Inflammation and Chronic Oxidative Stress in Radiation-Induced Late Normal Tissue Injury: Therapeutic Implications

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

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Radiation-Induced Normal Tissue Damage: Oxidative Stress and Epigenetic Mechanisms

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/3010342 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 14

Author(s):

Jinlong Wei ◽

Bin Wang ◽

Huanhuan Wang ◽

Lingbin Meng ◽

Qin Zhao ◽

...

Keyword(s):

Oxidative Stress ◽

Tissue Damage ◽

Normal Tissue ◽

Noncoding Rna ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Redox System ◽

Epigenetic Mechanisms ◽

Rna Regulation ◽

Normal Tissue Damage ◽

Radiation Induced

Radiotherapy (RT) is currently one of the leading treatments for various cancers; however, it may cause damage to healthy tissue, with both short-term and long-term side effects. Severe radiation-induced normal tissue damage (RINTD) frequently has a significant influence on the progress of RT and the survival and prognosis of patients. The redox system has been shown to play an important role in the early and late effects of RINTD. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the main sources of RINTD. The free radicals produced by irradiation can upregulate several enzymes including nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), lipoxygenases (LOXs), nitric oxide synthase (NOS), and cyclooxygenases (COXs). These enzymes are expressed in distinct ways in various cells, tissues, and organs and participate in the RINTD process through different regulatory mechanisms. In recent years, several studies have demonstrated that epigenetic modulators play an important role in the RINTD process. Epigenetic modifications primarily contain noncoding RNA regulation, histone modifications, and DNA methylation. In this article, we will review the role of oxidative stress and epigenetic mechanisms in radiation damage, and explore possible prophylactic and therapeutic strategies for RINTD.

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Radiation-induced kidney injury: a role for chronic oxidative stress?

Micron ◽

10.1016/s0968-4328(01)00006-3 ◽

2002 ◽

Vol 33 (2) ◽

pp. 133-141 ◽

Cited By ~ 52

Author(s):

Mike E.C Robbins ◽

Weiling Zhao ◽

Charles S Davis ◽

Shinya Toyokuni ◽

Stephen M Bonsib

Keyword(s):

Oxidative Stress ◽

Kidney Injury ◽

Chronic Oxidative Stress ◽

Radiation Induced

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350 speaker OXIDATIVE STRESS IN RADIATION-INDUCED NORMAL TISSUE DAMAGE AND STRATEGIES FOR INHIBITION OF THIS PROCESS

Radiotherapy and Oncology ◽

10.1016/s0167-8140(11)70472-8 ◽

2011 ◽

Vol 99 ◽

pp. S139

Author(s):

J. Williams

Keyword(s):

Oxidative Stress ◽

Tissue Damage ◽

Normal Tissue ◽

Normal Tissue Damage ◽

Radiation Induced

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Total Body Irradiation Causes Residual Bone Marrow Injury by Induction of Persistent Oxidative Stress in Murine Hematopoietic Stem Cells.

Blood ◽

10.1182/blood.v114.22.3209.3209 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3209-3209

Author(s):

Yong Wang ◽

Lingbo Liu ◽

Senthil Kumar Pazhanisamy ◽

Aimin Meng ◽

Daohong Zhou

Keyword(s):

Oxidative Stress ◽

Bone Marrow ◽

Total Body Irradiation ◽

Molecular Mechanisms ◽

Conflicts Of Interest ◽

Tissue Injury ◽

Hematopoietic Stem ◽

Chronic Oxidative Stress ◽

Total Body

Abstract Abstract 3209 Poster Board III-146 Ionizing radiation (IR) and/or chemotherapy cause not only acute tissue injury but also have late effects including long-term bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to induction of hematopoietic stem cell (HSC) senescence. However, neither the molecular mechanisms by which IR and/or chemotherapy induce HSC senescence have been clearly defined, nor has an effective treatment been developed to ameliorate the injury, which were investigated in the present study using a total body irradiation (TBI) mouse model. The results showed that exposure of mice to 6.5 Gy TBI induced a persistent increase in reactive oxygen species (ROS) production in HSCs only for up to 8 weeks, primarily via up-regulation of NADPH oxidase 4 (NOX4). This finding provides the foremost direct evidence demonstrating that in vivo exposure to IR causes persistent oxidative stress selectively in a specific population of BM hematopoietic cells (HSCs). The induction of chronic oxidative stress in HSCs was associated with sustained increases in oxidative DNA damage, DNA double strand breaks, inhibition of HSC clonogenic function, and induction of HSC senescence but not apoptosis. Treatment of the irradiated mice with N-acetyl-cysteine (NAC) after TBI significantly attenuated IR-induced inhibition of HSC clonogenic function and reduction of HSC long-term engraftment after transplantation. These findings suggest that selective induction of chronic oxidative stress in HSCs by TBI leads to induction of HSC senescence and residual BM injury and that antioxidant therapy may be used as an effective strategy to mitigate IR- and chemotherapy-induced residual BM injury. Disclosures No relevant conflicts of interest to declare.

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