scholarly journals Screening of X-ray responsive substances for the next generation of radiosensitizers

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Akihiro Moriyama ◽  
Takema Hasegawa ◽  
Lei Jiang ◽  
Hitoshi Iwahashi ◽  
Takashi Mori ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Organic Compounds ◽  
Hydroxyl Radicals ◽  
Structural Diversity ◽  
Direct Reaction ◽  
Oxygen Species ◽  
Next Generation ◽  
X Ray ◽  
Molecular Complexity ◽  
Derivatives Of

AbstractX-ray responsivity resulting in the generation of reactive oxygen species (ROS) was investigated in 9600 organic compounds that were selected by considering their structural diversity. We focused on superoxides that were primarily detected using dihydroethidium (DHE) and hydroxyl radicals, that were identified fluorometrically using 3’-(p-aminophenyl) Fluorescein (APF). Many organic compounds were discovered that responded to the DHE and/or APF assay using X-ray irradiation. These results suggest that some of these organic compounds emit either superoxides or hydroxyl radicals whereas others emit both under the influence of X-ray irradiation. The response of the derivatives of a hit compound with a partial change in the structure was also investigated. The products produced from DHE by X-ray irradiation were identified by HPLC to confirm the integrity of the process. Although, the reactions were suppressed by the superoxide dismutase (SOD), not only 2-hydroxyethidium (2-OH-E+), but also ethidium (E+) were detected. The results suggest that apart from a direct reaction, an indirect reaction may occur between DHE and the superoxides. Although X-ray responsiveness could not be inferred due to the molecular complexity of the investigated compounds, delineation of these reactions will facilitate the development of the next generation of radiosensitizers.

scholarly journals Rare-Earth-Doped Calcium Carbonate Exposed to X-ray Irradiation to Induce Reactive Oxygen Species for Tumor Treatment

2019 ◽  
Vol 20 (5) ◽  
pp. 1148 ◽  
Author(s):  
Chun-Chen Yang ◽  
Wei-Yun Wang ◽  
Feng-Huei Lin ◽  
Chun-Han Hou
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Light Source ◽  
Reactive Oxygen ◽  
Blood Analysis ◽  
Oxygen Species ◽  
Tumor Treatment ◽  
X Ray

Conventional photodynamic therapy (PDT) is limited by its penetration depth due to the photosensitizer and light source. In this study, we developed X-ray induced photodynamic therapy that applied X-ray as the light source to activate Ce-doped CaCO3 (CaCO3:Ce) to generate an intracellular reactive oxygen species (ROS) for killing cancer cells. The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-induced CaCO3:Ce. The cell viability significantly decreased and cell cytotoxicity obviously increased with CaCO3:Ce exposure under X-ray irradiation, which is less harmful than radiotherapy in tumor treatment. CaCO3:Ce produced significant ROS under X-ray irradiation and promoted A549 cancer cell death. CaCO3:Ce can enhance the efficacy of X-ray induced PDT, and tumor growth was inhibited in vivo. The blood analysis and hematoxylin and eosin stain (H&E) stain fully supported the safety of the treatment. The mechanisms underlying ROS and CO2 generation by CaCO3:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed. These findings and advances are of great importance in providing a novel therapeutic approach as an alternative tumor treatment.

scholarly journals Involvement of reactive oxygen species in ionizing radiation–induced upregulation of cell surface Toll-like receptor 2 and 4 expression in human monocytic cells

2017 ◽  
Vol 58 (5) ◽  
pp. 626-635 ◽  
Author(s):  
Hironori Yoshino ◽  
Ikuo Kashiwakura
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Synthesis ◽  
Ionizing Radiation ◽  
Cell Surface ◽  
Reactive Oxygen ◽  
Mitogen Activated Protein Kinase ◽  
Protein Synthesis Inhibitor ◽  
Oxygen Species ◽  
X Ray ◽  
Radiation Induced

Abstract Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and are indispensable for antibacterial and antiviral immunity. Our previous report showed that ionizing radiation increases the cell surface expressions of TLR2 and TLR4 and enhances their responses to agonists in human monocytic THP1 cells. The present study investigated how ionizing radiation increases the cell surface expressions of TLR2 and TLR4 in THP1 cells. The THP1 cells treated or not treated with pharmaceutical agents such as cycloheximide and N-acetyl-L-cysteine (NAC) were exposed to X-ray irradiation, following which the expressions of TLRs and mitogen-activated protein kinase were analyzed. X-ray irradiation increased the mRNA expressions of TLR2 and TLR4, and treatment with a protein synthesis inhibitor cycloheximide abolished the radiation-induced upregulation of their cell surface expressions. These results indicate that radiation increased those receptors through de novo protein synthesis. Furthermore, treatment with an antioxidant NAC suppressed not only the radiation-induced upregulation of cell surface expressions of TLR2 and TLR4, but also the radiation-induced activation of the c-Jun N-terminal kinase (JNK) pathway. Since it has been shown that the inhibitor for JNK can suppress the radiation-induced upregulation of TLR expression, the present results suggest that ionizing radiation increased the cell surface expressions of TLR2 and TLR4 through reactive oxygen species–mediated JNK activation.

scholarly journals Role of mitochondrial superoxide dismutase in contraction-induced generation of reactive oxygen species in skeletal muscle extracellular space

2004 ◽  
Vol 286 (5) ◽  
pp. C1152-C1158 ◽  
Author(s):  
A. McArdle ◽  
J. van der Meulen ◽  
G. L. Close ◽  
D. Pattwell ◽  
H. Van Remmen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Extracellular Space ◽  
Superoxide Anion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Superoxide Anions ◽  
Wild Type ◽  
Mnsod Activity

Contractions of skeletal muscles produce increases in concentrations of superoxide anions and activity of hydroxyl radicals in the extracellular space. The sources of these reactive oxygen species are not clear. We tested the hypothesis that, after a demanding isometric contraction protocol, the major source of superoxide and hydroxyl radical activity in the extracellular space of muscles is mitochondrial generation of superoxide anions and that, with a reduction in MnSOD activity, concentration of superoxide anions in the extracellular space is unchanged but concentration of hydroxyl radicals is decreased. For gastrocnemius muscles from adult (6–8 mo old) wild-type ( Sod2+/+) mice and knockout mice heterozygous for the MnSOD gene ( Sod2+/-), concentrations of superoxide anions and hydroxyl radical activity were measured in the extracellular space by microdialysis. A 15-min protocol of 180 isometric contractions induced a rapid, equivalent increase in reduction of cytochrome c as an index of superoxide anion concentrations in the extracellular space of Sod2+/+ and Sod2+/- mice, whereas hydroxyl radical activity measured by formation of 2,3-dihydroxybenzoate from salicylate increased only in the extracellular space of muscles of Sod2+/+ mice. The lack of a difference in increase in superoxide anion concentration in the extracellular space of Sod2+/+ and Sod2+/- mice after the contraction protocol supported the hypothesis that superoxide anions were not directly derived from mitochondria. In contrast, the data obtained suggest that the increase in hydroxyl radical concentration in the extracellular space of muscles from wild-type mice after the contraction protocol most likely results from degradation of hydrogen peroxide generated by MnSOD activity.

Effects of airway inflammation, ozone and exercise on the pulmonary antioxidant capacity of the horse: A war of nutrition

2004 ◽  
Vol 32 ◽  
pp. 129-131
Author(s):  
C Deaton
Keyword(s):  
Hydroxyl Radicals ◽  
Cell Damage ◽  
The Body ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Antioxidant Defences ◽  
Oxygen Utilisation ◽  
Derivatives Of ◽  
Normal Cellular Function

Within the body there is continual production of entities known as Reactive Oxygen Species (ROS). These include radical derivatives of oxygen that contain at least one unpaired electron and include species such as the superoxide and hydroxyl radicals. ROS also include nonradical derivatives of oxygen that are capable of oxidising biomolecules such as hydrogen peroxide, ozone and nitrogen dioxide. ROS are formed from processes such as the respiratory burst of phagocytes and from mitochondrial oxidative phosphorylation, so production is often increased by situations that elevate oxygen utilisation such as exercise. ROS may also act as “signalling” species within the body. Controlled production of ROS is therefore essential for normal cellular function and health, especially with respect to the functioning of the immune system. However, uncontrolled production of ROS can result in cell damage and death, the induction and propagation of inflammation and DNA damage. Thus, the body has evolved intricate and elaborate enzymatic and non–enzymatic antioxidant defences to control and buffer excess ROS production. In situations where the antioxidant defences are overwhelmed either due to their depletion, malfunction or simply due to excessive ROS bombardment, oxidative stress and oxidative damage are likely to occur.

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