In vivo radioprotection by α-TMG: preliminary studies

Abstract

α-TMG is a novel water-soluble derivative of Vitamin E that has shown excellent antioxidant activity. The parent compound has demonstrated protection against radiation induced chromosomal damage in vivo. Hence, the preliminary experiments to determine the radioprotective activity of α-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 intraperitoneal injection of 500–2000 mg/kg body weight of the drug. The drug LD 50 for 24 h and 72 h/30 day survival were found to be 1120 and 1000 mg/kg body weight, respectively. The optimum time of drug administration and drug dose-dependent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 600 mg/kg of the drug 15 min before or within 5, 15 or 30 min after 3 Gy whole body gamma radiation resulted in a significant decrease in the aberrant metaphases percent at 24 h post-irradiation; the maximum effect was seen when the drug was given immediately after irradiation. Injection of 200–800 mg/kg TMG within 5 min of irradiation with 3 Gy produced a significant dose-dependent reduction in the radiation induced percent aberrant metaphases and in the frequency of micronucleated erythrocytes at 24 h after exposure, with a corresponding decrease in the different types of aberrations. The optimum dose for protection without drug toxicity was 600 mg/kg body weight. At this dose, TMG produced 70 and >60% reduction in the radiation induced percent aberrant metaphases and micronucleated erythrocytes, respectively. The high water solubility and effectiveness when administered post-irradiation favor TMG as a likely candidate for protection in case of accidental exposures.