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 protection against radiation induced chromosomal damage in vivo. Hence, the preliminary 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 24h, 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 24h 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 30min after 3Gy whole body gamma radiation resulted in a significant decrease in the aberrant metaphases percent at 24h 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 24h 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.
Satyamitra
M
M
Department of Radiobiology, Kasturba Medical College, 576119, Manipal, India.
Devi
P U
PU
Murase
H
H
Kagiya
V T
VT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight; D001853:Bone Marrow / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology* / Q000633:toxicity; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000633:toxicity; D006027:Glycosides / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D015162:Micronucleus Tests; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000517:prevention & control; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors
C106323:2-(glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol; D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D006027:Glycosides; D011837:Radiation-Protective Agents