Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin.
Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD(10)) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and gamma-rays (n/gamma=1) or 60Co gamma-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/gamma=1 and gamma-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/gamma=1 irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.
Ledney
G D
GD
Armed forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA.
Elliott
T B
TB
Landauer
M R
MR
Vigneulle
R M
RM
Henderson
P L
PL
Harding
R A
RA
Tom
S P
SP
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D003311:Cord Factors / Q000627:therapeutic use; D005260:Female; D005720:Gamma Rays; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000209:etiology; D008099:Liver / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D009502:Neutrons; D015242:Ofloxacin / Q000627:therapeutic use*; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D015996:Survival Rate
D000276:Adjuvants, Immunologic; D000890:Anti-Infective Agents; D002511:Cephalosporins; D003311:Cord Factors; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D002443:Ceftriaxone; C048392:WR 151327; C043399:6,6'-dicorynomycolyl trehalose; D015242:Ofloxacin