Skip to main content
Log in

Sodium nitrite potentiates antimicrobial photodynamic inactivation: possible involvement of peroxynitrate

  • Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

We have recently shown that a wide range of different inorganic salts can potentiate antimicrobial photo-dynamic inactivation (aPDI) and TiO2-mediated antimicrobial photocatalysis. Potentiation has been shown with azide, bromide, thiocyanate, selenocyanate, and most strongly, with iodide. Here we show that sodium nitrite can also potentiate broad-spectrum aPDI killing of Gram-positive MRSA and Gram-negative Escherichia coli bacteria. Literature reports have previously shown that two photosensitizers (PS), methylene blue (MB) and riboflavin, when excited by broad-band light in the presence of nitrite could lead to tyrosine nitration. Addition of up to 100 mM nitrite gave 6 logs of extra killing in the case of Rose Bengal excited by green light against E. coli, and 2 logs of extra killing against MRSA (eradication in both cases). Comparable results were obtained for other PS (TPPS4 + blue light and MB + red light). Some bacterial killing was obtained when bacteria were added after light using a functionalized fullerene (LC15) + nitrite + blue light, and tyrosine ester amide was nitrated using both “in” and “after” modes with all four PS. The mechanism could involve formation of peroxynitrate by a reaction between superoxide radicals and nitrogen dioxide radicals; formation of the latter species was demonstrated by spin trapping with nitromethane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. J. O’Neill, Tackling a global health crisis:initial steps, The Review on Antimicrobial Resistance Chaired by Jim O’Neill, 2015.

  2. K. Bush, P. Courvalin, G. Dantas, J. Davies, B. Eisenstein, P. Huovinen, et al., Tackling antibiotic resistance, Nat. Rev. Microbiol., 2011, 9(12), 894–896.

    Article  CAS  Google Scholar 

  3. A. P. Castano, T. N. Demidova and M. R. Hamblin, Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization, Photodiagn. Photodyn. Ther., 2004, 1(4), 279–293.

    Article  CAS  Google Scholar 

  4. M. da Silva Baptista, J. Cadet, P. Di Mascio, A. A. Ghogare, A. Greer, M. R. Hamblin, et al., Type I and II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways, Photochem. Photobiol., 2017, 93(4), 912–919.

    Article  Google Scholar 

  5. S. K. Sharma, P. Mroz, T. Dai, Y. Y. Huang, T. G. St Denis and M. R. Hamblin, Photodynamic Therapy for Cancer and for Infections: What Is the Difference?, Isr. J. Chem., 2012, 52(8–9), 691–705.

  6. M. R. Hamblin, Potentiation of antimicrobial photodynamic inactivation by inorganic salts, Expert Rev. Anti-Infect. Ther., 2017, 15(11), 1059–1069.

  7. L. Huang, A. El-Hussein, W. Xuan and M. R. Hamblin, Potentiation by potassium iodide reveals that the anionic porphyrin TPPS4 is a surprisingly effective photosensitizer for antimicrobial photodynamic inactivation, J. Photochem. Photobiol., B, 2017, 178, 277–286.

    Article  Google Scholar 

  8. L. Huang, G. Szewczyk, T. Sarna and M. R. Hamblin, Potassium Iodide Potentiates Broad-Spectrum Antimicrobial Photodynamic Inactivation Using Photofrin, ACS Infect. Dis., 2017, 3(4), 320–328.

    Article  CAS  Google Scholar 

  9. D. Vecchio, A. Gupta, L. Huang, G. Landi, P. Avci, A. Rodas, et al., Bacterial photodynamic inactivation mediated by methylene blue and red light is enhanced by synergistic effect of potassium iodide, Antimicrob. Agents Chemother., 2015, 59(9), 5203–5212.

    Article  CAS  Google Scholar 

  10. X. Wu, Y. Y. Huang, Y. Kushida, B. Bhayana and M. R. Hamblin, Broad-spectrum antimicrobial photocatalysis mediated by titanium dioxide and UVA is potentiated by addition of bromide ion via formation of hypobromite, Free Radicals Biol. Med., 2016, 95, 74–81.

    Article  CAS  Google Scholar 

  11. T G. St Denis, D. Vecchio, A. Zadlo, A. Rineh, M. Sadasivam, P. Avci, et al., Thiocyanate potentiates antimicrobial photodynamic therapy: In situ generation of the sulfur trioxide radical anion by singlet oxygen, Free Radicals Biol. Med., 2013, 65C, 800–810.

  12. L. Huang, W. Xuan, A. Zadlo, A. Kozinska, T. Sarna and M. R. Hamblin, Antimicrobial photodynamic inactivation is potentiated by addition of selenocyanate: possible involvement of selenocyanogen?, J. Biophotonics, 2018, 11(8), e201800029.

  13. L. Huang, T. G. St Denis, Y. Xuan, Y. Y. Huang, M. Tanaka, A. Zadlo, et al., Paradoxical potentiation of methylene blue-mediated antimicrobial photodynamic inactivation by sodium azide: role of ambient oxygen and azide radicals, Free Radicals Biol. Med., 2012, 53(11), 2062–2071.

    Article  CAS  Google Scholar 

  14. L. Huang, Y. Xuan, Y. Koide, T. Zhiyentayev, M. Tanaka and M. R. Hamblin, Type I and Type II mechanisms of antimicrobial photodynamic therapy: An in vitro study on Gram-negative and Gram-positive bacteria, Lasers Surg. Med., 2012, 44(6), 490–499.

    Article  Google Scholar 

  15. K. R. Kasimova, M. Sadasivam, G. Landi, T. Sarna and M. R. Hamblin, Potentiation of photoinactivation of Gram-positive and Gram-negative bacteria mediated by six phenothiazinium dyes by addition of azide ion, Photochem. Photobiol. Sci., 2014, 13(11), 1541–1548.

    Article  CAS  Google Scholar 

  16. R. Yin, M. Wang, Y. Y. Huang, G. Landi, D. Vecchio, L. Y. Chiang, et al., Antimicrobial photodynamic inactivation with decacationic functionalized fullerenes: oxygen independent photokilling in presence of azide and new mechanistic insights, Free Radicals Biol. Med., 2015, 79,14–27.

  17. L. Pecci, G. Montefoschi, A. Antonucci, M. Costa, M. Fontana and D. Cavallini, Formation of nitrotyrosine by methylene blue photosensitized oxidation of tyrosine in the presence of nitrite, Biochem. Biophys. Res. Commun., 2001, 289(1), 305–309.

    Article  CAS  Google Scholar 

  18. M. Fontana, C. Blarzino and L. Pecci, Formation of 3-nitro-tyrosine by riboflavin photosensitized oxidation of tyrosine in the presence of nitrite, Amino Acids, 2012, 42(5), 1857–1865.

    Article  CAS  Google Scholar 

  19. P. Bilski, C. F. Chignell, J. Szychlinski, A. Borkowski, E. Oleksy and K. Reszka, Photooxidation of organic and inorganic substrates during UV photolysis of nitrite anion in aqueous solution, J. Am. Chem. Soc., 1992, 114, 549–556.

    Article  CAS  Google Scholar 

  20. X. Wen, X. Zhang, G. Szewczyk, A. El-Hussein, Y. Y. Huang, T. Sarna, et al., Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies, Antimicrob. Agents Chemother., 2017, 61(7), pii: e00467-17.

  21. Y. Y. Huang, H. Choi, Y. Kushida, B. Bhayana, Y. Wang and M. R. Hamblin, Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide, Antimicrob. Agents Chemother., 2016, 60(9), 5445–5453.

    Article  CAS  Google Scholar 

  22. G. Szewczyk, A. Zadlo, M. Sarna, S. Ito, K. Wakamatsu and T. Sarna, Aerobic photoreactivity of synthetic eumelanins and pheomelanins: generation of singlet oxygen and superoxide anion, Pigm. Cell Melanoma Res., 2016, 29(6), 669–678.

    Article  CAS  Google Scholar 

  23. K. J. Reszka, P. Bilski and C. F. Chignell, Spin trapping of nitric oxide by aci anions of nitroalkanes, Nitric Oxide, 2004, 10(2), 53–59.

    Article  CAS  Google Scholar 

  24. M. D. Pace, Spin Trapping of Nitrogen Dioxide from Photolysis of Sodium Nitrite, Ammonium Nitrate, Ammonium Dinitramide, and Cyclic Nitramines, J. Phys. Chem., 1994, 98, 6251–6257.

  25. C. Lambert, T. Sarna and T. G. Truscott, Rose bengal radicals and their reactivity, J. Chem. Soc., Faraday Trans., 1990, 86, 3879–3882.

    Article  CAS  Google Scholar 

  26. T. Nauser and W. H. Koppenol, The Rate Constant of the Reaction of Superoxide with Nitrogen Monoxide: Approaching the Diffusion Limit, J. Phys. Chem. A, 2002, 106, 4084–4086.

    Article  CAS  Google Scholar 

  27. T. Loegager and K. Sehested, Formation and decay of peroxynitric acid: a pulse radiolysis study, J. Phys. Chem., 1993, 97, 10047–10052.

    Article  CAS  Google Scholar 

  28. J. Zielonka, A. Sikora, M. Hardy, J. Joseph, B. P. Dranka and B. Kalyanaraman, Boronate probes as diagnostic tools for real time monitoring of peroxynitrite and hydroperoxides, Chem. Res. Toxicol., 2012, 25(9), 1793–1799.

    Article  CAS  Google Scholar 

  29. N. Ieda, H. Nakagawa, T. Peng, D. Yang, T. Suzuki and N. Miyata, Photocontrollable peroxynitrite generator based on, N-methyl-N-nitrosoaminophenol for cellular application, J. Am. Chem. Soc., 2012, 134(5), 2563–2568.

    Article  CAS  Google Scholar 

  30. L. Huang, W. Xuan, T. Sarna and M. R. Hamblin, Comparison of thiocyanate and selenocyanate for potentiation of antimicrobial photodynamic therapy, J. Biophotonics, 2018, e201800092.

  31. L. Huang, W. Xuan, A. Zadlo, A. Kozinska, T. Sarna and M. R. Hamblin, Antimicrobial photodynamic inactivation is potentiated by the addition of selenocyanate: Possible involvement of selenocyanogen?, J. Biophotonics, 2018, e201800029.

  32. T. Loegager and K. Sehested, Formation and decay of peroxynitrous acid: a pulse radiolysis study, J. Phys. Chem., 1993, 97, 6664–6669.

    Article  CAS  Google Scholar 

  33. L. P. Olson, M. D. Bartberger and K. N. Houk, Peroxynitrate and peroxynitrite: a complete basis set investigation of similarities and differences between these NOx species, J. Am. Chem. Soc., 2003, 125(13), 3999–4006.

    Article  CAS  Google Scholar 

  34. K. N. Houk, K. R. Condorski and W. A. Pryor, Radical and Concertaed Mechanisms in Oxidations of Amines, Sulfides, and Alkenes by Peroxynitrite, Peroxynitrous Acid, and the Peroxynitrite−CO2 Adduct: Density Functional Theory Transition Structures and Energetics, J. Am. Chem. Soc., 1996, 118, 13002–13006.

    Article  CAS  Google Scholar 

  35. S. Vayssie and H. Elias, Fast Oxidation of Organic Sulfides by Hydrogen Peroxide by In Situ Generated Peroxynitrous Acid, Angew. Chem., Int. Ed. Engl., 1998, 37(15), 2088–2090.

    Article  CAS  Google Scholar 

  36. H. K. Dahle, Nitrite as a food additive, NIPH Ann., 1979, 2(2), 17–24.

  37. M. C. Matallana Gonzalez, M. J. Martinez-Tome and M. E. Torija Isasa, Nitrate and nitrite content in organically cultivated vegetables, Food Addit. Contam., Part B, 2010, 3(1), 19–29.

    Article  CAS  Google Scholar 

  38. V. E. Nossaman, B. D. Nossaman and P. J. Kadowitz, Nitrates and nitrites in the treatment of ischemic cardiac disease, Cardiol. Rev., 2010, 18(4), 190–197.

    Article  Google Scholar 

  39. J. Tenovuo, The biochemistry of nitrates, nitrites, nitrosamines and other potential carcinogens in human saliva, J. Oral Pathol., 1986, 15(6), 303–307.

  40. A. Butler, Nitrites and nitrates in the human diet: Carcinogens or beneficial hypotensive agents?, J. Ethnopharmacol., 2015, 167, 105–107.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael R. Hamblin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, YY., Rajda, P.J., Szewczyk, G. et al. Sodium nitrite potentiates antimicrobial photodynamic inactivation: possible involvement of peroxynitrate. Photochem Photobiol Sci 18, 505–515 (2019). https://doi.org/10.1039/c8pp00452h

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c8pp00452h

Navigation