著者
Sugiyama Hideo Terada Hiroshi Isomura Kimio IIJIMA Ikuyo KOBAYASHI Jun KITAMURA Kiyoshi
出版者
日本毒性学会
雑誌
Journal of toxicological sciences (ISSN:03881350)
巻号頁・発行日
vol.34, no.4, pp.417-425, 2009-08-01
参考文献数
24
被引用文献数
2 15

The isotope <sup>210</sup>Po was suspected of being involved in the death of a former Russian intelligence agent in 2006 in the UK. Although human exposure to this natural radionuclide in foods is estimated to be high, few studies are available. UNSCEAR Report 2000 does not contain data on <sup>210</sup>Po concentrations of foodstuffs in Japan. We analyzed samples of the everyday Japanese diet cooked with foodstuffs purchased at supermarkets in 7 major domestic cities in 2007-2008. <sup>210</sup>Po was quantified by alpha spectrometry and natural radionuclides such as <sup>40</sup>K by gamma spectrometry. The daily intake and committed effective dose of <sup>210</sup>Po, <sup>40</sup>K, and other natural radionuclides for Japanese adults were calculated. Daily intake was 0.34-1.84 (mean &plusmn; σ : 0.66 &plusmn; 0.53) and 68.5-94.2 (81.5 &plusmn; 8.5) Bq/d and the committed effective dose was 0.15-0.81 (0.29 &plusmn; 0.24) and 0.16-0.21 (0.18 &plusmn; 0.02) mSv for <sup>210</sup>Po and <sup>40</sup>K, respectively, comprising a high percentage of the total exposure. The total of the mean committed effective dose for the two nuclides (0.47 mSv) was higher than the annual effective dose from ingestion of foods reported by UNSCEAR 2000 (0.29 mSv). The mean committed effective dose of <sup>40</sup>K in the 7 major Japanese cities was comparable to the global average (0.17 mSv). The dietary exposure of Japanese adults can be characterized by a higher <sup>210</sup>Po contribution than in other countries. Of the total daily dietary <sup>210</sup>Po exposure (13 food categories excluding water) for adults in Yokohama, about 70% was from fish/shellfish and 20% from vegetables/mushrooms/seaweeds, reflecting preferences of Japanese to eat a considerable amount of fish/shellfish containing high <sup>210</sup>Po concentrations.
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 8 5

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
Jeffrey C. Raber Sytze Elzinga Charles Kaplan
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.40, no.6, pp.797-803, 2015-12-01 (Released:2015-11-10)
参考文献数
9
被引用文献数
6 95

Cannabis concentrates are gaining rapid popularity in the California medical cannabis market. These extracts are increasingly being consumed via a new inhalation method called ‘dabbing’. The act of consuming one dose is colloquially referred to as “doing a dab”. This paper investigates cannabinoid transfer efficiency, chemical composition and contamination of concentrated cannabis extracts used for dabbing. The studied concentrates represent material available in the California medical cannabis market. Fifty seven (57) concentrate samples were screened for cannabinoid content and the presence of residual solvents or pesticides. Considerable residual solvent and pesticide contamination were found in these concentrates. Over 80% of the concentrate samples were contaminated in some form. THC max concentrations ranged from 23.7% to 75.9% with the exception of one outlier containing 2.7% THC and 47.7% CBD. Up to 40% of the theoretically available THC could be captured in the vapor stream of a dab during inhalation experiments. Dabbing offers immediate physiological relief to patients in need but may also be more prone to abuse by recreational users seeking a more rapid and intense physiological effect.
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
16 29

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
Kosuke Kawamoto Itaru Sato Midori Yoshida Shuji Tsuda
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.35, no.6, pp.929-933, 2010-12-01 (Released:2010-12-01)
参考文献数
16

Several appliance manufacturers have recently released new type air purifiers that can disinfect bacteria, fungi and viruses by diffusing reactive oxygen species (ROS) into the air. In this study, mice were exposed to the outlet air from each of 3 air purifiers from different manufacturers (A, B, C), and the lung was examined for DNA damage, lipid peroxidation and histopathology to confirm the safety of these air purifiers. Neither abnormal behavior during exposure nor gross abnormality at necropsy was observed. No histopathological changes were also observed in the lung. However, significant increase of DNA damage was detected by the comet assay in the lung immediately after the direct exposure for 48 hr to models A and B, and for 16 hr to model B. As for model B, DNA migration was also increased by 2 hr exposure in a 1 m3 plastic chamber but not by 48 hr exposure in a room (12.6 m3). Model C did not cause DNA damage. Lipid peroxidation and 8-hydroxy deoxyguanosine (8-OH-dG) was not increased under the conditions DNA damage was detected by the comet assay. The present results revealed that some models of air purifiers that diffuse ROS potentially cause DNA damage in the lung although the mechanism was left unsolved.
著者
Masahiko Yamaguchi Daisuke Araki Takeshi Kanamori Yasuko Okiyama Hirokazu Seto Masaki Uda Masahito Usami Yutaka Yamamoto Takuji Masunaga Hitoshi Sasa
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.42, no.6, pp.797-814, 2017-12-01 (Released:2017-11-16)
参考文献数
15
被引用文献数
6

Safety assessments of cosmetics are carried out by identifying possible harmful effects of substances in cosmetic products and assessing the exposure to products containing these substances. The present study provided data on the amounts of cosmetic products consumed in Japan to enhance and complement the existing data from Europe and the United States, i.e., the West. The outcomes of this study increase the accuracy of exposure assessments and enable more sophisticated risk assessment as a part of the safety assessment of cosmetic products. Actual amounts of products applied were calculated by determining the difference in the weight of products before and after use by approximately 300 subjects. The results of the study of skincare products revealed that in comparison with the West, large amounts of lotions and emulsions were applied, whereas lower amounts of cream and essence were applied in Japan. In the study of sunscreen products, actual measured values during outdoor leisure use were obtained, and these were lower than the values from the West. The study of the use of facial mask packs yielded data on typical Japanese sheet-type impregnated masks and revealed that high amounts were applied. Furthermore, data were obtained on cleansing foams, makeup removers and makeup products. The data from the present study enhance and complement existing information and will facilitate more sophisticated risk assessments. The present results should be extremely useful in safety assessments of newly developed cosmetic products and to regulatory authorities in Japan and around the world.
著者
Akifumi Eguchi Hidenobu Miyaso Chisato Mori
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.41, no.5, pp.667-675, 2016-10-01 (Released:2016-09-24)
参考文献数
52
被引用文献数
7

The toxicity of decabromodiphenyl ether (BDE-209) has been reported in several studies. However, there is not much known about the toxicological biomarkers that characterize BDE-209 exposure. In this study, we subcutaneously exposed mice to 0.025 mg/kg/day BDE-209 on postnatal days 1‑5 and sacrificed the animals at 12 weeks of age (day 84). Flow injection analysis and hydrophilic interaction chromatography-triple quadrupole mass spectrometry were used to determine the serum metabolomes of these mice in order to characterize the effects of BDE-209 exposure. Data analysis showed a good separation between control and exposed mice (R2 = 0.953, Q2 = 0.728, and ANOVA of the cross‑validated residuals (CV‑ANOVA): P‑value = 0.0317) and 54 metabolites were identified as altered in the exposed animals. These were selected using variable importance (VIP) and loadings scaled by a correlation coefficient criteria and orthogonal partial least squares discriminant analysis (OPLS‑DA). BDE‑209‑exposed mice showed lower levels of long-chain acylcarnitines and citrate cycle-related metabolites, and higher levels of some amino acids, long-chain phospholipids, and short-chain acylcarnitines. The disruption of fatty acid, carbohydrate, and amino acid metabolism observed in the serum metabolome might be related to the previously observed impaired spermatogenesis in mice with early postnatal exposure to a low dose of BDE-209.
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 2

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
Hyo Jin Kang Young Bin Hong Yong Weon Yi Chi-Heum Cho Antai Wang Insoo Bae
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.38, no.3, pp.355-361, 2013-06-01 (Released:2013-05-11)
参考文献数
29
被引用文献数
6 9

The risk factors for breast cancer, the most common female malignant cancer, include environmental factors such as radiation, tobacco, a high-fat diet, and xenoestrogens as well as hormones. In addition, BRCA1 and BRCA2 are the most well-known genetic factors that increase risk for breast cancer. Coincidence of those environmental and genetic factors might augment the risk of tumorigenesis of breast. To verify this hypothesis, we briefly evaluated the carcinogenic potency of various environmental factors in the absence or presence of BRCA1 as a genetic factor in a normal mammary epithelial cell line, MCF10A. Many environmental factors tested increased cellular ROS level in the absence of other insult. In addition, TCDD, DMBA, 3MC, and BPA enhanced the BaP-induced ROS production. BRCA1 knockdown (BRCA1-KD) cells by siRNA significantly induced cellular accumulation of ROS compared to control cells. In this setting, the addition of paraquat, TCDD, DMBA, 2OHE2 or 4OHE2 significantly augmented ROS generation in BRCA1-KD MCF10A cells. Measurements of BaP-DNA adduct formation as a marker of DNA damage also revealed that BRCA1 deficiency leads increased DNA damage. In addition, TCDD and DMBA significantly increased BaP-DNA adduct formation in the absence of BRCA1. These results imply that elevated level of ROS is correlated with increase of DNA damage in BRCA1 defective cells. Taken together, our study suggests that several environmental factors might increase the risk of tumorigenesis in BRCA1 defective breast epithelial cells.
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
8

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
Nozomi Asaoka Hiroyuki Kawai Naoya Nishitani Haruko Kinoshita Norihiro Shibui Kazuki Nagayasu Hisashi Shirakawa Shuji Kaneko
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.41, no.6, pp.813-816, 2016-12-01 (Released:2016-11-16)
参考文献数
16
被引用文献数
11

N-[[1-(5-fluoropentyl)-1H-indazol-3-yl]carbonyl]-3-methyl-D-valine methyl ester (5F-ADB) is one of the most potent synthetic cannabinoids and elicits severe psychotic symptoms in humans, sometimes causing death. To investigate the neuronal mechanisms underlying its toxicity, we examined the effects of 5F-ADB on midbrain dopaminergic and serotonergic systems, which modulate various basic brain functions such as those in reward-related behavior. 5F-ADB-induced changes in spontaneous firing activity of dopaminergic and serotonergic neurons were recorded by ex vivo electrophysiological techniques. In dopaminergic neurons, 5F-ADB (1 μM) significantly increased the spontaneous firing rate, while 5F-ADB failed to activate dopaminergic neurons in the presence of the CB1 antagonist AM251 (1 μM). However, the same concentration of 5F-ADB did not affect serotonergic-neuron activity. These results suggest that 5F-ADB activates local CB1 receptors and potentiates midbrain dopaminergic systems with no direct effects on midbrain serotonergic systems.
著者
Asuka Kaizaki Sachiko Tanaka Satoshi Numazawa
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.39, no.1, pp.1-6, 2014-02-01 (Released:2014-01-10)
参考文献数
23
被引用文献数
19 46

1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) is a new designer drug of the cathinone type. People who have taken drugs containing α-PVP or other synthetic cathinone reportedly lose consciousness, develop difficulty breathing, and at worst case, die. However, the mechanism underlying α-PVP-induced neurotoxicity is unknown. The objective of the present study was to investigate the effect of α-PVP on the central nervous system (CNS) and compare its neurotoxicity with that of methamphetamine (METH) in mice. Balb/c male mice (8 weeks old) were orally administered α-PVP (25 mg/kg) or METH (5 mg/kg). α-PVP induced a significant increase in locomotor activity, which occurred earlier than locomotor activity induced by METH. This increase was inhibited by the D1 receptor antagonist SCH23990 (50 µg/kg, i.p.) and the D2 receptor antagonist sulpiride (50 mg/kg, i.m.). The extracellular concentration of dopamine (DA) in the striatum, determined by in vivo microdialysis increased immediately after α-PVP administration. These results suggest that α-PVP stimulates DA release, causing an increase in locomotor activity, and that this stimulatory effect of α-PVP on CNS is mediated, at least in part, by the D1 and D2 receptors.
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
6 8

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
Hideo Sugiyama Hiroshi Terada Kimio Isomura Ikuyo Iijima Jun Kobayashi Kiyoshi Kitamura
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.34, no.4, pp.417-425, 2009-08-01 (Released:2009-08-01)
参考文献数
24
被引用文献数
9 15

The isotope 210Po was suspected of being involved in the death of a former Russian intelligence agent in 2006 in the UK. Although human exposure to this natural radionuclide in foods is estimated to be high, few studies are available. UNSCEAR Report 2000 does not contain data on 210Po concentrations of foodstuffs in Japan. We analyzed samples of the everyday Japanese diet cooked with foodstuffs purchased at supermarkets in 7 major domestic cities in 2007-2008. 210Po was quantified by alpha spectrometry and natural radionuclides such as 40K by gamma spectrometry. The daily intake and committed effective dose of 210Po, 40K, and other natural radionuclides for Japanese adults were calculated. Daily intake was 0.34-1.84 (mean ± σ : 0.66 ± 0.53) and 68.5-94.2 (81.5 ± 8.5) Bq/d and the committed effective dose was 0.15-0.81 (0.29 ± 0.24) and 0.16-0.21 (0.18 ± 0.02) mSv for 210Po and 40K, respectively, comprising a high percentage of the total exposure. The total of the mean committed effective dose for the two nuclides (0.47 mSv) was higher than the annual effective dose from ingestion of foods reported by UNSCEAR 2000 (0.29 mSv). The mean committed effective dose of 40K in the 7 major Japanese cities was comparable to the global average (0.17 mSv). The dietary exposure of Japanese adults can be characterized by a higher 210Po contribution than in other countries. Of the total daily dietary 210Po exposure (13 food categories excluding water) for adults in Yokohama, about 70% was from fish/shellfish and 20% from vegetables/mushrooms/seaweeds, reflecting preferences of Japanese to eat a considerable amount of fish/shellfish containing high 210Po concentrations.
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

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
4

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
Satoshi Hori Kosaku Kinoshita
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.41, no.6, pp.765-773, 2016-12-01 (Released:2016-11-16)
参考文献数
12
被引用文献数
7

OBJECTIVE: The purpose of this study was to identify the clinical aspects leading to overdose of multiple psychotropic drugs, in order to determine areas which need attention in the proper treatment of overdose patients. METHODS: Patients who were treated for overdose of psychotropic drugs at our emergency and critical center over two years were targeted. The clinical data was gathered from the medical records and database of all patients, including age, gender, vital signs, and laboratory data, drugs, and medical complications during hospital stay. In addition primary patient care at the emergency department was examined. RESULTS: Among the 277 patients treated during this study period, 255 (74.0%) used two or more types of psychotropic drugs. Risk factors associated with endotracheal intubation and aspiration pneumonitis included the use of antipsychotics and/or barbiturates as types of overdose drugs. The mean number of days in the ICU was 3.4 days. Seventy-four patients (26.7%) stayed 4 days or more in the ICU of which 16 patients (5.8%) still had suicidal thoughts. A significantly higher incidence of extended ICU stay or endotracheal intubation and aspiration pneumonitis was observed in the group who overdosed on more than 50 or 60 tablets of psychotropic drugs, respectively. CONCLUSIONS: Patients who ingested an overdose of more than 60 tablets of psychotropic drugs should be considered a high-risk group requiring intensive care with extended ICU stay. In case of including antipsychotics and/or barbiturates, the patient should be observed carefully due to a higher risk of medical complications.
著者
Jonggun Kim Yooheon Park Kyong Sup Yoon J. Marshall Clark Yeonhwa Park
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.38, no.5, pp.655-660, 2013-10-01 (Released:2013-09-11)
参考文献数
46
被引用文献数
4 23

Recently, scientific evidence supports a connection between environmental chemical exposures, which includes insecticides, and development of type 2 diabetes. However, there is limited information about the link between influences of neonicotinoid insecticides and incidence of type 2 diabetes. Thus, the purpose of the study was to determine effects of imidacloprid, a neonicotinoid insecticide, on glucose metabolism. Three different cell models were used; adipocytes (3T3-L1), hepatocytes (HepG2), and myotubes (C2C12). These cells were treated with imidacloprid (0, 10, and 20 μM) for 4-6 days followed by treatment with insulin for 15 min to determine responses. Insulin stimulated glucose uptake was reduced by imidacloprid in all three cell culture models. Treatment with imidacloprid reduced phosphorylation of protein kinase B (AKT), one of the major regulators of insulin signaling, without changing overall AKT expression. Subsequently, imidacloprid reduced phosphorylation of ribosomal S6 kinase (S6K), which is a downstream target of AKT and also a feed-back inhibitor of insulin signaling. These results suggest that imidacloprid could induce insulin resistance by affecting the insulin signaling cascade, particularly up-stream of AKT, in adipocytes, liver, and muscle.
著者
Kent R. Walters Jr. S. Indu Rupassara R.J. Cody Markelz Andrew D.B. Leakey William M. Muir Barry R. Pittendrigh
出版者
日本毒性学会
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.37, no.4, pp.773-790, 2012-08-01 (Released:2012-08-01)
参考文献数
55
被引用文献数
1 8 1

Methamphetamine (MA) appears to produce neurotoxic effects, in part, through disruptions of energy metabolism. A recent study of the whole-body proteome of Drosophila melanogaster showed many changes in energy metabolism-related proteins, leading us to hypothesize that MA toxicity may cause whole-body disruptions of energy metabolism. To test this, we monitored the response of energy reserves and other metabolites to MA-exposure with and without the addition of dietary glucose. We also monitored changes in feeding behavior, locomotor activity and respiration rates associated with MA-exposure to investigate how MA affects energy balance. We observed that glycogen and triglyceride levels decreased dramatically within 48 hr of MA-exposure, indicating a strongly negative caloric balance. Behavioral assays revealed that MA-treated flies decreased food consumption by 60-80% and exhibited a 2-fold increase in locomotion. Caloric expenditure decreased with MA-exposure, apparently due to a compensatory decrease in resting metabolism, showing that anorexia was the primary driver of the negative caloric balance. Additionally, we observed that glucose supplementation of MA-containing diet increased glycogen reserves by 44% at 48 hr, leading to a commensurate increase in survivorship. We conclude that dietary sugar supplementation enhances survivorship by partially compensating for decreased caloric intake resulting from MA-induced anorexia. The observation that MA produces similar behavioral changes in Drosophila and humans, i.e. increased locomotor activity and anorexia, further supports the use of Drosophila as a model organism for the study of the effects of MA.
著者
Yuto Amano Hiroshi Honda Ryusuke Sawada Yuko Nukada Masayuki Yamane Naohiro Ikeda Osamu Morita Yoshihiro Yamanishi
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.3, pp.137-149, 2020 (Released:2020-03-06)
参考文献数
47
被引用文献数
1

In silico models for predicting chemical-induced side effects have become increasingly important for the development of pharmaceuticals and functional food products. However, existing predictive models have difficulty in estimating the mechanisms of side effects in terms of molecular targets or they do not cover the wide range of pharmacological targets. In the present study, we constructed novel in silico models to predict chemical-induced side effects and estimate the underlying mechanisms with high general versatility by integrating the comprehensive prediction of potential chemical-protein interactions (CPIs) with machine learning. First, the potential CPIs were comprehensively estimated by chemometrics based on the known CPI data (1,179,848 interactions involving 3,905 proteins and 824,143 chemicals). Second, the predictive models for 61 side effects in the cardiovascular system (CVS), gastrointestinal system (GIS), and central nervous system (CNS) were constructed by sparsity-induced classifiers based on the known and potential CPI data. The cross validation experiments showed that the proposed CPI-based models had a higher or comparable performance than the traditional chemical structure-based models. Moreover, our enrichment analysis indicated that the highly weighted proteins derived from predictive models could be involved in the corresponding functions of the side effects. For example, in CVS, the carcinogenesis-related pathways (e.g., prostate cancer, PI3K-Akt signal pathway), which were recently reported to be involved in cardiovascular side effects, were enriched. Therefore, our predictive models are biologically valid and would be useful for predicting side effects and novel potential underlying mechanisms of chemical-induced side effects.