The Journal of toxicological sciences最新文献_第2页

A pilot study for construction of a new cadmium-sensing yeast strain carrying a reporter plasmid with the JLP1 promoter. 一种携带JLP1启动子的报告质粒的镉敏感酵母菌株的构建的初步研究。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.103

Sayoko Ito‐Harashima, Y. Mizutani, Motoshi Nishimura, Hyo Jeong Kim, Y. Kim, Hyun Soo Kim, Ji Hye Bae, Preeyaporn Koedrith, M. Kawanishi, Y. Seo, T. Yagi

引用次数: 3

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology. 信息时代数据密集型药物开发:系统生物学/药理学/毒理学的应用。

The Journal of toxicological sciences Pub Date : 2016-12-20 DOI: 10.2131/jts.41.SP15

N. Kiyosawa, S. Manabe

{"title":"Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.","authors":"N. Kiyosawa, S. Manabe","doi":"10.2131/jts.41.SP15","DOIUrl":"https://doi.org/10.2131/jts.41.SP15","url":null,"abstract":"Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130437797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Differential toxicity between perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). 全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)的毒性差异。

The Journal of toxicological sciences Pub Date : 2016-12-20 DOI: 10.2131/jts.41.SP27

S. Tsuda

{"title":"Differential toxicity between perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA).","authors":"S. Tsuda","doi":"10.2131/jts.41.SP27","DOIUrl":"https://doi.org/10.2131/jts.41.SP27","url":null,"abstract":"Perfluoroalkyl substances (PFASs) are persistent environmental contaminants. Perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) are representatives of PFASs. Recently, the U.S. Environmental Protection Agency (US EPA) set the health advisory level as 70 parts per trillion for lifetime exposure to PFOS and PFOA from drinking water, based on the EPA's 2016 Health Effects Support Documents. Then, a monograph on PFOA was made available online by the International Agency for Research on Cancer, where the agency classified PFOA as \"possibly carcinogenic to humans\" (Group 2B). The distinction between PFOS and PFOA, however, may not be easily understood from the above documents. This paper discussed differential toxicity between PFOS and PFOA focusing on neurotoxicity, developmental toxicity and carcinogenicity, mainly based on these documents. The conclusions are as follows: Further mechanistic studies may be necessary for ultrasonic-induced PFOS-specific neurotoxicity. To support the hypothesis for PFOS-specific neonatal death that PFOS interacts directly with components of natural lung surfactant, in vivo studies to relate the physicochemical effects to lung collapse may be required. PFOA-induced DNA damage secondary to oxidative stress may develop to mutagenicity under the condition where PFOA-induced apoptosis is not sufficient to remove the damaged cells. A study to find whether PFOA induces apoptosis in normal human cells may contribute to assessment of human carcinogenicity. Studies for new targets such as hepatocyte nuclear factor 4α (HNF4α) may help clarify the underlying mechanism for PFOA-induced carcinogenicity.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114334748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 55

Chemical toxicology of reactive species in the atmosphere: two decades of progress in an electron acceptor and an electrophile. 大气中活性物质的化学毒理学:电子受体和亲电试剂的二十年研究进展。

The Journal of toxicological sciences Pub Date : 2016-12-20 DOI: 10.2131/jts.41.SP37

Y. Kumagai, Y. Abiko, Nho Luong Cong

引用次数: 5

History and development of The Journal of Toxicological Sciences. 《毒理学杂志》的历史和发展。

The Journal of toxicological sciences Pub Date : 2016-12-20 DOI: 10.2131/jts.41.SP11

A. Naganuma

引用次数: 0

Endoplasmic reticulum stress is involved in 2,4-dichlorophenol-induced hepatotoxicity. 内质网应激参与2,4-二氯酚诱导的肝毒性。

The Journal of toxicological sciences Pub Date : 2016-12-01 DOI: 10.2131/JTS.41.745

Jianbo Fu, Xiaoning Zhang, Peng Chen, Yingmei Zhang

{"title":"Endoplasmic reticulum stress is involved in 2,4-dichlorophenol-induced hepatotoxicity.","authors":"Jianbo Fu, Xiaoning Zhang, Peng Chen, Yingmei Zhang","doi":"10.2131/JTS.41.745","DOIUrl":"https://doi.org/10.2131/JTS.41.745","url":null,"abstract":"2,4-Dichlorophenol (2,4-DCP) is an environmental pollutant exhibiting a wide spectrum of toxic effects. We investigated the toxic effects and potential mechanisms underlying 2,4-DCP-induced hepatotoxicity. In vitro, 2,4-DCP caused hepatotoxicity manifested by a decrease in cell viability and inhibition of colony formation. Bip and CHOP expression was up-regulated at the mRNA and protein levels. Moreover, 2,4-DCP induced eIF2α phosphorylation and Xbp1 mRNA splicing, indicating that endoplasmic reticulum (ER) stress was activated after exposure of HL7702 cells to 2,4-DCP for 12 hr. Furthermore, the mitochondrial membrane potential collapsed and apoptosis was triggered after exposure to 2,4-DCP for 24 hr. In vivo, 2,4-DCP caused histological changes in the liver, and dramatically elevated the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels of mice. ER stress was also triggered in the liver of mice on days 1 and 3. The ER stress inhibitor TUDCA could partly relieve the liver damage, as indicated by the restoration of serum ALT and AST levels. Taken together, our results demonstrated that ER stress may serve as an early warning mechanism against 2,4-DCP-induced hepatotoxicity, and severe ER stress may lead to apoptosis.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132674115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator. 醌通过增加芳烃受体与芳烃受体核转运子的相互作用诱导HepG2细胞的细胞色素P450 1A1。

The Journal of toxicological sciences Pub Date : 2016-12-01 DOI: 10.2131/JTS.41.775

Y. Abiko, Fang Lin, Hsinyu Lee, A. Puga, Y. Kumagai

引用次数: 9

A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice. 组成型雄甾受体(CAR)在伊马唑利小鼠肝肿瘤发生中的重要作用。

The Journal of toxicological sciences Pub Date : 2016-12-01 DOI: 10.2131/JTS.41.801

K. Tamura, Kaoru Inoue, Miwa Takahashi, S. Matsuo, Y. Kodama, Midori Yoshida

{"title":"A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice.","authors":"K. Tamura, Kaoru Inoue, Miwa Takahashi, S. Matsuo, Y. Kodama, Midori Yoshida","doi":"10.2131/JTS.41.801","DOIUrl":"https://doi.org/10.2131/JTS.41.801","url":null,"abstract":"To clarify the major pathway of liver tumor development induced by imazalil (IMA), an imidazole fungicide, male constitutive androstane receptor (CAR)-knockout (CARKO) and wild-type (WT) mice were treated with IMA at 500 ppm in the diet up to 27 weeks after initiation by diethylnitrosamine. After 27 weeks of treatment, neither altered foci nor adenomas were significantly increased in CARKO mice, whereas both eosinophilic altered foci and adenomas were increased in WT mice. After 4 or 13 weeks of IMA treatment, liver hypertrophy was observed at the tumor-inducible dose without differences among genotypes or durations. Analysis of hepatic drug metabolite enzymes, performed after administration of multiple doses during a 1-week period, indicated that pregnane X receptor might be involved in liver hypertrophy because IMA markedly elevated Cyp3a11 and Cyp2b10 expression levels in a dose-dependent manner in both genotypes. Our results demonstrated that the CAR pathway was the main mechanism of liver tumor development induced by IMA. The carcinogenic pathway was different from that of liver hypertrophy.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121959149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes. 三氟虫罗宾通过线粒体损伤诱导人皮肤角质形成细胞自噬。

The Journal of toxicological sciences Pub Date : 2016-12-01 DOI: 10.2131/JTS.41.731

Yoonjeong Jang, Ji-eun Kim, Sang-Hee Jeong, M. Paik, Jun Sung Kim, M. Cho

{"title":"Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes.","authors":"Yoonjeong Jang, Ji-eun Kim, Sang-Hee Jeong, M. Paik, Jun Sung Kim, M. Cho","doi":"10.2131/JTS.41.731","DOIUrl":"https://doi.org/10.2131/JTS.41.731","url":null,"abstract":"Trifloxystrobin is a strobilurin class fungicide, the mode of action of which is to block the mitochondrial electron transport chain and inhibit energy production in fungi. Although adverse effects have been reported by occupational or environmental exposure of fungicides, the pathophysiological mechanism in human cells remains poorly understood. In the present study, we investigated the impact of trifloxystrobin on exposed skin at the cellular organelle level using HaCaT, the human skin keratinocyte cell line. Cells were treated with trifloxystrobin for 48 hr and trifloxystrobin showed detrimental effects on mitochondria evidenced by altered mitochondrial membrane potential and morphology. To identify autophagic degradation of the damaged mitochondria, confocal imaging and Western blotting were performed. Trifloxystrobin induced autophagy-related proteins in HaCaT cells. The mitochondrial reactive oxygen species scavenger mitoTEMPO was applied to further explore the mechanism of trifloxystrobin-mediated mitophagy in human skin cells. PINK1 and Parkin were overexpressed by trifloxystrobin, and mitoTEMPO alleviated the effects on mitophagy induction. Taken together, our findings indicated that mitochondrial damage and mitophagy may play a role in trifloxystrobin-induced toxicity in human keratinocytes and this could be suggested as a mechanism of cutaneous diseases developed by exposure.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114371345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Clinical characteristics of patients who overdose on multiple psychotropic drugs in Tokyo. 东京地区多种精神药物过量患者的临床特征。

The Journal of toxicological sciences Pub Date : 2016-12-01 DOI: 10.2131/JTS.41.765

S. Hori, K. Kinoshita

{"title":"Clinical characteristics of patients who overdose on multiple psychotropic drugs in Tokyo.","authors":"S. Hori, K. Kinoshita","doi":"10.2131/JTS.41.765","DOIUrl":"https://doi.org/10.2131/JTS.41.765","url":null,"abstract":"OBJECTIVE\u0000The 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.\u0000\u0000\u0000METHODS\u0000Patients 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.\u0000\u0000\u0000RESULTS\u0000Among 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.\u0000\u0000\u0000CONCLUSIONS\u0000Patients 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.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122384169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11