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Journal of Toxicological Sciences | Page 2

Wei Zhang, Ruiguo Wang, John P Giesy, Yang Li, Peilong Wang
Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) is the most widely used organophosphorus flame retardant, which is now used instead of polybrominated diphenyl ethers (PBDEs). TDCPP has frequently been detected in inorganic environmental matrices, such as soil, water and air as well as biota. In vitro effects of TDCPP on cells had not been previously elucidated. Therefore, in the present study, cytotoxicity, DNA damage, cell cycle distribution, apoptosis caused by TDCPP was studied in RAW264.7 macrophage cells...
2019: Journal of Toxicological Sciences
Takeshi Tanaka, Kota Nakajima, Yasunori Masubuchi, Yuko Ito, Satomi Kikuchi, Maky Ideta-Ohtsuka, Gye-Hyeong Woo, Toshinori Yoshida, Katsuhide Igarashi, Makoto Shibutani
Maternal exposure to 3,3'-iminodipropionitrile (IDPN) affects hippocampal neurogenesis in mouse offspring, with biphasic disruption, which facilitates neurogenesis during exposure and reduces the broad range of the granule cell lineage population at the adult stage. The present study investigated the epigenetically hypermethylated and downregulated genes related to the IDPN-induced disrupted neurogenesis. Mated female mice were treated with IDPN at 0 or 1200 ppm in drinking water from gestational day 6 to postnatal day (PND) 21 on weaning...
2019: Journal of Toxicological Sciences
Hiromasa Tsuyama, Hitomi Fujishiro, Seiichiro Himeno, Daigo Sumi
Immunological functions are disturbed in humans who have been chronically exposed to arsenic via contaminated groundwater. Little is known about the specific mechanisms underlying the impairment of immunological defense system caused by arsenic. The activation of macrophage cells upon infection with bacteria and viruses plays important roles in the defense against these pathogens. Here we show that exposure to arsenite (As(III)) suppresses nitric oxide (NO) production in murine RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS) and poly(I:C), the compounds mimicking bacterial and viral infection, respectively...
2019: Journal of Toxicological Sciences
Tadashi Hirata, Young-Man Cho, Isamu Suzuki, Takeshi Toyoda, Jun-Ichi Akagi, Yasushi Nakamura, Satoshi Numazawa, Kumiko Ogawa
To investigate the chemopreventive mechanisms of 4-Methylthio-3-butenyl isothiocyanate (MTBITC), we analyzed cell viability, cell cycle distribution, and expression levels for cell cycle and apoptosis-related proteins in MTBITC-treated malignant esophageal KYSE510 cells, with and without the reactive oxygen species (ROS) scavenger N-acethyl-L-Cysteine (NAC). MTBITC dose-dependently reduced cell viability and Bcl2 protein expression, while it induced cleavages of caspase-3, caspase-9, and PARP-1, suggesting that reduced cell viability occurred through the mitochondrial apoptotic pathway in KYSE510 cells...
2019: Journal of Toxicological Sciences
Qingshu Li, Chunxia Gao, Hong Deng, Quancai Song, Li Yuan
Benzo(α)pyrene (BaP) possesses a forceful hepatotoxicity, and is ubiquitous in foods and ambient air. Our previous study found that BaP induced pyroptotic and autophagic death in HL-7702 human liver cells; the relevant mechanisms, however, remain unknown. This work was therefore to unravel the effects of the PI3K/Akt signaling pathway on pyroptotic and autophagic death triggered by BaP. Cells were treated with or without LY294002 (PI3K/Akt inhibitor) and IGF-1 (PI3K/Akt activator) before BaP exposure, and the results showed that compared with the control, the protein expression of p-Akt was markedly decreased by BaP (p < 0...
2019: Journal of Toxicological Sciences
Tomoya Fujie, Taro Yamamoto, Chika Yamamoto, Toshiyuki Kaji
Although cytotoxicity of inorganic metals has been well investigated, little is known about the cytotoxicity of organic-inorganic hybrid molecules. The cytotoxicity of zinc complexes was evaluated using a culture system of vascular endothelial cells. We found that bis(1,4-dihydro-2-methyl-1-phenyl-4-thioxo-3-pyridiolato)zinc(II), termed Zn-06, exhibited strong cytotoxicity in vascular smooth muscle cells, epithelial cells, fibroblastic cells, and vascular endothelial cells. This study showed that the tetracoordinate structure of the Zn-06 molecule, which contains two sulfur and two oxygen atoms attached to the zinc atom, facilitated its accumulation within vascular endothelial cells whereas the whole structure of the zinc complex was involved in its cytotoxicity in the cells...
2019: Journal of Toxicological Sciences
Kana Unuma, Toshihiko Aki, Ayaka Yamashita, Ayaka Yoshikawa, Koichi Uemura
Inhalation of toxic gases is dangerous to humans; experiments using toxic gases themselves are also hazardous to researchers. Gas-releasing molecules are widely used as alternatives to toxic gases, but their impacts on the whole body remain to be examined. To investigate responses during hydrogen sulfide (H2 S) poisoning, rats (Sprague-Dawley, male, 8-week-old) were intraperitoneally (i.p.) administered H2 S donor, NaHS, and sacrificed 24 hr after the administration. The main histopathological finding commonly observed in NaHS-administered rat heart, liver, brain, and lung was congestion...
2019: Journal of Toxicological Sciences
Sung Ha Ryu, Jung Dae Lee, Ji Won Kim, Siwon Kim, Suhkmann Kim, Kyu-Bong Kim
Cisplatin (CP) is an anti-cancer drug used for treatment of solid tumors, but the major adverse effect is drug-induced nephrotoxicity. The current study aimed to determine biomarkers that might predict nephrotoxicity induced by CP using serum or urinary proton nuclear magnetic resonance (1 H NMR) spectral data in male Sprague-Dawley (S-D) rats. CP (0, 0.5 or 5 mg/kg) was intraperitoneally (i.p.) administered for single dose. Animals were sacrificed 2 days (D2) or 8 days (D8) after administration of CP in order to perform analysis of serum biochemistries and histopathologic examination...
2019: Journal of Toxicological Sciences
Dawei Wang, Dong You, Lei Li
Galectin-3 (Gal-3) is a multifunctional carbohydrate-binding protein associated with cell migration, cell proliferation, cell adhesion, and cell-cell interaction in tumor cells. It has been implied to be involved in the tumor progression and chemoresistance of epithelial ovarian cancer (EOC). However, it is unclear whether the Gal-3-mediated regulation on the EOC chemosensitivity is associated with hypoxia or mitochondrial dysfunction. In the present study, we examined the regulation by Gal-3 overexpression on cisplatin-sensitivity or cisplatin-resistance in EOC cells in vitro...
2019: Journal of Toxicological Sciences
Qian Zhang, Zhimin Liu, Junting Du, Wei Qin, Manman Lu, Haiyan Cui, Xiaoxiao Li, Shumao Ding, Rui Li, Junlin Yuan
Due to its excellent properties such as ultraviolet obscuration, chemical stability and small particle size, nano-titanium dioxide (nano-TiO2 ) is widely used, particularly in sunblock products. The skin is therefore a chief route for exposure. Studies have found that oral or respiratory exposure to nano-TiO2 has an adverse impact on the cardiovascular system. The relationship between dermal exposure to nano-TiO2 and cardiovascular system toxicity, particularly the causative mechanisms, remain unclear. In this study, we used Balb/c mice to evaluate cardiovascular toxicity from nano-TiO2 dermal exposure, and the underlying mechanisms associated with the human umbilical vein endothelial cells (HUVECs) were explored...
2019: Journal of Toxicological Sciences
Taku Nishijo, Masaaki Miyazawa, Kazutoshi Saito, Yuki Otsubo, Hideyuki Mizumachi, Hitoshi Sakaguchi
Cosmetic ingredients often comprise complex mixtures, such as botanical extracts, which may contain skin sensitizing constituents. In our previous study for the sensitivity of the evaluations of skin sensitizing constituents in mixtures using the binary in vitro test battery with KeratinoSensTM and h-CLAT, some sensitizers showed higher detection limits in in vitro test methods than in murine local lymph node assays (LLNA). Thus, to minimize the uncertainty associated with decreased sensitivity for these sensitizers, a risk assessment strategy was developed for mixtures with negative results from the binary test battery...
2019: Journal of Toxicological Sciences
Taku Nishijo, Masaaki Miyazawa, Kazutoshi Saito, Yuki Otsubo, Hideyuki Mizumachi, Hitoshi Sakaguchi
Cosmetic ingredients are often complex mixtures from natural sources such as botanical extracts that might contain minute amounts of constituents with sensitizing potential. The sensitivity of in vitro skin sensitization test methods such as KeratinoSensTM and h-CLAT for the detection of minute amounts of sensitizer in mixtures remains unclear. In this study, we assessed the detection sensitivity of the binary test battery comprising KeratinoSensTM and h-CLAT for minute amounts of sensitizers by comparing the LLNA EC3 (estimated concentration of a substance expected to produce a stimulation index of 3) values to the minimum detection concentrations (MDCs) exceeding the positive criteria for each of the two in vitro test methods...
2019: Journal of Toxicological Sciences
Florencio Villester Arce, Narumi Asano, Keita Yamashita, Ayaka Oda, Takashi Uchida, Tomohiko Sano, Hiroaki Todo, Kenji Sugibayashi
Cosmetics containing rhododendrol (RD) were voluntarily recalled after incidents of leukoderma related to their use. Users reported using up to five different RD-containing products by layered application. In this study, we investigated the effects of layered application, formulations, and their components on the skin permeation of cosmetics containing RD. Experiments were designed to simulate actual in-use conditions, such as varying application volumes, physical mixing of formulations, sequence of cosmetics application and time interval between applications, to establish their effect on the skin permeation of RD...
2019: Journal of Toxicological Sciences
Mariko Sugiyama, Masaharu Akita, Nathalie Alépée, Miyuki Fujishiro, Shigenobu Hagino, Yuki Handa, Hidefumi Ikeda, Noriyasu Imai, Setsuko Jitsukawa, Masakazu Katoh, Koji Kurihara, Daiki Kyotani, Shigeyuki Nomura, Yuko Okamoto, Hidenobu Okumura, Takashi Omori, Kenji Sugibayashi, Hiroaki Todo, Akemi Toyoda, Yasuo Ohno
The Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 439 is an in vitro test method of reconstructed human epidermis (RhE), which was developed for hazard identification of irritating chemicals in accordance with a primary skin irritation test using rabbits with 4-hr exposure. A regulation for quasi-drugs in Japan requires data from primary skin irritation tests using rabbits to undergo 24-hr exposure, and this is used as an evidence for 24-hr closed patch tests in humans. In this study with the same chemicals, primary skin irritation test data using rabbits undergoing 24-hr exposure and a 24-hr occlusive human patch test data were analyzed by comparing the results obtained with four test methods adopted in OECD TG 439...
2018: Journal of Toxicological Sciences
Yutaka Kimura, Mika Watanabe, Noriyuki Suzuki, Tomoko Iwaki, Kohji Yamakage, Koichi Saito, Yoshihiro Nakajima, Chizu Fujimura, Yoshihiro Ohmiya, Takashi Omori, Hajime Kojima, Setsuya Aiba
In all current in vitro skin sensitisation assays, DMSO is used to dissolve water-insoluble chemicals. However, our previous study suggested the superiority of the modified IL-8 Luc assay (mIL-8 Luc), in which X-VIVOTM 15 is used to dissolve chemicals, over the original assay using DMSO (oIL-8 Luc). In this study, to confirm the superiority of the mIL-8 Luc, we first increased the number of chemicals examined and demonstrated the superiority of the mIL-8 Luc, in which the mIL-8 Luc provided 87.6% of sensitivity, 74...
2018: Journal of Toxicological Sciences
Takato Hara, Yoshihiro Nonaka, Shuji Yasuike, Toshiyuki Kaji, Chika Yamamoto
It has been well established that organic-inorganic hybrid molecules can exhibit biological activities that are different from those of either their intramolecular metals in inorganic forms or their organic structures. We have previously reported that organoantimony compound Sb-phenyl-N-methyl-5,
6,7,12-tetrahydrodibenz[c,f][1,5]azastibocine (PMTAS) is nontoxic, but that the compound exhibits cytotoxicity in vascular endothelial cells when the antimony atom is replaced with a bismuth atom. In the present study, we investigated the cytotoxicity and intracellular accumulation of PMTAS and its analogs and found that the cytotoxicity of PMTAS analogs also decrease depending on the electron-withdrawing property of the substituent bound to the intramolecular antimony atom...
2018: Journal of Toxicological Sciences
Shigeru Yamada, Daiju Yamazaki, Yasunari Kanda
5-fluorouracil (5-FU) has been widely used for the treatment of tumors. Regardless of its widespread use as an anti-cancer drug, 5-FU therapy can cause several side effects, including developmental toxicity and neurotoxicity. However, the potential action of 5-FU at the early fetal stage has not yet been completely elucidated. In the present study, we investigated the effect of 5-FU exposure on neural induction, using human induced pluripotent stem cells (iPSCs) as a model of human fetal stage. 5-FU exposure reduced the expression of several neural differentiation marker genes, such as OTX2, in iPSCs...
2018: Journal of Toxicological Sciences
Galen Guo, Emmanuel Yumvihoze, Alexandre J Poulain, Hing Man Chan
Monomethylmercury (MMHg) is a potent neurotoxicant that can be bioaccumulated and biomagnified through trophic levels. Human populations whose diets contain MMHg are at risk of MMHg toxicity. The gut microbiota was identified as a potential factor causing variation in MMHg absorption and body burden. However, little is known about the role of gut microbiota on Hg transformations. We conducted a series of in vitro experiments to study the effects of dietary nutrient change on Hg metabolism and the human gut microbiota using anoxic fecal slurry incubations...
2018: Journal of Toxicological Sciences
Tomofumi Fujino, Rina Yokokawa, Toshiyuki Oshima, Makio Hayakawa
SIRT1, an NAD+ -dependent deacetylase, causes deacetylation and down-regulation of its target p53. Given that p53 is an upstream regulator of the transcription of the cyclin-dependent kinase inhibitor p21/Cip1, SIRT1 is hypothesized to play a stimulatory role in carcinoma cell proliferation. We previously reported that down-regulation of SIRT1 caused the increase in p21/Cip1 in a post-transcriptional manner, suggesting that p53 is not involved in the p21/Cip1 increase and raising the question whether SIRT1 exhibits the activity other than deacetylase...
2018: Journal of Toxicological Sciences
Abdelli Nouara, Peng Lü, Liang Chen, Yan Pan, Yanhua Yang, Keping Chen
Silver nanoparticles (Ag-NPs) are known as a noble metal, and owing to their exclusive properties, their use is widespread in consumer products and they are mostly incorporated into food packaging and food contact products. The aim of this work was to evaluate the effects of direct ingestion of Ag-NPs through food to assess their toxicity effects on the growth and development of silkworms at different concentrations (1 mg·L-1 to 100 mg·L-1 ), in addition to the examination of the distribution of Ag-NPs in the silkworm body and midgut histopathological analysis...
2018: Journal of Toxicological Sciences
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