Sodium orthovanadate (vanadate), a potent mitigator of radiation-induced damage to the hematopoietic system in mice.
Previous in vitro and in vivo studies have shown that sodium orthovanadate (vanadate), an inorganic vanadium compound, could effectively suppress radiation-induced p53-mediated apoptosis via both transcription-dependent and transcription-independent pathways. As a potent radiation protector administered at a dose of 20 mg/kg body weight (20 mg/kg) prior to total body irradiation (TBI) by intra-peritoneal (ip) injection, it completely protected mice from hematopoietic syndrome and partially from gastrointestinal syndrome. In the present study, radiation mitigation effects from vanadate were investigated by ip injection of vanadate after TBI in mice. Results showed that a single administration of vanadate at a dose of 20 mg/kg markedly improved the 30-day survival rate and the peripheral blood hemogram, relieved bone marrow aplasia and decreased occurrence of the bone marrow micronucleated erythrocytes in the surviving animals. The dose reduction factor was 1.2 when a single dose of 20 mg/kg was administered 15 min after TBI in mice using the 30-day survival test as the endpoint. Results also showed that either doubling the vanadate dose (40 mg/kg) in a single administration or continuing the vanadate treatment (after a single administration at 20 mg/kg) from the following day at a dose of 5 mg/kg per day for 4 consecutive days further significantly improved the efficacy for rescuing bone marrow failure in the 30-day survival test. Taken together, these findings indicate that vanadate would be a potent mitigator suppressing the acute lethality (hematopoietic syndrome) and minimizing the detrimental effects (anhematopoiesis and delayed genotoxic effects) induced by TBI in mice.
Radiation Risk Reduction Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan.
Bing
B
Wang
Kaoru
K
Tanaka
Akinori
A
Morita
Yasuharu
Y
Ninomiya
Kouichi
K
Maruyama
Kazuko
K
Fujita
Yoshio
Y
Hosoi
Mitsuru
M
Nenoi
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D006413:Hematopoietic System / Q000187:drug effects* / Q000528:radiation effects*; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*; D014916:Whole-Body Irradiation; D014965:X-Rays
D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D014638:Vanadates
Vanadate; bone marrow micronucleated erythrocytes; mice; mitigator; radiation-induced hematopoietic syndrome