Radioprotection by polysaccharides alone and in combination with aminothiols.
We demonstrated that glucan, a beta-1,3 polysaccharide immunomodulator, enhances survival of mice when administered before radiation exposure.  Glucan's prophylactic survival-enhancing effects are mediated by several mechanisms including (1) increasing macrophage-mediated resistance to potentially lethal postirradiation opportunistic infections, (2) increasing the D(o) of hematopoietic progenitor cells, and (3) accelerating hematopoietic reconstitution.  In addition, even when administered shortly after some otherwise lethal doses of radiation, glucan increases survival.  Glucan's therapeutic survival-enhancing effects are also mediated through its ability to enhance macrophage function and to accelerate hematopoietic reconstitution; glucan's therapeutic potential, however, is ultimately dependent on the survival of a critical number of hematopoietic stem cells capable of responding to glucan's stimulatory effects.  Preirradiation administration of the traditional aminothiol radioprotectants WR-2721 and WR-3689 has been previously demonstrated to be an extremely effective means to increase hematopoietic stem cell survival.  Therapeutic glucan treatment administered in combination with preirradiation WR-2721 or WR-3689 treatment synergistically increases both hematopoietic reconstitution and survival.  Such combined modality treatments offer new promise in treating acute radiation injury.
Patchen
M L
ML
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5145, USA.
MacVittie
T J
TJ
Solberg
B D
BD
D'Alesandro
M M
MM
Brook
I
I
D004999:Amifostine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005720:Gamma Rays; D005936:Glucans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors
D005936:Glucans; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; C049344:S-2-(3-methylaminopropylamino)ethylphosphorothioic acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004999:Amifostine