MnSOD-plasmid liposome gene therapy decreases ionizing irradiation-induced lipid peroxidation of the esophagus.
BACKGROUND
Ionizing irradiation-induced cellular and tissue damage is mediated in part by resultant radiochemical reactions and resultant oxidative stress. Irradiation-induced reactive oxygen and nitrogen species include: superoxide, nitric oxide, hydroxyl radical and hydrogen peroxide. The biochemical combination of superoxide and nitric oxide radicals forms peroxynitrite, a potent oxidant known to induce lipid peroxidation.


METHODS
The antioxidant capacity and lipid peroxidation of the esophagus were determined following irradiation.


RESULTS
In the present studies, measurements of total antioxidant capacity did not change in the esophagus of control irradiated or control plasmid pNGVL3-PL intraesophageally-injected mice. In contrast, manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intraesophageally-treated mice showed a significant increase in antioxidant capacity persisting for seven days. Lipid peroxidative changes induced in the control irradiated mouse esophagus decreased over seven days after irradiation of C3H/HeNHsd mice exposed to 37 Gy in a single fraction. MnSOD-PL radioprotective gene therapy administered intraorally 24 hours prior to irradiation did not significantly reduce the kinetics of induction of total peroxidated lipids over the first seven days after irradiation but did decrease lipid peroxidation at days 14 and 21.


CONCLUSIONS
These studies demonstrate the antioxidant function of MnSOD-PL gene therapy to the esophagus, which is detectable as a reduction in irradiation-induced lipid peroxidation.
Epperly
Michael W
MW
Department of Radiation Oncology, University of Pittsburgh Cancer Institute and School of Environmental Health, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Tyurina
Yulia Y
YY
Nie
Suhua
S
Niu
Yun Yun
YY
Zhang
Xichen
X
Kagan
Valerian
V
Greenberger
Joel S
JS
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004947:Esophagus / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D015316:Genetic Therapy; D015227:Lipid Peroxidation / Q000528:radiation effects*; D008081:Liposomes; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D010078:Oxazines; D010957:Plasmids; D011833:Radiation Injuries, Experimental / Q000473:pathology* / Q000517:prevention & control; D011839:Radiation, Ionizing; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution; D019076:Transgenes
D000975:Antioxidants; D005456:Fluorescent Dyes; D008081:Liposomes; D010078:Oxazines; C470430:Amplex Red; D008315:Malondialdehyde; D013482:Superoxide Dismutase