Gamma-tocopherol-N,N-dimethylglycine ester as a potent post-irradiation mitigator against whole body X-irradiation-induced bone marrow death in mice

Abstract

We examined the radioprotective and mitigative effects of gamma-tocopherol-N,N-dimethylglycine ester (GTDMG), a novel water-soluble gamma-tocopherol derivative, against X-irradiation-induced bone marrow death in mice. Mice (C3H, 10 weeks, male) were injected intraperitoneally with GTDMG suspended in a 0.5% methyl cellulose solution before or after receiving of 7.5-Gy whole body X-irradiation. GTDMG significantly enhanced the 30-day survival rate when given 30 min before or immediately after the irradiation. Its mitigative activity (administered after exposure) was examined further in detail. The optimal concentration of GTDMG given immediately after irradiation was around 100 mg/kg body weight (bw) and the 30-day survival rate was 97.6 ± 2.4%. When GTDMG was administered 1, 10 and 24 h post-irradiation, the survival rate was 85.7 ± 7.6, 75.0 ± 9.7 and 36.7 ± 8.8%, respectively, showing significant mitigation even at 24 h after irradiation (P < 0.05). The value of the dose reduction factor (100 mg/kg bw, given intraperitoneally (i.p.) immediately after irradiation) was 1.25. GTDMG enhanced the recovery of red blood cell-, white blood cell-, and platelet-counts after irradiation and significantly increased the number of endogenous spleen colonies (P < 0.05). Subcutaneous (s.c.) administration also had mitigative effects. In conclusion, GTDMG is a potent radiation mitigator.

Preparation of an experimental mouse model lacking selenium-dependent glutathione peroxidase activities by feeding a selenium-deficient diet

“…This mouse strain was used in our previous animal experiments to estimate the biological effects of artificial oxidative stresses such as hyperthermia, X-rays, and/or heavy-ion (carbon-ion) beam irradiation. (18)(19)(20)(21)(22)(23)(24) High linear energy transfer (LET) beams, such as heavy-ion beams, yield more H 2 O 2 than low LET photon radiation such as X-rays and/or gammarays. (25) High LET beams can create H 2 O 2 independently of oxygen, but low LET radiation creates H 2 O 2 mainly in an oxygendependent manner.…”

Combined Mitigation of the Gastrointestinal and Hematopoietic Acute Radiation Syndromes by an LPA 2 Receptor-Specific Nonlipid Agonist

“…DBIBB was effective in mitigating HEM-ARS in the TBI model when administration began up to 72 h postirradiation. There are few reports in the literature on radioprotective and radiomitigative compounds (Anzai, et al, 2013; Basile, et al, 2012; Berbee, et al, 2011; Burdelya, et al, 2008; Gaberman, et al, 2013; Gao, et al, 2012; Geiger, et al, 2012; Haydont, et al, 2007; Kim, et al, 2013; Saha, et al, 2011; Sridharan, et al, 2013; Wang, et al, 2013), however, most of these interventions lose efficacy when administered 24 h postinjury or they are efficacious only in treating single-organ injury. The effective protection we detected with delayed administration of DBIBB indicates that the initial tissue damage sustained during the first 72 postirradiation hours can be effectively treated.…”

Radiation Protection and Mitigation by Natural Antioxidants and Flavonoids: Implications to Radiotherapy and Radiation Disasters

“…They showed that treatment with this derivative can mitigate the detrimental effects of an exposure to 7.5 Gy x-rays. Their results indicated that gammatocopherol-N,N-dimethylglycine ester stimulates the recovery of bone marrow cells following exposure [233].…”