Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice

Abstract

Purpose

Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models.

Methods

Female ICR mice were given a single injection of vanadate or vehicle, followed by a lethal dose of TBI or PBI. Radioprotective effects of vanadate against the irradiations were evaluated by analyzing survival rate, body weight, hematopoietic parameters, and histological changes in the bone marrow and intestinal epithelium.

Results

TBI-induced HP syndrome was effectively suppressed by vanadate treatment. After TBI, the vanadate-treated mice retained better bone marrow cellularity and showed markedly higher survival rate compared to the vehicle-treated animals. In contrast, vanadate did not relieve loss of intestinal crypts and failed to rescue mice from GI death after PBI.

Conclusion

Vanadate is a p53 inhibitor that has been shown to be beneficial as a radiation protective agent against HP but was not effective in protecting against acute GI radiation injury.

Keywords:

• Vanadate
• p53 inhibitor
• partial-body irradiation
• gastrointestinal syndrome
• hematopoietic syndrome

Acknowledgements

We are grateful to staff of the Support Center for Advanced Medical Sciences, Tokushima University Graduate School of Biomedical Sciences, for their technical supports.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, Akinori Morita, upon reasonable request.

Additional information

Funding

This research was supported by KAKENHI [grant number 16K10396, 19K17143, 19H03604, and 21K07644] from the Japan Society for the Promotion of Science. Dwi Ramadhani was a fellow of the Nuclear Researchers Exchange Program 2017 supported by the Ministry of Education, Culture, Sport, Sciences and Technology (MEXT), Japan, and the Nuclear Safety Research Association, Japan.

Notes on contributors

Yuichi Nishiyama

Yuichi Nishiyama is an assistant professor in the Department of Biomedical Science and Technology, Graduate School of Biomedical Sciences, Tokushima University.

Akinori Morita

Akinori Morita is a professor in the Department of Biomedical Science and Technology, Graduate School of Biomedical Sciences, Tokushima University.

Bing Wang

Bing Wang is a group leader in the Department of Radiation Effects Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology.

Takuma Sakai

Takuma Sakai is a graduate student in the Department of Biomedical Science and Technology, Graduate School of Biomedical Sciences, Tokushima University.

Dwi Ramadhani

Dwi Ramadhani was a fellow of the Nuclear Researchers Exchange Program 2017 supported by the Ministry of Education, Culture, Sport, Sciences and Technology (MEXT), Japan, and the Nuclear Safety Research Association, Japan.

Hidetoshi Satoh

Hidetoshi Satoh is a graduate student in the Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science.

Kaoru Tanaka

Kaoru Tanaka is a professional staff in the Department of Radiation Effects Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology.

Megumi Sasatani

Megumi Sasatani is an associate professor in the Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University.

Shintaro Ochi

Shintaro Ochi was a graduate student in the Department of Biomedical Science and Technology, Graduate School of Biomedical Sciences, Tokushima University.

Masahide Tominaga

Masahide Tominaga is a lecturer in the Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Tokushima University.

Hitoshi Ikushima

Hitoshi Ikushima is a professor in the Department of Therapeutic Radiology, Graduate School of Biomedical Sciences, Tokushima University.

Junji Ueno

Junji Ueno is a professor emeritus at Tokushima University. He was a professor in the Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Tokushima University.

Mitsuru Nenoi

Mitsuru Nenoi is a director in the Department of Safety Administration, National Institutes for Quantum and Radiological Science and Technology.

Shin Aoki

Shin Aoki is a professor in the Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science.