<p><b>OBJECTIVE</b>To find the signaling pathway of triptolide (TP)-induced
liver injury and to reveal whether
NF-E2-related factor 2 (Nrf2)
plays an important
role in cellular
self-
protection.</p><p><b>
METHODS</b>The L-02 and
HepG2 cells were cultured and treated with various concentrations of TP. The
cell viability was observed, and the
cell medium was collected for detecting the
aspartate aminotransferase (ALT),
alanine aminotransferase (AST),
lactate dehydrogenase (LDH),
superoxide dismutase (SOD) and L-
glutathione production (GSH) levels. Nrf2 and its
downstream target
NAD(P)H
quinine oxidoreductase 1 (NQO1) and
heme oxygenase-1 (HO-1) expression, the nuclear translocation of Nrf2, and the binding
ability of Nrf2 and
antioxidant response element (ARE) were also identified. Meanwhile,
shRNA was used to silence Nrf2 in L-02
cells to find out whether Nrf2
plays a protective
role.</p><p><b>RESULTS</b>The viability of the L-02 and
HepG2 cells treated with TP decreased in a doseand
time-dependent manner, and TP (20-80 μg/mL) markedly induced the release of ALT, AST and LDH (P<0.05 or P<0.01), reduced the levels of SOD and GSH (P<0.01), and increased the intracellular
reactive oxygen species. Meanwhile, TP augmented the Nrf2 expression in L-02 and
HepG2 cells (P<0.05 or P<0.01), induced Nrf2 nuclear translocation, increased the Nrf2 ARE binding activity, and increased HO-1 and NQO1 expressions. Nrf2 knockdown revealed a more severe toxic effect of TP (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>
Human hepatic cells treated with TP induced
oxidative stress, and led to cytotoxicity.
Self-
protection against TP-induced
toxicity in
human hepatic cells might be via Nrf2-ARE-NQO1 transcriptional pathway.</p>