著者

Akemi SAITO Masaharu YAMAMOTO

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.21, no.3, pp.195-200, 1996-08-25 (Released:2008-02-21)

参考文献数

18

被引用文献数

40 54

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The oral toxicity of capsaicin was investigated in mice and rats. Oral LD50 values were 118.8 mg/kg for male and 97.4 mg/kg for female mice, and 161.2 mg/kg for male and 148.1 mg/kg for female rats. Major toxic symptoms in mice were salivation, erythema of skin, staggering gait, bradypnea and cyanosis. Some animals showed tremor, clonic convulsion, dyspnea and lateral or prone position and then died 4 to 26 min after dosing. Survivors recovered within 6 hr in mice and 24 hr in rats. Toxic symptoms of fats were almost the same as mice, but rats showing higher incidence of cyanosis, clonic or tonic convulsion, dyspnea and lateral position, and the recovery was later than mice. The cause of death by capsaicin may be due to hypotension and respiratory paralysis in both animals, although the pathophysiology of death is not clearly understood. At pathological examination, erosion and ulcer of gastric fundus were seen in dead animals, while no pathological change was seen in surviving ones.

著者

Harumi Okuyama Naoki Ohara Kenjiro Tatematsu Shinya Fuma Tomoyuki Nonogaki Kazuyo Yamada Yuko Ichikawa Daisuke Miyazawa Yuko Yasui Seijiro Honma

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.35, no.5, pp.743-747, 2010-10-01 (Released:2010-10-01)

参考文献数

25

被引用文献数

7 13 5

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Canola and some other types of oil unusually shorten the survival of stroke-prone spontaneously hypertensive rats (SHRSP), compared with soybean oil, perilla oil and animal fats. Since differential effects of canola and soybean oil on steroid hormone metabolism were suggested by a preliminary DNA microarray analysis as a reason for this, the steroid hormone levels in the serum and tissues of SHRSP fed different oils were investigated. The testosterone levels in the serum and the testes were found to be significantly lower in the canola oil group than in the soybean oil group, while no significant differences were detected in the corticosterone and estradiol levels in tissues. In a second experiment, it was found that hydrogenated soybean oil, with a survival-shortening activity comparable to that of canola oil, also decreased the testosterone level in testes to a similar degree. The testosterone-lowering activity of canola and hydrogenated soybean oil observed in SHRSP was considered in relation to other factors possibly affecting the physiology of SHRSP.

著者

Sanghwa Kim Seong-Ho Hong Choon-Keun Bong Myung-Haing Cho

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.40, no.5, pp.535-550, 2015-10-01 (Released:2015-09-10)

参考文献数

100

被引用文献数

31 49

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Air freshener could be one of the multiple sources that release volatile organic compounds (VOCs) into the indoor environment. The use of these products may be associated with an increase in the measured level of terpene, such as xylene and other volatile air freshener components, including aldehydes, and esters. Air freshener is usually used indoors, and thus some compounds emitted from air freshener may have potentially harmful health impacts, including sensory irritation, respiratory symptoms, and dysfunction of the lungs. The constituents of air fresheners can react with ozone to produce secondary pollutants such as formaldehyde, secondary organic aerosol (SOA), oxidative product, and ultrafine particles. These pollutants then adversely affect human health, in many ways such as damage to the central nervous system, alteration of hormone levels, etc. In particular, the ultrafine particles may induce severe adverse effects on diverse organs, including the pulmonary and cardiovascular systems. Although the indoor use of air freshener is increasing, deleterious effects do not manifest for many years, making it difficult to identify air freshener-associated symptoms. In addition, risk assessment recognizes the association between air fresheners and adverse health effects, but the distinct causal relationship remains unclear. In this review, the emitted components of air freshener, including benzene, phthalate, and limonene, were described. Moreover, we focused on the health effects of these chemicals and secondary pollutants formed by the reaction with ozone. In conclusion, scientific guidelines on emission and exposure as well as risk characterization of air freshener need to be established.

著者

Toshi WATANABE Yoshihiro KISHIKAWA Wataru SHIRAI

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.22, no.2, pp.141-152, 1997-05-25 (Released:2008-02-21)

参考文献数

17

被引用文献数

11 12

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Alkaline ionized water (AKW) produced by the electrolysis of tap water (TPW) was given to pregnant rats throughout gestation. AKW was subsequently given to infants as a test group until 15 weeks old to determine changes in body and organ weights, erythrocyte hexokinase (HK) activity and histological preparations of myocardiac muscle. The results were compared with those for rats given TPW. Body weight of male and female rats given AKW at 3 to 11 weeks of age after birth significantly increased beyond control group values. Organ weights of offspring at 15weeks-old showed no statistical difference for either group. HK activity, the rate-determining enzyme in erythrocyte glycolysis, significantly increased in males given AKW at 15 weeks-old. This suggests that AKW intake causes elevation of metabolic activity. Hyperkalemia was observed in males and females given AKW at 15 weeks-old. Especially in males, pathological changes of necrosis in myocardiac muscle were observed.

著者

Shohei Kanie Mitsuhiro Fujieda Tomoaki Hitotsumachi Satoshi Suzuki Fumio Morita Kazuo Hakoi Hirofumi Yasui

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.42, no.3, pp.291-300, 2017-06-01 (Released:2017-05-11)

参考文献数

28

被引用文献数

3 3

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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. Ten beagle dogs (5 males and 5 females) were orally administered 3 mg/kg/day of S-1 for up to 21 days. Five drops of artificial tears were instilled to the left eye, eight times daily, within 6 hr after S-1 administration. The mean cornea staining score tended to be low in the left eye with repeated artificial tear instillation. In 4 out of 10 dogs, the corneal staining score of the left eye was more than 2-fold lower than that of the right eye. The incidence of dogs indicating normal tear drainage increased and stenosed tear drainage decreased by repeated artificial tear instillation. In conclusion, we demonstrated that artificial tear instillation can alleviate corneal surface damage induced by S-1 in dogs.

著者

Nobuyuki Suzuki Ryuichi Kambayashi Ai Goto Hiroko Izumi-Nakaseko Yoshinori Takei Atsuhiko T Naito Atsushi Sugiyama

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.48, no.12, pp.645-654, 2023 (Released:2023-12-01)

参考文献数

27

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Antiparasitic ivermectin has been reported to induce cardiovascular adverse events, including orthostatic hypotension, tachycardia and cardiopulmonary arrest, of which the underlying pathophysiology remains unknown. Since its drug repurposing as an antiviral agent is underway at higher doses than those for antiparasitic, we evaluated the cardiovascular safety pharmacology of ivermectin using isoflurane-anesthetized beagle dogs (n=4). Ivermectin in doses of 0.1 followed by 1 mg/kg was intravenously infused over 10 min with an interval of 20 min, attaining peak plasma concentrations of 0.94 ± 0.04 and 8.82 ± 1.25 μg/mL, which were 29-31 and 276-288 times higher than those observed after its antiparasitic oral dose of 12 mg/body, respectively. The latter peak concentration was > 2 times greater than those inhibiting proliferation of dengue virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hepatitis B virus in vitro. Ivermectin decreased heart rate without altering mean blood pressure, suggesting that ivermectin does not cause hypotension or tachycardia directly. Ivermectin hardly altered atrioventricular nodal or intraventricular conduction, indicating a lack of inhibitory action on Ca2+ or Na+ channel in vivo. Ivermectin prolonged QT interval/QTcV in a dose-related manner and tended to slow the repolarization speed in a reverse frequency-dependent manner, supporting previously described its IKr inhibition, which would explain Tpeak-Tend prolongation and heart-rate reduction in this study. Meanwhile, ivermectin did not significantly prolong J-Tpeakc or terminal repolarization period, indicating torsadogenic potential of ivermectin leading to the onset of cardiopulmonary arrest would be small. Thus, ivermectin has a broad range of cardiovascular safety profiles, which will help facilitate its drug repurposing.

著者

Masayo Hirao-Suzuki Shuso Takeda Takayuki Koga Masufumi Takiguchi Akihisa Toda

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.45, no.4, pp.227-236, 2020 (Released:2020-04-01)

参考文献数

38

被引用文献数

1 15

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A growing body of experimental evidence strongly suggests that cannabidiolic acid (CBDA), a major component of the fiber-type cannabis plant, exerts a variety of biological activities. We have reported that CBDA can abrogate cyclooxygenase-2 (COX-2) expression and its enzymatic activity. It is established that aberrant expression of COX-2 correlates with the degree of malignancy in breast cancer. Although the reduction of COX-2 expression by CBDA offers an attractive medicinal application, the molecular mechanisms underlying these effects have not fully been established. It has been reported that COX-2 expression is positively controlled by peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in some cancerous cells, although there is “no” modulatory element for PPARβ/δ on the COX-2 promoter. No previous studies have examined whether an interaction between PPARβ/δ-mediated signaling and COX-2 expression exists in MDA-MB-231 cells. We confirmed, for the first time, that COX-2 expression is positively modulated by PPARβ/δ-mediated signaling in MDA-MB-231 cells. CBDA inhibits PPARβ/δ-mediated transcriptional activation stimulated by the PPARβ/δ-specific agonist, GW501516. Furthermore, the disappearance of cellular actin stress fibers, a hallmark of PPARβ/δ and COX-2 pathway activation, as evoked by the GW501516, was effectively reversed by CBDA. Activator protein-1 (AP-1)-driven transcriptional activity directly involved in the regulation of COX-2 was abrogated by the PPARβ/δ-specific inverse agonists (GSK0660/ST-247). Thus, it is implicated that there is positive interaction between PPARβ/δ and AP-1 in regulation of COX-2. These data support the concept that CBDA is a functional down-regulator of COX-2 through the abrogation of PPARβ/δ-related signaling, at least in part, in MDA-MB-231 cells.

著者

West Brett J. Su Chen X. C. Jarakae Jensen

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.34, no.5, pp.581-585, 2009-10-01 (Released:2009-10-01)

参考文献数

15

被引用文献数

24 31

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Morinda citrifolia (noni) fruit juice has been approved as a safe food in many nations. A few cases of hepatitis in people who had been drinking noni juice have been reported, even though no causal link could be established between the liver injury and ingestion of the juice. To more fully evaluate the hepatotoxic potential of noni fruit juice, in vitro hepatotoxicity tests were conducted in human liver cells, HepG2 cell line. A subchronic oral toxicity test of noni fruit was also performed in Sprague-Dawley (SD) rats to provide benchmark data for understanding the safety of noni juice, without the potential confounding variables associated with many commercial noni juice products. Freeze-dried filtered noni fruit puree did not decrease HepG2 cell viability or induce neutral lipid accumulation and phospholipidosis. There were no histopathological changes or evidence of dose-responses in hematological and clinical chemistry measurements, including liver function tests. The no-observed-adverse-effect level (NOAEL) for freeze-dried noni fruit puree is greater than 6.86 g/kg body weight, equivalent to approximately 90 ml of noni fruit juice/kg. These findings corroborate previous conclusions that consumption of noni fruit juice is unlikely to induce adverse liver effects.

著者

Galen Guo Emmanuel Yumvihoze Alexandre J. Poulain Hing Man Chan

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.43, no.12, pp.717-725, 2018 (Released:2018-12-04)

参考文献数

45

被引用文献数

22

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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. We used stable Hg isotope tracers to track MMHg production and degradation and characterized the microbiota using high throughput sequencing of the 16S rRNA gene. We show that the magnitude of MMHg degradation is individual dependent and rapidly responds to changes in nutrient amendments, leading to complete degradation of the MMHg present. Although the mechanism involved remains unknown, it does not appear to involve the well-known mer operon. Our data are the first to show a nutrient dependency on the ability of the simulated human gut microbiota to demethylate MMHg. This work provides much-needed insights into individual variations in Hg absorption and potential toxicity.

著者

Natsumi Seki Masahiro Akiyama Hiroto Yamakawa Koji Hase Yoshito Kumagai Yun-Gi Kim

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.46, no.2, pp.91-97, 2021 (Released:2021-02-02)

参考文献数

29

被引用文献数

5 12

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Methylmercury (MeHg), an environmental electrophile, binds covalently to the cysteine residues of proteins in organs, altering protein function and causing cytotoxicity. MeHg has also been shown to alter the composition of gut microbes. The gut microbiota is a complex community, the disturbance of which has been linked to the development of certain diseases. However, the relationship between MeHg and gut bacteria remains poorly understood. In this study, we showed that MeHg binds covalently to gut bacterial proteins via cysteine residues. We examined the effects of MeHg on the growth of selected Lactobacillus species, namely, L. reuteri, L. gasseri, L. casei, and L. acidophilus, that are frequently either positively or negatively correlated with human diseases. The results revealed that MeHg inhibits the growth of Lactobacillus to varying degrees depending on the species. Furthermore, the growth of L. reuteri, which was inhibited by MeHg exposure, was restored by Na2S2 treatment. By comparing mice with and without gut microbiota colonization, we found that gut bacteria contribute to the production of reactive sulfur species such as hydrogen sulfide and hydrogen persulfide in the gut. We also discovered that the removal of gut bacteria accelerated accumulation of mercury in the cerebellum, liver, and lungs of mice subsequent to MeHg exposure. These results accordingly indicate that MeHg is captured and inactivated by the hydrogen sulfide and hydrogen persulfide produced by intestinal microbes, thereby providing evidence for the role played by gut microbiota in reducing MeHg toxicity.

著者

Keerthi S. Guruge Hirokazu Hikono Nobuaki Shimada Kenji Murakami Jun Hasegawa Leo W.Y. Yeung Noriko Yamanaka Nobuyoshi Yamashita

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.34, no.6, pp.687-691, 2009-12-01 (Released:2009-12-01)

参考文献数

14

被引用文献数

51 74

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Recent studies showed that perfluorooctane sulfonate (PFOS) affects the mammalian immune system at levels reportedly found in the general human population. It has been demonstrated that exposure to immunotoxic chemicals may diminish the host resistance of animals to various pathogenic challenges and enhance mortality. Therefore, the current study was carried out to characterize the effect of a 21 day pre-administration of zero, 5, or 25 μg PFOS/kg bw/day in female B6C3F1 mice on host resistance to influenza A virus infection. At the end of PFOS exposure, body/organ weights did not significantly change whereas PFOS distribution in blood plasma, spleen, thymus and lung was dose-dependently increased. PFOS exposure in mice resulted a significant increase in emaciation and mortality in response to influenza A virus. The effective plasma concentrations in female mice were at least several fold lower than reported mean blood PFOS levels from occupationally exposed humans, and fell in the upper range of blood concentrations of PFOS in the normal human population and in a wide range of wild animals. Hence, it should be important to clarify the precise mechanism(s) for excess mortality observed in the high dose group.

著者

中川 静紀 政本 浩二 住吉 博道 原田 浩

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.9, no.1, pp.57-60, 1984-02-25 (Released:2008-02-21)

参考文献数

5

被引用文献数

25 36

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The acute toxicity test of garlic extract was studied in Wistar rats and ddY mice. The LD<50> values of garlic extract by P.O., I.P. and S.C. administration were estimated over 30 ml/kg respectively in male and female of both rodents. In 30 ml/kg of I.P. group, five of ten in male rats and one of ten in female rats were died within a day after administration, however no specific signs due to garlic extract were observed in survivals for 7 days.

著者

Koichi Tomoda Kaoru Kubo Kazuo Hino Yasunori Kondoh Yasue Nishii Noriko Koyama Yoshifumi Yamamoto Masanori Yoshikawa Hiroshi Kimura

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.39, no.2, pp.331-337, 2014-04-01 (Released:2014-03-18)

参考文献数

23

被引用文献数

5 7

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Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

著者

Anna K. Kopec Ryuji Yokokawa Nasir Khan Ikuo Horii James E. Finley Christine P. Bono Carol Donovan Jessica Roy Julie Harney Andrew D. Burdick Bart Jessen Shuyan Lu Mark Collinge Ramin Banan Sadeghian Mazin Derzi Lindsay Tomlinson John E. Burkhardt

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.46, no.3, pp.99-114, 2021 (Released:2021-03-01)

参考文献数

68

被引用文献数

1 18

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Microphysiological systems (MPS) are making advances to provide more standardized and predictive physiologically relevant responses to test articles in living tissues and organ systems. The excitement surrounding the potential of MPS to better predict human responses to medicines and improving clinical translation is overshadowed by their relatively slow adoption by the pharmaceutical industry and regulators. Collaboration between multiorganizational consortia and regulators is necessary to build an understanding of the strengths and limitations of MPS models and closing the current gaps. Here, we review some of the advances in MPS research, focusing on liver, intestine, vascular system, kidney and lung and present examples highlighting the context of use for these systems. For MPS to gain a foothold in drug development, they must have added value over existing approaches. Ideally, the application of MPS will augment in vivo studies and reduce the use of animals via tiered screening with less reliance on exploratory toxicology studies to screen compounds. Because MPS support multiple cell types (e.g. primary or stem-cell derived cells) and organ systems, identifying when MPS are more appropriate than simple 2D in vitro models for understanding physiological responses to test articles is necessary. Once identified, MPS models require qualification for that specific context of use and must be reproducible to allow future validation. Ultimately, the challenges of balancing complexity with reproducibility will inform the promise of advancing the MPS field and are critical for realization of the goal to reduce, refine and replace (3Rs) the use of animals in nonclinical research.

著者

Keiichi Itoh Shoji Masumori Daisuke Mukai Hiroyuki Sakakibara Michiko Yasuda Kayoko Shimoi

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.44, no.4, pp.273-282, 2019 (Released:2019-04-03)

参考文献数

46

被引用文献数

3

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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. However, no differences were observed for the other chemicals. In the comet assay, more DNA damage was induced by ENU in the ZT15 than the ZT3 treatment. Furthermore, the plasma erythropoietin (EPO) level, a known effector of MN induction with anti-apoptotic activity mediated by Bcl-xL expression, was higher in the dark than in the light period. EPO did not increase the frequency of MNRETs. However, in the ENU treatment group at ZT3 following EPO injection a significant increase of MNRETs was observed similar to the ZT15 treatment. Higher expression of apoptosis-related genes such as Bcl-xL was induced in bone marrow cells from mice treated with ENU at ZT15 compared with ZT3. From these results, it was speculated that the differences in MN induction in the peripheral blood of mice exposed to monofunctional alkylating agents such as ENU depend on apoptotic or anti-apoptotic conditions related to the circadian rhythms of EPO in bone marrow.

著者

Hiroki Yoshioka Tsunemasa Nonogaki Yasuro Shinohara Masumi Suzui Yurie Mori Gi-Wook Hwang Katsumi Ohtani Nobuhiko Miura

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.43, no.2, pp.129-134, 2018 (Released:2018-02-26)

参考文献数

28

被引用文献数

7

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The aim of the present study is to investigate the “chronotoxicity” of seven metal compounds (Hg, Pb, Ni, Cr, Cu, Zn, or Fe) by assessing how their toxicity varies with circadian periodicity. Male ICR mice were injected with each metal compound intraperitoneally at 6 different time points over the course of a day (zeitgeber time [ZT]: ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22). Mortality was then monitored until 14 days after the injection. Our investigation demonstrated that mice were tolerant against Ni toxicity during dark phase, on the other hand, they were tolerant against Cr toxicity during light phase. The chronotoxicity of Hg and Pb seemed to be biphasic. Further, mice were susceptible to toxicities against Cu and Zn in the time zone during which light and dark were reversed. Interestingly, no significant differences were observed for Fe exposure at any time of the day. Our results propose that the chronotoxicology may provide valuable information regarding the importance of injection timing for not only toxicity evaluation tests but also the reproducibility of animal experiments. Furthermore, our data suggests that chronotoxicology may be an important consideration when evaluating the quality of risk assessments for night shift workers who may be exposed to toxic substances at various times of the day.

著者

Takato Hara Reina Kumagai Tohru Tanaka Tsuyoshi Nakano Tomoya Fujie Yasuyuki Fujiwara Chika Yamamoto Toshiyuki Kaji

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.48, no.12, pp.655-663, 2023 (Released:2023-12-01)

参考文献数

39

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Vascular endothelial cell growth is essential for the repair of intimal injury. Perlecan, a large heparan sulfate proteoglycan, intensifies fibroblast growth factor-2 (FGF-2) signaling as a co-receptor for FGF-2 and its receptor, and promotes the proliferation of vascular endothelial cells. Previously, we reported that 2 µM of lead, a toxic heavy metal, downregulated perlecan core protein expression and then suppressed the growth of vascular endothelial cells. However, since the mechanisms involved in the repression of perlecan by lead remains unclear, we analyzed its detailed signaling pathway using cultured bovine aortic endothelial cells. Our findings indicate that 2 µM of lead inhibited protein tyrosine phosphatase (PTP) activity and induced cyclooxygenase-2 (COX-2) via phosphorylation of the epidermal growth factor receptor (EGFR) and its downstream extracellular signal-regulated kinases (ERK1/2). In addition, among the prostanoids regulated by COX-2, prostaglandin I2 (PGI2) specifically contributes to the downregulation of perlecan expression by lead. This study revealed an intracellular pathway—the EGFR-ERK1/2-COX-2-PGI2 pathway activated by inhibition of PTP by lead—as a pathway that downregulates endothelial perlecan synthesis. The pathway is suggested to serve as a mechanism for the repression of perlecan expression, which leads to a delay in cell proliferation by lead.

著者

Hirokatsu Saito Kentaro Tanemura Yusuke Furukawa Takahiro Sasaki Jun Kanno Satoshi Kitajima

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.48, no.4, pp.203-210, 2023 (Released:2023-04-03)

参考文献数

32

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Acetamiprid (ACE), a neonicotinoid chemical, is widely used as a pesticide due to its rapid insecticidal activity. Although neonicotinoids exert very low toxicity in mammals, the effects of early exposure to neonicotinoids on the adult central nervous system are poorly understood. This study investigated the effects of ACE exposure in early life on brain function in adult mice. We exposed male C57BL/6N mice to ACE (10 mg/kg) orally when they were two (postnatal lactation) or 11 weeks old (adult). We examined the effects of ACE on the central nervous system using the mouse behavioral test battery, consisting of the open field test, light/dark transition test, elevated plus-maze test, contextual/cued fear conditioning test, and pre-pulse inhibition test at 12–13 weeks old. In the mouse behavioral test battery, learning memory abnormalities were detected in the mature treatment group. In addition, learning memory and emotional abnormalities were detected in the postnatal lactation treatment group. These results suggest that the behavioral effects of postnatal lactation treatment with ACE were qualitatively different from the behavioral abnormalities in the mature treatment group.

著者

Toshi WATANABE

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.20, no.2, pp.135-142, 1995-05-25 (Released:2008-02-21)

参考文献数

8

被引用文献数

8 13

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Alkaline ionized water (AKW) produced by electrolysis was given to gestational and lactational rats, and its effect on dams, growth of fetuses and offsprings were investigated. The results showed that the intake of food and water in dams increased significantly when AKW was given from the latter half of the gestation period and from the former half of the lactation period. Body weight of the offsprings in the test group, both males and females, increased significantly from the latter half of the lactation period. During the lactation period and after weaning, the offsprings in the test group showed significantly hastened appearance of abdominal hair, eruption of upper incisors, opening of eyelids and other postnatal morphological developments both in males and females, as well as earlier separation of auricle and descent of testes in males compared with the control was noted. As mentioned above, it was suggested from the observations conducted that the AKW has substantial biological effects on postnatal growth, since intake of food and water and body weight of the offsprings increased and postnatal morphological development was also accelerated.

著者

Yuto Ishibashi Shingo Kimura Ikuro Suzuki

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.47, no.10, pp.429-437, 2022 (Released:2022-10-01)

参考文献数

28

被引用文献数

1

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Antibiotic-associated encephalopathy (AAE) is a central nervous system disorder caused by antibiotics administration and classified into three types based on clinical symptoms. Type 1 AAE causes seizures and myoclonus, type 2 causes psychiatric symptoms, and type 3 is characterized by cerebellar ataxia. In this study, we investigated whether the electrical activity of in vitro human iPSC-derived neurons to antibiotics could be classified based on the 3 types of AAEs classified by clinical symptoms. Glutamatergic, GABAergic neurons and astrocytes differentiated from human iPS cells were seeded on micro-electrode array (MEA). The cumulative administration of 13 different antimicrobials detected changes in neural activity that differed according to AAE type. Next, we classified the antimicrobials by principal component analysis (PCA) and confirmed the AAE type of each agent. We found that Types 1–3 AAE agents were distributed separately. The classification of antibiotics depending on electrophysiological response characteristics was consistent with the clinical practice classification of AAEs. In conclusion, the combination of electrophysiological responses of human iPS cell-derived neural networks measured by MEA plus multivariate analysis methods will effectively detect and classify antibiotics developmental risks.