Schisandrin B protects against nephrotoxicity induced by cisplatin in HK-2 cells via Nrf2-ARE activation.
- Author:
Mei LI
1
;
Jing JIN
;
Jia LI
;
Cui-Wen GUAN
;
Wen-Wen WANG
;
Yu-Wen QIU
;
Zhi-Ying HUANG
Author Information
1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
toxicity;
Antioxidants;
isolation & purification;
pharmacology;
Cell Line;
Cell Survival;
drug effects;
Cisplatin;
toxicity;
Cyclooctanes;
isolation & purification;
pharmacology;
Glutamate-Cysteine Ligase;
genetics;
metabolism;
Glutathione;
metabolism;
Heme Oxygenase-1;
genetics;
metabolism;
Humans;
Kidney Tubules, Proximal;
cytology;
metabolism;
L-Lactate Dehydrogenase;
metabolism;
Lignans;
isolation & purification;
pharmacology;
NAD(P)H Dehydrogenase (Quinone);
genetics;
metabolism;
NF-E2-Related Factor 2;
genetics;
metabolism;
Polycyclic Compounds;
isolation & purification;
pharmacology;
RNA, Messenger;
metabolism;
Reactive Oxygen Species;
metabolism;
Schisandra;
chemistry;
Signal Transduction;
Superoxide Dismutase;
metabolism
- From:
Acta Pharmaceutica Sinica
2012;47(11):1434-1439
- CountryChina
- Language:Chinese
-
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.
