Mitigation of radiation-induced lung injury by genistein and EUK-207

Abstract

Purpose: We examined the effects of genistein and/or Eukarion (EUK)-207 on radiation-induced lung damage and investigated whether treatment for 0–14 weeks (wks) post-irradiation (PI) would mitigate late lung injury.

Materials and methods: The lungs of female Sprague-Dawley (SD) rats were irradiated with 10 Gy. EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (post irradiation [PI]) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1β, IL-6, Tumor necrosis factor (TNF)-α and Transforming growth factor (TGF)-β1, and macrophage activation were analyzed by immunohistochemistry.

Results: Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4–14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines.

Conclusion: Genistein and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI.

Keywords:

• genistein
• EUK-207
• ROS
• rat lung
• radiation

Acknowledgements

This work was supported by funds from an NIAID/NIH U19 program (U19 AI-067734) and by funds from the Canadian Institutes of Health Research (#144089). Partial support was also provided by the Ontario Ministry of Health and Long Term Care (OMHLTC). The views expressed do not necessarily reflect those of OMHLTC.

Declaration of interest:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.