Schisandrin B protects against nephrotoxicity induced by cisplatin in HK-2 cells via Nrf2-ARE activation

This study is to investigate the protection effect of schisandrin B (Sch B) against oxidation stress of HK-2 cells induced by cisplatin and the mechanisms involved.  HK-2 cells were cultured and divided into different groups: solvent control group, cisplatin exposure group, positive group, Sch B treatment group.  Cell viability and toxicity were evaluated by MTT and LDH assay.  GSH level and SOD enzymes activities were also measured.  DCFH-DA as fluorescence probe was used to detect ROS level by fluorescence microplate reader.  Nrf2 translocation was detected by Western blotting.  Real time Q-PCR was used to detect expressions of NQO1, HO-1and GCLC mRNA level.  The results showed that Sch B could significantly inhibit the decline of cell viability induced by cisplatin treatment (P < 0.05) and the protective effect was in a dose dependent manner.  Furthermore, Sch B treatment significantly inhibited the increase of ROS level induced by cisplatin and reversed the decrease of GSH level (P < 0.05).  When Sch B concentration was up to 5 μmol·L⁻¹, SOD enzyme activities were also enhanced significantly compared with that of the cisplatin group (P < 0.05).  It was shown that Sch B could cause nuclear accumulation of Nrf2 in association with downstream activation of Nrf2 mediated oxidative response genes such as GCLC, NQO1 and HO-1.  These results suggested Sch B could protect against the oxidative damage of HK-2 cells induced by cisplatin via the activation of Nrf2/ARE signal pathway.