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

Int J Nanomedicine. 2018 Dec 27:14:215-229. doi: 10.2147/IJN.S184804. eCollection 2019.

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.

Keywords: acute kidney injury; inflammation; ischemia/reperfusion; oxidative stress; porous Se@SiO2 nanospheres.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / chemistry
  • Inflammation / etiology
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Kidney Function Tests
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanospheres / administration & dosage*
  • Nanospheres / chemistry
  • Oxidative Stress / drug effects*
  • Reperfusion Injury / complications*
  • Selenium / administration & dosage*
  • Selenium / chemistry
  • Silicon Dioxide / administration & dosage*
  • Silicon Dioxide / chemistry

Substances

  • Antioxidants
  • Silicon Dioxide
  • Selenium