Exploring the role of oxidative stress and the effect of N-acetylcysteine in thiopurine-induced liver injury in inflammatory bowel disease: A randomized crossover pilot study

Dirk P. van Asseldonk, Femke Crouwel, Margien L. Seinen, Peter G. Scheffer, Agnes I. Veldkamp, Nanne K. de Boer, Birgit Lissenberg-Witte, Godefridus J. Peters, Adriaan A. van Bodegraven

Research output: Contribution to journalArticleAcademicpeer-review


Thiopurine treatment is regularly complicated by drug-induced liver injury. It has been suggested that oxidative stress may play a synergistic role. To assess whether thiopurine-induced liver injury coincides with increased oxidative stress and whether co-administration with N-acetylcysteine is protective, we performed a randomized open label crossover pilot study in inflammatory bowel disease patients with thiopurine-induced increased serum liver tests. The study comprised four stages of 4 weeks. Patients received no additional therapy followed by N-acetylcysteine 1200 mg twice a day, or the other way around, alongside ongoing thiopurine treatment. The third and fourth stages comprised a washout period and thiopurine reintroduction period. Nine patients completed the study, and the addition of N-acetylcysteine decreased myeloperoxidase concentrations (33.6–24.5 pmol/L, p = 0.038). The other biomarkers remained unchanged, including thiopurine metabolites, xanthine oxidase activity, thiopurine S-methyltransferase activity and serum liver enzyme activity tests. Reintroduction of thiopurines led to an increase of F2-isoprostanes (101–157 ng/mmol, p = 0.038), but not of serum liver enzyme activity tests. Results suggests that thiopurines may increase oxidative stress and although the addition of N-acetylcysteine led to a decrease in plasma myeloperoxidase concentrations, it does not protect from thiopurine-induced increase of serum liver tests.
Original languageEnglish
Pages (from-to)507-518
Number of pages12
JournalBasic & clinical pharmacology & toxicology
Issue number4
Early online date2024
Publication statusPublished - Apr 2024


  • Crohn's disease
  • N-acetylcysteine
  • chemical and drug-induced liver injury
  • thiopurines
  • ulcerative colitis

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