The Journal of toxicological sciences最新文献

Dose- and time-dependent systemic adverse reactions of sodium carboxy methyl cellulose after intraperitoneal application in rats. 大鼠腹腔注射羧甲基纤维素钠后的剂量和时间依赖性全身不良反应。

The Journal of toxicological sciences Pub Date : 2020-12-10 DOI: 10.21203/rs.3.rs-122972/v1

Chunguang Fan, L. Hou, Guoxi Che, Yanping Shi, Xiangdong Liu, Li-kui Sun, Wensi Jia, Fuyu Zhu, Zenglin Zhao, Ming Xu, Xiaoxiao Gai, Chenghu Liu

{"title":"Dose- and time-dependent systemic adverse reactions of sodium carboxy methyl cellulose after intraperitoneal application in rats.","authors":"Chunguang Fan, L. Hou, Guoxi Che, Yanping Shi, Xiangdong Liu, Li-kui Sun, Wensi Jia, Fuyu Zhu, Zenglin Zhao, Ming Xu, Xiaoxiao Gai, Chenghu Liu","doi":"10.21203/rs.3.rs-122972/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-122972/v1","url":null,"abstract":"Sodium carboxy methyl cellulose (SCMC) is an important absorbable biomaterial for anti-adhesion and hemostasis medical devices used in the abdominal cavity. However, the systemic toxicity of SCMC following intraperitoneal route has not been revealed sufficiently. Three SCMC solutions with gradient concentrations were intraperitoneally injected into 3 groups of rats with the doses of 50 mg/kg, 320 mg/kg and 2000 mg/kg respectively all at once to observe the dose-dependence of systemic reactions of SCMC and 10 rats (5 rats per sex) of each group were sacrificed 3 days, 7 days, 28 days and 90 days after injection to evaluate the time-dependence of the reactions. A range of adverse effects were shown in rats of the high-dose group which were found varied with time extending and virtually disappeared 90 days after injection. Slight reactions were observed in the medium-dose group while negligible effects were found in the low-dose group. The intraperitoneal application of SCMC can induce reversible systemic adverse effects to rats at the dose higher than 320 mg/kg and it is essential to take both dose- and time-dependent effects into account while designing a systemic toxicity study for absorbable biomaterials.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114870538","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: 2

Selenium uptake through cystine transporter mediated by glutathione conjugation. 谷胱甘肽偶联介导的胱氨酸转运体对硒的摄取。

The Journal of toxicological sciences Pub Date : 2017-04-01 DOI: 10.2131/jts.42.85

T. Tobe, K. Ueda, Akira Aoki, Yoshinori Okamoto, N. Kojima, H. Jinno

{"title":"Selenium uptake through cystine transporter mediated by glutathione conjugation.","authors":"T. Tobe, K. Ueda, Akira Aoki, Yoshinori Okamoto, N. Kojima, H. Jinno","doi":"10.2131/jts.42.85","DOIUrl":"https://doi.org/10.2131/jts.42.85","url":null,"abstract":"Selenium (Se) is an essential trace element and is regarded as a protective agent against cancer. In particular, antioxidant effects of selenoenzymes contribute to cancer prevention. Se can also produce reactive oxygen species and, thereby, exert cancer-selective cytotoxicity. Selenodiglutathione (SDG) is a primary Se metabolite conjugated to two glutathione (GSH) moieties. SDG increases intracellular Se accumulation and is more toxic than selenous acid (H2SeO3), but the mechanisms for importing Se compounds into cells are not fully understood. Here, we propose a novel mechanism for importing Se, in the form of SDG. Cellular intake of Se compounds was assessed based on Se accumulation, as detected by ICP-MS. SDG incorporation was decreased in the presence of thiols (GSH, cysteine or their oxidized forms, GSSG and cystine), whereas H2SeO3 uptake was increased by addition of GSH or cysteine. Cellular SDG uptake was decreased by pretreatment with specific inhibitors against gamma-glutamyl transpeptidase (GGT) or the cystine/glutamate antiporter (system xc-). Furthermore, siRNA against xCT, which is the light chain component of system xc-, significantly decreased SDG incorporation. These data suggest an involvement of SDG in Se incorporation, with SDG processed at the cell surface by GGT, leading to formation of selenodicysteine which, in turn, is likely to be imported via xCT. Because GGT and xCT are highly expressed in cancer cells, these mechanisms mediated by the cystine transporter might underlie the cancer-selective toxicity of Se. In addition, the system described in our study appears to represent a physiological transport mechanism for the essential element Se.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122498432","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: 6

Pharmacological characterization of microminipig as a model to assess the drug-induced cardiovascular responses for non-clinical toxicity and/or safety pharmacology studies. 在非临床毒性和/或安全性药理学研究中，以微型猪为模型评估药物诱导的心血管反应的药理学特征。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.93

H. Yokoyama, Yuji Nakamura, Hiroyuki Saito, Yukitoshi Nagayama, K. Hoshiai, Takeshi Wada, Hiroko Izumi‐Nakaseko, Kentaro Ando, Y. Akie, A. Sugiyama

{"title":"Pharmacological characterization of microminipig as a model to assess the drug-induced cardiovascular responses for non-clinical toxicity and/or safety pharmacology studies.","authors":"H. Yokoyama, Yuji Nakamura, Hiroyuki Saito, Yukitoshi Nagayama, K. Hoshiai, Takeshi Wada, Hiroko Izumi‐Nakaseko, Kentaro Ando, Y. Akie, A. Sugiyama","doi":"10.2131/jts.42.93","DOIUrl":"https://doi.org/10.2131/jts.42.93","url":null,"abstract":"We tried to establish the halothane-anesthetized microminipigs as an alternative animal model for non-clinical toxicity and/or safety pharmacology studies. In order to characterize the halothane-anesthetized microminipigs, we firstly clarified the effects of halothane anesthesia on their cardiovascular system (n = 5). Then, we examined the cardiovascular effects of dl-sotalol in doses of 0.1, 0.3 and 1 mg/kg, i.v. on the halothane-anesthetized microminipigs (n = 6). Induction of the halothane anesthesia by itself prolonged the QT interval as well as QTcF, suggesting that the halothane anesthesia can reduce the cardiac repolarization reserve in microminipigs like in dogs. dl-Sotalol showed more potent negative chronotropic, dromotropic and hypotensive effects together with repolarization delay in microminipigs than in dogs, although each cardiovascular response to dl-sotalol was directionally similar between them, suggesting greater basal sympathetic tone and/or smaller volume of distribution of the drug in microminipigs than in dogs. Analyses of proarrhythmic surrogate markers indicate that Tpeak-Tend and short-term variability of QT interval may be more sensitive to detect the dl-sotalol-induced direct electrophysiological changes in microminipigs than in dogs, but its reverse will be true for J-Tpeakc. Thus, these results may help better understand the drug-induced cardiovascular responses in microminipigs.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"42 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130026061","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: 13

A monkey model of acetaminophen-induced hepatotoxicity; phenotypic similarity to human. 对乙酰氨基酚肝毒性动物模型的建立表型与人类相似。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.73

S. Tamai, Takuma Iguchi, Noriyo Niino, Kei Mikamoto, Ken Sakurai, Ayako Sayama, H. Shimoda, W. Takasaki, K. Mori

{"title":"A monkey model of acetaminophen-induced hepatotoxicity; phenotypic similarity to human.","authors":"S. Tamai, Takuma Iguchi, Noriyo Niino, Kei Mikamoto, Ken Sakurai, Ayako Sayama, H. Shimoda, W. Takasaki, K. Mori","doi":"10.2131/jts.42.73","DOIUrl":"https://doi.org/10.2131/jts.42.73","url":null,"abstract":"Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes. Plasma levels of APAP and its reactive metabolite N-acethyl-p-benzoquinone imine (NAPQI) increased 4 to 7 hr after the APAP treatment. The mean Cmax level of APAP at 2,000 mg/kg with BSO was approximately 200 µg/mL, which was comparable to high-risk cutoff value of the Rumack-Matthew nomogram. Interestingly, plasma alanine aminotransferase (ALT) did not change until 7 hr and increased 24 hr or later after the APAP treatment, indicating that this phenotypic outcome was similar to that in humans. In addition, circulating liver-specific miR-122 and miR-192 levels also increased 24 hr or later compared with ALT, suggesting that circulating miR-122 and miR-192 may serve as potential biomarkers to detect hepatotoxicity in cynomolgus monkeys. These results suggest that the hepatotoxicity induced by APAP in the monkey model shown here was translatable to humans in terms of toxicokinetics and its toxic nature, and this model would be useful to investigate mechanisms of drug-induced liver injury and also potential translational biomarkers in humans.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115415046","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: 9

Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol. 肥胖大鼠模型对3-一氯丙烷-1,2-二醇13周亚慢性毒性的易感性改变

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.1

T. Toyoda, Young-Man Cho, Jun-ichi Akagi, Y. Mizuta, K. Matsushita, A. Nishikawa, K. Imaida, K. Ogawa

{"title":"Altered susceptibility of an obese rat model to 13-week subchronic toxicity induced by 3-monochloropropane-1,2-diol.","authors":"T. Toyoda, Young-Man Cho, Jun-ichi Akagi, Y. Mizuta, K. Matsushita, A. Nishikawa, K. Imaida, K. Ogawa","doi":"10.2131/jts.42.1","DOIUrl":"https://doi.org/10.2131/jts.42.1","url":null,"abstract":"3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"173 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128662309","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

Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse. AhR信号的过度激活破坏了发育中的小鼠海马CA1区域的神经元迁移。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.25

E. Kimura, K. Kubo, Toshihiro Endo, K. Nakajima, M. Kakeyama, C. Tohyama

{"title":"Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse.","authors":"E. Kimura, K. Kubo, Toshihiro Endo, K. Nakajima, M. Kakeyama, C. Tohyama","doi":"10.2131/jts.42.25","DOIUrl":"https://doi.org/10.2131/jts.42.25","url":null,"abstract":"The aryl hydrocarbon receptor (AhR) avidly binds dioxin, a ubiquitous environmental contaminant. Disruption of downstream AhR signaling has been reported to alter neuronal development, and rodent offspring exposed to dioxin during gestation and lactation showed abnormalities in learning and memory, emotion, and social behavior. However, the mechanism behind the disrupted AhR signaling and developmental neurotoxicity induced by xenobiotic ligands remains elusive. Therefore, we studied how excessive AhR activation affects neuronal migration in the hippocampal CA1 region of the developing mouse brain. We transfected constitutively active (CA)-AhR, AhR, or control vector plasmids into neurons via in utero electroporation on gestational day 14 and analyzed neuronal positioning in the hippocampal CA1 region of offspring on postnatal day 14. CA-AhR transfection affected neuronal positioning, whereas no change was observed in AhR-transfected or control hippocampus. These results suggest that constitutively activated AhR signaling disrupts neuronal migration during hippocampal development. Further studies are needed to investigate whether such developmental disruption in the hippocampus leads to the abnormal cognition and behavior of rodent offspring upon maternal exposure to AhR xenobiotic ligands.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131339354","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

Apoptosis and surfactant protein-C expression inhibition induced by lipopolysaccharide in AEC II cell may associate with NF-κB pathway. 脂多糖诱导AEC II细胞凋亡及表面活性剂蛋白c表达抑制可能与NF-κB通路有关。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.53

Jinle Lin, Jun Tian, Li Wang, Weigang Wu, Hua-Yi Li, Xueyan Wang, Xiaobin Zeng, Wenwu Zhang

{"title":"Apoptosis and surfactant protein-C expression inhibition induced by lipopolysaccharide in AEC II cell may associate with NF-κB pathway.","authors":"Jinle Lin, Jun Tian, Li Wang, Weigang Wu, Hua-Yi Li, Xueyan Wang, Xiaobin Zeng, Wenwu Zhang","doi":"10.2131/jts.42.53","DOIUrl":"https://doi.org/10.2131/jts.42.53","url":null,"abstract":"Lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, is one of the major causes of septic shock. Herein we investigate LPS-induced apoptosis of rat alveolar epithelial type II cells (AEC II) and the effects of LPS on surfactant protein-C (SP-C) expression in AEC II, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of AEC II significantly in concentration-dependent manner embodied in increased caspase-3 expression and the activity of caspase-3. Simultaneously, our results also indicated that LPS inhibited surfactant protein-C (SP-C) expression in AEC II. Mechanistic studies revealed that LPS treatment significantly increased the expression of NF-κB p50, NF-κB p65 and IKKβ proteins as well as induced IκB-α phosphorylation. Moreover, pretreatment with IKK inhibitor IKK-16 or NF-κB inhibitor PDTC ameliorated LPS-caused alterations in cleaved caspase-3 expression, the activity of caspase-3 and SP-C expression. Taken together, these results demonstrate that LPS can induce apoptosis of AEC II and decrease SP-C expression partly through activating the NF-κB pathway.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129353045","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: 10

Effects of reduced food intake for 4 weeks on physiological parameters in toxicity studies in dogs. 在狗的毒性研究中，连续4周减少食物摄入对生理参数的影响。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.31

Junya Morita, T. Izumi, Bun-ichiro Ogawa, Y. Ban, H. Takagi, M. Sasaki, S. Tsutsumi

{"title":"Effects of reduced food intake for 4 weeks on physiological parameters in toxicity studies in dogs.","authors":"Junya Morita, T. Izumi, Bun-ichiro Ogawa, Y. Ban, H. Takagi, M. Sasaki, S. Tsutsumi","doi":"10.2131/jts.42.31","DOIUrl":"https://doi.org/10.2131/jts.42.31","url":null,"abstract":"This study sought to clarify the effects of reduced feeding on physiological parameters in dogs to enable appropriate evaluations of the safety and toxicity of test compounds. We measured alkaline phosphatase isozymes and the circulating blood volume, as well as clinical signs, body weight, hematology, blood chemistry, electrocardiography, organ weight, and histopathology, in male beagle dogs fed a diet consisting of 300 g/day or 150 g/day for 4 weeks. There were no abnormal clinical signs in any of the dogs. In the 150-g/day feeding group, a decreased alkaline phosphatase 3 suggesting effects on the bone and a decreased circulating blood volume associated with body weight loss were observed. Additionally, the following changes were also observed in the 150-g/day group: a decrease in body weight; hematologic changes including decreases in white blood cells, neutrophils, red blood cells, hemoglobin, hematocrit and reticulocytes; blood chemical changes including decreases in aspartate aminotransferase, lactate dehydrogenase and calcium and an increase in the creatinine at week 1 or thereafter; electrocardiographic changes including a decrease in the heart rate, a prolonged QRS duration and the occurrence of a second-degree atrioventricular block at week 3 or thereafter; and pathological changes including decreases in the weights of the liver and thymus, a decrease in hepatocyte rarefaction, and thymic atrophy. These results provide useful information for assessing the safety of compounds in toxicological studies, enabling direct treatment effects and secondary changes caused by decreased food intake to be distinguished.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125474490","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

Comparative photodynamic therapy cytotoxicity of mannose-conjugated chlorin and talaporfin sodium in cultured human and rat cells. 甘露糖共轭氯和他拉波芬钠光动力疗法对培养的人和大鼠细胞的细胞毒性比较。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.111

Y. Shinoda, Tsutomu Takahashi, J. Akimoto, Megumi Ichikawa, H. Yamazaki, A. Narumi, S. Yano, Y. Fujiwara

{"title":"Comparative photodynamic therapy cytotoxicity of mannose-conjugated chlorin and talaporfin sodium in cultured human and rat cells.","authors":"Y. Shinoda, Tsutomu Takahashi, J. Akimoto, Megumi Ichikawa, H. Yamazaki, A. Narumi, S. Yano, Y. Fujiwara","doi":"10.2131/jts.42.111","DOIUrl":"https://doi.org/10.2131/jts.42.111","url":null,"abstract":"Photodynamic therapy (PDT) is a Food and Drug Administration authorized method for cancer treatment, which uses photosensitizer and laser photo-irradiation to generate reactive oxygen species to induce cell death in tumors. Photosensitizers have been progressively developed, from first to third generation, with improvements in cell specificity, reduced side effects and toxicity, increased sensitivity for irradiation and reduced persistence of photosensitizer in healthy cells. These improvements have been achieved by basic comparative experiments between current and novel photosensitizers using cell lines; however, photosensitizers should be carefully evaluated because they may have cell type specificity. In the present study, we compared a third-generation photosensitizer, β-mannose-conjugated chlorin (β-M-chlorin), with the second generation, talaporfin sodium (NPe6), using seven different rat and human cell lines and a neuronal/glial primary culture prepared from rat embryos. NPe6 was more effective than β-M-chlorin in human-derived cell lines, and β-M-chlorin was more effective than NPe6 in rat primary cultures and rat-derived cell lines, except for the rat pheochromocytoma cell line, PC12. These differences of phototoxicity in different cell types are not because of differences in photosensitivity between the photosensitizers, but rather are associated with different distribution and accumulation rates in the different cell types. These data suggest that evaluation of photosensitizers for PDT should be carried out using as large a variety of cell types as possible because each photosensitizer may have cell type specificity.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134059512","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

Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines. 褪黑素抑制甲基苯丙胺引发的C6胶质瘤细胞系内质网应激。

The Journal of toxicological sciences Pub Date : 2017-02-01 DOI: 10.2131/jts.42.63

Wanida Tungkum, Pichaya Jumnongprakhon, C. Tocharus, P. Govitrapong, J. Tocharus

{"title":"Melatonin suppresses methamphetamine-triggered endoplasmic reticulum stress in C6 cells glioma cell lines.","authors":"Wanida Tungkum, Pichaya Jumnongprakhon, C. Tocharus, P. Govitrapong, J. Tocharus","doi":"10.2131/jts.42.63","DOIUrl":"https://doi.org/10.2131/jts.42.63","url":null,"abstract":"Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood. This study investigated the protective effect of melatonin against METH toxicity-mediated ER stress in glial cells. Our study demonstrated that METH increased glial cell toxicity related to METH-induced ER stress by stimulating the unfolded protein response (UPR) to activate the expression of ER stress transducers, including phosphorylated double-stranded RNA-activated protein kinase (PKR)-like ER kinase (p-PERK), activating transcription factor (ATF6), and phosphorylated inositol-requiring enzyme 1 (p-IRE1). Moreover, the expression of binding immunoglobulin protein (Bip), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, phosphorylated eukaryotic translation initiation factor 2 alpha (p-eIF2α) and spliced X-box-binding protein-1 (XBP-1) mRNA were also increased. Melatonin reduced ER stress induced by METH toxicity by reducing the expression of ER stress response genes and proteins in a concentration-dependent manner. In addition, melatonin promoted the expression of Bip chaperone in a concentration-dependent manner. Taken together, our findings suggest that melatonin can protect against ER stress-induced glial cell death induced by METH.","PeriodicalId":231048,"journal":{"name":"The Journal of toxicological sciences","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123168166","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: 22