Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation
| Autor: | S.J Defilippi, Joel S. Greenberger, Valerian E. Kagan, Dapha Bar-Sagi, Michael W. Epperly, Joan Gretton, Christine A. Sikora |
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| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Antioxidant Time Factors animal diseases medicine.medical_treatment Biology Pharmacology Dinoprost Lipid peroxidation chemistry.chemical_compound Epitopes Mice Plasmid medicine Animals Esophagitis Cells Cultured Chromatography High Pressure Liquid Liposome Mice Inbred C3H Dose-Response Relationship Drug Radiotherapy Superoxide Superoxide Dismutase Vitamin E fungi Glutathione medicine.disease Lipid Metabolism Mice Inbred C57BL Hemagglutinins Oncology chemistry Biochemistry Lac Operon Liposomes Fatty Acids Unsaturated Female Lipid Peroxidation Biomarkers Plasmids |
| Zdroj: | International journal of cancer. 96(4) |
| ISSN: | 0020-7136 |
| Popis: | 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 β-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 μl of plasmid/liposomes containing 200 μg 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. © 2001 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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