Abstract
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.
Highlights
Our results demonstrate that the chemical group succinate significantly affected the radioprotective effects of α, γ- and δ-TOS and promoted granulocyte colony-stimulating factor (G-CSF) stimulation. δ-TOS was a stronger radioprotector among the succinate ester derivatives of tocopherols. δ-TOS treatment ameliorates radiation-induced pancytopenia, augments cellular recovery in bone marrow, improves the colony forming ability of bone marrow cells in sub-lethal irradiated mice, and promotes hematopoietic stem and progenitor cell recovery following irradiation
Synthesis of tocopherol succinate ester derivatives and MTD in mice. α, γ- and δ-TOS were synthesized by chemical processes, as showed in Figs S1 and S5
Because α-TOS is superior to α-tocopherol in reducing lethality in mice and increasing circulating G-CSF following total body irradiation (TBI), we hypothesized succinate may enhance the radioprotective potential of tocopherols
Summary
Because α-TOS are superior to α-TOH in reducing lethality following total body irradiation (TBI) and increasing circulating G-CSF in mice, we hypothesized the chemical group succinate may enhance the radioprotective potential of tocopherols. We synthesized α-, γ-and δ-TOS and compared their radioprotective efficacy by determining 30-day efficacy at lethal radiation doses and circulating G-CSF levels in mice.
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