Genistein treatment protects mice from ionizing radiation injury.
The radioprotective and behavioral effects of an acute administration of the isoflavone genistein (4',5,7-trihydroxyflavone) were investigated in adult CD2F1 male mice. Mice were administered a single subcutaneous (s.c.) dose of genistein either 24 h or 1 h before a lethal dose of gamma radiation (9.5-Gy of cobalt-60 at 0.6 Gy min(-1)). Mice received saline, PEG-400 vehicle or genistein at 3.125, 6.25, 12.5, 25, 50, 100, 200, or 400 mg kg(-1) body weight. For mice treated 24 h before irradiation there was a significant increase in 30-day survival for animals receiving genistein doses of 25 to 400 mg kg(-1) (p<0.001). In contrast, the 30-day survival rates of mice treated with genistein 1 h before irradiation were not significantly different from those of the vehicle control group. Additionally, the acute toxicity of genistein was evaluated in non-irradiated male mice administered a single s.c. injection of saline, vehicle, or genistein at 100, 200 or 400 mg kg(-1). At these genistein doses there were no adverse effects, compared with controls, on locomotor activity, grip strength, motor coordination, body weight, testes weight, or histopathology. These results demonstrate that a single s.c. administration of the flavonoid genistein at non-toxic doses provides protection against acute radiation injury.
Landauer
Michael R
MR
Radiation Casualty Management Team, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA. landauer@afrri.usuhs.mil
Srinivasan
Venkataraman
V
Seed
Thomas M
TM
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D015996:Survival Rate; D013737:Testis / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors
D011837:Radiation-Protective Agents; D019833:Genistein