Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-7-27
pubmed:abstractText
Intraesophageal administration of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) prior to single fraction radiation has been shown to protect mice from lethal esophagitis. In our study, C3H/HeNsd mice received fractionated radiation in two protocols: (i) 18 Gy daily for four days with MnSOD-PL administration 24 hr prior to the first and third fraction, or (ii) 12 Gy daily for six days with MnSOD-PL 24 hr prior to the first, third, and fifth fraction. Control radiated mice received either no liposomes only or LacZ (bacterial beta-galactosidase gene)-plasmid/liposome (LacZ-PL) by the same schedules. We measured thiol depletion and lipid peroxidation (LP) in whole esophagus and tested the effectiveness of a new plasmid, hemagglutinin (HA) epitope-tagged MnSOD (HA-MnSOD). In fractionation protocols, mice receiving MnSOD-PL, but not LacZ-PL (200 microl of plasmid/liposomes containing 200 microg of plasmid DNA), showed a significant reduction in morbidity, decreased weight loss, and improved survival. Four and seven days after 37 Gy single fraction radiation, the esophagus demonstrated a significant increase in peroxidized lipids and reduction in overall antioxidant levels, reduced thiols, and decreased glutathione (GSH). These reductions were modulated by MnSOD-PL administration. The HA-MnSOD plasmid product was detected in the basal layers of the esophageal epithelium 24 hr after administration and provided significant radiation protection compared to glutathione peroxidase-plasmid/liposome (GPX-PL), or liposomes containing MnSOD protein, vitamin E, co-enzyme Q10, or 21-aminosteroid. Thus, MnSOD-PL administration significantly improved tolerance to fractionated radiation and modulated radiation effects on levels of GSH and lipid peroxidation (LP). These studies provide further support for translation of MnSOD-PL treatment into human esophageal radiation protection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11474496-Animals, pubmed-meshheading:11474496-Biological Markers, pubmed-meshheading:11474496-Cells, Cultured, pubmed-meshheading:11474496-Chromatography, High Pressure Liquid, pubmed-meshheading:11474496-Dinoprost, pubmed-meshheading:11474496-Dose-Response Relationship, Drug, pubmed-meshheading:11474496-Epitopes, pubmed-meshheading:11474496-Esophagitis, pubmed-meshheading:11474496-Fatty Acids, Unsaturated, pubmed-meshheading:11474496-Female, pubmed-meshheading:11474496-Hemagglutinins, pubmed-meshheading:11474496-Lac Operon, pubmed-meshheading:11474496-Lipid Metabolism, pubmed-meshheading:11474496-Lipid Peroxidation, pubmed-meshheading:11474496-Liposomes, pubmed-meshheading:11474496-Mice, pubmed-meshheading:11474496-Mice, Inbred C3H, pubmed-meshheading:11474496-Mice, Inbred C57BL, pubmed-meshheading:11474496-Plasmids, pubmed-meshheading:11474496-Radiotherapy, pubmed-meshheading:11474496-Superoxide Dismutase, pubmed-meshheading:11474496-Time Factors
pubmed:year
2001
pubmed:articleTitle
Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation.
pubmed:affiliation
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.