The Journal of toxicological sciences最新文献_第7页

Cigarette smoke extract-induced interleukin-6 expression is regulated by phospholipase D1 in human bronchial epithelial cells. 香烟烟雾提取物诱导的白细胞介素-6在支气管上皮细胞中的表达受磷脂酶D1调控。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.77

Jun Bon Koo, Joong-Soo Han

{"title":"Cigarette smoke extract-induced interleukin-6 expression is regulated by phospholipase D1 in human bronchial epithelial cells.","authors":"Jun Bon Koo, Joong-Soo Han","doi":"10.2131/jts.41.77","DOIUrl":"https://doi.org/10.2131/jts.41.77","url":null,"abstract":"Cigarette smoking is known to be associated with various kinds of diseases, including atherosclerotic cardiovascular disease, cancer, and chronic obstructive pulmonary disease (COPD). Many of the diseases associated with cigarette smoking are also associated with changes in interleukin-6 (IL-6) expression. In this study, we investigated the role of phospholipase D1 (PLD1) in IL-6 expression induced by cigarette smoke extract (CSE). Treatment with CSE increased PLD1 and IL-6 expressions in human bronchial epithelial (BEAS-2B) cells. In addition, CSE treatment activated PLC, PKC, and MAPK pathway through the Gi protein-coupled receptor. Pertussis toxin (PTX, Gi protein-coupled receptor inhibitor), PAO (PLC inhibitor), Go6976 (PKC inhibitor) and SB203580 (p38MAPK inhibitor) decreased CSE-induced PLD1 expression. The results show that Gi protein, PLC, PKC, and p38MAPK act as upstream regulators of PLD1 in CSE-treated BEAS-2B cells. Moreover, PLD1 siRNA transfection decreased CSE-induced ATF2 phosphorylation and IL-6 expression. In addition, inhibitors of Gi protein, PLC, PKC, and p38MAPK, and ATF2 siRNA transfection decreased CSE-induced IL-6 expression, suggesting that CSE-induced IL-6 expression is regulated via Gi protein/PLC/PKC/p38MAPK/PLD1/ATF2 pathway. Taken together, the results suggest that PLD1 is an important regulator of IL-6 expression induced by CSE in BEAS-2B cells.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"41 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130662771","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: 16

Safety evaluation of a newly-developed dietary fiber: resistant glucan mixture. 一种新型膳食纤维:抗葡聚糖混合物的安全性评价。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.33

H. Bito, Norihisa Hamaguchi, Hirokazu Hirai, Koichi Ogawa

{"title":"Safety evaluation of a newly-developed dietary fiber: resistant glucan mixture.","authors":"H. Bito, Norihisa Hamaguchi, Hirokazu Hirai, Koichi Ogawa","doi":"10.2131/jts.41.33","DOIUrl":"https://doi.org/10.2131/jts.41.33","url":null,"abstract":"Resistant glucan mixture (RGM), a water-soluble dietary fiber produced by the random polymerization of glucose with activated carbon as a catalyst at a high temperature, has been recently developed by our group. There has been little physiological and safety research into RGM and therefore we now present our research into its safety. A reverse mutation assay indicated that RGM is not mutagenic either with or without metabolic activation. We conducted a 90-day subchronic oral toxicity study in rats. Male and female rats fed either a 3% or 5% w/w RGM diet had no muddy or watery stools, and there was no RGM-related death in any group. Although some parameters in the 3% and 5% w/w groups were significantly different from those in the control group, these changes were not due to any toxicity from RGM. The results indicated that the No Observed Adverse Effect Level (NOAEL) of RGM was 3.3 and 3.9 g/kg body weight (BW) per day in male and female rats, respectively. We then studied the gastrointestinal effects of RGM in healthy adult humans. Gastrointestinal symptoms, such as gurgling sounds, flatus and tenesmus, were mild and transient. In men and women, the maximum no-effect dose for diarrhea was more than 0.9 g RGM /kg BW. The results of our current safety assessment studies suggest that RGM is safe for human consumption.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124194527","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: 5

Molecular identification of poisonous mushrooms using nuclear ITS region and peptide toxins: a retrospective study on fatal cases in Thailand. 利用核ITS区域和肽毒素对毒蘑菇进行分子鉴定:对泰国致命病例的回顾性研究。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.65

S. Parnmen, Sujitra Sikaphan, Siriwan Leudang, Thitiya Boonpratuang, A. Rangsiruji, Khwanruan Naksuwankul

{"title":"Molecular identification of poisonous mushrooms using nuclear ITS region and peptide toxins: a retrospective study on fatal cases in Thailand.","authors":"S. Parnmen, Sujitra Sikaphan, Siriwan Leudang, Thitiya Boonpratuang, A. Rangsiruji, Khwanruan Naksuwankul","doi":"10.2131/jts.41.65","DOIUrl":"https://doi.org/10.2131/jts.41.65","url":null,"abstract":"Cases of mushroom poisoning in Thailand have increased annually. During 2008 to 2014, the cases reported to the National Institute of Health included 57 deaths; at least 15 died after ingestion of amanitas, the most common lethal wild mushrooms inhabited. Hence, the aims of this study were to identify mushroom samples from nine clinically reported cases during the 7-year study period based on nuclear ITS sequence data and diagnose lethal peptide toxins using a reversed phase LC-MS method. Nucleotide similarity was identified using BLAST search of the NCBI database and the Barcode of Life Database (BOLD). Clade characterization was performed by maximum likelihood and Bayesian phylogenetic approaches. Based on BLAST and BOLD reference databases our results yielded high nucleotide similarities of poisonous mushroom samples to A. exitialis and A. fuliginea. Detailed phylogenetic analyses showed that all mushroom samples fall into their current classification. Detection of the peptide toxins revealed the presence of amatoxins and phallotoxins in A. exitialis and A. fuliginea. In addition, toxic α-amanitin was identified in a new provisional species, Amanita sp.1, with the highest toxin quantity. Molecular identification confirmed that the mushrooms ingested by the patients were members of the lethal amanitas in the sections Amanita and Phalloideae. In Thailand, the presence of A. exitialis was reported here for the first time and all three poisonous mushroom species provided new and informative data for clinical studies.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128402547","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: 33

MEIS3 is repressed in A549 lung epithelial cells by deoxynivalenol and the repression contributes to the deleterious effect. MEIS3在A549肺上皮细胞中被脱氧雪腐烯醇抑制，这种抑制有助于产生有害作用。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.25

Takahito Toyotome, Hiroki Takahashi, K. Kamei

引用次数: 2

Development of an in vitro photosensitization test based on changes of cell-surface thiols and amines as biomarkers: the photo-SH/NH₂ test. 基于细胞表面硫醇和胺作为生物标志物的变化的体外光敏试验的发展:光sh /NH₂测试。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.129

Shiho Oeda, Morihiko Hirota, Hayato Nishida, T. Ashikaga, H. Sasa, S. Aiba, Y. Tokura, H. Kouzuki

{"title":"Development of an in vitro photosensitization test based on changes of cell-surface thiols and amines as biomarkers: the photo-SH/NH₂ test.","authors":"Shiho Oeda, Morihiko Hirota, Hayato Nishida, T. Ashikaga, H. Sasa, S. Aiba, Y. Tokura, H. Kouzuki","doi":"10.2131/jts.41.129","DOIUrl":"https://doi.org/10.2131/jts.41.129","url":null,"abstract":"As a part of our studies to develop a cell-based in vitro photosensitization assay, we examined whether changes of cell-surface thiols and amines on human monocytic cell line THP-1 could be used to predict photosensitizing potential of chemicals. First, we identified a suitable ultraviolet A (UV-A) irradiation dose to be 5.0 J/cm(2) by investigating the effect of UV-A on the levels of cell-surface thiols and amines in ketoprofen (KP; a representative photoallergen)-treated THP-1 cells. Next, we confirmed that phenol red, a known photoirritant used as a pH indicator in the culture medium, did not affect the KP-induced changes of cell-surface thiols and amines. Using the criterion of more than 15% change of cell-surface thiols and/or amines in response to UV-A irradiation, 22 of 26 known photosensitizers (15 of 18 photoallergens, 7 of 8 photoirritants) were judged positive. Seven of 7 known non-phototoxins did not alter cell-surface thiols or amines. The accuracy for predicting photosensitizers was 87.9% (sensitivity/specificity; 84.6%/100%), and the accuracy for predicting photoallergens was 69.7% (sensitivity/specificity; 83.3%/53.3%). Our results suggest that changes of cell-surface thiols and/or amines may be useful biomarkers for predicting photosensitization potential, including photoallergenicity, of compounds. We designate this test as the photo-SH/NH2 test.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"41 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130880503","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: 7

Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens. 大鼠反复给药28天后纺锤体检查点功能的破坏。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.91

M. Kimura, S. Mizukami, Yousuke Watanabe, Yasuko Hasegawa-Baba, N. Onda, Toshinori Yoshida, M. Shibutani

{"title":"Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.","authors":"M. Kimura, S. Mizukami, Yousuke Watanabe, Yasuko Hasegawa-Baba, N. Onda, Toshinori Yoshida, M. Shibutani","doi":"10.2131/jts.41.91","DOIUrl":"https://doi.org/10.2131/jts.41.91","url":null,"abstract":"We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116625401","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: 3

shRNA-mediated AMBRA1 knockdown reduces the cisplatin-induced autophagy and sensitizes ovarian cancer cells to cisplatin. shrna介导的AMBRA1敲低可降低顺铂诱导的自噬，使卵巢癌细胞对顺铂敏感。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.45

Xiaoyan Li, Lijuan Zhang, Lili Yu, Wei Wei, Xueyan Lin, Xiaoman Hou, Yongjie Tian

{"title":"shRNA-mediated AMBRA1 knockdown reduces the cisplatin-induced autophagy and sensitizes ovarian cancer cells to cisplatin.","authors":"Xiaoyan Li, Lijuan Zhang, Lili Yu, Wei Wei, Xueyan Lin, Xiaoman Hou, Yongjie Tian","doi":"10.2131/jts.41.45","DOIUrl":"https://doi.org/10.2131/jts.41.45","url":null,"abstract":"Recent research has revealed a role for Ambra1, an autophagy-related gene-related (ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells and cancer cells. However, whether Ambra1 plays an important role in the autophagy pathway in ovarian cancer cells is unknown. In this study, we hypothesized that Ambra1 is an important regulator of autophagy and apoptosis in ovarian cancer cells. We firstly confirmed autophagic activity in ovarian cancer OVCAR-3 cells which were treated with cisplatin by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) localization and the presence of autophagosomes and LC3 protein levels in OVCAR-3 cells. Cell apoptosis and viability were measured by annexin-V and PI staining and MTT assays. We then knocked down Ambra1 expression with transfection with the plasmid expressing the small hairpin RNA (shRNA) targeting AMBRA1, then re-evaluated autophagy in the OVCAR-3 cells subject to cisplatin treatment, and re-determined the sensitivity of OVCAR-3 cells to cisplatin. Results demonstrated that cisplatin treatment induced autophagy in OVCAR-3 cells in association with Ambra1 upregulation in the ovarian cancer cells. When Ambra1 expression was reduced by shRNA, the ovarian cancer cells were more sensitive to cisplatin. In conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis in ovarian cancer cells subject to cisplatin to maintain the balance between autophagy and apoptosis. And the Ambra1-targeting inhibition might be an effective method to sensitize ovarian cancer cells to chemotherapy.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"41 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131233590","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

Upregulations of metallothionein gene expressions and tolerance to heavy metal toxicity by three dimensional cultivation of HepG2 cells on VECELL 3-D inserts. 在VECELL三维插入物上三维培养HepG2细胞，上调金属硫蛋白基因表达及对重金属毒性的耐受。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.147

T. Kubo, Y. Kuroda, S. Horiuchi, Su-ryang Kim, Y. Sekino, S. Ishida

引用次数: 4

Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450. 青霉素类抗生素阿莫西林、氨苄西林和哌拉西林对人肝细胞色素P450药物代谢活性的影响。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.143

T. Niwa, Mari Morimoto, Takako Hirai, Tomomi Hata, Misato Hayashi, Yurie Imagawa

{"title":"Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450.","authors":"T. Niwa, Mari Morimoto, Takako Hirai, Tomomi Hata, Misato Hayashi, Yurie Imagawa","doi":"10.2131/jts.41.143","DOIUrl":"https://doi.org/10.2131/jts.41.143","url":null,"abstract":"The effects of three kinds of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activity of human hepatic cytochrome P450 (P450 or CYP) were investigated. Metabolic activities of P450s expressed in recombinant Escherichia coli at substrate concentrations around the Michaelis constant were compared in the presence or absence of the antibiotics. Amoxicillin, ampicillin, and piperacillin at 0.5 or 1 mM concentrations neither inhibited nor stimulated CYP2C9-mediated tolbutamide methylhydroxylation, CYP2D6-mediated dopamine formation from p-tyramine, or CYP3A4- or CYP3A5-mediated testosterone 6β-hydroxylation. However, amoxicillin and piperacillin inhibited CYP2C8-mediated aminopyrine N-demethylation at 50% inhibitory concentration of 0.83 and 1.14 mM, respectively. These results suggest that piperacillin might inhibit CYP2C8 clinically, although the interactions between these three penicillin-based antibiotics and other drugs that are metabolized by P450s investigated would not be clinically significant.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134467935","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: 24

Protective effects of geniposide against Tripterygium glycosides (TG)-induced liver injury and its mechanisms. 京尼平苷对雷公藤多苷(TG)所致肝损伤的保护作用及其机制。

The Journal of toxicological sciences Pub Date : 2016-02-01 DOI: 10.2131/jts.41.165

Junming Wang, M. Miao, Lingbo Qu, Ying Cui, Yue-yue Zhang

{"title":"Protective effects of geniposide against Tripterygium glycosides (TG)-induced liver injury and its mechanisms.","authors":"Junming Wang, M. Miao, Lingbo Qu, Ying Cui, Yue-yue Zhang","doi":"10.2131/jts.41.165","DOIUrl":"https://doi.org/10.2131/jts.41.165","url":null,"abstract":"Tripterygium glycosides (TG) are commonly used for basic medicine in curing rheumatoid arthritis but with a high incidence of liver injury. Geniposide (GP) has broad and diverse bioactivities, but until now it is still unknown whether GP can protect against TG-induced liver injury. This study, for the first time, observed the possible protection of GP against TG-induced liver injury in mice and its mechanisms underlying. Oral administration of TG (270 mg/kg) induced significant elevation in the levels of serum alanine / aspartate transaminase (ALT/AST), hepatic malondialdehyde (MDA) and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) (all P < 0.01). On the other hand, remarkably decreased biomarkers, including hepatic glutathione (GSH) level, activities of glutathione transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and anti-inflammatory cytokine interleukin (IL)-10, were observed following TG exposure (all P < 0.01). Nevertheless, all of these phenotypes were evidently reversed by pre-administration of GP for 7 continuous days. Further analysis showed that the mRNA expression of hepatic growth factor-beta1 (TGF-β1), one of tissue repair and regeneration cytokines, was enhanced by GP. Taken together, the current research suggests that GP protects against TG-induced liver injury in mice probably involved during attenuating oxidative stress and inflammation, and promoting tissue repair and regeneration.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"99 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124881716","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: 26