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1.
Yonsei Medical Journal ; : 886-894, 2014.
Artigo em Inglês | WPRIM | ID: wpr-137016

RESUMO

PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-alpha compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.


Assuntos
Humanos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Queratinócitos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Protetores contra Radiação/química , Espécies Reativas de Oxigênio/metabolismo
2.
Yonsei Medical Journal ; : 886-894, 2014.
Artigo em Inglês | WPRIM | ID: wpr-137010

RESUMO

PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-alpha compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.


Assuntos
Humanos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Queratinócitos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Protetores contra Radiação/química , Espécies Reativas de Oxigênio/metabolismo
3.
Indian J Exp Biol ; 2003 Dec; 41(12): 1365-71
Artigo em Inglês | IMSEAR | ID: sea-59461

RESUMO

Tocopherol monoglucoside (TMG), a water soluble derivative of vitamin E offers protection against deleterious effects of ionizing radiation, both under in vivo and in vitro conditions, to biological systems. TMG was found to be a potent antioxidant and an effective free radical scavenger. It forms a phenoxyl radical similar to trolox upon reaction with various one-electron oxidants. TMG protected DNA from radiation-induced strand breaks. It also protected thymine glycol formation induced by gamma-radiation. Gamma-radiation-induced loss of viability of EL-tumor cells and peroxidation of lipids in microsomal and mitochondrial membranes were prevented by TMG. TMG was nontoxic to mice when administered orally up to 7.0 g/kg body weight. The LD50 dose of TMG for ip administration in mice was 1.15 g/kg body wt. In rats, following oral and ip administration of TMG, the absorption (distribution) half lives were 5.8 and 3.0 min respectively and elimination half lives were 6.7 and 3.1 min respectively. Embryonic mortality resulting from exposure of pregnant mice to ionizing radiation (2 Gy) was reduced by 75% by ip administration of TMG (0.6 g/kg, body wt) prior to irradiation. TMG offered protection to mice against whole body gamma-radiation-induced lethality and weight loss. The LD50(30) of mice increased from 6 to 6.72 Gy upon post irradiation administration of a single dose of TMG (0.6 g/kg, body wt) by ip.


Assuntos
Animais , Relação Dose-Resposta a Droga , Feminino , Gravidez , Protetores contra Radiação/química , Vitamina E/sangue
4.
Bol. Soc. Bras. Hematol. Hemoter ; 20(178): 69-74, maio-ago. 1998.
Artigo em Português | LILACS | ID: lil-273905

RESUMO

A medula óssea é bastante radiosensível e dependendo da intensidade, suas alteraçöes podem causar a morte de indivíduos expostos, pela Síndrome Aguda da Radiaçäo.Constitui-se também num tecido crítico para a interaçäo de drogas e radiaçäo, durante o tratamento de doenças malignas, às vezes, limitando tais procedimentos. No presente artigo säo abordadas as características do radioprotetor amifostina e seu papel na proteçäo da medula óssea irradiada.


Assuntos
Humanos , Amifostina/administração & dosagem , Amifostina/química , Medula Óssea/química , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/química , Radiação Ionizante
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