Iranian Journal of Medical Sciences

Document Type: Original Article(s)


1 Department of Radiobiology and Radiation Protection, Babol University of Medical Sciences, Babol, Iran

2 Cellular & Molecular Biology Research Center, Department of Medical physics, Babol University of Medical Sciences, Babol, Iran

3 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

4 Laboratory of Cytogenetic, Novin Medical Radiation Institute, Tehran, Iran

5 Department of Biochemistry, Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran


Background: Interactions of free radicals from ionizing radiation with DNA can induce DNA damage and lead to mutagenesis and carsinogenesis. With respect to radiation damage to human, it is important to protect humans from side effects induced by ionizing radiation.In the present study, the effects of arbutin were investigated by using the micronucleus test for anti-clastogenic activity, to calculate the ratio of polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte (PCE/PCE+NCE) in order to show cell proliferation activity.Methods: Arbutin (50, 100, and 200 mg/kg) was intraperitoneally (ip) administered to NMRI mice two hours before gamma radiation at 2 and 4 gray (Gy). The frequency of micronuclei in 1000 PCEs (MnPCEs) and the ratio of PCE/PCE+NCE were calculated for each sample. Data were statistically evaluated using one-way ANOVA, Tukey HSD test, and t-test.Results: The findings indicated that gamma radiation at 2 and 4 Gy extremely increased the frequencies of MnPCE (P<0.001) while reducing PCE/PCE+NCE (P<0.001) compared to the control group. All three doses of arbutin before irradiation significantly reduced the frequencies of MnPCEs and increased the ratio of PCE/PCE+NCE in mice bone marrow compared to the non-drug-treated irradiated control (P<0.001). All three doses of arbutin had no toxicity effect on bone marrow cells. The calculated dose reduction factor (DRF) showed DRF=1.93 for 2Gy and DRF=2.22 for 4 Gy.Conclusion: Our results demonstrated that arbutin gives significant protection to rat bone against the clastogenic and cytotoxic effects of gamma irradiation.


  1. - Alsbeih G, El-Sebaie M, Al-Harbi N, Al-Buhairi M, Al-Hadyan K, Al-Rajhi N. Radiosensitivity of human fibroblasts is associated with amino acid substitution variants in susceptible genes and correlates with the number of risk alleles. Int J Radiat Oncol Biol Phys. 2007;68:229-35. doi: 10.1016/j.ijrobp.2006.12.050. PubMed PMID: 17331670.
  2. - Lenarczyk M, Goddu SM, Rao DV, Howell RW. Biologic dosimetry of bone marrow: induction of micronuclei in reticulocytes after exposure to 32P and 90Y. J Nucl Med. 2001;42:162-9. PubMed PMID: 11197968.
  3. - Watanabe N, Kanegane H, Kinuya S, Shuke N, Yokoyama K, Kato H, et al. The radiotoxicity of 131I therapy of thyroid cancer: assessment by micronucleus assay of B lymphocytes. J Nucl Med. 2004;45:608-11. PubMed PMID: 15073256.
  4. - Eberlein U, Haenscheid H, Biko J, Reiners C, Lassmann M. Blood-based dosimetry and the formation of micronuclei in thyroid cancer patients. J Nucl Med. 2012;53:1498.
  5. - Fenech M. Cytokinesis-block micronucleus cytome assay. Nat Protoc. 2007;2:1084-104. doi: 10.1038/nprot.2007.77. PubMed PMID: 17546000.
  6. - Tsai MH, Hwang JS, Chen KC, Lin YP, Hsieh WA, Chang WP. Dynamics of changes in micronucleus frequencies in subjects post cessation of chronic low-dose radiation exposure. Mutagenesis. 2001;16:251-5. doi: 10.1093/mutage/16.3.251. PubMed PMID: 11320151.
  7. - Cardoso R, Takahashi‐Hyodo S, Peitl P, Ghilardi‐Neto T, Sakamoto‐Hojo E. Evaluation of chromosomal aberrations, micronuclei, and sister chromatid exchanges in hospital workers chronically exposed to ionizing radiation. Teratog., Carcinog. Mutagen.. 2001;21:431-9. doi: 10.1002/tcm.1030.
  8. - Lubsandorzhieva P, Zhigzhitov B, Dargaeva T, Bazarova ZG, Nagaslaeva L. Chromatospectrophotometric determination of arbutin in the leaves of Bergenia crassifolia (L.) Fritsch. Pharmaceutical Chemistry Journal. 2000;34:261-4.
  9. - Couteau C, Coiffard LJ. Photostability determination of arbutin, a vegetable whitening agent. Farmaco. 2000;55:410-3. doi: 10.1016/S0014-827X(00)00049-5. PubMed PMID: 10983289.
  10. - Kang MJ, Ha HW, Kim HG, Lee DH, Kong MJ, Ahn YT, et al. Role of metabolism by intestinal bacteria in arbutin-induced toxicity in vitro. Arch Pharm Res. 2011;34:687-93. doi: 10.1007/s12272-011-0420-9. PubMed PMID: 21544735.
  11. - Schmid W. The micronucleus test. Mutat Res. 1975;31:9-15. doi: 10.1016/0165-1161(75)90058-8. PubMed PMID: 48190.
  12. - Hosseinimehr SJ, Tavakoli H, Pourheidari G, Sobhani A, Shafiee A. Radioprotective effects of citrus extract against gamma-irradiation in mouse bone marrow cells. J Radiat Res. 2003;44:237-41. PubMed PMID: 14646227.
  13. - Wallner M, Blassnigg SM, Marisch K, Pappenheim MT, Mullner E, Molzer C, et al. Effects of unconjugated bilirubin on chromosomal damage in individuals with Gilbert's syndrome measured with the micronucleus cytome assay. Mutagenesis. 2012;27:731-5. doi: 10.1093/mutage/ges039. PubMed PMID: 22874647.
  14. - McNamee JP, Flegal FN, Greene HB, Marro L, Wilkins RC. Validation of the cytokinesis-block micronucleus (CBMN) assay for use as a triage biological dosimetry tool. Radiat Prot Dosimetry. 2009;135:232-42. doi: 10.1093/rpd/ncp119. PubMed PMID: 19628702.
  15. - Maffei F, Angelini S, Forti GC, Lodi V, Violante FS, Mattioli S, et al. Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: influence of smoking status and other factors. Mutagenesis. 2002;17:405-9. doi: 10.1093/mutage/17.5.405 PubMed PMID: 12202628..
  16. - Thierens H, Vral A, Morthier R, Aousalah B, De Ridder L. Cytogenetic monitoring of hospital workers occupationally exposed to ionizing radiation using the micronucleus centromere assay. Mutagenesis. 2000;15:245-9. doi: 10.1093/mutage/15.3.245. PubMed PMID: 10792018.
  17. - Khosravifarsani M, Monfared AS, Elahimanesh F, Borzoueisileh S, Hajian-Tilaki K, Seyfizadeh N, et al. Is there association between handedness and radiosensitivity in breast cancer women? Medical Oncology. 2012;29:2552-5. doi: 10.1007/s12032-011-0153-0.
  18. - Hosseinimehr SJ, Nemati A. Radioprotective effects of hesperidin against gamma irradiation in mouse bone marrow cells. Br J Radiol. 2006;79:415-8. doi: 10.1259/bjr/40692384. PubMed PMID: 16632622.
  19. - Shahidi M, Mozdarani H. Potent radioprotective effect of therapeutic doses of ranitidine and famotidine against gamma-rays induced micronuclei in vivo. Iran J Radiat Res. 2003;1:29-35.
  20. - Shokrzadeh M, Naghshvar F, Ahmadi A, Chabra A, Jeivad F. The potential ameliorative effects of melatonin against cyclophosphamide-induced DNA damage in murine bone marrow cells. Eur Rev Med Pharmacol Sci. 2014;18:605-11. PubMed PMID: 24668699.
  21. - Hori I, Nihei K, Kubo I. Structural criteria for depigmenting mechanism of arbutin. Phytother Res. 2004;18:475-9. doi: 10.1002/ptr.1456. PubMed PMID: 15287073.
  22. Pavlovic RD, Lakusic B, Doslov-Kokorus Z, Kovacevic N. Arbutin content and antioxidant activity of some Ericaceae species. Pharmazie. 2009;64:656-9. PubMed PMID: 19947168.
  23. - Takebayashi J, Ishii R, Chen J, Matsumoto T, Ishimi Y, Tai A. Reassessment of antioxidant activity of arbutin: multifaceted evaluation using five antioxidant assay systems. Free Radic Res. 2010;44:473-8. doi: 10.3109/10715761003610760. PubMed PMID: 20166881.
  24. - Lukas B, Schmiderer C, Mitteregger U, Novak J. Arbutin in marjoram and oregano. Food Chemistry. 2010;121:185-90. doi: 10.1016/j.foodchem.2009.12.028.
  25. - Gholizadeh N, KHAN BZ, HABIBNEZHAD F, Lakzaei M, POURAMIR M. Effects of pyrus boissieriana buhse leaves extract on antihyperglycemic, antioxidant and antilipidproxidative in rats. 2009. Journal of Babul University of Medical Sciences. 2009;11:7-12.
  26. - Shahaboddin ME, Pouramir M, Moghadamnia AA, Parsian H, Lakzaei M, Mir H. Pyrus biossieriana Buhse leaf extract: An antioxidant, antihyperglycaemic and antihyperlipidemic agent. Food Chem. 2011;126:1730-3. doi: 10.1016/j.foodchem.2010.12.069. PubMed PMID: 25213951.
  27. - Mazur L. Radioprotective effects of the thiols GSH and WR-2721 against X-ray-induction of micronuclei in erythroblasts. Mutat Res. 2000;468:27-33. doi: 10.1016/S1383-5718(00)00037-1. PubMed PMID: 10863155.
  28. - Mozdarani H, Gharbali A. Radioprotective effects of cimetidine in mouse bone marrow cells exposed to gamma-rays as assayed by the micronucleus test. Int J Radiat Biol. 1993;64:189-94. PubMed PMID: 8103543.
  29. - Cheng SL, Liu RH, Sheu JN, Chen ST, Sinchaikul S, Tsay GJ. Toxicogenomics of A375 human malignant melanoma cells treated with arbutin. J Biomed Sci. 2007;14:87-105. doi: 10.1007/s11373-006-9130-6. PubMed PMID: 17103032.
  30. - Mozdarani H. Radioprotective properties of histamine H2 receptor antagonists: present and future prospects. J Radiat Res. 2003;44:145-9. PubMed PMID: 13678344.