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.