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Journal of Toxicological Sciences

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https://www.readbyqxmd.com/read/30626780/-1-h-nmr-toxicometabolomics-following-cisplatin-induced-nephrotoxicity-in-male-rats
#1
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
https://www.readbyqxmd.com/read/30626779/galectin-3-regulates-chemotherapy-sensitivity-in-epithelial-ovarian-carcinoma-via-regulating-mitochondrial-function
#2
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
https://www.readbyqxmd.com/read/30626778/dermal-exposure-to-nano-tio-2-induced-cardiovascular-toxicity-through-oxidative-stress-inflammation-and-apoptosis
#3
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
https://www.readbyqxmd.com/read/30626777/the-dermal-sensitization-threshold-dst-approach-for-mixtures-evaluated-as-negative-in-in-vitro-test-methods-mixture-dst
#4
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
https://www.readbyqxmd.com/read/30626776/sensitivity-of-keratinosens-tm-and-h-clat-for-detecting-minute-amounts-of-sensitizers-to-evaluate-botanical-extract
#5
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
https://www.readbyqxmd.com/read/30626775/effect-of-layered-application-on-the-skin-permeation-of-a-cosmetic-active-component-rhododendrol
#6
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
https://www.readbyqxmd.com/read/30518713/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
#7
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
https://www.readbyqxmd.com/read/30518712/the-performance-of-an-in-vitro-skin-sensitisation-test-il-8-luc-assay-oecd442e-and-the-integrated-approach-with-direct-peptide-reactive-assay-dpra
#8
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
https://www.readbyqxmd.com/read/30518711/structure-activity-relationship-of-1-5-azastibocines-in-cytotoxicity-to-vascular-endothelial-cells
#9
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
https://www.readbyqxmd.com/read/30518710/5-fluorouracil-inhibits-neural-differentiation-via-mfn1-2-reduction-in-human-induced-pluripotent-stem-cells
#10
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
https://www.readbyqxmd.com/read/30518709/monomethylmercury-degradation-by-the-human-gut-microbiota-is-stimulated-by-protein-amendments
#11
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
https://www.readbyqxmd.com/read/30518708/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
#12
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
https://www.readbyqxmd.com/read/30518707/silver-effects-on-silkworm-bombyx-mori
#13
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
https://www.readbyqxmd.com/read/30405001/approaches-of-validation-of-a-2-week-combined-repeated-oral-dose-toxicity-study-with-plasma-micro-sampling-toxicokinetics-pms-tk-in-common-marmosets
#14
Hidemi Mochizuki, Naoya Murota, Shin-Ichi Sato, Kazuo Nii, Yoko Kouhei, Masahiro Taniguchi, Ryo Inoue, Chiyoko Nishime, Hideki Tsutsumi
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...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/30405000/thalidomide-protects-against-acute-pentylenetetrazol-and-pilocarpine-induced-seizures-in-mice
#15
Ana Mara Islas-Espinoza, Carolina Campos-Rodriguez, Eduardo Ramírez San Juan
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. The effect of an NO and COX inhibitor (7-NI and ibuprofen, respectively) was also examined...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/30404999/melatonin-antagonizes-oxidative-stress-induced-mitochondrial-dysfunction-in-retinal-pigmented-epithelium-cells-via-melatonin-receptor-1-mt1
#16
Guigang Yan, Lianzhi Yu, Songmei Jiang, Jianfeng Zhu
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 (H2 O2 )-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 H2 O2 or (and) with Melatonin...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/30404998/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
#17
Li Xiong, Hao Liyue, Zeng Fancai, Li Maoting, Li Ya, He Ting, Yang Zhen, Zhu Shanshan, Gu Wenwen, Tang Yan
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...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/30404997/social-behavior-neuroimmune-markers-and-glutamic-acid-decarboxylase-levels-in-a-rat-model-of-valproic-acid-induced-autism
#18
Tin-Tin Win-Shwe, Nay Chi Nway, Motoki Imai, Thet-Thet Lwin, Ohn Mar, Hidehiro Watanabe
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 12.5 of gestation. Both 11- to 13-week-old male and female rat models of VPA-induced autism showed impaired sociability and impaired preference for social novelty as compared to the corresponding control SD rats...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/30404996/low-level-lead-exposure-and-cardiovascular-disease-the-roles-of-telomere-shortening-and-lipid-disturbance
#19
REVIEW
Liyun He, Zhenying Chen, Bo Dai, Guilin Li, Gaochun Zhu
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. Hence, telomere shortening and lipid disturbance might play an important role in the pathophysiological process of chronic low levels of lead exposure contributing to cardiovascular diseases...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/30298849/differential-impacts-of-mineralocorticoid-receptor-antagonist-potassium-canrenoate-on-liver-and-renal-changes-in-high-fat-diet-mediated-early-hepatocarcinogenesis-model-rats
#20
Misato Nakamura, Ayumi Eguchi, Mari Inohana, Rei Nagahara, Hirotada Murayama, Masashi Kawashima, Sayaka Mizukami, Mihoko Koyanagi, Shim-Mo Hayashi, Robert R Maronpot, Makoto Shibutani, Toshinori Yoshida
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)...
2018: Journal of Toxicological Sciences
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