the subtype mediating glucocorticoid signaling in the medaka. We also found that progestins could activate or inactivate GR2-mediated transcription, depending on the presence or absence of cortisol. These findings advance understanding of the basic mechanisms of GR-mediated transcription in medaka.

    10. Impact of acute arsenic and cadmium exposure on the expression of two haeme oxygenase genes and other antioxidant markers in common carp (Cyprinus carpio) (pages 310–318)

      Zsanett Jancsó and Edit Hermesz

      Article first published online: 7 APR 2014 | DOI: 10.1002/jat.3000

      The response of an organism to exposure to toxic metals is in many cases brought about by changes at the level of gene expression. In this study, the heme oxygenases genes (ho-1 and ho-2) of common carp Cyprinus carpio were identified, and the changes in gene expressions were analyzed from the aspect of Cd and As accumulation. Both ho-1 and ho-2 are transcriptionally induced by Cd and As, but their inductions differ in time course, dose response and tissue specificity.

    11. Toxicity profiles and solvent–toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure (pages 319–326)

      An-Sofie Stevens, Nicky Pirotte, Michelle Plusquin, Maxime Willems, Thomas Neyens, Tom Artois and Karen Smeets

      Article first published online: 25 JUN 2014 | DOI: 10.1002/jat.3011

      The solvent dimethylsulfoxide (DMSO) is used to investigate the toxicity of hydrophobic test compounds, but can bias the interpretation of test compound-induced responses. We assessed the effects of low DMSO concentrations on the planarian Schmidtea mediterranea, paying special attention to long-term exposures and stem cell responses, two important parameters in carcinogenicity assays. Above 500 µ l−1, DMSO affected different biological levels. We propose to avoid higher DMSO concentrations, or statistically take into account DMSO-induced effects and solvent–toxicant interactions.

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