TY - JOUR
T1 - Radiation-induced gastrointestinal syndrome is exacerbated in vitamin C–insufficient SMP30/GNL knockout mice
AU - Saga, Reina
AU - Uchida, Takahiro
AU - Takino, Yuka
AU - Kondo, Yoshitaka
AU - Kobayashi, Hiroaki
AU - Kinoshita, Manabu
AU - Saitoh, Daizoh
AU - Ishigami, Akihito
AU - Makishima, Makoto
N1 - Funding Information:
This work was supported in part by a grant for advanced defense medical research from Japan Ministry of Defense (to MK). RS and MM conceived and designed the research. RS, TU, YT, and YK performed the experiments and analyzed the data. RS and MM prepared the figures and drafted the manuscript. RS, AI, and MM edited and revised the manuscript. All authors interpreted the results of the experiments and approved the final version of manuscript. The authors have no conflicts of interest to declare.
Funding Information:
The authors acknowledge Akira Senoo and Kosaku Miyai for helpful comments in histological analysis; Takami Saiki for technical assistance; Taisuke Yamamoto, Tetsuo Yamamoto, and Hiromi Miyazaki for valuable comments; other members of Military Medicine Research Unit, Test and Evaluation Command, Ground Self-Defense Force for helpful assistance; and Andrew I. Shulman for editorial assistance. This study was based on the 2019 doctoral thesis of RS at Nihon University Graduate School of Medicine.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/1
Y1 - 2021/1
N2 - Objectives: Accidental exposure to high-dose radiation causes life-threatening acute radiation syndrome, features that include gastrointestinal syndrome (GIS) and hematopoietic syndrome (HS). Administration of vitamin C (VC), a free radical scavenger, has been reported to increase survival of mice in GIS and HS models. The effect of nutritional VC status on radiation injury remains unknown because, unlike humans, mice can synthesize VC. The aim of this study was to investigate the effect of VC insufficiency on acute radiation syndrome using senescence marker protein 30 (SMP30)/gluconolactonase knockout (SMP30-KO) mice. Methods: SMP30-KO mice, which cannot synthesize VC, were given water with or without sufficient VC supplementation, and were analyzed in GIS and HS models. Results: In the GIS model, in which bone marrow failure is rescued by bone marrow transplantation, VC-insufficient mice had a lower survival rate than VC-sufficient mice. The intestine of VC-insufficient GIS mice showed epithelial cell atrophy, inflammatory cell infiltration, and decreased crypt cell proliferation. We observed rapid VC oxidation after total body irradiation in the intestine of mice supplemented with VC-sufficient water. In the HS model, which was not combined with bone marrow transplantation, there was no difference in survival between VC-insufficient and -sufficient mice. Conclusion: The results of this study demonstrated that nutritionally sufficient VC exerts a radioprotective effect against radiation-induced GIS.
AB - Objectives: Accidental exposure to high-dose radiation causes life-threatening acute radiation syndrome, features that include gastrointestinal syndrome (GIS) and hematopoietic syndrome (HS). Administration of vitamin C (VC), a free radical scavenger, has been reported to increase survival of mice in GIS and HS models. The effect of nutritional VC status on radiation injury remains unknown because, unlike humans, mice can synthesize VC. The aim of this study was to investigate the effect of VC insufficiency on acute radiation syndrome using senescence marker protein 30 (SMP30)/gluconolactonase knockout (SMP30-KO) mice. Methods: SMP30-KO mice, which cannot synthesize VC, were given water with or without sufficient VC supplementation, and were analyzed in GIS and HS models. Results: In the GIS model, in which bone marrow failure is rescued by bone marrow transplantation, VC-insufficient mice had a lower survival rate than VC-sufficient mice. The intestine of VC-insufficient GIS mice showed epithelial cell atrophy, inflammatory cell infiltration, and decreased crypt cell proliferation. We observed rapid VC oxidation after total body irradiation in the intestine of mice supplemented with VC-sufficient water. In the HS model, which was not combined with bone marrow transplantation, there was no difference in survival between VC-insufficient and -sufficient mice. Conclusion: The results of this study demonstrated that nutritionally sufficient VC exerts a radioprotective effect against radiation-induced GIS.
KW - Acute radiation syndrome
KW - Oxidative stress
KW - Radiation-induced intestinal injury
KW - Vitamin C insufficiency
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U2 - 10.1016/j.nut.2020.110931
DO - 10.1016/j.nut.2020.110931
M3 - Article
C2 - 32755744
AN - SCOPUS:85088861080
SN - 0899-9007
VL - 81
JO - Nutrition
JF - Nutrition
M1 - 110931
ER -
