Photoprotective and radioprotective properties of nitroxides and their application in magnetic resonance imaging

COMMENTARY ON THE LAW

Photoprotective and radioprotective properties of nitroxides and their application in magnetic resonance imaging

Marcin Lewandowski 1 , Krzysztof Gwoździński 1

1. Katedra Biofizyki Molekularnej Uniwersytetu Łódzkiego

Published: 2016-10-14
DOI: 10.5604/17322693.1222099
GICID: 01.3001.0009.6888
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2016; 70 : 1101-1111

 

Abstract

Nitroxides are a group of stable organic radicals of low molecular weight having a nitroxyl group > N-.O, which has an unpaired electron. The presence of this group allows a nitroxide to participate in redox reactions. They serve as mimics of superoxide dismutase (SOD) and have stimulative properties towards haemoproteins with catalase-like activity. Nitroxides oxidize Fe (II) to Fe (III) preventing the Fenton and Haber-Weiss reactions. As the radicals have the ability to scavenge other free radicals. Nitroxides are not immunogenic, and mutagenic and do not show toxicity to the human cells.The review discusses the use of nitroxide in protecting cells and tissues from the effects of UVA radiation. Preliminary studies indicate that they are more effective than conventionally used vitamins C and E and UV filters. They also protect the biological material from the effects of ionizing radiation. Nitroxides protect healthy cells and simultaneously they do not protect cancer cells from ionizing radiation. The differences in the nitroxide activity are associated with conditions prevailing in the oxidizing environment of the tumor as opposed to reducing conditions in normal cells.Nitroxides can be used as contrast agents in the magnetic resonance imaging (MR). They have ability of detection of subtle changes in redox equilibrium in the tumor tissue. Application of nitroxides in MR method allow to distinguish normal and pathological state of tissue. Successful investigations using this technique were conducted in mice with colon and brain cancer.

References

  • 1. Berhane H., Shinde A., Kalash R., Xu K., Epperly M.W., Goff J.,Franicola D., Zhang X., Dixon T., Shields D., Wang H., Wipf P., Li S.,Gao X., Greenberger J.S.: Amelioration of radiation-induced oralcavity mucositis and distant bone marrow suppression in Fanconianemia Fancd2-/ – (FVB/N) mice by intraoral GS-nitroxide JP4-039.Radiat. Res., 2014; 182: 35-49
    Google Scholar
  • 2. Bernard M.E., Kim H., Berhane H., Epperly M.W., Franicola D.,Zhang X., Houghton F., Shields D., Wang H., Bakkenist C.J., FrantzM.C., Forbeck E.M., Goff J.P., Wipf P., Greenberger J.S.: GS-nitroxide(JP4-039)-mediated radioprotection of human Fanconi anemia celllines. Radiat. Res., 2011; 176: 603-612
    Google Scholar
  • 3. Bernstein E.F., Kong, S.K., Brown D.B., Kwak, B.C., Takeuchi T.,Gasparro F.P., Uitto J.: The nitroxide tempol affords protectionagainst ultraviolet radiation in a transgenic murine fibroblast culturemodel of cutaneous photoaging. Exp. Dermatol., 2001; 10: 55-61
    Google Scholar
  • 4. Bose B., Agarwal S., Chatterjee S.N.: UV-A induced lipid peroxidationin liposomal membrane. Radiat. Enivron. Biophys., 1989;28: 59-65
    Google Scholar
  • 5. Bose B., Chatterjee S.N.: Correlation between UVA-inducedchanges in microviscosity, permeability and malondialdehyde formationin liposomal membrane. J. Photochem. Photobiol. B, 1995;28: 149-153
    Google Scholar
  • 6. Bujak S., Gwoździński K.: Nitroxides lead to reduced level ofglutathione in red blood cells. W: Free radical and oxidative stress:chemistry and pathological implications, red.: Galaris G. MedimondInternational Proceedings, 2003; 105-108
    Google Scholar
  • 7. Carroll R.T., Galatsis P., Borosky S., Kopec K.K., Kumar V., AlthausJ.S., Hall E.D.: 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol)inhibits peroxynitrite-mediated phenol nitration. Chem. Res.Toxicol., 2000; 13: 294-300
    Google Scholar
  • 8. Charloux C., Paul M., Loisance D., Astier A.: Inhibition of hydroxylradical production by lactobionate, adenine, and tempol.Free Radic. Biol. Med., 1995; 19: 699-704
    Google Scholar
  • 9. Chateauneuf J., Lusztyk J., Ingold K.U.: Absolute rate constantsfor the reactions of some carbon-centered radicals with 2,2,6,6-tetramethylpiperidine-N-oxyl.J. Org. Chem., 1988; 53: 1629-1632
    Google Scholar
  • 10. Czepas J., Koceva-Chyła A., Gwoździński K., Jóźwiak Z.: Differenteffectiveness of piperidine nitroxides against oxidative stressinduced by doxorubicin and hydrogen peroxide. Cell Biol. Toxicol.,2008; 24: 101-112Piśmiennictwo
    Google Scholar
  • 11. Damiani E., Castagna R., Greci L.: The effects of derivatives ofthe nitroxide tempol on UVA-mediated in vitro lipid and proteinoxidation. Free Radic. Biol. Med., 2002; 33: 128-136
    Google Scholar
  • 12. Davis R.M., Matsumoto S., Bernardo M., Sowers A., MatsumotoK., Krishna M.C., Mitchell J.B.: Magnetic resonance imaging oforganic contrast agents in mice: capturing the whole-body redoxlandscape. Free Radic. Biol. Med., 2011; 50: 459-468
    Google Scholar
  • 13. Davis R.M., Sowers A.L., DeGraff W., Bernardo M., Thetford A.,Krishna M.C., Mitchell J.B.: A novel nitroxide is an effective brainredox imaging contrast agent and in vivo radioprotector. Free Radic.Biol. Med., 2011; 51: 780-790
    Google Scholar
  • 14. Dikalov S., Grigor’ev I.A., Voinov M., Bassenge E.: Detection ofsuperoxide radicals and peroxynitrite by 1-hydroxy-4-phosphonooxy-2,2,6,6-tetramethylpiperidine:quantification of extracellularsuperoxide radicals formation. Biochem. Biophys. Res. Commun.,1998; 248: 211-215
    Google Scholar
  • 15. Dilip A., Cheng G., Joseph J., Kunnimalaiyaan S., KalyanaramanB., Kunnimalaiyaan M., Gamblin T.C.: Mitochondria-targeted antioxidantand glycolysis inhibition: synergistic therapy in hepatocellularcarcinoma. Anticancer Drugs, 2013; 24: 881-888
    Google Scholar
  • 16. Emoto M., Yamada K., Yamato M., Fujii H.G.: Novel ascorbicacid-resistive nitroxide in a lipid emulsion: an efficient brain imagingcontrast agent for MRI of small rodents. Neurosci. Lett., 2013;546: 11-15
    Google Scholar
  • 17. Gariboldi M.B., Lucchi S., Caserini C., Supino R., Oliva C., MontiE.: Antiproliferative effect of piperidine nitroxide tempol on neoplasticand nonneoplastic mammalian cell lines. Free Radic. Biol.Med., 1998; 24: 913-923
    Google Scholar
  • 18. Gariboldi M.B., Rimoldi V., Supino R., Favini E., Monti E.: Thenitroxide tempol induces oxidative stress, p21waf1/cip1, and cell deathin HL60 cells. Free Radic. Biol. Med., 2000; 29: 633-641
    Google Scholar
  • 19. Głębska J., Gwoździński K.: Oxygen-dependent reduction of nitroxidesby ascorbic acid and glutathione. EPR investigations. Curr.Top. Biophys. (Suppl.), 1998; 22: 75-82
    Google Scholar
  • 20. Głębska J., Gwoździński K.: Nitroxides as protectors againstoxidative damage induced by Fenton system. Curr. Top. Biophys.,2000; 24: 57-63
    Google Scholar
  • 21. Głębska J., Skolimowski J., Kudzin Z., Gwoździński K., GrzelakA., Bartosz G.: Pro-oxidative activity of nitroxides in their reactionswith glutathione. Free Radic. Biol. Med., 2003; 35: 310-316
    Google Scholar
  • 22. Goralska M., Holley B., McGahan M.C.: The effects of tempolon ferritin synthesis and Fe metabolism in lens epithelial cells.Biochim. Biophys. Acta, 2000; 1497: 51-60
    Google Scholar
  • 23. Greenberger J.S., Berhane H., Shinde A., Rhieu B.H., Bernard M.,Wipf P., Skoda E.M., Epperly M.W.: Can radiosensitivity associatedwith defects in DNA repair be overcome by mitochondrial-targetedantioxidant radioprotectors. Front. Oncol., 2014; 4: 24
    Google Scholar
  • 24. Grinberg L.N., Samuni A.: Nitroxide stable radical preventsprimaquine-induced lysis of red blood cell. Biochim. Biophys. Acta,1994; 1201: 284-288
    Google Scholar
  • 25. Guo J., Zhang Y., Zhang J., Liang J., Zeng L., Guo G.: Anticancereffect of tert-butyl-2 (4,5-dihydrogen-4,4,5,5-tetramethyl-3-O-1Himidazole-3-cationic-1-oxyl-2)-pyrrolidine-1-carboxylicester onhuman hepatoma HepG2 cell line. Chem. Biol. Interact., 2012; 199:38-48
    Google Scholar
  • 26. Gupta S.C., Hevia D., Patchva S., Park B., Koh W., Aggarwal B.B.:Upsides and downsides of reactive oxygen species for cancer: theroles of reactive oxygen species in tumorigenesis, prevention, andtherapy. Antioxid. Redox Signal., 2012; 16:1295-1322
    Google Scholar
  • 27. Gwoździński K.: Effect of cupric ions on the permeability oferythrocyte membrane to non-electrolyte spin labels. Physiol.Chem. Phys. Med. NMR, 1985; 17: 431-434
    Google Scholar
  • 28. Gwoździński K.: Effect of thiol reactive reagents and ionizingradiation on the permeability of erythrocyte membrane for nonelectrolytespin labels. Radiat. Environ. Biophys., 1986; 25: 107-111
    Google Scholar
  • 29. Gwoździński K., Bartosz G.: Nitroxide reduction in human redblood cells. Curr. Top. Biophys., 1996; 20: 60-65
    Google Scholar
  • 30. Gwoździński K., Bartosz G., Leyko W.: Effect of γ radiation onthe transport of spin-labeled compounds across the erythrocytemembrane. Radiat. Environ. Biophys., 1981; 19: 275-285
    Google Scholar
  • 31. Gwoździński K., Bartosz G., Leyko W.: Effect of γ radiation onthe transport of electrolyte spin labels across human erythrocyte.Stud. Biophys., 1982; 89: 141-145
    Google Scholar
  • 32. Gwoździński K., Bartosz G., Leyko W.: Effect of thiol reactivereagents and ionizing radiation on the permeability of erythrocytemembrane for spin-labeled non-electrolytes. Radiat. Environ.Biophys, 1983; 22: 53-59
    Google Scholar
  • 33. Huang Z., Jiang J., Belikova N.A., Stoyanovsky D.A., Kagan V.E.,Mintz A.H.: Protection of normal brain cells from γ-irradiationinducedapoptosis by a mitochondria-targeted triphenyl-phosphonium-nitroxide:a possible utility in glioblastoma therapy. J.Neurooncol., 2010; 100: 1-8
    Google Scholar
  • 34. Hyodo F., Matsumoto K., Matsumoto A., Mitchell J.B., KrishnaM.C.: Probing the intracellular redox status of tumors with magneticresonance imaging and redox-sensitive contrast agents. CancerRes., 2006; 66: 9921-9928
    Google Scholar
  • 35. Jiang J., Belikova N.A., Hoye A.T., Zhao Q., Epperly M.W., GreenbergerJ.S., Wipf P., Kagan V.E.: A mitochondria-targeted nitroxide/hemigramicidinS conjugate protects mouse embryonic cellsagainst gtamma. Int. J. Radiat. Oncol. Biol. Phys., 2008; 70: 816-825
    Google Scholar
  • 36. Kim H., Bernard M.E., Epperly M.W., Shen H., Amoscato A.,Dixon T.M., Doemling A.S., Li S., Gao X., Wipf P., Wang H., ZhangX., Kagan V.E., Greenberger J.S.: Amelioration of radiation esophagitisby orally administered p53/Mdm2/Mdm4 inhibitor (BEB55)or GS-nitroxide. In Vivo, 2011; 25: 841-848
    Google Scholar
  • 37. Koceva-Chyla A., Kochman A., Głębska J., Gwoździński K.,Jóźwiak Z., Metodiewa D.: Tempicol-3, a novel low toxic piperidinen-oxidestable radical and antioxidant, acts as apoptosis inducerand cell proliferation modifier of Yoshida sarcoma cells in vivo.Anticancer Res., 2000; 20: 4611-4618
    Google Scholar
  • 38. Krishna M.C., Russo A., Mitchell J.B., Goldstein S., Dafni H.,Samuni A.: Do nitroxide antioxidants act as scavengers of o2. – oras SOD mimics? J. Biol. Chem., 1996; 271: 26026-26031
    Google Scholar
  • 39. Krishna M.C., Samuni A., Taira J., Goldstein S., Mitchell J.B.,Russo A.: Stimulation by nitroxides of catalase-like activity ofhemeproteins. Kinetics and mechamism. J. Biol. Chem., 1996; 271:26018-26025
    Google Scholar
  • 40. Lewandowski M., Gwoździński K.: Wykorzystanie nitroksydówjako leków oraz przeciwutleniaczy w stresie oksydacyjnym indukowanymprzez chemioterapeutyki stosowane w terapii nowotworów.Postępy Biol. Kom., 2015; 42: 667-686
    Google Scholar
  • 41. Miura Y., Utsumi H., Hamada A.: Antioxidant activity of nitroxideradicals in lipid peroxidation of rat liver microsomes. Arch.Biochem. Biophys., 1993; 300: 148-156
    Google Scholar
  • 42. Nilsson U.A., Olsson L.I., Carlin G., Bylund-Fellenius A.C.: Inhibitionof lipid peroxidation by spin labels: relationships betweenstructure and function. J. Biol. Chem., 1989; 264: 11131-11135
    Google Scholar
  • 43. Samuni A.M., DeGraff W., Krishna M.C., Mitchell J.B.: Cellularsites of H2O2-induced damage and their protection by nitroxides.Biochim. Biophys. Acta, 2001; 1525: 70-76
    Google Scholar
  • 44. Schaefer H., Chardon A., Moyal D.: Photoprotection of skinagainst ultraviolet A damage. Methods Enzymol., 2000; 319: 445-465
    Google Scholar
  • 45. Selvendiran K., Ahmed S., Dayton A., Kuppusamy M.L., TaziM., Bratasz A., Tong L., Rivera B.K., Kalai T., Hideg K., KuppusamyP.: Safe and targeted anticancer efficacy of a novel class of antioxidant-conjugateddifluorodiarylidenyl piperidones: differentialcytotoxicity in healthy and cancer cells. Free Radic. Biol. Med.,2010; 48: 1228-1235
    Google Scholar
  • 46. Sen’ V.D., Terentiev A.A., Konovalova N.P.: Platinum complexeswith bioactive nitroxyl radicals: synthesis and antitumor properties.W: Nitroxides – theory, experiment and applications, red.:Kokorin A. Intech, 2012, 385-406
    Google Scholar
  • 47. Skolimowski J., Metodiewa D., Kochman A., Gwoździński K.:Novel complex rutoxyl as antioxidant and radioprotector: a comparisonwith rutin action. J. Biochem. Mol. Biol. Biophys., 1999;3: 87-97
    Google Scholar
  • 48. Szatrowski T.P., Nathan C.F.: Production of large amounts ofhydrogen peroxide by human tumor cells. Cancer Res., 1991; 51:794-798
    Google Scholar
  • 49. Tomizawa A., Hadjidekov G., Ishii I., Bakalova R., Zhelev Z., AokiI., Saga T., Kitada M.: Nitroxide derivatives for imaging of hypercholesterolemia-inducedkidney dysfunction and assessing the effectivenessof antilipidemic drugs. Mol. Pharm., 2011; 8: 1962-1969
    Google Scholar
  • 50. Venditti E., Bruge F., Astolfi P., Kochevar I., Damiani E.: Nitroxidesand a nitroxide-based UV filter have the potential to photoprotectUVA-irradiated human skin fibroblasts against oxidativedamage. J. Dermatol. Sci., 2011; 63: 55-61
    Google Scholar
  • 51. Venditti E., Scire A., Tanfani F., Greci L., Damiani E.: Nitroxidesare more efficient inhibitors of oxidative damage to calf skin collagenthan antioxidant vitamins. Biochim. Biophys. Acta., 2008;1780: 58-68
    Google Scholar
  • 52. Vitolo J.M., Cotrim A.P., Sowers A.L., Russo A., Wellner R.B.,Pillemer S.R., Mitchell J.B., Baum B.J.: The stable nitroxide tempolfacilitates salivary gland protection during head and neck irradiationin mouse model. Clin. Cancer Res., 2004; 10: 1807-1812
    Google Scholar
  • 53. Warburg O.: The metabolism of tumors. Arnold Constable,London. 1930; 254-270
    Google Scholar
  • 54. Warburg O.: On the origin of cancer cells. Science, 1956; 123:309-314
    Google Scholar
  • 55. Warburg O.P., Posener K., Negelein E.: Üeber den Stoffwechselder Tumoren. Biochem. Z., 1924; 152: 319-344
    Google Scholar
  • 56. Wu Y.J., Li W.G., Zhang Z.M., Tian X.: Antioxidative activity of4-oxy – and 4-hydroxy-nitroxides in tissues and erythrocytes fromrats. Zhongguo Yao Li Xue Bao, 1997; 18: 150-154
    Google Scholar
  • 57. Yan S.X., Hong X.Y., Hu Y., Liao K.H.: Tempol, one of nitroxides, is a novel ultraviolet-A1 radiation protector for human dermal fibroblasts.J. Dermatol. Sci., 2005; 37: 137-143
    Google Scholar
  • 58. Yoshino F., Shoji H., Lee M.C.: Vascular effects of singlet oxygen(1O2) generated by photo-excitation on adrenergic neurotransmissionin isolated rabbit mesenteric vein. Redox Rep., 2002; 7: 266-270
    Google Scholar
  • 59. Zhelev Z., Aoki I., Gadjeva V., Nikolova B., Bakalova R., Saga T.:Tissue redox activity as a sensing platform for imaging of cancerbased on nitroxide redox cycle. Eur. J. Cancer, 2013; 49: 1467-1478
    Google Scholar
  • 60. Zhelev Z., Bakalova R., Aoki I., Lazarova D., Saga T.: Imagingof superoxide generation in the dopaminergic area of the brain in Parkinson’s disease, using mito-TEMPO. ACS Chem. Neurosci.,2013; 4: 1439-1445
    Google Scholar
  • 61. Zhelev Z., Gadjeva V., Aoki I., Bakalova R., Saga T.: Cell-penetratingnitroxides as molecular sensors for imaging of cancer invivo, based on tissue redox activity. Mol. Biosyst., 2012; 8: 2733-2740
    Google Scholar
  • 62. Zienolddiny S., Ryberg D., Haugen A.: Induction of microsatellitemutations by oxidative agents in human lung cancer celllines. Carcinogenesis, 2000; 21: 1521-1526
    Google Scholar

Full text

Skip to content