Aripiprazole reduces liver cell division

PLoS One. 2020 Oct 26;15(10):e0240754. doi: 10.1371/journal.pone.0240754. eCollection 2020.

Abstract

Effects of aripiprazole on dopamine regulation are being tested as a treatment for patients with a dual diagnosis of schizophrenia and addictions, often cocaine dependence. Aripiprazole has one of the fewest side-effects among the second-generation antipsychotics. Nevertheless, severe aripiprazole hepatotoxicity was reported in persons with a history of cocaine and alcohol abuse. Here we report that therapeutically relevant aripiprazole concentrations, equal to laboratory alert levels in patients' serum, reduce the rate of hepatocytes' division. This could be an underlying mechanism of severe liver injury development in the patients with a history of alcohol and cocaine abuse, the two hepatotoxic agents that require increased ability of liver self-regeneration. Monitoring liver functions is, therefore, important in the cases when aripiprazole is co-prescribed or used with drugs with potential hepatotoxic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aripiprazole / pharmacology*
  • Cell Count
  • Cell Division / drug effects*
  • Cell Division / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cellular Senescence / drug effects
  • Gene Expression Regulation / drug effects
  • Liver / cytology*
  • Rats

Substances

  • Aripiprazole

Grants and funding

This work was supported by the Slovenian Research Agency in the form of funding awarded to DS, IM, adn KBR (research core funding no. P3-0019) and TPM. This work was also partially supported by H2020 Excellent Science in the form of project funding awarded to BK and IM (H2020-MSCA-ITN:721236 TREATMENT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.