Radioprotection of Lung Tissue by Soy Isoflavones

Abstract

Introduction Radiation-induced pneumonitis and fibrosis have restricted radiotherapy for lung cancer. In a pre-clinical lung tumor model, soy isoflavones showed the potential to enhance radiation damage in tumor nodules and simultaneously protect normal lung from radiation injury. We have further dissected the role of soy isoflavones in the radioprotection of lung tissue. Methods Naïve Balb/c mice were treated with oral soy isoflavones for 3 days before and up to 4 months after radiation. Radiation was administered to the left lung at 12 Gy. Mice were monitored for toxicity and breathing rates at 2, 3 and 4 months after radiation. Lung tissues were processed for histology for in situ evaluation of response. Results Radiation caused damage to normal hair follicles, leading to hair loss in the irradiated left thoracic area. Supplementation with soy isoflavones protected mice against radiation-induced skin injury and hair loss. Lung irradiation also caused an increase in mouse breathing rate that was more pronounced by 4 months after radiation, probably due to late effects of radiation-induced injury to normal lung tissue. However, this effect was mitigated by soy isoflavones. Histological examination of irradiated lungs revealed a chronic inflammatory infiltration involving alveoli and bronchioles and a progressive increase in fibrosis. These adverse effects of radiation were alleviated by soy isoflavones. Conclusion Soy isoflavones given pre- and post-radiation protected the lungs against adverse effects of radiation including skin injury, hair loss, increased breathing rates, inflammation, pneumonitis and fibrosis, providing evidence for a radioprotective effect of soy.

Innate Immune Pathways Associated with Lung Radioprotection by Soy Isoflavones

“…We have previously demonstrated that soy isoflavones protect against radiation-induced pneumonitis and fibrosis in naïve mice and xenografted lung tumor-bearing mice (10–12). In naïve mice, soy isoflavones given preradiation and postradiation reduced radiation injury to skin and hair follicles, protected respiratory function, and decreased inflammatory infiltrates and fibrosis (12).…”

“…In naïve mice, soy isoflavones given preradiation and postradiation reduced radiation injury to skin and hair follicles, protected respiratory function, and decreased inflammatory infiltrates and fibrosis (12). Significant decreases in pneumonitis, vascular damage, and fibrosis were also observed in lung tumor-bearing mice treated with soy isoflavones and radiation (10, 11).…”

Radioprotective Agents for Radiation Therapy: Future Trends

“…Genistein is well tolerated, easily administered and it has recently been reported that soy isoflavones such as genistein act as radiosensitizers of tumor tissue as well as radioprotectors of normal tissue [69]. Genistein is a nonspecific protein kinase inhibitor that acts as a scavenger REviEW Johnke, Sattler & Allison future science group for ROS [14].…”

Radioprotective effect and other biological benefits associated with flavonoids

“…In mice, Hillman et al [62] investigated the role of soy isoflavones in the radiation protection of lung tissue. Histological examination of irradiated lungs revealed a chronic inflammatory infiltration involving the alveoli and bronchioles and a progressive increase in fibrosis.…”