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

Abstract

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 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 other hand, 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.

Radiation Protection and Mitigation by Natural Antioxidants and Flavonoids: Implications to Radiotherapy and Radiation Disasters

“…In animal model, it has shown that upregulation of prooxidant enzymes such as NOX1, NOX4, COX-2, iNOS and also increased superoxide production by mitochondria are involved in the development of pneumonitis and fibrosis [25][26][27]. Similar results have shown for intestinal cells, vascular endothelial cells, mice brain, etc [28][29][30].…”

Phytoestrogen genistein hinders ovarian oxidative damage and apoptotic cell death-induced by ionizing radiation: co-operative role of ER-β, TGF-β, and FOXL-2

“…One of the critical pathways triggered by γ-radiation is the apoptotic pathway that could be resulted from DNA damage and oxidative stress. The intrinsic pathway is activated at the mitochondrial level, which subsequently triggers follicular apoptosis by caspases activation 42 . The follicular apoptosis is regulated both by pro-apoptotic factors (e.g., Bax) and anti-apoptotic factors (e.g., Bcl-2 and anti-oxidative agents) 43 .…”

1α,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway

“…ROS can be derived from different sources, including the mitochondria electron transport chain, xanthine oxidase, the cytochrome P450 system, uncoupled nitric oxide synthase, and myeloperoxidase. ROS also mainly comes from two main parts, mitochondrial and NADPH oxidase after radiation ( Bedard and Krause, 2007 ; Bhattacharyya et al., 2014 ; Cho et al., 2017 ; Pei et al., 2017 ; Kawamura et al., 2018 ; Sakai et al., 2018 ; Shimura et al., 2018 ; Mortezaee et al., 2019 ). To explore the origin of ROS induced by 1α,25(OH) 2 D 3 , both NADPH oxidase inhibitors, DPI and Apocynin, and the mitochondrial membrane potential were used to determine the source of ROS ( Bedard and Krause, 2007 ).…”