title: Intraesophageal administration of GS-nitroxide (JP4-039) protects against ionizing irradiation-induced esophagitis.
abstract: OBJECTIVE
  this study evaluated esophageal radioprotection by the Gramicidin S (GS) derived-nitroxide, JP4-039, a mitochondrial targeting peptide-isostere covalently-linked to 4-amino-Tempo, delivered in a novel swallowed oil-based (F15) formulation.
  
  
  METHODS
  C57BL/6HNsd female mice received intraesophageal F15 formulation containing JP4-039 (4 mg/ml in 100 microl volumes) 10 minutes before 28 or 29 Gy upper body irradiation compared to MnSOD-PL (100 microl containing 100 microg plasmid) 24 hours prior to irradiation. Subgroups received 1 × 10(7) C57BL/6HNsd, GFP(+) male bone marrow cells intravenously 5 days after irradiation.
  
  
  RESULTS
  JP4-039/F15 or MnSOD-PL increased survival compared to irradiated controls (p<0.0001 for either). Marrow injection further increased survival (p=0.0462 and 0.0351, respectively). Esophagi removed at 1, 3, 7, 14, 24, or 60 days showed bone marrow-derived cells in the esophagi.
  
  
  CONCLUSIONS
  intraesophageal GS-nitroxide radioprotection is mediated primarily through recovery of endogenous esophageal progenitor cells.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, U.S.A.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.forename: Julie P
authors.initials: JP
authors.lastname: Goff
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Tracy
authors.initials: T
authors.lastname: Dixon
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Darcy
authors.initials: D
authors.lastname: Franicola
authors.forename: Hongmei
authors.initials: H
authors.lastname: Shen
authors.forename: Jean-Claude M
authors.initials: JC
authors.lastname: Rwigema
authors.forename: Valerian
authors.initials: V
authors.lastname: Kagan
authors.forename: Mark
authors.initials: M
authors.lastname: Bernard
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D019610:Cytoprotection; D016503:Drug Delivery Systems; D004941:Esophagitis / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D004947:Esophagus / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D008081:Liposomes / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009589:Nitrogen Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy
chemical_list: C544775:JP4-039; D008081:Liposomes; D009589:Nitrogen Oxides