ABSTRACT
<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>
ABSTRACT
Sclerosing angiomatoid nodular transformation (SANT) of the spleen, a newly defined primary lesion of the spleen, is very rare. Immunohistochemistry is the only way to confirm the diagnosis of SANT. We present the clinical characteristics and postoperative outcomes of five SANT cases that underwent splenectomy from January 2007 to October 2010. Although SANT had specific imaging findings, differential diagnosis from other splenic tuomrs or malignant lesions preoperatively was difficult. The hand-assisted laparoscopic splenectomy was a useful and effective technique for the management and postoperative diagnosis of SANT. All SANT patients had good prognosis without recurrence after splenectomy.