Protective effect of superoxide dismutase in radiation-induced intestinal inflammation.
OBJECTIVE
To analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects.


METHODS
Mice were subjected to abdominal irradiation with 10 Gy or sham irradiation and studied 24 or 72 hours after radiation. Groups of mice were treated with 0.1, 4, or 6 mg/kg/day of SOD1 or vehicle. Leukocyte-endothelial cell interactions in intestinal venules were assessed by intravital microscopy. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was determined with radiolabeled antibodies. Effects of SOD1 on histologic damage and levels of lipid hydroperoxides were also measured.


RESULTS
A significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules was observed at 24 and 72 hours after irradiation. Treatment with SOD1 had no effect on leukocyte rolling but significantly and dose-dependently decreased firm leukocyte adhesion to intestinal venules. Treatment with SOD1 at doses that reduced leukocyte recruitment abrogated the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, was also significantly reduced by SOD1.


CONCLUSIONS
Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response.
Mollà
Meritxell
M
Department of Gastroenterology, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Gironella
Meritxell
M
Salas
Antonio
A
Closa
Daniel
D
Biete
Albert
A
Gimeno
Mercedes
M
Coronel
Pilar
P
Piqué
Josep M
JM
Panés
Julián
J
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004751:Enteritis / Q000209:etiology / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000528:radiation effects*; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000097:blood / Q000627:therapeutic use*; D014699:Venules / Q000528:radiation effects
D016166:Free Radical Scavengers; D018799:Intercellular Adhesion Molecule-1; D013482:Superoxide Dismutase