Archives of Toxicology最新文献

筛选
英文 中文
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":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 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
{"title":"A multi-biomarker micronucleus assay using imaging flow cytometry","authors":"Danielle S. G. Harte,&nbsp;Anthony M. Lynch,&nbsp;Jatin Verma,&nbsp;Paul Rees,&nbsp;Andrew Filby,&nbsp;John W. Wills,&nbsp;George E. Johnson","doi":"10.1007/s00204-024-03801-7","DOIUrl":"10.1007/s00204-024-03801-7","url":null,"abstract":"<div><p>Genetic toxicity testing assesses the potential of compounds to cause DNA damage. There are many genetic toxicology screening assays designed to assess the DNA damaging potential of chemicals in early drug development aiding the identification of promising drugs that have low-risk potential for causing genetic damage contributing to cancer risk in humans. Despite this, in vitro tests generate a high number of misleading positives, the consequences of which can lead to unnecessary animal testing and/or the abandonment of promising drug candidates. Understanding chemical Mode of Action (MoA) is vital to identifying the true genotoxic potential of substances and, therefore, the risk translation into the clinic. Here we demonstrate a simple, robust protocol for staining fixed, human-lymphoblast p53 proficient TK6 cells with antibodies against ɣH2AX, p53 and pH3S28 along with DRAQ5™ DNA staining that enables analysis of un-lysed cells via microscopy approaches such as imaging flow cytometry. Here, we used the Cytek® Amnis® ImageStream®X Mk II which provides a high-throughput acquisition platform with the sensitivity of flow cytometry and spatial morphological information associated with microscopy. Using the ImageStream manufacturer’s software (IDEAS® 6.2), a masking strategy was developed to automatically detect and quantify micronucleus events (MN) and characterise biomarker populations. The gating strategy developed enables the generation of a template capable of automatically batch processing data files quantifying cell-cycle, MN, ɣH2AX, p53 and pH3 populations simultaneously. In this way, we demonstrate how a multiplex system enables DNA damage assessment alongside MN identification using un-lysed cells on the imaging flow cytometry platform. As a proof-of-concept, we use the tool chemicals carbendazim and methyl methanesulphonate (MMS) to demonstrate the assay’s ability to correctly identify clastogenic or aneugenic MoAs using the biomarker profiles established.</p></div>","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589451","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
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,&nbsp;Shizhi Wang,&nbsp;Xing Zhang,&nbsp;Wenjing Yan,&nbsp;Haohan Liu,&nbsp;Xue Chen,&nbsp;Yamei Nie,&nbsp;Fengying Liu,&nbsp;Yun Zheng,&nbsp;Yiran Lu,&nbsp;Hua Jin","doi":"10.1007/s00204-024-03820-4","DOIUrl":"10.1007/s00204-024-03820-4","url":null,"abstract":"<div><p>Genetic variants can affect gene expression by altering the level of N6-methyladenosine (m<sup>6</sup>A) 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 m<sup>6</sup>A-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&gt;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 m<sup>6</sup>A modification of TAPBP compared with the A allele. This modification was facilitated by the m<sup>6</sup>A 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.</p></div>","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
{"title":"Targeting ferroptosis by natural products in pathophysiological conditions","authors":"Daheng Zheng,&nbsp;Shikai Jin,&nbsp;Pu-Ste Liu,&nbsp;Jianping Ye,&nbsp;Xin Xie","doi":"10.1007/s00204-024-03812-4","DOIUrl":"10.1007/s00204-024-03812-4","url":null,"abstract":"<div><p>Ferroptosis is a form of cell death that is induced by iron-mediated accumulation of lipid peroxidation. The involvement of ferroptosis in different pathophysiological conditions has offered new perspectives on potential therapeutic interventions. Natural products, which are widely recognized for their significance in drug discovery and repurposing, have shown great promise in regulating ferroptosis by targeting various ferroptosis players. In this review, we discuss the regulatory mechanisms of ferroptosis and its implications in different pathological conditions. We dissect the interactions between natural products and ferroptosis in cancer, ischemia/reperfusion, neurodegenerative diseases, acute kidney injury, liver injury, and cardiomyopathy, with an emphasis on the relevance of ferroptosis players to disease targetability.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578824","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
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,&nbsp;Tao Chen,&nbsp;Minghang Zhang,&nbsp;Xing Li,&nbsp;Rongkun Fu,&nbsp;Jianzhong Xu,&nbsp;Andreas Nüssler,&nbsp;Chenxi Gu","doi":"10.1007/s00204-024-03817-z","DOIUrl":"10.1007/s00204-024-03817-z","url":null,"abstract":"<div><p>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.</p></div>","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
Identification of phase-I and phase-II metabolites and the metabolic pathway of the novel synthetic cannabinoid 5F-EDMB-PICA in vitro 新型合成大麻素 5F-EDMB-PICA 体外第一阶段和第二阶段代谢物及代谢途径的鉴定。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-02 DOI: 10.1007/s00204-024-03790-7
Yujie Gao, Kaiting Shi, Peipei Wang, Xinyu Liu, Chenxi Liu, Liya Luo, Yanchen Lin, Lin Yang, Rongji Yang, Linchuan Liao
{"title":"Identification of phase-I and phase-II metabolites and the metabolic pathway of the novel synthetic cannabinoid 5F-EDMB-PICA in vitro","authors":"Yujie Gao,&nbsp;Kaiting Shi,&nbsp;Peipei Wang,&nbsp;Xinyu Liu,&nbsp;Chenxi Liu,&nbsp;Liya Luo,&nbsp;Yanchen Lin,&nbsp;Lin Yang,&nbsp;Rongji Yang,&nbsp;Linchuan Liao","doi":"10.1007/s00204-024-03790-7","DOIUrl":"10.1007/s00204-024-03790-7","url":null,"abstract":"<div><p>5F-EDMB-PICA is a newly emerged synthetic cannabinoid which has been characterized in relevant literature in recent years. Although phase-I metabolites of 5F-EDMB-PICA have been partly reported, the phase-II metabolism of this synthetic cannabinoid has not been studied yet. In this study, we established a phase-I and phase-II metabolism model in vitro by using pooled human liver microsomes, NADPH regeneration system, and UGT incubation system, with 1 mg/ml 5F-EDMB-PICA added and incubated at 37 °C for 60 min. The metabolites were analyzed by Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer, via which we discovered and identified 14 phase-I metabolites and 4 phase-II metabolites of 5F-EDMB-PICA, involving pathways such as ester hydrolysis, dehydrogenation, hydrolytic defluorination, hydroxylation, dihydroxylation, glucuronidation, and combinations of the pathways mentioned above. We recommend considering the monohydroxylation metabolites (M9, M10) with higher content and intact ester and 5-fluoropentyl structures as potential biomarkers of 5F-EDMB-PICA.</p></div>","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":"141490690","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,&nbsp;Faezeh Sadrabadi,&nbsp;Albert Braeuning,&nbsp;Pim E. G. Leonards,&nbsp;Thorsten Buhrke,&nbsp;Timo Hamers","doi":"10.1007/s00204-024-03814-2","DOIUrl":"10.1007/s00204-024-03814-2","url":null,"abstract":"<div><p>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 <i>PPARA</i> 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.</p></div>","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402862/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Screening for ferroptosis genes related to endometrial carcinoma and predicting of targeted drugs based on bioinformatics Correction to:基于生物信息学筛选与子宫内膜癌相关的铁蛋白沉积基因并预测靶向药物。
IF 4.8 2区 医学
Archives of Toxicology Pub Date : 2024-07-02 DOI: 10.1007/s00204-024-03804-4
Rui Wang, Wei Lang, Qian Xue, Le Zhang, Yunzhu Xujia, Chaofan Wang, Xin Fang, Shidi Gao, Li Guo
{"title":"Correction to: Screening for ferroptosis genes related to endometrial carcinoma and predicting of targeted drugs based on bioinformatics","authors":"Rui Wang,&nbsp;Wei Lang,&nbsp;Qian Xue,&nbsp;Le Zhang,&nbsp;Yunzhu Xujia,&nbsp;Chaofan Wang,&nbsp;Xin Fang,&nbsp;Shidi Gao,&nbsp;Li Guo","doi":"10.1007/s00204-024-03804-4","DOIUrl":"10.1007/s00204-024-03804-4","url":null,"abstract":"","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":"141490688","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,&nbsp;Frederike Nordmeier,&nbsp;Nadja Walle,&nbsp;Matthias W. Laschke,&nbsp;Michael D. Menger,&nbsp;Markus R. Meyer,&nbsp;Peter H. Schmidt,&nbsp;Nadine Schaefer","doi":"10.1007/s00204-024-03815-1","DOIUrl":"10.1007/s00204-024-03815-1","url":null,"abstract":"<div><p>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.</p></div>","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402846/pdf/","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":"OA","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,&nbsp;Viviani Nardini,&nbsp;Raul Moyses Veronezes,&nbsp;Jéssica Burlamaque Maciel,&nbsp;Amanda Cristina Trabuco,&nbsp;Mirian Félix De Carvalho,&nbsp;Caroline Fontanari,&nbsp;Marco Aurélio Sartim,&nbsp;Luiz Alberto Beraldo de Moraes,&nbsp;Lúcia Helena Faccioli","doi":"10.1007/s00204-024-03809-z","DOIUrl":"10.1007/s00204-024-03809-z","url":null,"abstract":"<div><p>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 <i>Bothrops moojeni</i> 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.</p></div>","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信