Protective effects of dietary antioxidants on proton total-body irradiation-mediated hematopoietic cell and animal survival.
Abstract Dietary antioxidants have radioprotective effects after gamma-radiation exposure that limit hematopoietic cell depletion and improve animal survival. The purpose of this study was to determine whether a dietary supplement consisting of l-selenomethionine, vitamin C, vitamin E succinate, alpha-lipoic acid and N-acetyl cysteine could improve survival of mice after proton total-body irradiation (TBI). Antioxidants significantly increased 30-day survival of mice only when given after irradiation at a dose less than the calculated LD(50/30); for these data, the dose-modifying factor (DMF) was 1.6. Pretreatment of animals with antioxidants resulted in significantly higher serum total white blood cell, polymorphonuclear cell and lymphocyte cell counts at 4 h after 1 Gy but not 7.2 Gy proton TBI. Antioxidants significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGFbeta1 and increased bone marrow cell counts and spleen mass after TBI. Maintenance of the antioxidant diet resulted in improved recovery of peripheral leukocytes and platelets after sublethal and potentially lethal TBI. Taken together, oral supplementation with antioxidants appears to be an effective approach for radioprotection of hematopoietic cells and improvement of animal survival after proton TBI.
Wambi
Chris O
CO
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Sanzari
Jenine K
JK
Sayers
Carly M
CM
Nuth
Manunya
M
Zhou
Zhaozong
Z
Davis
James
J
Finnberg
Niklas
N
Lewis-Wambi
Joan S
JS
Ware
Jeffrey H
JH
El-Deiry
Wafik S
WS
Kennedy
Ann R
AR
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002470:Cell Survival / Q000528:radiation effects*; D019587:Dietary Supplements; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011522:Protons / Q000009:adverse effects; D011832:Radiation Injuries / Q000178:diet therapy / Q000401:mortality* / Q000517:prevention & control / Q000662:veterinary; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D016019:Survival Analysis; D015996:Survival Rate; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D000975:Antioxidants; D011522:Protons; D011837:Radiation-Protective Agents