Pharmacological Modulation of Radiation Damage. Does It Exist a Chance for Other Substances than Hematopoietic Growth Factors and Cytokines?
Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články, přehledy
PubMed
28657605
PubMed Central
PMC5535878
DOI
10.3390/ijms18071385
PII: ijms18071385
Knihovny.cz E-zdroje
- Klíčová slova
- acute radiation syndrome, hematopoiesis, radiomitigators, radioprotectors,
- MeSH
- akutní radiační syndrom farmakoterapie prevence a kontrola MeSH
- cytokiny metabolismus MeSH
- hematopoetický systém účinky léků metabolismus MeSH
- lidé MeSH
- radioprotektivní látky terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cytokiny MeSH
- radioprotektivní látky MeSH
In recent times, cytokines and hematopoietic growth factors have been at the center of attention for many researchers trying to establish pharmacological therapeutic procedures for the treatment of radiation accident victims. Two granulocyte colony-stimulating factor-based radiation countermeasures have been approved for the treatment of the hematopoietic acute radiation syndrome. However, at the same time, many different substances with varying effects have been tested in animal studies as potential radioprotectors and mitigators of radiation damage. A wide spectrum of these substances has been studied, comprising various immunomodulators, prostaglandins, inhibitors of prostaglandin synthesis, agonists of adenosine cell receptors, herbal extracts, flavonoids, vitamins, and others. These agents are often effective, relatively non-toxic, and cheap. This review summarizes the results of animal experiments, which show the potential for some of these untraditional or new radiation countermeasures to become a part of therapeutic procedures applicable in patients with the acute radiation syndrome. The authors consider β-glucan, 5-AED (5-androstenediol), meloxicam, γ-tocotrienol, genistein, IB-MECA (N⁶-(3-iodobezyl)adenosine-5'-N-methyluronamide), Ex-RAD (4-carboxystyryl-4-chlorobenzylsulfone), and entolimod the most promising agents, with regards to their contingent use in clinical practice.
Zobrazit více v PubMed
Dörr H., Meineke V. Acute radiation syndrome caused by accidental radiation exposure—Therapeutic principles. BMC Med. 2011;9:1–6. doi: 10.1186/1741-7015-9-126. PubMed DOI PMC
Pellmar T.C., Rockwell S. Priority list of research areas for radiological nuclear threat countermeasures. Radiat. Res. 2005;163:115–123. doi: 10.1667/RR3283. PubMed DOI
Singh V.K., Romaine P.L.P., Newman V.L., Seed T.M. Medical countermeasures for unwanted CBRN exposures: Part II radiological and nuclear threats with review of recent countermeasure patents. Expert Opin. Ther. Pat. 2016;26:1399–1408. doi: 10.1080/13543776.2016.1231805. PubMed DOI PMC
Singh V.K., Romaine P.L.P., Seed T.M. Medical countermeasures for radiation exposure and related injuries: Charcaterization of medicines, FDA-approval status and inclusion into the strategic national stockpile. Health Phys. 2015;108:607–630. doi: 10.1097/HP.0000000000000279. PubMed DOI PMC
Strohl W.R. Fusion proteins for half-life extension of biologics as a strategy to make biobetters. BioDrugs. 2015;29:215–239. doi: 10.1007/s40259-015-0133-6. PubMed DOI PMC
Hérodin F., Roy L., Grenier N., Delaunay C., Bauge S., Vaurijoux A., Gregoire E., Martin C., Alonso A., Mayol L.F., et al. Antiapoptotic cytokines in combination with pegfilgrastim soon after irradiation mitigate myelosuppression in nonhuman primates exposed to high radiation dose. Exp. Hematol. 2007;35:1172–1181. doi: 10.1016/j.exphem.2007.04.017. PubMed DOI
Hirouchi T., Ito K., Nakano M., Monzen S., Yoshino H., Chiba M., Hazawa M., Nakano A., Ishikawa J., Yamaguchi M., et al. Mitigative effects of a combination of multiple pharmaceutical drugs on the survival of mice exposed to lethal ionizing radiation. Curr. Pharm. Biotechnol. 2016;17:190–199. doi: 10.2174/1389201016666150826125331. PubMed DOI
Singh V.K., Newman V.L., Seed T.M. Colony-stimulating factors for the treatment of the hematopoietic compartment of the acute radiation syndrome (H-ARS): A review. Cytokine. 2015;71:22–37. doi: 10.1016/j.cyto.2014.08.003. PubMed DOI
Dunlap J., Minami E., Bhagwat A.A., Keister D.L., Stacey G. Nodule development induced by mutants of Bradyrhizobium japonicum defective in cyclic β-glucan synthesis. Mol. Plant Microbe Interact. 1996;9:546–555. doi: 10.1094/MPMI-9-0546. PubMed DOI
Magnani M., Castro-Gomez R.H., Aoki M.N., Gregorio E.P., Libos F., Watanabe M.A.E. Effects of carboxymethyl-glucan from Saccharomyces cerevisiae on the peripheral blood of patients with advanced prostate cancer. Exp. Ther. Med. 2010;5:859–862. doi: 10.3892/etm.2010.121. DOI
Ohno N., Miura N.N., Nakajima M., Yadomae T. Antitumor 1,3-β-glucan from cultured fruit body of Sparassis crispa. Biol Pharm. Bull. 2000;23:866–872. doi: 10.1248/bpb.23.866. PubMed DOI
Chang R. Bioactive polysaccharides from traditional Chinese medicine herbs as anticancer adjuvants. J. Altern. Complement. Med. 2002;8:559–565. doi: 10.1089/107555302320825066. PubMed DOI
Patchen M.L., MacVittie T.J. Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of the immunomodulating agent glucan. Immunopharmacology. 1983;5:303–313. doi: 10.1016/0162-3109(83)90046-2. PubMed DOI
Pospíšil M., Jarý J., Netíková J., Marek M. Glucan-induced enhancement of hemopoietic recovery in γ-irradiated mice. Experientia. 1982;38:1232–1234. doi: 10.1007/BF01959759. PubMed DOI
Pospíšil M., Šandula J., Pipalová I., Hofer M., Viklická Š. Hemopoiesis stimulating and radioprotective effects of carboxymethylglucan. Physiol. Res. 1991;40:377–380. PubMed
Hofer M., Pospíšil M., Viklická Š., Pipalová I., Holá J., Šandula J. Effects of postirradiation carboxymethylglucan administration in mice. Int. J. Immunopharmacol. 1995;17:167–174. doi: 10.1016/0192-0561(95)00002-J. PubMed DOI
Hofer M., Pospíšil M., Pipalová I., Holá J., Šandula J. Haemopoiesis-enhancing effects of repeatedly administered carboxymethylglucan in mice exposed to fractionated irradiation. Folia Biol. 1995;41:249–256. PubMed
Hofer M., Pospíšil M. Glucan as stimulator of hematopoiesis in normal and γ-irradiated mice. A survey of the authors’ own results. Int. J. Immunopharmacol. 1997;19:607–609. doi: 10.1016/S0192-0561(97)00057-X. PubMed DOI
Patchen M.L., MacVittie T.J. In: Macrophages and Natural Killer Cells. Borman J.J., Sorkin E., editors. Plenum Publishing Corporation; New York, NY, USA: 1982. pp. 267–272.
Patchen M.L., MacVittie T.J. Stimulated hemopoiesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice. Int. J. Immunopharmacol. 1985;7:923–932. doi: 10.1016/0192-0561(85)90056-6. PubMed DOI
Patchen M.L., MacVittie T.J., Wathen L.M. Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells. Experientia. 1984;40:1240–1244. doi: 10.1007/BF01946654. PubMed DOI
Patchen M.L., MacVittie T.J., Brook I. Glucan-induced hemopoietic and immune stimulation: Therapeutic effects in sublethally and lethally irradiated mice. Meth. Find. Exp. Clin. Pharmacol. 1986;8:151–155. PubMed
Patchen M.L., D’Alesandro M.M., Brook I., Blakely W.F., MacVittie T.J. Glucan: Mechanisms involved in its “radioprotective” effect. J. Leukoc. Biol. 1987;42:95–105. PubMed
Patchen M.L., DiLuzio N.R., Jacques P., MacVittie T.J. Soluble polyglycans enhance recovery from cobalt-60-induced hemopoietic injury. J. Biol. Response Mod. 1984;3:627–633. PubMed
Patchen M.L., Brook I., Elliott T.B., Jackson W.E. Adverse effects of pefloxacin in irradiated C3H/HeN mice: Correction with glucan therapy. Antimicrob. Agents Chemother. 1993;37:1882–1889. doi: 10.1128/AAC.37.9.1882. PubMed DOI PMC
Pospíšil M., Netíková J., Pipalová I., Jarý J. Combined radioprotection by preirradiation peroral cystamine and postirradiation glucan administration. Folia Biol. 1991;37:117–124. PubMed
Patchen M.L., D’Alesandro M.M., Chirigos M.A., Weiss J.F. Radioprotection by biological response modifiers alone and in combination with WR-2721. Pharmacol. Ther. 1988;39:247–254. doi: 10.1016/0163-7258(88)90068-X. PubMed DOI
Patchen M.L., MacVittie T.J., Weiss J.F. Combined modality radioprotection: The use of glucan and selenium with WR-2721. Int. J. Radiat. Oncol. Biol. Phys. 1990;18:1069–1075. doi: 10.1016/0360-3016(90)90442-M. PubMed DOI
Patchen M.L., MacVittie T.J., Solberg B.D., Souza L.M. Survival enhancement and hemopoietic regeneration following radiation exposure: Therapeutic approach using glucan and granulocyte colony-stimulating factor. Exp. Hematol. 1990;18:1042–1048. PubMed
Pospíšil M., Hofer M., Pipalová I., Viklická Š., Netíková J., Šandula J. Enhancement of hematopoietic recovery in γ-irradiated mice by the joint use of diclofenac, an inhibitor of prostaglandin synthesis, and glucan, a macrophage activator. Exp. Hematol. 1992;20:891–896. PubMed
Hofer M., Pospíšil M., Viklická Š., Vacek A., Pipalová I., Bartoníčková A. Hematopoietic recovery in repeatedly irradiated mice can be enhanced by a repeatedly administered combination of diclofenac and glucan. J. Leukoc. Biol. 1993;53:185–189. PubMed
Hofer M., Pospíšil M. Modulation of animal and human hematopoiesis by β-glucans: A review. Molecules. 2011;16:7969–7979. doi: 10.3390/molecules16097969. PubMed DOI PMC
Cramer D.E., Allendorf D.J., Baran J.T., Hansen R., Marroquin J., Li B., Ratajcza J., Ratajczak M.Z. β-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury. Blood. 2006;107:835–840. doi: 10.1182/blood-2005-07-2705. PubMed DOI PMC
Salama S.F. β-glucan ameliorates γ-rays induced oxidative in jury in male Swiss albino rats. Pak. J. Zool. 2011;43:933–939.
Pillai T.G., Devi P.U. Mushroom β glucan: Potential candidate for post irradiation protection. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2013;751:109–115. doi: 10.1016/j.mrgentox.2012.12.005. PubMed DOI
Rondanelli M., Opizzi A., Monteferrario F. The biological activity of β-glucans. Minerva Med. 2009;3:237–245. PubMed
Whitnall M.H., Elliott T.B., Harding R.A., Inal C.E., Landauer M.R., Wilhelmsen C.L., McKinney L., Miner V.L., Jackson W.E., Loria R.M., et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in γ-irradiated mice. Int. J. Immunopharmacol. 2000;22:1–14. doi: 10.1016/S0192-0561(99)00059-4. PubMed DOI
Whitnall M.H., Inal C.E., Jackson W.E., Miner V.L., Villa V., Seed T.M. In vivo radioprotection by 5-androstenediol: Stimulation of the innate immune system. Radiat. Res. 2001;156:283–293. doi: 10.1667/0033-7587(2001)156[0283:IVRBAS]2.0.CO;2. PubMed DOI
Whitnall M.H., Wilhelmsen C.L., McKinney L., Miner V., Seed T.M., Jackson W.E. Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice. Immunopharmacol. Immunotoxicol. 2002;24:595–626. doi: 10.1081/IPH-120016038. PubMed DOI
Singh V.K., Shafran R.L., Inal C.E., Jackson W.E., Whitnal M.H. Effects of whole-body γ irradiation and 5-androstenediol administration on serum G-CSF. Immunopharmacol. Immunotoxicol. 2005;27:521–534. doi: 10.1080/08923970500416707. PubMed DOI
Whitnall M.H., Villa V., Seed T.M., Banjack J., Miner V., Lewbart M.L., Dowding C.A., Jackson W.E. Molecular specificity of 5-androstenediol as a systemic radioprotectant in mice. Immunopharmacol. Immunotoxicol. 2005;27:15–32. doi: 10.1081/IPH-51289. PubMed DOI
Stickney D.R., Dowding C., Garsd A., Ahlem C., Whitnall M., McKeon M., Reading C., Frincke J. 5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression. Int. Immunopharmacol. 2006;6:1706–1713. doi: 10.1016/j.intimp.2006.07.005. PubMed DOI
Stickney D.R., Dowding C., Authier S., Garsd A., Onizuka-Handa N., Reading C., Frincke J.M. 5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression. Int. Immunopharmacol. 2007;7:500–505. doi: 10.1016/j.intimp.2006.12.005. PubMed DOI
Xiao M., Inal C.E., Parekh V.I., Chang C.M., Whitnall M.H. 5-androstenediol promotes survival of γ-irradiated human hematopoietic progenitors through induction of nuclear factor-κB activation and granulocyte colony-stimulating factor expression. Mol. Pharmacol. 2007;72:370–379. doi: 10.1124/mol.107.035394. PubMed DOI
Singh V.K., Grace M.B., Jacobsen K.O., Chang C.M., Parekh V.L., Inal C.E., Shafran R.L., Whitnall A.D., Kao T.C., Jackson W.E., et al. Administration of 5-androstenediol to mice: Pharmacokinetics and cytokine gene expression. Exp. Mol. Pathol. 2008;84:178–188. doi: 10.1016/j.yexmp.2007.12.001. PubMed DOI
Grace M.B., Singh V.K., Rhee J.G., Jackson W.E., Kao T.C., Whitnall M.H. 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. Radiat. Res. 2012;53:840–853. doi: 10.1093/jrr/rrs060. PubMed DOI PMC
Arts-Kaya F.S.F., Visser T.P., Arshad S., Frincke J., Stickney D.R., Reading C.L., Wagemaker G. 5-androstene-3β,17β-diol promotes recovery of immature hematopoietic cells following myelosuppressive radiation and synergizes with thrombopoietin. Int. J. Radiat. Oncol. Biol. Phys. 2012;84:E401–E407. doi: 10.1016/j.ijrobp.2012.04.021. PubMed DOI
Kim J.S., Jang W.S., Lee S., Son Y., Park S., Lee S.S. A study of the effects of sequential injection of 5-androstenediol on radiation-induced myelosuppression in mice. Arch. Pharm. Res. 2015;38:1213–1222. doi: 10.1007/s12272-014-0483-5. PubMed DOI
Singh V.K., Newman V.L., Romaine P.L.P., Wise S.Y., Seed T.M. Radiation countermeasure agents: An update (2011–2014) Exp. Opin. Ther. Pat. 2014;24:1229–1255. doi: 10.1517/13543776.2014.964684. PubMed DOI PMC
Stickney D.R., Groothuis J.R., Ahlem C., Kennedy M., Miller B.S., Onizuka-Handa N., Schlangen K.M., Destiche D., Reading C., Garsd A., et al. Preliminary clinical findings on Nemunne as a potential treatment for acute radiation syndrome. J. Radiol. Prot. 2010;30:687–698. doi: 10.1088/0952-4746/30/4/004. PubMed DOI
Ainsworth E.J., Hatch M.H. Decreased X-ray mortality in endotoxin-treated mice. Radiat. Res. 1957;9:84.
Hanks G.E., Ainsworth E.J. Endotoxin protection and colony-forming units. Radiat. Res. 1967;32:367–382. doi: 10.2307/3572254. PubMed DOI
Opal S.M. Endotoxins and other sepsis triggers. Contrib. Nephrol. 2010;67:14–24. PubMed
Bertok L., Sztanyik L.B., Bertok L. The effect of kanamycin treatment of rats on the development of gastrointestinal syndrome of radiation disease. Acta Microbiol. Hung. 1992;39:155–158. PubMed
Fedoročko P., Brezáni P. Radioprotection of mice by the bacterial extract Broncho-Vaxom—Comparison of survival 5 inbred mouse strains. Int. J. Immunother. 1992;8:185–190. PubMed
Fedoročko P., Brezáni P., Macková N.O. Radioprotection of mice by the bacterial extract Broncho-Vaxom®—Hematopoietic stem-cells and survival enhancement. Int. J. Radiat. Biol. 1992;61:511–518. doi: 10.1080/09553009214551271. PubMed DOI
Macková N.O., Fedoročko P. Preirradiation hematological effects of the bacterial extract Broncho-Vaxom® and postirradiation acceleration recovery from radiation-induced hematopoietic depression. Drug Exp. Clin. Res. 1993;19:143–150. PubMed
Fedoročko P., Macková N.O., Kopka M. Administration of the bacterial extract Broncho-Vaxom® enhances radiation recovery and myelopoietic regeneration. Immunopharmacology. 1994;28:163–170. doi: 10.1016/0162-3109(94)90032-9. PubMed DOI
Fedorocko P., Brezani P., Mackova N.O. Radioprotective effects of WR-2721, Broncho-Vaxom® and their combinations—Survival, myelopoietic restoration and induction of colony-stimulating activity in mice. Int. J. Immunopharmacol. 1994;16:177–184. doi: 10.1016/0192-0561(94)90074-4. PubMed DOI
Macková N.O., Fedoročko P. Combined radioprotective effect of Broncho-Vaxom® and WR-2721 on hematopoiesis and circulating blood cells. Neoplasma. 1995;42:25–30. PubMed
Saada H.N., Azab K.S., Zahran A.M. Post-irradiation effect of Broncho-Vaxom, OM-85 BV, and its relationship to anti-oxidant activities. Pharmazie. 2001;56:654–656. PubMed
Madonna G.S., Ledney G.D., Elliott T.B., Brook I., Ulrich J.T., Myers K.R., Patchen M.L., Walker R.I. Trehalose dimycolate enhances resistence to infection in neutropenic animals. Infect. Immun. 1989;57:2495–2501. PubMed PMC
Madonna G.S., Ledney G.D., Moore M.M., Elliott T.B., Brook I. Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicornomycolate (S-TDCM) J. Trauma. 1991;31:316–325. doi: 10.1097/00005373-199103000-00003. PubMed DOI
Crescenti E., Croci M., Medina V., Sambucco L., Bergoc R., Rivera E. Radioprotective potential of a novel therapeutic formulation of oligoelements Se, Zn, Mn plus Lachesis muta venom. J. Radiat. Res. 2009;50:537–544. doi: 10.1269/jrr.09060. PubMed DOI
Crescenti E.J.V., Medina V.A., Croci M., Sambuco L.A., Prestifilippo J.P., Elverdin J.C., Bergoc R.M., Rivera E.S. Radioprotection of sensitive rat tissues by oligoelements Se, Zn, Mn plus Lachesis muta venom. J. Radiat. Res. 2011;52:557–567. doi: 10.1269/jrr.11031. PubMed DOI
Liu W., Chen Q., Wu S., Xia X.C., Wu A.Q., Cui F.M., Gu Y.P., Zhang X.G., Cao J.P. Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage. J. Radiat. Res. 2015;56:278–286. doi: 10.1093/jrr/rru100. PubMed DOI PMC
Li N., Shen X.R., Liu Y.M., Zhang J.L., He Y., Liu Q., Jiang D.W., Zong J., Li J.M., Hou D.Y., et al. Isolation, characterization, and radiation protection of Sipunculus nudus L. polysaccharide. Int. J. Biol. Macromol. 2016;83:288–296. doi: 10.1016/j.ijbiomac.2015.11.071. PubMed DOI
Cui F.M., Li M., Chen Y.J., Liu Y.M., He Y., Jiang D.W., Tong J., Li J.X., Shen X.R. Protective effects of polysaccharides from Sipunculus nudus on beagle dogs exposed to γ-radiation. PLoS ONE. 2014;9:e104299. doi: 10.1371/journal.pone.0104299. PubMed DOI PMC
Jiang S.Q., Shen X.R., Liu Y.M., He Y., Jiang D.W., Chen W. Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR-2721, rhIL-11 and rhG-CSF on radiation-injured mice. J. Radiat. Res. 2015;56:515–522. doi: 10.1093/jrr/rrv009. PubMed DOI PMC
Hanson W.R., Thomas C. 16,16-dimethyl prostaglandin-E2 increases survival of murine intestinal stem-cells when given before photon radiation. Radiat. Res. 1983;96:393–398. doi: 10.2307/3576222. PubMed DOI
Hanson W.R. Radiation protection of murine intestine by WR-2721, 16,16-dimethyl prostaglandin-E2, and the combination of both agents. Radiat. Res. 1987;111:361–373. doi: 10.2307/3576992. PubMed DOI
Hanson W.R., Houseman K.A., Nelson A.K., Collins P.W. Radiation protection of the murine intestine by misoprostol, a prostaglandin-E1 analog, given alone or with WR-2721, is stereospecific. Prostagl. Leukot. Essent. Fatty Acids. 1988;32:101–105. PubMed
Satoh H., Amagase K., Ebara S., Akiba Y., Takeuchi K. Cyclooxygenase (COX)-1 and COX-2 both play an important role in the protection of the duodenal mucosa in cats. J. Pharmacol. Exp. Ther. 2013;344:189–195. doi: 10.1124/jpet.112.199182. PubMed DOI
Mahmud T., Scott D.-L., Bjarnason I. A unifying hypothesis for the mechanism of NSAID related gastrointestinal toxicity. Ann. Rheum. Dis. 1996;55:211–231. doi: 10.1136/ard.55.4.211. PubMed DOI PMC
Hanson W.R., Ainsworth E.J. 16,16-dimethyl prostaglandin E2 induces radioprotection in murine intestinal and hematopoietic stem-cells. Radiat. Res. 1985;103:196–203. doi: 10.2307/3576574. PubMed DOI
Lu L., Pelus L.M., Broxmeyer H.E. Modulation of the expression of HLA-DR (Ia) antigens and the proliferation of human erythroid (BFU-E) and multipotential (CFU-GEMM) progenitor cells by prostaglandin E2. Exp. Hematol. 1984;12:741–748. PubMed
Lu L., Pelus L.M., Piacibello W., Moore M.A.S., Hu W., Broxmeyer H.E. Prostaglandin E acts at two levels to enhance colony formation in vitro by erythroid (BFU-E) progenitor cells. Exp. Hematol. 1987;15:765–771. PubMed
Kurland J., Moore M.A.S. Modulation of hemopoiesis by prostaglandins. Exp. Hematol. 1977;7:119–126. PubMed
Gentile P., Byer D., Pelus L.M. In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2. Blood. 1983;62:1100–1107. PubMed
Frölich J.C. A classification of NSAIDs according to the relative inhibition of cyclooxygenase isoenzymes. Trends Pharmacol. Sci. 1997;18:30–34. doi: 10.1016/S0165-6147(96)01017-6. PubMed DOI
Furuta Y., Hunter N., Barkley T., Hall E., Milas L. Increase in radioresponse of murine tumors by treatment with indomethacin. Radiat. Res. 1988;48:3008–3013. PubMed
Kozubík A., Pospíšil M., Netíková J. The stimulatory effect of single-dose pre-irradiation administration of indomethacin and dicofenac on hematopoietic recovery in the spleen of γ-irradiated mice. Studia Biophys. 1989;131:93–101.
Nishiguchi I., Furuta Y., Hunter N., Murray D., Milas L. Radioprotection of haematopoietic tissue by indomethacin. Radiat. Res. 1990;122:188–192. doi: 10.2307/3577605. PubMed DOI
Kozubík A., Hofmanová J., Holá J., Netíková J. The effect of nordihydroguairetic acid, an inhibitor of prostaglandin and leukotriene biosynthesis, on hematopoiesis of γ-irradiated mice. Exp. Hematol. 1993;21:138–142. PubMed
Pospíšil M., Netíková J., Kozubík A. Enhancement of haemopoietic recovery by indomethacin after sublethal whole-body γ irradiation. Acta Radiol. Oncol. 1986;25:195–198. doi: 10.3109/02841868609136404. PubMed DOI
Pospíšil M., Netíková J., Kozubík A., Pipalová I. Effect of indomethacin, diclofenac sodium and sodium salicylate on peripheral blood cell counts in sublethally γ-irradiated mice. Strahlenther. Onkol. 1989;165:627–631. PubMed
Serushago B.A., Tanaka K., Koga Y., Taniguchi K., Nomoto K. Positive effects of indomethacin on restoration of splenic nucleated cell population in mice given sublethal irradiation. Immunopharmacology. 1987;14:21–26. PubMed
Sklobovskaya I.E., Zhavoronkov L.P., Dubovik R.V. Haemostimulating efficiency of prostaglandin biosynthesis inhibitors in conditions of fractionated irradiation. Radiobiologiya. 1986;26:185–188. PubMed
Hofer M., Pospíšil M., Pipalová I. Radioprotective effects of flurbiprofen. Folia Biol. 1996;42:267–269. PubMed
Hofer M., Pospíšil M., Pipalová I., Holá J. Modulation of haemopoietic radiation response of mice by diclofenac in fractionated treatment. Physiol. Res. 1996;45:213–220. PubMed
Hofer M., Pospíšil M., Tkadleček L., Viklická Š., Pipalová I. Low survival of mice following lethal γ-irradiation after administration of inhibitors of prostaglandin synthesis. Physiol. Res. 1992;41:157–161. PubMed
Floersheim G.L. Allopurinol, indomethacin and riboflavin enhance radiation lethality in mice. Radiat. Res. 1994;139:240–247. doi: 10.2307/3578670. PubMed DOI
Hofer M., Pospíšil M., Hoferová Z., Weiterová L., Komůrková D. Stimulatory action of cyclooxygenase inhibitors on hematopoiesis. A review. Molecules. 2012;17:5615–5625. doi: 10.3390/molecules17055615. PubMed DOI PMC
Hofer M., Pospíšil M., Znojil V., Holá J., Vacek A., Weiterová L., Štreitová D., Kozubík A. Meloxicam, a cyclooxygenase-2 inhibitor, supports hematopoietic recovery in γ-irradiated mice. Radiat. Res. 2006;166:556–560. doi: 10.1667/RR3598.1. PubMed DOI
Hofer M., Pospíšil M., Znojil V., Holá J., Vacek A., Štreitová D. Meloxicam, an inhibitor of cyclooxygenase-2, increases the level of G-CSF and might be usable as an auxiliary means in G-CSF therapy. Physiol. Res. 2008;57:307–310. PubMed
Hofer M., Pospíšil M., Dušek L., Hoferová Z., Weiterová L. A single dose of an inhibitor of cyclooxygenase 2, meloxicam, administered shortly after irradiation increases survival of lethally irradiated mice. Radiat. Res. 2011;176:269–272. doi: 10.1667/RR2614.1. PubMed DOI
Hoggatt J., Singh P., Sampath J., Pelus L.M. Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood. 2009;113:5444–5455. doi: 10.1182/blood-2009-01-201335. PubMed DOI PMC
Hoggatt J., Singh P., Stilger K.N., Plett P.A., Sampson C.H., Chua H.L., Orschell C.M., Pelus L.M. Recovery from hematopoietic injury by modulating prostaglandin E2 signaling post-irradiation. Blood Cells Mol. Dis. 2013;50:147–153. doi: 10.1016/j.bcmd.2012.11.006. PubMed DOI PMC
Arora R., Gupta D., Chawla R., Sagar R., Sharma A., Kumar R., Prasad J., Singh S., Samanta N., Sharma R.K. Radioprotection by plant products: Present status and future prospects. Phytother. Res. 2005;19:1–22. doi: 10.1002/ptr.1605. PubMed DOI
Liu W.C., Wang S.C., Tsai M.L., Chen M.C., Wang Y.C., Hong J.H., McBride W.H., Chiang C.S. Protection against radiation-induced bone marrow and intestinal injuries by Cordyceps sinensis, a Chinese herbal medicine. Radiat. Res. 2006;166:900–907. doi: 10.1667/RR0670.1. PubMed DOI
Gupta M.L., Sankwar S., Verma S., Devi M., Samanta N., Agarwala P.K., Kumar R., Singh P.K. Whole-body protection to lethally irradiated mice by oral administration of semipurified fraction of Podophyllum hexandrum and post irradiation treatment with Picrorhizza kurroa. Tokai J. Exp. Clin. Med. 2008;33:6–12. PubMed
Lata M., Prasad J., Singh S., Kumar R., Singh L., Chaudhary P., Arora R., Chawla R., Tyagi S., Soni N.L., et al. Whoe body protection against lethal ionizing radiation in mice by REC-2001: A semi-purified fraction of Podophyllum hexandrum. Phytomedicine. 2009;16:47–55. doi: 10.1016/j.phymed.2007.04.010. PubMed DOI
Pratheeshkumar P., Kuttan G. Protective role of Vernonia cinerea L. against γ radiation-induced immunosuppression and oxidative stress in mice. Hum. Exp. Toxicol. 2011;30:1022–1038. doi: 10.1177/0960327110385959. PubMed DOI
Shakeri-Boroujeni A., Mozdaravi H., Mahmmoudzadeh M., Faeghi F. Potent radioprotective effect of herbal immunomodulator drug (IMOD) on mouse bone marrow erythrocytes as assayed by the micronucleus test. Int. J. Radiat. Res. 2016;14:221–228. doi: 10.18869/acadpub.ijrr.14.3.221. DOI
Wasserman T.H., Brizel D.M. The role of amifostine as a radioprotector. Oncolohy N. Y. 2001;15:1349–1354. PubMed
Upadhyay S.N., Dwarakanath B.S., Ravindranath T., Mathew T.L. Chemical radioprotectors. Def. Sci. J. 2005;55:402–425. doi: 10.14429/dsj.55.2003. DOI
Upadhay S.N., Ghose A. Radioprotection by chemical means with the help of combined regimen radio-protectors—A short review. J. Ind. Chem. Soc. 2017;94:321–325.
Mell L.K., Movsas B. Pharmacologic normal tissue protection in clinical radiation oncology: Focus on amifostine. Expert Opin. Drug Met. 2008;4:1341–1350. doi: 10.1517/17425255.4.10.1341. PubMed DOI
Gu J.D., Zhu S.W., Li X.B., Wu H., Li Y., Hua F. Effects of amifostine in head and neck cancer patients treated with radiotherapy: A systematic review and meta-analysis based on randomized controlled trials. PLoS ONE. 2014;9:e95968. doi: 10.1371/journal.pone.0095968. PubMed DOI PMC
Singh V.K., Fatanami O.O., Wise S.Y., Newman V.L., Romaine L.P., Seed T.M. The potentiation of the radioprotective efficacy of two medical countermeasures, γ-tocotrienol and amifostine, by a combination prophylactic modality. Radiat. Prot. Dosim. 2016;172:302–310. doi: 10.1093/rpd/ncw223. PubMed DOI PMC
Weiss J.F., Landauer M.R. Radioprotection by antioxidants. Ann. N. Y. Acad. Sci. 1998;899:44–60. doi: 10.1111/j.1749-6632.2000.tb06175.x. PubMed DOI
Palozza P., Simone R., Picci N., Buzzoni L., Ciliberti N., Natangelo A., Manfredini S., Vertuani S. Design, synthesis, and antioxidant potency of novel α-tocopherol analogues in isolated membranes and intact cells. Free Radic. Biol. Med. 2008;44:1452–1454. doi: 10.1016/j.freeradbiomed.2008.01.001. PubMed DOI
Sen C.K., Khanna S., Roy S., Packer L. Molecular basis of vitamin E action tocotrienol potently inhibits glutamate-induced pp60c-Src kinase activation and death of HT4 neuronal cells. J. Biol. Chem. 2000;275:13049–13055. doi: 10.1074/jbc.275.17.13049. PubMed DOI
Kamal-Eldin A., Appelqist L.A. The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids. 1996;31:671–701. doi: 10.1007/BF02522884. PubMed DOI
Bichay T.J., Roy R.M. Modification of survival and hematopoiesis in mice by tocopherol injection following irradiation. Strahlenther. Onkol. 1986;162:391–399. PubMed
Srinivasan V., Weiss J.F. Radioprotection by vitamin E: Injectable vitamin E administered alone or with WR-3689 enhances survival in irradiated mice. Int. J. Radiat. Oncol. Biol. Phys. 1992;23:841–845. doi: 10.1016/0360-3016(92)90657-4. PubMed DOI
Kumar K.S., Srinivasan V., Toles R. Nutritional approaches to radioprotection. Vitamin E. Mil. Med. 2002;167:57–59. PubMed
Roy R.M., Petrella M., Shateri H. Effects of administering tocopherol after irradiation on survival and proliferation of murine lymphocytes. Pharmacol. Ther. 1988;39:393–395. doi: 10.1016/0163-7258(88)90089-7. PubMed DOI
Satyamitra M., Uma Devi P., Murase H., Kagiya V.T. In vivo postirradiation protection by a vitamin E analog, α-TMG. Radiat. Res. 2003;160:655–661. doi: 10.1667/RR3077. PubMed DOI
Cherdyntseva N., Shishkina A., Butorin I., Murase H., Gervas P., Kagiya T.V. Effect of tocopherol-monoglucoside (TMG), a water-soluble glycosylated derivate of vitamin E, on hematopoietic recovery in irradiated mice. J. Radiat. Res. 2005;46:37–41. doi: 10.1269/jrr.46.37. PubMed DOI
Ueno M., Inano H., Onoda M., Murase H., Ikota N., Kagiya T.V., Anzai K. Modification of mortality and tumorigenesis by tocopherol-mono-glucoside (TMG) administered after irradiation in mice and rats. Radiat. Res. 2009;172:519–524. doi: 10.1667/RR1695.1. PubMed DOI
Singh V.K., Brown D.S., Kao T.C. Tocopherol succinate: A promising radiation countermeasure. Int. Immunopharmacol. 2009;9:1423–1430. doi: 10.1016/j.intimp.2009.08.020. PubMed DOI
Singh P.K., Wise S.Y., Ducey E.J., Fatanmi O.O., Elliott T.B., Singh V.K. α-tocopherol succinate protects mice against radiation-induced intestinal injury. Radiat. Res. 2012;177:133–145. doi: 10.1667/RR2627.1. PubMed DOI
Singh P.K., Wise S.Y., Ducey E.J., Brown D.S., Singh V.K. Radioprotective efficacy of α-tocopherol succinate is mediated through granulocyte-colony stimulating factor. Cytokine. 2011;56:411–421. doi: 10.1016/j.cyto.2011.08.016. PubMed DOI
Palozza P., Verdecchia S., Avanzi L., Vartuani S., Serini S., Manfredini S. Comparative antioxidant activity of tocotrienols and the novel chromanyl-polyisoprenyl molecule PeAox-6 in isoleted membranes and intact cells. Mol. Cell Biochem. 2006;287:21–32. doi: 10.1007/s11010-005-9020-7. PubMed DOI
Li X.H., Fu D.D., Latif N.H., Mullaney C.P., Ney P.H., Mog S.R., Whitnall M.H., Srinivasan V., Xiao M. δ-tocotrienol protects mouse and human hematopoietic progenitors from γ-irradiation through extracellular signal-regulated kinase/mammalian target of rapamycin signaling. Haematologica. 2010;95:1996–2004. doi: 10.3324/haematol.2010.026492. PubMed DOI PMC
Satyamitra M., Kulkarni S., Ghosh S.P., Mullaney C.P., Condliffe D., Srinivasan V. Hematopoietic recovery and amelioration of radiation-induced lethality by the vitamin E isoform, δ-tocotrienol. Radiat. Res. 2011;175:736–745. doi: 10.1667/RR2460.1. PubMed DOI
Baliarsingh S., Beg Z.H., Ahmad J. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyprlipidemia. Atherosclerosis. 2005;182:367–374. doi: 10.1016/j.atherosclerosis.2005.02.020. PubMed DOI
Kulkarni S.S., Ghosh S.P., Satyamitra M., Mog S., Hieber K., Romanyukha L., Gambles K., Toles R., Kao T.C., Hauer-Jensen M., et al. γ-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation. Radiat. Res. 2010;173:738–747. doi: 10.1667/RR1824.1. PubMed DOI
Ghosh S.P., Kulkarni S., Hieber K., Toles R., Romayukha L., Kao T.C., Hauer-Jensen M., Kumar K.S. γ-tocotrienol, a tocol antioxidant as a potent radioprotector. Int. J. Radiat. Biol. 2009;85:598–606. doi: 10.1080/09553000902985128. PubMed DOI
Kulkarni S., Singh P.K., Ghosh S.P., Posarac A., Singh V.K. Granulocyte colony-stimulating factor antibody abrogates radioprotective efficacy of γ-tocotrienol, a promising radiation countermeasure. Cytokine. 2013;62:278–285. doi: 10.1016/j.cyto.2013.03.009. PubMed DOI
Singh V.K., Kulkarni S., Fatanmi O.O., Wise S.Y., Newman V.L., Romaine P.L.P., Hendrickson H., Gulani J., Ghosh S.P., Kumar K.S., et al. Radioprotective efficacy of γ-tocotrienol in nonhuman primates. Radiat. Res. 2016;185:285–298. doi: 10.1667/RR14127.1. PubMed DOI
Singh V.K., Beattie L.A., Seed T.M. Vitamin E: Tocopherols and tocotrienols as potential radiation countermeasures. J. Radiat. Res. 2013;54:973–988. doi: 10.1093/jrr/rrt048. PubMed DOI PMC
Singh V.K., Hauer-Jensen M. γ-tocotrienol as a promising countermeasure for acute radiation syndrome: Current status. Int. J. Mol. Sci. 2016;17:663. doi: 10.3390/ijms17050663. PubMed DOI PMC
Whanger P.D. Selenocompounds in plants and animals and their biological significance. J. Am. Coll. Nutr. 2002;21:223–232. doi: 10.1080/07315724.2002.10719214. PubMed DOI
Weiss J.F., Srinivasan V., Kumar K.S., Landauer M.R. Radioprotection by metals: Selenium. Adv. Space Res. 1992;12:223–231. doi: 10.1016/0273-1177(92)90112-B. PubMed DOI
Kiremidjian-Schumacher L., Stotzky G. Selenium and immune responses. Environ. Res. 1987;42:227–303. doi: 10.1016/S0013-9351(87)80194-9. PubMed DOI
Weiss J.F., Srinivasan V., Kumar K.S., Landauer M.R., Patchen M.L. Radioprotection by selenium compounds. In: Favier A.E., Neve J., Fauve P., editors. Trace Elements and Free Radicals in Oxidative Diseases. AOCS Press; Champain, IL, USA: 1994. pp. 211–222.
Weiss J.F., Landauer M.R. Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology. 2003;189:1–20. doi: 10.1016/S0300-483X(03)00149-5. PubMed DOI
Karabulut-Bulan O., Bolkent S., Kizir A., Yanardag R. Protective effects of vitamin E and selenium administration on small intestinal damage prior to abdominal radiation. Pak. J. Zool. 2016;48:1225–1232.
Okunieff P. Interactions between ascorbic acid and the radiation of bone marrow, skin, and tumor. Am. J. Clin. Nutr. 1991;54:1281S–1283S. PubMed
Seifter E., Rettura G., Padawar J., Stratford F., Weinzweig J., Demetriou A.A., Levenson S.M. Morbidity and mortality reduction by supplemental vitamin A or β-carotene in CBA mice given total-body-irradiation. J. Natl. Cancer Inst. 1984;73:1167–1177. PubMed
Jeong B.K., Song J.H., Jeong H., Choi H.S., Jung J.H., Hahm J.R., Woo S.H., Jung M.H., Choi B.H., Kim J.H., et al. Effect of α-lipoic acid on radiation-induced small intestine injury in mice. Oncotarget. 2016;7:15105–15117. PubMed PMC
Wambi C., Sanzari J., Wan X.S., Nuth M., Davis J., Ko Y.H., Sayers C.M., Baran M., Ware J.H., Kennedy A.R. Dietary antioxidants protect hematopoietic cells and improve survival after total-body irradiation. Radiat. Res. 2008;169:384–396. doi: 10.1667/RR1204.1. PubMed DOI PMC
Wambi C.O., Sanzari J.K., Sayers C.M., Nuth M., Zhou Z.Z., Davis J., Finnberg N., Lewis-Wambi J.S., Ware J.H., El-Deiry W.S., et al. Protective effects of dietary antioxidants on proton total-body irradiation-mediated hematopoietic cell and animal survival. Radiat. Res. 2009;172:175–186. doi: 10.1667/RR1708.1. PubMed DOI PMC
Weiss J.F., Landauer M.R. History and development of radiation-protective agents. Int. J. Radiat. Biol. 2009;85:539–573. doi: 10.1080/09553000902985144. PubMed DOI
Han R.M., Tian Y.X., Liu Y., Chen C.H., Ai X.C., Zhang J.P., Skibsted L.H. Comparison of flavonoinds and isoflavonoids as antioxidants. J. Agric. Food Chem. 2009;57:3780–3785. PubMed
Zhou Y., Mi M.T. Genistein stimulates hematopoiesis and increases survioval in irradiated mice. J. Radiat. Res. 2005;46:425–433. doi: 10.1269/jrr.46.425. PubMed DOI
Landauer M.R., Srinivasan V., Seed T.M. Genistein protects mice from ionizing radiation injury. J. Appl. Toxicol. 2003;23:379–385. doi: 10.1002/jat.904. PubMed DOI
Davis T.A., Clarke T.K., Mog S.R., Landauer M.R. Subcutaneous administration of genistein prior to lethal irradiation suports multilineage, hematopoietic progenitor cell recovery and survival. Int. J. Radiat. Biol. 2007;83:141–151. doi: 10.1080/09553000601132642. PubMed DOI
Landauer M.R. Radioprotection by the soy isoflavone genistein. In: Arora R., editor. Herbal Radiomodulators: Applications in Medicine, Homeland Defence and Space. Cabi Publishing; Wallingford, UK: 2008. pp. 163–173.
Day R.M., Davis T.A., Barshishat-Kupper M., McCart E.A., Tipton A.J., Landauer M.R. Enhanced hematopoietic protection from radiation by the combination of genistein and captopril. Int. Immunopharmacol. 2013;15:348–356. doi: 10.1016/j.intimp.2012.12.029. PubMed DOI
Ha C.T., Li X.H., Fu D.D., Xiao N., Landauer M.R. Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after γ irradiation. Radiat. Res. 2013;180:316–325. doi: 10.1667/RR3326.1. PubMed DOI
Thorn J.A., Jarvis S.M. Adenosine transporters. Gen. Pharmacol. 1996;27:613–620. doi: 10.1016/0306-3623(95)02053-5. PubMed DOI
Gordon E.L., Pearson J.D., Dickinson E.S., Moreau D., Slakey L.L. The hydrolysis of extracellular adenine nucleotides by arterial smooth muscle cells—Regulation of adenosine production at the cell surface. J. Biol. Chem. 1989;264:18986–18992. PubMed
Pospíšil M., Hofer M., Netíková J., Viklická Š., Pipalová I., Bartoníčková A. Effect of dipyridamole and adenosine monophosphate on cell proliferation in the hemopoietic tissue of normal and γ-irradiated mice. Experientia. 1992;48:253–257. PubMed
Pospíšil M., Hofer M., Netíková J., Pipalová I., Vacek A., Bartoníčková A., Volenec K. Elevation of extracellular adenosine induces radioprotective effects in mice. Radiat. Res. 1993;134:323–330. doi: 10.2307/3578192. PubMed DOI
Hofer M., Pospíšil M., Netíková J., Znojil V., Vácha J. Enhancement of of haemopoietic spleen colony formation by drugs elevating extracellular adenosine: Effects of repeated in vivo treatment. Physiol. Res. 1997;46:285–290. PubMed
Pospíšil M., Hofer M., Znojil V., Vácha J., Netíková J., Holá J. Radioprotection of mouse hemopoiesis by dipyridamole and adenosine monophosphate in fractionated treatment. Radiat. Res. 1995;142:16–22. doi: 10.2307/3578962. PubMed DOI
Hofer M., Pospíšil M., Netíková J., Znojil V., Vácha J., Holá J. Radioprotective efficacy of dipyridamole and AMP combination in fractionated radiation regimen, and its dependence on the time of administration of the drugs prior to irradiation. Physiol. Res. 1995;44:93–98. PubMed
Hofer M., Pospisil M., Weiterova L., Hoferova Z. The role of adenosine receptor agonists in regulation of hematopoiesis. Molecules. 2011;16:675–685. doi: 10.3390/molecules16010675. PubMed DOI PMC
Hofer M., Pospíšil M., Znojil V., Holá J., Vacek A., Štreitová D. Adenosine A3 receptor agonist acts as a homeostatic regulator of bone marrow hematopoiesis. Biomed. Pharmacother. 2007;61:356–359. doi: 10.1016/j.biopha.2007.02.010. PubMed DOI
Hofer M., Pospíšil M., Šefc L., Dušek L., Vacek A., Holá J., Hoferová Z., Šteritová D. Activation of adenosine A3 receptors supports hematopoiesis-stimulating effects of granulocyte colony-stimulating factor in sublethally irradiated mice. Int. J. Radiat. Biol. 2010;86:649–656. doi: 10.3109/09553001003746075. PubMed DOI
Hofer M., Pospíšil M., Dušek L., Hoferová Z., Weiterová L. Inhibition of cyclooxygenase-2 promotes the stimulatory action of adenosine A3 receptor agonist on hematopoiesis in sublethally γ-irradiated mice. Biomed. Pharmacother. 2011;65:427–431. doi: 10.1016/j.biopha.2011.04.033. PubMed DOI
Hofer M., Pospíšil M., Dušek L., Hoferová Z., Komůrková D. Agonist of the adenosine A3 receptor, IB-MECA, and inhibitor of cyclooxygenase-2, meloxicam, given alone or in a combination early after total body irradiation enhance survival of γ-irradiated mice. Radiat. Environ. Biophys. 2014;53:211–215. doi: 10.1007/s00411-013-0500-y. PubMed DOI
Ghosh S.P., Perkins M.W., Hieber K., Kulkarni S., Kao T.C., Reddy E.P., Reddy M.V.R., Maniar M., Seed T.M., Kumar K.S. Radiation protection by a new chemical entity, Ex-Rad™: Efficacy and mechanisms. Radiat. Res. 2009;171:173–179. doi: 10.1667/RR1367.1. PubMed DOI
Suman S., Datta K., Doiron K., Ren C., Kumar R., Taft D.R., Fornace A.J., Maniar M. Radioprotective effects of ON 01210.Na upon oral administration. J. Radiat. Res. 2012;53:368–376. doi: 10.1269/jrr.11191. PubMed DOI
Ghosh S.P., Kulkarni S., Perkins M.W., Hieber K., Pessu R.L., Gambles K., Maniar M., Kao T.C., Seed T.M., Kumar K.S. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD® in mice. J. Radiat. Res. 2012;53:526–536. doi: 10.1093/jrr/rrs001. PubMed DOI PMC
Suman S., Maniar M., Fornace A.J., Datta K. Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response. Radiat. Oncol. 2012;7:6. doi: 10.1186/1748-717X-7-6. PubMed DOI PMC
Kang A.D., Coscenza S.C., Bonagura M., Manair M., Reddy M.V.R., Reddy E.P. ON01210.Na (Ex-RAD®) mitigates radiation damage through activation of the AKT pathway. PLoS ONE. 2013;8:e58355. doi: 10.1371/journal.pone.0058355. PubMed DOI PMC
Miller R.C., Murley J.S., Grdina D.J. Metformin exhibits radiation countermeasures efficacy when used alone or in combination with sulfhydryl containing drugs. Radiat. Res. 2014;181:464–470. doi: 10.1667/RR13672.1. PubMed DOI PMC
Burdelya L.G., Krivokrysenko V.I., Tallant T.C., Strom E., Gleiberman A.S., Gupta D., Kurnasov O.V., Fort F.L., Osterman A.L., DiDonato J.A., et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science. 2008;320:226–230. doi: 10.1126/science.1154986. PubMed DOI PMC
Krivokrysenko V.I., Toshkov I.A., Gleiberman A.S., Krasnov P., Shyshynova I., Bespalov I., Maitra R.K., Narizhneva N.V., Singh V.K., Whitnall M.H., et al. The toll-like receptor 5 agonist entolimod mitigates lethal acute radiation syndrome in no-human primates. PLoS ONE. 2015;10:e0135388. doi: 10.1371/journal.pone.0135388. PubMed DOI PMC
Toshkov I.A., Gleiberman A.S., Mett V.L., Hutson A.D., Singh A.K., Gudkov A.V., Burdelya L.G. Mitigation of radiation-induced epithelial damage by the TLR5 agonist entolimod in a mouse model of fractionated head and neck irradiation. Radiat. Res. 2017;187:570–580. doi: 10.1667/RR14514.1. PubMed DOI PMC
Krivokrysenko V.I., Shakhov A.N., Singh V.K., Bone F., Kononov Y., Shyshynova I., Cheney A., Maitra R.K., Purmal A., Whitnall M.H., et al. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J. Pharmacol. Exp. Ther. 2012;343:497–508. doi: 10.1124/jpet.112.196071. PubMed DOI PMC
Zhang L.R., Sun W.M., Wang J.J., Zhank M., Yang S.M., Tian Y.P., Vidyasagar S., Pena L.A., Zhang K.Z., Cao Y.B., et al. Mitigation effect of an FGF-2 peptide on acute gastrointestinal syndrome after high-dose ionizing radiation. Int. J. Radiat. Oncol. Biol. Phys. 2010;77:261–268. doi: 10.1016/j.ijrobp.2009.11.026. PubMed DOI PMC
Deng W.L., Kimura Y., Gududuru V., Wu W.J., Balogh A., Szabo E., Thompson K.E., Yates C.R., Balasz L., Johnson L.R., et al. Mitigation of the hematopoietic and gastrointestinal acute radiation syndrome by octadecenyl thiophosphate, a small molecule mimic of lysophosphatidic acid. Radiat. Res. 2015;183:465–475. doi: 10.1667/RR13830.1. PubMed DOI PMC
Taniguchi C.M., Miao Y.R., Diep A.N., Wu C., Rankin E.B., Atwood T.F., Xing L., Giaccia A.J. PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2. Sci. Transl. Med. 2014;6:236ra64. doi: 10.1126/scitranslmed.3008523. PubMed DOI PMC
Olcina M.M. Reducing radiation-induced gastrointestinal toxicity—The role of the PHD/HIF axis. J. Clin. Investig. 2016;126:3708–3715. doi: 10.1172/JCI84432. PubMed DOI PMC
Dainiak N., Gent R.N., Carr Z., Schneider R., Bader J., Buglova E., Chao N., Coleman C.N., Ganser A., Gorin C., et al. Literature review and global consensus on management of acute radiation syndrome affecting non-hematopoietic organ systems. Disaster Med. Public Health Prep. 2011;5:183–201. doi: 10.1001/dmp.2011.73. PubMed DOI PMC
Hirama T., Tanosaki S., Kandatsu S., Kuroiwa N., Kamada T., Tsuji H., Yamada S., Katoh H., Yamamoto N., Tsuji H., et al. Initial medical management of patients severely irradiated in the Tokai-mura criticality accident. Br. J. Radiol. 2003;76:246–352. doi: 10.1259/bjr/82373369. PubMed DOI
Delanian S., Porcher R., Balla-Mekias S., Lefaix J.L. Randomize, placebo-controlled trial of combined petoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J. Clin. Oncol. 2003;13:2545–2550. doi: 10.1200/JCO.2003.06.064. PubMed DOI
Bey E., Prat M., Duhamel P., Benderitter M., Brachet M., Trompier F., Battaglini P., Emou I., Boutin L., Gourven M., et al. Emerging therapy for improving wound repair of severe radiation burns using local bone marrow-derived stem cell administrations. Wound Repair Regen. 2010;18:50–58. doi: 10.1111/j.1524-475X.2009.00562.x. PubMed DOI
Agay D., Scherthan H., Forcheron F., Grenier N., Herodin F., Meineke V., Drouet M. Multipotent mesenchymal stem cell grafting to treat cutaneous radiation syndrome: Development of a new minipig model. Exp. Hematol. 2010;38:945–956. doi: 10.1016/j.exphem.2010.06.008. PubMed DOI
Riccobono D., Agay D., Francois S., Scherthan H., Drouet M., Forcheron F. Contribution of intramuscular autologous adipose tissue-derived stem cell injection to treat cutaneous radiation syndrome: Preliminary results. Health Phys. 2016;111:117–126. doi: 10.1097/HP.0000000000000515. PubMed DOI