Archives of Toxicology最新文献_第10页

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, 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","doi":"10.1007/s00204-024-03824-0","DOIUrl":"https://doi.org/10.1007/s00204-024-03824-0","url":null,"abstract":"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 Bothrops erythromelas venom (BeV) 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 BeV, 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.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"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, Marko Gerić, Luka Kazensky, Mirta Milić, Vilena Kašuba, Ante Cvitković, Mandica Sanković, Antun Šumanovac, Peter Møller, Goran Gajski","doi":"10.1007/s00204-024-03823-1","DOIUrl":"https://doi.org/10.1007/s00204-024-03823-1","url":null,"abstract":"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 (N = 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.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"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, 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","doi":"10.1007/s00204-024-03821-3","DOIUrl":"https://doi.org/10.1007/s00204-024-03821-3","url":null,"abstract":"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 Electrophorus eel, 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.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"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 genetic variant in the TAPBP gene enhances cervical cancer susceptibility by increasing m⁶A modification. TAPBP 基因中的一个遗传变异会通过增加 m6A 修饰来提高宫颈癌的易感性。

IF 4.8 2区医学

Archives of Toxicology Pub Date : 2024-07-12 DOI: 10.1007/s00204-024-03820-4

Jing Hu, Shizhi Wang, Xing Zhang, Wenjing Yan, Haohan Liu, Xue Chen, Yamei Nie, Fengying Liu, Yun Zheng, Yiran Lu, Hua Jin

{"title":"A genetic variant in the TAPBP gene enhances cervical cancer susceptibility by increasing m6A modification.","authors":"Jing Hu, Shizhi Wang, Xing Zhang, Wenjing Yan, Haohan Liu, Xue Chen, Yamei Nie, Fengying Liu, Yun Zheng, Yiran Lu, Hua Jin","doi":"10.1007/s00204-024-03820-4","DOIUrl":"https://doi.org/10.1007/s00204-024-03820-4","url":null,"abstract":"Genetic variants can affect gene expression by altering the level of N6-methyladenosine (m6A) modifications. A better understanding of the association of these genetic variants with susceptibility to cervical cancer (CC) can promote advances in disease screening and treatment. Genome-wide identification of m6A-associated functional SNPs for CC was performed using the TCGA and JENGER databases, incorporating the data from RNA-seq and MeRIP-seq. The screened risk-associated SNP rs1059288 (A>G), which is located in the 3' UTR of TAPBP, was further validated in a case-control study involving 921 cases and 1077 controls. The results revealed a significant association between rs1059288 and the risk of CC (OR 1.48, 95% CI 1.13-1.92). Mechanistically, the presence of the risk G allele of rs1059288 was associated with increased m6A modification of TAPBP compared with the A allele. This modification was facilitated by the m6A methyltransferase METTL14 and the reading protein YTHDF2. Immunohistochemical staining of tissue microarrays containing 61 CC and 45 normal tissues showed an overexpression of TAPBP in CC. Furthermore, the upregulation of TAPBP promoted the growth and migration of CC cells as well as tumor-forming ability, inhibited apoptosis, and conferred increased resistance to commonly used chemotherapeutic drugs such as bleomycin, cisplatin, and doxorubicin. Knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway in CC cells and upregulated certain immune genes including ISG15, IRF3, PTPN6, and HLA-A. These findings offer insights into the involvement of genetic variations in TAPBP in the development and progression of CC.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589450","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

Targeting ferroptosis by natural products in pathophysiological conditions. 在病理生理条件下利用天然产品靶向铁蛋白沉积。

IF 4.8 2区医学

Archives of Toxicology Pub Date : 2024-07-10 DOI: 10.1007/s00204-024-03812-4

Daheng Zheng, Shikai Jin, Pu-Ste Liu, Jianping Ye, Xin Xie

引用次数: 0

Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release. 阿托伐他汀通过调节 Wnt5a 的释放对类固醇诱发的股骨头坏死有预防作用。

IF 4.8 2区医学

Archives of Toxicology Pub Date : 2024-07-07 DOI: 10.1007/s00204-024-03817-z

Junfeng Wu, Tao Chen, Minghang Zhang, Xing Li, Rongkun Fu, Jianzhong Xu, Andreas Nüssler, Chenxi Gu

{"title":"Atorvastatin exerts a preventive effect against steroid-induced necrosis of the femoral head by modulating Wnt5a release.","authors":"Junfeng Wu, Tao Chen, Minghang Zhang, Xing Li, Rongkun Fu, Jianzhong Xu, Andreas Nüssler, Chenxi Gu","doi":"10.1007/s00204-024-03817-z","DOIUrl":"https://doi.org/10.1007/s00204-024-03817-z","url":null,"abstract":"Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent form of osteonecrosis in young individuals. More efficacious clinical strategies must be used to prevent and treat this condition. One of the mechanisms through which SONFH operates is the disruption of normal differentiation in bone marrow adipocytes and osteoblasts due to prolonged and extensive use of glucocorticoids (GCs). In vitro, it was observed that atorvastatin (ATO) effectively suppressed the impact of dexamethasone (DEX) on bone marrow mesenchymal stem cells (BMSCs), specifically by augmenting their lipogenic differentiation while impeding their osteogenic differentiation. To investigate the underlying mechanisms further, we conducted transcriptome sequencing of BMSCs subjected to different treatments, leading to the identification of Wnt5a as a crucial gene regulated by ATO. The analyses showed that ATO exhibited the ability to enhance the expression of Wnt5a and modulate the MAPK pathway while regulating the Wnt canonical signaling pathway via the WNT5A/LRP5 pathway. Our experimental findings provide further evidence that the combined treatment of ATO and DEX effectively mitigates the effects of DEX, resulting in the upregulation of osteogenic genes (Runx2, Alpl, Tnfrsf11b, Ctnnb1, Col1a) and the downregulation of adipogenic genes (Pparg, Cebpb, Lpl), meanwhile leading to the upregulation of Wnt5a expression. So, this study offers valuable insights into the potential mechanism by which ATO can be utilized in the prevention of SONFH, thereby holding significant implications for the prevention and treatment of SONFH in clinical settings.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544501","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

In vitro screening of understudied PFAS with a focus on lipid metabolism disruption. 体外筛选未充分研究的全氟辛烷磺酸，重点关注脂质代谢干扰。

IF 4.8 2区医学

Archives of Toxicology Pub Date : 2024-07-02 DOI: 10.1007/s00204-024-03814-2

Lackson Kashobwe, Faezeh Sadrabadi, Albert Braeuning, Pim E G Leonards, Thorsten Buhrke, Timo Hamers

{"title":"In vitro screening of understudied PFAS with a focus on lipid metabolism disruption.","authors":"Lackson Kashobwe, Faezeh Sadrabadi, Albert Braeuning, Pim E G Leonards, Thorsten Buhrke, Timo Hamers","doi":"10.1007/s00204-024-03814-2","DOIUrl":"https://doi.org/10.1007/s00204-024-03814-2","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals used in many industrial applications. Exposure to PFAS is associated with several health risks, including a decrease in infant birth weight, hepatoxicity, disruption of lipid metabolism, and decreased immune response. We used the in vitro cell models to screen six less studied PFAS [perfluorooctane sulfonamide (PFOSA), perfluoropentanoic acid (PFPeA), perfluoropropionic acid (PFPrA), 6:2 fluorotelomer alcohol (6:2 FTOH), 6:2 fluorotelomer sulfonic acid (6:2 FTSA), and 8:2 fluorotelomer sulfonic acid (8:2 FTSA)] for their capacity to activate nuclear receptors and to cause differential expression of genes involved in lipid metabolism. Cytotoxicity assays were run in parallel to exclude that observed differential gene expression was due to cytotoxicity. Based on the cytotoxicity assays and gene expression studies, PFOSA was shown to be more potent than other tested PFAS. PFOSA decreased the gene expression of crucial genes involved in bile acid synthesis and detoxification, cholesterol synthesis, bile acid and cholesterol transport, and lipid metabolism regulation. Except for 6:2 FTOH and 8:2 FTSA, all tested PFAS downregulated PPARA gene expression. The reporter gene assay also showed that 8:2 FTSA transactivated the farnesoid X receptor (FXR). Based on this study, PFOSA, 6:2 FTSA, and 8:2 FTSA were prioritized for further studies to confirm and understand their possible effects on hepatic lipid metabolism.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490691","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

Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs? 猪肺部给药后，组织和体液中 7 种氮杂环吲哚衍生合成大麻素 5F-MDMB-P7AICA 的浓度是否会受到死后重新分布的影响？

IF 4.8 2区医学

Archives of Toxicology Pub Date : 2024-07-02 DOI: 10.1007/s00204-024-03815-1

Adrian A Doerr, Frederike Nordmeier, Nadja Walle, Matthias W Laschke, Michael D Menger, Markus R Meyer, Peter H Schmidt, Nadine Schaefer

{"title":"Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs?","authors":"Adrian A Doerr, Frederike Nordmeier, Nadja Walle, Matthias W Laschke, Michael D Menger, Markus R Meyer, Peter H Schmidt, Nadine Schaefer","doi":"10.1007/s00204-024-03815-1","DOIUrl":"https://doi.org/10.1007/s00204-024-03815-1","url":null,"abstract":"Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC-MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490689","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

Characterizing lipid constituents of B. moojeni snake venom: a comparative approach for chemical and biological investigations. B. moojeni 蛇毒脂质成分的特征：化学和生物学研究的比较方法。

IF 4.8 2区医学

Archives of Toxicology Pub Date : 2024-07-01 DOI: 10.1007/s00204-024-03809-z

Nathalia Santos Carvalho, Viviani Nardini, Raul Moyses Veronezes, Jéssica Burlamaque Maciel, Amanda Cristina Trabuco, Mirian Félix De Carvalho, Caroline Fontanari, Marco Aurélio Sartim, Luiz Alberto Beraldo de Moraes, Lúcia Helena Faccioli

{"title":"Characterizing lipid constituents of B. moojeni snake venom: a comparative approach for chemical and biological investigations.","authors":"Nathalia Santos Carvalho, Viviani Nardini, Raul Moyses Veronezes, Jéssica Burlamaque Maciel, Amanda Cristina Trabuco, Mirian Félix De Carvalho, Caroline Fontanari, Marco Aurélio Sartim, Luiz Alberto Beraldo de Moraes, Lúcia Helena Faccioli","doi":"10.1007/s00204-024-03809-z","DOIUrl":"https://doi.org/10.1007/s00204-024-03809-z","url":null,"abstract":"Snake venoms are complex mixtures majorly composed of proteins with well-studied biological effects. However, the exploration of non-protein components, especially lipids, remains limited despite their potential for discovering bioactive molecules. This study compares three liquid-liquid lipid extraction methods for both chemical and biological analyses of Bothrops moojeni snake venom. The methods evaluated include the Bligh and Dyer method (methanol, chloroform, water), considered standard; the Acunha method, a modification of the Bligh and Dyer protocol; and the Matyash method (MTBE/methanol/water), featuring an organic phase less dense than the aqueous phase. Lipidomic analysis using liquid chromatography with high-resolution mass spectrometry (LC-HRMS) system revealed comparable values of lipid constituents' peak intensity across different extraction methods. Our results show that all methods effectively extracted a similar quantity of lipid species, yielding approximately 17-18 subclasses per method. However, the Matyash and Acunha methods exhibited notably higher proportions of biologically active lipids compared to the Bligh and Dyer method, particularly in extracting lipid species crucial for cellular structure and function, such as sphingomyelins and phosphatidylinositol-phosphate. In conclusion, when selecting a lipid extraction method, it is essential to consider the study's objectives. For a biological approach, it is crucial to evaluate not only the total quantity of extracted lipids but also their quality and biological activity. The Matyash and Acunha methods show promise in this regard, potentially offering a superior option for extracting biologically active lipids compared to the Bligh and Dyer method.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475802","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

Avoiding a reproducibility crisis in regulatory toxicology-on the fundamental role of ring trials. 避免监管毒理学的再现性危机--环试的基本作用。

IF 6.1 2区医学

Archives of Toxicology Pub Date : 2024-07-01 Epub Date: 2024-04-30 DOI: 10.1007/s00204-024-03736-z

Miriam N Jacobs, Sebastian Hoffmann, Heli M Hollnagel, Petra Kern, Susanne N Kolle, Andreas Natsch, Robert Landsiedel

{"title":"Avoiding a reproducibility crisis in regulatory toxicology-on the fundamental role of ring trials.","authors":"Miriam N Jacobs, Sebastian Hoffmann, Heli M Hollnagel, Petra Kern, Susanne N Kolle, Andreas Natsch, Robert Landsiedel","doi":"10.1007/s00204-024-03736-z","DOIUrl":"10.1007/s00204-024-03736-z","url":null,"abstract":"The ongoing transition from chemical hazard and risk assessment based on animal studies to assessment relying mostly on non-animal data, requires a multitude of novel experimental methods, and this means that guidance on the validation and standardisation of test methods intended for international applicability and acceptance, needs to be updated. These so-called new approach methodologies (NAMs) must be applicable to the chemical regulatory domain and provide reliable data which are relevant to hazard and risk assessment. Confidence in and use of NAMs will depend on their reliability and relevance, and both are thoroughly assessed by validation. Validation is, however, a time- and resource-demanding process. As updates on validation guidance are conducted, the valuable components must be kept: Reliable data are and will remain fundamental. In 2016, the scientific community was made aware of the general crisis in scientific reproducibility-validated methods must not fall into this. In this commentary, we emphasize the central importance of ring trials in the validation of experimental methods. Ring trials are sometimes considered to be a major hold-up with little value added to the validation. Here, we clarify that ring trials are indispensable to demonstrate the robustness and reproducibility of a new method. Further, that methods do fail in method transfer and ring trials due to different stumbling blocks, but these provide learnings to ensure the robustness of new methods. At the same time, we identify what it would take to perform ring trials more efficiently, and how ring trials fit into the much-needed update to the guidance on the validation of NAMs.","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851194","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