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

Epperly, MW and Goff, JP and Li, S and Gao, X and Wipf, P and Dixon, T and Wang, H and Franicola, D and Shen, H and Rwigema, JCM and Kagan, V and Bernard, M and Greenberger, JS (2010) Intraesophageal administration of GS-nitroxide (JP4-039) protects against ionizing irradiation-induced esophagitis. In Vivo, 24 (6). 811 - 819. ISSN 0258-851X

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Abstract

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 μl volumes) 10 minutes before 28 or 29 Gy upper body irradiation compared to MnSOD-PL (100 μl containing 100 μg plasmid) 24 hours prior to irradiation. Subgroups received 1×10 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. 7 +


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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Epperly, MW
Goff, JP
Li, Ssol4@pitt.eduSOL4
Gao, X
Wipf, Ppwipf@pitt.eduPWIPF
Dixon, T
Wang, Hhow8@pitt.eduHOW80000-0003-0477-2908
Franicola, D
Shen, Hhos1@pitt.eduHOS1
Rwigema, JCM
Kagan, Vkagan@pitt.eduKAGAN
Bernard, M
Greenberger, JSjoelg@pitt.eduJOELG
Date: 1 January 2010
Date Type: Publication
Journal or Publication Title: In Vivo
Volume: 24
Number: 6
Page Range: 811 - 819
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0258-851X
MeSH Headings: Animals; Bone Marrow Transplantation; Cytoprotection; Drug Delivery Systems; Esophagitis--pathology; Esophagitis--prevention & control; Esophagitis--therapy; Esophagus--drug effects; Esophagus--pathology; Esophagus--radiation effects; Female; Liposomes--therapeutic use; Male; Mice; Mice, Inbred C57BL; Nitrogen Oxides--administration & dosage; Nitrogen Oxides--pharmacokinetics; Nitrogen Oxides--pharmacology; Radiation Injuries, Experimental--pathology; Radiation Injuries, Experimental--prevention & control; Radiation Injuries, Experimental--therapy
Other ID: NLM NIHMS426447, NLM PMC3521523
PubMed Central ID: PMC3521523
PubMed ID: 21164038
Date Deposited: 31 Jul 2014 20:45
Last Modified: 13 Apr 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/22340

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