Evidence map›Paper›PMID 28965233›Full record

ArticleArchives of toxicology2018

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

Tzutzuy Ramirez, Alexander Strigun, Andreas Verlohner, Hans-Albrecht Huener, Erik Peter, Michael Herold, Natalie Bordag, Werner Mellert, Tilmann Walk, Michael Spitzer and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.

  1. Pooled it
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  8. Review
  9. Comparison of popular enrichment methods for untargeted in vitro metabolomics.Metabolomics : Official journal of the Metabolomic Society · 2025
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  13. Protective Effects ofJournal of microbiology and biotechnology · 2024
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Tzutzuy RamirezBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
Alexander StrigunMetanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany.
Andreas VerlohnerBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
Hans-Albrecht HuenerBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
Erik PeterMetanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany.
Michael HeroldMetanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany.
Natalie BordagMetanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany.
Werner MellertBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
Tilmann WalkMetanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany.
Michael SpitzerMetanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany.
Xiaoqi JiangBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
Saskia SperberBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
Thomas HofmannBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany. thomas.b.hofmann@basf.com.ORCID http://orcid.org/0000-0002-3235-823X
Thomas HartungJohns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), Baltimore, MD, USA.
Hennicke KampBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
Ben van RavenzwaayBASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
BASF (Germany) · DEBASF (United States) · USJohns Hopkins University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Toxicity TestsAnimal Testing AlternativesEnzyme InductionHep G2 CellsHumansLiverMetabolomeMetabolomicsHepG2 cellsIn vitroLiver toxicityMetabolomics

Identifiers

PMID28965233
PMCPMC5818600
OpenAlexW2759884959

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.