title: [Schisandrin B protects against nephrotoxicity induced by cisplatin in HK-2 cells via Nrf2-ARE activation].
abstract: 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-1 and 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 micromol x 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.
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Mei
authors: M
authors: Li
authors: Jing
authors: J
authors: Jin
authors: Jia
authors: J
authors: Li
authors: Cui-Wen
authors: CW
authors: Guan
authors: Wen-Wen
authors: WW
authors: Wang
authors: Yu-Wen
authors: YW
authors: Qiu
authors: Zhi-Ying
authors: ZY
authors: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000633:toxicity*; D034242:Cyclooctanes / Q000302:isolation & purification / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D034242:Cyclooctanes; D017705:Lignans; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D011083:Polycyclic Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C015499:schizandrin B; D007770:L-Lactate Dehydrogenase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D002945:Cisplatin