Abstract
Sometimes, people can be exposed to moderate or high doses of radiation accidentally or through the environment. Radiation can cause great harm to several systems within organisms, especially the hematopoietic system. Several types of drugs protect the hematopoietic system against radiation damage in different ways. They can be classified as “synthetic drugs” and “natural compounds.” Their cellular mechanisms to protect organisms from radiation damage include free radical-scavenging, anti-oxidation, reducing genotoxicity and apoptosis, and alleviating suppression of the bone marrow. These topics have been reviewed to provide new ideas for the development and research of drugs alleviating radiation-induced damage to the hematopoietic system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ali H, Galal O, Urata Y, Goto S, Guo CY, Luo L, Abdelrahim E, Ono Y, Mostafa E, Li TS (2014) The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures. Biochem Biophys Res Commun 452:548–553. https://doi.org/10.1016/j.bbrc.2014.08.112
Amini P, Ashrafizadeh M, Motevaseli E, Najafi M, Shirazi A (2020) Mitigation of radiation-induced hematopoietic system injury by melatonin. Environ Toxicol 35:815–821. https://doi.org/10.1002/tox.22917
Banerjee S, Aykin-Burns N, Krager KJ, Shah SK, Melnyk SB, Hauer-Jensen M, Pawar SA (2016) Loss of C/EBPδ enhances IR-induced cell death by promoting oxidative stress and mitochondrial dysfunction. Free Radic Biol Med 99:296–307. https://doi.org/10.1016/j.freeradbiomed.2016.08.022
Banerjee S, Shah SK, Melnyk SB, Pathak R, Hauer-Jensen M, Pawar SA (2018) Cebpd is essential for gamma-tocotrienol mediated protection against radiation-induced hematopoietic and intestinal injury. Antioxidants (basel) 7:55. https://doi.org/10.3390/antiox7040055
Bartolini D, Wang Y, Zhang J, Giustarini D, Rossi R, Wang GY, Torquato P, Townsend DM, Tew KD, Galli F (2019) A seleno-hormetine protects bone marrow hematopoietic cells against ionizing radiation-induced toxicities. PLoS ONE 14:e0205626. https://doi.org/10.1371/journal.pone.0205626
Brackett CM, Greene KF, Aldrich AR, Trageser NH, Pal S, Molodtsov I, Kandar BM, Burdelya LG, Abrams SI, Gudkov AV (2021) Signaling through TLR5 mitigates lethal radiation damage by neutrophil-dependent release of MMP-9. Cell Death Discov 7:266. https://doi.org/10.1038/s41420-021-00642-6
Bunin DI, Bakke J, Green CE, Javitz HS, Fielden M, Chang PY (2020) Romiplostim (Nplate®) as an effective radiation countermeasure to improve survival and platelet recovery in mice. Int J Radiat Biol 96:145–154. https://doi.org/10.1080/09553002.2019.1605465
Cao J, Li H, Yuan R, Dong Y, Wu J, Wang M, Li D, Tian H, Dong H (2020) Protective effects of new aryl sulfone derivatives against radiation-induced hematopoietic injury. J Radiat Res 61:388–398. https://doi.org/10.1093/jrr/rraa009
Cao J, Peng X, Li H, Ren L, Xu T, Sun K, Zhang Y, Li D (2021) Ultrasound-assisted continuous-flow synthesis of PEGylated MIL-101(Cr) nanoparticles for hematopoietic radioprotection. Mater Sci Eng C 129:112369. https://doi.org/10.1016/j.msec.2021.112369
Cary L, Noutai D, Salber R, Fadiyimu O, Gross A, Almeida-Porada G, Kidane Y, Whitnall M (2019) Bone marrow endothelial cells influence function and phenotype of hematopoietic stem and progenitor cells after mixed neutron/gamma radiation. Int J Mol Sci 20:1795. https://doi.org/10.3390/ijms20071795
Chen Y, Ma X, Zhang M, Wang X, Wang C, Wang H, Guo P, Yuan W, Rudolph KL, Zhan Q, Ju Z (2014a) Gadd45a regulates hematopoietic stem cell stress responses in mice. Blood 123:851–862. https://doi.org/10.1182/blood-2013-05-504084
Chen JJ, Gao Y, Tian Q, Liang YM, Yang L (2014b) Platelet factor 4 protects bone marrow mesenchymal stem cells from acute radiation injury. Br J Radiol 87:20140184. https://doi.org/10.1259/bjr.20140184
Christensen DM, Iddins CJ, Sugarman SL (2014) Ionizing radiation injuries and illnesses. Emerg Med Clin N Am 32:245–265. https://doi.org/10.1016/j.emc.2013.10.002
Comazzetto S, Shen B, Morrison SJ (2021) Niches that regulate stem cells and hematopoiesis in adult bone marrow. Dev Cell 56(13):1848–1860. https://doi.org/10.1016/j.devcel.2021.05.018
Cornacchia S, La Tegola L, Maldera A, Pierpaoli E, Tupputi U, Ricatti G, Eusebi L, Salerno S, Guglielmi G (2020) Radiation protection in non-ionizing and ionizing body composition assessment procedures. Quant Imaging Med Surg 10:1723–1738. https://doi.org/10.21037/qims-19-1035
Da F, Guo J, Yao L, Gao Q, Jiao S, Miao X, Liu J (2021) Pretreatment with metformin protects mice from whole-body irradiation. J Radiat Res 62:618–625. https://doi.org/10.1093/jrr/rrab012
Di CX, Han L, Zhang H, Xu S, Mao AH, Sun C, Liu Y, Si J, Li HY, Zhou X, Liu B, Miao GY (2015) Diallyl disulfide attenuated carbon ion irradiation-induced apoptosis in mouse testis through changing the ratio of Tap73/ΔNp73 via mitochondrial pathway. Sci Rep 5:16020. https://doi.org/10.1038/srep16020
Dobrzyńska MM, Gajowik A, Radzikowska J (2016) The effect of in vivo resveratrol supplementation in irradiated mice on the induction of micronuclei in peripheral blood and bone marrow reticulocytes. Mutagenesis 31:393–399. https://doi.org/10.1093/mutage/gev084
Dong L, Yang Y, Lu Y, Lu C, Lv J, Jiang N, Xu Q, Gao Y, Chang Q, Liu X (2018) Radioprotective effects of dammarane sapogenins against 60 Co-induced myelosuppression in mice. Phytother Res 32:741–749. https://doi.org/10.1002/ptr.6027
Du J, Cheng Y, Dong S, Zhang P, Guo J, Han J, Gao F, Zhao H, Sun D, Cui J, Cai J, Liu C (2017) Zymosan-a protects the hematopoietic system from radiation-induced damage by targeting TLR2 signaling pathway. Cell Physiol Biochem 43:457–464. https://doi.org/10.1159/000480472
Du J, Zhang P, Zhao H, Dong S, Yang Y, Cui J, Gao F, Cai J, Liu C (2018) The mechanism for the radioprotective effects of zymosan-A in mice. J Cell Mol Med 22:2413–2421. https://doi.org/10.1111/jcmm.13538
Dutta A, Dahiya A, Verma S (2021) Quercetin-3-rutinoside protects against gamma radiation inflicted hematopoietic dysfunction by regulating oxidative, inflammatory, and apoptotic mediators in mouse spleen and bone marrow. Free Radic Res 55:230–245. https://doi.org/10.1080/10715762.2021.1914334
Einor D, Bonisoli-Alquati A, Costantini D, Mousseau TA, Møller AP (2016) Ionizing radiation, antioxidant response and oxidative damage: a meta-analysis. Sci Total Environ 548–549:463–471. https://doi.org/10.1016/j.scitotenv.2016.01.027
Estaphan S, Abdel-Malek R, Rashed L, Mohamed EA (2020) Cimetidine a promising radio-protective agent through modulating Bax/Bcl2 ratio: an in vivo study in male rats. J Cell Physiol 235:8495–8506. https://doi.org/10.1002/jcp.29692
Fang S, Chen S, Nurmi H, Leppänen VM, Jeltsch M, Scadden D, Silberstein L, Mikkola H, Alitalo K (2020a) VEGF-C protects the integrity of the bone marrow perivascular niche in mice. Blood 136:1871–1883. https://doi.org/10.1182/blood.2020005699
Fang T, Zhang Y, Chang VY, Roos M, Termini CM, Signaevskaia L, Quarmyne M, Lin PK, Pang A, Kan J, Yan X, Javier A, Pohl K, Zhao L, Scott P, Himburg HA, Chute JP (2020b) Epidermal growth factor receptor-dependent DNA repair promotes murine and human hematopoietic regeneration. Blood 136:441–454. https://doi.org/10.1182/blood.2020005895
Gaetani S, Monaco F, Bracci M, Ciarapica V, Impollonia G, Valentino M, Tomasetti M, Santarelli L, Amati M (2018) DNA damage response in workers exposed to low-dose ionising radiation. Occup Environ Med 75:724–729. https://doi.org/10.1136/oemed-2018-105094
Gillies M, Haylock R, Hunter N, Zhang W (2019) Risk of leukemia associated with protracted low-dose radiation exposure: updated results from the national registry for radiation workers study. Radiat Res 192:527–537. https://doi.org/10.1667/RR15358.1
Ha CT, Li XH, Fu D, Xiao M, Landauer MR (2013) Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation. Radiat Res 180:316–325. https://doi.org/10.1667/RR3326.1
Han X, Xue X, Zhao Y, Li Y, Liu W, Zhang J, Fan S (2017a) Rutin-enriched extract from Coriandrum sativum L. ameliorates ionizing radiation-induced hematopoietic injury. Int J Mol Sci 18:942. https://doi.org/10.3390/ijms18050942
Han X, Zhang J, Xue X, Zhao Y, Lu L, Cui M, Miao W, Fan S (2017b) Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the NRF2 pathway. Free Radic Biol Med 113:59–70. https://doi.org/10.1016/j.freeradbiomed.2017.09.014
Han X, Gao P, Zhang Y, Wang J, Sun F, Liu Q, Zhang S (2019) Protective effect of the antioxidative peptide SS31 on ionizing radiation-induced hematopoietic system damage in mice. Blood Cells Mol Dis 77:82–87. https://doi.org/10.1016/j.bcmd.2019.04.001
Harrold J, Gisleskog PO, Perez-Ruixo JJ, Delor I, Chow A, Jacqmin P, Melhem M (2020) Prediction of survival benefit of filgrastim in adult and pediatric patients with acute radiation syndrome. Clin Transl Sci 13:807–817. https://doi.org/10.1111/cts.12777
Hazbavi M, Zarei M, Nazaralivand R, Shahbazian H, Cheki M (2019) Protection from ionizing radiation-induced genotoxicity and apoptosis in rat BMCs by HESA-A: a new herbal-marine compound. J Bioenerg Biomembr 51:371–379. https://doi.org/10.1007/s10863-019-09808-5
Himburg HA, Doan PL, Quarmyne M, Yan X, Sasine J, Zhao L, Hancock GV, Kan J, Pohl KA, Tran E, Chao NJ, Harris JR, Chute JP (2017) Dickkopf-1 promotes hematopoietic regeneration via direct and niche-mediated mechanisms. Nat Med 23:91–99. https://doi.org/10.1038/nm.4251
Hourigan CS, Savani BN (2018) Leukaemia risk associated with low-dose radiation. Lancet Haematol 5:e324–e325. https://doi.org/10.1016/S2352-3026(18)30106-6
Hsieh WH, Lin IF, Ho JC, Chang PW (2017) 30 years follow-up and increased risks of breast cancer and leukaemia after long-term low-dose-rate radiation exposure. Br J Cancer 117:1883–1887. https://doi.org/10.1038/bjc.2017.350
Hsu WL, Preston DL, Soda M, Sugiyama H, Funamoto S, Kodama K, Kimura A, Kamada N, Dohy H, Tomonaga M, Iwanaga M, Miyazaki Y, Cullings HM, Suyama A, Ozasa K, Shore RE, Mabuchi K (2013) The incidence of leukemia, lymphoma and multiple myeloma among atomic bomb survivors: 1950–2001. Radiat Res 179:361–382. https://doi.org/10.1667/RR2892.1
Hu B, Jin C, Li HB, Tong J, Ouyang X, Cetinbas NM, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Yilmaz O, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA (2016) The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 354:765–768. https://doi.org/10.1126/science.aaf7532
Hu L, Yin X, Zhang Y, Pang A, Xie X, Yang S, Zhu C, Li Y, Zhang B, Huang Y, Tian Y, Wang M, Cao W, Chen S, Zheng Y, Ma S, Dong F, Hao S, Feng S, Ru Y, Cheng H, Jiang E, Cheng T (2021) Radiation-induced bystander effects impair transplanted human hematopoietic stem cells via oxidative DNA damage. Blood 137:3339–3350. https://doi.org/10.1182/blood.2020007362
Huang L, Zhang Z, Lv W, Zhang M, Yang S, Yin L, Hong J, Han D, Chen C, Swarts S (2013) Interleukin 11 protects bone marrow mitochondria from radiation damage. Adv Exp Med Biol 789:257–264. https://doi.org/10.1007/978-1-4614-7411-1_35
Huang P, Li X, Meng Y, Yuan B, Liu T, Jiao M, Wang X, Liu Y, Yin H (2019) Interleukin-33 regulates hematopoietic stem cell regeneration after radiation injury. Stem Cell Res Ther 10:123. https://doi.org/10.1186/s13287-019-1221-1
Jiang DW, Wang QR, Shen XR, He Y, Qian TT, Liu Q, Hou DY, Liu YM, Chen W, Ren X, Li KX (2017) Radioprotective effects of cimetidine on rats irradiated by long-term, low-dose-rate neutrons and 60Co γ-rays. Mil Med Res 4:7. https://doi.org/10.1186/s40779-017-0116-7
Joshi HA, Patwardhan RS, Sharma D, Sandur SK, Devarajan PV (2021) Pre-clinical evaluation of an innovative oral nano-formulation of baicalein for modulation of radiation responses. Int J Pharm 595:120181. https://doi.org/10.1016/j.ijpharm.2020.120181
Kang AD, Cosenza SC, Bonagura M, Manair M, Reddy MV, Reddy EP (2013) ON01210.Na (Ex-RAD®) mitigates radiation damage through activation of the AKT pathway. PLoS ONE 8:e58355. https://doi.org/10.1371/journal.pone.0058355
Karabulutoglu M, Finnon R, Imaoka T, Friedl AA, Badie C (2019) Influence of diet and metabolism on hematopoietic stem cells and leukemia development following ionizing radiation exposure. Int J Radiat Biol 95:452–479. https://doi.org/10.1080/09553002.2018.1490042
Katoch O, Khan GA, Dwarakanath BS, Agrawala PK (2012) Mitigation of hematopoietic radiation injury by diallyl sulphide. J Environ Pathol Toxicol Oncol 31:357–365. https://doi.org/10.1615/jenvironpatholtoxicoloncol.2013005833
Kawakatsu M, Urata Y, Imai R, Goto S, Ono Y, Nishida N, Li TS (2013) Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor cells in mice. PLoS ONE 8:e60023. https://doi.org/10.1371/journal.pone.0060023
Khan S, Adhikari JS, Rizvi MA, Chaudhury NK (2017) Melatonin attenuates 60 Co γ-ray-induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice. Environ Toxicol 32:501–518. https://doi.org/10.1002/tox.22254
Kiang JG, Zhai M, Bolduc DL, Smith JT, Anderson MN, Ho C, Lin B, Jiang S (2017) combined therapy of pegylated G-CSF and Alxn4100TPO improves survival and mitigates acute radiation syndrome after whole-body ionizing irradiation alone and followed by wound trauma. Radiat Res 188:476–490. https://doi.org/10.1667/RR14647.1
Kim JH, Thimmulappa RK, Kumar V, Cui W, Kumar S, Kombairaju P, Zhang H, Margolick J, Matsui W, Macvittie T, Malhotra SV, Biswal S (2014) NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation. J Clin Invest 124:730–741. https://doi.org/10.1172/JCI70812
Kim JS, Jang WS, Lee S, Son Y, Park S, Lee SS (2015) A study of the effect of sequential injection of 5-androstenediol on irradiation-induced myelosuppression in mice. Arch Pharm Res 38:1213–1222. https://doi.org/10.1007/s12272-014-0483-5
Kim A, Shim S, Kim MJ, Myung JK, Park S (2018) Mesenchymal stem cell-mediated Notch2 activation overcomes radiation-induced injury of the hematopoietic system. Sci Rep 8:9277. https://doi.org/10.1038/s41598-018-27666-w
Kumar A, Selvan TG, Tripathi AM, Choudhary S, Khan S, Adhikari JS, Chaudhury NK (2015) Sesamol attenuates genotoxicity in BMCs of whole-body γ-irradiated mice. Mutagenesis 30:651–661. https://doi.org/10.1093/mutage/gev026
Kumar A, Choudhary S, Adhikari JS, Chaudhury NK (2018) Sesamol ameliorates radiation induced DNA damage in hematopoietic system of whole body γ-irradiated mice. Environ Mol Mutagen 59:79–90. https://doi.org/10.1002/em.22118
Lee SG, Kalidindi TM, Lou H, Gangangari K, Punzalan B, Bitton A, Lee CJ, Vargas HA, Park S, Bodei L, Kharas MG, Singh VK, Kishore Pillarsetty NV, Larson SM (2021) γ-Tocotrienol-loaded liposomes for radioprotection from hematopoietic side effects caused by radiotherapeutic drugs. J Nucl Med 62:584–590. https://doi.org/10.2967/jnumed.120.244681
Legesse B, Kaur A, Kenchegowda D, Hritzo B, Culp WE, Moroni M (2019) Neulasta regimen for the hematopoietic acute radiation syndrome: effects beyond neutrophil recovery. Int J Radiat Oncol Biol Phys 103:935–944. https://doi.org/10.1016/j.ijrobp.2018.11.043
Li Q, Sun H, Xiao F, Wang X, Yang Y, Liu Y, Zhang Q, Wu C, Wang H, Wang LS (2014) Protection against radiation-induced hematopoietic damage in bone marrow by hepatocyte growth factor gene transfer. Int J Radiat Biol 90:36–44. https://doi.org/10.3109/09553002.2014.847294
Li D, Tian Z, Tang W, Zhang J, Lu L, Sun Z, Zhou Z, Fan F (2016) The protective effects of 5-methoxytryptamine-α-lipoic acid on ionizing radiation-induced hematopoietic injury. Int J Mol Sci 17:935. https://doi.org/10.3390/ijms17060935
Li X, Cui W, Hull L, Smith JT, Kiang JG, Xiao M (2018a) Effects of low-to-moderate doses of gamma radiation on mouse hematopoietic system. Radiat Res 190:612–622. https://doi.org/10.1667/RR15087.1
Li Y, Kong S, Yang F, Xu W (2018b) Protective effects of 2-amino-5,6-dihydro-4H-1,3-thiazine and its derivative against radiation-induced hematopoietic and intestinal injury in mice. Int J Mol Sci 19:1530. https://doi.org/10.3390/ijms19051530
Li K, Zhang J, Cao J, Li X, Tian H (2019) 1,4-Dithiothreitol treatment ameliorates hematopoietic and intestinal injury in irradiated mice: potential application of a treatment for acute radiation syndrome. Int Immunopharmacol 76:105913. https://doi.org/10.1016/j.intimp.2019.105913
Little MP, Wakeford R, Borrego D, French B, Zablotska LB, Adams MJ, Allodji R, de Vathaire F, Lee C, Brenner AV, Miller JS, Campbell D, Pearce MS, Doody MM, Holmberg E, Lundell M, Sadetzki S, Linet MS, Berrington de González A (2018) Leukaemia and myeloid malignancy among people exposed to low doses (< 100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies. Lancet Haematol 5:e346–e358. https://doi.org/10.1016/S2352-3026(18)30092-9
Liu L, Li H, Patterson AM, Plett PA, Sampson CH, Mohammad KS, Capitano ML, Singh P, Yao C, Orschell CM, Pelus LM (2022) Upregulation of SIRT1 contributes to dmPGE2-dependent radioprotection of hematopoietic stem cells. Stem Cell Rev Rep 18:1478–1494. https://doi.org/10.1007/s12015-022-10368-2
Long W, Zhang G, Dong Y, Li D (2018) Dark tea extract mitigates hematopoietic radiation injury with antioxidative activity. J Radiat Res 59:387–394. https://doi.org/10.1093/jrr/rrx072
Lu L, Dong J, Li D, Zhang J, Fan S (2016) 3,3′-Diindolylmethane mitigates total body irradiation-induced hematopoietic injury in mice. Free Radic Biol Med 99:463–471. https://doi.org/10.1016/j.freeradbiomed.2016.09.007
Lv W, Zhang M, Zhang Z, Huang L, Yang S, Yin L, Hong J, Han D, Chen C, Vidyasagar S, Okunieff P, Zhang L (2013) Amifostine acts upon mitochondria to stimulate growth of bone marrow and regulate cytokines. Adv Exp Med Biol 789:195–201. https://doi.org/10.1007/978-1-4614-7411-1_27
Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426. https://doi.org/10.1146/annurev-pharmtox-011112-140320
Martinel Lamas DJ, Carabajal E, Prestifilippo JP, Rossi L, Elverdin JC, Merani S, Bergoc RM, Rivera ES, Medina VA (2013) Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand. PLoS ONE 8:e69106. https://doi.org/10.1371/journal.pone.0069106
McBride WH, Schaue D (2020) Radiation-induced tissue damage and response. J Pathol 250:647–655. https://doi.org/10.1002/path.5389
Mu H, Sun J, Li L, Yin J, Hu N, Zhao W, Ding D, Yi L (2018) Ionizing radiation exposure: hazards, prevention, and biomarker screening. Environ Sci Pollut Res Int 25:15294–15306. https://doi.org/10.1007/s11356-018-2097-9
Nakajima T, Vares G, Ninomiya Y, Wang B, Katsube T, Tanaka K, Maruyama K, Nenoi M (2019) Diallyl disulfide mitigates DNA damage and spleen tissue effects after irradiation. Med Sci Monit 25:8920–8927. https://doi.org/10.12659/MSM.917207
Nikkilä A, Raitanen J, Lohi O, Auvinen A (2018) Radiation exposure from computerized tomography and risk of childhood leukemia: finnish register-based case-control study of childhood leukemia (FRECCLE). Haematologica 105:849–850. https://doi.org/10.3324/haematol.2019.245704
Nishiyama Y, Morita A, Wang B, Sakai T, Ramadhani D, Satoh H, Tanaka K, Sasatani M, Ochi S, Tominaga M, Ikushima H, Ueno J, Nenoi M, Aoki S (2021) Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice. Int J Radiat Biol 97:1241–1251. https://doi.org/10.1080/09553002.2021.1941377
O’Brien G, Cruz-Garcia L, Zyla J, Brown N, Finnon R, Polanska J, Badie C (2020) Kras mutations and PU.1 promoter methylation are new pathways in murine radiation-induced AML. Carcinogenesis 41:1104–1112. https://doi.org/10.1093/carcin/bgz175
Omer H (2021) Radiobiological effects and medical applications of non-ionizing radiation. Saudi J Biol Sci 28:5585–5592. https://doi.org/10.1016/j.sjbs.2021.05.071
Ott E, Kawaguchi Y, Kölbl D, Rabbow E, Rettberg P, Mora M, Moissl-Eichinger C, Weckwerth W, Yamagishi A, Milojevic T (2020) Molecular repertoire of Deinococcus radiodurans after 1 year of exposure outside the International Space Station within the Tanpopo mission. Microbiome 8:150. https://doi.org/10.1186/s40168-020-00927-5
Patterson AM, Liu L, Sampson CH, Plett PA, Li H, Singh P, Mohammad KS, Hoggatt J, Capitano ML, Orschell CM, Pelus LM (2020) A single radioprotective dose of prostaglandin E2 blocks irradiation-induced apoptotic signaling and early cycling of hematopoietic stem cells. Stem Cell Rep 15:358–373. https://doi.org/10.1016/j.stemcr.2020.07.004
Porter RL, Georger MA, Bromberg O, McGrath KE, Frisch BJ, Becker MW, Calvi LM (2013) Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury. Stem Cells 31:372–383. https://doi.org/10.1002/stem.1286
Puukila S, Lemon JA, Lees SJ, Tai TC, Boreham DR, Khaper N (2017) Impact of ionizing radiation on the cardiovascular system: a review. Radiat Res 188:539–546. https://doi.org/10.1667/RR14864.1
Qi Y, Chen S, Lu Y, Zhang Z, Wang S, Chen N, Shen M, Chen F, Chen M, Quan Y, Yang L, Xu Y, Su Y, Hu M, Wang J (2021) Grape seed proanthocyanidin extract ameliorates ionizing radiation-induced hematopoietic stem progenitor cell injury by regulating Foxo1 in mice. Free Radic Biol Med 174:144–156. https://doi.org/10.1016/j.freeradbiomed.2021.08.010
Qu X, Li Q, Zhang X, Wang Z, Wang S, Zhou Z (2019) Amentoflavone protects the hematopoietic system of mice against γ-irradiation. Arch Pharm Res 42:1021–1029. https://doi.org/10.1007/s12272-019-01187-0
Rageh MM, El-Gebaly RH, Abou-Shavey H, Amin DG (2015) Melanin nanoparticles (MNPs) provide protection against whole-body ɣ-irradiation in mice via restoration of hematopoietic tissues. Mol Cell Biochem 399:59–69. https://doi.org/10.1007/s11010-014-2232-y
Ramachandran L, Nair CKK (2012) Prevention of γ-radiation induced cellular genotoxicity by tempol: protection of hematopoietic system. Environ Toxicol Pharmacol Environ Toxicol Pharmacol 34:253–262. https://doi.org/10.1016/j.etap.2012.04.008
Rittase WB, McCart EA, Muir JM, Bouten RM, Slaven JE, Mungunsukh O, Bylicky MA, Wilkins WL, Lee SH, Gudmundsson KO, Di Pucchio T, Olsen CH, Du Y, Day RM (2021) Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome. PLoS ONE 16:e0256208. https://doi.org/10.1371/journal.pone.0256208
Rodrigues-Moreira S, Moreno SG, Ghinatti G, Lewandowski D, Hoffschir F, Ferri F, Gallouet AS, Gay D, Motohashi H, Yamamoto M, Joiner MC, Gault N, Romeo PH (2017) Low-dose irradiation promotes persistent oxidative stress and decreases self-renewal in hematopoietic stem cells. Cell Rep 20:3199–3211. https://doi.org/10.1016/j.celrep.2017.09.013
Sanguri S, Gupta D (2021) Prebiotic mannan oligosaccharide pretreatment improves mice survival against lethal effects of gamma radiation by protecting GI tract and hematopoietic systems. Front Oncol 11:677781. https://doi.org/10.3389/fonc.2021.677781
Sekhar KR, Freeman ML (2015) Nrf2 promotes survival following exposure to ionizing radiation. Free Radic Biol Med 88:268–274. https://doi.org/10.1016/j.freeradbiomed.2015.04.035
Shao L, Feng W, Li H, Gardner D, Luo Y, Wang Y, Liu L, Meng A, Sharpless NE, Zhou D (2014a) Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner. Blood 123:3105–3115. https://doi.org/10.1182/blood-2013-07-515619
Shao L, Luo Y, Zhou D (2014b) Hematopoietic stem cell injury induced by ionizing radiation. Antioxid Redox Signal 20:1447–1462. https://doi.org/10.1089/ars.2013.5635
Shimura T, Koyama M, Aono D, Kunugita N (2019) Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells. FASEB J 33:6867–6876. https://doi.org/10.1096/fj.201802246RR
Singh VK, Fatanmi OO, Wise SY, Carpenter A, Nakamura-Peek S, Serebrenik AA, Kaytor MD (2022) A novel oral formulation of BIO 300 confers prophylactic radioprotection from acute radiation syndrome in mice. Int J Radiat Biol 98:958–967. https://doi.org/10.1080/09553002.2021.1981556
Sinha M, Das DK, Manna K, Datta S, Ray T, Sil AK, Dey S (2012) Epicatechin ameliorates ionising radiation-induced oxidative stress in mouse liver. Free Radic Res 46:842–849. https://doi.org/10.3109/10715762.2012.684245
Skobowiat C, Brożyna AA, Janjetovic Z, Jeayeng S, Oak ASW, Kim TK, Panich U, Reiter RJ, Slominski AT (2018) Melatonin and its derivatives counteract the ultraviolet B radiation-induced damage in human and porcine skin ex vivo. J Pineal Res 65:e12501. https://doi.org/10.1111/jpi.12501
Song XR, Cheng YQ, Su DF, Liu AJ (2019) The Sirt1 activator resveratrol improved hematopoiesis in pancytopenia mice induced by irradiation. J Pharmacol Sci 140:79–85. https://doi.org/10.1016/j.jphs.2019.05.004
Song X, Yue Z, Nie L, Zhao P, Zhu K, Wang Q (2021) Biological functions of diallyl disulfide, a garlic-derived natural organic sulfur compound. Evid Based Complement Altern Med 2021:5103626. https://doi.org/10.1155/2021/5103626
Su B, Su J, Zeng Y, Ding E, Liu F, Tan T, Xia H, Wu YH, Zeng X, Ling H, Jiang H, Ai XH, Su Q (2018) Diallyl disulfide inhibits TGF-β1-induced upregulation of Rac1 and β-catenin in epithelial-mesenchymal transition and tumor growth of gastric cancer. Oncol Rep 39:2797–2806. https://doi.org/10.3892/or.2018.6345
Suman S, Maniar M, Fornace AJ Jr, Datta K (2012) Administration of ON 01210Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response. Radiat Oncol 7:6. https://doi.org/10.1186/1748-717X-7-6
Sun Z, Wu K, Lin Q, Fei H, Jiang H, Chen T, Yuan Y (2019) Toll-like receptor 4 protects against irradiation-induced hematopoietic injury by promoting granulopoiesis and alleviating marrow adipogenesis. Biochem Biophys Res Commun 520:420–427. https://doi.org/10.1016/j.bbrc.2019.10.027
Sundaramoorthy P, Wang Q, Zheng Z, Jiao Y, Chen BJ, Doan PL, Chao NJ, Kang Y (2017) Thioredoxin mitigates radiation-induced hematopoietic stem cell injury in mice. Stem Cell Res Ther 8:263. https://doi.org/10.1186/s13287-017-0711-2
Targhi RG, Banaei A, Saba V (2019) Radioprotective effect of grape seed extract against gamma irradiation in mouse bone marrow cells. J Cancer Res Ther 15:512–516. https://doi.org/10.4103/jcrt.JCRT_243_17
Tenkanidiyoor YS, Vasudeva V, Rao S, Gowda D, Rao C, Sanjeev G, Nalilu SK (2016) Haematopoietic, antioxidant and membrane stabilizing property of diallyl disulphide in irradiated mice. J Clin Diagn Res 10:BF01-5. https://doi.org/10.7860/JCDR/2016/16371.7246
Tiwari M, Dixit B, Parvez S, Agrawala PK (2017) EGCG, a tea polyphenol, as a potential mitigator of hematopoietic radiation injury in mice. Biomed Pharmacother 88:203–209. https://doi.org/10.1016/j.biopha.2016.12.129
Venkateswaran K, Shrivastava A, Agrawala PK, Prasad A, Kalra N, Pandey PR, Manda K, Raj HG, Parmar VS, Dwarakanath BS (2016) Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice. Sci Rep 6:37305. https://doi.org/10.1038/srep37305
Verbiest T, Bouffler S, Nutt SL, Badie C (2015) PU.1 downregulation in murine radiation-induced acute myeloid leukaemia (AML): from molecular mechanism to human AML. Carcinogenesis 36:413–419. https://doi.org/10.1093/carcin/bgv016
Verma S, Gupta ML, Kumar K (2020) A combined prophylactic modality of podophyllotoxin and rutin alleviates radiation induced injuries to the lymphohematopoietic system of mice by modulating cytokines, cell cycle progression, and apoptosis. Free Radic Res 54:497–516. https://doi.org/10.1080/10715762.2020.1805447
Wang K, Tepper JE (2021) Radiation therapy-associated toxicity: etiology, management, and prevention. CA Cancer J Clin 71:437–454. https://doi.org/10.3322/caac.21689
Wang K, Li PF, Han CG, Du L, Liu C, Hu M, Lian SJ, Liu YX (2014a) Protective effects of kojic acid on the periphery blood and survival of beagle dogs after exposure to a lethal dose of gamma radiation. Radiat Res 182:666–673. https://doi.org/10.1667/RR13823.1
Wang H, Yang YL, Zhang H, Yan H, Wu XJ, Zhang CZ (2014b) Administration of the resveratrol analogues isorhapontigenin and heyneanol-A protects mice hematopoietic cells against irradiation injuries. Biomed Res Int 2014:282657. https://doi.org/10.1155/2014/282657
Wang C, Zhou M, Li T, Wang Y, Xing B, Kong T, Dong W (2015) Effects of Scorpion venom peptide B5 on hematopoietic recovery in irradiated mice and the primary mechanisms. Sci Rep 5:15363. https://doi.org/10.1038/srep15363
Wang Y, Chang J, Li X, Pathak R, Sridharan V, Jones T, Mao XW, Nelson G, Boerma M, Hauer-Jensen M, Zhou D, Shao L (2017) Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice. PLoS ONE 12:e0189466. https://doi.org/10.1371/journal.pone.0189466
Wang X, Liao W, Chen J, Wu Y, Liu C, Chen S, Xu Y, Wang S, Su Y, Du C, Wang J (2021) Caffeic acid attenuates irradiation-induced hematopoietic stem cell apoptosis through inhibiting mitochondrial damage. Exp Cell Res 409:112934. https://doi.org/10.1016/j.yexcr.2021.112934
Wu T, Liu W, Fan T, Zhong H, Zhou H, Guo W, Zhu X (2020) 5-Androstenediol prevents radiation injury in mice by promoting NF-κB signaling and inhibiting AIM2 inflammasome activation. Biomed Pharmacother 121:109597. https://doi.org/10.1016/j.biopha.2019.109597
Xia L, Lin J, Su J, Oyang L, Wang H, Tan S, Tang Y, Chen X, Liu W, Luo X, Tian Y, Liang J, Su Q, Liao Q, Zhou Y (2019) Diallyl disulfide inhibits colon cancer metastasis by suppressing Rac1-mediated epithelial-mesenchymal transition. Onco Targets Ther 12:5713–5728. https://doi.org/10.2147/OTT.S208738
Xiao X, Luo H, Vanek KN, LaRue AC, Schulte BA, Wang GY (2015) Catalase inhibits ionizing radiation-induced apoptosis in hematopoietic stem and progenitor cells. Stem Cells Dev 24:1342–1351. https://doi.org/10.1089/scd.2014.0402
Xie X, Huang X, Tang H, Ye F, Yang L, Guo X, Tian Z, Xie X, Peng C, Xie X (2018) Diallyl disulfide inhibits breast cancer stem cell progression and glucose metabolism by targeting CD44/PKM2/AMPK signaling. Curr Cancer Drug Targets 18:592–599. https://doi.org/10.2174/1568009617666171024165657
Xu G, Wu H, Zhang J, Li D, Wang Y, Wang Y, Zhang H, Lu L, Li C, Huang S, Xing Y, Zhou D, Meng A (2015) Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice. Free Radic Biol Med 87:15–25. https://doi.org/10.1016/j.freeradbiomed.2015.05.045
Xu W, Yang F, Zhang Y, Shen X (2016) Protective effects of rosmarinic acid against radiation-induced damage to the hematopoietic system in mice. J Radiat Res 57:356–362. https://doi.org/10.1093/jrr/rrw021
Xue J, Du R, Ling S, Song J, Yuan X, Liu C, Sun W, Li Y, Zhong G, Wang Y, Yuan G, Jin X, Liu Z, Zhao D, Li Y, Xing W, Fan Y, Liu Z, Pan J, Zhen Z, Zhao Y, Yang Q, Li J, Chang YZ, Li Y (2022) Osteoblast derived exosomes alleviate radiation-induced hematopoietic injury. Front Bioeng Biotechnol 10:850303. https://doi.org/10.3389/fbioe.2022.850303
Yu H, Shen H, Yuan Y, XuFeng R, Hu X, Garrison SP, Zhang L, Yu J, Zambetti GP, Cheng T (2010) Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose gamma-irradiation. Blood 115:3472–3480. https://doi.org/10.1182/blood-2009-10-248278
Yu X, Li M, Zhu L, Li J, Zhang G, Fang R, Wu Z, Jin Y (2020) Amifostine-loaded armored dissolving microneedles for long-term prevention of ionizing radiation-induced injury. Acta Biomater 112:87–100. https://doi.org/10.1016/j.actbio.2020.05.025
Zeng H, Hu M, Lu Y, Zhang Z, Xu Y, Wang S, Chen M, Shen M, Wang C, Chen F, Du C, Tang Y, Su Y, Chen S, Wang J (2019) MicroRNA 34a promotes ionizing radiation-induced DNA damage repair in murine hematopoietic stem cells. FASEB J 33:8138–8147. https://doi.org/10.1096/fj.201802639R
Zhang H, Wang YA, Meng A, Yan H, Wang X, Niu J, Li J, Wang H (2013) Inhibiting TGFβ1 has a protective effect on mouse bone marrow suppression following ionizing radiation exposure in vitro. J Radiat Res 54:630–636. https://doi.org/10.1093/jrr/rrs142
Zhang J, Xue X, Han X, Yao C, Lu L, Li D, Hou Q, Miao W, Meng A, Fan S (2016) Vam3 ameliorates total body irradiation-induced hematopoietic system injury partly by regulating the expression of Nrf2-targeted genes. Free Radic Biol Med 101:455–464. https://doi.org/10.1016/j.freeradbiomed.2016.10.501
Zhang J, Xue X, Han X, Li Y, Lu L, Li D, Fan S (2017) Hydrogen-rich water ameliorates total body irradiation-induced hematopoietic stem cell injury by reducing hydroxyl radical. Oxid Med Cell Longev 2017:8241678. https://doi.org/10.1155/2017/8241678
Zhang P, Du J, Zhao H, Cheng Y, Dong S, Yang Y, Li B, Gao F, Sun X, Cai J, Liu C (2019) Radioprotective effects of roxadustat (FG-4592) in haematopoietic system. J Cell Mol Med 23:349–356. https://doi.org/10.1111/jcmm.13937
Zhong Y, Pouliot M, Downey AM, Mockbee C, Roychowdhury D, Wierzbicki W, Authier S (2021) Efficacy of delayed administration of sargramostim up to 120 hours post exposure in a nonhuman primate total body radiation model. Int J Radiat Biol 97(sup1):S100–S116. https://doi.org/10.1080/09553002.2019.1673499
Zhou J, Pang H, Li W, Liu Q, Xu L, Liu Q, Liu Y (2016) Effects of Lycium barbarum polysaccharides on apoptosis, cellular adhesion, and oxidative damage in bone marrow mononuclear cells of mice exposed to ionizing radiation injury. Biomed Res Int 2016:4147879. https://doi.org/10.1155/2016/4147879
Zhu L, Yu X, Li Q, Zhang Y, Jin Y, Du L (2021) Estriol dissolving microneedle patches for protection against ionizing radiation-induced injury. Eur J Pharm Sci 163:105881. https://doi.org/10.1016/j.ejps.2021.105881
Acknowledgements
This work was supported by Key Scientific Research Project of Hunan Health Commission (Grant No. 202102051816), Hunan Natural Science Foundation (Grant No. 2019JJ40238), Hunan Health Commission (Grant No. C2019096), the project of Hengyang Science and Technology Bureau (Grant No. 2020jh042), Hunan Provincial Natural Science Foundation of China (Grant No. 2019JJ50509), the Hunan Province Education Department (Grant No. 18C0479).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Wei, Y., Gong, Y., Wei, S. et al. Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments. Arch. Pharm. Res. 45, 558–571 (2022). https://doi.org/10.1007/s12272-022-01400-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-022-01400-7