In VivoPostirradiation Protection by a Vitamin E Analog, α-TMG

Abstract

The water-soluble vitamin E derivative alpha-TMG is an excellent radical scavenger. A dose of 600 mg/kg TMG significantly reduced radiation clastogenicity in mouse bone marrow when administered after irradiation. The present study was aimed at investigating the radioprotective effect of postirradiation treatment with alpha-TMG against a range of whole-body lethal (8.5-12 Gy) and sublethal (1-5 Gy) doses of radiation in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from micronuclei and chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 600 mg/kg TMG within 10 min of lethal irradiation increased survival, giving a dose modification factor (DMF) of 1.09. TMG at doses of 400 mg/kg and 600 mg/kg significantly reduced the percentage of aberrant metaphases, the different types of aberrations, and the number of micronucleated erythrocytes. DMFs of 1.22 and 1.48 for percentage aberrant metaphases and 1.6 and 1.98 for micronuclei were obtained for 400 mg/kg and 600 mg/kg TMG, respectively. No drug toxicity was observed at these doses. The effectiveness of TMG when administered postirradiation suggests its possible utility for protection against unplanned radiation exposures.

Normal Tissue Protectors Against Radiation Injury

“…of TMG 5 min after irradiation provided the maximum protection 46 , giving a DMF of ~1.1 for mouse survival 47 , which is similar to that reported for vitamin E 41 . DMFs of ~1.5 and ~2 were obtained for reducing chromosomal aberrations and micronuclei, respectively, in mouse bone marrow 47 . 48 .…”

“…The vitamins C and E have been reported to protect mouse bone marrow chromosomes even when administered shortly after irradiation found that vitamin E was effective post-irradiation administration scenario. a-TMG gave maximum protection against whole-body irradiation when administered within a short time after irradiation 46,47 . The possibility of developing these into drugs for human application in nuclear emergencies is worth considering.…”

Tocopherol succinate: A promising radiation countermeasure

“…It forms a phenoxyl radical similar to trolox upon reaction with various one-electron oxidants. TMG protected mice against TBI, protected DNA strand breaks and thymine glycol formation induced by γ-irradiation [29,30], reduced the percentage of aberrant metaphase and the number of micronucleated erythrocytes [31], and enhanced hematopoietic recovery in irradiated mice [32].…”

PROTECTION OF FEMALE C3H MICE AGAINST WHOLE-BODY gamma-IRRADIATION WITH 2,3-DIMETHYL-6-((2-DIMETHYLAMINO)ETHYL)-6H-INDOLO[2,3-b]QUINOXALINE (B220)

“…18 Flavonoids, α-TMG, H2, and Tempol presumably react with or modify free radicals and ROS. 5,6,8,11 Ex-Rad™ was reported to manifest its protective effects through up-regulation of PI3-Kinase/AKT pathways in cells exposed to radiation. 19 A suggested protective mechanism for DIM proceeds through activation of the nuclear kinase at axiateleangiectasia mutated (ATM) regulating responses to DNA damage and oxidative stress, and NF-κB activation.…”

“…the central nervous system). 1,5 More recently, however, some interesting examples have been reported including flavonoids, 6 caffeine, 7 α-TMG (vitamin E analog), 8 Mentha arvensis (mint), 9 5-androstenediol, 10 Tempol, 11 molecular hydrogen (H2) containing water, 5 Ex-Rad™, 12 JNJ7777120 (indole), 13 and particularly the recently studied indole 3,3'-diindolylmethane (DIM; derived from ingestion of indole-3-carbinol found in cruciferous vegetables such as cabbage, Brussels sprouts and broccoli) that offered astonishing radioprotection also at very high doses (up to 13 Gy) both in vivo and in cell culture. 14 The synthetic indole-drug 2,3-dimethyl-6-((2-(dimethylamino)ethyl)-6H-indolo [2,3-b]quinoxaline (B220, structure shown in figure 1) has been found to be well tolerated, having preventative effects on growth of 12-Otetradecanoylphorbol-13-acetate (TPA) promoted skin tumours in vivo possibly by interfering with enzymes involved in the generation of ROS in the inflammatory response to TPA, 15 and was found to downregulate phagocyte NADPH-oxidase activity in vitro, inhibiting release of ROS, by affecting signalling downstream of protein kinase C (PKC).…”