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)
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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