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Updated: Jun 16, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

Circadian regulation of hepatic detoxification: implications for drug-induced liver injury

Ruiming Wen1, Haixia Wang1, Songtao Wang2

  • 1School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong Province, China.

Archives of Toxicology
|June 15, 2026
PubMed

Insights

The liver

Area of Science:

  • Chronobiology
  • Hepatology
  • Pharmacology

Background:

  • Hepatic xenobiotic detoxification shows significant circadian rhythmicity.
  • This rhythm is driven by clock-controlled genes (CCGs) regulating drug-metabolizing enzymes (DMEs) and transporters.
  • CCG dysfunction, affecting genes like Rev-erbα, Bmal1, Clock, and Per, disrupts metabolic timing and increases susceptibility to toxicants.

Purpose of the Study:

  • To review the circadian characteristics of hepatic detoxification.
  • To analyze the CCG network's role in hepatotoxicity.
  • To explore how external factors (zeitgebers) and drug timing impact liver injury outcomes.

Main Methods:

  • Literature review focusing on circadian rhythms in liver function.
  • Analysis of molecular mechanisms involving CCGs and hepatotoxicity.
  • Examination of the influence of zeitgebers and drug administration timing on liver injury.

Main Results:

  • Hepatic detoxification efficacy varies significantly throughout the day due to circadian rhythms.
  • CCGs form feedback loops that control the temporal expression of DMEs and transporters.
  • Disruption of these rhythms by CCG dysfunction or external factors alters liver injury susceptibility.

Conclusions:

  • Circadian rhythms are crucial for hepatic detoxification and managing drug-induced liver injury (DILI).
  • Understanding the CCG network provides insights into hepatotoxicity mechanisms.
  • Chronopharmacological strategies, including optimized drug timing and lifestyle management, can prevent and mitigate DILI.
Keywords:
ChronopharmacologyCircadian rhythmDrug-metabolizing enzymesHepatotoxicityZeitgeber

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