Role of NADPH oxidase in radiation-induced pro-oxidative and pro-inflammatory pathways in mouse brain

Int J Radiat Biol. 2017 Nov;93(11):1257-1266. doi: 10.1080/09553002.2017.1377360.


Purpose: The present study was designed to investigate our hypothesis that NADPH oxidase plays a role in radiation-induced pro-oxidative and pro-inflammatory environments in the brain.

Materials and methods: C57BL/6 mice received either fractionated whole brain irradiation or sham-irradiation. The mRNA expression levels of pro-inflammatory mediators, such as TNF-α and MCP-1, were determined by quantitative real-time RT-PCR. The protein expression levels of TNF-α, MCP-1, NOX-2 and Iba1 were detected by immunofluorescence staining. The levels of ROS were visualized by in situ DHE fluorescence staining.

Results: A significant up-regulation of mRNA and protein expression levels of TNF-α and MCP-1 was observed in irradiated mouse brains. Additionally, immunofluorescence staining of Iba1 showed a marked increase of microglial activation in mouse brain after irradiation. Moreover, in situ DHE fluorescence staining revealed that fractionated whole brain irradiation significantly increased production of ROS. Furthermore, a significant increase in immunoreactivity of NOX-2 was detected in mouse brain after irradiation. On the contrary, an enhanced ROS generation in mouse brain after irradiation was markedly attenuated in the presence of NOX inhibitors or NOX-2 neutralizing antibody.

Conclusions: These results suggest that NOX-2 may play a role in fractionated whole brain irradiation-induced pro-oxidative and pro-inflammatory pathways in mouse brain.

Keywords: Fractionated whole brain irradiation; NOX-2; ROS; inflammation.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / enzymology
  • Brain / metabolism*
  • Brain / radiation effects*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Dose Fractionation, Radiation
  • Gene Expression Regulation, Enzymologic / radiation effects
  • Inflammation / enzymology
  • Inflammation / metabolism
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microglia / radiation effects
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism*
  • Oxidation-Reduction / radiation effects
  • Oxidative Stress / radiation effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / radiation effects


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Membrane Glycoproteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases