Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation.
While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.
Yamamoto
Tetsuo
T
Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Kinoshita
Manabu
M
Shinomiya
Nariyoshi
N
Hiroi
Sadayuki
S
Sugasawa
Hidekazu
H
Matsushita
Yoshitaro
Y
Majima
Takashi
T
Saitoh
Daizoh
D
Seki
Shuhji
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001205:Ascorbic Acid / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D020169:Caspases / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D003967:Diarrhea / Q000209:etiology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005609:Free Radicals / Q000097:blood; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D007421:Intestine, Small / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011292:Premedication; D011828:Radiation Chimera; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D014916:Whole-Body Irradiation / Q000009:adverse effects
D051017:Apoptosis Regulatory Proteins; D005609:Free Radicals; D011837:Radiation-Protective Agents; D020169:Caspases; D001205:Ascorbic Acid