چکیده (انگلیسی):

Objective: To generate insights into the mechanism of NVP induced hepatotoxicity.
Methods: Liver (HepG2) cells were cultured with various concentrations of NVP. This
cell line was chosen because it has low expression of cytochrome P450, allowing evaluation
of the effects of NVP rather than specific metabolites. Cytotoxicity was determined
using a proliferation assay and cell numbers were monitored using trypan blue exclusion
assay for long term culture experiments and apoptosis induction was determined by
morphological and biochemical investigation.
Results: HepG2 cells treated with the highest concentration of NVP tested (819 mM)
initially showed a rounded morphology and all cells had died by week three of exposure.
Nuclear condensation and fragmentation, increased Annexin V/propidium iodide staining
and caspase 9 activation all supported the induction of apoptosis in HepG2 cells in
response to NVP treatment.
Conclusions: There is a clear induction of apoptosis in response to NVP which suggests
that NVP has significant cytotoxicity, over and above any cytotoxicity of metabolites and
may contribute directly to patient hepatotoxicity.