Porous Se@SiO2 nanospheres attenuate ischemia/ reperfusion (I/R)-induced acute kidney injury (AKI) and inflammation by antioxidative stress

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Abstract

Objectives: Acute kidney injury (AKI) is a growing global health concern, and is associated with high rates of mortality and morbidity in intensive care units. Se is a trace element with antioxidant properties. This study aimed to determine whether porous Se@SiO2 nanospheres could relieve oxidative stress and inflammation in ischemia/reperfusion (I/R)-induced AKI. Methods: Male 6-to 8-week-old C57bl/6 mice were divided into four groups: sham + saline, sham + Se@SiO2, I/R + saline, and I/R + Se@SiO2. Mice in the I/R groups experienced 30 minutes of bilateral renal I/R to induce an AKI. Porous Se@SiO2 nanospheres (1 mg/kg) were intraperitoneally injected into mice in the I/R + Se@SiO2 group 2 hours before I/R, and the same dose was injected every 12 hours thereafter. Hypoxia/reoxygenation (H/R) was used to mimic I/R in vitro. PBS was used as a control treatment. Human kidney 2 cells were seeded into 12-well plates (5×105 cells/well) and divided into four groups: control + PBS group, control + Se@SiO2 group, H/R + PBS group, and H/R + Se@SiO2 group (n=3 wells). We then determined the expression levels of ROS, glutathione, inflammatory cytokines and proteins, fibrosis proteins, and carried out histological analysis upon kidney tissues. Results: In vitro, intervention with porous Se@SiO2 nanospheres significantly reduced levels of ROS (P<0.05), inflammatory cytokines (P<0.05), and inflammation-associated proteins (P<0.05). In vivo, tubular damage, cell apoptosis, and interstitial inflammation during AKI were reduced significantly following treatment with porous Se@SiO2 nanospheres. Moreover, the occurrence of fibrosis and tubular atrophy after AKI was attenuated by porous Se@SiO2 nanospheres. Conclusion: Porous Se@SiO2 nanospheres exhibited a protective effect in I/R-induced AKI by resisting oxidative stress and inflammation. This suggests that porous Se@SiO2 nanospheres may represent a new therapeutic method for AKI.

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Zheng, Z., Deng, G., Qi, C., Xu, Y., Liu, X., Zhao, Z., … Liu, J. (2019). Porous Se@SiO2 nanospheres attenuate ischemia/ reperfusion (I/R)-induced acute kidney injury (AKI) and inflammation by antioxidative stress. International Journal of Nanomedicine, 14, 215–229. https://doi.org/10.2147/IJN.S184804

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