Evidence map›Paper›PMID 25916701›Full record

ArticleCell biology and toxicology2015

Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro.

Mark M T J Broekman, Hennie M J Roelofs, Dennis R Wong, Mariska Kerstholt, Alex Leijten, Frank Hoentjen, Wilbert H M Peters, Geert J A Wanten, Dirk J de Jong

Open access · hybridAbstract 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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Ruthenium (II)/allopurinol complex inhibits breast cancer progression via multiple targets.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021
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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

9 authors at 2 institutions in 1 country.

Mark M T J BroekmanDepartment of Gastroenterology, Radboud University Nijmegen Medical Center, 455, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands, mark.broekman@radboudumc.nl.
Hennie M J Roelofs
Dennis R Wong
Mariska Kerstholt
Alex Leijten
Frank Hoentjen
Wilbert H M Peters
Geert J A Wanten
Dirk J de Jong
Radboud University Nijmegen · NLZuyderland Medisch Centrum · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe use of thiopurines is frequently accompanied by hepatotoxicity. Studies on hepatocyte cultures showed a time- and dose-dependent increase of thiopurine toxicity. 5-Aminosalicylic acid (5-ASA) and allopurinol can influence thiopurine metabolism; however, it is unknown whether this affects in vitro cytotoxicity.

methodsHuman hepatoma cells (Huh7, HepG2 and HepaRG) were incubated with increasing concentrations of thiopurines, 5-ASA or allopurinol. Water-soluble tetrazolium salt-1 (WST-1) cytotoxicity assays were used to calculate cell survival curves and half maximal inhibitory concentrations (IC50). Combination experiments with thiopurines with a fixed dose of 200 μM 5-ASA or 100 μM allopurinol were conducted in HepaRG cells. Caspase-3/7 activation was evaluated, and single cell electrophoresis analysis was performed.

resultsA time- and dose-related cytotoxic effect was seen with azathioprine (AZA) in all hepatoma cells, whereas Huh7 and HepG2 cells did not show toxicity to 6-mercaptopurine (6-MP). HepaRG cells expressed the highest levels of drug metabolising enzymes, and therefore, combination experiments were conducted in HepaRG cells. Addition of a non-toxic dose of allopurinol resulted in a twofold to threefold increased cytotoxicity of all thiopurines, which seemed to be mediated by apoptosis/DNA damage.

conclusionThe addition of allopurinol to thiopurines leads to a two-threefold increased cytotoxicity in HepaRG cells.

Indexed as

AllopurinolAnti-Inflammatory Agents, Non-SteroidalAntimetabolitesAzathioprineCell Line, TumorHepatocytesHumansMercaptopurineMesalamineAllopurinolAnti-Inflammatory Agents, Non-SteroidalAntimetabolitesAzathioprineMercaptopurineMesalamine

Identifiers

PMID25916701
PMCPMC4441745
OpenAlexW2032825637

What OpenQuestion holds

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LicenceCC BY
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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.