Behavioral Toxicity of Radioprotective Bioactive Lipids
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The ideal radioprotective agent for use in radiotherapy and civil defense should provide effective protection with minimal behavioral disruption. The bioactive lipids are among the compounds that have demonstrated radioprotective efficacy in cellular assays or animal survival studies. Members of this group that have been determined to be radioprotective include prostaglandins, leukotrienes, and platelet-activating factor (PAF). While protective agents have been identified in both the cyclooxygenase and lipoxygenase pathways, as well as for the phospholipid derived PAF, not all bioactive lipids provide radioprotection (1). The most promising radioprotective compounds include the synthetic methylated derivative of the naturally occurring prostaglandin E2, 16,16-dimethyl prostaglandin E2 (DiPGE2), leukotriene C4 (LTC4), and PAF. In our laboratory, they are maximally effective for enhancing animal survival when administered 5–10 minutes before irradiation, and provide dose reduction factors (DRF) ranging from 1.45 to 1.9 (2–4). The radioprotective mechanisms of the bioactive lipids have not been clearly elucidated, but they are believed to act through different receptor systems. Mechanisms ranging from alterations of biological mediators, such as cyclic AMP, to hypoxia and cardiovascular effects have been postulated (5,6).
KeywordsLocomotor Activity Vehicle Control Group Bioactive Lipid Civil Defense Walter Reed Army Institute
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