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| Mesoporous Silica Nanoparticles-Induced Oxidative Stress Involved with GSK-3β Caused Renal Cytotoxicity |
| Lv Yinyin1,Li Ke1,Yi Wei1,Liu Supeng1,Zhou Jie1,2* |
1(Faculty of Basic Medicine, School of Medicine, Yichun University, Yichun 336000, Jiangxi, China)
2(The Center For Translational Medicine,Yichun University, Yichun 336000, Jiangxi, China) |
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Abstract The purpose of the research is to investigate the roles of oxidative stress and GSK-3β in mesoporous silica nanoparticles (MSNs)-induced nephrotoxicity, and the potential protective effects of N-acetylcysteine (NAC). The NRK-52E cells were exposed to 400 μg/mL MSNs, or were pre-treated with 1 μmol/L NAC followed by MSNs. After the treatments, the viability of NKR-52E cells was determined using a 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) assay. The fluorescent probe JC-1 was used to determine the mitochondrial membrane potential (ΔΨm). The levels of GSK-3β related proteinswere measured by using western blot. And the activities of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) were detected to evaluate the antioxidant effects. After 24 h of exposure, MSNs produced severe cytotoxicity in the NRK-52E cells with an IC50 value of (438.6±7.1) μg/mL. After treatment with 400 μg/mL MSNs for 24 h, the rate of NRK-52E cell viability was significantly decreased to 47.57%±2.03%, and the activities of SOD, GSH, CAT were respectively decreased to 39.74%±2.23%、51.42%±3.08%、46.05%±3.71% (P<0.001). 400 μg/mL MSNs also significantly activated the GSK-3β pathway and subsequently triggered cell death by depolarizing the ΔΨm, which opened the mitochondrial permeability transition pores, released cytochrome c (Cyt C) and, ultimately, activated caspase-3 (P<0.001). And the 400 μg/mL MSNs-induced significantly toxic injuries of NRK-52E cells could be attenuated by the pretreatment of NAC (P<0.01). MSNs induced renal cytotoxicity via oxidative stress, which was associated with up-regulation GSK-3β activation. NAC can attenuate mitochondrial dysfunction, enhance the antioxidative ability of renal cells and prevent oxidative stress injury induced by MSNs.
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Received: 27 December 2017
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