Apigenin Attenuates Mesoporous Silica Nanoparticles-Induced Nephrotoxicity by Activating FOXO3a

Mesoporous silica nanoparticles (MSNs) are widely used in many biomedical applications and clinical fields. However, the applications of MSNs are limited by their severe toxicity. Apigenin (AG) has demonstrated pharmacological effects with low toxicity. The aim of this study was to clarify the role of AG in the progression of MSNs-induced renal injury. BALB/c mice and NRK-52E cells were exposed to MSNs with or without AG. AG protected mice and NRK-52E cells from the MSNs-induced pathological variations in renal tissues and decreased cell viability. AG significantly reduced the levels of serum blood urea nitrogen (BUN) and serum creatinine (Scr), upregulated the levels of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and improved the pathological changes of the kidney in MSNs-treated mice. The protective effects of AG were associated with its ability to increase the levels of antioxidants, reduce the accumulation of ROS, and inhibit the expression of the inflammatory mediators (TNF-alpha, IL-6). In addition, AG treatment upregulated the activity of FOXO3a, increased the level of IkB alpha, and reduced the nuclear translocation of NF-kappa B, which ultimately alleviated MSNs-induced inflammation. Nuclear FOXO3a translocation also triggered antioxidant gene transcription and protected nephrocyte from oxidative damage. However, knockdown of FOXO3a significantly blocked the protective effects of AG. These findings suggested that AG could be a promising therapeutic strategy for MSNs-induced nephrotoxicity, and this protective effect might be related to the suppression of oxidative stress and inflammation via the FOXO3a/NF-kappa B pathway.

Automated summary

Apigenin (AG) protects mice and cells from mesoporous silica nanoparticles (MSNs)-induced renal injury by increasing antioxidant levels, reducing oxidative stress, and inhibiting inflammatory gene expression. The protective effect of AG is associated with the FOXO3a/NF-κB pathway, suggesting its potential as a therapeutic strategy for MSNs-induced nephrotoxicity.