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Involvement of endoplasmic reticulum stress in rifampicin-induced liver injury

Wanqing Hou1, Bernard Nsengimana1, Chuyun Yan1

  • 1Department of Hepatobiliary Surgery, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Frontiers in Pharmacology
|November 7, 2022
PubMed

Insights

Rifampicin, a key tuberculosis drug, can cause liver injury. This review explores how endoplasmic reticulum (ER) stress contributes to this toxicity, linking adaptive responses and cell death pathways.

Area of Science:

  • Hepatology
  • Toxicology
  • Molecular Biology

Background:

  • Rifampicin is a crucial first-line drug for tuberculosis treatment.
  • Hepatocyte toxicity from rifampicin presents a significant clinical challenge.
  • The precise mechanisms underlying rifampicin-induced liver injury remain unclear.

Purpose of the Study:

  • To review the functional characteristics of endoplasmic reticulum (ER) stress.
  • To elucidate the pathogenic role of ER stress in rifampicin-induced liver injury.
  • To connect ER stress to both adaptive and apoptotic responses in liver cells.

Main Methods:

  • Literature review of studies on rifampicin, hepatotoxicity, and ER stress.
  • Analysis of mechanisms linking rifampicin to ER stress activation (e.g., bile acid accumulation, CYP enzyme activity).
  • Examination of the dual role of ER stress (protective vs. proapoptotic) in liver injury.

Main Results:

  • Rifampicin induces ER stress through mechanisms including bile acid buildup and toxic metabolite production via PXR.
  • Short-term ER stress can be protective, but persistent stress exacerbates liver damage.
  • ER stress is implicated in both the adaptive response and apoptotic toxicity of rifampicin.

Conclusions:

  • Endoplasmic reticulum stress is closely associated with rifampicin-induced liver injury.
  • The persistence of ER stress shifts its role from adaptive to pathogenic, aggravating liver damage.
  • Understanding ER stress mechanisms is vital for managing rifampicin hepatotoxicity.
Keywords:
ER stressadaptive mechanismhepatocyte toxicityliver injuryrifampicin

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