Medical Radiology and Radiation Safety. 2023. Vol. 68. № 5


S.A. Abdullaev1, 4, D.V. Saleeva1, M.V. Dushenko1, 2,
N.F. Raeva1, А.I. Abdullaeva1, G.D. Zasukhina1, 3, A.N. Osipov1, 2

Protective Properties of Compound Aicar in Vivo Exposed to Radiation

1 A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

2 N.N. Semenov Federal Research Center for Chemical Physics, Moscow, Russia

3 N.I. Vavilov Institute of General Genetics, Moscow, Russia

4 Institute of Theoretical and Experimental Biophysics, Pushchino, Russia

Contact person: S.A. Abdullaev, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


Purpose: To study the effect of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on the survival rate of mice and proportion of polychromatophilic erythrocytes (PCE) in the bone marrow cells with micronuclei (MN), as well as post-irradiation urinary excretion of cell-free nuclear DNA (cf-nDNA) and mitochondrial DNA (cf-mtDNA) in rats.

Material and methods: Male Balb/c mice aged 2 months and Fisher-344 male rats aged 3 months were used. To determine the survival rate of mice, X-irradiation was performed at a dose of 8 Gy, and to analysis the proportion of PCE in the bone marrow cells with MN, at a dose of 2 Gy. Rats were X-irradiated at a dose of 5 Gy. AICAR was administered to animals intraperitoneally at a dose of 400 mg/kg. The drug was administered 30 min before and 20 min after irradiation of the animals. The DNA content was measured by real-time PCR.

Results: The results of the study showed that the introduction of AICAR causes a statistically significant increase in the survival rate of irradiated animals. The greatest effect was shown in the group of mice treated with AICAR 20 min after their irradiation at a lethal dose. The introduction of AICAR before irradiation reduces the proportion of PCE with MN by 30 %, and after irradiation ‒ by 70 %, in comparison to the control. AICAR promoted enhanced urinary excretion of cf-nDNA and cf-mtDNA fragments in rats after irradiation.

Conclusion: The results show that AICAR acts as a radiomitigation effector and promotes active DNA excretion of damaged cell from animal tissues in the post-radiation period.

Keywords: X-rays, AICAR, survival rate, micronuclei, cell-free DNA in the urine, rats, mice

For citation: Abdullaev SA, Saleeva DV, Dushenko MV, Raeva NF, Abdullaeva АI, Zasukhina GD, Osipov AN. Protective Properties of Compound Aicar in Vivo Exposed to Radiation. Medical Radiology and Radiation Safety. 2023;68(5):5–10. (In Russian). DOI:10.33266/1024-6177-2023-68-5-5-10



1. Jackson S.P., Bartek J. The DNA-Damage Response in Human Biology and Disease. Nature. 2009;461;7267:1071-1078. doi: 10.1038/nature08467.

2. Iyama T., Wilson D.M., 3rd. DNA Repair Mechanisms in Dividing and Non-Dividing Cells. DNA Repair (Amst). 2013;12;8:620-636. doi: 10.1016/j.dnarep.2013.04.015.

3. Wan G., Liu Y., Han C., Zhang X., Lu X. Noncoding RNAs in DNA Repair and Genome Integrity. Antioxid Redox Signal. 2014;20;4:655-677. doi: 10.1089/ars.2013.5514.

4. Clapier C.R., Cairns B.R. The Biology of Chromatin Remodeling Complexes. Annu. Rev. Biochem. 2009;78:273-304. doi: 10.1146/annurev.biochem.77.062706.153223.

5. House N.C., Koch M.R., Freudenreich C.H. Chromatin Modifications and DNA Repair: Beyond Double-Strand Breaks. Front. Genet. 2014;5:296. doi: 10.3389/fgene.2014.00296.

6. Christmann M., Kaina B. Transcriptional Regulation of Human DNA Repair Genes Following Genotoxic Stress: Trigger Mechanisms, Inducible Responses and Genotoxic Adaptation. Nucleic Acids Res. 2013;41;18:8403-8420. doi: 10.1093/nar/gkt635.

7. Ding L.H., Shingyoji M., Chen F., Hwang J.J., Burma S., Lee C., et al. Gene Expression Profiles of Normal Human Fibroblasts after Exposure to Ionizing Radiation: A Comparative Study of Low and High Doses. Radiat. Res. 2005;164;1:17-26. doi: 10.1667/rr3354.

8. Finn K., Lowndes N.F., Grenon M. Eukaryotic DNA Damage Checkpoint Activation in Response to Double-Strand Breaks. Cell. Mol. Life Sci. 2012;69;9:1447-1473. doi: 10.1007/s00018-011-0875-3.

9. Lim S., Kaldis P. Cdks, Cyclins and CKIs: Roles Beyond Cell Cycle Regulation. Development. 2013;140;15:3079-3093. doi: 10.1242/dev.091744.

10. Nosel I., Vaurijoux A., Barquinero J.F., Gruel G. Characterization of Gene Expression Profiles at Low and Very Low Doses of Ionizing Radiation. DNA Repair (Amst). 2013;12;7:508-517. doi: 10.1016/j.dnarep.2013.04.021.

11. Bonner W.M., Redon C.E., Dickey J.S., Nakamura A.J., Sedelnikova O.A., Solier S., et al. GammaH2AX and Cancer. Nat. Rev. Cancer. 2008;8;12:957-967. doi: 10.1038/nrc2523.

12. Hoeijmakers J.H. DNA Damage, Aging, and Cancer. N. Engl. J. Med. 2009;361;15:1475-1485. doi: 10.1056/NEJMra0804615.

13. Caldecott K.W. Protein ADP-Ribosylation and the Cellular Response to DNA Strand Breaks. DNA Repair (Amst). 2014;19:108-113. doi: 10.1016/j.dnarep.2014.03.021.

14. Andrabi S.A., Umanah G.K., Chang C., Stevens D.A., Karuppagounder S.S., Gagne J.P., et al. Poly(ADP-ribose) Polymerase-Dependent Energy Depletion Occurs Through Inhibition of Glycolysis. Proc. Natl. Acad. Sci. USA. 2014;111;28:10209-10214. doi: 10.1073/pnas.1405158111.

15. David K.K., Andrabi S.A., Dawson T.M., Dawson V.L. Parthanatos, a Messenger of Death. Front. Biosci. (Landmark Ed). 2009;14;3:1116-1128. doi: 10.2741/3297.

16. Газиев А.И. пути сохранения целостности митохондриальной днк и функций митохондрий в клетках, подвергшихся воздействию ионизирующей радиации // Радиационная биология. Радиоэкология. 2013. Т.53, № 2. С. 117-136. doi: 10.7868/s0869803113020045. [Gaziev A.I. Pathways for Maintenance of Mitochondrial DNA Integrity and Mitochondrial Functions in Cells Exposed to Ionizing Radiation. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 2013;53;2:117-136. doi: 10.7868/s0869803113020045. (In Russ.)].

17. Hardie D.G. AMP-Activated Protein Kinase: Maintaining Energy Homeostasis at the Cellular and Whole-Body Levels. Annu. Rev. Nutr. 2014;34:31-55. doi: 10.1146/annurev-nutr-071812-161148.

18. Oakhill J.S., Steel R., Chen Z.P., Scott J.W., Ling N., Tam S., et al. AMPK Is a Direct Adenylate Charge-Regulated Protein Kinase. Science. 2011;332;6036:1433-1435. doi: 10.1126/science.1200094.

19. Wang Z., Liu P., Chen Q., Deng S., Liu X., Situ H., et al. Targeting AMPK Signaling Pathway to Overcome Drug Resistance for Cancer Therapy. Curr. Drug. Targets. 2016;17;8:853-864. doi: 10.2174/1389450116666150316223655.

20. Kim H.J., Kim Y.J., Seong J.K. AMP-Activated Protein Kinase Activation in Skeletal Muscle Modulates Exercise-Induced Uncoupled Protein 1 Expression in Brown Adipocyte in Mouse Model. J. Physiol. 2022;600;10:2359-2376. doi: 10.1113/JP282999.

21. Si W., Xie Y., Dong J., Wang C., Zhang F., Yue J., et al. AMPK Activation Enhances Neutrophil’s Fungicidal Activity in Vitro and Improves the Clinical Outcome of Fusarium Solani Keratitis in Vivo. Curr. Eye Res. 2022;47;8:1131-1143. doi: 10.1080/02713683.2022.2078494.

22. Tripathi V., Jaiswal P., Assaiya A., Kumar J., Parmar H.S. Anti-Cancer Effects of 5-Aminoimidazole-4-Carboxamide-1-beta-D-Ribofuranoside (AICAR) on Triple-negative Breast Cancer (TNBC) Cells: Mitochondrial Modulation as an Underlying Mechanism. Curr. Cancer Drug. Targets. 2022;22;3:245-256. doi: 10.2174/1568009622666220207101212.

23. Wu Y., Duan X., Gao Z., Yang N., Xue F. AICAR Attenuates Postoperative Abdominal Adhesion Formation by Inhibiting Oxidative Stress and Promoting Mesothelial Cell Repair. PLoS One. 2022;17;9:e0272928. doi: 10.1371/journal.pone.0272928.

24. Schmid W. The Micronucleus Test. Mutat. Res. 1975;31;1:9-15. doi: 10.1016/0165-1161(75)90058-8.

25. Visnjic D., Lalic H., Dembitz V., Tomic B., Smoljo T. AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review. Cells. 2021;10;5. doi: 10.3390/cells10051095.

26. Kobashigawa S., Kashino G., Suzuki K., Yamashita S., Mori H. Ionizing Radiation-Induced Cell Death is Partly Caused by Increase of Mitochondrial Reactive Oxygen Species in Normal Human Fibroblast Cells. Radiat. Res. 2015;183;4:455-464. doi: 10.1667/RR13772.1.

27. Zhang B., Davidson M.M., Zhou H., Wang C., Walker W.F., Hei T.K. Cytoplasmic Irradiation Results in Mitochondrial Dysfunction and DRP1-Dependent Mitochondrial Fission. Cancer Res. 2013;73;22:6700-6710. doi: 10.1158/0008-5472.CAN-13-1411.

28. Azzam E.I., Jay-Gerin J.P., Pain D. Ionizing Radiation-Induced Metabolic Oxidative Stress and Prolonged Cell Injury. Cancer Lett. 2012;327;1-2:48-60. doi: 10.1016/j.canlet.2011.12.012.

29. Kawashima H., Ozawa Y., Toda E., Homma K., Osada H., Narimat-
su T., et al. Neuroprotective and Vision-Protective Effect of Preserving ATP Levels by AMPK Activator. FASEB J. 2020;34;4:5016-5026. doi: 10.1096/fj.201902387RR.

30. Habib S.L., Yadav A., Kidane D., Weiss R.H., Liang S. Novel Protective Mechanism of Reducing Renal Cell Damage in Diabetes: Activation AMPK by AICAR Increased NRF2/OGG1 Proteins and Reduced Oxidative DNA Damage. Cell. Cycle. 2016;15;22:3048-3059. doi: 10.1080/15384101.2016.1231259

31. Krishnan U.A., Viswanathan P., Venkataraman A.C. AMPK Activation by AICAR Reduces Diet Induced Fatty Liver in C57BL/6 Mice. Tissue Cell. 2023;82:102054. doi: 10.1016/j.tice.2023.102054.

32. Pyla R., Hartney T.J., Segar L. AICAR Promotes Endothelium-Independent Vasorelaxation by Activating AMP-Activated Protein Kinase Via Increased ZMP and Decreased ATP/ADP Ratio in Aortic Smooth Muscle. J. Basic. Clin. Physiol. Pharmacol. 2022;33;6:759-768. doi: 10.1515/jbcpp-2021-0308.

33. Sanli T., Steinberg G.R., Singh G., Tsakiridis T. AMP-Activated Protein Kinase (AMPK) Beyond Metabolism: A Novel Genomic Stress Sensor Participating in the DNA Damage Response Pathway. Cancer Biol. Ther. 2014;15;2:156-169. doi: 10.4161/cbt.26726.

34. Hinkle J.S., Rivera C.N., Vaughan R.A. AICAR Stimulates Mitochondrial Biogenesis and BCAA Catabolic Enzyme Expression in C2C12 Myotubes. Biochimie. 2022;195:77-85. doi: 10.1016/j.biochi.2021.11.004.

35. Dombi E., Mortiboys H., Poulton J. Modulating Mitophagy in Mitochondrial Disease. Curr. Med. Chem. 2018;25;40:5597-5612. doi: 10.2174/0929867324666170616101741.

36. Yamano K., Matsuda N., Tanaka K. The Ubiquitin Signal and Autophagy: an Orchestrated Dance Leading to Mitochondrial Degradation. EMBO Rep. 2016;17;3:300-316. doi: 10.15252/embr.201541486.

37. Tripathi A., Scaini G., Barichello T., Quevedo J., Pillai A. Mitophagy in Depression: Pathophysiology and Treatment Targets. Mitochondrion. 2021;61:1-10. doi: 10.1016/j.mito.2021.08.016. 



 PDF (RUS) Full-text article (in Russian)


Conflict of interest. The authors declare no conflict of interest.

Financing. The work was carried out on the topic of the A.I. Burnazyan Federal State Budgetary Research Center «Technology-3» (state task
No. 123011300105-3).

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.04.2023. Accepted for publication: 27.05.2023.