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Triptolide induces toxicity in inner ear stem cells via promoting DNA damage

Xuxia Tang1, Congpin Wang2, Yuelin Hsieh2

  • 1Department of Otolaryngology, the First Affiliated Hospital of Zhejiang Traditional Chinese Medical University, Hangzhou 310006, Zhejiang, China.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|July 10, 2019
PubMed

Insights

Triptolide causes significant toxicity in mouse inner ear stem cells, inhibiting proliferation and inducing apoptosis. This study reveals triptolide

Area of Science:

  • Ototoxicology
  • Stem Cell Biology
  • Molecular Toxicology

Background:

  • Clinical reports suggest triptolide may have cytotoxic effects.
  • Understanding triptolide's impact on inner ear stem cells is crucial for patient safety.
  • Inner ear stem cells are vital for auditory and vestibular system regeneration.

Purpose of the Study:

  • To investigate the toxicological effects of triptolide on mouse inner ear stem cells.
  • To elucidate the mechanisms underlying triptolide-induced ototoxicity.
  • To provide a basis for the safe clinical application of triptolide.

Main Methods:

  • Isolation and culture of inner ear stem cells from adult BALB/C6 mice.
  • Sphere formation assay to assess stemness.
  • Cell viability, proliferation (CCK-8, BrdU), apoptosis (Annexin V/PI), DNA damage markers (γH2AX, 53BP1), and mitochondrial function (OPA-1 cleavage, MitoGreen dye) were analyzed.

Main Results:

  • Triptolide significantly inhibited stem cell viability, proliferation, and sphere formation.
  • Triptolide induced apoptosis and increased expression of DNA damage markers (γH2AX, 53BP1).
  • Triptolide impaired mitochondrial function, evidenced by OPA-1 cleavage.

Conclusions:

  • Triptolide exhibits significant toxicity towards mouse inner ear stem cells.
  • Mechanisms include suppressed stemness, induced apoptosis, DNA damage, and mitochondrial dysfunction.
  • Findings offer insights into triptolide's ototoxicology and inform clinical use considerations.
Keywords:
DNA damageMitochondrial functionMouse inner ear stem cellsTriptolide

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