Preliminary Study of Protective Effects of Flavonoids against Radiation-induced Lung Injury in Mice

  • Wang, Juan (Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences) ;
  • Xu, Heng-Wei (Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences) ;
  • Li, Bao-Sheng (Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences) ;
  • Zhang, Jian (Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences) ;
  • Cheng, Jian (Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences)
  • Published : 2012.12.31


Background: Radiation therapy plays an important role in lung carcinoma treatment. However, the incidence of symptomatic radiation-induced lung injury is high. This study aimed to evaluate radioprotective effects of flavonoids extracted from Astragalus complanatus and mechanisms of action against radiation damage. Methods: Alteration in antioxidant status and levles of several cytokines were investigated in BABL/C mice treated with 4 mg/kg b.wt. flavonoids after exposure to 10Gy thoracic radiation. Results: Serum levels of SOD in the flavonoids+radiation group were significantly higher compared to the radiation control group, while TGF-${\beta}1$ and IL-6 were lower. Mice in the radiation control group displayed more severe lung damage compared with the flavonoids+radiation group. The expression of TGF-${\beta}1$ and TNF-${\alpha}$ in the radiation control group was markedly increased in alveolar epithelial cells and macrophages of the alveolar septum. Conclusions: From the results of the present study, flavonoids could be excellent candidates as protective agents against radiation-induced lung injury.


Radiation-induced lung injury;flavonoids of Astragalus complanatus;ELISA;immunohistochemistry


  1. Piguet PF (1990). Is "tumor necrosis factor" the major effector of pulmonary fibrosis? Eur Cytokine Netw, 1, 257-8.
  2. Qi L, Liu CY, Wu WQ, et al (2011). Protective effect of flavonoids from Astragalus complanatus on radiation induced damages in mice. Fitoterapia, 82, 383-92.
  3. Rube CE, Uthe D, Schmid KW, et al (2000). Dose-dependent induction of transforming growth factor ${\beta}$ (TGF-${\beta}$) in the lung tissue of fibrosis-prone mice after thoracic irradiation. Int J Radiat Oncol Biol Phys, 47, 1033-42.
  4. Rube CE, Uthe D, Wilfert F, et al (2005). The bronchiolar epithelium as a prominent source of pro-inflammatory cytokines after lung irradiation. Int J Radiat Oncol Biol Phys, 61, 1482-92.
  5. Rube CE, Wilfert F, Uthe D, et al (2002). Modulation of radiation-induced tumour necrosis factor a (TNF-a) expression in the lung tissue by pentoxifylline. Radiother Oncol, 64, 177-87.
  6. Rube CE, Wilfert F, Uthe D, et al (2004). Increased expression of pro-inflammatory cytokines as a cause of lung toxicity after combined treatment with gemcitabine and thoracic irradiation. Radiother Oncol, 72, 231-41.
  7. Rubin P, Johnston CJ, Williams JP, et al (1995). A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys, 33, 99-109.
  8. Singh NP (2000). Microgels for estimation of DNA sreand breaks, DNA protein crosslinks and apoptosis. Mutat Res, 455, 111-27.
  9. Terao J, Piskula M, Yao Q (1994). Protective effect of epicatechin, epicatechin gallate, and quercetin on lipid peroxidation in phospholipid bilayers. Arch Biochem Biophys, 308, 278-84.
  10. Tsan, M. F (1997). Superoxide dismutase and pulmonary oxygen toxicity. Proc Soc Exp Biol Med, 214, 107-13.
  11. Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, et al (2002). A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic propertiesprotects lungs from radiation-induced injury. Free Radic Biol Med, 33, 857-63.
  12. Vujaskovic Z, Marks LB, Anscher MS (2000). The physical parameters and molecular events associated with radiationinduced lung toxicity. Radiat Oncol, 10, 296-307.
  13. Wei H, Bowen R, Cai Q, et al (1995). Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med, 208, 124-30.
  14. Wei H, Cai Q, Rahn RO (1996). Inhibition of UV light and Fenton reaction-induced oxidative DNA damage by soybean isoflavone genistein. Carcinogenesis, 17, 73-7.
  15. Yi ES, Bedoya A, Lee H, et al (1996). Radiation-induced lung injury in vivo: expression of transforming growth factor-beta precedes fibrosis. Inflammation, 20, 339-52.
  16. Agarwal OP, Nagaratnam A (1981). Radioprotective property of flavonoids in mice. Toxicon, 19, 201-4.
  17. Arora A, Byrem TM, Nair MG, et al (2000). Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids. Arch Biochem Biophys, 373, 102-9.
  18. Cai Q, Rahn RO, Zhang R (1997). Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench. Cancer Lett, 119, 99-107.
  19. Chen Y, Hyrien O, Williams J, et al (2005). Interleukin (IL)-1A and IL-6: Applications to the predictive diagnostic testing of radiation pneumonitis. Int J Radiat Oncol Biol Phys, 2, 260-6.
  20. Di Carlo G, Mascolo N, Izzo AA, et al (1999). Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sci, 65, 337-53.
  21. Emami B, Lyman J, Brown A, et al (1991). Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys, 21, 109-22.
  22. Epperly MW, Defilippi S, Sikora C, et al (2000). Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation. Gene Ther, 7, 1011-8.
  23. Epperly MW, Kagan VE, Sikora CA, et al (2001). Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation. Int J Cancer, 96, 221-31.
  24. Harborne JB, Williams CA (2000). Advances in flavonoid research since 1992. Phytochemistry, 55, 481-504.
  25. Hertog MG, Hollman PC, Katan MB, et al (1993). Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands. Nutr Cancer, 20, 21-9.
  26. Kotloff RM, Little J, Elias JA. Human alveolar macrophage and blood monocyte interleukin-6 production (1990). Am J Respir Cell Mol Biol, 3, 497-505.
  27. Krol W, Czuba ZP, Threadgill MD, et al (1995). Inhibition of nitric oxide (NO.) production in murine macrophages by flavones. Biochem Pharmacol, 50, 1031-5.
  28. Malekirad AA, Ranjbar A, Rahzani K, et al (2005). Oxidative stress in radiology staff. Environ Toxicol Pharmaco, 20, 215-8.
  29. Martin M, Lefaix J, Delanian S (2000). TGF-${\beta}1$ and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys, 47, 277-90.
  30. Martins EA, Chubatsu LS, Meneghini R (1991). Role of antioxidants in protecting cellular DNA from damage by oxidative stress. Mutat Res, 250, 95-101.
  31. Mittal A, Pathania V, Agrawala PK, et al (2001). Influence of Podophyllum hexandrum on endogenous antioxidant defense system in mice: possible role in radioprotection. J Ethnopharmacol, 76, 253-62.

Cited by

  1. Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review vol.15, pp.6, 2014,
  2. Preventive and Therapeutic Effects of Quercetin on Experimental Radiation Induced Lung Injury in Mice vol.16, pp.7, 2015,
  3. Identification of drug-specific pathways based on gene expression data: application to drug induced lung injury vol.7, pp.8, 2015,