Toxicology Mechanisms and Methods最新文献

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Vitamin E supplementation modulates the biological effects of omega-3 fatty acids in naturally aged rats 补充维生素E可调节自然衰老大鼠体内omega-3脂肪酸的生物学效应
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-08 DOI: 10.1080/15376516.2016.1273431
A. Narayanankutty, Anagha Kottekkat, S. E. Mathew, S. P. Illam, I. Suseela, A. Raghavamenon
{"title":"Vitamin E supplementation modulates the biological effects of omega-3 fatty acids in naturally aged rats","authors":"A. Narayanankutty, Anagha Kottekkat, S. E. Mathew, S. P. Illam, I. Suseela, A. Raghavamenon","doi":"10.1080/15376516.2016.1273431","DOIUrl":"https://doi.org/10.1080/15376516.2016.1273431","url":null,"abstract":"Abstract Omega-3 fatty acids are well-known class of nutraceuticals with established health benefits. Recently, the oxidation products of these fatty acids are gaining attention, as they are likely to disturb body redox balance. Therefore, the efficacy of omega-3 fats under conditions of diminished antioxidant status, such as aging, is always a concern. Present study assessed the effects of omega-3 fats (DHA and EPA) together with or without vitamin-E in naturally aged rats. It was found that in omega-3 fats alone consumed rats the lipid profile was improved, while in omega-3 fat with vitamin-E-consumed group (OMVE), the hepato protective and antioxidant properties were pronounced, especially the redox status of brain tissue. It is possible that vitamin-E might have reduced the peroxidation of omega-3 fats, thereby allowing their synergistic effects. Hence, the use of vitamin-E along with omega-3 fat may be beneficial under aged conditions.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1273431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47827679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 22
Antioxidant and neuroprotector effect of Lepidium meyenii (maca) methanol leaf extract against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells 麦地子甲醇叶提取物对6-羟基多巴胺(6-OHDA)诱导PC12细胞毒性的抗氧化和神经保护作用
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-08 DOI: 10.1080/15376516.2016.1275908
Ángel Rodríguez-Huamán, Sandra Casimiro-Gonzales, Jorge Antonio Chávez-Pérez, Carla Gonzales-Arimborgo, Richard Cisneros-Fernández, Luis Ángel Aguilar-Mendoza, G. Gonzales
{"title":"Antioxidant and neuroprotector effect of Lepidium meyenii (maca) methanol leaf extract against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells","authors":"Ángel Rodríguez-Huamán, Sandra Casimiro-Gonzales, Jorge Antonio Chávez-Pérez, Carla Gonzales-Arimborgo, Richard Cisneros-Fernández, Luis Ángel Aguilar-Mendoza, G. Gonzales","doi":"10.1080/15376516.2016.1275908","DOIUrl":"https://doi.org/10.1080/15376516.2016.1275908","url":null,"abstract":"Abstract Reactive oxygen species (ROS) are normally produced during cell metabolism, there is strong evidence to suggest that ROS produced in excess impair the cell and may be etiologically related to various neurodegenerative diseases. This study was undertaken to examine the effects of Lepidium meyenii (MACA) methanol leaf extract on neurotoxicity in PC12 cell exposed to 6-hydroxydopamine (6-OHDA). Fresh samples of “maca” leaves were processed in order to obtain foliar extracts and to evaluate the neurobiological activity on PC12 cells, subjected to the cytotoxic effect of 6-OHDA through the determination of the capacity antioxidant, cell viability and cytotoxicity assays on PC12 cells. The results of the tests of antioxidant activity, showed maximum values of 2262.37 and 1305.36 expressed in Trolox equivalents (TEAC), for the methanolic and aqueous fractions respectively. Cell viability assays at a dose of 10 μg extract showed an increase of 31% and 60% at 6 and 12 h of pretreatment, respectively. Cytotoxicity assays at the same dose and exposure time showed a 31.4% and 47.8% reduction in lactate dehydrogenase (LDH) activity and an increase in superoxide dismutase (SOD) activity. The results allow us to affirm that the methanolic foliar extract of “maca” presents in vitro neurobiological activity of antioxidant protection, increase in cell viability and reduction of cytotoxicity against oxidative stress generated by 6-OHDA. In conclusion, the present study shows a protective role for Lepidium meyenii leaf extract on 6-OHDA-induced toxicity by an antioxidant effect.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1275908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47739755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 23
Phytotherapeutic approach: a new hope for polycyclic aromatic hydrocarbons induced cellular disorders, autophagic and apoptotic cell death 植物治疗方法:多环芳烃诱导细胞紊乱、自噬和凋亡的新希望
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.1080/15376516.2016.1268228
D. N. Das, P. Panda, P. P. Naik, Subhadip Mukhopadhyay, N. Sinha, S. Bhutia
{"title":"Phytotherapeutic approach: a new hope for polycyclic aromatic hydrocarbons induced cellular disorders, autophagic and apoptotic cell death","authors":"D. N. Das, P. Panda, P. P. Naik, Subhadip Mukhopadhyay, N. Sinha, S. Bhutia","doi":"10.1080/15376516.2016.1268228","DOIUrl":"https://doi.org/10.1080/15376516.2016.1268228","url":null,"abstract":"Abstract Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their genotoxic, teratogenic, mutagenic and carcinogenic property. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) has the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development. The carcinogenicity potential of PAHs is related to their ability to bind to DNA, thereby enhances DNA cross-linking, causing a series of disruptive effects which can result in tumor initiation. They induce cellular toxicity by regulating the generation of reactive oxygen species (ROS), which arbitrate apoptosis. Additionally, cellular toxicity-mediated apoptotic and autophagic cell death and immune suppression by industrial pollutants PAH, provide fertile ground for the proliferation of mutated cells, which results in cancer growth and progression. PAHs play a foremost role in angiogenesis necessary for tumor metastasization by promoting the upregulation of metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF) in human cancer cells. This review sheds light on the molecular mechanisms of PAHs induced cancer development as well as autophagic and apoptotic cell death. Besides that authors have unraveled how phytotherapeutics is an alternate potential therapeutics acting as a savior from the toxic effects of PAHs for safer and cost effective perspectives.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1268228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41890614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 31
Toxicological effects of three types of silver nanoparticles and their salt precursors acting on human U-937 and HL-60 cells 三种银纳米粒子及其盐前体对人U-937和HL-60细胞的毒性作用
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.1080/15376516.2016.1251520
A. Barbasz, M. Oćwieja, S. Walas
{"title":"Toxicological effects of three types of silver nanoparticles and their salt precursors acting on human U-937 and HL-60 cells","authors":"A. Barbasz, M. Oćwieja, S. Walas","doi":"10.1080/15376516.2016.1251520","DOIUrl":"https://doi.org/10.1080/15376516.2016.1251520","url":null,"abstract":"Abstract The growing popularity of nanomaterials requires a systematic study of their effects on the human body. Silver nanoparticles (AgNPs), due to their antiseptic properties, are used in almost every area of life. The purpose of the study was to examine whether the precursor used for the synthesis of nanoparticles affects their bio-influence and modifies their impact on cells of the human immune system. To compare the effects of precursor silver salts (AgNO3, CH3COOAg and AgClO4) and corresponding nanoparticles (TAN TAA and TAC) cytotoxicity study was conducted on two cell lines U-937 and HL-60. For both cell lines, silver salts are more toxic than the corresponding nanoparticles. Cell viability after treatment with the two forms of silver (salt/particle) is dependent on silver dose and degree of cells differentiation. Addition of the silver salt of doses greater than 5 mg/L results in decreased cell viability by over 60%, whereas nanoparticles’ addition reduces cell viability on average by 30%. On the basis of the determined LD50 values it can be stated that for the tested cells the most toxic are AgClO4 and TAC. Production of nitric oxide, which is a mediator of inflammation, is the greatest after treatment of the cells by TAC. Different interactions of studied nanoparticles with albumin has been found and it was shown that addition of albumin to the cells treated by nanoparticles reduces their toxic effects. Obtained by us highly purified, mono-disperse AgNPs exhibit diverse effects relative to the biological systems, depending on the precursor salt used.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1251520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42153566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Characterization of Tilapia (Oreochromis niloticus) aldehyde reductase (AKR1A1) gene, promoter and expression pattern in benzo-a-pyrene exposed fish 罗非鱼(Oreochromis niloticus)醛还原酶(AKR1A1)基因、启动子及其在苯并芘暴露鱼类中的表达特征
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.1080/15376516.2016.1238529
A. Hassanin, Y. Kaminishi, T. Itakura
{"title":"Characterization of Tilapia (Oreochromis niloticus) aldehyde reductase (AKR1A1) gene, promoter and expression pattern in benzo-a-pyrene exposed fish","authors":"A. Hassanin, Y. Kaminishi, T. Itakura","doi":"10.1080/15376516.2016.1238529","DOIUrl":"https://doi.org/10.1080/15376516.2016.1238529","url":null,"abstract":"Abstract This study planned to isolation and characterization of AKR1A1 cDNA from Bap injected nile tilapia (Oreochromis niloticus), comparison of its characteristic structures with those of other species, characterization of AKR1A1 gene and promoter, and investigation of AKR1A1 mRNA expression in various organs of Bap injected tilapia. The cDNA was 1172 bp long which includes an open reading frame of 975 bp encoding a 324 amino acids protein and a stop codon. The sequence showed 3' and 5' non-coding regions of 179 and 18 bp. The amino acid sequence of O. niloticus AKR1A1 shows similarities of 60, 60, 60.6, 61.2 62.2, and 57.8% with mouse AKR1A1, Norway rat AKR1A1, zebrafish AKR1A1, African clawed frog AKR1A1, human, and yellow perch AKR1A1, respectively. Nucleotide sequence investigation of AKR1A1 gene and 5′-flanking region showed that the structural gene and the 5′-flanking region were approximately 2975 bp and 4006 bp in length, respectively. The protein-coding region contained eight exons, and one additional upstream exon. Real-time polymerase chain reaction (PCR) results showed that the highest level of AKR1A1 expression was found in bile (108.7), followed by kidney (77.9), muscles (37.3), and liver (24.7). mRNA levels of AKR1A1 were almost negligible in gills (0.6) while no detectable (ND) constitutive expression was detected in gut. In conclusion, our results concluded that tilapia AKR1A1 is inducible by BaP and have a significant function in the metabolism of xenobiotics and, therefore, may used as biomarker in fish","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1238529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41677893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Comparative evaluation of 11 in silico models for the prediction of small molecule mutagenicity: role of steric hindrance and electron-withdrawing groups 11个预测小分子致突变性的计算机模型的比较评价:空间位阻和吸电子基团的作用
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.1080/15376516.2016.1174761
Kevin A. Ford, Gregory A. Ryslik, Bryan K. Chan, Sock-Cheng Lewin-Koh, D. Almeida, Michael Stokes, Stephen Gomez
{"title":"Comparative evaluation of 11 in silico models for the prediction of small molecule mutagenicity: role of steric hindrance and electron-withdrawing groups","authors":"Kevin A. Ford, Gregory A. Ryslik, Bryan K. Chan, Sock-Cheng Lewin-Koh, D. Almeida, Michael Stokes, Stephen Gomez","doi":"10.1080/15376516.2016.1174761","DOIUrl":"https://doi.org/10.1080/15376516.2016.1174761","url":null,"abstract":"Abstract The goal of this investigation was to perform a comparative analysis on how accurately 11 routinely-used in silico programs correctly predicted the mutagenicity of test compounds that contained either bulky or electron-withdrawing substituents. To our knowledge this is the first study of its kind in the literature. Such substituents are common in many pharmaceutical agents so there is a significant need for reliable in silico programs to predict precisely whether they truly pose a risk for mutagenicity. The predictions from each program were compared to experimental data derived from the Ames II test, a rapid reverse mutagenicity assay with a high degree of agreement with the traditional Ames assay. Eleven in silico programs were evaluated and compared: Derek for Windows, Derek Nexus, Leadscope Model Applier (LSMA), LSMA featuring the in vitro microbial Escherichia coli–Salmonella typhimurium TA102 A-T Suite (LSMA+), TOPKAT, CAESAR, TEST, ChemSilico (±S9 suites), MC4PC and a novel DNA docking model. The presence of bulky or electron-withdrawing functional groups in the vicinity of a mutagenic toxicophore in the test compounds clearly affected the ability of each in silico model to predict non-mutagenicity correctly. This was because of an over reliance on the part of the programs to provide mutagenicity alerts when a particular toxicophore is present irrespective of the structural environment surrounding the toxicophore. From this investigation it can be concluded that these models provide a high degree of specificity (ranging from 71% to 100%) and are generally conservative in their predictions in terms of sensitivity (ranging from 5% t o 78%). These values are in general agreement with most other comparative studies in the literature. Interestingly, the DNA docking model was the most sensitive model evaluated, suggesting a potentially useful new mode of screening for mutagens. Another important finding was that the combination of a quantitative structure–activity relationship and an expert rules system appeared to offer little advantage in terms of sensitivity, despite of the requirement for such a screening paradigm under the ICH M7 regulatory guideline.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1174761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47182222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Antioxidant response and biocompatibility of curcumin-loaded triblock copolymeric micelles 姜黄素负载三嵌段共聚胶束的抗氧化反应及生物相容性
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.1080/15376516.2016.1253811
V. Tzankova, Cvetelina Gorinova, M. Kondeva-Burdina, R. Simeonova, Stanislav Philipov, S. Konstantinov, P. Petrov, Dimitar Galabov, K. Yoncheva
{"title":"Antioxidant response and biocompatibility of curcumin-loaded triblock copolymeric micelles","authors":"V. Tzankova, Cvetelina Gorinova, M. Kondeva-Burdina, R. Simeonova, Stanislav Philipov, S. Konstantinov, P. Petrov, Dimitar Galabov, K. Yoncheva","doi":"10.1080/15376516.2016.1253811","DOIUrl":"https://doi.org/10.1080/15376516.2016.1253811","url":null,"abstract":"Abstract To evaluate the safety profile of cationic micelles, based on triblock copolymer poly(dimethylaminoethyl methacrylate)–poly(e-caprolactone)–poly(dimethylaminoethyl methacrylate) (PDMAEMA9– PCL70–PDMAEMA9), the effects of empty (PM) and curcumin loaded micelles (PM-Curc) on nonenzyme induced lipid peroxidation (LPO) in vitro, hemolytic activity and morphological changes in some organs after repeated intraperitoneal administration in vivo were studied. To induce LPO, rat liver microsomes were incubated with a solution of iron sulfate and ascorbinic acid (Fe2+/AA). The effect of empty PM (40 and 100 μg/ml), PM-Curc and free curcumin (both at 3.48 and 8.7 μg curcumin/ml) was assessed at 20 min incubation time. In the non-enzyme induced LPO model, the investigated substances at all concentrations significantly decreased the formation of malondialdehyde (MDA), compared to the Fe2+/AA induced LPO group. According to the results it can be concluded that curcumin alone and loaded in PM, exert significant antioxidant activity. In the biocompatibility safety studies, the mean hemolytic index for polymeric carrier was less than 2%, indicating it was non-hemolytic. The general appearance of the organ tissues from Wistar rats, treated in vivo with curcumin loaded PM was similar to that of controls, thus showing no apparent toxicity after repeated 14-days treatment.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1253811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46726142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase 凝血酶通过激活c-Jun-N末端激酶诱导神经元凋亡
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.3109/15376516.2016.1172691
Lei Bao, J. Zu, Qian-qian He, Hui Zhao, Su Zhou, X. Ye, Xinxin Yang, Kun Zan, Zuohui Zhang, Hongjuan Shi, G. Cui
{"title":"Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase","authors":"Lei Bao, J. Zu, Qian-qian He, Hui Zhao, Su Zhou, X. Ye, Xinxin Yang, Kun Zan, Zuohui Zhang, Hongjuan Shi, G. Cui","doi":"10.3109/15376516.2016.1172691","DOIUrl":"https://doi.org/10.3109/15376516.2016.1172691","url":null,"abstract":"Abstract Context: Studies have shown that thrombin activation played a central role in cell injuries associated with intracerebral hemorrhage (ICH). Objective: Here, our study investigated the cytotoxicity of thrombin on neurons, and determined the involvement of JNK pathways in thrombin-induced neuronal apoptosis. Materials and methods: Primary cultured neurons were treated with different doses of thrombin. Some neurons were given either SP600125 or vehicle. LDH release assay and flow cytometry were used to measure neuronal apoptosis caused by thrombin. The activation of JNK and capases-3 were measured by Western blot. Results: Our results showed large doses of thrombin that increased the LDH release, the level of cleaved caspase-3 and apoptosis rate of neurons. JNK was activated by thrombin in a time-dependent manner. Administration of SP600125 protects neurons from thrombin-induced apoptosis. Conclusion: These data indicate that the activation of JNK is crucial for thrombin-induced neuronal apoptosis, and inhibition of JNK may be a potential therapeutic target for ICH.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/15376516.2016.1172691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45843757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Evaluation of an in vitro screening model to assess phosgene inhalation injury 评估光气吸入损伤的体外筛选模型的评价
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.1080/15376516.2016.1243183
D. Olivera, Heidi M Hoard-Fruchey, A. Sciuto
{"title":"Evaluation of an in vitro screening model to assess phosgene inhalation injury","authors":"D. Olivera, Heidi M Hoard-Fruchey, A. Sciuto","doi":"10.1080/15376516.2016.1243183","DOIUrl":"https://doi.org/10.1080/15376516.2016.1243183","url":null,"abstract":"Abstract Therapeutic development against exposure to toxic gases is hindered by the lack of appropriate models to evaluate candidate compounds prior to animal efficacy studies. In this study, an in vitro, air-liquid interface exposure model has been tested to examine its potential application for screening treatments for phosgene (carbonyl chloride)-induced pulmonary injury. Epithelial cultures on Transwell® inserts, combined with a Vitrocell® exposure apparatus, provided a physiologically relevant exposure environment. Differentiated human bronchial epithelial (16HBE) cultures were exposed for 8 min to phosgene ranging from 0 to 64 ppm and assessed for changes in transepithelial electrical resistance (TEER, epithelial barrier integrity), cellular viability (XTT) and post-exposure (PE) cellular metabolic energy status. Exposure to phosgene concentrations ≥8 ppm caused dose-dependent and significant decreases in TEER and XTT which did not recover within 24-h PE. In addition, at 64 ppm the rate of oxidative glutamine metabolism was significantly inhibited at 6 and 24 h after exposure. Glycolytic activities (glucose utilization and lactate production) were also inhibited, but to a lesser extent. Decreased glycolytic function can translate to insufficient energy sources to counteract barrier function failure. Consistent and sensitive markers of phosgene exposure were TEER, cell viability and decreased metabolism. As such, we have assessed an appropriate in vitro model of phosgene inhalation that produced quantifiable alterations in markers of lung cell metabolism and injury in human airway epithelial cells. Data indicate the suitability of this model for testing classes of anti-edemagenic compounds such as corticosteroids or phosphodiesterase inhibitors for evaluating phosgene therapeutics.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1243183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49530400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Protective effect of amifostine on busulfan induced DNA damage in human hepatoma cells 氨磷汀对丁硫凡诱导的人肝癌细胞DNA损伤的保护作用
IF 3.2 4区 医学
Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI: 10.1080/15376516.2016.1243601
Nasrin Ghassemi-Barghi, M. Etebari, A. Jafarian-dehkordi
{"title":"Protective effect of amifostine on busulfan induced DNA damage in human hepatoma cells","authors":"Nasrin Ghassemi-Barghi, M. Etebari, A. Jafarian-dehkordi","doi":"10.1080/15376516.2016.1243601","DOIUrl":"https://doi.org/10.1080/15376516.2016.1243601","url":null,"abstract":"Abstract Busulfan is one of the most effective chemotherapeutic agents used for the treatment of chronic myeloid leukemia. However, as a bifunctional alkylating agent, during clinical use several side effects may occur. In addition, several in vivo and in vitro studies of busulfan have shown a range of genotoxic effects including DNA strand break and inhibition of DNA synthesis. Amifostine, an organic thiophosphate compound, has been shown to exert an important cyto-protective effect in many tissues. The aim of this study was to explore whether amifostine protects against busulfan-induced genotoxicity in HepG2 cell line. Our results showed that amifostine reduced the genotoxic effects of busulfan significantly in both type of experiment conditions, as measured via comet assay. Furthermore, amifostine decreased the intracellular ROS generation induced by busulfan and also increased the intracellular GSH levels in HepG2 cells. Altogether, our results suggest a protective action of amifostine against busulfan cytotoxicity and genotoxicity via various pathways. The most protective effect was observed with amifostine when it was administrated 24 h before busulfan treatment.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1243601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43941325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
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