DOI QR코드

DOI QR Code

Radioprotective Effects of Post-Treatment with Hesperetin against γ-Irradiation-Induced Tissue Damage and Oxidative Stress in BALB/c Mice

BALB/c 마우스에서 감마선 조사로 유도된 조직 손상과 산화적 스트레스에 대한 헤스페레틴 투여 후의 방사선방호 효과

  • Kang, Jung Ae (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Nam, You Ree (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Rho, Jong Kook (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Jang, Beom-Su (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Chung, Young-Jin (Department of Food and Nutrition, Chungnam National University) ;
  • Park, Sang Hyun (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
  • 강정애 (한국원자력연구원 첨단방사선연구소) ;
  • 남유리 (한국원자력연구원 첨단방사선연구소) ;
  • 노종국 (한국원자력연구원 첨단방사선연구소) ;
  • 장범수 (한국원자력연구원 첨단방사선연구소) ;
  • 정영진 (충남대학교 식품영양학과) ;
  • 박상현 (한국원자력연구원 첨단방사선연구소)
  • Received : 2014.12.29
  • Accepted : 2015.02.10
  • Published : 2015.05.31

Abstract

Ionizing radiation induces cell damage through formation of reactive oxygen species. The present study was designed to evaluate the protective effects of post-treatment with hesperetin against ${\gamma}$-irradiation-induced cellular damage and oxidative stress in BALB/c mice. Healthy female BALB/c mice were exposed to ${\gamma}$-irradiation and administered hesperetin (25 mg/kg and 50 mg/kg, b.w., orally) for 7 days after 6 Gy of ${\gamma}$-irradiation. Exposure to ${\gamma}$-irradiation resulted in hematopoietic system damage manifested as decreases in spleen indexes and WBC count. In addition, hepatocellular damage characterized by increased levels of aspartate aminoransferase (AST) and alanine aminotransferase (ALT) in plasma. However, post-irradiation treatment with hesperetin provided significant protection against hematopoietic system damage and decreased AST and ALT levels in plasma. The results indicate that ${\gamma}$-irradiation induced increases in lipid peroxidation and xanthine oxidase (XO) as well as decreases in antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione (GSH) in the liver. These effects were also attenuated by post-treatment with hesperetin, which decreased lipid peroxidation and XO as well as increased antioxidant enzymes and GSH. These results show that post-treatment with hesperetin offers protection against ${\gamma}$-irradiation-induced tissue damage and oxidative stress and can be developed as an effective radioprotector during radiotherapy.

본 연구는 BALB/c 마우스에 감마선 조사 후 헤스페레틴과 헤스페리딘을 7일 동안 경구투여하여 감마선 조사로 유도된 조직 손상과 산화적 스트레스에 대한 회복 효과를 검토하였다. 감마선 조사 7일 후의 체중 변화에서 감마선 조사 후 헤스페레틴을 투여한 군이 감마선 조사군에 비해 유의적으로 증가하여 회복됨을 보여주었다. 감마선 조사 후 헤스페레틴을 투여한 군의 비장 지수는 감마선 조사군에 비해 유의적으로 증가하여 조혈면역계의 손상에 대해 치료 효과가 있음을 확인하였다. 감마선 조사 후 헤스페레틴을 50 mg/kg 투여한 군의 ALT와 AST가 감마선 조사군에 비해 유의적으로 감소하여 간세포 손상에 대해 치료 효과를 확인하였다. 감마선 조사 후 헤스페레틴을 투여한 군의 지질과산화는 감마선 조사군에 비해 유의적으로 낮게 나타남을 보여 방사선에 의한 장해를 회복시킨 것으로 판단된다. 감마선 조사 후 헤스페레틴을 50 mg/kg 투여한 군의 XO는 감마선 조사군에 비해 유의적으로 감소하였다. 감마선 조사 후 헤스페레틴을 투여한 군의 GSH는 감마선 조사군에 비해 유의적으로 증가하여 생체 내 항산화 방어 체계를 정상 범위로 회복시켰다. 감마선 조사 후 헤스페레틴을 25 mg/kg 투여한 군의 항산화 효소의 활성이 감마선 조사군에 비해 유의적으로 증가하여 방어체계를 회복시켰다. 이상의 결과를 통해 방사선 조사후 헤스페레틴의 투여가 방사선에 의한 조혈계 및 간세포 손상과 산화적 스트레스에 대해 회복 효과가 있음을 확인하였다. 따라서 헤스페레틴은 방사선 노출에 있어서 방사선방호제로서 유용하게 사용될 수 있을 것으로 사료된다.

Keywords

References

  1. Meister M. 2005. The health effects of low-level radiation. American Council on Science and Health, New York, NY, USA. p 2-4.
  2. Hosoda M, Tokonami S, Sorimachi A, Monzen S, Osanai M, Yamada M, Kashiwakura I, Akiba S. 2011. The time variation of dose rate artificially increased by the Fukushima nuclear crisis. Sci Rep 1: 87. https://doi.org/10.1038/srep00087
  3. Hosoda M, Tokonami S, Tazoe H, Sorimachi A, Monzen S, Osanai M, Akata N, Kakiuchi H, Omori Y, Ishikawa T, Sahoo SK, Kovacs T, Yamada M, Nakata A, Yoshida M, Yoshino H, Mariya Y, Kashiwakura I. 2013. Activity concentrations of environmental samples collected in Fukushima Prefecture immediately after the Fukushima nuclear accident. Sci Rep 3: 2283. https://doi.org/10.1038/srep02283
  4. Morino Y, Ohara T, Watanabe M, Hayashi S, Nishizawa M. 2013. Episode analysis of deposition of radiocesium from the Fukushima Daiichi nuclear power plant accident. Environ Sci Technol 47: 2314-2322. https://doi.org/10.1021/es304620x
  5. Nuclear Safety and Security Commission. 2012. Act on safety control of radioactive rays around living environment. Ministry of Government Legislation, Seoul, Korea. Article 1.
  6. Dormand EL, Banwell PE, Goodacre TE. 2005. Radiotherapy and wound healing. Int Wound J 2: 112-127. https://doi.org/10.1111/j.1742-4801.2005.00079.x
  7. Halliwell B, Gutterige JM. 1999. Free radical in biology and medicine. 3rd ed. Oxford University Press, New York, NY, USA. p 604-607.
  8. Phillips TL. 1981. Sensitizers and protectors in clinical oncology. Semin Oncol 8: 65-82.
  9. Hosseinimehr SJ. 2007. Trends in the development of radioprotective agents. Drug Discov Today 12: 794-805. https://doi.org/10.1016/j.drudis.2007.07.017
  10. Rauha JP, Vuorela H, Kostiainen R. 2001. Effect of eluent on the ionization efficiency of flavonoids by ion spray, atmospheric pressure chemical ionization, and atmospheric pressure photoionization mass spectrometry. J Mass Spectrom 36: 1269-1280. https://doi.org/10.1002/jms.231
  11. Korkina LG, Afanas'ev IB. 1997. Antioxidant and chelating properties of flavonoids. Adv Pharmacol 38: 151-163.
  12. Garg A, Garg S, Zaneveld LJ, Singla AK. 2001. Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res 15: 655-669. https://doi.org/10.1002/ptr.1074
  13. Ameer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL. 1996. Flavanone absorption after naringin, hesperidin, and citrus administration. Clin Pharmacol Ther 60: 34-40. https://doi.org/10.1016/S0009-9236(96)90164-2
  14. Tanaka T, Makita H, Kawabata K, Mori H, Kakumoto M, Satoh K, Hara A, Sumida T, Tanaka T, Ogawa H. 1997. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesiss 18: 957-965. https://doi.org/10.1093/carcin/18.5.957
  15. Yang M, Tanaka T, Hirose Y, Deguchi T, Mori H, Kawada Y. 1997. Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice. Int J Cancer 73: 719-724. https://doi.org/10.1002/(SICI)1097-0215(19971127)73:5<719::AID-IJC18>3.0.CO;2-0
  16. Shirazi A, Ghobadi G, Ghazi-Khansari M. 2007. A radiobiological review on melatonin: a novel radioprotector. J Radiat Res 48: 263-272. https://doi.org/10.1269/jrr.06070
  17. Cai YZ, Sun M, Xing J, Luo Q, Corke H. 2006. Structure-radical scavenging activity relationships of phenolic compounds from traditional Chinese medicinal plants. Life Sci 78: 2872-2888. https://doi.org/10.1016/j.lfs.2005.11.004
  18. Pradeep K, Ko KC, Choi MH, Kang JA, Chung YJ, Park SH. 2012. Protective effect of hesperidin, a citrus flavanoglycone, against ${\gamma}$-radiation-induced tissue damage in Sprague-Dawley rats. J Med Food 15: 419-427. https://doi.org/10.1089/jmf.2011.1737
  19. Bergmeyer HU, Scheibe P, Wahlefeld AW. 1978. Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin Chem 24: 58-73.
  20. Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358. https://doi.org/10.1016/0003-2697(79)90738-3
  21. Bradford MM. 1976. A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254. https://doi.org/10.1016/0003-2697(76)90527-3
  22. Lin IH, Hau DM, Chen WC, Chen KT, Lin JG. 1996. Effects of glycyrrhizae and glycyrrhizic acid on cellular immunocompetence of gamma-ray-irradiated mice. Chin Med J (Engl) 109: 138-142.
  23. Pradeep K, Park SH, Ko KC. 2008. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats. Eur J Pharmacol 587: 273-280. https://doi.org/10.1016/j.ejphar.2008.03.052
  24. Gough GR, Boggs SS, Schwartz GN. 1977. Changes in thymus size observed radiographically during the course of spontaneous lymphoma in the AKR/J mouse. Lab Anim Sci 27: 627-634.
  25. Patchen ML, MacVittie TJ, Williams JL, Schwartz GN, Souza LM. 1991. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression. Blood 77: 472-480.
  26. Recknagel RO, Glende EA Jr, Dolak JA, Waller RL. 1989. Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 43: 139-154. https://doi.org/10.1016/0163-7258(89)90050-8
  27. Emerit J, Edeas M, Bricaire F. 2003. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58: 39-46.
  28. McCord JM. 1985. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312: 159-163. https://doi.org/10.1056/NEJM198501173120305
  29. Fridovich I. 1986. Biological effects of the superoxide radical. Arch Biochem Biophys 247: 1-11. https://doi.org/10.1016/0003-9861(86)90526-6
  30. Pratheeshkumar P, Kuttan G. 2011. Protective role of Vernonia cinerea L. against gamma radiation-induced immunosupression and oxidative stress in mice. Hum Exp Toxicol 30: 1022-1038. https://doi.org/10.1177/0960327110385959

Cited by

  1. 백하수오 에탄올추출물이 방사선조사에 따른 흰쥐의 혈구 및 장기에 미치는 영향 vol.39, pp.3, 2015, https://doi.org/10.17946/jrst.2016.39.3.21
  2. 감마선을 조사한 마우스의 세포 손상과 산화적 스트레스에 대한 나린진과 나린제닌의 방사선방호 효과 vol.49, pp.6, 2017, https://doi.org/10.9721/kjfst.2017.49.6.659