Radioprotective effects of lipid A, liposomes, and liposomes containing lipid A in mice.
Lipid A from Gram-negative bacterial lipopolysaccharide (endotoxin) was incorporated into liposomal membranes and examined as a prophylactic radioprotectant compound in lethally irradiated mice. Splenic hematopoietic activity, resulting in increased numbers of spleen cell colonies, was induced both by lipid A alone or more strongly by liposomal lipid A. Increased survival of lethally irradiated animals was induced to a slight extent by liposomes alone, to a greater extent by lipid A, and at the highest level by liposomes containing lipid A. Under conditions where 100% of untreated or saline-treated animals died of acute radiation syndrome after 20 days, more than 90% of the animals pretreated with liposomal lipid A were still alive 30 days after irradiation. We conclude that lipid A had substantial radioprotectant activity by itself, and the activity was enhanced by incorporation into liposomes. Liposomes alone also exhibited mild radioprotectant effects.
Richardson
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Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Alving
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D000818:Animals; D002452:Cell Count; D005260:Female; D005720:Gamma Rays; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D008050:Lipid A / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008813:Mice, Inbred ICR; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents; D013154:Spleen / Q000166:cytology / Q000528:radiation effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D014916:Whole-Body Irradiation
D008050:Lipid A; D008081:Liposomes; D011837:Radiation-Protective Agents