ArticleCell biology and toxicology2015
Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro.
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.
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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.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- 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 · 2021Article
- Hepatic Bioactivation of Skin-Sensitizing Drugs to Immunogenic Reactive Metabolites.ACS omega · 2019Article
- Iron induces insulin resistance in cardiomyocytes via regulation of oxidative stress.Scientific reports · 2019Article
- Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease.Inflammatory bowel diseases · 2017Review
- Article
- Effects of anti-human T lymphocyte immune globulins in patients: new or old.Journal of cellular and molecular medicine · 2016Article
- Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser.Lasers in medical science · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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