Log in

Relevant bibliographies by topics / Toxicometabolomics / Journal articles

To see the other types of publications on this topic, follow the link: Toxicometabolomics.

Journal articles on the topic 'Toxicometabolomics'

Author: Grafiati

Published: 5 June 2025

Last updated: 16 July 2025

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 36 journal articles for your research on the topic 'Toxicometabolomics.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Araújo, Ana Margarida, Félix Carvalho, Paula Guedes de Pinho, and Márcia Carvalho. "Toxicometabolomics: Small Molecules to Answer Big Toxicological Questions." Metabolites 11, no. 10 (2021): 692. http://dx.doi.org/10.3390/metabo11100692.

Full text

Abstract:

Given the high biological impact of classical and emerging toxicants, a sensitive and comprehensive assessment of the hazards and risks of these substances to organisms is urgently needed. In this sense, toxicometabolomics emerged as a new and growing field in life sciences, which use metabolomics to provide new sets of susceptibility, exposure, and/or effects biomarkers; and to characterize in detail the metabolic responses and altered biological pathways that various stressful stimuli cause in many organisms. The present review focuses on the analytical platforms and the typical workflow employed in toxicometabolomic studies, and gives an overview of recent exploratory research that applied metabolomics in various areas of toxicology.

APA, Harvard, Vancouver, ISO, and other styles

2

Bouhifd, Mounir, Thomas Hartung, Helena T. Hogberg, Andre Kleensang, and Liang Zhao. "Review: Toxicometabolomics." Journal of Applied Toxicology 33, no. 12 (2013): 1365–83. http://dx.doi.org/10.1002/jat.2874.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

García-Barrera, Tamara, Gema Rodríguez-Moro, Belén Callejón-Leblic, Borrego Ana Arias, and José Luis Gómez-Ariza. "Mass spectrometry based analytical approaches and pitfalls for toxicometabolomics of arsenic in mammals: A tutorial review." Analytica Chimica Acta 1000 (November 2, 2017): 41e66. https://doi.org/10.1016/j.aca.2017.10.019.

Full text

Abstract:

The present review focus on the analytical platforms and the workflow for toxicometabolomics with a special emphasis on their strengths and pitfalls presenting as a case study the toxicometabolomics of arsenic in mammals. Although powerful analytical methods and techniques are currently available for metabolomics, the main “bottleneck” is still the absence of unified protocols for sample preparation (e.g. quenching, solvents used) as well as several important factors in toxicometabolomics, which drastically affect the metabolism (e.g. selection of model organisms, xenobiotic doses, chemical form of the xenobiotic, exposure route, biological sample). In this context, the applicability to complex samples, higher sensitivity, specificity and the possibility to perform quantitative analysis offered by MS is crucial to probe xenobiotic induced metabolic changes to evaluate the stress responses.Nowadays, the use of different metabolomic platforms allowed determining important changes in the metabolism induced by arsenic in mammals such as alterations in the energy (e.g. Glycolysis, Kreb's cycle), amino acid, lipid, nucleotide and androgen metabolisms.

APA, Harvard, Vancouver, ISO, and other styles

4

da Silva, Katyeny Manuela, Elias Iturrospe, Chloe Bars, et al. "Mass Spectrometry-Based Zebrafish Toxicometabolomics: A Review of Analytical and Data Quality Challenges." Metabolites 11, no. 9 (2021): 635. http://dx.doi.org/10.3390/metabo11090635.

Full text

Abstract:

Metabolomics has achieved great progress over the last 20 years, and it is currently considered a mature research field. As a result, the number of applications in toxicology, biomarker, and drug discovery has also increased. Toxicometabolomics has emerged as a powerful strategy to provide complementary information to study molecular-level toxic effects, which can be combined with a wide range of toxicological assessments and models. The zebrafish model has gained importance in recent decades as a bridging tool between in vitro assays and mammalian in vivo studies in the field of toxicology. Furthermore, as this vertebrate model is a low-cost system and features highly conserved metabolic pathways found in humans and mammalian models, it is a promising tool for toxicometabolomics. This short review aims to introduce zebrafish researchers interested in understanding the effects of chemical exposure using metabolomics to the challenges and possibilities of the field, with a special focus on toxicometabolomics-based mass spectrometry. The overall goal is to provide insights into analytical strategies to generate and identify high-quality metabolomic experiments focusing on quality management systems (QMS) and the importance of data reporting and sharing.

APA, Harvard, Vancouver, ISO, and other styles

5

Ribbenstedt, Anton, Malte Posselt, Carl Brunius, and Jonathan P. Benskin. "In-plate toxicometabolomics of single zebrafish embryos." Molecular Omics 16, no. 3 (2020): 185–94. http://dx.doi.org/10.1039/d0mo00007h.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Radilov, Andrey Stanislavovich, and Anton Igorevich Ukolov. "Toxicometabolomics — integration of preventive and analytical toxicology." Toxicological Review 30, no. 5 (2022): 286–96. http://dx.doi.org/10.47470/0869-7922-2022-30-5-286-296.

Full text

Abstract:

Introduction. This paper considers aspects of the development of a toxicokinetically based model for scaling the limit concentrations of toxic compounds in the air, estimating the coefficients of their material cumulation, as well as estimating the concentrations of toxicants in biological media expected in the course of biological control. The results of testing the model on the example of organophosphorus pesticides (OP) and volatile industrial pollutants (VIP) are presented. Material and methods. For experimental modeling of intoxication, male chinchilla rabbits obtained from the Rappolovo nursery were used. Blood sampling was carried out from the marginal vein of the ear. For the highly sensitive determination of OP and VIP in biological samples, previously developed highly sensitive gas chromatographic techniques were used. Calculation of toxicokinetic parameters was made using a two-compartment model. Results. A toxicokinetically based model for scaling the limit concentrations of toxic compounds in the air, estimating the coefficients of their material cumulation, and estimating the concentrations of toxicants in biological media expected in the course of biological control is proposed. Research limitations. The proposed algorithm for scaling toxicokinetic parameters can be applied under the condition that the bioavailability of chemical compounds for the animal and human body is close, as well as the area under the toxicokinetic curve that is close to a linear dependence on the dose. Conclusion. Using the proposed toxicokinetically substantiated model for scaling the threshold concentrations, recommendations were made on chemical-analytical methods of biological control in the working area and atmospheric air for OP and VIP.

APA, Harvard, Vancouver, ISO, and other styles

7

Gebreab, Kiflom Y., Muhamed N. H. Eeza, Tianyu Bai, et al. "Comparative toxicometabolomics of perfluorooctanoic acid (PFOA) and next-generation perfluoroalkyl substances." Environmental Pollution 265 (October 2020): 114928. http://dx.doi.org/10.1016/j.envpol.2020.114928.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Silva, T. D., C. Alves, G. M. Pereira, et al. "P10-23: Toxicometabolomics of atmospheric particulate matter (PM) in neuronal cells." Toxicology Letters 384 (September 2023): S154. http://dx.doi.org/10.1016/s0378-4274(23)00630-6.

Full text

APA, Harvard, Vancouver, ISO, and other styles

9

Kim, Kyu-Bong, Ji-Young Yang, Seung Jun Kwack, et al. "Toxicometabolomics of Urinary Biomarkers for Human Gastric Cancer in a Mouse Model." Journal of Toxicology and Environmental Health, Part A 73, no. 21-22 (2010): 1420–30. http://dx.doi.org/10.1080/15287394.2010.511545.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Ryu, Sung Ha, Ji Won Kim, Dahye Yoon, Suhkmann Kim, and Kyu-Bong Kim. "Serum and urine toxicometabolomics following gentamicin-induced nephrotoxicity in male Sprague-Dawley rats." Journal of Toxicology and Environmental Health, Part A 81, no. 11 (2018): 408–20. http://dx.doi.org/10.1080/15287394.2018.1451180.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Ryu, Sung Ha, Jung Dae Lee, Ji Won Kim, Siwon Kim, Suhkmann Kim, and Kyu-Bong Kim. "¹H NMR toxicometabolomics following cisplatin-induced nephrotoxicity in male rats." Journal of Toxicological Sciences 44, no. 1 (2019): 57–71. http://dx.doi.org/10.2131/jts.44.57.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

Ukolov, A. I., E. D. Kessenikh, A. S. Radilov, and N. V. Goncharov. "Toxicometabolomics: Identification of markers of chronic exposure to low doses of aliphatic hydrocarbons." Journal of Evolutionary Biochemistry and Physiology 53, no. 1 (2017): 25–36. http://dx.doi.org/10.1134/s0022093017010033.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Araújo, A. M., M. Carvalho, V. M. Costa, et al. "Early pathways of toxicity triggered by 3,4-methylene-dioxypyrovalerone unveiled by in vivo toxicometabolomics." Toxicology Letters 350 (September 2021): S130—S131. http://dx.doi.org/10.1016/s0378-4274(21)00553-1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Magny, Romain, Bruno Mégarbane, Pauline Guillaud, et al. "Life-Threatening Cardiogenic Shock Related to Venlafaxine Poisoning—A Case Report with Metabolomic Approach." Metabolites 13, no. 3 (2023): 353. http://dx.doi.org/10.3390/metabo13030353.

Full text

Abstract:

Metabolomics in clinical toxicology aim at reliably identifying and semi-quantifying a broad array of endogenous and exogenous metabolites using dedicated analytical methods. Here, we developed a three-step-based workflow to investigate the metabolic impact of the antidepressant drug venlafaxine in a poisoned patient who developed life-threatening cardiac failure managed with extracorporeal membrane oxygenation. Both targeted quantitative and untargeted semi-quantitative metabolomic analyses using liquid chromatography hyphenated to high-resolution tandem mass spectrometry were performed to determine the plasma kinetics of venlafaxine, O-desmethyl-venlafaxine, and N-desmethyl-venlafaxine and to identify sixteen different venlafaxine-derived metabolites including one unknown (i.e., venlafaxine conjugated to a hexosyl-radical), respectively. Correlations between the quantitative metabolomic data and annotated endogenous metabolites suggested impaired amino acid and lipid metabolism, Krebs cycle, and kynurenine pathway. This preliminary study represents a first step towards a more extensive application of toxicometabolomics in clinical toxicology and a useful workflow to identify the biomarkers of toxicity.

APA, Harvard, Vancouver, ISO, and other styles

15

García-Barrera, T., G. Rodríguez-Moro, B. Callejón-Leblic, A. Arias-Borrego, and J. L. Gómez-Ariza. "Mass spectrometry based analytical approaches and pitfalls for toxicometabolomics of arsenic in mammals: A tutorial review." Analytica Chimica Acta 1000 (February 2018): 41–66. http://dx.doi.org/10.1016/j.aca.2017.10.019.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Chang, Hao, Xi Zhang, Zhonghua Lu, Biling Gao, and Heqing Shen. "Metabolite correlation permutation after mice acute exposure to PM2.5: Holistic exploration of toxicometabolomics by network analysis." Environmental Pollution 352 (July 2024): 124128. http://dx.doi.org/10.1016/j.envpol.2024.124128.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Khoshkam, Maryam, Yasamin Baghdadchi, Roghaye Arezumand, and Ali Ramazani. "Synthesis, characterization and in vivo evaluation of cadmium telluride quantum dots toxicity in mice by toxicometabolomics approach." Toxicology Mechanisms and Methods 28, no. 7 (2018): 539–46. http://dx.doi.org/10.1080/15376516.2018.1471635.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Hemmer, Selina, Lea Wagmann, Benedikt Pulver, Folker Westphal, and Markus R. Meyer. "In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS/MS." Metabolites 12, no. 12 (2022): 1209. http://dx.doi.org/10.3390/metabo12121209.

Full text

Abstract:

Synthetic cathinones are one important group amongst new psychoactive substances (NPS) and limited information is available regarding their toxicokinetics and -dynamics. Over the past few years, nontargeted toxicometabolomics has been increasingly used to study compound-related effects of NPS to identify important exogenous and endogenous biomarkers. In this study, the effects of the synthetic cathinone PCYP (2-cyclohexyl-1-phenyl-2-(1-pyrrolidinyl)-ethanone) on in vitro and in vivo metabolomes were investigated. Pooled human-liver microsomes and blood and urine of male Wistar rats were used to generate in vitro and in vivo data, respectively. Samples were analyzed by liquid chromatography and high-resolution mass spectrometry using an untargeted metabolomics workflow. Statistical evaluation was performed using univariate and multivariate statistics. In total, sixteen phase I and one phase II metabolite of PCYP could be identified as exogenous biomarkers. Five endogenous biomarkers (e.g., adenosine and metabolites of tryptophan metabolism) related to PCYP intake could be identified in rat samples. The present data on the exogenous biomarker of PCYP are crucial for setting up analytical screening procedures. The data on the endogenous biomarker are important for further studies to better understand the physiological changes associated with cathinone abuse but may also serve in the future as additional markers for an intake.

APA, Harvard, Vancouver, ISO, and other styles

19

Ribbenstedt, Anton, Malte Posselt, and Jonathan P. Benskin. "Toxicometabolomics and Biotransformation Product Elucidation in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant to Morphologically Altering Doses." Chemical Research in Toxicology 35, no. 3 (2022): 431–39. http://dx.doi.org/10.1021/acs.chemrestox.1c00335.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Lee, Hwa-Kyung, Kyeongnam Kim, Junghak Lee, et al. "Targeted toxicometabolomics of endosulfan sulfate in adult zebrafish (Danio rerio) using GC-MS/MS in multiple reaction monitoring mode." Journal of Hazardous Materials 389 (May 2020): 122056. http://dx.doi.org/10.1016/j.jhazmat.2020.122056.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Kim, Kyu-Bong, So Young Um, Myeon Woo Chung, et al. "Toxicometabolomics approach to urinary biomarkers for mercuric chloride (HgCl2)-induced nephrotoxicity using proton nuclear magnetic resonance (1H NMR) in rats." Toxicology and Applied Pharmacology 249, no. 2 (2010): 114–26. http://dx.doi.org/10.1016/j.taap.2010.08.017.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Hemmer, Selina, Lea Wagmann, and Markus R. Meyer. "Altered metabolic pathways elucidated via untargeted in vivo toxicometabolomics in rat urine and plasma samples collected after controlled application of a human equivalent amphetamine dose." Archives of Toxicology 95, no. 10 (2021): 3223–34. http://dx.doi.org/10.1007/s00204-021-03135-8.

Full text

Abstract:

AbstractAmphetamine is widely consumed as drug of abuse due to its stimulating and cognitive enhancing effects. Since amphetamine has been on the market for quite a long time and it is one of the most commonly used stimulants worldwide, to date there is still limited information on its effects on the metabolome. In recent years, untargeted toxicometabolomics have been increasingly used to study toxicity-related pathways of such drugs of abuse to find and identify important endogenous and exogenous biomarkers. In this study, the acute effects of amphetamine intake on plasma and urinary metabolome in rats were investigated. For this purpose, samples of male Wistar rats after a single dose of amphetamine (5 mg/kg) were compared to a control group using an untargeted metabolomics approach. Analysis was performed using normal and reversed phase liquid chromatography coupled to high-resolution mass spectrometry using positive and negative ionization mode. Statistical evaluation was performed using Welch’s two-sample t test, hierarchical clustering, as well as principal component analysis. The results of this study demonstrate a downregulation of amino acids in plasma samples after amphetamine exposure. Furthermore, four new potential biomarkers N-acetylamphetamine, N-acetyl-4-hydroxyamphetamine, N-acetyl-4-hydroxyamphetamine glucuronide, and amphetamine succinate were identified in urine. The present study complements previous data and shows that several studies are necessary to elucidate altered metabolic pathways associated with acute amphetamine exposure.

APA, Harvard, Vancouver, ISO, and other styles

23

Lawson, Ariel, Mark Annunziato, Narmin Bashirova, et al. "High-Resolution Magic-Angle Spinning Nuclear Magnetic Resonance Identifies Impairment of Metabolism by T-2 Toxin, in Relation to Toxicity, in Zebrafish Embryo Model." Toxins 16, no. 10 (2024): 424. http://dx.doi.org/10.3390/toxins16100424.

Full text

Abstract:

Among the widespread trichothecene mycotoxins, T-2 toxin is considered the most toxic congener. In the present study, we utilized high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR), coupled to the zebrafish (Danio rerio) embryo model, as a toxicometabolomics approach to elucidate the cellular, molecular and biochemical pathways associated with T-2 toxicity. Aligned with previous studies in the zebrafish embryo model, exposure to T-2 toxin was lethal in the high parts-per-billion (ppb) range, with a median lethal concentration (LC50) of 105 ppb. Exposure to the toxins was, furthermore, associated with system-specific alterations in the production of reactive oxygen species (ROS), including decreased ROS production in the liver and increased ROS in the brain region, in the exposed embryos. Moreover, metabolic profiling based on HRMAS NMR revealed the modulation of numerous, interrelated metabolites, specifically including those associated with (1) phase I and II detoxification, and antioxidant pathways; (2) disruption of the phosphocholine lipids of cell membranes; (3) mitochondrial energy metabolism, including apparent disruption of the tricarboxylic acid (TCA) cycle, and the electron transport chain of oxidative phosphorylation, as well as “upstream” effects on carbohydrate, i.e., glucose metabolism; and (4) several compensatory catabolic pathways. Taken together, these observations enabled development of an integrated, system-level model of T-2 toxicity in relation to human and animal health.

APA, Harvard, Vancouver, ISO, and other styles

24

Zuberi, Zain, Muhamed N. H. Eeza, Joerg Matysik, John P. Berry, and A. Alia. "NMR-Based Metabolic Profiles of Intact Zebrafish Embryos Exposed to Aflatoxin B1 Recapitulates Hepatotoxicity and Supports Possible Neurotoxicity." Toxins 11, no. 5 (2019): 258. http://dx.doi.org/10.3390/toxins11050258.

Full text

Abstract:

Aflatoxin B1 (AFB1) is a widespread contaminant of grains and other agricultural crops and is globally associated with both acute toxicity and carcinogenicity. In the present study, we utilized nuclear magnetic resonance (NMR), and specifically high-resolution magic angle spin (HRMAS) NMR, coupled to the zebrafish (Danio rerio) embryo toxicological model, to characterize metabolic profiles associated with exposure to AFB1. Exposure to AFB1 was associated with dose-dependent acute toxicity (i.e., lethality) and developmental deformities at micromolar (≤ 2 µM) concentrations. Toxicity of AFB1 was stage-dependent and specifically consistent, in this regard, with a role of the liver and phase I enzyme (i.e., cytochrome P450) bioactivation. Metabolic profiles of intact zebrafish embryos exposed to AFB1 were, furthermore, largely consistent with hepatotoxicity previously reported in mammalian systems including metabolites associated with cytotoxicity (i.e., loss of cellular membrane integrity), glutathione-based detoxification, and multiple pathways associated with the liver including amino acid, lipid, and carbohydrate (i.e., energy) metabolism. Taken together, these metabolic alterations enabled the proposal of an integrated model of the hepatotoxicity of AFB1 in the zebrafish embryo system. Interestingly, changes in amino acid neurotransmitters (i.e., Gly, Glu, and GABA), as a key modulator of neural development, supports a role in recently-reported neurobehavioral and neurodevelopmental effects of AFB1 in the zebrafish embryo model. The present study reinforces not only toxicological pathways of AFB1 (i.e., hepatotoxicity, neurotoxicity), but also multiple metabolites as potential biomarkers of exposure and toxicity. More generally, this underscores the capacity of NMR-based approaches, when coupled to animal models, as a powerful toxicometabolomics tool.

APA, Harvard, Vancouver, ISO, and other styles

25

Manier, Sascha K., Florian Schwermer, Lea Wagmann, Niels Eckstein, and Markus R. Meyer. "Liquid Chromatography-High-Resolution Mass Spectrometry-Based In Vitro Toxicometabolomics of the Synthetic Cathinones 4-MPD and 4-MEAP in Pooled Human Liver Microsomes." Metabolites 11, no. 1 (2020): 3. http://dx.doi.org/10.3390/metabo11010003.

Full text

Abstract:

Synthetic cathinones belong to the most often seized new psychoactive substances on an international level. This study investigated the toxicometabolomics, particularly the in vitro metabolism of 2-(methylamino)-1-(4-methylphenyl)-1-pentanone (4-MPD) and 2-(ethylamino)-1-(4-methylphenyl)-1-pentanone (4-MEAP) in pooled human liver microsomes (pHLM) using untargeted metabolomics techniques. Incubations were performed with the substrates in concentrations ranging from 0, 12.5, and 25 µM. Analysis was done by means of high-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS/MS) in full scan only and the obtained data was evaluated using XCMS Online and MetaboAnalyst. Significant features were putatively identified using a separate parallel reaction monitoring method. Statistical analysis was performed using Kruskal-Wallis test for prefiltering significant features and subsequent hierarchical clustering, as well as principal component analysis (PCA). Hierarchical clustering or PCA showed a distinct clustering of all concentrations with most of the features z-scores rising with the concentration of the investigated substances. Identification of significant features left many of them unidentified but revealed metabolites of both 4-MPD and 4-MEAP. Both substances formed carboxylic acids, were hydroxylated at the alkyl chain, and formed metabolites after combined hydroxylation and reduction of the cathinone oxo group. 4-MPD additionally formed a dihydroxy metabolite and a hydroxylamine. 4-MEAP was additionally found reduced at the cathinone oxo group, N-dealkylated, and formed an oxo metabolite. These findings are the first to describe the metabolic pathways of 4-MPD and to extend our knowledge about the metabolism of 4-MEAP. Findings, particularly the MS data of the metabolites, are essential for setting up metabolite-based toxicological (urine) screening procedures.

APA, Harvard, Vancouver, ISO, and other styles

26

Malinowska, Julia M., Taina Palosaari, Jukka Sund, et al. "Automated Sample Preparation and Data Collection Workflow for High-Throughput In Vitro Metabolomics." Metabolites 12, no. 1 (2022): 52. http://dx.doi.org/10.3390/metabo12010052.

Full text

Abstract:

Regulatory bodies have started to recognise the value of in vitro screening and metabolomics as two types of new approach methodologies (NAMs) for chemical risk assessments, yet few high-throughput in vitro toxicometabolomics studies have been reported. A significant challenge is to implement automated sample preparation of the low biomass samples typically used for in vitro screening. Building on previous work, we have developed, characterised and demonstrated an automated sample preparation and analysis workflow for in vitro metabolomics of HepaRG cells in 96-well microplates using a Biomek i7 Hybrid Workstation (Beckman Coulter) and Orbitrap Elite (Thermo Scientific) high-resolution nanoelectrospray direct infusion mass spectrometry (nESI-DIMS), across polar metabolites and lipids. The experimental conditions evaluated included the day of metabolite extraction, order of extraction of samples in 96-well microplates, position of the 96-well microplate on the instrument’s deck and well location within a microplate. By using the median relative standard deviation (mRSD (%)) of spectral features, we have demonstrated good repeatability of the workflow (final mRSD < 30%) with a low percentage of features outside the threshold applied for statistical analysis. To improve the quality of the automated workflow further, small method modifications were made and then applied to a large cohort study (4860 sample infusions across three nESI-DIMS assays), which confirmed very high repeatability of the whole workflow from cell culturing to metabolite measurements, whilst providing a significant improvement in sample throughput. It is envisioned that the automated in vitro metabolomics workflow will help to advance the application of metabolomics (as a part of NAMs) in chemical safety, primarily as an approach for high throughput screening and prioritisation.

APA, Harvard, Vancouver, ISO, and other styles

27

Manier, Sascha K., Lea Wagmann, Veit Flockerzi та Markus R. Meyer. "Toxicometabolomics of the new psychoactive substances α-PBP and α-PEP studied in HepaRG cell incubates by means of untargeted metabolomics revealed unexpected amino acid adducts". Archives of Toxicology 94, № 6 (2020): 2047–59. http://dx.doi.org/10.1007/s00204-020-02742-1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Chousidis, Ieremias, Theodoros Chatzimitakos, Dimitrios Leonardos, Michaela D. Filiou, Constantine D. Stalikas, and Ioannis D. Leonardos. "Cannabinol in the spotlight: Toxicometabolomic study and behavioral analysis of zebrafish embryos exposed to the unknown cannabinoid." Chemosphere 252 (August 2020): 126417. http://dx.doi.org/10.1016/j.chemosphere.2020.126417.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

García-Sevillano, M. A., T. García-Barrera, F. Navarro, et al. "Combination of direct infusion mass spectrometry and gas chromatography mass spectrometry for toxicometabolomic study of red blood cells and serum of mice Mus musculus after mercury exposure." Journal of Chromatography B 985 (March 2015): 75–84. http://dx.doi.org/10.1016/j.jchromb.2015.01.029.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Al Sultan, Abdullah, Zahra Rattray, and Nicholas J. W. Rattray. "Toxicometabolomics-based cardiotoxicity evaluation of Thiazolidinedione exposure in human-derived cardiomyocytes." Metabolomics 20, no. 2 (2024). http://dx.doi.org/10.1007/s11306-024-02097-z.

Full text

Abstract:

Abstract Introduction Thiazolidinediones (TZDs), represented by pioglitazone and rosiglitazone, are a class of cost-effective oral antidiabetic agents posing a marginal hypoglycaemia risk. Nevertheless, observations of heart failure have hindered the clinical use of both therapies. Objective Since the mechanism of TZD-induced heart failure remains largely uncharacterised, this study aimed to explore the as-yet-unidentified mechanisms underpinning TZD cardiotoxicity using a toxicometabolomics approach. Methods The present investigation included an untargeted liquid chromatography–mass spectrometry-based toxicometabolomics pipeline, followed by multivariate statistics and pathway analyses to elucidate the mechanism(s)of TZD-induced cardiotoxicity using AC16 human cardiomyocytes as a model, and to identify the prognostic features associated with such effects. Results Acute administration of either TZD agent resulted in a significant modulation in carnitine content, reflecting potential disruption of the mitochondrial carnitine shuttle. Furthermore, perturbations were noted in purine metabolism and amino acid fingerprints, strongly conveying aberrations in cardiac energetics associated with TZD usage. Analysis of our findings also highlighted alterations in polyamine (spermine and spermidine) and amino acid (L-tyrosine and valine) metabolism, known modulators of cardiac hypertrophy, suggesting a potential link to TZD cardiotoxicity that necessitates further research. In addition, this comprehensive study identified two groupings – (i) valine and creatine, and (ii) L-tryptophan and L-methionine – that were significantly enriched in the above-mentioned mechanisms, emerging as potential fingerprint biomarkers for pioglitazone and rosiglitazone cardiotoxicity, respectively. Conclusion These findings demonstrate the utility of toxicometabolomics in elaborating on mechanisms of drug toxicity and identifying potential biomarkers, thus encouraging its application in the toxicological sciences. (245 words)

APA, Harvard, Vancouver, ISO, and other styles

31

Bernhard, Annette, Rikke Poulsen, Anna M. Brun Hansen, and Martin Hansen. "Toxicometabolomics as a tool for next generation environmental risk assessment." EFSA Journal 21 (November 2023). http://dx.doi.org/10.2903/j.efsa.2023.e211005.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Hemmer, Selina, Sascha K. Manier, Lea Wagmann, and Markus R. Meyer. "Comparison of reversed-phase, hydrophilic interaction, and porous graphitic carbon chromatography columns for an untargeted toxicometabolomics study in pooled human liver microsomes, rat urine, and rat plasma." Metabolomics 20, no. 3 (2024). http://dx.doi.org/10.1007/s11306-024-02115-0.

Full text

Abstract:

Abstract Introduction Untargeted metabolomics studies are expected to cover a wide range of compound classes with high chemical diversity and complexity. Thus, optimizing (pre-)analytical parameters such as the analytical liquid chromatography (LC) column is crucial and the selection of the column depends primarily on the study purpose. Objectives The current investigation aimed to compare six different analytical columns. First, by comparing the chromatographic resolution of selected compounds. Second, on the outcome of an untargeted toxicometabolomics study using pooled human liver microsomes (pHLM), rat plasma, and rat urine as matrices. Methods Separation and analysis were performed using three different reversed-phase (Phenyl-Hexyl, BEH C18, and Gold C18), two hydrophilic interaction chromatography (HILIC) (ammonium-sulfonic acid and sulfobetaine), and one porous graphitic carbon (PGC) columns coupled to high-resolution mass spectrometry (HRMS). Their impact was evaluated based on the column performance and the size of feature count, amongst others. Results All three reversed-phase columns showed a similar performance, whereas the PGC column was superior to both HILIC columns at least for polar compounds. Comparing the size of feature count across all datasets, most features were detected using the Phenyl-Hexyl or sulfobetaine column. Considering the matrices, most significant features were detected in urine and pHLM after using the sulfobetaine and in plasma after using the ammonium-sulfonic acid column. Conclusion The results underline that the outcome of this untargeted toxicometabolomic study LC-HRMS metabolomic study was highly influenced by the analytical column, with the Phenyl-Hexyl or sulfobetaine column being the most suitable. However, column selection may also depend on the investigated compounds as well as on the investigated matrix. Graphical abstract

APA, Harvard, Vancouver, ISO, and other styles

33

Al Sultan, Abdullah, Zahra Rattray, and Nicholas J. W. Rattray. "Integrative analysis of toxicometabolomics and toxicoproteomics data: new molecular insights into thiazolidinedione-induced cardiotoxicity." Metabolomics 21, no. 1 (2024). https://doi.org/10.1007/s11306-024-02201-3.

Full text

Abstract:

Abstract Introduction Despite the well-established efficacy of thiazolidinediones (TZDs), including pioglitazone and rosiglitazone, in type II diabetes management, their potential contribution to heart failure risk remains a significant area of uncertainty. This incomplete understanding, which persists despite decades of clinical use of TZDs, has generated ongoing controversy and unanswered questions regarding their safety profiles, ultimately limiting their broader clinical application. Objective and methods This study presented a multi-omics approach, integrating toxicoproteomics and toxicometabolomics data with the goal of uncovering novel mechanistic insights into TZD cardiotoxicity and identifying molecular signatures predictive of side effect progression. Results Network analysis of proteo-metabolomic data revealed a distinct fingerprint of disrupted biochemical pathways, which were primarily related to energy metabolism. Downregulation of oxidative phosphorylation and fatty acid synthesis was coupled with increased activity in anaerobic glycolysis, the pentose phosphate pathway, and amino acid and purine metabolism. This suggests a potential metabolic shift in AC16 cells from fatty acid oxidation towards anaerobic glycolysis, potentially contributing to observed cardiotoxicity. Additionally, the study identified a marked disruption in the glutathione system, indicating an imbalanced redox state triggered by TZD exposure. Importantly, our analysis identified key molecular signatures across omics datasets, including prominent signatures of amino acids like L-ornithine, L-tyrosine and glutamine, which are evidently associated with heart failure, supporting their potential use for the early prediction of cardiotoxicity progression. Conclusion By uncovering a novel mechanistic explanation for TZD cardiotoxicity, this study simultaneously illuminates potential therapeutic interventions, opening avenues for future research to improve the safety profile of TZD agents. (250 words) Graphical abstracts

APA, Harvard, Vancouver, ISO, and other styles

34

Yuan, Xiu, Junghak Lee, Eunyoung Park, Hwa-Kyung Lee, and Jeong-Han Kim. "Toxicometabolomics of lindane in adult zebrafish (Danio rerio) using GC-MS/MS and LC-Orbitrap-MS/MS." Applied Biological Chemistry 64, no. 1 (2021). http://dx.doi.org/10.1186/s13765-021-00623-4.

Full text

Abstract:

AbstractLindane is a broad-spectrum persistent organochlorine pesticide that has been used to control pests for many years. In this study, its toxic mechanisms in adult zebrafish were investigated using targeted metabolomics with GC-MS/MS and non-targeted metabolomics with LC-Orbitrap-MS/MS. Zebrafish was exposed to lindane in water for 48 h in three groups: control, low exposure (1/10 LC50) and high exposure (LC50). In the zebrafish exposed to low concentration of lindane, 2.24–3.98 mg/kg of lindane were determined, while 35.67–56.46 mg/kg were observed in the zebrafish exposed to high concentration. A total of 118 metabolites were identified from 394 metabolites on GC-MS/MS and 45 metabolites were selected as biomarkers. A total of 62 metabolites were identified on LC-Orbitrap-MS/MS and 7 metabolites were selected as biomarkers. Three groups were well separated on partial least squares-discriminant analysis (PLS-DA), and a total of 52 metabolites in both the targeted and non-targeted metabolites were selected as biomarkers through VIP and ANOVA tests to construct a heatmap. Five metabolic pathways such as the pentose phosphate pathway (PPP), histidine metabolism, phenylalanine metabolism, alanine/aspartate/glutamate metabolism, and phenylalanine/tyrosine/tryptophan biosynthesis, were observed to show toxicologically significant alterations. Oxidative stress was also confirmed through MDA and ROS assays. Such perturbations of the metabolic pathways of zebrafish caused by the exposure to lindane resulted in significant toxicological effects.

APA, Harvard, Vancouver, ISO, and other styles

35

Araújo, Ana Margarida, Márcia Carvalho, Vera Marisa Costa, et al. "In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV)." Archives of Toxicology, November 19, 2020. http://dx.doi.org/10.1007/s00204-020-02949-2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Garcia-Llorens, Guillem, Teresa Martínez-Sena, Eugenia Pareja, Laia Tolosa, José V. Castell, and Roque Bort. "A robust reprogramming strategy for generating hepatocyte-like cells usable in pharmaco-toxicological studies." Stem Cell Research & Therapy 14, no. 1 (2023). http://dx.doi.org/10.1186/s13287-023-03311-w.

Full text

Abstract:

Abstract Background High-throughput pharmaco-toxicological testing frequently relies on the use of established liver-derived cell lines, such as HepG2 cells. However, these cells often display limited hepatic phenotype and features of neoplastic transformation that may bias the interpretation of the results. Alternate models based on primary cultures or differentiated pluripotent stem cells are costly to handle and difficult to implement in high-throughput screening platforms. Thus, cells without malignant traits, optimal differentiation pattern, producible in large and homogeneous amounts and with patient-specific phenotypes would be desirable. Methods We have designed and implemented a novel and robust approach to obtain hepatocytes from individuals by direct reprogramming, which is based on a combination of a single doxycycline-inducible polycistronic vector system expressing HNF4A, HNF1A and FOXA3, introduced in human fibroblasts previously transduced with human telomerase reverse transcriptase (hTERT). These cells can be maintained in fibroblast culture media, under standard cell culture conditions. Results Clonal hTERT-transduced human fibroblast cell lines can be expanded at least to 110 population doublings without signs of transformation or senescence. They can be easily differentiated at any cell passage number to hepatocyte-like cells with the simple addition of doxycycline to culture media. Acquisition of a hepatocyte phenotype is achieved in just 10 days and requires a simple and non-expensive cell culture media and standard 2D culture conditions. Hepatocytes reprogrammed from low and high passage hTERT-transduced fibroblasts display very similar transcriptomic profiles, biotransformation activities and show analogous pattern behavior in toxicometabolomic studies. Results indicate that this cell model outperforms HepG2 in toxicological screening. The procedure also allows generation of hepatocyte-like cells from patients with given pathological phenotypes. In fact, we succeeded in generating hepatocyte-like cells from a patient with alpha-1 antitrypsin deficiency, which recapitulated accumulation of intracellular alpha-1 antitrypsin polymers and deregulation of unfolded protein response and inflammatory networks. Conclusion Our strategy allows the generation of an unlimited source of clonal, homogeneous, non-transformed induced hepatocyte-like cells, capable of performing typical hepatic functions and suitable for pharmaco-toxicological high-throughput testing. Moreover, as far as hepatocyte-like cells derived from fibroblasts isolated from patients suffering hepatic dysfunctions, retain the disease traits, as demonstrated for alpha-1-antitrypsin deficiency, this strategy can be applied to the study of other cases of anomalous hepatocyte functionality.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!