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Abstract

Radiation-induced intestinal toxicity is common among cancer patients after radiotherapy. Endothelial cell dysfunction is believed to be a critical contributor to radiation tissue injury in the intestine. Geranylgeranylacetone (GGA) has been used to treat peptic ulcers and gastritis. However, the protective capacity of GGA against radiation-induced intestinal injury has not been addressed. Therefore, we investigated whether GGA affects intestinal damage in mice and vascular endothelial cell damage in vitro. GGA treatment significantly ameliorated intestinal injury, as evident by intestinal crypt survival, villi length and the subsequently prolonged survival time of irradiated mice. In addition, intestinal microvessels were also significantly preserved in GGA-treated mice. To clarify the effect of GGA on endothelial cell survival, we examined endothelial function by evaluating cell proliferation, tube formation, wound healing, invasion and migration in the presence or absence of GGA after irradiation. Our findings showed that GGA plays a role in maintaining vascular cell function; however, it does not protect against radiation-induced vascular cell death. GGA promoted endothelial function during radiation injury by preventing the loss of VEGF/VEGFR1/eNOS signaling and by down-regulating TNFα expression in endothelial cells. This finding indicates the potential impact of GGA as a therapeutic agent in mitigating radiation-induced intestinal damage. 

Author information

Han NK1, Jeong YJ2, Pyun BJ3, Lee YJ4, Kim SH5, Lee HJ6.

1Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul 01812 Korea. gmxvz@hanmail.net.2Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul 01812 Korea. brightwisdm0914@gmail.com.3Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. bjpyun@kiom.re.kr.4Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul 01812 Korea. yjlee8@kirams.re.kr.5College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea. shokim@chonnam.ac.kr.6Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul 01812 Korea. hjlee@kirams.re.kr.