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Micronutrients in Protecting Against Lethal Doses of Ionizing Radiation
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
A pilot study was performed at the Armed Forces of Radiobiology Research Institute (AFRRI) to evaluate the effects of a mixture of multiple antioxidants (same as used in sheep) in mice. The results showed that a dose of 8.5 Gy produced bone marrow syndrome with a 100% lethality in 30 days. An oral administration of the antioxidant mixture daily for 7 days or 24 hours before whole-body gamma-irradiation increased the survival rate of irradiated animals from 0% to 40% (Table 19.3). Placebo treatment of irradiated mice was ineffective. To our knowledge, this level of protection has not been achieved by an oral administration of a single antioxidant or its derivatives before whole-body gamma-irradiation with a dose that produced bone marrow syndrome with a 100% mortality.
Combined radiation injury and its impacts on radiation countermeasures and biodosimetry
Published in International Journal of Radiation Biology, 2023
Juliann G. Kiang, William F. Blakely
In animal models of combined radiation injury (CI), there are rats (Alpen and Sheline 1954; Valeriote and Baker 1964), guinea pigs (Korlof 1956), dogs (Brooks et al. 1952), and swine (Baxter et al. 1953) with burns and wounds; they usually rise mortality after otherwise non-lethal radiation exposures. In 1970s, Armed Forces Radiobiology Research Institute (AFRRI) began CI investigations. In mice, radiation exposure followed by burns or other wounds further reduced survival compared to burns alone, wounds alone or radiation exposure alone (Ledney et al. 1992; Kiang and Ledney 2013), and radiation delays wound healing times (Ledney et al. 1981). Subsequently, CI resulted in acute suppression of myeloid, inhibition of the immune system, fluid imbalance, macro/microcirculation failure, massive cellular damage and death, and vital organ dysfunctions. Then, multiple organ dysfunction syndrome (MODS) occurs, which is the most frequent cause of death after CI (Koenig et al. 2005; Lausevic et al. 2008; Zou et al. 2008; Kiang and Olabisi 2019).
Development of gamma-tocotrienol as a radiation medical countermeasure for the acute radiation syndrome: current status and future perspectives
Published in Expert Opinion on Investigational Drugs, 2023
GT3, delta-tocotrienol, tocopherol succinate, and their derivatives have been shown to effectively protect mice against high, acute and potentially fatal doses of ionizing radiation [27]. GT3 has been most extensively evaluated for its radioprotective efficacy in both rodents (mice) and nonhuman primates (NHPs) [35,36]. After comparing various attributes of different tocotrienols and tocopherols, GT3 was selected for advanced development as a radiation MCM [27,35,36]. The initial studies showed GT3 to have significant levels of radioprotectiveness for both H-ARS and GI-ARS when tested in a murine model of acute radiation injury. These initial findings prompted investigators at the Armed Forces Radiobiology Research Institute and elsewhere to initiate advanced, large animal studies (e.g. NHPs) [36–42]. As such and with further development, this candidate MCM may prove to be highly useful and have safe prophylaxis for use in warding off potentially lethal effects of acute radiation exposure and associated injuries. Current research and development on this agent (GT3), along with the positive findings of the agent’s safety and efficacy profiles, seem to be setting the stage for possible approval by the US FDA for human use. This article provides the current status of GT3 as a radioprotective MCM.
Medical countermeasures for radiation induced health effects: report of an Interagency Panel Session held at the NASA Human Research Program Investigator’s Workshop, 26 January 2017
Published in International Journal of Radiation Biology, 2021
Lisa S. Carnell, Mary Homer, Keith Hoots, Heather Meeks, Pataje G. S. Prasanna, Carmen Rios, Lisa C. Simonsen, Lanyn P. Taliaferro, Lynne K. Wathen
The Interagency Panel Session was organized to address specific questions regarding radiation-induced health effects, exposure concerns, and MCM research and development of interest to each participating agency. It included presentations from several institutes under the National Institutes of Health (NIH) including the National Cancer Institute (NCI), National Institute for Allergy and Infectious Disease (NIAID), National Heart Lung and Blood Institute (NHLBI), Biomedical Advanced Research and Development Authority (BARDA), the Defense Threat Reduction Agency (DTRA), and NASA, along with attendance by the Armed Forces Radiobiology Research Institute (AFRRI). Each agency and institute identified unique requirements and goals for MCM development and implementation. Illustrated in Figure 1 (Carnell 2019) are the highlights for each agency and institute’s key areas of interest based on their requirements and goals.