著者

Takashi Toyama Gi-Wook Hwang Akira Naganuma

出版者

一般社団法人日本毒性学会

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.2, no.5, pp.227-228, 2015-12-09 (Released:2015-12-09)

参考文献数

5

被引用文献数

1 1

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This study attempted to identify substances that are driven out of HEK293 cells by methylmercury. Metabolomic analysis revealed that the levels of 3-phenylpropionic acid, citrulline, lactic acid, ornithine, proline and beta-alanine in the cell culture medium were increased by the treatment of cells with methylmercury. Address to the mechanism underlying the release of these substances will provide useful information to elucidate the toxicity mechanism of methylmercury.

著者

Yusuke Aratsu Reo Odagiri Rie Shoji Kouki Watanabe Takeshi Kumagai Sawako Shindo Takamitsu Sasaki Kiyoshi Nagata

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.4, no.5, pp.229-239, 2017-10-05 (Released:2017-10-05)

参考文献数

27

被引用文献数

1 1

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CYP3A4 is an important drug-metabolizing enzyme induced by various compounds causing drug-drug interactions. However, the molecular mechanism of CYP3A4 induction is not completely understood. CYP3A4 induction is caused by pregnane X receptor (PXR) through binding to some PXR binding elements. These elements comprise an everted repeat separated by six nucleotides in the promoter region and distal nuclear receptor binding element 1 (dNR-1) as well as the essential distal nuclear receptor binding element for CYP3A4 induction (eNR3A4) in the enhancer region of the CYP3A4 gene. Recently, we found that polycyclic aromatic hydrocarbons including anthracene induce CYP3A4 in HepG2 cells with a different induction profile from that of rifampicin (RF), a typical PXR ligand. When a CYP3A4 reporter plasmid in which the eNR3A4 DNA fragment binds directly to the CYP3A4 promoter (-362 bases) was evaluated in a reporter assay, dibenz[a,h]anthracene (DBA) induced reporter activity, while RF did not. To be induced reporter activity by RF, more 14 nucleotides 5′ upstream of the eNR3A4 (rifampicin eNR3A4: reNR3A4) DNA fragment were required. However, eNR3A4 and reNR3A4 did not respond to recombinant PXR without dNR-1. These results suggest that eNR3A4 and reNR3A4 are necessary for CYP3A4 induction by DBA and RF, respectively, and that dNR-1 is indispensable for full induction through PXR.

著者

Eisuke Kume Yuya Okayama Mituru Sugiyama Hiroyuki Takahashi Tomoko Muto Michael F. Wempe Hiroshi Ikegami Shin Wakui

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.10, no.3, pp.R1, 2023 (Released:2023-06-06)

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Editor’s Announcement Quantitative morphometric analysis of vimentin filaments in Sertoli cells of rats after in utero DBP exposureEisuke Kume, Yuya Okayama, Mituru Sugiyama, Hiroyuki Takahashi, Tomoko Muto, Michael F. Wempe, Hiroshi Ikegami, Shin Wakui(Fundamental Toxicological Sciences, 4, 85-93, 2017) I have retracted the above paper as Editor-in-Chief of Fundamental Toxicological Sciences since I have serious concerns about it, primarily due to inappropriate authorship on a non-negligible scale.Since the possibility of inappropriate authorship in this paper was raised, I contacted the co-authors to confirm this point. I found out that several of them considered their listing as co-authors to be inappropriate. In addition, more than half of the co-authors agreed to the retraction of this paper.These facts raise concerns about the paper. From the standpoint of maintaining the integrity of the research community, I felt that such a paper should be retracted at once.Accordingly, I sent a summary of my concerns about this paper to the corresponding author, Dr. Shin Wakui. I also had an online interview with him to discuss this matter. I told Dr. Wakui that inappropriate authorship on a non-negligible scale is a serious problem that raises concerns about the paper.I prepared a draft of this Editor’s Announcement and sent it to Dr. Wakui for review prior to revision and release. Although he did not agree to the retraction, I have decided to take this action from the standpoint of maintaining the integrity of the research community.I coordinated my response to this issue with Dr. Toshiyuki Kaji, Editor-in-Chief of The Journal of Toxicological Sciences, a sister journal of Fundamental Toxicological Sciences.Akira Naganuma, Ph.D.Editor-in-ChiefFundamental Toxicological Sciences

著者

Eisuke Kume Yuya Okayama Mituru Sugiyama Hiroyuki Takahashi Tomoko Muto Michael F. Wempe Hiroshi Ikegami Shin Wakui

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.4, no.2, pp.85-93, 2017-05-13 (Released:2017-05-13)

参考文献数

18

被引用文献数

1 1

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This article was retracted. See the Notification.

著者

Berenyce González-Marín María Elena Calderón-Segura Ana Karen González Pérez Luis Gerardo Moreno Ciénega

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.8, no.3, pp.81-88, 2021 (Released:2021-07-27)

参考文献数

43

被引用文献数

1

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Movento® 240SC and Envidor® 240SC are new insecticide derivatives of tetramic acid belonging to a keto-enol pesticide family. However, few studies have reported genotoxic effects in nontarget organisms. In the present study, the genotoxic effects of Movento® 240SC and Envidor® 240SC on Drosophila melanogaster ovaries were analyzed using the alkaline comet assay. Simultaneously, we determined the LD50 for both insecticides. Virgin females were exposed to food at three sublethal concentrations (11.2, 22.4, 37.3 mg/L) of Movento® 240SC and (12.3, 24.6, 41.1 mg/L) of Envidor® 240SC for 72 hr. As a negative control group, females were exposed to food without insecticides, and as a positive control group, females were exposed to 17.5 mg/L bleomycin under the same experimental conditions. We analyzed three genotoxic parameters, tail length, tail moment, and tail intensity, in ovarian cells. The results showed that 11.2 mg/L Movento® 240SC insecticide significantly increased the tail intensity mean in ovarian cells compared with the negative control. However, 22.4 and 37.3 mg/L Movento® 240SC significantly increased tail length and tail moment means compared with the negative control. Envidor® 240SC insecticide at 12.3, 24.6, 41.1 mg/L significantly increased the three genotoxic parameters in ovarian cells compared with the negative control. The LD50 values of Movento® 240SC and Envidor® 240SC insecticides were 79.1 mg/L and 78.0 mg/L, respectively. The genotoxic response of the two keto-enol pesticides was dependent on the concentration of each pesticide. The results demonstrated that Movento® 240SC and Envidor® 240SC keto-enol insecticides are genotoxic agents in D. melanogaster ovaries.

著者

Misuzu Tanaka Akane Kanasaki Noriko Hayashi Tetsuo Iida Koji Murao

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.8, no.1, pp.23-31, 2021 (Released:2021-04-22)

参考文献数

37

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D-allulose is a non-caloric natural sugar with health benefits. A few clinical trials with continuous D-allulose intake have been reported; one indicated significant increase in low-density lipoprotein cholesterol (LDL-C) levels, though the study was not a randomized controlled trial. D-allulose is predicted to be widely used in the near future by various people; therefore, the influence of D-allulose on those who have high risk for LDL-C elevation needs to be determined. Here, the effects of D-allulose on LDL-C levels in patients with hypercholesterolemia under statin therapy were investigated in a randomized controlled trial. Twenty subjects were randomly assigned to two groups: 15 g D-allulose/day or 15 g erythritol/day (placebo); each subject consumed a daily test substance for 48 weeks. Clinical examinations were performed every eight weeks, from initial consumption until week 52. No significant increase in LDL-C was observed, although significant decrease was observed in high-density lipoprotein cholesterol (HDL-C) in the D-allulose group. HDL-C values stayed within the standard ranges during the consumption period, and the mechanism was reported to be anti-atherosclerotic. In terms of risk assessment, D-allulose did not affect all risk factors that were measured for atherosclerotic cardiovascular disease. Taken together, these results suggested that long-term D-allulose consumption did not affect LDL-C values and atherosclerotic cardiovascular disease risk in patients with hypercholesterolemia under statin therapy.

著者

Mai Nishikawa Naoki Ohara Yukiko Naito Chihiro Amma Yoshiaki Saito Kenjiro Tatematsu Jinhua Baoyindugurong Daisuke Miyazawa Yoko Hashimoto Harumi Okuyama

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.9, no.1, pp.7-16, 2022 (Released:2022-01-15)

参考文献数

30

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The present study was conducted to survey the influence of canola oil (CAN) ingestion on the steroid hormone production in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP were fed a diet containing 10 wt/wt% soybean oil (SOY, the control) or CAN as the sole dietary fat for 8 weeks. Plasma concentration of luteinizing hormone (LH) was similar in the 2 dietary groups. However, the plasma testosterone level in the CAN group, 1.36 ± 0.271 ng/mL, was lower than in the SOY group, 2.79 ± 0.514 ng/mL (p < 0.05, unpaired t-test; n = 10), and plasma concentration of aldosterone in the CAN group, 345 ± 79.6 pg/mL, was higher than in the SOY group, 159 ± 33.7 pg/mL (p < 0.05, unpaired t-test; n = 10). In the testis, the expressions of mRNA for StAR, CYP11A1, CYP17, 3βHSD and 17βHSD and the amounts of the corresponding proteins were significantly decreased. However, in the adrenal gland, the expressions of mRNA for StAR, CYP11A1, 3βHSD and CYP11B1 in the CAN group were not different from those in the SOY group, but the expression of mRNA and the amount of the corresponding protein for CYP11B2 were increased significantly in the CAN group. These findings are indicative of a peripheral, testicular toxicity of CAN. The decreased testosterone and the concomitantly increased aldosterone may play a role in the aggravation by CAN of the genetic diseases (i.e., metabolic syndrome-like complications) in male SHRSP.

著者

Yuhji Taquahashi Shuji Tsuruoka Koichi Morita Masaki Tsuji Kousuke Suga Ken-ich Aisaki Satoshi Kitajima

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.9, no.1, pp.17-21, 2022 (Released:2022-01-18)

参考文献数

10

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Carbon-nanotube yarn (CNT-Y) made from high-purity, highly crystalized, double-walled carbon nanotubes is an advanced material with excellent electrical conductivity and flexibility; hence, it could potentially be used as a novel electrode for biopotential measurements. To our knowledge, the present study is the first in which CNT-Y electrodes were used to conduct electrocardiography (ECG) and electroencephalography (EEG) on experimental animals. All procedures and biopotential measurements were performed under isoflurane anesthesia. The CNT-Y electrodes were attached to the animals by creating a single interrupting suture on the skin. The lead II electrode configuration was used for ECG recording, i.e., the positive, negative, and body-earth electrodes were placed on the left apex of the auricular surface, the interscapular region, and the cervical region, respectively. The bipolar lead was used for EEG recording, with the exploring and reference electrodes on the bregma and base of the right auricular surface, respectively. Using CNT-Y electrodes, we obtained a clear ECG waveform from rats and a guinea pig; the QRS amplitude was ~1.4 mV. In rats, we obtained an EEG waveform with an amplitude of ~150 µV; the peak frequency was 0.8 Hz and the range was ~3 Hz according to power spectral density analysis. In the guinea pig, we obtained an EEG waveform with an amplitude of ~500 µV; the first peak was 0.1 Hz, the second peak was 1 Hz, and the range was ~3 Hz. These results show that CNT-Y could be used in toxicology studies to easily and inexpensively obtain high-resolution biological signals.

著者

Osamu Ohgoda Ian N. Robinson

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.7, no.2, pp.55-76, 2020 (Released:2020-03-03)

参考文献数

33

被引用文献数

1 4

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In the inhalation field, lipids such as egg phosphatidylcholine (PC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and dipalmitoylphosphatidylcholine (DPPC), are considered to be generally recognized as safe (GRAS), comprising materials that are endogenous to the lungs and locally present in large quantities. Indeed, PC, DSPC and DPPC may be used to form liposomes which are known to promote an increase in drug retention time and reduce the toxicity of drugs after administration. Unfortunately, published literature guidance about the safety evaluation of these lipids as pharmaceutical excipients for use in inhaled products and about application for marketing authorization, is very limited. The purpose of this article is to review the potential toxicity of DSPC for pulmonary administration. Given the use of air and vehicle controls in a range of inhalation toxicology studies as well as negative genotoxicity and also reproductive toxicity results, it is thought that the use of DSPC is shown to be safe for pulmonary administration.

著者

Yoshitaka Hirasawa Atsushi Fujiwara Kazuya Tabata Kenji Yoshida Tsutomu Negama Takayuki Anzai Shin-ichi Sato

出版者

The Japanese Society of Toxicology

雑誌

Fundamental Toxicological Sciences (ISSN:2189115X)

巻号頁・発行日

vol.7, no.2, pp.105-114, 2020 (Released:2020-03-27)

参考文献数

33

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The purpose of this study was to profile cytokine storms (cytokine release syndrome) in the LPS-induced disseminated intravascular coagulation (DIC)-cynomolgus monkey model by measuring changes in 22 cytokines using Luminex. In this study, increases were noted in 20 cytokines, excluding IL-4 and IL-17A. Specifically, IL-6, IL-8, G-CSF and TNF-α, pro-inflammatory cytokines, and IL-10, an anti-inflammatory cytokine, as well as MCP-1, markedly increased by 10,000 pg/mL or more. In addition to the marked increases in the pro-inflammatory cytokines IL-6 and G-CSF, the concentrations of IL-5, IL-18, IFN-γ, VEGF and IL-15 increased continuously. Also, in addition to the marked increases in the pro-inflammatory cytokine IL-8 as well as in MCP-1, the concentrations of IL-1ra, IL-2, IL-1β, IL-12/23 (p40), GM-CSF and TGF-α gradually decreased after initially increasing. On the other hand, in addition to the marked increases in the pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10, MIP-1β and MIP-1α transiently increased and then rapidly disappeared from serum. IL-13 increased at 6 hr after administration only. Since the behavior of cytokines in this monkey model was similar to those noted in DIC in humans, this model will be useful for evaluating the efficacy of anti-DIC drugs. In addition, this model will also be useful for assessing the risk of cytokine storm development, which is a serious adverse effect of certain types of antibody drugs and CAR-T cell-based therapies.