In vivo radioprotection by alpha-TMG: preliminary studies

alpha -TMG is a novel water-soluble derivative of Vitamin E that has shown excellent antioxidant activity. The parent compound has demonstrated protec tion against radiation induced chromosomal damage in vivo. Hence, the preli minary experiments to determine the radioprotective activity of alpha -TMG were carried out in adult Swiss albino mice. Acute toxicity of the drug was studied taking 24 h, 72 h and 30 day mortality after a single intraperiton eal injection of 500-2000 mg/kg body weight of the drug. The drug LD50 for 24h and 72h/30 day survival were found to be 1120 and 1000mg/kg body weight , respectively. The optimum time of drug administration and drug dose-depen dent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 600mg/kg of the drug 15 min before or within 5, 15 or 30 min after 3 Gy whole body gamma radiation resulted in a signifi cant decrease in the aberrant metaphases percent at 24 h post-irradiation; the maximum effect was seen when the drug was given immediately after irrad iation. Injection of 200-800mg/kg TMG within 5 min of irradiation with 3 Gy produced a significant dose-dependent reduction in the radiation induced p ercent aberrant metaphases and in the frequency of micronucleated erythrocy tes at 24h after exposure, with a corresponding decrease in the different t ypes of aberrations. The optimum dose for protection without drug toxicity was 600mg/kg body weight. At this dose, TMG produced 70 and > 60% reduction in the radiation induced percent aberrant metaphases and micronucleated er ythrocytes, respectively. The high water solubility and effectiveness when administered post-irradiation favor TMG as a likely candidate for protectio n in case of accidental exposures. (C) 2001 Elsevier Science B.V. All right s reserved.