Nanocurcumin as a radioprotective agent against radiation-induced mortality in mice

Document Type: Research Paper


1 Department of Radiology Technology, Allied Medical Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Urology and Nephrology Research Center, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Physiology Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

4 Department of Radiotherapy, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Objective(s): Curcumin, a natural plant product, is commonly known as wonder drug of life, but the poor bioavailability of its free form has hindered its clinical development. The aim of the present study was to investigate the radioprotective effect of nanocurcumin on survival of mice under whole body X-ray irradiation.
Materials and Methods: The Naval Medical Research Institute (NMRI) mice randomly assigned to separate groups and received nanocurcumin via oral gavage at different time points related to irradiation. The survival of mice was evaluated daily for 30 days post-irradiation and finally, the LD50/30 was calculated using Probit analysis. The 30-day survival curve was plotted using the Kaplan-Meier survival curve and the median survival of different subgroups was compared using log-rank test. The P-values less than 0.05 were considered significant.
Results: Our results showed that the administration of oral nanocurcumin could effectively reduce the mortality rate in the irradiated mice. Five days pretreatment with nanocurcumin (4 mg/kg/day) induced maximum radioprotective effect. The LD50/30 was 7.18 Gray (Gy) (95% confidence interval [CI]: 6.59-7.77) and 8.78 Gy (95% CI: 8.14-9.50) for irradiation-only and the optimum nanocurcumin group (pre-irradiation group), respectively (dose reduction factor [DRF] = 1.22). Continued administration of nanocurcumin up to seven days post-irradiation resulted in no further radioprotection.
Conclusions: The results obtained in this study confirmed the efficacy of nanocurcumin as a radioprotective agent against radiation-induced mortality in mice. The specific characteristics of nanocurcumin, such as non-toxicity, edibility, availability, make this phytochemical as a potential radioprotective agent in the radiotherapy setting and radiation accidents. Further clinical studies are highly recommended.


1.Heger M, van Golen RF, Broekgaarden M, Michel MC. The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacol Rev. 2014; 66(1): 222-307.
2.Kunnumakkara AB, Bordoloi D, Padmavathi G, Monisha J, Roy NK, Prasad S, Aggarwal BB. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. 2017; 174(11): 1325-1348.
3.Verma V. Relationship and interactions of curcumin with radiation therapy. World J Clin Oncol. 2016; 7(3): 275-283.
4.Rauf A, Imran M, Orhan IE, Bawazeer S. Health perspectives of a bioactive compound curcumin: A review. Trends Food Sci Technol. 2018; 74: 33-45.
5.Aprotosoaie AC, Trifan A, Gille E, Petreus T, Bordeianu G, Miron A. Can phytochemicals be a bridge to develop new radioprotective agents?. Phytochem Rev. 2015; 14(4): 555-566.
6.Paul P, Unnikrishnan M, Nagappa A. Phytochemicals as radioprotective agents-A review. Indian J Nat Prod Resour. 2011; 2(2): 137-150.
7.C. Jagetia G. Radioprotective Potential of Plants and Herbs against the Effects of Ionizing Radiation. J Clin Biochem Nutr. 2007; 40(2): 74-81.
8.Kalman NS, Zhao SS, Anscher MS, Urdaneta AI. Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature. Int J Radiat Oncol Biol Phys. 2017; 98(3): 662-682.
9.Mishra K, Alsbeih G. Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development. 3 Biotech. 2017; 7(5): 292.
10.Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 2010; 62(7): 919-930.
11.Jagetia GC. Radioprotection and radiosensitization by curcumin. Adv Exp Med Biol. 2007; 595: 301-320.
12.Hewlings SJ, Kalman DS. Curcumin: A Review of Its' Effects on Human Health. Foods. 2017; 6(10): E92.
13.Liu W, Zhai Y, Heng X, Che FY, Chen W, Sun D, Zhai G. Oral bioavailability of curcumin: problems and advancements. J Drug Target. 2016; 24(8): 694-702.
14.Mollaei H, Babaei E. Therapeutic Potential of Novel Nano-Based Curcumin Compounds In Vitro and In Vivo. Asian Pac J Cancer Prev. 2017; 18(4): 885-888.
15.Lu PS, Inbaraj BS, Chen BH. Determination of oral bioavailability of curcuminoid dispersions and nanoemulsions prepared from Curcuma longa Linnaeus. J Sci Food Agric. 2018; 98(1): 51-63.
16.Gera M, Sharma N, Ghosh M, Huynh DL, Lee SJ, Min T, Kwon T, Jeong DK. Nanoformulations of curcumin: an emerging paradigm for improved remedial application. Oncotarget. 2017; 8(39): 66680-66698.
17.Albus U. Guide for the Care and Use of Laboratory Animals (8th edn): SAGE Publications Sage UK: London, England; 2012.
18.Singh VK, Romaine PL, Seed TM. Medical Countermeasures for Radiation Exposure and Related Injuries: Characterization of Medicines, FDA-Approval Status and Inclusion into the Strategic National Stockpile. Health physics. 2015; 108(6): 607-630.
19.Hosseinimehr SJ. Trends in the development of radioprotective agents. Drug Discov Today. 2007; 12(19-20): 794-805.
20.Yuhas JM, Storer JB. Chemoprotection against three modes of radiation death in the mouse. Int J Radiat Biol Relat Stud Phys Chem Med. 1969; 15(3): 233-237.
21.Stone HB, Coleman CN, Anscher MS, McBride WH. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 2003; 4(9): 529-536.
22.Spitz DR, Hauer-Jensen M. Ionizing Radiation-Induced Responses: Where Free Radical Chemistry Meets Redox Biology and Medicine. Antioxid Redox Signal. 2014; 20(9): 1407-1409.
23.Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007; 12(6): 738-747.
24.Millender LE. CHAPTER 14 - Complications of Radiation Therapy A2 - Eisele, David W. In: Smith RV, editor. Complications in Head and Neck Surgery (Second Edition). Philadelphia: Mosby; 2009; 167-179.
25.Koch CJ, Parliament MB, Brown JM, Urtasun RC. 4 - Chemical Modifiers of Radiation Response A2 - Hoppe, Richard T. In: Phillips TL, Roach M, editors. Leibel and Phillips Textbook of Radiation Oncology (Third Edition). Philadelphia: Content Repository Only. 2010; 55-68.
26.Fan X, Zhang C, Liu DB, Yan J, Liang HP. The clinical applications of curcumin: current state and the future. Curr Pharm Des. 2013; 19(11): 2011-2031.
27.Sunagawa Y, Katanasaka Y, Hasegawa K, Morimoto T. Clinical applications of curcumin. PharmaNutrition. 2015; 3(4): 131-135.
28.Ahmadi M, Agah E, Nafissi S, Jaafari MR, Harirchian MH, Sarraf P, Faghihi-Kashani S, Hosseini SJ, Ghoreishi A, Aghamollaii V, Hosseini M, Tafakhori A. Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial. Neurotherapeutics. 2018; 15(2): 430-438.
29.Alizadeh F, Javadi M, Karami AA, Gholaminejad F, Kavianpour M, Haghighian HK. Curcumin nanomicelle improves semen parameters, oxidative stress, inflammatory biomarkers, and reproductive hormones in infertile men: A randomized clinical trial. Phytother Res. 2018; 32(3): 514-521.
30.Dolati S, Aghebati-Maleki L, Ahmadi M, Marofi F, Babaloo Z, Ayramloo H, Jafarisavari Z, Oskouei H, Afkham A, Younesi V, Nouri M, Yousefi M. Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis, randomized, double-blind, placebo-controlled trial. J Cell Physiol. 2018; 233(7): 5222-5230.
31.Inano H, Onoda M. Radioprotective action of curcumin extracted from Curcuma longa LINN: inhibitory effect on formation of urinary 8-hydroxy-2'-deoxyguanosine, tumorigenesis, but not mortality, induced by gamma-ray irradiation. Int J Radiat Oncol Biol Phys. 2002; 53(3): 735-743.
32.Soltani B, Ghaemi N, Sadeghizadeh M, Najafi F. Redox maintenance and concerted modulation of gene expression and signaling pathways by a nanoformulation of curcumin protects peripheral blood mononuclear cells against gamma radiation. Chem-Biol Interact. 2016; 257: 81-93.
33.Shi H-s, Gao X, Li D, Zhang Q-w, Wang Y-s, Zheng Y, Cai L, Zhong R, Rui A, Li Z, Zheng H, Chen X, Chen L. A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation. Int J Nanomed. 2012; 7: 2601-2611.
34.Okunieff P, Xu J, Hu D, Liu W, Zhang L, Morrow G, Pentland A, Ryan JL, Ding I. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines. Int J Radiat Oncol Biol Phys. 2006; 65(3): 890-8.
35.Thekkekkara D, Basavan D, Chandna S, Nanjan MJ. A combination of resveratrol and 3,3'-diindolylmethane, a potent radioprotector. Int J Radiat Biol. 2018: 1-11.
36.Zangeneh M, Mozdarani H, Mahmoudzadeh A. Potent radioprotective effects of combined regimens of famotidine and vitamin C against radiation-induced micronuclei in mouse bone marrow erythrocytes. Radiat Environ Biophys. 2015; 54(2): 175-181.
37.Vasilyeva I, Bespalov V, Baranova A. Radioprotective combination of alpha-tocopherol and ascorbic acid promotes apoptosis that is evident by release of low-molecular weight DNA fragments into circulation. Int J Radiat Biol. 2015; 91(11): 872-877.
38.Damron TA, Horton JA, Naqvi A, Loomis RM, Margulies BS, Strauss JA, Farnum CE, Spadaro JA. Combination radioprotectors maintain proliferation better than single agents by decreasing early parathyroid hormone-related protein changes after growth plate irradiation. Radiat Res. 2006; 165(3): 350-358.
39.Singh VK, Fatanmi OO, Wise SY, Newman VL, Romaine PL, Seed TM. The Potentiation of the Radioprotective Efficacy of Two Medical Countermeasures, Gamma-tocotrienol and Amifostine, by a Combination Prophylactic Modality. Radiat Prot Dosimetry. 2016; 172(1-3): 302-310.
40.Zhang H, Yu T, Wen L, Wang HUI, Fei DAN, Jin C. Curcumin enhances the effectiveness of cisplatin by suppressing CD133(+) cancer stem cells in laryngeal carcinoma treatment. Exp Ther Med. 2013; 6(5): 1317-1321.
41.Baharuddin P, Satar N, Fakiruddin KS, Zakaria N, Lim MN, Yusoff NM, Zakaria Z, Yahaya BH.. Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines. Oncol Rep. 2016; 35(1): 13-25.
42.Yunos NM, Beale P, Yu JQ, Huq F. Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells. Anticancer Res. 2011; 31(4): 1131-1140.
43.Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S. Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male mice: possible role in protection against chemical carcinogenesis and toxicity. Pharmacol Toxicol. 2003; 92(1): 33-38.
44.Ak T, Gulcin I. Antioxidant and radical scavenging properties of curcumin. Chem-Biol Interact. 2008; 174(1): 27-37.
45.Nishinaka T, Ichijo Y, Ito M, Kimura M, Katsuyama M, Iwata K, Miura T, Terada T, Yabe-Nishimura C. Curcumin activates human glutathione S-transferase P1 expression through antioxidant response element. Toxicol Lett. 2007; 170(3): 238-247.
46.Biswas SK, McClure D, Jimenez LA, Megson IL, Rahman I. Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity. Antioxid Redox Signal. 2005; 7(1-2): 32-41.
47.Saadipoor A, Razzaghdoust A, Simforoosh N, Mahdavi A, Bakhshandeh M, Moghadam M, Abdollahi H, Mofid B. Randomized, double‐blind, placebo‐controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy. Phytother Res. 2018 Nov 14. 6230