Novel Synthetic Compound, KR-22332, has radio-protective effect through inhibition of Mitochondrial Dysfunction and ROS Generation

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dc.contributor.authorBaek, Seung Jae-
dc.description학위논문(석사)아주대학교 일반대학원 :의학과,2013. 2-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.titleNovel Synthetic Compound, KR-22332, has radio-protective effect through inhibition of Mitochondrial Dysfunction and ROS Generation-
dc.contributor.affiliation아주대학교 일반대학원-
dc.contributor.department일반대학원 의학과- 2-
dc.description.alternativeAbstractRadiation is widely used for treatment of head and neck cancer. But the acute side effect of radiation, especially oral mucositis, is observed almost all patients. Several radio-protective agents are developed but there is no definite agent to prevent. We found novel synthetic compound 3-Amino-3-(4-fluoto-phenyl)-1H-quinoliune-2,4-dione (KR-22332) as an candidate of radio-protective agent and the aim of this study is to investigate the effectiveness of KR-22332 in vitro. The cell viability, apoptosis, reactive oxygen species generation, and mitochondrial membrane potential as well as changes in the signal pathway related to apoptosis were investigated. Then, the embryotoxicity of KR-22332 were explored in a zebrafish model. Radiation-induced apoptosis and altered mitochondrial membrane potential in primary human keratinocyte (HaCaT) was observed. KR-22332 inhibited radiation-induced apoptosis and intracellular reactive oxygen species generation. KR-22332 significantly reduced the expression of ATM, p53, and TNF-α compared to their significant increase after radiation treatment. The results of this study suggest that KR-22332 significantly inhibited radiation-induced apoptosis in human keratinocyte and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.-
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