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Journal of Toxicological Sciences

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https://www.readbyqxmd.com/read/28496044/comparison-of-nephrotoxicity-between-two-gadolinium-contrasts-gadodiamide-and-gadopentetate-in-patients-with-mildly-diminished-renal-failure
#1
Shokichi Naito, Hiromi Tazaki, Tomoko Okamoto, Kazuhiro Takeuchi, Shinichi Kan, Yasuo Takeuchi, Kouju Kamata
Although gadolinium (Gd)-based contrast media have been found to be nephrotoxic, their nephrotoxicity, and the dependence of nephrotoxicity on chelate types, have not been assessed in patients with normal or mildly diminished renal failure. This prospective, randomized study compared the nephrotoxicity of low doses of the nonionic Gd-based contrast medium gadodiamide (Omniscan®) and the ionic Gd-based contrast medium gadopentetate (Magnevist®) in patients with serum creatinine < 1.6 mg/dL. Patients aged 20 to 80 years, weighing 45 to 70 kg and with normal or < 1...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496043/length-effects-of-single-walled-carbon-nanotubes-on-pulmonary-toxicity-after-intratracheal-instillation-in-rats
#2
Makoto Ema, Hiroshi Takehara, Masato Naya, Hiromichi Kataura, Katsuhide Fujita, Kazumasa Honda
We aimed to evaluate the effects of the length of single-walled carbon nanotubes (SWCNTs) on pulmonary toxicity in rats. Each rat received a single intratracheal instillation of short (S-) (average length of 0.40 μm) or long (L-) (average length of 2.77 μm) SWCNTs at a dose of 1 mg/kg and was observed for the next 6 months. Neither S- nor L-SWCNTs affected clinical signs, body weight, or autopsy findings. An increase in lung weight was observed after instillation of S- or L-SWCNTs; however, lung weights were slightly higher in the rats that were administered the S-SWCNTs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496042/high-sensitivity-of-testicular-function-to-titanium-nanoparticles
#3
Nobuhiko Miura, Katsumi Ohtani, Tatsuya Hasegawa, Hiroki Yoshioka, Gi-Wook Hwang
Titanium dioxide nanoparticles (TiNPs) present toxicity in organs such as the liver, lung, and intestine. The testis has also been reported as a target organ of TiNPs. We recently reported that TiNPs had no genotoxic effect in the liver and bone marrow, while showing clear testicular dysfunction. In this paper, therefore, we systematically compared the sensitivity of hepatic function using biochemical markers and testicular function against TiNPs. Male C57BL/6J mice were injected intravenously with TiNPs (Aeroxide-P25, at doses of 0...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496041/a-rapid-mitochondrial-toxicity-assay-utilizing-rapidly-changing-cell-energy-metabolism
#4
Yosuke Sanuki, Tetsuro Araki, Osamu Nakazono, Kazuyuki Tsurui
Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496040/induction-of-human-cytochrome-p450-3a-enzymes-in-cultured-placental-cells-by-thalidomide-and-relevance-to-bioactivation-and-toxicity
#5
Norie Murayama, Yasuhiro Kazuki, Daisuke Satoh, Kazuya Arata, Tasuku Harada, Norio Shibata, F Peter Guengerich, Hiroshi Yamazaki
Evidence has been presented for auto-induced human cytochrome P450 3A enzyme involvement in the teratogenicity and clinical outcome of thalidomide due to oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers. In this study, more relevant human placenta preparations and placental BeWo cells showed low but detectable P450 3A4/5 mRNA expression and drug oxidation activities. Human placental microsomal fractions from three subjects showed detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496039/pyrolysis-of-ur-144-a-synthetic-cannabinoid-augments-an-affinity-to-human-cb1-receptor-and-cannabimimetic-effects-in-mice
#6
Asuka Kaizaki-Mitsumoto, Kyoko Hataoka, Masahiko Funada, Yuki Odanaka, Hiroki Kumamoto, Satoshi Numazawa
Drug abusers most often smoke 'herbal incense' as a cigarette or inhale it using a smoking tool. Smoking may cause pyrolysis of the drug and produce decomposed products of which biological effect has never been investigated. The synthetic cannabinoid UR-144 is known to undergo thermal degradation, giving a ring-opened isomer, so-called UR-144 degradant. The present study demonstrates by using UR-144 as a model drug that the smoke of burned UR-144 contains the UR-144 degradant. The UR-144 degradant showed approximately four fold higher agonist activity to human CB1 receptor and augmented hypothermic and akinetic actions in mice compared to UR-144...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496038/methylmercury-induces-hyaluronan-synthesis-in-cultured-human-brain-microvascular-endothelial-cells-and-pericytes-via-different-mechanisms
#7
Takashi Hirooka, Eiko Yoshida, Komyo Eto, Toshiyuki Kaji
In a cerebrum damaged by methylmercury, where neuropathological lesions tend to localize along deep sulci and fissures, edematous changes in white matter have been proposed as the cause of such localization. Since hyaluronan has a high water-retention capability and can contribute to the progression of edematous changes, we hypothesize that methylmercury increases hyaluronan in brain microvascular cells. Our experimental results indicate that methylmercury induces the expression of hyaluronan in cultured human microvascular endothelial cells and pericytes through the induction of expressed UDP-glucose dehydrogenase and hyaluronan synthase 2, respectively...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496037/mono-butyl-phthalate-induced-mouse-testis-injury-is-associated-with-oxidative-stress-and-down-regulated-expression-of-sox9-and-dazl
#8
Junting Du, Di Xiong, Qian Zhang, Xiaoxiao Li, Xudong Liu, Huihui You, Shumao Ding, Xu Yang, Junlin Yuan
Mono-butyl phthalate (MBP) has reproductive toxicity but the related mechanisms have not been fully elucidated in vivo. We exposed male Balb/c mice to MBP by gavage at doses of 0, 25, 50, 100, 200 mg/kg for 14 days, and then evaluated the testicular alterations at the histological and molecular levels. MBP reduced mouse sperm count along with sperm malformation and seminiferous tubule degeneration in a dose-dependent manner. MBP dosed at 200 mg/kg significantly increased reactive oxygen species and malondialdehyde content in mouse testes...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496036/tissue-toxicokinetics-of-perfluoro-compounds-with-single-and-chronic-low-doses-in-male-rats
#9
Katsumi Iwabuchi, Norimasa Senzaki, Daichi Mazawa, Itaru Sato, Michihiro Hara, Fukiko Ueda, Wei Liu, Shuji Tsuda
To examine the kinetics of low doses of perfluoro compounds (PFCs), we administered perfluorohexanoic acid (C6A), perfluorooctanoic acid (C8A), perfluorononanoic acid (C9A) and perfluorooctane sulfonate (C8S) with a single oral dose (50-100 μg/kg BW), and in drinking water at 1, 5, and 25 μg/L for one and three months to male rats; and examined the distribution in the brain, heart, liver, spleen, kidney, whole blood and serum. C6A was very rapidly absorbed, distributed and eliminated from the tissues with nearly the same tissue t1/2 of 2-3 hr...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496035/alleviating-effects-of-artificial-tear-instillation-on-s-1-induced-ocular-toxicity-in-dogs
#10
Shohei Kanie, Mitsuhiro Fujieda, Tomoaki Hitotsumachi, Satoshi Suzuki, Fumio Morita, Kazuo Hakoi, Hirofumi Yasui
S-1 is an anticancer agent that consists of tegafur, gimeracil, and oteracil potassium at a molar ratio of 1:0.4:1. S-1 is used to treat metastatic and resectable gastric cancer. However, the extensive use of S-1 in clinical practice results in watery eyes, a serious clinical problem, which worsens patients' quality of life. Although repeated instillation of artificial tears is recommended, therapy or prophylaxis against S-1-induced ocular toxicity has not been established. In the present study, we evaluated the alleviating effects of repeated artificial tear instillation on S-1-induced ocular toxicity in dogs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496034/effect-of-perinatal-exposure-to-bisphenol-a-on-dna-methylation-and-histone-acetylation-in-cerebral-cortex-and-hippocampus-of-postnatal-male-mice
#11
Dhiraj Kumar, Mahendra Kumar Thakur
Bisphenol-A (BPA) is an estrogenic endocrine disruptor mostly used for the production of polycarbonate plastics and epoxy resins. Recently we have reported that perinatal BPA exposure impaired spatial memory through upregulation of synaptic proteins Neurexin1 and Neuroligin3 in male mice. As epigenetic mechanism is a key regulator of memory, we hypothesized that BPA might influence memory through epigenetic regulation of gene expression. Here we provide evidence that perinatal exposure to BPA decreased 5-mC DNA but increased histone H3 acetylation in cerebral cortex and hippocampus of postnatal 3 and 8 weeks male mice...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496033/joint-toxicity-of-fluoroquinolone-and-tetracycline-antibiotics-to-zebrafish-danio-rerio-based-on-biochemical-biomarkers-and-histopathological-observation
#12
Lihe Ding, Luxiu Zang, Yuna Zhang, Yuhuan Zhang, Xuedong Wang, Weiming Ai, Nani Ding, Huili Wang
Herein, we report on the joint toxicity of four fluoroquinolones and two tetracyclines (β-diketone antibiotics-DKAs) to zebrafish based on a series of toxicological endpoints and histopathological observations. A positive dose-dependence was observed in DKA-exposure groups with a 72-hpf EC50 of 130.3 mg/L for hatching rate, 120-hpf LC50 of 149.8 mg/L, and 120-hpf EC50 of 135.1 mg/L for malformation rate. When zebrafish at 60 dpf were exposed to a series of DKA concentrations (45, 60 and 90 mg/L) for 7, 14 and 21 days, creatine kinase and AChE activities were significantly induced, and intracellular malondialdehyde increased in all treatments except for the 45 mg/L treatment...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28496032/farnesoid-x-receptor-regulates-the-growth-of-renal-adenocarcinoma-cells-without-affecting-that-of-a-normal-renal-cell-derived-cell-line
#13
Tomofumi Fujino, Ryosuke Sakamaki, Haruka Ito, Yumiko Furusato, Nami Sakamoto, Toshiyuki Oshima, Makio Hayakawa
The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor which is abundant in the liver, intestine, and kidney. FXR is a pivotal factor in cholesterol/bile acid homeostasis but is involved in the growth of hepatocellular carcinoma cells. In the present study, we investigated whether FXR is also involved in the growth of renal adenocarcinoma cells. The cell growth of renal adenocarcinoma cell line ACHN was inhibited by FXR knockdown and stimulated by FXR ligand, while that of a normal renal cell-derived cell line, HK-2, was not affected...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321051/chronotoxicity-of-bromobenzene-induced-hepatic-injury-in-mice
#14
Hiroki Yoshioka, Tsunemasa Nonogaki, Nobuyuki Fukuishi, Yasuro Shinohara, Gi-Wook Hwang, Katsumi Ohtani, Nobuhiko Miura
The aim of the present study is to investigate whether or not bromobenzene (BB) toxicity varies with circadian periodicity. Seven-week-old male ICR mice were injected with 900 mg/kg (5.73 mmol/kg) BB intraperitoneally at 4 different time points of a day (zeitgeber time [ZT]: ZT0, ZT6, ZT12, and ZT18). Mortality was then monitored for 7 days after injection. Interestingly, mice were sensitive to BB acute toxicity at ZT6 while tolerant at ZT18. Moreover, in mice that were given a non-lethal dose of BB (540 mg (3...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321050/alteration-of-gut-microbial-community-after-n-n-dimethylformamide-exposure
#15
Man Zhang, Min Zheng, Zhijun Wu, Mingyue Guan, Shuai Liu, Wenjin Zhao, Juan Cheng
N,N-Dimethylformamide (DMF), a solvent commonly used in factories, can induce liver toxicities, including hepatitis, fibrosis, cirrhosis and hepatoma. It is well known that the gut microbial community plays a role in the metabolism of many toxic substance and in liver regeneration. However, the effect of DMF on rat gut microbial community is poorly understood. The gut microbiotas in control rats and rats exposed to DMF were characterized by high-throughput sequencing of the bacterial 16S rRNA gene. The levels of biochemical parameters in the serum of rats, including cholesterol, bile acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321049/protective-effect-of-senp3-mediated-sumoylation-against-cadmium-toxicity
#16
Hongquan Zhu
SUMOylation is widely reported as a cytoprotective response against cell stress induced by ischemia and reperfusion. However, it is still unclear what other cell stressors trigger protein SUMOylation, what mechanisms enhance and maintain the enhanced SUMOylation, and if it is a general protective mediator against other cytotoxic stresses, toxic heavy metal cadmium for instance. Here, we show increased levels of SUMOylation and decreased levels of the deSUMOylation enzyme SENP3 in PC12 cells exposed to CdCl2...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321048/evaluation-of-the-effects-of-power-frequency-magnetic-fields-on-the-electrical-activity-of-cardiomyocytes-differentiated-from-human-induced-pluripotent-stem-cells
#17
Masayuki Takahashi, Atsushi Saito, Yasuhiko Jimbo, Satoshi Nakasono
Although cardiac activity is known to differ between species in many respects, most evaluations of the cardiac effects of low-frequency electric and magnetic fields, which have a stimulant effect on electrically activated cells, have been performed in non-human experimental animals and cells, and the effects in humans have been assessed using theoretical models. In recent years, it has been verified that human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CM) are useful for evaluating human responses to various cardioactive compounds...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321047/chemically-induced-strong-cellular-hypertrophy-often-reduces-the-accuracy-of-cytotoxicity-measurements-obtained-using-the-atp-assay
#18
Haruna Tahara, Yusuke Yamamoto, Shun Matsuda, Hiroe Yoshizawa, Masaharu Fujita, Takanori Hioki, Toshihiko Kasahara
The ATP assay is a highly sensitive and versatile method for measuring cytotoxicity. However, the correlation between the cell viability results obtained using the ATP assay and those obtained using direct cell counting has not been widely reported. Therefore, to evaluate the reliability and limitations of the ATP assay, we compared the results of ATP assay with those of automatic cell counter, which can measure the number and diameter of cells directly, by using 24 compounds and repeating individual experiments thrice...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321046/tobacco-nitrosamine-nnk-increases-aldh-positive-cells-via-ros-wnt-signaling-pathway-in-a549-human-lung-cancer-cells
#19
Naoya Hirata, Shigeru Yamada, Yuko Sekino, Yasunari Kanda
Epidemiological studies suggest that lung cancer, which is a major cause of cancer death, has a critical association with cigarette smoking. Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in cigarette smoke is a major risk factor for carcinogenesis. However, the mechanisms by which NNK promotes cancer development have not been fully elucidated. Growing evidence suggests that lung cancer originates from cancer stem cells (CSCs), which are a minor population of lung cancer cells...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28321045/characterization-of-human-ips-cell-derived-cardiomyocyte-sheets-as-a-model-to-detect-drug-induced-conduction-disturbance
#20
Hiroko Izumi-Nakaseko, Yuji Nakamura, Takeshi Wada, Kentaro Ando, Yasunari Kanda, Yuko Sekino, Atsushi Sugiyama
In order to characterize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets as a model for detecting drug-induced conduction disturbance, we examined their electrophysiological and electropharmacological properties by using the multi-electrode array system with a programmed electrical stimulation protocol. At pre-drug control, the conduction speed, effective refractory period and field potential duration were 0.14 ± 0.01 m/sec, 453 ± 10 msec and 361 ± 9 msec, respectively at a cycle length of 1,000 msec (n = 18)...
2017: Journal of Toxicological Sciences
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