Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice
Ionizing radiation (IR) acts as an external stimulating factor, when it acts on the body, it will activate NF- κ B and cause the up-regulation of inducible nitric oxide synthase (iNOS) and induce a large amount of nitric oxide (NO) production. NO and other reactive nitrogen and oxygen...
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doaj-7b17d66f8a9e490babf54bb35ed2bc392020-11-25T00:38:23ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-05-01195153010.3390/ijms19051530ijms19051530Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in MiceYuanyuan Li0Shaofan Kong1Fujun Yang2Wenqing Xu3Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, ChinaInstitute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, ChinaInstitute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, ChinaInstitute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, ChinaIonizing radiation (IR) acts as an external stimulating factor, when it acts on the body, it will activate NF- κ B and cause the up-regulation of inducible nitric oxide synthase (iNOS) and induce a large amount of nitric oxide (NO) production. NO and other reactive nitrogen and oxygen species (RNS and ROS) can cause damage to biological molecules and affect their physiological functions. Our study investigated the protective role of 2-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-ADT) and 2-acetylamino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-AADT), two nitric oxide synthase inhibitors, against radiation-induced hematopoietic and intestinal injury in mice. Pretreatment with 2-ADT and 2-AADT improved the survival of mice exposed to a lethal dose of radiation, especially, the survival rate of the 2-ADT 20 mg/kg group was significantly higher than that of the vehicle group (p < 0.001). Our findings indicated that the radioprotective actions of 2-ADT and 2-AADT are achieved via accelerating hematopoietic system recovery, decreasing oxidative and nitrosative stress by enhancing the antioxidant defense system and reducing NO as well as peroxynitrite (ONOO − ) content, and mitigating the radiation-induced DNA damage evaluated by comet assay. These results suggest that 2-ADT and 2-AADT may have great application potential in ameliorating the damages of radiotherapy.http://www.mdpi.com/1422-0067/19/5/15302-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-ADT)2-acetylamino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-AADT)radioprotectionhematopoieticintestinal injury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuanyuan Li Shaofan Kong Fujun Yang Wenqing Xu |
spellingShingle |
Yuanyuan Li Shaofan Kong Fujun Yang Wenqing Xu Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice International Journal of Molecular Sciences 2-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-ADT) 2-acetylamino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-AADT) radioprotection hematopoietic intestinal injury |
author_facet |
Yuanyuan Li Shaofan Kong Fujun Yang Wenqing Xu |
author_sort |
Yuanyuan Li |
title |
Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice |
title_short |
Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice |
title_full |
Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice |
title_fullStr |
Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice |
title_full_unstemmed |
Protective Effects of 2-Amino-5,6-dihydro-4H-1,3-thiazine and Its Derivative against Radiation-Induced Hematopoietic and Intestinal Injury in Mice |
title_sort |
protective effects of 2-amino-5,6-dihydro-4h-1,3-thiazine and its derivative against radiation-induced hematopoietic and intestinal injury in mice |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-05-01 |
description |
Ionizing radiation (IR) acts as an external stimulating factor, when it acts on the body, it will activate NF- κ B and cause the up-regulation of inducible nitric oxide synthase (iNOS) and induce a large amount of nitric oxide (NO) production. NO and other reactive nitrogen and oxygen species (RNS and ROS) can cause damage to biological molecules and affect their physiological functions. Our study investigated the protective role of 2-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-ADT) and 2-acetylamino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-AADT), two nitric oxide synthase inhibitors, against radiation-induced hematopoietic and intestinal injury in mice. Pretreatment with 2-ADT and 2-AADT improved the survival of mice exposed to a lethal dose of radiation, especially, the survival rate of the 2-ADT 20 mg/kg group was significantly higher than that of the vehicle group (p < 0.001). Our findings indicated that the radioprotective actions of 2-ADT and 2-AADT are achieved via accelerating hematopoietic system recovery, decreasing oxidative and nitrosative stress by enhancing the antioxidant defense system and reducing NO as well as peroxynitrite (ONOO − ) content, and mitigating the radiation-induced DNA damage evaluated by comet assay. These results suggest that 2-ADT and 2-AADT may have great application potential in ameliorating the damages of radiotherapy. |
topic |
2-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-ADT) 2-acetylamino-5,6-dihydro-4H-1,3-thiazine hydrobromide (2-AADT) radioprotection hematopoietic intestinal injury |
url |
http://www.mdpi.com/1422-0067/19/5/1530 |
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