Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells

Ramirez, Tzutzuy; Strigun, Alexander; Verlohner, Andreas; Huener, Hans-Albrecht; Peter, Erik; Herold, Michael; Bordag, Natalie; Mellert, Werner; Walk, Tilmann; Spitzer, Michael; Jiang, Xiaoqi; Sperber, Saskia; Hofmann, Thomas; Hartung, Thomas; Kamp, Hennicke; van Ravenzwaay, Ben

doi:10.1007/s00204-017-2079-6

Cited by 164Drug-Induced Hepatotoxicity and ProtectionMetabolomics and Mass Spectrometry StudiesAnimal testing and alternatives

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Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells

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Ramirez, Tzutzuy, Strigun, Alexander, Verlohner, Andreas, Huener, Hans-Albrecht, Peter, Erik, Herold, Michael, Bordag, Natalie, Mellert, Werner, Walk, Tilmann, Spitzer, Michael, Jiang, Xiaoqi, Sperber, Saskia, Hofmann, Thomas, Hartung, Thomas, Kamp, Hennicke, van Ravenzwaay, Ben·2018·Archives of Toxicology

DOI 10.1007/s00204-017-2079-6PMC PMC5818600

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Abstract

Liver toxicity is a leading systemic toxicity of drugs and chemicals demanding more human-relevant, high throughput, cost effective in vitro solutions. In addition to contributing to animal welfare, in vitro techniques facilitate exploring and understanding the molecular mechanisms underlying toxicity. New 'omics technologies can provide comprehensive information on the toxicological mode of action of compounds, as well as quantitative information about the multi-parametric metabolic response of cellular systems in normal and patho-physiological conditions. Here, we combined mass-spectroscopy metabolomics with an in vitro liver toxicity model. Metabolite profiles of HepG2 cells treated with 35 test substances resulted in 1114 cell supernatants and 3556 intracellular samples analyzed by metabolomics. Control samples showed relative standard deviations of about 10-15%, while the technical replicates were at 5-10%. Importantly, this procedure revealed concentration-response effects and patterns of metabolome changes that are consistent for different liver toxicity mechanisms (liver enzyme induction/inhibition, liver toxicity and peroxisome proliferation). Our findings provide evidence that identifying organ toxicity can be achieved in a robust, reliable, human-relevant system, representing a non-animal alternative for systemic toxicology.

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HepG2 is suitable for studying general mechanisms of cytotoxicity and cellular stress response but limited for quantitative prediction of metabolism and biotransformation of many compounds.
“Recent reviews and experimental studies directly interpret HepG2 as a model suitable for solving certain toxicological problems, in particular for studying general mechanisms of cytotoxicity and cellular stress response (e.g., activation of transcription factors activator protein-1 (AP1), p53, nuclear factor-erythroid 2 related factor 2 (Nrf2), and nuclear factor kappa B (NF-κB)) [109,110,111],”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [110]
The Results section (page not provided) describes HepG2 as a robust in vitro model and reports metabolite changes associated with cytotoxicity and specific toxicity mechanisms. The Discussion notes its limited metabolic capacity. However, the cited paper does not establish the sentence’s specific claim about studying cellular stress responses through AP1, p53, Nrf2, or NF-κB activation. (LLM, conf=0.84)
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Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., et al. (2000) · Regulatory Toxicology and Pharmacology · doi:10.1006/rtph.2000.1399 · Cited by 2,050
Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties
Wilkening, S., Stahl, F., & Bader, A. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.8.1035 · Cited by 794
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Gerets, H. H. J., Tilmant, K., Gerin, B., Chanteux, H., Depelchin, B. O., Dhalluin, S., & Atienzar, F. A. (2012) · Cell Biology and Toxicology · doi:10.1007/s10565-011-9208-4 · Cited by 698
Toxicology for the twenty-first century
Härtung, T. (2009) · Nature · doi:10.1038/460208a · Cited by 686
PPARα Agonist-Induced Rodent Tumors: Modes of Action and Human Relevance
Klaunig, J. E., Babich, M. A., Baetcke, K. P., Cook, J. C., Corton, J. C., David, R. M., DeLuca, J. G., Lai, D. Y., McKee, R. H., Peters, J. M., et al. (2003) · Critical Reviews in Toxicology · doi:10.1080/713608372 · Cited by 614
Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2
Raucy, J. L., Lasker, J. M., Lieber, C. S., & Black, M. (1989) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(89)90278-6 · Cited by 478
Regulation of bile acid synthesis
Chiang, J. Y. L. (1998) · Frontiers in bioscience · doi:10.2741/a273 · Cited by 400
Metabolomics in toxicology and preclinical research
Ramı́rez, T. (2013) · ALTEX · doi:10.14573/altex.2013.2.209 · Cited by 221
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van Ravenzwaay, B., Cunha, G. C.-P., Leibold, E., Looser, R., Mellert, W., Prokoudine, A., Walk, T. B., & Wiemer, J. C. (2007) · Toxicology Letters · doi:10.1016/j.toxlet.2007.05.021 · Cited by 207
Self-citation
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Bouhifd, M., Härtung, T., Högberg, H. T., Kleensang, A., & Zhao, L. (2013) · Journal of Applied Toxicology · doi:10.1002/jat.2874 · Cited by 200
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Attene‐Ramos, M. S., Huang, R., Michael, S., Witt, K. L., Richard, A., Tice, R. R., Simeonov, A. M., Austin, C. P., & Xia, M. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1408642 · Cited by 172
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Corton, J. C., & Lapinskas, P. J. (2004) · Toxicological Sciences · doi:10.1093/toxsci/kfi011 · Cited by 168
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Liu, J., Mansouri, K., Judson, R., Martin, M. T., Hong, H., Chen, M., Xu, X., Thomas, R. S., & Shah, I. (2015) · Chemical Research in Toxicology · doi:10.1021/tx500501h · Cited by 166
In Vitro and Modelling Approaches to Risk Assessment from the U.S. Environmental Protection Agency ToxCast Programme
Judson, R., Houck, K. A., Martin, M. T., Knudsen, T. B., Thomas, R. S., Sipes, N. S., Shah, I., Wambaugh, J. F., & Crofton, K. M. (2014) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12239 · Cited by 149
A decade of change
Arrowsmith, J. E. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3630 · Cited by 140
Metabolic characterization of cell systems used in in vitro toxicology testing: Lung cell system BEAS-2B as a working example
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Yoshitomi, S., Ikemoto, K., Takahashi, J., Miki, H., Namba, M., & Asahi, S. (2001) · Toxicology in Vitro · doi:10.1016/s0887-2333(01)00011-x · Cited by 112
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Snouber, L. C., Bunescu, A., Naudot, M., Legallais, C., Brochot, C., Dumas, M., Elena‐Herrmann, B., & Leclerc, É. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs230 · Cited by 98
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Hoivik, D. J., Qualls, C. W., Mirabile, R. C., Cariello, N. F., Kimbrough, C. L., Colton, H. M., Anderson, S. P., Santostefano, M. J., Morgan, R. J. O., Dahl, R. R., et al. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh182 · Cited by 73
Human Upcyte Hepatocytes: Characterization of the Hepatic Phenotype and Evaluation for Acute and Long-Term Hepatotoxicity Routine Testing
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Detection of Hepatotoxicity Potential with Metabolite Profiling (Metabolomics) of Rat Plasma
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Mizuno, K., Katoh, M., Okumura, H., Nakagawa, N., Negishi, T., Hashizume, T., Nakajima, M., & Yokoi, T. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.024521 · Cited by 47
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Reily, M. D., & Tymiak, A. A. (2015) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2015.03.001 · Cited by 20
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van Ravenzwaay, B., Brunborg, G., Kleinjans, J. C. S., Galay‐Burgos, M., & Vrijhof, H. (2012) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2012.04.004 · Cited by 13
Fast Sampling of Adherent Cell Cultures for Optimal Metabolomics Results
Bordag, N., & Rennefahrt, U. E. E. (2016) · Journal of Postgenomics Drug & Biomarker Development · doi:10.4172/2153-0769.1000164 · Cited by 11
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Ramı́rez, T., Ramı́rez, T., Ahlbory-Dieker, D. L., Fux, E., Kamp, H., Walk, T. B., Wagner, S., Looser, R., & van Ravenzwaay, B. (2012) · Toxicology Letters · doi:10.1016/j.toxlet.2012.03.582 · Cited by 2
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Cabaton, N. J., Poupin, N., Canlet, C., Tremblay‐Franco, M., Audebert, M., Cravedi, J., Riu, A., Jourdan, F., & Zalko, D. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00571 · Cited by 24
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Morad, H. M., Abou‐Elzahab, M. M., Aref, S., & El-Sokkary, A. M. A. (2022) · ACS Omega · doi:10.1021/acsomega.2c00083 · Cited by 25
Commentary: Novel strategies and new tools to curtail the health effects of pesticides
Benbrook, C., Perry, M. J., Belpoggi, F., Landrigan, P. J., Perro, M., Mandrioli, D., Antoniou, M. N., Winchester, P., & Mesnage, R. (2021) · Environmental Health · doi:10.1186/s12940-021-00773-4 · Cited by 24
13C isotope-based metabolic flux analysis revealing cellular landscape of glucose metabolism in human liver cells exposed to perfluorooctanoic acid
Zhang, R., Chen, B., Lin, L., Zhang, H., & Luan, T. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.145329 · Cited by 22
Acoustic Mist Ionization Mass Spectrometry for Ultrahigh-Throughput Metabolomics Screening
Smith, M. J., Ivanov, D. P., Weber, R. J. M., Wingfield, J. M., & Viant, M. R. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c01616 · Cited by 22
Toxicity prediction using target, interactome, and pathway profiles as descriptors
Füzi, B., Mathai, N., Kirchmair, J., & Ecker, G. F. (2023) · Toxicology Letters · doi:10.1016/j.toxlet.2023.04.005 · Cited by 22
Revisiting silibinin as a novobiocin-like Hsp90 C-terminal inhibitor: Computational modeling and experimental validation
Cuyàs, E., Verdura, S., Micol, V., Joven, J., Bosch‐Barrera, J., Encinar, J. A., & Menéndez, J. A. (2019) · Food and Chemical Toxicology · doi:10.1016/j.fct.2019.110645 · Cited by 23
Carba Analogues of Flupirtine and Retigabine with Improved Oxidation Resistance and Reduced Risk of Quinoid Metabolite Formation
Wurm, K. W., Bartz, F., Schulig, L., Bodtke, A., Bednarski, P. J., & Link, A. (2022) · ChemMedChem · doi:10.1002/cmdc.202200262 · Cited by 19
Derivation of metabolic point of departure using high-throughput in vitro metabolomics: investigating the importance of sampling time points on benchmark concentration values in the HepaRG cell line
Malinowska, J. M., Palosaari, T., Sund, J., Carpi, D., Weber, R. J. M., Lloyd, G. R., Whelan, M., & Viant, M. R. (2023) · Archives of Toxicology · doi:10.1007/s00204-022-03439-3 · Cited by 20
The ligand exchange of citrates to thioabiraterone on gold nanoparticles for prostate cancer therapy
Stolarczyk, E. U., Leś, A., Łaszcz, M., Kubiszewski, M., Strzempek, W., Menaszek, E., Fusaro, M., Sidoryk, K., & Stolarczyk, K. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119319 · Cited by 20
Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole
Stryjska, K., Radko, L., Chęcińska, L., Kusz, J., Posyniak, A., & Ochocki, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103629 · Cited by 20
The enantioselective study of the toxicity effects of chiral acetochlor in HepG2 cells
Wang, S., Zhang, Y., Gao, J., Zhang, J., Tao, L., & Xu, W. (2021) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2021.112261 · Cited by 18
Olive Mill Wastewater Fermented with Microbial Pools as a New Potential Functional Beverage
Foti, P., Occhipinti, P. S., Russo, N., Scilimati, A., Miciaccia, M., Caggia, C., Perrone, M. G., Randazzo, C. L., & Romeo, F. V. (2023) · Molecules · doi:10.3390/molecules28020646 · Cited by 18
1,2,3-Triazole Tethered 2-Mercaptobenzimidazole Derivatives: Design, Synthesis and Molecular Assessment Toward C6 Glioma Cell Line
de Andrade, P., Dias, A. D. F., Figueiró, F., Torres, F., Kawano, D. F., Battastini, A. M. O., Carvalho, I., da Silva, C. H. T. D. P., & Rosa, J. M. C. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2019-0227 · Cited by 18
The alternative analog plasticizer BPS displays similar phenotypic and metabolomic responses to BPA in HepG2 and INS-1E cells
Azevedo, L. F., Masiero, M. M., Cherkaoui, S., Carneiro, M. F. H., Barbosa, F., & Zamboni, N. (2022) · Food and Chemical Toxicology · doi:10.1016/j.fct.2022.113266 · Cited by 17
Design, Synthesis, and Antiprotozoal Evaluation of New Promising 2,9-Bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline Derivatives, a Potential Alternative Scaffold to Drug Efflux
Guillon, J., Cohen, A., Boudot, C., Monic, S., Savrimoutou, S., Moreau, S., Albenque-Rubio, S., Lafon-Schmaltz, C., Dassonville‐Klimpt, A., Mergny, J., et al. (2022) · Pathogens · doi:10.3390/pathogens11111339 · Cited by 17
Computational Studies towards the Identification of Novel Rhodopsin-Binding Compounds as Chemical Chaperones for Misfolded Opsins
Pasqualetto, G., Schepelmann, M., Varricchio, C., Pileggi, E., Khogali, C., Morgan, S. R., Boostrom, I., Rôżanowska, M., Brancale, A., Ferla, S., et al. (2020) · Molecules · doi:10.3390/molecules25214904 · Cited by 17
Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles
Li, L., Zou, T., Liang, M., Mezhuev, Y. O., Tsatsakis, A. M., Djordjević, A. B., Lan, M., Liu, F., Cai, T., Gong, P., et al. (2021) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2021.05.025 · Cited by 17
Moringa oleifera Lam Leaf Extract Stimulates NRF2 and Attenuates ARV-Induced Toxicity in Human Liver Cells (HepG2)
Ndlovu, S. S., Chuturgoon, A. A., & Ghazi, T. (2023) · Plants · doi:10.3390/plants12071541 · Cited by 15
Natural Triterpenoids Isolated from Akebia trifoliata Stem Explants Exert a Hypoglycemic Effect via α‐Glucosidase Inhibition and Glucose Uptake Stimulation in Insulin‐Resistant HepG2 Cells
Bian, G., Yang, J. B., Elango, J., Wu, W., Bao, B., & Bao, C. (2021) · Chemistry & Biodiversity · doi:10.1002/cbdv.202001030 · Cited by 16
Towards a clinical application of freeze-dried squalene-based nanomedicines
Rouquette, M., Roux, K. S., Polrot, M., Bourgaux, C., Michel, J., Testard, F., Gobeaux, F., & Lepêtre‐Mouelhi, S. (2019) · Journal of drug targeting · doi:10.1080/1061186x.2019.1566340 · Cited by 14
Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
Doß, S., Blessing, C., Haller, K., Richter, G., & Sauer, M. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44100317 · Cited by 13
Arecoline-Induced Hepatotoxicity in Rats: Screening of Abnormal Metabolic Markers and Potential Mechanisms
Sun, J., Zhang, K., Yin, Y., Qi, Y., Li, S., Sun, H., Luo, M., Sun, Y., Yu, Z., Yang, J., et al. (2023) · Toxics · doi:10.3390/toxics11120984 · Cited by 13
Synephrine and caffeine combination promotes cytotoxicity, DNA damage and transcriptional modulation of apoptosis-related genes in human HepG2 cells
Leão, T. K., Ribeiro, D. L., Machado, A. R. T., Costa, T. R., Sampaio, S. V., & Antunes, L. M. G. (2021) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2021.503375 · Cited by 13
Hematopoietic effect of echinochrome on phenylhydrazine-induced hemolytic anemia in rats
El-Shehry, M. S. E. F., Amrymi, R. A., Atia, T. A., Lotfy, B. M. M., Ahmed, S. H. A.-F., Qutb, S. A., Ali, S. B., Mohamed, A. S., Mousa, M. R., Damanhory, A. A., et al. (2023) · PeerJ · doi:10.7717/peerj.16576 · Cited by 13
Fundamentals of environmental metabolomics
Kovacevic, V., & Simpson, M. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818196-6.00001-7 · Cited by 15
A new strategy for the rapid identification and validation of direct toxicity targets of psoralen-induced hepatotoxicity
Sun, S.-T., Wang, M., Yu, Y., Wang, S., Ding, H., Liang, C., Li, X., Fan, S., & Li, Y. (2022) · Toxicology Letters · doi:10.1016/j.toxlet.2022.05.002 · Cited by 13
Dynamic Metabolic and Transcriptional Responses of Proteasome-Inhibited Neurons
Suciu, I., Delp, J., Gutbier, S., Ückert, A.-K., Spreng, A.-S., Eberhard, P., Karreman, C., Schreiber, F., Madjar, K., Rahnenführer, J., et al. (2023) · Antioxidants · doi:10.3390/antiox12010164 · Cited by 11
A high-throughput metabolomics in vitro platform for the characterization of hepatotoxicity
Ramirez‐Hincapie, S., Birk, B., Ternes, P., Giri, V., Haake, V., Herold, M. J., Zickgraf, F. M., Verlohner, A., Huener, H.-A., Kamp, H., et al. (2023) · Cell Biology and Toxicology · doi:10.1007/s10565-023-09809-6 · Cited by 12
Self-citation
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van Wyk, R. J., Serem, J. C., Oosthuizen, C. B., Semenya, D., Serian, M., Lorenz, C. D., Mason, A. J., Bester, M. J., & Gaspar, A. R. M. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00580 · Cited by 12
Low concentrations of 4-ABP promote liver carcinogenesis in human liver cells and a zebrafish model
Lin, H.-D., Tseng, Y., Yuh, C., & Chen, S. (2021) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.126954 · Cited by 12
Identification of novel αβ-tubulin modulators with antiproliferative activity directed to cancer therapy using ligand and structure-based virtual screening
Federico, L. B., Silva, G. M., Dias, A. D. F., Figueiró, F., Battastini, A. M. O., Santos, C. B. R., da Costa, L. T., Rosa, J. M. C., & da Silva, C. H. T. D. P. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.10.136 · Cited by 13
Application of high throughput in vitro metabolomics for hepatotoxicity mode of action characterization and mechanistic-anchored point of departure derivation: a case study with nitrofurantoin
Ramirez‐Hincapie, S., Birk, B., Ternes, P., Giri, V., Zickgraf, F. M., Haake, V., Herold, M. J., Kamp, H., Driemert, P., Landsiedel, R., et al. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03572-7 · Cited by 11
Self-citation
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Sarkar, K., Chatterjee, A., Bankura, B., Bank, S., Paul, N., Chatterjee, S., Das, A., Dutta, K., Chakraborty, S., De, S., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0307166 · Cited by 16
A metabolomics approach to reveal the mechanism of developmental toxicity in zebrafish embryos exposed to 6-propyl-2-thiouracil
Wilhelmi, P., Giri, V., Zickgraf, F. M., Haake, V., Henkes, S., Driemert, P., Michaelis, P., Busch, W., Scholz, S., Flick, B., et al. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110565 · Cited by 11
Self-citation
Metabolomics reveals the effects of Lactiplantibacillus plantarum dy-1 fermentation on the lipid-lowering capacity of barley β-glucans in an in vitro model of gut-liver axis
Fan, S., Zhou, Y., Zhao, Y., Daglia, M., Zhang, J., Zhu, Y. G., Bai, J., Zhu, L., & Xiao, X. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.126861 · Cited by 11
Novel approaches to liver disease diagnosis and modeling
de Oliveira, A. G., & Fiorotto, R. (2020) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh-20-109 · Cited by 10
LC-MS based metabolomics reveals metabolic pathway disturbance in retinal pigment epithelial cells exposed to hydroxychloroquine
Li, J., Xu, Z.-Y., Li, M., Zheng, W.-L., Huang, X., Xiao, F., Cui, Y., & Pan, H. (2020) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109212 · Cited by 11
The Interrelationship between Liver Function Test and the Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.
Zahedi, M., Yousefi, M., Abounoori, M., Malekan, M., Tajik, F., Heydari, K., Mortazavi, P., Ghahramani, S., Ghazaeian, M., Sheydaee, F., et al. (2021) · PubMed Central · doi:10.30476/ijms.2021.87555.1793 · Cited by 11
Highlight report: Metabolomics in hepatotoxicity testing
Ghallab, A. (2017) · EXCLI journal · doi:10.17179/excli2017-1041 · Cited by 10
Glyoxal-derived advanced glycation end-products, Nε-carboxymethyl-lysine, and glyoxal-derived lysine dimer induce apoptosis-related gene expression in hepatocytes
Kang, J., Jeong, Y., Ha, S. K., Lee, H. H., & Lee, K. (2023) · Molecular Biology Reports · doi:10.1007/s11033-022-08130-5 · Cited by 10
Mechanisms of hepatocellular toxicity associated with the components of St. John’s Wort extract hypericin and hyperforin in HepG2 and HepaRG cells
Abegg, V. F., Panajatovic, M. V., Mancuso, R. V., Allard, J. A., Duthaler, U., Odermatt, A., Krähenbühl, S., & Bouitbir, J. (2024) · Toxicology Letters · doi:10.1016/j.toxlet.2024.01.008 · Cited by 10
Exposure to Di(2‐Ethylhexyl) Phthalate Increases the Internalization of Polystyrene Microplastics by Human Hepatocellular Carcinoma Cells and Leads to Cell Damage
Zhang, H., Hao, H., Fan, W., Gao, W., & Liang, J. L. (2025) · Journal of Applied Toxicology · doi:10.1002/jat.4771 · Cited by 10
Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer’s disease mice
Cohn, W., Campagna, J. J., Wi, D., Lee, J. T., Beniwal, S., Elezi, G., Zhu, C., Jagodzinska, B. M., Whitelegge, J. P., Damoiseaux, R. D., et al. (2025) · npj Drug Discovery. · doi:10.1038/s44386-025-00009-2 · Cited by 11
Synthesis, characterization and toxicity profiling of graphene oxide-metformin hydrogel as a sustained release system for metformin in-vitro
Singh, V., Sandhir, R., & Singhal, N. K. (2020) · Materials Today Proceedings · doi:10.1016/j.matpr.2020.06.590 · Cited by 10
Metabolite Patterns in Human Myeloid Hematopoiesis Result from Lineage-Dependent Active Metabolic Pathways
Kaiser, L., Weinschrott, H., Quint, I., Wenzel, F., Blaess, M. F., Jung, M., Kohl, M., & Deigner, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176092 · Cited by 10
Promotion of cadmium uptake and cadmium-induced toxicity by the copper transporter CTR1 in HepG2 and ZFL cells
Kwok, M. L., Li, Z. P., Law, T. Y. S., & Chan, K. M. (2020) · Toxicology Reports · doi:10.1016/j.toxrep.2020.11.005 · Cited by 10
LC–MS-Based Metabolomics in the Study of Drug-Induced Liver Injury
Lu, Y., Zhao, X., Hu, Z., Wang, L. A., & Li, F. (2018) · Current Pharmacology Reports · doi:10.1007/s40495-018-0144-3 · Cited by 11
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Bottoni, P., Pontoglio, A., Scarà, S., Pieroni, L., Urbani, A., & Scatena, R. (2022) · Cells · doi:10.3390/cells11071169 · Cited by 10
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Wurm, K. W., Bartz, F., Schulig, L., Bodtke, A., Bednarski, P. J., & Link, A. (2022) · Archiv der Pharmazie · doi:10.1002/ardp.202200473 · Cited by 10
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Zhao, J., Li, J., Zhang, X., Shi, S., Wang, L., Yuan, M., Liu, Y., & Wang, Y. (2023) · Molecules · doi:10.3390/molecules28041932 · Cited by 9
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Jacques, C., Jamin, E. L., Jouanin, I., Canlet, C., Tremblay‐Franco, M., Martin, J., Zalko, D., Brunel, Y., Bessou‐Touya, S., Debrauwer, L., et al. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-03136-7 · Cited by 9
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Štancl, P., Gršković, P., Držaić, S., Vičić, A., Karlić, R., & Korać, P. (2024) · Genes · doi:10.3390/genes15111460 · Cited by 9
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Bellini, C., Atxabal, U., Bősze, S. E., Dobay, O., Horváth, A., Szigyártó, I. C., Beke‐Somfai, T., Jiménez‐Barbero, J., Puskás, I., & Horváti, K. (2025) · Aggregate · doi:10.1002/agt2.741 · Cited by 6
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García‐Cañaveras, J. C., Jiménez, N., Gómez‐Lechón, M. J., Castell, J. V., Donato, M. T., & Lahoz, A. (2015) · ELECTROPHORESIS · doi:10.1002/elps.201500095 · Cited by 41
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A high-throughput metabolomics in vitro platform for the characterization of hepatotoxicity
Ramirez‐Hincapie, S., Birk, B., Ternes, P., Giri, V., Haake, V., Herold, M. J., Zickgraf, F. M., Verlohner, A., Huener, H.-A., Kamp, H., et al. (2023) · Cell Biology and Toxicology · doi:10.1007/s10565-023-09809-6 · Cited by 12
Self-citation
A metabolomics cell-based approach for anticipating and investigating drug-induced liver injury
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Authors: Ramirez, T., Strigun, A., Verlohner, A., Huener, H.-A., Peter, E., Herold, M., Bordag, N., Mellert, W., Walk, T., Spitzer, M., Jiang, X., Sperber, S., Hofmann, T., Hartung, T., Kamp, H., & van Ravenzwaay, B.
Affiliations: BASF (Germany) (DE)
Corresponding author: Hofmann, Thomas
ORCID: Verlohner, Andreas
Huener, Hans-Albrecht
Herold, Michael
Bordag, Natalie
Walk, Tilmann
Jiang, Xiaoqi
Sperber, Saskia
Hofmann, Thomas
Kamp, Hennicke
Venue: Archives of Toxicology
Publisher: Springer Science and Business Media LLC
Published: 2017-09-30
Volume: 92
Issue: 2
Pages: 893-906
ISSN: 0340-5761 (ISSN-L)
1432-0738
DOI: 10.1007/s00204-017-2079-6
PMC: PMC5818600
OpenAlex: W2759884959
Cited by: 164
References: 39
Citations by year: 2026: 14 · 2025: 13 · 2024: 14 · 2023: 26 · 2022: 25 · 2021: 25 · 2020: 23 · 2019: 13 · 2018: 10 · 2017: 1
FWCI: 13.67
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (unspecified)
Locations: Archives of Toxicology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
KOPS (University of Konstanz) (submittedVersion, cc-by)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Keywords: hepatotoxicity, metabolomics, HepG2 cells, in vitro toxicity models, mechanism of action, non-animal alternatives, liver enzyme induction, liver enzyme inhibition, peroxisome proliferation, concentration-dependent effects, intracellular metabolites, mass spectrometry metabolomics
MeSH terms: Animal Testing Alternatives, Enzyme Induction, Humans, Liver, Toxicity Tests, Metabolomics, Metabolome, Hep G2 Cells

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Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells

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