Prevention of Gamma Radiation-Induced Mortality in Mice by the Isoflavone Genistein
Abstract
There is a need to develop medical countermeasures to protect first-responders and remediation workers from the biomedical effects of ionizing radiation. Agents that can protect against ionizing radiation and that can be administered before radiation would permit rescue workers to perform needed operations. The ideal radioprotector would be nontoxic and would not degrade performance. Soy phytoestrogens have strong antioxidant activity and have been reported to have many beneficial health effects, including a reduction in bone loss and the incidence of some types of cancer. The most plentiful isoflavone from soybeans is genistein (4', 5, 7- trihydroxy-flavone). In the present study, the radioprotective and behavioral effects of an acute administration of the isoflavone genistein were investigated in adult CD2F1 male mice. They were administered a single subcutaneous dose of genistein, either 24 hr or 1 hr before a lethal dose of gamma radiation (9.5 Gy cobalt-60 at 0.6 Gy/min). The mice received vehicle or genistein at 3.12, 6.25, 12.5, 25, 50, 100, 200, or 400 mg/kg. For mice treated 24 hr before irradiation, there was a significant increase in 30-day survival for animals receiving genistein doses of 25 to 400 mg/kg (p < 0.001) compared to the vehicle control group. In contrast, the 30- day survival rates of mice treated with genistein 1 hr before irradiation were not significantly different from those of the vehicle control group. In a separate experiment, the toxicity of genistein was evaluated in nonirradiated male mice administered a single subcutaneous injection of vehicle, or genistein at 100, 200, or 400 mg/kg. Compared with controls at these genistein doses, there were no adverse effects on locomotor activity, grip strength, body weight, testes weight, or histopathology. The results demonstrate that a single subcutaneous administration of the flavonoid genistein at nontoxic doses provides protection against acute radiation injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA438759
Entities
People
- C. M. Chang
- M. B. Grace
- M. R. Landauer
- T. K. Clarke
- V. Srinivasan
- Viral Parekh
- W. E. Jackson Iii
Organizations
- Armed Forces Radiobiology Research Institute