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In vitro and in vivo protective effects of granulocyte colony-stimulating factor against radiation-induced intestinal injury
Authors:Joong-Sun Kim  Miyoung Yang  Chang-Geun Lee  Sung-Dae Kim  Jung-Ki Kim  Kwangmo Yang
Institution:1. Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, Republic of Korea
4. Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI, USA
2. Department of Radiation Oncology, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, Republic of Korea
3. Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences (KIRMAS), Seoul, 139-706, Republic of Korea
Abstract:Intestinal injury is a major cause of death after high-dose radiation exposure. The use of granulocyte-colony stimulating factor (G-CSF) to treat radiation injury has focused on enhancing recovery from hematopoietic radiation syndrome. We evaluated G-CSF for its ability to protect against radiation-induced intestinal injury in rat intestinal epithelial cells (IEC-6) and BALB/c mouse models. For in vitro tests, pre-radiation addition of G-CSF to IEC-6 prevented cytotoxicity and the loss of cell viability. Pre-radiation G-CSF treatment also reduced radiation-induced cleavage of caspase-3 and p53 in IEC-6. For in vivo tests, examination 12 h after abdominal irradiation showed that G-CSF-treated mice were protected against apoptosis of the jejunal crypts. G-CSF-treated mice also showed attenuated intestinal morphological changes 3.5 days after abdominal radiation (10 Gy). G-CSF also reduced the levels of proinflammatory cytokines interleukin-6 and tumor necrosis factor-α after radiation. This study showed that G-CSF may protect against radiation-induced intestinal damage through its anti-apoptotic and anti-inflammatory effects. These results suggest that G-CSF is promising candidate for protection against intestinal mucosal injury following irradiation.
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