Document Type: Original Research


1 MSc, Department of Medical Physics Radiobiology and Radiation Protection, School of Medicine, Babol University of Medical Sciences, Babol, Iran

2 PhD, Medical Physics Department, Faculty of medical Sciences, Tarbiat Modares University, Tehran, Iran

3 MSc, Medical Physics Department, Faculty of medical Sciences, Tarbiat Modares University, Tehran, Iran

4 PhD, Department of Radiology, Faculty of paramedical Sciences, AJA University of Medical Sciences, Tehran, Iran

5 MSc, Department of Radiology Technology, Faculty of Paramedical Sciences, Babol University of Medical Science, Babol, Iran

6 MSc, Department of Radiation Sciences, Yasuj University of Medical Sciences, Yasuj, Iran



Background: Medical use of ionizing radiation has direct/indirect undesirable effects on normal tissues. In this study, the radioprotective effect of arbutin in megavoltage therapeutic x-irradiated mice was investigated using serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), and asparate amniotransferase (AST) activity measurements.
Material and Methods: In this analytical and experimental lab study, sixty mice (12 identical groups) were irradiated with 6 MV x-ray beam (2 and 4 Gy in one fraction). Arbutin concentrations were chosen 50, 100, and 200 mg/kg and injected intraperitoneal 2 hours before irradiation. Samples of peripheral blood cells were collected and serum was separated on the 1, 3, and 7 days post-x-radiation; in addition, the level of ALP, ALT, and AST were measured. Data were analyzed using one-way ANOVA, and Tukey HSD test.
Results: X-radiation (2 and 4 Gy) increased the ALT and AST activity levels on the 1, 3, and 7 days post- irradiation, but the ALP level significantly increased on the 1 and 7 days and decreased on the third day compared to the control group (P< 0.001). ALP, ALT and AST activity levels in “2 and 4 Gy x irradiation + distilled water” groups were significantly higher than “2 and 4 Gy irradiation + 50, 100, and 200 mg/kg arbutin” groups on the first and seventh day post-irradiation (P< 0.001).
Conclusion: Arbutin is a strong radioprotector for reducing the radiation effect on the whole-body tissues by measuring ALP, ALT and AST enzyme activity levels. Furthermore, the concentration of 50 mg/kg arbutin showed higher radioprotective effect.


  1. Abdi Goushbolagh N, Abedi Firouzjah R, Ebrahimnejad Gorji K, Khosravanipour M, Moradi S, Banaei A, et al. Estimation of radiation dose-reduction factor for cerium oxide nanoparticles in MRC-5 human lung fibroblastic cells and MCF-7 breast-cancer cells. Artif Cells Nanomed Biotechnol. 2018;46:S1215-S25. doi: 10.1080/21691401.2018.1536062. PubMed PMID: 30481078.
  2. Firouzjah RA, Banaei A, Farhood B, Bakhshandeh M. Dosimetric Comparison of Four Different Techniques for Supraclavicular Irradiation in 3D-conformal Radiotherapy of Breast Cancer. Health Phys. 2019;116:631-6. doi: 10.1097/HP.0000000000000991. PubMed PMID: 30608247.
  3. Benkovic V, Orsolic N, Knezevic AH, Ramic S, Dikic D, Basic I, et al. Evaluation of the radioprotective effects of propolis and flavonoids in gamma-irradiated mice: the alkaline comet assay study. Biol Pharm Bull. 2008;31:167-72. doi: 10.1248/bpb.31.167. PubMed PMID: 18175964.
  4. Karbownik M, Reiter RJ. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proc Soc Exp Biol Med. 2000;225:9-22. doi: 10.1046/j.1525-1373.2000.22502.x. PubMed PMID: 10998194.
  5. Bertelsen A, Hansen CR, Johansen J, Brink C. Single Arc Volumetric Modulated Arc Therapy of head and neck cancer. Radiother Oncol. 2010;95:142-8. doi: 10.1016/j.radonc.2010.01.011. PubMed PMID: 20188427.
  6. Jin T, Song T, Deng S, Wang K. Radiation-induced secondary malignancy in prostate cancer: a systematic review and meta-analysis. Urol Int. 2014;93:279-88. doi: 10.1159/000356115. PubMed PMID: 25139441.
  7. Velpula N, Ugrappa S, Kodangal S. A role of radioprotective agents in cancer therapeutics: a review. Int J Basic Clin Pharmacol. 2013;2:677-82. doi: 10.5455/2319-2003.ijbcp20131203.
  8. Nadi S, Monfared AS, Mozdarani H, Mahmodzade A, Pouramir M. Effects of Arbutin on Radiation-Induced Micronuclei in Mice Bone Marrow Cells and Its Definite Dose Reduction Factor. Iran J Med Sci. 2016;41:180-5. PubMed PMID: 27217601; PubMed Central PMCID: PMCPMC4876295.
  9. Lubsandorzhieva P, Zhigzhitov B, Dargaeva T, Bazarova ZG, Nagaslaeva L. Chromatospectrophotometric determination of arbutin in the leaves ofBergenia crassifolia (L.) Fritsch. Pharmaceutical Chemistry Journal. 2000;34:261-4. doi: 10.1007/bf02524636.
  10. 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.
  11. Jin Y, Yuan MQ, Chen JQ, Zhang YP. Serum alkaline phosphatase predicts survival outcomes in patients with skeletal metastatic nasopharyngeal carcinoma. Clinics (Sao Paulo). 2015;70:264-72. doi: 10.6061/clinics/2015(04)08. PubMed PMID: 26017793; PubMed Central PMCID: PMCPMC4449461.
  12. Sharma U, Pal D, Prasad R. Alkaline phosphatase: an overview. Indian J Clin Biochem. 2014;29:269-78. doi: 10.1007/s12291-013-0408-y. PubMed PMID: 24966474; PubMed Central PMCID: PMCPMC4062654.
  13. He S, Wang Y, Peng H, Yang L, Chen H, Liang S, et al. Pretreatment Alkaline Phosphatase and Epstein-Barr Virus DNA Predict Poor Prognosis and Response to Salvage Radiotherapy in Patients with Nasopharyngeal Carcinoma and Metachronous Bone-Only Metastasis. J Cancer. 2017;8:417-24. doi: 10.7150/jca.17310. PubMed PMID: 28261343; PubMed Central PMCID: PMCPMC5332893.
  14. Li G, Gao J, Tao YL, Xu BQ, Tu ZW, Liu ZG, et al. Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma. Chin J Cancer. 2012;31:197-206. doi: 10.5732/cjc.011.10283. PubMed PMID: 22237040; PubMed Central PMCID: PMCPMC3777475.
  15. Rosen E, Sabel AL, Brinton JT, Catanach B, Gaudiani JL, Mehler PS. Liver dysfunction in patients with severe anorexia nervosa. Int J Eat Disord. 2016;49:151-8. doi: 10.1002/eat.22436. PubMed PMID: 26346046.
  16. Sun J, Zhao J, Bao X, Wang Q, Yang X. Alkaline Phosphatase Assay Based on the Chromogenic Interaction of Diethanolamine with 4-Aminophenol. Anal Chem. 2018;90:6339-45. doi: 10.1021/acs.analchem.8b01371. PubMed PMID: 29683655.
  17. Beydilli H, Yilmaz N, Cetin ES, Topal Y, Celik OI, Sahin C, et al. Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver. Iran Red Crescent Med J. 2015;17:e25310. doi: 10.5812/ircmj.17(4)2015.25310. PubMed PMID: 26023342; PubMed Central PMCID: PMCPMC4443388.
  18. Ramadan LA, Roushdy HM, Abu Senna GM, Amin NE, El-Deshw OA. Radioprotective effect of silymarin against radiation induced hepatotoxicity. Pharmacol Res. 2002;45:447-54. doi: 10.1006/phrs.2002.0990 . PubMed PMID: 12162944.
  19. Kind D, King E. Practical clinical biochemistry 1. In: Varley H, Gownlock AH, Bell M, editors. Practical clinical biochemistry. 5th ed. London: William Heinemann Medical Books Ltd. 1954. p. 892.
  20. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957;28:56-63. doi: 10.1093/ajcp/28.1.56. PubMed PMID: 13458125.
  21. Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC. Public Policy Committee of the American Association for the Study of Liver D. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008;47:1363-70. doi: 10.1002/hep.22109. PubMed PMID: 18366115.
  22. Khamis F, Roushdy M. Synergistic radioprotective action of imidazole and serotonin on serum and liver enzymes in rats. Arab Journal of Nuclear Sciences and Applications. 1991;24:19-36.