Archives of Toxicology最新文献

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Author Correction: Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health 作者更正:Alternaria 毒素的危害特征描述,以确定数据缺口并改进对人类健康的风险评估。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-30 DOI: 10.1007/s00204-024-03818-y
Henriqueta Louro, Ariane Vettorazzi, Adela López de Cerain, Anastasia Spyropoulou, Anita Solhaug, Anne Straumfors, Anne-Cathrin Behr, Birgit Mertens, Bojana Žegura, Christiane Kruse Fæste, Dieynaba Ndiaye, Eliana Spilioti, Elisabeth Varga, Estelle Dubreil, Eszter Borsos, Francesco Crudo, Gunnar Sundstøl Eriksen, Igor Snapkow, Jérôme Henri, Julie Sanders, Kyriaki Machera, Laurent Gaté, Ludovic Le Hegarat, Matjaž Novak, Nicola M. Smith, Solveig Krapf, Sonja Hager, Valérie Fessard, Yvonne Kohl, Maria João Silva, Hubert Dirven, Jessica Dietrich, Doris Marko
{"title":"Author Correction: Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health","authors":"Henriqueta Louro, Ariane Vettorazzi, Adela López de Cerain, Anastasia Spyropoulou, Anita Solhaug, Anne Straumfors, Anne-Cathrin Behr, Birgit Mertens, Bojana Žegura, Christiane Kruse Fæste, Dieynaba Ndiaye, Eliana Spilioti, Elisabeth Varga, Estelle Dubreil, Eszter Borsos, Francesco Crudo, Gunnar Sundstøl Eriksen, Igor Snapkow, Jérôme Henri, Julie Sanders, Kyriaki Machera, Laurent Gaté, Ludovic Le Hegarat, Matjaž Novak, Nicola M. Smith, Solveig Krapf, Sonja Hager, Valérie Fessard, Yvonne Kohl, Maria João Silva, Hubert Dirven, Jessica Dietrich, Doris Marko","doi":"10.1007/s00204-024-03818-y","DOIUrl":"10.1007/s00204-024-03818-y","url":null,"abstract":"","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3513 - 3514"},"PeriodicalIF":4.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differences in endocrine and reproductive responses to substance exposure across generations: highlighting the importance of complementary findings 各代人的内分泌和生殖系统对药物接触反应的差异:强调补充性研究结果的重要性。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-18 DOI: 10.1007/s00204-024-03813-3
Ingo Bichlmaier
{"title":"Differences in endocrine and reproductive responses to substance exposure across generations: highlighting the importance of complementary findings","authors":"Ingo Bichlmaier","doi":"10.1007/s00204-024-03813-3","DOIUrl":"10.1007/s00204-024-03813-3","url":null,"abstract":"<div><p>This article analyzes the results from 112 Extended One-Generation Reproductive Toxicity studies. The objective was to determine if test animals show consistent endocrine and reproductive effects within the same and across different generations and life stages. The analysis, grounded in a comprehensive Binary Matrix, included 530 observed effects and 193 unique, statistically significant associations. Associations’ strength was quantified using Jaccard (<b><i>J</i></b>) coefficients to measure effect co-occurrence in the same study. Associated effects co-occur infrequently across the whole dataset (median <b><i>J</i></b> = 0.231). However, specific patterns emerged: associations of same effects across generations exhibited a higher strength (median <b><i>J</i></b> = 0.400) compared to associations of different effects (median <b><i>J</i></b> = 0.222). Notably, associations with effects observed in both the parental animals of the adult first filial generation (P1) and developing second filial generations (dF2) demonstrated <b><i>J</i></b> coefficients (with medians ranging from 0.300 to 0.430) that were approximately twofold higher than those of other associations. Consistently, equivalent life stage associations across generations revealed statistically significant higher association strengths for the P1 and dF2 generations (median<i>s</i> of 0.375 and 0.333, respectively) compared to other generations (medians of 0.200 and 0.174), possibly due to longer exposure duration and altered cross-talk between pregnant P1 dam and its conceptus. Overall, it is concluded that co-occurrence of associated effects in the same study is rather infrequent and that associations with effects in P1 and dF2 are stronger than all other associations. In general, the findings underscore the importance of independently analyzing each effect per generation due to the generally low co-occurrence rates of associated effects, challenging traditional expectations of generational continuity in toxic effects.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3215 - 3230"},"PeriodicalIF":4.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of reversible OATP1B1 and time-dependent CYP3A4 inhibition as the major risk factors for drug-induced cholestasis (DIC) 确定可逆性 OATP1B1 和时间依赖性 CYP3A4 抑制是药物性胆汁淤积症 (DIC) 的主要风险因素。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-18 DOI: 10.1007/s00204-024-03794-3
Vlasia Kastrinou-Lampou, Raquel Rodríguez-Pérez, Birk Poller, Felix Huth, Zsuzsanna Gáborik, Beáta Mártonné-Tóth, Csilla Temesszentandrási-Ambrus, Heiko S. Schadt, Gerd A. Kullak-Ublick, Michael Arand, Gian Camenisch
{"title":"Identification of reversible OATP1B1 and time-dependent CYP3A4 inhibition as the major risk factors for drug-induced cholestasis (DIC)","authors":"Vlasia Kastrinou-Lampou,&nbsp;Raquel Rodríguez-Pérez,&nbsp;Birk Poller,&nbsp;Felix Huth,&nbsp;Zsuzsanna Gáborik,&nbsp;Beáta Mártonné-Tóth,&nbsp;Csilla Temesszentandrási-Ambrus,&nbsp;Heiko S. Schadt,&nbsp;Gerd A. Kullak-Ublick,&nbsp;Michael Arand,&nbsp;Gian Camenisch","doi":"10.1007/s00204-024-03794-3","DOIUrl":"10.1007/s00204-024-03794-3","url":null,"abstract":"<div><p>Hepatic bile acid regulation is a multifaceted process modulated by several hepatic transporters and enzymes. Drug-induced cholestasis (DIC), a main type of drug-induced liver injury (DILI), denotes any drug-mediated condition in which hepatic bile flow is impaired. Our ability in translating preclinical toxicological findings to human DIC risk is currently very limited, mainly due to important interspecies differences. Accordingly, the anticipation of clinical DIC with available in vitro or in silico models is also challenging, due to the complexity of the bile acid homeostasis. Herein, we assessed the in vitro inhibition potential of 47 marketed drugs with various degrees of reported DILI severity towards all metabolic and transport mechanisms currently known to be involved in the hepatic regulation of bile acids. The reported DILI concern and/or cholestatic annotation correlated with the number of investigated processes being inhibited. Furthermore, we employed univariate and multivariate statistical methods to determine the important processes for DILI discrimination. We identified time-dependent inhibition (TDI) of cytochrome P450 (CYP) 3A4 and reversible inhibition of the organic anion transporting polypeptide (OATP) 1B1 as the major risk factors for DIC among the tested mechanisms related to bile acid transport and metabolism. These results were consistent across multiple statistical methods and DILI classification systems applied in our dataset. We anticipate that our assessment of the two most important processes in the development of cholestasis will enable a risk assessment for DIC to be efficiently integrated into the preclinical development process.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3409 - 3424"},"PeriodicalIF":4.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
The relative nature of the standards for proof of safety: a review of FDA’s safety standards for various consumer products 安全证明标准的相对性:食品和药物管理局对各种消费品安全标准的审查。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-17 DOI: 10.1007/s00204-024-03816-0
George A. Burdock, Erik Hedrick
{"title":"The relative nature of the standards for proof of safety: a review of FDA’s safety standards for various consumer products","authors":"George A. Burdock,&nbsp;Erik Hedrick","doi":"10.1007/s00204-024-03816-0","DOIUrl":"10.1007/s00204-024-03816-0","url":null,"abstract":"<div><p>Are all food ingredients, dietary supplement ingredients and even foods, required to meet the same safety standards? Are they all equally safe? If so, then why do the various categories have different expressions describing their safety, such as “reasonable <i>certainty</i> of no harm” for food ingredients and “reasonable <i>expectation</i> of no harm” for dietary supplement ingredients? The basis for these different expressions is that they are not standards of safety, but <i>standards of proof</i> of safety. Just as in criminal vs. civil courts, the threshold for proving guilt or fault is different, so too are there differences between various categories of consumer products regulated by the US Food and Drug Administration. This manuscript describes the threshold requirements for each standard, as well as to the identity of the decision makers on what is safe, their credentials as decision makers and the databases mandated for their use.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3209 - 3214"},"PeriodicalIF":4.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development 整合系统功能筛选和精细图谱,破解 RPS19 在结直肠癌发展中的作用和遗传调控。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-16 DOI: 10.1007/s00204-024-03822-2
Can Chen, Wenzhuo Wang, Caibo Ning, Zequn Lu, Ming Zhang, Ying Zhu, Jianbo Tian, Haijie Li, Yue Ge, Beifang Yang, Xiaoping Miao
{"title":"Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development","authors":"Can Chen,&nbsp;Wenzhuo Wang,&nbsp;Caibo Ning,&nbsp;Zequn Lu,&nbsp;Ming Zhang,&nbsp;Ying Zhu,&nbsp;Jianbo Tian,&nbsp;Haijie Li,&nbsp;Yue Ge,&nbsp;Beifang Yang,&nbsp;Xiaoping Miao","doi":"10.1007/s00204-024-03822-2","DOIUrl":"10.1007/s00204-024-03822-2","url":null,"abstract":"<div><p>Despite genome-wide association studies (GWAS) have identified more than 200 risk loci associated with colorectal cancer (CRC), the causal genes or risk variants within these loci and their biological functions remain not fully revealed. Recently, the genomic locus 19q13.2, with the lead SNP rs1800469 was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here we employed an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk locus 19q13.2. Notably, we found that <i>RPS19</i> exhibited the most significant effect among the identified genes and acted as a critical oncogene facilitating CRC cell proliferation. Subsequently, combining integrative fine-mapping analysis and a large-scale population study consisting of 6027 cases and 6099 controls, we prioritized rs1025497 as a potential causal candidate for CRC risk, demonstrating that rs1025497[A] allele significantly reduced the risk of CRC (OR 0.70, 95% confidence interval = 0.56–0.83, <i>P</i> = 1.12 × 10<sup>–6</sup>), which was further validated in UK Biobank cohort comprising 5,313 cases and 21,252 controls. Mechanistically, we experimentally elucidated that variant rs1025497 might acted as an allele-specific silencer, inhibiting the expression level of oncogene <i>RPS19</i> mediated by the transcription suppressive factor HBP1. Taken together, our sturdy unveils the significant role of <i>RPS19</i> during CRC pathogenesis and delineates its distal regulatory mechanism mediated by rs1025497, advancing our understanding of the etiology of CRC and provided new insights into the personalized medicine of human cancer.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3453 - 3465"},"PeriodicalIF":4.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
Sirtuin 3-activated superoxide dismutase 2 mediates fluoride-induced osteoblastic differentiation in vitro and in vivo by down-regulating reactive oxygen species Sirtuin 3激活的超氧化物歧化酶2通过下调活性氧介导氟化物诱导的体外和体内成骨细胞分化。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-16 DOI: 10.1007/s00204-024-03819-x
Liu Yang, Qiao Li, Sa Wang, Yi Ji, Xinbo Ma, Ming Qin, Yanhui Gao, Yanmei Yang
{"title":"Sirtuin 3-activated superoxide dismutase 2 mediates fluoride-induced osteoblastic differentiation in vitro and in vivo by down-regulating reactive oxygen species","authors":"Liu Yang,&nbsp;Qiao Li,&nbsp;Sa Wang,&nbsp;Yi Ji,&nbsp;Xinbo Ma,&nbsp;Ming Qin,&nbsp;Yanhui Gao,&nbsp;Yanmei Yang","doi":"10.1007/s00204-024-03819-x","DOIUrl":"10.1007/s00204-024-03819-x","url":null,"abstract":"<div><p>Skeletal fluorosis is a chronic metabolic bone disease caused by long-term excessive fluoride intake. Abnormal differentiation of osteoblasts plays an important role in disease progression. Research on the mechanism of fluoride-mediated bone differentiation is necessary for the prevention and treatment of skeletal fluorosis. In the present study, a rat model of fluorosis was established by exposing it to drinking water containing 50 mg/L F<sup>−</sup>. We found that fluoride promoted Runt-related transcription factor 2 (RUNX2) as well as superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) expression in osteoblasts of rat bone tissue. In vitro, we also found that 4 mg/L sodium fluoride promoted osteogenesis-related indicators as well as SOD2 and SIRT3 expression in MG-63 and Saos-2 cells. In addition, we unexpectedly discovered that fluoride suppressed the levels of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) in osteoblasts. When SOD2 or SIRT3 was inhibited in MG-63 cells, fluoride-decreased ROS and mtROS were alleviated, which in turn inhibited fluoride-promoted osteogenic differentiation. In conclusion, our results suggest that SIRT3/SOD2 mediates fluoride-promoted osteoblastic differentiation by down-regulating reactive oxygen species.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3351 - 3363"},"PeriodicalIF":4.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
A new 3D model of L929 fibroblasts microtissues uncovers the effects of Bothrops erythromelas venom and its antivenom 一种新的 L929 成纤维细胞微组织三维模型揭示了红腹锦鸡毒液及其抗毒血清的作用。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-15 DOI: 10.1007/s00204-024-03824-0
F. R. S. Andrade, E. L. da Silva, A. D. Marinho, A. C. X. Oliveira, D. Sánchez-Porras, F. Bermejo-Casares, R. C. Montenegro, V. Carriel, H. S. A. Monteiro, R. J. B. Jorge
{"title":"A new 3D model of L929 fibroblasts microtissues uncovers the effects of Bothrops erythromelas venom and its antivenom","authors":"F. R. S. Andrade,&nbsp;E. L. da Silva,&nbsp;A. D. Marinho,&nbsp;A. C. X. Oliveira,&nbsp;D. Sánchez-Porras,&nbsp;F. Bermejo-Casares,&nbsp;R. C. Montenegro,&nbsp;V. Carriel,&nbsp;H. S. A. Monteiro,&nbsp;R. J. B. Jorge","doi":"10.1007/s00204-024-03824-0","DOIUrl":"10.1007/s00204-024-03824-0","url":null,"abstract":"<div><p>In Brazil, around 80% of snakebites are caused by snakes of the genus Bothrops. A three-dimensional culture model was standardized and used to perform treatments with <i>Bothrops erythromelas</i> venom (<i>Be</i>V) and its antivenom (AV). The MRC-5 and L929 cell lines were cultured at increasing cell densities. Morphometric parameters were evaluated through images obtained from an inverted microscope: solidity, circularity, and Feret diameter. L929 microtissues (MT) showed better morphometric data, and thus they were used for further analysis. MT viability was assessed using the acridine orange and ethidium bromide staining method, which showed viable cells in the MT on days 5, 7, and 10 of cultivation. Histochemical and histological analyses were performed, including hematoxylin/eosin staining, which showed a good structure of the spheroids. Alcian blue staining revealed the presence of acid proteoglycans. Immunohistochemical analysis with ki-67 showed different patterns of cell proliferation. The MT were also subjected to pharmacological tests using the <i>Be</i>V, in the presence or absence of its AV. The results showed that the venom was not cytotoxic, but it caused morphological changes. The MT showed cell detachment, losing their structure. The antivenom was able to partially prevent the venom activities.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3503 - 3512"},"PeriodicalIF":4.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
Comparison of DNA damage in fresh and frozen blood samples: implications for the comet assay in human biomonitoring studies 新鲜和冷冻血液样本中 DNA 损伤的比较:彗星试验在人类生物监测研究中的意义。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-14 DOI: 10.1007/s00204-024-03823-1
Katarina Matković, Marko Gerić, Luka Kazensky, Mirta Milić, Vilena Kašuba, Ante Cvitković, Mandica Sanković, Antun Šumanovac, Peter Møller, Goran Gajski
{"title":"Comparison of DNA damage in fresh and frozen blood samples: implications for the comet assay in human biomonitoring studies","authors":"Katarina Matković,&nbsp;Marko Gerić,&nbsp;Luka Kazensky,&nbsp;Mirta Milić,&nbsp;Vilena Kašuba,&nbsp;Ante Cvitković,&nbsp;Mandica Sanković,&nbsp;Antun Šumanovac,&nbsp;Peter Møller,&nbsp;Goran Gajski","doi":"10.1007/s00204-024-03823-1","DOIUrl":"10.1007/s00204-024-03823-1","url":null,"abstract":"<div><p>The use of the comet assay in large biomonitoring studies may present logistical and technical challenges because of the processing of numerous samples. Proper sample preservation becomes imperative to prevent spurious DNA breakage. Previous research has shown the feasibility of conducting the comet assay on frozen blood samples, highlighting the potential of freezing at – 80 °C in preserving DNA integrity. Nonetheless, this approach presents challenges, including potential DNA damage during freezing and thawing, variability in processing, and the need for standardized protocols. Our objective was to evaluate whether there are comparable results in DNA migration assessed by the comet assay between fresh and frozen blood samples on a larger scale (<i>N</i> = 373). In our findings, elevated DNA migration was evident in frozen samples relative to fresh ones. Additionally, smoking, alcohol consumption, and season were linked to increased DNA damage levels in whole blood cells. Based on our results and available literature, conducting the comet assay on frozen blood samples emerges as a practical and efficient approach for biomonitoring and epidemiological research. This method enables the assessment of DNA damage in large populations over time, with samples, if properly cryopreserved, that may be used for years, possibly even decades. These observations hold significant implications for large-scale human biomonitoring and long-term epidemiological studies, particularly when samples are collected during fieldwork or obtained from biobanks. Continued method optimization and validation efforts are essential to enhance the utility of this approach in environmental and occupational health studies, emphasizing caution when comparing data obtained between fresh and frozen blood samples.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3467 - 3476"},"PeriodicalIF":4.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
Synthesis and in vitro assessment of the reactivation profile of clinically available oximes on the acetylcholinesterase model inhibited by A-230 nerve agent surrogate 合成和体外评估临床可用的肟类化合物对受 A-230 神经毒剂替代物抑制的乙酰胆碱酯酶模型的再激活情况。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-14 DOI: 10.1007/s00204-024-03821-3
Leandro B. Bernardo, Caio V. N. Borges, Pedro A. G. Buitrago, Kamil Kuča, Samir F. A. Cavalcante, Roberto B. Sousa, Antônio L. S. Lima, Daniel A. S. Kitagawa
{"title":"Synthesis and in vitro assessment of the reactivation profile of clinically available oximes on the acetylcholinesterase model inhibited by A-230 nerve agent surrogate","authors":"Leandro B. Bernardo,&nbsp;Caio V. N. Borges,&nbsp;Pedro A. G. Buitrago,&nbsp;Kamil Kuča,&nbsp;Samir F. A. Cavalcante,&nbsp;Roberto B. Sousa,&nbsp;Antônio L. S. Lima,&nbsp;Daniel A. S. Kitagawa","doi":"10.1007/s00204-024-03821-3","DOIUrl":"10.1007/s00204-024-03821-3","url":null,"abstract":"<div><p>The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC “Annex on Chemicals” some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman’s assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from <i>Electrophorus eel</i>, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3397 - 3407"},"PeriodicalIF":4.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
A multi-biomarker micronucleus assay using imaging flow cytometry 利用成像流式细胞仪进行多生物标记微核检测。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-12 DOI: 10.1007/s00204-024-03801-7
Danielle S. G. Harte, Anthony M. Lynch, Jatin Verma, Paul Rees, Andrew Filby, John W. Wills, George E. Johnson
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