title: High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines.
abstract: There is an urgent need to develop non-toxic radioprotectors. We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion. Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of 60Co radiation. Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin). Peripheral blood cell profile and 60-day survival were used as indices of protection. At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days. Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation. Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion. The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines. These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines. Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls.
authors.affiliation: Radiation Casualty Management Team, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA. kumar@afrri.usuhs.mil
authors.forename: K Sree
authors.initials: KS
authors.lastname: Kumar
authors.forename: V
authors.initials: V
authors.lastname: Srinivasan
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Toles
authors.forename: Venita L
authors.initials: VL
authors.lastname: Miner
authors.forename: William E
authors.initials: WE
authors.lastname: Jackson
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Seed
mesh_terms: D000818:Animals; D001803:Blood Transfusion; D002440:Cefoxitin / Q000627:therapeutic use*; D002506:Cephalexin / Q000627:therapeutic use*; D004285:Dogs; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005839:Gentamicins / Q000627:therapeutic use*; D016285:Iloprost / Q000627:therapeutic use*; D007928:Lethal Dose 50; D007958:Leukocyte Count; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016595:Misoprostol / Q000627:therapeutic use*; D011832:Radiation Injuries / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D004338:Drug Combinations; D005839:Gentamicins; D008050:Lipid A; D016595:Misoprostol; D002440:Cefoxitin; D016285:Iloprost; C048436:monophosphoryl lipid A; D002506:Cephalexin