Nevirapine induces apoptosis in liver (HepG2) cells

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Jeerang Wongtrakul1, Atchara Paemanee2, Phitchayapak Wintachai2

  • 1Research Institute for Health Sciences, Chiang Mai University, 110 Intavaroros Road, Sriphum, Muang District, Chiang Mai 50200, Thailand.

Asian Pacific Journal of Tropical Medicine
|June 5, 2016
PubMed
Abstract

Insights

NVP exposure directly induces apoptosis in liver cells, indicating significant cytotoxicity. This mechanism may contribute to NVP-related patient hepatotoxicity, independent of its metabolites.

Area of Science:

  • Hepatotoxicity Research
  • Cellular Toxicology
  • Drug Metabolism

Background:

  • Hepatotoxicity is a significant concern with certain drug therapies.
  • Understanding the direct cellular mechanisms of drug-induced liver injury is crucial for patient safety.

Purpose of the Study:

  • To elucidate the mechanism by which NVP induces hepatotoxicity.
  • To investigate the direct cytotoxic effects of NVP on liver cells, independent of metabolic activation.

Main Methods:

  • Hepatocellular carcinoma (HepG2) cells, chosen for low cytochrome P450 expression, were exposed to varying NVP concentrations.
  • Cytotoxicity was assessed via proliferation assays, cell counting (trypan blue exclusion), and apoptosis induction analysis (morphological and biochemical markers).

Main Results:

  • High NVP concentrations (819 μM) induced cellular rounding and complete cell death within three weeks.
  • Apoptosis was confirmed by nuclear condensation/fragmentation, increased Annexin V/propidium iodide staining, and caspase 9 activation.

Conclusions:

  • NVP directly induces apoptosis in liver cells, demonstrating significant intrinsic cytotoxicity.
  • This direct apoptotic effect of NVP may be a key contributor to patient hepatotoxicity, separate from metabolite-induced toxicity.
Keywords:
ApoptosisCytotoxicityHepatotoxicityNevirapine

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