Journal of Applied Toxicology

Cover image for Vol. 35 Issue 8

August 2015

Volume 35, Issue 8

Pages 870–969

  1. Review Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Sertoli cell as a model in male reproductive toxicology: Advantages and disadvantages (pages 870–883)

      Mariana M. S. Reis, Ana C. Moreira, Mário Sousa, Premendu P. Mathur, Pedro F. Oliveira and Marco G. Alves

      Article first published online: 18 FEB 2015 | DOI: 10.1002/jat.3122

      Several chemicals and mixtures impair male fertility. It is essential to use reliable in vitro models to determine cellular targets and intracellular pathways that mediate chemical toxicity in the males. Sertoli cell (SC), within the testis, is a major target for hormonal signaling. Here, we intend to clarify the unique features that render SCs as excellent candidates for a robust in vitro model to study the deleterious effects of chemicals on male reproductive health.

  2. Research Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Maternal exposure to 3,3’-iminodipropionitrile targets late-stage differentiation of hippocampal granule cell lineages to affect brain-derived neurotrophic factor signaling and interneuron subpopulations in rat offspring (pages 884–894)

      Megu Itahashi, Hajime Abe, Takeshi Tanaka, Sayaka Mizukami, Yoh Kikuchihara, Toshinori Yoshida and Makoto Shibutani

      Article first published online: 25 NOV 2014 | DOI: 10.1002/jat.3086

      This study investigated the maternal 3,3’-iminodipropionitrile (IDPN) exposure effect on hippocampal neurogenesis in rat offspring. Pregnant rats were supplemented with IDPN in drinking water during gestation and lactation. Female offspring subjected to analysis had decreased parvalbumin+, reelin+ and phospho-TrkB+ interneurons in the dentate hilus at 200 ppm and increased Arc+ and c-Fos+ granule cells at ≥ 67 ppm. The results suggest that IDPN targets neuronal plasticity of granule cell lineages to cause BDNF downregulation resulting in reduction in GABAergic interneurons.

    2. Tributyltin alters secretion of interleukin 1 beta from human immune cells (pages 895–908)

      Shyretha Brown and Margaret Whalen

      Article first published online: 7 NOV 2014 | DOI: 10.1002/jat.3087

      Tributyltin (TBT) has been used as a biocide in industrial applications such as wood preservation, antifouling paint and antifungal agents. Owing to its many uses, it contaminates the environment and has been found in human blood samples. Interleukin-1 beta (IL-1β) is a pro-inflammatory cytokine that promotes cell growth, tissue repair and immune response regulation. Produced predominately by both monocytes and macrophages, IL-1β appears to increase the invasiveness of certain tumors.

    3. HepaRG culture in tethered spheroids as an in vitro three-dimensional model for drug safety screening (pages 909–917)

      Zenan Wang, Xiaobei Luo, Chukwuemeka Anene-Nzelu, Yu Yu, Xin Hong, Nisha Hari Singh, Lei Xia, Side Liu and Hanry Yu

      Article first published online: 15 DEC 2014 | DOI: 10.1002/jat.3090

      We described the evaluation of HepaRG-tethered spheroids as an in vitro three-dimensional culture system for drug safety testing. The liver specific gene expression level and drug metabolizing enzyme activities in HepaRG tethered spheorids were markedly higher than those in 2D cultures throughout the culture period of seven days. The inducibility of three major cytochrome P450 enzymes was improved in tethered spheroids. Its potential for high throughput drug safety screening could be in favor of by the pharmaceutical industry.

    4. Combined exposure to lead, inorganic mercury and methylmercury shows deviation from additivity for cardiovascular toxicity in rats (pages 918–926)

      Tanja M. Wildemann, Lynn P. Weber and Steven D. Siciliano

      Article first published online: 18 DEC 2014 | DOI: 10.1002/jat.3092

      The cardiovascular effects of lead and mercury species and their mixtures were investigated in male rats. Exposure occurred for 28 days through the drinking water. A single exposure to methylmercury [MeHg(I)] increased blood pressure and decreased cardiac output, whereas mixtures reversed the effect (antagonism). A single exposure to lead [Pb(II)], mercury [Hg(II)] and MeHg(I) did not affect cardiac electrical activity, whereas co-exposure aggravated it (synergism). Single metal exposures cannot predict the adverse cardiovascular effects of Pb and Hg mixtures.

    5. Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C δ in human neuroblastoma dopaminergic SH-SY5Y cell lines (pages 927–944)

      Yunsung Nam, Myung Bok Wie, Eun-Joo Shin, Thuy-Ty Lan Nguyen, Seung-Yeol Nah, Sung Kwon Ko, Ji Hoon Jeong, Choon-Gon Jang and Hyoung-Chun Kim

      Article first published online: 18 DEC 2014 | DOI: 10.1002/jat.3093

      We examined the effects of dopaminergic protectant ginsenoside Re against methamphetamine toxicity using SH-SY5Y neuroblastoma cells. Re treatment exhibited significant protections against mitochondrial oxidative burdens, mitochondrial dysfunctions, mitochondrial translocation of PKCδ and apoptotic events induced by methamphetamine. These protective effects of Re were comparable to those of PKCδ antisense oligonucleotide. Re did not significantly provide additional effects on the protection mediated by PKCδ inhibition. The results suggest that PKCδ is a specific target for Re-mediated protective activity against methamphetamine toxicity.

    6. Culture conditions profoundly impact phenotype in BEAS-2B, a human pulmonary epithelial model (pages 945–951)

      Fei Zhao and Walter T. Klimecki

      Article first published online: 19 DEC 2014 | DOI: 10.1002/jat.3094

      BEAS-2B, an immortalized, human lung epithelial cell line, has been used to model pulmonary epithelial function for over 30 years. The BEAS-2B phenotype can be modulated by culture conditions that include the presence or absence of fetal bovine serum (FBS). The popularity of BEAS-2B as a model of arsenic toxicology, and the common use of BEAS-2B cultured both with and without FBS, led us to investigate the impact of FBS on BEAS-2B in the context of arsenic toxicology.

    7. Tl(I) and Tl(III) alter the expression of EGF-dependent signals and cyclins required for pheochromocytoma (PC12) cell-cycle resumption and progression (pages 952–969)

      María T. L. Pino and Sandra V. Verstraeten

      Article first published online: 22 DEC 2014 | DOI: 10.1002/jat.3096

      The effects of thallium [Tl(I) and Tl(III)] (5–100 μM) on the PC12 cell cycle were evaluated without (EGF) or with (EGF+) media supplementation with epidermal growth factor (EGF). These cations did not activate EGF receptor (EGFR) in EGF cells, but induced ERK1/2 and Akt phosphorylation. Tl(I) promoted both EGF and EGF+ cell proliferation. In contrast, Tl(III) promoted EGF cell proliferation but delayed EGF+ cell-cycle resumption, which may be related to the toxic effects of this cation in PC12 cells.

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