Intraesophageal administration of GS-nitroxide (JP4-039) protects against ionizing irradiation-induced esophagitis.

BACKGROUND/AIM 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. MATERIALS AND 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. CONCLUSION intraesophageal GS-nitroxide radioprotection is mediated primarily through recovery of endogenous esophageal progenitor cells.