title: Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin.
abstract: 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.
authors.affiliation: Armed forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Ledney
authors.forename: T B
authors.initials: TB
authors.lastname: Elliott
authors.forename: M R
authors.initials: MR
authors.lastname: Landauer
authors.forename: R M
authors.initials: RM
authors.lastname: Vigneulle
authors.forename: P L
authors.initials: PL
authors.lastname: Henderson
authors.forename: R A
authors.initials: RA
authors.lastname: Harding
authors.forename: S P
authors.initials: SP
authors.lastname: Tom
mesh_terms: 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
chemical_list: 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