Genistein treatment protects mice from ionizing radiation injury

Abstract

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.

Effects of genistein following fractionated lung irradiation in mice

“…Genistein has been reported to reduce acute lung injury from inflammation after lipopolysaccharide treatment [142,144]. Genistein has also been used as a radioprotector and has been shown to increase survival following whole body irradiation [145]. In addition to radioprotection studies, genistein has been investigated as an anti-cancer therapeutic [146].…”

Phenylpropanoids in radioregulation: double edged sword

“…One study demonstrated that administration of genistein (6) resulted in alleviation of the lethal effects of radiation exposure in mice without changes in behavior, body weight or histopathology. In that investigation, genistein (6) was shown to be radioprotective when administered 24 h prior to γ-irradiation (9.5 Gy), but was not effective when administered 1 hr prior to irradiation, possibly due to the antioxidant properties and immuno-stimulatory activity of genistein (6) (Landauer et al, 2003). Genistein (6) treatment resulted in reduced expression of inflammatory cytokines including TNF-α, IL-1β, and TGF-β and resulted in a reduction of oxidative stress and protection against DNA damage in lungs of rats after irradiation (Calveley et al, 2010).…”

“…Indeed, curcumin (4) induced significant inhibition of IRinduced NF-κB activation in neuroblastoma cells, SK-N-MC and SH-SY5Y, resulting in suppression of NF-κB-mediated transcription, such as hTERT mRNA, which is essential for activation of telomerase (Aravindan et al, 2011). In addition, curcumin (4) also induced suppression of many NF-κB-regulated gene products including cyclin D1, c-myc, Bcl-2, Bcl-xL, cellular inhibitor of apoptosis protein-1, cyclooxygenase-2, matrix metalloproteinase-9, and vascular endothelial growth factor, which could be induced by radiation therapy and mediate radioresistance (Kunnumakkara et al, 2008 Landauer, et al, 2003;Calveley et al, 2010 Cell cycle arrest, Inhibition of AKT activation 0-100 μM; 5 mg/day p.o. ; Hillman et al, 2001;Hillman et al, 2004;Yashar et al, 2005;Raffoul et al, 2006;Zhang et al, 2006;Hillman et al, 2007 Quercetin (7) Antioxidant activity et al, 2010 --i.g., intragastrically; i.p., intraperitoneally; i.v., intravenously; p.o., orally; s.c., subcutaneously administered.…”

Overview of Radiation-protective Agent Research and Prospects for the Future

“…BIO300 LANDAUER et al have investigated the radioprotective and behavioral effects of an acute administration of the iso avone genistein (4', 5, 7-trihydroxy avone) using the mouse model. 52) The 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 ). They demonstrated that a single s. c. administration of the avonoid genistein at non-toxic doses, 25 to 400 mg kg -1 , revealed 60 to 88% survival in irradiated mice.…”