2,592 results match your criteria Journal of Toxicological Sciences[Journal]


Long-term cadmium exposure enhances metallothionein-1 induction after subsequent exposure to high concentrations of cadmium in P1798 mouse lymphosarcoma cells.

J Toxicol Sci 2019 ;44(4):309-316

Department of Life Science, Faculty of Science and Engineering, Setsunan University.

Cadmium, a ubiquitous heavy metal, is a toxic industrial and environmental pollutant. The initial biological response to cadmium exposure is induction of metallothioneins (MTs), a family of cysteine-rich, low-molecular-weight proteins that bind primarily zinc, cadmium, or both. This MT induction protects against cadmium toxicity by quenching cadmium. Read More

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http://dx.doi.org/10.2131/jts.44.309DOI Listing
January 2019
1 Read

Effects of infection of MRSA on the expression and activity of renal cytochrome P450s in mice.

J Toxicol Sci 2019 ;44(4):299-307

School of Laboratory Medicine, Chengdu Medical College, China.

Methicillin-resistant Staphylococcus aureus (MRSA) leads to serious infections, but it is not known whether it changes the expression of kidney drug metabolizing enzymes during infection. The mice were infected with different doses of MRSA and the oxidative stress and inflammation levels in the kidney were examined. The mRNA expression and activity of cytochrome P450 enzyme was analysed. Read More

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http://dx.doi.org/10.2131/jts.44.299DOI Listing
January 2019
2 Reads

Eliminating the contribution of lipopolysaccharide to protein allergenicity in the human cell-line activation test (h-CLAT).

J Toxicol Sci 2019 ;44(4):283-297

Department of Chemical and Energy Engineering, Yokohama National University.

We previously developed a test for detecting naturally occurring protein-induced skin sensitization based on the markers and criteria of the human cell-line activation test (h-CLAT) and showed that the h-CLAT was useful for assessing the allergenic potency of proteins. However, test proteins were contaminated with varying amounts of lipopolysaccharide (LPS), which might have contributed to the stimulation of CD86 and CD54 expression. In this study, we developed a method to exclude the effects of LPS in the assessment of skin sensitization by naturally occurring proteins. Read More

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https://www.jstage.jst.go.jp/article/jts/44/4/44_283/_articl
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http://dx.doi.org/10.2131/jts.44.283DOI Listing
January 2019
2 Reads

Dosage time affects alkylating agents induced micronuclei in mouse peripheral blood reticulocytes through the function of erythropoietin.

J Toxicol Sci 2019 ;44(4):273-282

Graduate School of Integrated Pharmaceutical and Nutritional Science, University of Shizuoka.

Previously, we reported that the frequency of micronucleated reticulocytes (MNRETs) in the peripheral blood of male C3H/He mice intraperitoneally administered ethylnitrosourea (ENU) (25 mg/kg body weight) in the dark period (zeitgeber time, ZT15) was higher than in the light period (ZT3). In this study, to clarify the mechanism underlying this phenomenon, we investigated the differences in micronucleus (MN) induction observed between ZT3 and ZT15 using five chemicals, methylnitrosourea (MNU), ethylmethane sulfonate (EMS), mitomycin C, cyclophosphamide and vincristin. MNU and EMS, monofunctional alkylating agents, showed higher frequencies of MNRETs in the ZT15 than the ZT3 treatment similar to ENU. Read More

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http://dx.doi.org/10.2131/jts.44.273DOI Listing
January 2019
1 Read

Long-term dietary intake of excessive vitamin A impairs spermatogenesis in mice.

J Toxicol Sci 2019 ;44(4):257-271

Department of Hygiene Chemistry, Ohu University School of Pharmaceutical Sciences.

Vitamin A and its derivatives contribute to many physiological processes, including vision, neural differentiation, and reproduction. Vitamin A deficiency causes early cessation of spermatogenesis, characterized by a marked depletion of germ cells. However, there has been no clear understanding about the role of chronic intake of vitamin A excess (VAE) in spermatogenesis. Read More

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http://dx.doi.org/10.2131/jts.44.257DOI Listing
January 2019
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Comparison of the developmental/reproductive toxicity and hepatotoxicity of phthalate esters in rats using an open toxicity data source.

J Toxicol Sci 2019 ;44(4):245-255

Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University.

Phthalate esters (PEs) are widely used as plasticizers in various kinds of plastic products. Some PEs have been known to induce developmental and reproductive toxicity (DART) as well as hepatotoxicity in laboratory animals. In some cases of DART, the strength of toxicity of PEs depends on the side chain lengths, while the relationship between hepatotoxicity and side chain length is unknown. Read More

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http://dx.doi.org/10.2131/jts.44.245DOI Listing
January 2019

Di(2-ethylhexyl) phthalate promotes lung cancer cell line A549 progression via Wnt/β-catenin signaling.

Authors:
Jin Hee Kim

J Toxicol Sci 2019 ;44(4):237-244

Department of Internal Medicine, Seoul National University Bundang Hospital, Korea.

Di(2-ethylhexyl) phthalate (DEHP) is widely used in polyvinylchloride-based materials and remains intact in the environment. Lungs are one route of entry of DEHP into the body; however, there is limited information on the effects and mechanism of action of DEHP on non-small cell lung cancer (NSCLC). Here, we addressed this by examining the effect of DEHP on the proliferation of A549 human lung adenocarcinoma cells by MTS assay. Read More

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http://dx.doi.org/10.2131/jts.44.237DOI Listing
January 2019
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Safety biomarker applications in drug development.

J Toxicol Sci 2019 ;44(4):225-235

Drug Safety R&D, Pfizer, Inc, CT, USA.

Biomarkers are invaluable drug development tools to assess and monitor safety in early clinical trials especially when exposure margins are limiting for promising therapeutics. Although progress has been made towards identifying and implementing translational safety biomarkers for a number of organ toxicities such as kidney and liver, significant biomarker gaps still exist to monitor toxicities for testis, pancreas, etc. Several precompetitive consortia [e. Read More

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http://dx.doi.org/10.2131/jts.44.225DOI Listing
January 2019
1.378 Impact Factor

Some non-sensitizers upregulate CD54 expression by activation of the NLRP3 inflammasome in THP-1 cells.

J Toxicol Sci 2019 ;44(3):213-224

Department of Chemical and Energy Engineering, Yokohama National University.

The human cell line activation test (h-CLAT) is a skin sensitization test that measures the expression of cell surface proteins CD86 and CD54 to evaluate the skin sensitization potential of test chemicals. However, some skin irritants have been reported to induce dramatically high CD54 expression leading to false-positive h-CLAT results. Furthermore, CD54 expression is strongly induced by cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, or danger signals that activate its signaling pathways. Read More

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http://dx.doi.org/10.2131/jts.44.213DOI Listing

Novel risk assessment of reactive metabolites from discovery to clinical stage.

J Toxicol Sci 2019 ;44(3):201-211

Drug Metabolism & Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute.

This study was aimed to predict drug-induced liver injury caused by reactive metabolites. Reactive metabolites covalently bind to proteins and could result in severe outcomes in patients. However, the relation between the extent of covalent binding and clinical hepatotoxicity is still unclear. Read More

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http://dx.doi.org/10.2131/jts.44.201DOI Listing

Methylmercury-induced neural degeneration in rat dorsal root ganglion is associated with the accumulation of microglia/macrophages and the proliferation of Schwann cells.

J Toxicol Sci 2019 ;44(3):191-199

Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.

Exposure to organic mercury, especially methylmercury (MeHg), causes Minamata disease, a severe chronic neurological disorder. Minamata disease predominantly affects the central nervous system, and therefore, studies on the mechanisms of MeHg neurotoxicity have focused primarily on the brain. Although the peripheral nervous system is also affected by the organometallic compound and shows signs of neural degeneration, the mechanisms of peripheral MeHg neurotoxicity remain unclear. Read More

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http://dx.doi.org/10.2131/jts.44.191DOI Listing
March 2019
1 Read

Suberoylanilide hydroxamic acid (SAHA) alleviates the learning and memory impairment in rat offspring caused by maternal sevoflurane exposure during late gestation.

J Toxicol Sci 2019 ;44(3):177-189

Department of Immunology, Jiangxi Medical College, Nanchang University, China.

Recent studies have shown that sevoflurane can cause long-term neurotoxicity and learning and memory impairment in developing and progressively neurodegenerative brains. Sevoflurane is a widely used volatile anesthetic in clinical practice. Late gestation is a rapidly developing period in the fetal brain, but whether sevoflurane anesthesia during late gestation affects learning and memory of offspring is not fully elucidated. Read More

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http://dx.doi.org/10.2131/jts.44.177DOI Listing
March 2019
1 Read

Astragaloside IV protects against cisplatin-induced liver and kidney injury via autophagy-mediated inhibition of NLRP3 in rats.

J Toxicol Sci 2019 ;44(3):167-175

Department of Pharmacy, the First Hospital of Jilin University, China.

The aim of this study was to explore the role of the NOD-like receptor family, pyrin domain containing (NLRP3) inflammasome and autophagy in Astragaloside IV (AS IV)-mediated protection against cisplatin-induced liver and kidney injury in rats. Rats were intraperitoneally administered cisplatin at a dose of 15 mg/kg and orally administered AS IV for 7 days. Histopathological and biochemical analysis were used to assess liver and kidney function. Read More

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http://dx.doi.org/10.2131/jts.44.167DOI Listing
March 2019
2 Reads

Mechanisms of silver nanoparticles-induced cytotoxicity and apoptosis in rat tracheal epithelial cells.

J Toxicol Sci 2019 ;44(3):155-165

College of Life and Environmental Sciences, Hangzhou Normal University, China.

Silver nanoparticles (AgNPs) are increasingly utilized in a number of applications. This study was designed to investigate AgNPs induced cytotoxicity, oxidative stress and apoptosis in rat tracheal epithelial cells (RTE). The RTE cells were treated with 0, 100 μg/L and 10,000 μg/L of the AgNPs with diameters of 10 nm and 100 nm for 12 hr. Read More

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http://dx.doi.org/10.2131/jts.44.155DOI Listing
March 2019
1 Read

Effect of the metabolic capacity in rat liver S9 on the positive results of in vitro micronucleus tests.

J Toxicol Sci 2019 ;44(3):145-153

Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

A high incidence of positive results is obtained with in vitro genotoxicity tests, which do not correlate with the in vivo negative results in many cases. To address this issue, the metabolic profile of rat liver 9000 × g supernatant fraction (S9) pretreated with phenobarbital (PB) and 5,6-benzoflavone (BNF) was characterized. Furthermore, the in vitro micronucleus tests of 10 compounds were performed with PB-BNF-induced rat S9. Read More

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http://dx.doi.org/10.2131/jts.44.145DOI Listing
March 2019
1 Read

Tris (1,3-dichloro-2-propyl) phosphate treatment induces DNA damage, cell cycle arrest and apoptosis in murine RAW264.7 macrophages.

J Toxicol Sci 2019 ;44(3):134-144

Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, China.

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. Read More

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http://dx.doi.org/10.2131/jts.44.134DOI Listing
March 2019
1.378 Impact Factor

Aberrant epigenetic gene regulation in hippocampal neurogenesis of mouse offspring following maternal exposure to 3,3'-iminodipropionitrile.

J Toxicol Sci 2019 ;44(2):93-105

Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology.

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. Read More

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http://dx.doi.org/10.2131/jts.44.93DOI Listing
February 2019
1 Read

Arsenite suppresses NO production evoked by lipopolysaccharide and poly(I:C) via the suppression of interferon-β expression in RAW264.7 cells.

J Toxicol Sci 2019 ;44(2):83-92

Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University.

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. Read More

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http://dx.doi.org/10.2131/jts.44.83DOI Listing
February 2019
4 Reads

4-Methylthio-3-butenyl isothiocyanate (MTBITC) induced apoptotic cell death and G2/M cell cycle arrest via ROS production in human esophageal epithelial cancer cells.

J Toxicol Sci 2019 ;44(2):73-81

Division of Pathology, National Institute of Health Sciences.

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. In cell cycle distribution analysis, MTBITC (20-40 µM) induced cell cycle arrest at G2/M phase. Read More

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http://dx.doi.org/10.2131/jts.44.73DOI Listing
February 2019
1 Read

Benzo[a]pyrene induces pyroptotic and autophagic death through inhibiting PI3K/Akt signaling pathway in HL-7702 human normal liver cells.

J Toxicol Sci 2019 ;44(2):121-131

College of Food Engineering and Nutritional Science, Shaanxi Normal University, China.

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. Read More

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http://dx.doi.org/10.2131/jts.44.121DOI Listing
February 2019
1 Read
1.378 Impact Factor

Bis(1,4-dihydro-2-methyl-1-phenyl-4-thioxo-3-pyridiolato)zinc(II) exhibits strong cytotoxicity and a high intracellular accumulation in cultured vascular endothelial cells.

J Toxicol Sci 2019 ;44(2):113-120

Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science.

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. Read More

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http://dx.doi.org/10.2131/jts.44.113DOI Listing
February 2019
1 Read

Hydrogen sulfide donor NaHS causes bronchitis with enhanced respiratory secretion in rats.

J Toxicol Sci 2019 ;44(2):107-112

Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University.

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 (HS) poisoning, rats (Sprague-Dawley, male, 8-week-old) were intraperitoneally (i. Read More

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http://dx.doi.org/10.2131/jts.44.107DOI Listing
February 2019
2 Reads

H NMR toxicometabolomics following cisplatin-induced nephrotoxicity in male rats.

J Toxicol Sci 2019 ;44(1):57-71

College of Pharmacy, Dankook University, Korea.

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 (H NMR) spectral data in male Sprague-Dawley (S-D) rats. CP (0, 0. Read More

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https://www.jstage.jst.go.jp/article/jts/44/1/44_57/_article
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http://dx.doi.org/10.2131/jts.44.57DOI Listing
January 2019
9 Reads

Galectin-3 regulates chemotherapy sensitivity in epithelial ovarian carcinoma via regulating mitochondrial function.

J Toxicol Sci 2019 ;44(1):47-56

Department of Obstetrics, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, China.

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. Read More

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https://www.jstage.jst.go.jp/article/jts/44/1/44_47/_article
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http://dx.doi.org/10.2131/jts.44.47DOI Listing
January 2019
9 Reads
1.378 Impact Factor

Dermal exposure to nano-TiO induced cardiovascular toxicity through oxidative stress, inflammation and apoptosis.

J Toxicol Sci 2019 ;44(1):35-45

Laboratory of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, China.

Due to its excellent properties such as ultraviolet obscuration, chemical stability and small particle size, nano-titanium dioxide (nano-TiO) 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-TiO has an adverse impact on the cardiovascular system. Read More

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http://dx.doi.org/10.2131/jts.44.35DOI Listing
January 2019
15 Reads

The dermal sensitization threshold (DST) approach for mixtures evaluated as negative in in vitro test methods; mixture DST.

J Toxicol Sci 2019 ;44(1):23-34

Safety Science Research Laboratories, Kao Corporation.

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 KeratinoSens 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. Read More

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http://dx.doi.org/10.2131/jts.44.23DOI Listing
January 2019
2 Reads

Sensitivity of KeratinoSens and h-CLAT for detecting minute amounts of sensitizers to evaluate botanical extract.

J Toxicol Sci 2019 ;44(1):13-21

Safety Science Research Laboratories, Kao Corporation.

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 KeratinoSens 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 KeratinoSens 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. Read More

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http://dx.doi.org/10.2131/jts.44.13DOI Listing
January 2019
3 Reads

Effect of layered application on the skin permeation of a cosmetic active component, rhododendrol.

J Toxicol Sci 2019 ;44(1):1-11

Graduate School of Pharmaceutical Sciences, Josai University.

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. Read More

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https://www.jstage.jst.go.jp/article/jts/44/1/44_1/_article
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http://dx.doi.org/10.2131/jts.44.1DOI Listing
January 2019
13 Reads

Comparative assessment of 24-hr primary skin irritation test and human patch test data with in vitro skin irritation tests according to OECD Test Guideline 439 (for quasi-drugs in Japan).

J Toxicol Sci 2018 ;43(12):751-768

Working Group on Alternatives to Primary Skin Irritation Test, Japanese Society of Alternatives to Animal Experiments (JSAAE).

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. Read More

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https://www.jstage.jst.go.jp/article/jts/43/12/43_751/_artic
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http://dx.doi.org/10.2131/jts.43.751DOI Listing
January 2019
37 Reads

The performance of an in vitro skin sensitisation test, IL-8 Luc assay (OECD442E), and the integrated approach with direct peptide reactive assay (DPRA).

J Toxicol Sci 2018 ;43(12):741-749

Department of Dermatology, Tohoku University Graduate School of Medicine.

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-VIVO 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. Read More

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https://www.jstage.jst.go.jp/article/jts/43/12/43_741/_artic
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http://dx.doi.org/10.2131/jts.43.741DOI Listing
January 2019
6 Reads

Structure-activity relationship of [1,5]azastibocines in cytotoxicity to vascular endothelial cells.

J Toxicol Sci 2018 ;43(12):735-740

Faculty of Pharmaceutical Sciences, Toho University.

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. Read More

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https://www.jstage.jst.go.jp/article/jts/43/12/43_735/_artic
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http://dx.doi.org/10.2131/jts.43.735DOI Listing
January 2019
3 Reads

5-Fluorouracil inhibits neural differentiation via Mfn1/2 reduction in human induced pluripotent stem cells.

J Toxicol Sci 2018 ;43(12):727-734

Division of Pharmacology, National Institute of Health Sciences, Japan.

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. Read More

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http://dx.doi.org/10.2131/jts.43.727DOI Listing
January 2019
10 Reads

Monomethylmercury degradation by the human gut microbiota is stimulated by protein amendments.

J Toxicol Sci 2018 ;43(12):717-725

Department of Biology, Faculty of Science, University of Ottawa, Ottawa, Canada K1N 9B4.

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. Read More

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http://dx.doi.org/10.2131/jts.43.717DOI Listing
January 2019
1 Read

SIRT1 knockdown up-regulates p53 and p21/Cip1 expression in renal adenocarcinoma cells but not in normal renal-derived cells in a deacetylase-independent manner.

J Toxicol Sci 2018 ;43(12):711-715

Department of Hygiene and Health Sciences, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Japan.

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. Read More

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http://dx.doi.org/10.2131/jts.43.711DOI Listing
January 2019
1 Read

Silver effects on silkworm, Bombyx mori.

J Toxicol Sci 2018 ;43(12):697-709

School of Food and Biological Engineering, Jiangsu University, China.

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 to 100 mg·L), in addition to the examination of the distribution of Ag-NPs in the silkworm body and midgut histopathological analysis. RNA sequencing was performed to investigate the transcriptomic responses to Ag-NPs exposure. Read More

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http://dx.doi.org/10.2131/jts.43.697DOI Listing
January 2019
4 Reads

Approaches of validation of a 2-week combined repeated oral dose toxicity study with plasma micro sampling toxicokinetics (PMS-TK) in common marmosets.

J Toxicol Sci 2018 ;43(11):685-695

Central Institute for Experimental Animals.

We investigated the viability of a combined repeated dose toxicity study, including toxicokinetics (TK), in common marmosets according to the ICH-S4, ICH-S3A and ICH-S7A Guidelines using valsartan as test article whose non-clinical repeated dose toxicity studies had been conducted using this species for regulatory purpose. Valsartan was administered orally to 3 animals/sex at 200 mg/kg/day for 2 weeks. In addition to the routine parameters in repeated dose toxicity studies, safety pharmacology parameters (examinations of the central nervous, respiratory and cardiovascular systems) were also evaluated. Read More

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https://www.jstage.jst.go.jp/article/jts/43/11/43_685/_artic
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http://dx.doi.org/10.2131/jts.43.685DOI Listing
November 2018
15 Reads

Thalidomide protects against acute pentylenetetrazol and pilocarpine-induced seizures in mice.

J Toxicol Sci 2018 ;43(11):671-684

Physiology Department, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Unidad Profesional Adolfo López Mateos, Mexico.

Thalidomide was originally developed to treat primary neurological and psychiatric diseases. There are reports of anticonvulsant effects of thalidomide in rats and antiepileptic effects in patients. Hence, thalidomide (100, 200 and 400 mg/kg) was herein administered to mice to evaluate possible protection against seizures induced by the systemic administration of neurotoxins: 10 mg/kg of 4-aminopyridine (4-AP), 90 mg/kg of pentylenetetrazol (PTZ), or 380 mg/kg of pilocarpine. Read More

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http://dx.doi.org/10.2131/jts.43.671DOI Listing
November 2018
11 Reads

Melatonin antagonizes oxidative stress-induced mitochondrial dysfunction in retinal pigmented epithelium cells via melatonin receptor 1 (MT1).

J Toxicol Sci 2018 ;43(11):659-669

Depertment of Ophthalmology, Linyi People's Hospital, China.

High energy-consumption in retinal pigmented epithelium (RPE) cells poses oxidative stress (OS) and contributes to mitochondrial dysfunction (MD) for retinal degeneration-associated diseases. In the present study, we evaluated the protective role of Melatonin, a natural antioxidant, against the hydrogen peroxide (HO)-induced damage to RPE cells. The cellular viability, apoptosis, the expression of apoptosis-associated proteins and mitochondrial function were examined in the retinal ARPE-19 cells, post the treatment with HO or (and) with Melatonin. Read More

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http://dx.doi.org/10.2131/jts.43.659DOI Listing
November 2018
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Effect of decabrominated diphenyl ether exposure on spatial learning and memory, the expression and phosphorylation of hippocampal glutamate receptor subunits in adult Sprague-Dawley rats.

J Toxicol Sci 2018 ;43(11):645-657

School of Public Health, Southwest Medical University, China.

Previous studies have reported the potential developmental neurobehavioral effects of decabrominated diphenyl ethers (BDE 209) on developing animals, but the effects on adult animals are rare or controversial and the mechanism is not fully understood. In the present study, male adult Sprague-Dawley rats performed poor spatial learning and memory in Morris water maze after exposure to BDE 209 by gavage for 30 days. The expression of hippocampal glutamate receptor subunits NR1, NR2B and GluR1, the phosphorylation of NR2B subunit at Ser1301 (p-NR2B Ser1303) and GluR1 subunit at Ser831 (p-GluR1 Ser831) were all decreased, and the phosphorylation ratio of NR2B revealed an increasing trend after BDE 209 exposure. Read More

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November 2018
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Social behavior, neuroimmune markers and glutamic acid decarboxylase levels in a rat model of valproic acid-induced autism.

J Toxicol Sci 2018 ;43(11):631-643

National Institute for Environmental Studies.

Autism is a complex neurodevelopmental disorder characterized by impaired social communication and social interactions, and repetitive behaviors. The etiology of autism remains unknown and its molecular basis is not yet well understood. Pregnant Sprague-Dawley (SD) rats were administered 600 mg/kg of valproic acid (VPA) by intraperitoneal injection on day 12. Read More

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http://dx.doi.org/10.2131/jts.43.631DOI Listing
November 2018
13 Reads

Low-level lead exposure and cardiovascular disease: the roles of telomere shortening and lipid disturbance.

J Toxicol Sci 2018 ;43(11):623-630

Department of Anatomy, Medical College of Nanchang University, China.

Lead exposure contributing to cardiovascular diseases is known and recognized widely. As the deleterious effects of low lead exposure attained increasing attention over the last decades, there have been numerous studies exploring the association of low levels of lead exposure and cardiovascular diseases. Moreover, it has been observed that lead exposure could cause telomere shortening and lipid disturbance, and that telomere shortening and lipid disturbance are closely related with cardiovascular diseases. Read More

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http://dx.doi.org/10.2131/jts.43.623DOI Listing
November 2018

Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats.

J Toxicol Sci 2018 ;43(10):611-621

Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology.

Mineralocorticoid receptor (MR)/NADPH oxidase (NOX) signaling is involved in the development of obesity, insulin resistance, and renal diseases; however, the role of this signaling on steatotic preneoplastic liver lesions is not fully elucidated. We determined the effects of the MR antagonist potassium canrenoate (PC) on MR/NOX signaling in hepatic steatosis and preneoplastic glutathione S-transferase placental form (GST-P)-positive liver foci. Rats were subjected to a two-stage hepatocarcinogenesis model and fed with basal diet or high fat diet (HFD) that was co-administered with PC alone or in combination with the antioxidant alpha-glycosyl isoquercitrin (AGIQ). Read More

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November 2018
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Plasma 2-hydroxyglutarate, a promising prognostic biomarker candidate for skeletal muscle injury in Fischer 344 rats.

J Toxicol Sci 2018 ;43(10):601-610

Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Azabu University.

Previously, we have demonstrated the potential of plasma 2-hydroxyglutarate (2HG) as an easily detectable biomarker for skeletal muscle injury in rats. Here, we examined whether plasma 2HG was superior to conventional skeletal muscle damage biomarkers, including aspartate aminotransferase (AST), creatine kinase (CK), and skeletal muscle-type CK isoenzyme (CK-MM) levels, in rats. Skeletal muscle injury was induced in 4- or 9-week-old male Fischer 344 rats by cerivastatin (CER) or tetramethyl-p-phenylenediamine (TMPD) administration. Read More

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http://dx.doi.org/10.2131/jts.43.601DOI Listing
November 2018
2 Reads

Comparative study for carcinogenicity of 7 different multi-wall carbon nanotubes with different physicochemical characteristics by a single intraperitoneal injection in male Fischer 344 rats.

J Toxicol Sci 2018 ;43(10):587-600

Department of Nutritional Science and Food Safety, Faculty of Applied Biosciences, Tokyo University of Agriculture.

The present study comparatively examined carcinogenicity of 7 different multi-wall carbon nanotubes (MWCNTs) with different physicochemical characteristics. Physicochemical characteristics of MWCNTs (referred to as M-, N-, WL-, SD1-, WS-, SD2- and T-CNTs in the present study) were determined using scanning electron and light microscopes and a collision type inductively coupled plasma mass spectrometer. Male Fischer 344 rats (10 weeks old, 15 animals per group) were administered MWCNTs at a single intraperitoneal dose of 1 mg/kg body weight, and sacrificed up to 52 weeks after the commencement. Read More

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http://dx.doi.org/10.2131/jts.43.587DOI Listing
November 2018
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Inhibition of L-type calcium channels by Bisphenol A in rat aorta smooth muscle.

J Toxicol Sci 2018 ;43(10):579-586

CICS-UBI - Centro de Investigação em Ciências da Saúde, University of Beira Interior, Portugal.

Bisphenol A (BPA) is an endocrine disrupting chemical used on a wide range in industry. This compound has been used in the production of polycarbonate plastics and epoxy resins. For this reason and their global use, BPA is one of the most common environmental chemicals to which humans are exposed. Read More

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November 2018
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Principles of precision medicine and its application in toxicology.

J Toxicol Sci 2018 ;43(10):565-577

Pfizer Worldwide Research and Development, Groton, CT 06340.

Precision medicine is an approach to developing drugs that focuses on employing biomarkers to stratify patients in clinical trials with the goal of improving efficacy and/or safety outcomes, ultimately increasing the odds of clinical success and drug approval. Precision medicine is an important tool for toxicologists to utilize, because its principles can be used to decide whether to pursue a drug target, to understand interindividual differences in response to drugs in both nonclinical and clinical settings, to aid in selecting doses that optimize efficacy or reduce adverse events, and to facilitate understanding of a drug's mode-of-action. Nonclinical models such as the mouse and non-human primate can be used to understand genetic variation and its potential translation to humans, and are available for toxicologists to employ in advance of drugs moving into clinical development. Read More

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November 2018
4 Reads

Verification of a false positive in a two-year rat carcinogenicity study using dual control groups.

J Toxicol Sci 2018 ;43(9):557-563

Department Molecular Pathology, Osaka City University.

There is sometimes controversy over whether or not statistically significant responses produced in carcinogenicity studies have biologically significance. Ambiguous results from our previous two-year oral carcinogenicity study on acotiamide hydrochloride hydrate (acotiamide-HH), a prokinetic drug for functional dyspepsia, in rats made it unclear whether the drug may exhibit uterine carcinogenicity. To check this finding, we performed a second long-term carcinogenicity study using two identical control groups to more accurately evaluate uterine carcinogenesis by considering the incidence of spontaneous neoplasms. Read More

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October 2018
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MnTMPyP inhibits paraquat-induced pulmonary epithelial-like cell injury by inhibiting oxidative stress.

J Toxicol Sci 2018 ;43(9):545-555

Department of Emergency, the First Hospital, China Medical University, China.

Objective: To investigate the protective effect and underlying mechanism of the superoxide dismutase mimic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), on paraquat (PQ)-induced lung alveolar epithelial-like cell injury.

Methods: Lung alveolar epithelial-like cells (A549) were pretreated with 10 μM MnTMPyP for 1.5 hr and then cultured with or without PQ (750 uM) for 24 hr. Read More

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October 2018
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Cadmium down-regulates apolipoprotein E (ApoE) expression during malignant transformation of rat liver cells: direct evidence for DNA hypermethylation in the promoter region of ApoE.

J Toxicol Sci 2018 ;43(9):537-543

Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU).

There is adequate evidence for the carcinogenicity of cadmium (Cd). However, a significant unaddressed question remains as to how this metal actually causes malignant transformation (tumor initiation). Since it has been shown that Cd only has the weak direct interaction potential with DNA, the metal is recognized as an indirect genotoxicant and mutagen. Read More

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October 2018
7 Reads

Prenatal bisphenol A exposure is associated with medial amygdala neuron hyperresponsiveness to predator odor in rats.

J Toxicol Sci 2018 ;43(9):531-536

Department of Human Intelligence Systems, Kyushu Institute of Technology.

Perinatal exposure to bisphenol A (BPA) causes several alterations in brain function and behavior. In previous studies, we showed that prenatal treatment with low-level BPA impaired gender-specific behavior, enhanced depression-like behavior, and augmented behavioral responses to predator odor in rats. On this premise, we hypothesized that BPA-treated rats were more susceptible to predator odor stress. Read More

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October 2018
1 Read