Fundamental Toxicological Sciences

2019 - Vol. 6 No. 2

2019 - Vol. 6

Original Article
Effects of benzotriazole ultraviolet stabilizers on rat PXR, CAR and PPARα transcriptional activities Vol.6, No.2, p.57-63
Yoko Watanabe , Shoko Hattori , Chieri Fujino , Ken Tachibana , Hiroyuki Kojima , Kouichi Yoshinari , Shigeyuki Kitamura
Released: March 19, 2019
Abstract Full Text PDF[1M]

Benzotriazole ultraviolet stabilizers (BUVSs) are widely used as ultraviolet filters in various consumer and industrial products. For this purpose, we examined the effects of 10 BUVSs and benzotriazole itself on transcriptional activation mediated by nuclear receptors: pregnane X receptor (PXR), constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor alpha (PPARα). UV-090 and UV-9 showed rat PXR-agonistic activity in the concentration range of 1-30 μM in reporter gene assay using simian kidney COS-1 cells. UV-090 showed the highest activity (REC20 value: 3.85 × 10-6 M). UV-090 was also positive in rat CAR activation assay, while UV-P showed inverse agonistic activity towards CAR. In the presence of the CAR agonist artemisinin (10 μM), UV-P also showed dose-dependent CAR-antagonistic activity in the concentration range of 10-30 μM. UV-090 and UV-9 activated rat PPARα. Overall, these results suggest that UV-090, UV-9 and UV-P modulate PXR, CAR and/or PPARα activation.

Original Article
Cytotoxic effects of parathion, paraoxon, and their methylated derivatives on a mouse neuroblastoma cell line NB41A3 Vol.6, No.2, p.45-56
Yunbiao Wang , ByungHoon Kim , Ashley Walker , Shayla Williams , Ashley Meeks , Yong-Jin Lee , Seong S. Seo
Released: March 12, 2019
Abstract Full Text PDF[2M]

Organophosphorus compounds (OPCs) are widely used as pesticides, but often show high toxicity in mammalian cells. To assess the toxic potential of OPCs, we examined the cytotoxicity of paraoxon, methyl-paraoxon, parathion, and methyl-parathion exposures on NB41A3 neuroblastoma mouse cell lines. The LC50s (median lethal concentrations) at 24 hr of exposure were determined from the acute toxicity test including time course experiments. The LC50 values suggest higher toxicity of paraoxon (0.42 mM) compared to parathion (0.66 mM). In addition, the methylated derivatives of both OPCs indicated similar but slightly lower levels of toxicity compared to paraoxon and parathion (0.46 mM for methyl-paraoxon and 0.77 mM for methyl-parathion). However, the results from time course experiments indicated obvious reduction of cell viability for parathion and methyl-parathion as early as 1 hr of exposure, whereas the effects of paraoxon and methyl-paraoxon were not significant before 6 hr of exposure. We also report the most affected biological processes in NB41A3 cells in response to parathion exposure using microarray experiment. Among the statistically overrepresented biological processes are the ones related to neuronal development, apoptosis, cell stress, and cell signaling.

Original Article
Acute hepatotoxicity and drug/chemical interaction toxicity of 10-nm silver nanoparticles in mice Vol.6, No.2, p.37-44
Katsuhiro Isoda , Naoki Kobayashi , Yuichiro Taira , Ikuko Taira , Yoshimi Shimizu , Yoshihiro Akimoto , Hayato Kawakami , Isao Ishida
Released: March 06, 2019
Abstract Full Text PDF[4M]

Nanomaterials with nanoscale microstructures have new properties in which reactions to stimuli such as heat, light, and voltage differ from those of macroscale materials. For that reason, the development of nanotechnology using nanomaterials has been remarkable, and these technologies have been put to practical use in various fields such as medicine and electronics. Nanomaterials have been researched as new materials with superior properties that have not been seen in the past, but concerns remain about the influence of nanomaterials on living bodies. Silver nanoparticles are materials with excellent optical, electrical, and antibacterial properties. However, few reports have described the influence of silver nanoparticles on the living body and interactions between chemicals such as pharmaceuticals. We therefore investigated the effect of silver nanoparticles on the living body and drug interactions. We administered silver nanoparticles with particle diameters of 10, 50, and 200 nm (SnP10, SnP50, and SnP200, respectively) to mice through the tail vein. As a result, acute liver injury was induced only in the SnP10 group. Furthermore, liver injury was induced by co-administering SnP10 with carbon tetrachloride, streptomycin, or cisplatin. SnP10 appears to induce liver injury through acute and drug interactions.

Toxicomics Report
Effects of lithium on developmental toxicity, teratogenicity and transcriptome in medaka embryos Vol.6, No.2, p.31-36
Nobuaki Tominaga , Seiya Shino , Masaya Uchida , Hiroshi Ishibashi , Midori Iida , Tadashi Okobira , Kayla Arizono , Noriaki Yoshida , Koji Arizono
Released: February 15, 2019
Abstract Full Text PDF[2M]

In this study, we assessed embryonic developmental toxicity and teratogenicity of lithium (Li) on medaka (Oryzias latipes) and predict the molecular mechanisms of their effects using a nanosecond pulsed electric field (nsPEF) technique and bioinformatics analysis. The microscopic observation revealed that the 1 mg/L LiCl treatment causes the most severe deformation effects, such as thrombus, heart hypertrophy, deformation of eyes, and growth retardation to embryos. The RNA-seq analysis identified 2,483 up- and down-regulated genes, such as histogenesis and organ growth related genes, in 2 day post-fertilization embryos after treatment with nsPEF and 1 mg/L LiCl. In addition, bioinformatic analyses showed that LiCl affects several aspects of gene ontology, such as molecular functions and cellular components, and some pathways, such as spliceosome, cell cycle, selenocompound metabolism, TGF-β signaling, and RNA degradation. The upregulation of GSK3B (signal transduction and cell growth), BAX (apoptosis), and MAP3K8 (cell death, arrest of cell cycle, and inflammation) genes were also observed in embryos exposed to LiCl. Our results suggest that the incorporation of Li compounds into medaka eggs using nsPEF shows adverse effects to the development and teratogenicity, and that these toxic effects may be affected by the alterations of certain gene expression in medaka embryos.