Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation.
The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy (60)Co, 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-beta receptor (TGFbetaR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFbetaRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries.
Day
Regina M
RM
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. rday@usuhs.mil
Barshishat-Kupper
Michal
M
Mog
Steven R
SR
McCart
Elizabeth A
EA
Prasanna
P G S
PG
Davis
Thomas A
TA
Landauer
Michael R
MR
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000378:metabolism* / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000517:prevention & control*; D016019:Survival Analysis; D015996:Survival Rate; D014916:Whole-Body Irradiation
D015415:Biomarkers; D016207:Cytokines; D011837:Radiation-Protective Agents; D019833:Genistein