[1]张源,杨福军,徐文清.辐射防护药物研究最新进展[J].国际放射医学核医学杂志,2017,41(5):353-358.[doi:10.3760/cma.j.issn.1673-4114.2017.05.009]
 Zhang Yuan,Yang Fujun,Xu Wenqing.Recent advances in radioprotective agents[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(5):353-358.[doi:10.3760/cma.j.issn.1673-4114.2017.05.009]
点击复制

辐射防护药物研究最新进展(/HTML)
分享到:

《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
41
期数:
2017年第5期
页码:
353-358
栏目:
综述
出版日期:
2017-09-25

文章信息/Info

Title:
Recent advances in radioprotective agents
作者:
张源 杨福军 徐文清
300192 天津, 中国医学科学院放射医学研究所, 天津市放射医学与分子核医学重点实验室
Author(s):
Zhang Yuan Yang Fujun Xu Wenqing
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China
关键词:
辐射防护药胃肠综合征造血综合征电离辐射临床研究
Keywords:
Radioprotective agentsGastrointestinal syndromeHematopoietic syndromeIonizing radiationClinical research
DOI:
10.3760/cma.j.issn.1673-4114.2017.05.009
摘要:
电离辐射损伤不仅是一个公众健康问题,同时也是一个国家安全问题。如何获得治疗效果优良、安全性高和不良反应小的辐射防护药物一直是科学家努力研究的目标。近年来,伴随着分子生物学、免疫学等学科的发展,辐射防护药物的研究也取得了较大的突破。目前,诸如5-雄烯二醇(5-AED)、CBLB502、Ex-RAD和HemaMax等药物已获得美国食品药品监督管理局的批准进入临床试验;而新发现的具有潜在价值的LY294002和17-DMAG等药物也正处于研发之中。笔者基于近年来辐射防护领域国外相关刊物和专利的最新发现和进展进行综述。重点放在近几年来出现的药物新进展以及这一时间内治疗急性放射综合征的抗辐射新药上。
Abstract:
Ionizing radiation damage is not only a public health problem but is also a national security issue. Excellent treatment effect, high safety, and small side effects of radioprotective agents have been the goal of scientists attempting to study this concern. In recent years, research on radioprotective agents, along with the development of molecular biology, immunology, and other disciplines, has reached an advanced breakthrough. At present, drugs such as 5-androstenediol (5-AED), CBLB502, Ex-RAD, and HemaMax have been approved by the US Food and Drug Administration for clinical trials, and newly discovered drugs such as LY294002 and 17 -DMAG are under development. This paper is based on the recent discoveries and progress of foreign -related publications and patents in the field of radiation protection. New advances in drugs, as well as anti-radiation drugs for acute radiation syndrome, have been the focus of recent studies.

参考文献/References:

[1] Whitnall MH, Villa V, Seed TM, et al. Molecular specificity of 5-androstenediol as a systemic radioprotectant in mice[J]. Immunoph-armacol Immunotoxicol, 2005, 27(1):15-32. DOI:10.1081/IPH-200051289.
[2] Whitnall MH, Elliott TB, Harding RA, et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice[J]. Int J Immunopharmacol, 2000, 22(1):1-14. DOI:10.1016/S0192-0561(99)00059-4.
[3] Kim JS, Jang WS, Lee S, et al. A study of the effect of sequential injection of 5-androstenediol on irradiation-induced myelosuppression in mice[J]. Arch Pharm Res, 2015, 38(6):1213-1222. DOI:10.1007/s12272-014-0483-5.
[4] Stickney DR, Dowding C, Garsd A, et al. 5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression[J]. Int Immunopharmacol, 2006, 6(11):1706-1713. DOI:10.1016/j.intimp.2006.07.005.
[5] Mark HW, Catherine L. W, Luann M, et al. Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice[J]. Immunopharmacol Immunotoxicol, 2002, 24(4):595-626. DOI:10.1081/IPH-120016038.
[6] Stickney DR, Dowding C, Authier S, et al. 5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression[J]. Int Immunopharmacol, 2007, 7(4):500-505. DOI:10.1016/j.intimp.2006.12.005.
[7] Singh VK, Shafran RL, Inal CE, et al. Effects of whole-body gamma irradiation and 5-androstenediol administration on serum G-CSF[J]. Immunopharmacol Immunotoxicol, 2005, 27(4):521-534. DOI:10.1080/08923970500416707.
[8] Grace MB, Singh VK, Rhee JG, et al. 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis[J]. J Radiat Res, 2012, 53(6):840-853. DOI:10.1093/jrr/rrs060.
[9] Stickney DR, Groothuis JR, Ahlem CA, et al. Preliminary clinical findings on NEUMUNE as a potential treatment for acute radiation syndrome[J]. J Radiol Prot, 2010, 30(4):687-698. DOI:10.1088/0952-4746/30/4/004.
[10] Nguyen HQ, Chupin VV, Prokhorov DI, et al. Creation and study of triterpenoid nanoparticles and radioprotective substance genistein[J]. Dokl Biochem Biophys, 2015, 464(1):338-340. DOI:10.1134/S160767291505018X.
[11] Day RM, Barshishat-Kupper M, Mog SR, et al. Genistein protects against biomarkers of delayed lung sequelae in mice surviving High-Dose total body irradiation[J]. Radiat Res, 2008, 49(4):361-372. DOI:10.1269/jrr.07121.
[12] Singh VK, Grace MB, Parekh VI, et al. Effects of genistein administration on cytokine induction in whole-body gamma irradiated mice[J]. Int Immunopharmacol, 2009, 9(12):1401-1410. DOI:10.1016/j.intimp.2009.08.012.
[13] Abernathy LM, Fountain MD, Rothstein SE, et al. Soy isoflavones promote radioprotection of normal lung tissue by inhibition of Radiation-Induced-Activation-of Macrophages-and-Neutrophils[J]. J Thorac Oncol, 2015, 10(12):1703-1712. DOI:10.1097/JTO. 0000000000000677.
[14] Davis TA, Clarke TK, Mog SR, et al. Subcutaneous administration of genistein prior to lethal irradiation supports multilineage,hematopoietic progenitor cell recovery and survival[J]. Int J Radiat Biol, 2009, 83(3):141-151. DOI:10.1080/09553000601132642.
[15] Yong Z, Man-Tian M. Genistein stimulates hematopoiesis and increases survival in irradiated mice[J]. Radiat Res, 2005, 46(4):425-33. DOI:10.1517/3794923930876.
[16] Dominello MM, Fountain MD, Rothstein SE, et al. Radiation injury to cardiac arteries and myocardium is reduced by soy isoflavones[J]. J Radiat Oncol, 2017, 6(3):307-315. DOI:10.1007/s13566-017-0301-z.
[17] Ha CT, Li XH, Fu D, et al. Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation[J]. Radiat Res, 2013, 180(3):316-325. DOI:10. 1667/RR3326.1.
[18] Dumont F, Le Roux A, Bischoff P. Radiation countermeasure agents:an update[J]. Expert Opin Ther Pat, 2010, 20(1):73-101. DOI:10.1517/13543770903490429.
[19] Zenk JL. New therapy for the prevention and prophylactic treatment of acute radiation syndrome[J]. Expert Opin Investig Drugs, 2007, 16(6):767-770. DOI:10.1517/13543784.16.6.767.
[20] Shi T, Li LQ, Zhou GC, et al. Toll-like receptor 5 agonist CBLB502 induces radioprotective effects in vitro[J]. Acta Biochim Biophys Sin (Shanghai), 2017, 49(6):487-495. DOI:10.1093/abbs/gmx034.
[21] Burdelya LG, Krivokrysenko VI, Tallant TC, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and Primate models[J]. Science, 2008, 320(5873):226-230. DOI:10. 1126/science.1154986.
[22] Toshkov IA, Gleiberman AS, Mett VL, et al. Mitigation of Radiation-Induced epithelial damage by the TLR5 agonist entolimod in a mouse model of fractionated head and neck irradiation[J]. Radiat Res,2017,187(5):570-580. DOI:10.1667/RR14514.1.
[23] Krivokrysenko VI, Shakhov AN, Singh VK, et al. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation counter-measure[J]. J Pharmacol Exp Ther, 2012, 343(2):497-508. DOI:10.1124/jpet.112.196071.
[24] Xu Y, Dong H, Ge C, et al. CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation[J]. Ann Transl Med, 2016, 4(16):301. DOI:10.21037/atm.2016.08.25.
[25] Colombo MP, Trinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy[J]. Cytokine Growth Factor Rev, 2002, 13(2):155-168. DOI:10.1016/S1359-6101(01)00032-6.
[26] Guo N, Wang WQ, Gong XJ, et al. Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients[J]. World J Clin Oncol, 2017, 8(2):158-167. DOI:10.5306/wjco.v8.i2.158.
[27] Chen T, Burke KA, Zhan Y, et al. IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation[J]. Exp Hematol, 2007, 35(2):203-213. DOI:10.1016/j.exphem.2006.10.002.
[28] Basile LA, Gallaher TK, Shibata D, et al. Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice[J/OL]. J Transl Med, 2008, 6:26[2017-06-02]. https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC2424034.DOI:10.1186/1479-5876-6-26.
[29] Gluzman-Poltorak Z, Vainstein V, Basile LA. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care:evidence for the development of a frontline radiation medical countermeasure[J]. Am J Hematol, 2014, 89(9):868-873. DOI:10.1002/ajh.23770.
[30] Gluzman-Poltorak Z, Vainstein V, Basile LA. Association of hematological nadirs and survival in a nonhuman Primate model of hematopoietic syndrome of acute radiation syndrome[J]. Radiat Res, 2015, 184(2):226-230. DOI:10.1667/RR13962.1.
[31] Suman S, Maniar M, Fornace AJ Jr, et al. Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response[J/OL]. Radiat Oncol, 2012, 7:6[2017-06-02]. http://dx.doi.org/10.1186/1748-717X-7-6.DOI:10.1186/1748-717X-7-6.
[32] Suman S, Datta K, Doiron K, et al. Radioprotective effects of ON 01210. Na upon oral administration[J]. J Radiat Res, 2012, 53(3):368-376. DOI:10.1269/jrr.11191.
[33] Zhou N, Feng T, Shen X, et al. Synthesis, characterization, and radioprotective activity of α, β-unsaturated aryl sulfone analogs and their Tempol conjugates[J]. Med Chem Comm, 2017, 8(5):1063-1068. DOI:10.1039/c7md00017k.
[34] Ghosh SP, Kulkarni S, Perkins MW, et al. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD (R) in mice[J]. J Radiat Res, 2012, 53(4):526-536. DOI:10.1093/jrr/rrs001.
[35] Zhang Y, Zhang XW, Rabbani ZN, et al. Oxidative stress mediates radiation lung injury by inducing apoptosis[J]. Int J Radiat Oncol Biol Phys, 2012, 83(2):740-748. DOI:10.1016/j.ijrobp.2011. 08. 005.
[36] Macvittie TJ, Gibbs A, Farese AM, et al. AEOL 10150 mitigates Radiation-Induced lung injury in the nonhuman Primate:morbidity and mortality are administration Schedule-Dependent[J]. Radiat Res, 2017, 187(3):298-318. DOI:10.1667/RR4413.1.
[37] Murigi FN, Mohindra P, Hung C, et al. Dose optimization study of AEOL 10150 as a mitigator of Radiation-Induced lung injury in CBA/J mice[J]. Radiat Res, 2015, 184(4):422-432. DOI:10.1667/RR14110.1.
[38] Kiang JG, Zhai M, Liao PJ, et al. Thrombopoietin receptor agonist mitigates hematopoietic radiation syndrome and improves survival after Whole-Body ionizing irradiation followed by wound trauma[J/OL]. Mediators Inflamm, 2017:9[2017-06-02]. http://dx.doi.org/10.1155/2017/7582079.DOI:10.1155/2017/7582079.
[39] Satyamitra M, Lombardini E, Graves IJ, et al. A TPO receptor agonist, ALXN4100TPO, mitigates Radiation-Induced lethality and stimulates hematopoiesis in CD2F1 mice[J]. Radiat Res, 2011, 175(6):746-758. DOI:10.1667/RR2462.1.
[40] Satyamitra M, Lombardini E, Peng T, et al. Preliminary nonclinical toxicity, pharmacokinetics, and pharmacodynamics of ALXN4100 TPO, a thrombopoietin receptor agonist, in CD2F1 mice[J]. Int J Toxicol, 2013, 32(2):100-112. DOI:10.1177/1091581813482336.
[41] Cary LH, Ngudiankama BF, Salber RE, et al. Efficacy of radiation countermeasures depends on radiation quality[J]. Radiat Res, 2012, 177(5):663-675. DOI:10.1667/RR2783.1.
[42] Cai Y, Wang W, Liang H, et al. Keratinocyte growth factor pretreatment prevents radiation-induced intestinal damage in a mouse model[J]. Scand J Gastroenterol, 2013, 48(4):419-426. DOI:10.3109/00365521.2013.772227.
[43] Finch PW, Mark Cross LJ, McAuley DF, et al. Palifermin for the protection and regeneration of epithelial tissues following injury:new findings in basic research and pre-clinical models[J]. J Cell Mol Med, 2013, 17(9):1065-1087. DOI:10.1111/jcmm.12091.
[44] Lucchese A, Matarese G, Ghislanzoni LH, et al. Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia[J]. Leuk Lymphoma, 2016, 57(4):820-827. DOI:10.3109/10428194.2015.1081192.
[45] Stiff PJ, Leinonen M, Kullenberg T, et al. Long-Term safety outcomes in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation treated with palifermin to prevent oral mucositis[J]. Biol Blood Marrow Transplant, 2016, 22(1):164-169. DOI:10.1016/j.bbmt.2015.08.018.
[46] Vadhan-Raj S, Goldberg JD, Perales MA, et al. Clinical applications of palifermin:amelioration of oral mucositis and other potential indications[J]. J Cell Mol Med, 2013, 17(11):1371-1384. DOI:10. 1111/jcmm.12169.
[47] Lazo JS, Sharlow ER, Epperly MW, et al. Pharmacologic profiling of phosphoinositide 3-kinase inhibitors as mitigators of ionizing radiation-induced cell death[J]. J Pharmacol Exp Ther, 2013, 347(3):669-680. DOI:10.1124/jpet.113.208421.
[48] Casey-Sawicki K, Zhang M, Kim S, et al. A basic fibroblast growth factor analog for protection and mitigation against acute radiation syndromes[J]. Health Phys, 2014, 106(6):704-712. DOI:10.1097/HP.0000000000000095.
[49] Saito K, Funayama T, Yokota Y, et al. Histone deacetylase inhibitors sensitize murine B16F10 melanoma cells to Carbon ion irradiation by inducing G1 phase arrest[J]. Biol Pharm Bull, 2017, 40(6):844-851. DOI:10.1248/bpb.b16-01025.
[50] Zhou Y, Niu J, Li S, et al. Radioprotective effects of valproic acid, a histone deacetylase inhibitor, in the rat brain[J]. Biomed Rep, 2015, 3(1):63-69. DOI:10.3892/br.2014.367.
[51] Miller AC, Cohen S, Stewart M, et al. Radioprotection by the histone deacetylase inhibitor phenylbutyrate[J]. Radiat Environ Biophys, 2011, 50(4):585-596. DOI:10.1007/s00411-011-0384-7.
[52] Lu X, Nurmemet D, Bolduc DL, et al. Radioprotective effects of oral 17-dimethylaminoethylamino-17-demethoxygeldanamycin in mice:bone marrow and small intestine[J/OL]. Cell Biosci, 2013, 3(1):36[2017-06-02]. http://dx.doi.org/10.1186/2045-3701-3-36.DOI:10.1186/2045-3701-3-36.
[53] Kiang JG, Zhai M, Liao PJ, et al. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn[J/OL]. Oxid Med Cell Longev, 2014:481392[2017-06-02]. https://www.ncbi.nlm.nih.gov/pubmed/?term=PMC3964894.DOI:10.1155/2014/481392.

相似文献/References:

[1]闵锐.辐射损伤防护药及细胞因子治疗研究动态[J].国际放射医学核医学杂志,2004,28(4):173.
 MIN Rui.Status of the research on radioprotective drugs and treatment of radiation damage by cytokines[J].International Journal of Radiation Medicine and Nuclear Medicine,2004,28(5):173.

备注/Memo

备注/Memo:
收稿日期:2017-06-22。
基金项目:国家自然科学基金(81273005);中国医学科学院放射医学研究所发展基金(SF1528)
通讯作者:徐文清,Email:xuwenqing@irm-cams.ac.cn
更新日期/Last Update: 2017-09-25