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Radioprotective effect of naringin and naringenin against cellular damage and oxidative stress of γ-irradiated mice

감마선을 조사한 마우스의 세포 손상과 산화적 스트레스에 대한 나린진과 나린제닌의 방사선방호 효과

  • Received : 2017.06.30
  • Accepted : 2017.08.24
  • Published : 2017.12.31

Abstract

The present study was designed to evaluate the antioxidant activity and radioprotective effects of Naringin and Naringenin in ${\gamma}$-irradiated mice. The antioxidant activity of Naringin and Naringenin was evaluated by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assays. Healthy female BALB/c mice were administered Naringin and Naringenin orally ($90{\mu}M/dose$ and $180{\mu}M/dose$) for 7 consecutive days prior to ${\gamma}$-irradiation (6 Gy). Naringenin displayed a much higher antioxidant activity in ABTS and FRAP than naringin. ${\gamma}$-irradiation resulted in cellular damage with decreased spleen and thymus indices and white blood cells (WBC) count. Additionally, ${\gamma}$-irradiation significantly increased lipid peroxidation and decreased the levels of antioxidant enzymes and glutathione (GSH) in the liver tissue. Strikingly, prior administration of Naringenin resulted in considerable prevention of these symptoms. Protection against ${\gamma}$-irradiation-induced cellular damage by Naringenin is likely due to its higher its antioxidant activity. Together, these results confirm that Naringenin is a potent antioxidant and radioprotector.

Keywords

naringin;naringenin;${\gamma}$-irradiation;radioprotective;cellular damage

References

  1. Srinivasa E, Rangaswamy DR, Sannappa J. Study on natural gamma radiation hazards in and around Hassan district, Karnataka state, India. Int. J. Adv. Res. Sci. Technol. 4: 237-240 (2015)
  2. Hosoda M, Tokonami S, Sorimachi A, Monzen S, Osanai M, Yamada M, Kashiwakura I, Akiba S. The time variation of dose rate artificially increased by the Fukushima nuclear crisis. Sci. Rep. 1: 87 (2011) https://doi.org/10.1038/srep00087
  3. Morino Y, Ohara T, Watanabe M, Hayashi S, Nishizawa M. Episode analysis of deposition of radiocesium from the Fukushima Daiichi nuclear power plant accident. Environ. Sci. Technol. 47: 2314-2322 (2013) https://doi.org/10.1021/es304620x
  4. Dormand EL, Banwell PE, Goodacre TE. Radiotherapy and wound healing. Int. Wound J. 2: 112-127 (2015)
  5. Bolus NE. Basic review of radiation biology and terminology. J. Nucl. Med. Technol. 29: 67-73 (2014)
  6. Upadhyay SN, Dwarakanath BS, Ravindranath T. Chemical Radioprotectors. Defence Sci. J. 55: 403-425 (2005) https://doi.org/10.14429/dsj.55.2003
  7. Hosseinimehr SJ. Trends in the development of radioprotective agents. Drug Discov. Today 12: 794-805 (2007) https://doi.org/10.1016/j.drudis.2007.07.017
  8. Pradeep K, Park SH, Ko K. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats. Eur. J. Pharmacol. 587: 273-280 (2008) https://doi.org/10.1016/j.ejphar.2008.03.052
  9. Kang KA, Lee IK, Zhang R, Piao MJ, Kim KC, Kim SY, Shin T, Kim BJ, Lee NH, Hyun JW. Radioprotective effect of geraniin via the inhibition of apoptosis triggered by ${\gamma}$-radiation-induced oxidative stress. Cell Biol. Toxicol. 27: 83-94 (2011) https://doi.org/10.1007/s10565-010-9172-4
  10. Kim HO, Park YB, Lee M, Seo H, Choi M. Naringin alters the cholesterol biosynthsis and antioxidant enzyme activities in LDL recetpor-Knockout mice under cholesterol fed condition. Life Sci. 74: 1621-1634 (2004) https://doi.org/10.1016/j.lfs.2003.08.026
  11. Cvetnic Z, Vladimir-Knezevic S. Antimicrobial activity of grapefruit seed and pulp ethanolic extract. Acta. Pharmaceutica. 54: 243-250 (2004)
  12. Balestrieri ML, Castaldo D, Balestrieri C, Quagliuolo L, Giovane A, Servillo L. Modulation by flavonoids of PAF and related phospholipids in endothelial cells during oxidative stress. J. Lipid Res. 44: 380-387 (2003) https://doi.org/10.1194/jlr.M200292-JLR200
  13. Jung, UJ, Lee MK, Park YB, Kang MA, Choi MS. Effects of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA level in type-2 diabetic mice. Int. J. Biochem. Cell Biol. 38: 1134-1145 (2006) https://doi.org/10.1016/j.biocel.2005.12.002
  14. Kim DL, Lee SJ, Lee SB. Requirement for Ras/Raf/ERK pathway in naringin-induced G1-cell-cycle arrest via p21WAF1 expression. Carcinogensis 29: 1701-1709 (2008) https://doi.org/10.1093/carcin/bgn055
  15. Dupuy J, Larrieu JF, Sutra A, Alvinerie M. Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: Quercetin. Vet. Parasitol. 112: 337-347 (2003) https://doi.org/10.1016/S0304-4017(03)00008-6
  16. Hodek, P, Trefil P, Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem. Biol. Interact. 139: 1-21 (2002) https://doi.org/10.1016/S0009-2797(01)00285-X
  17. Doostdar H, Burke MD, Mayer RT. Bioflavonoids: Selective substrated and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicol. 144: 31-38 (2000) https://doi.org/10.1016/S0300-483X(99)00215-2
  18. Van Acker FA, Schouten O, Haenen GR, Van der Vijgh WJ, Bast A. Flavonoids can replace ${\alpha}$-tocopherol as an antioxidant. FEBS. Lett. 473: 145-148 (2000) https://doi.org/10.1016/S0014-5793(00)01517-9
  19. So FV, Guthrie A, Chambers AF, Carroll KK. Inhibition of proliferation of estrogen receptor-positive MCF-7 human. Cancer Lett. 112: 127-133 (1997) https://doi.org/10.1016/S0304-3835(96)04557-0
  20. Cai YZ, Sun M, Xing J, Luo Q, Corke H. Structure-radical scavenging activity relationships of phenolic compounds from traditional Chinise medicinal plants. Life Sci. 78: 2872-2888 (2006) https://doi.org/10.1016/j.lfs.2005.11.004
  21. Jagetia GC, Reddy TK. Modulation of radiation induced alteration in the antioxidant status of mice by naringin. Life Sci. 77: 780-794 (2005) https://doi.org/10.1016/j.lfs.2005.01.015
  22. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Ree. Radic. Biol. Med. 26: 1231-1237 (1999) https://doi.org/10.1016/S0891-5849(98)00315-3
  23. Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of 'antioxidant power': The FRAP assay. Anal. Biochem. 239: 70-76 (1996) https://doi.org/10.1006/abio.1996.0292
  24. Kang JA, Nam YR, Rho JK, Jang BS, Chung YJ, Park SH. Radioprotective effect of post-treatment with hesperetin on ${\gamma}$-irradiation-induced tissue damage and oxidative stress in BALB/c mice. J. Korean Soc. Food Sci. Nutr. 44: 657-663 (2015) https://doi.org/10.3746/jkfn.2015.44.5.657
  25. Ohkawa H, Ohishi N, Yagi A. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95: 351-358 (1979) https://doi.org/10.1016/0003-2697(79)90738-3
  26. Bradford MM. A rapid and sensitive method for quantitation of micogram quantities of protein utilizing the principle of proteindye binding. Anal Biochem. 72: 248-254 (1976) https://doi.org/10.1016/0003-2697(76)90527-3
  27. Gough GR, Boggs SS, Schwartz GN. Changes in thymus size observed radiographically during the course of spontaneous lymphoma in the AKR/J mouse. Lab. Anim. Sci. 27: 627-634 (1977)
  28. Patchen ML, Mac Vittie TJ, Williams JL, Schwartz GN, Souza LM. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression. Blood 77: 472-480 (1991)
  29. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 245: 194-205 (2008) https://doi.org/10.1016/j.tox.2007.11.021
  30. Recknagel RO, Glende JE, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol. Ther. 43: 139-154 (1989) https://doi.org/10.1016/0163-7258(89)90050-8
  31. Pradeep K, Ko KC, Choi MH, Kang JA, Chung YJ, Park SH. Protective effect of hesperidin, a citrus flavanoglycone, against ${\gamma}$-radiation-induced tissue damage in Sprague-Dawley rats. J. Med. Food 15: 419-427 (2012) https://doi.org/10.1089/jmf.2011.1737
  32. Leelavinothan P, Muthurangam G. Influence of naringenin on oxytetracycline mediated oxidative damage in rat liver. Basic Clin. Pharmacol. Toxicol. 98: 456-461 (2006) https://doi.org/10.1111/j.1742-7843.2006.pto_351.x
  33. Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed. Pharmacother. 58: 39-46 (2003)
  34. Loku K, Tsushida T, Takei Y, Nakatani N, Terao J. Antioxidative activity of quercetin and quercetin monoglucosides in solution and phospholipid bilayers. Biophysica. Acta. 1234: 99-104 (1995) https://doi.org/10.1016/0005-2736(94)00262-N
  35. Sau AK, Mondal MS, Mitra S. Reaction of milk xanthine oxidase with o-phenanthroline and 1,7-dimethylxanthine: a mechanistic study. J. Chem. Soc. Dalton Trans. 24: 4173-4178 (1998)
  36. Pratheeshkumar P, Kuttan G. Protective role of Vernonia cinerea L. against gamma radiation-induced immunosupression and oxidative stress in mice. Hum. Exp. Toxicol. 30: 1022-1038 (2011) https://doi.org/10.1177/0960327110385959
  37. Fridovich I. Biological effects of the superoxide radical. Arch. Biochem. Biophys. 247: 1-11 (1986) https://doi.org/10.1016/0003-9861(86)90526-6

Acknowledgement

Supported by : 미래창조과학부