Mitigation of radiation-induced lung injury by genistein and EUK-207 - PubMed (original) (raw)

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

Javed Mahmood et al. Int J Radiat Biol. 2011 Aug.

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.

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Conflict of interest statement

Disclosure Statement:

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

Figures

Figure 1

Figure 1

Breathing rate (mean breaths per minute) as a function of time after irradiation (10 Gy) for rats receiving no radiation or radiation only on the control diet, rats irradiated with 10 Gy lung irradiation with genistein, EUK-207 or combination treatment (G+E). All drug treatments started immediately after irradiation and finished at 14 wks. Each point represents the mean (±Standard Error of the Mean -SEM) for all rats available for analysis at the different times.

Figure 2

Figure 2

A) Micronucleus yield (MN/1000BN) in fibroblasts from rat lungs and B) percent positivity of 8-OHdG staining following lung irradiation (10 Gy) with Genistein, EUK-207 and combination (G+E) treatment. All drug treatments started immediately after irradiation and finished at 14 wks. The assays were performed at 0, 4, 8, 14 and 28 wks following irradiation. Percent positivity is the ratio of positive pixels/total number of positive and negative pixels in the tissue section (air spaces excluded). Each bar (A) or each point (B) represents the mean (±SEM).

Figure 3

Figure 3

A) Hydroxyproline content (µg of hydroxyproline/100 mg of wet lung tissue) at 28 wks following lung irradiation (10 Gy) with Genistein, EUK-207 and combination (G+E) treatment. All drug treatments started immediately after irradiation and finished at 14 wks. Each bar represents the mean (±SEM). B) Protein expression of TGF-β at 0, 4, 8, 14 and 28 wks following lung irradiation (10 Gy) with Genistein, EUK-207 and combination (G+E) treatment. All drug treatments started immediately after irradiation and finished at 14 wks. Percent positivity is the ratio of positive pixels/total number of positive and negative pixels in the tissue section (air spaces excluded). Each point represents the mean (±SEM).

Figure 4

Figure 4

Protein expression of cytokines IL-1α (A), IL-1β (B), IL-6 (C), TNF-α (D) staining at 0, 4, 8, 14 and 28 wks following lung irradiation (10 Gy) with Genistein, EUK-207 and combination (G+E) treatment. All drug treatments started immediately after irradiation and finished at 14 wks. Percent positivity is the ratio of positive pixels/total number of positive and negative pixels in the tissue section (air spaces excluded). Each bar represents the mean (±SEM).

Figure 5

Figure 5

ED-1 staining for activated macrophages in the rat lung at 0, 4, 8, 14 and 28 wks following lung irradiation (10 Gy) with genistein, EUK-207 and combination (G+E) treatment. All drug treatments started immediately after irradiation and finished at 14 wks. Percent positivity is the ratio of positive pixels/total number of positive and negative pixels in the tissue section (air spaces excluded). Each bar represents the mean (±SEM).

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