Evidence map›Paper›PMID 26377104›Full record

ArticleCell biology and toxicology2015

Evaluation of CYP3A4 inhibition and hepatotoxicity using DMSO-treated human hepatoma HuH-7 cells.

Yitong Liu, Thomas J Flynn, Menghang Xia, Paddy L Wiesenfeld, Martine S Ferguson

Open access · greenAbstract read
In one paragraph

Article in Cell biology and toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.2field-weighted citation impact, top 10% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Yitong LiuDivision of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD, USA. yitong.liu@fda.hhs.gov.ORCID http://orcid.org/0000-0002-4300-4349
Thomas J FlynnDivision of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD, USA.
Menghang XiaDivision of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
Paddy L WiesenfeldDivision of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD, USA.
Martine S FergusonDivision of Public Health Informatics & Analytics, Office of Analytics and Outreach, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD, USA.
Center for Food Safety and Applied Nutrition · USNational Institutes of Health · US

Funding

Small molecule screening programZ01HG200319 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI AUSTIN, CHRISTOPHER P · 2004 to 2008
$32.3M
Toxicology in the 21st Century Program (Tox21) - Systems ToxicologyZIATR000038 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI XIA, MENGHANG · 2015 to 2025
$5.7M
Intramural NIH HHS Z01 HG200319
6 · The paper itself

Abstract

A human hepatoma cell line (HuH-7) was evaluated as a metabolically competent cell model to investigate cytochrome P450 3A4 (CYP3A4) inhibition, induction, and hepatotoxicity. First, CYP3A4 gene expression and activity were determined in HuH-7 cells under three culture conditions: 1-week culture, 3-week culture, or 1 % dimethyl sulfoxide (DMSO) treatment. HuH-7 cells treated with DMSO for 2 weeks after confluence expressed the highest CYP3A4 gene expression and activity compared to the other two culture conditions. Furthermore, CYP3A4 activity in DMSO-treated HuH-7 cells was compared to that in a human hepatoma cell line (HepG2/C3A) and human bipotent progenitor cell line (HepaRG), which yielded the following ranking: HepaRG > DMSO-treated HuH-7 >> HepG2/C3A cells. The effects of three known CYP3A4 inhibitors were evaluated using DMSO-treated HuH-7 cells. CYP3A4 enzyme inhibition in HuH-7 cells was further compared to human recombinant CYP3A4, indicating similar potency for reversible inhibitors (IC 50 within 2.5-fold), but different potency for the irreversible inhibitor. Next, induction of CYP3A4 activity was compared between DMSO-treated HuH-7 and HepaRG cells using two known inducers. DMSO-treated HuH-7 cells yielded minimal CYP3A4 induction compared to that in the HepaRG cells after 48-h treatments. Finally, the cytotoxicity of five known hepatotoxicants was evaluated in DMSO-treated HuH-7, HepG2/C3A, and HepaRG cells, and significant differences in cytotoxic sensitivity were observed. Overall, DMSO-treated HuH-7 cells are a valuable model for medium- or high-throughput screening of chemicals for CYP3A4 inhibition and hepatotoxicity.

Indexed as

Carcinoma, HepatocellularCell Line, TumorCytochrome P-450 CYP3ACytochrome P-450 Enzyme InhibitorsDimethyl SulfoxideGene ExpressionHepatocytesHep G2 CellsHumansLiver NeoplasmsToxicity TestsCYP3A4 protein, humanCytochrome P-450 CYP3ACytochrome P-450 Enzyme InhibitorsDimethyl SulfoxideCYP3A4DMSOHepatotoxicityHuH-7 cellsInductionInhibition

Identifiers

PMID26377104
PMCPMC4970208
OpenAlexW1837043810

What OpenQuestion holds

Textmetadata
LicenceTDM
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.