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1.
Sci Rep ; 7: 40380, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28145432

RESUMEN

α-tocopherol succinate (α-TOS), γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have drawn large attention due to their efficacy as radioprotective agents. α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI). Because α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI), we hypothesized succinate may be contribute to the radioprotection of α-TOS. To study the contributions of succinate and to identify stronger radioprotective agents, we synthesized α-, γ- and δ-TOS. Then, we evaluated their radioprotective effects and researched further mechanism of δ-TOS on hematological recovery post-irradiation. Our results demonstrated that the chemical group of succinate enhanced the effects of α-, γ- and δ-TOS upon radioprotection and granulocyte colony-stimulating factor (G-CSF) induction, and found δ-TOS a higher radioprotective efficacy at a lower dosage. We further found that treatment with δ-TOS ameliorated radiation-induced pancytopenia, augmenting cellular recovery in bone marrow and the colony forming ability of bone marrow cells in sublethal irradiated mice, thus promoting hematopoietic stem and progenitor cell recovery following irradiation exposure. δ-TOS appears to be an attractive radiation countermeasure without known toxicity, but further exploratory efficacy studies are still required.


Asunto(s)
Radioisótopos de Cobalto/química , Factor Estimulante de Colonias de Granulocitos/farmacología , Hematopoyesis/efectos de los fármacos , Protectores contra Radiación/farmacología , alfa-Tocoferol/análogos & derivados , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/efectos de la radiación , Ensayo de Unidades Formadoras de Colonias , Relación Dosis-Respuesta en la Radiación , Hematopoyesis/efectos de la radiación , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/efectos de la radiación , Masculino , Dosis Máxima Tolerada , Ratones Endogámicos C57BL , alfa-Tocoferol/síntesis química , alfa-Tocoferol/química , alfa-Tocoferol/farmacología
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