经食管给予 GS-氮氧自由基（JP4-039）可预防放射性食管炎。

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.

背景/目的：本研究评估了经线粒体靶向肽 JP4-039 衍生的革兰氏菌素 S（GS）-氮氧化物对食管的放射防护作用，该靶向肽与 4-氨基-Tempo 以共价键连接，并以新型口服油基（F15）制剂递送。

材料和方法

C57BL/6HNsd 雌性小鼠在接受 28 或 29 Gy 全身照射前 10 分钟经食管内给予 F15 制剂 JP4-039（100 微升体积中含 4 毫克/毫升），与 MnSOD-PL（照射前 24 小时给予 100 微升含 100 微克质粒）进行比较。亚组在照射后 5 天接受 1×10(7) C57BL/6HNsd、GFP(+)雄性骨髓细胞静脉内注射。