Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms23094643
Keywords
gamma-tocotrienol; intestine; radiation; nonhuman primates; radiation countermeasure
Funding
- Congressionally Directed Medical Research Programs [W81XWH-15-C-0117, JW140032]
- US Department of Defense
- National Institute of Health Center of Biological Research Excellence [P20GM109005]
- CDMRP [793907, JW140032] Funding Source: Federal RePORTER
Ask authors/readers for more resources
This study evaluated the effects of the vitamin E analog gamma-tocotrienol (GT3) on GI recovery in nonhuman primates (NHPs) after total-body irradiation. The results showed that GT3 promoted the survival and proliferation of intestinal stem cells, reduced cell apoptosis, and had a radioprotective function. Therefore, GT3 has the potential to be used as a prophylactic medical countermeasure for radiation-induced GI injury.
The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated GI recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques were divided into two groups; eight received vehicle and eight GT3 24 h prior to 12 Gy TBI. Proximal jejunum was assessed for structural injuries and crypt survival on day 4 and 7. Apoptotic cell death and crypt cell proliferation were assessed with TUNEL and Ki-67 immunostaining. Irradiation induced significant shortening of the villi and reduced mucosal surface area. GT3 induced an increase in crypt depth at day 7, suggesting that more stem cells survived and proliferated after irradiation. GT3 did not influence crypt survival after irradiation. GT3 treatment caused a significant decline in TUNEL-positive cells at both day 4 (p < 0.03) and 7 (p < 0.0003). Importantly, GT3 induced a significant increase in Ki-67-positive cells at day 7 (p < 0.05). These data suggest that GT3 has radioprotective function in intestinal epithelial and crypt cells. GT3 should be further explored as a prophylactic medical countermeasure for radiation-induced GI injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available