Next Article in Journal
Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure
Previous Article in Journal
Combined Virtual and Experimental Screening for CK1 Inhibitors Identifies a Modulator of p53 and Reveals Important Aspects of in Silico Screening Performance
Open AccessArticle

Geranylgeranylacetone Ameliorates Intestinal Radiation Toxicity by Preventing Endothelial Cell Dysfunction

Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul 01812 Korea
Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(10), 2103;
Received: 14 September 2017 / Revised: 30 September 2017 / Accepted: 3 October 2017 / Published: 7 October 2017
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: radiation enteropathy; endothelial dysfunction; geranylgeranylacetone (GGA); angiogenesis radiation enteropathy; endothelial dysfunction; geranylgeranylacetone (GGA); angiogenesis
Show Figures

Figure 1

MDPI and ACS Style

Han, N.-K.; Jeong, Y.J.; Pyun, B.-J.; Lee, Y.-J.; Kim, S.-H.; Lee, H.-J. Geranylgeranylacetone Ameliorates Intestinal Radiation Toxicity by Preventing Endothelial Cell Dysfunction. Int. J. Mol. Sci. 2017, 18, 2103.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop