Genistein Can Mitigate the Effect of Radiation on Rat Lung Tissue

Abstract

We investigated whether genistein could protect the lung from radiation-induced injury. We hypothesized that genistein would reduce the levels of inflammatory cytokines and ROS after irradiation and therefore lead to reduced DNA damage and functional deficits. Whole lungs of Sprague-Dawley rats were irradiated with 18 Gy at ~0.5 Gy/min. At 28 weeks a micronucleus assay was used to examine DNA damage and, using immunohistochemical analysis, expression of IL-1α, IL-1β, IL-6, TNF-α and TGF-β, macrophage activation, oxidative stress (8-OHdG) and collagen levels were measured. A TBARS assay was used to measure the level of malondialdehyde. Functional damage was assessed by measuring the breathing rate of the rats over the course of the experiment. The increase in breathing rate after irradiation was damped in rats receiving genistein during the phase of pneumonitis (6–10 weeks), and there was a 50–80-day delay in lethality in this group. Genistein treatment also decreased the levels of the inflammatory cytokines TNF-α, IL-1β and TGF-β and led to a reduction in collagen content, a reduction in 8-OHdG levels, and complete protection against DNA damage measured in surviving rats at 28 weeks after irradiation. These results demonstrates that genistein treatment can provide partial protection against the early (pneumonitis) effects of lung irradiation and reduce the extent of fibrosis, although not sufficiently to prevent lethality at the radiation dose used in this study.

Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review

“…However, examination of lung tissue from irradiated animals pre-treated with GN at 90 days post-irradiation showed no such foci. Supporting data on the radioprotection role of GN in lung tissue of other experimental models has also been reported (Para et al, 2009;Calveley et al, 2010).…”

Phenylpropanoids in radioregulation: double edged sword

“…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.…”

Radioprotective Agents for Radiation Therapy: Future Trends

“…Animal studies demonstrate both radiation protection in normal tissues and radiation sensitization in tumor tissue [4,[14][15][16] Cytokines and growth factors Palifermin Stimulates proliferation and differentiation; DNA repair; ROS detoxification…”