Riboflavin in photodynamic inactivation of pathogens and photodynamic therapy
Keywords:
riboflavin, photodynamic, antimicrobial, antiviral, UVA, UVBAbstract
Riboflavin, besides its key role in providing cellular metabolism in humans and animals, is used as a compound of antimicrobial photodynamic therapy (aPDT) owing to its photosensitizing capability. PDT is a promising approach for the photoinactivation of pathogens in blood and blood derivatives. It has been reported, that the advantage of antimicrobial photodynamic therapy is that there are no resistant strains to it. Flavins are photoreducible and photon-induced excitation of them in the ultraviolet-blue (UV-blue) spectral band can lead to formation of either singlet oxygen via energy transfer to environmental oxygen, or hydrogen peroxide and derivatives via radicalisation – altogether termed reactive oxygen species (ROS) and used hereafter. Exactly the ROS production property of riboflavin is used for antiviral and antibacterial disinfection; for strengthening the corneal tissue in photorefractive surgery by the ROS-induced collagen cross-linking. Several studies reveal the antimicrobial photodynamic potential of riboflavin irradiated with the ultraviolet-blue and with visible light against methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis, enterohemorrhagic Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Bacillus subtilis in vitro. It was shown, that riboflavin/UV-A and allowed effectiveness against such fungal pathogens as Candida albicans, Candida parapsilosis, Fusarium spр, and A. fumigatusas which may cause infection keratomycosis. The photoilluminated riboflavin significantly reduced the activity of superoxide dismutase (SOD) and reduced the level of cellular antioxidant metabolite - glutathione (GSH). Along with that the specific activity of glutathione S-transferase (GST) - which is involved in detoxification process - was increased significantly in cells exposed to photoilluminated riboflavin. Riboflavin, illuminated by UVA or visible light, has also been developed as a nucleic acid-binding agent to be used for photoinactivation of such nucleic acid-containing pathogens in plasma, platelets, and RBCs as viruses. Several studies have revealed the effectiveness of reduction in some viruses’ infectivity, including human immunodeficiency virus 1 (HIV-1), bovine viral diarrhea virus (BVDV), hepatitis B virus (HCV), pseudorabies virus. Thus, the «riboflavin+UVB» system has found their application in pathogen reduction technology – «Mirasol»® Pathogen Reduction Technology (PRT) system. Riboflavin has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Several studies reveal that of PDT-mediated cytotoxicity occur in three ways: apoptotic, necrotic and autophagy-associated cell death. Some findings, show that certain PDT techniques acting via inducing of apoptotic cell death that is highly immunogenic and can stimulate antitumor immunity. Thus, we can conclude that, the «riboflavin+UVB» system is suitable for photoinactivation of bacteria, fungi and viruses and has a potential in antitumor treatment strategies. Further studies will reveal more and more aspects of riboflavin capabilities.
References
Sousa V, Gomes ATPC, Freitas A, Faustino MAF, Neves MGPMS, Almeida A. Photodynamic Inactivation of Candida albicans in Blood Plasma and Whole Blood. Antibiotics (Basel). 2019;8(4):221. Published 2019 Nov 13. doi:10.3390/antibiotics8040221
Abrahamse H, Hamblin MR. New photosensitizers for photodynamic therapy. Biochem J. 2016;473(4):347–364. doi:10.1042/BJ20150942
Makdoumi K, Backman A, Mortensen J, Crafoord S. Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA) Graefes Arch Clin Exp Ophthalmol. 2010;248:207–212.
Ettinger A, Miklauz MM, Bihm DJ, Maldonado-Codina G, Goodrich RP. Preparation of cryoprecipitate from riboflavin and UV light-treated plasma. Transfus Apher Sci. 2012;46:153–158.
Chan TC, Lau TW, Lee JW, Wong IY, Jhanji V, Wong RL. Corneal collagen cross-linking for infectious keratitis: an update of clinical studies. Acta Ophthalmol 2015
Abrahamse H, Hamblin MR. New photosensitizers for photodynamic therapy. Biochem J. 2016;473(4):347–364. doi:10.1042/BJ20150942
Maisch T, Eichner A, Spath A, Gollmer A, Konig B, Regensburger J, Baumler W. Fast and effective photodynamic inactivation of multiresistant bacteria by cationic riboflavin derivatives. PLoS One. 2014;9:e111792.
Hamblin MR. Antimicrobial photodynamic inactivation: a bright new technique to kill resistant microbes. Curr Opin Microbiol. 2016;33:67–73. doi:10.1016/j.mib.2016.06.008
Conrad K. S., Bilwes A. M. & Crane B. R. Light-Induced Subunit Dissociation by a Light-Oxygen-Voltage Domain Photoreceptor from Rhodobacter
Agostinis P. et al.. Photodynamic Therapy of Cancer: An Update. Ca-a Cancer Journal for Clinicians 61, 250–281, doi: 10.3322/caac.20114 (2011).
Ruane P. H. et al.. Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light. Transfusion 44, 877–885, doi: 10.1111/j.1537-2995.2004.03355.x (2004).
Wollensak G., Spoerl E. & Seiler T. Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. American Journal of Ophthalmology 135, 620–627, doi: 10.1016/s0002-9394(02)02220-1 (2003).
Sheraz M.A., Kazi S.H., Ahmed S., Anwar Z., Ahmad I. Photo, thermal and chemical degradation of riboflavin. Beilstein J. Org. Chem. 2014;10:1999–2012.
Khan S., Naseem I. Photocatalytic interaction of aminophylline-riboflavin leads to ROS-mediated DNA damage and cell death: a novel phototherapeutic mechanism for cancer. IUBMB Life. 2017;69:611–622.
Bouillaguet S., Wataha J.C., Zapata O., Campo M., Lange N., Schrenzel J. Production of reactive oxygen species from photosensitizers activated with visible light sources available in dental offices. Photomed. Laser Surg. 2010;28:519–525.
Khan S, P MR, Rizvi A, [et al.]. ROS mediated antibacterial activity of photoilluminated riboflavin: A photodynamic mechanism against nosocomial infections // Toxicol. 2019. Vol. 6. P. 136-142.
Maisch T., Eichner A., Späth A. [et al.] Fast and effective photodynamic inactivation of multiresistant bacteria by cationic riboflavin derivatives // PLoS One. 2014. Vol. 9(12):e111792.
Thakuri PS, Joshi R, Basnet S, [et al.] Antibacterial photodynamic therapy on Staphylococcus aureus and Pseudomonas aeruginosa in vitro // Nepal Med. Coll. J. 2011. Vol. 13(4). P. 281-284.
O'Rourke JF, Dowds BC. Dye-mediated photodynamic inactivation of Bacillus subtilis // Biochem. Soc. Trans. 1992. Vol. 20(1). P. 76S.
Yin R, Hamblin MR. Antimicrobial Photosensitizers: Drug Discovery Under the Spotlight // Curr Med Chem. 2015. Vol. 22(18). P. 2159-2185.
Makdoumi K, Goodrich R, Bäckman A. Photochemical eradication of methicillin-resistant Staphylococcus aureus by blue light activation of riboflavin // Acta Ophthalmol. 2017. Vol. 95(5). P. 498-502.
Sauer A, Letscher-Bru V, Speeg-Schatz C, [et al.]. In vitro efficacy of antifungal treatment using riboflavin/UV-A (365 nm) combination and amphotericin B // Invest Ophthalmol Vis Sci. 2010. Vol. 51(8). P. 3950-3953.
Tunccan ÖG, Kalkanci A, Unal EA, [et al.] The in vitro effect of antimicrobial photodynamic therapy on Candida and Staphylococcus biofilms // Turk. J. Med. Sci. 2018.Vol. 48(4). P. 873–879.
Schuyler R. Use of riboflavin for photoinactivation of pathogens in blood components // Transfus. Apher. Sci. 2001. Vol. 25. P. 189–190.
Zhu L, Tong H, Wang S, [et al.] Effectiveness of a flow-based device using riboflavin photochemistry in damaging blood-borne viral nucleic acids // J. Photochem. Photobiol. B. 2018. Vol. 183. P. 391-396.
Faddy HM, Fryk JJ, Watterson D, [et al.] Riboflavin and ultraviolet light: impact on dengue virus infectivity // Vox Sang. 2016. Vol. 111(3). P. 235-241.
Keil SD, Bowen R, Marschner S. Inactivation of Middle East respiratory syndrome coronavirus (MERS-CoV) in plasma products using a riboflavin-based and ultraviolet light-based photochemical treatment // Transfusion. 2016. Vol. 56(12). P. 2948-2952.
Cap AP, Pidcoke HF, Keil SD, [et al.] Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro // Transfusion. 2016. Vol. 56. Suppl 1. S6-15.
Hermida-Nogueira L, Barrachina MN, Izquierdo I, [et al.] Proteomic analysis of extracellular vesicles derived from platelet concentrates treated with Mirasol® identifies biomarkers of platelet storage lesion // J. Proteomics. 2020. Vol. 210. P. 103529.
Perez‐Pujol S., Tonda R., Lozano M., [et al.] Effects of a new pathogen‐reduction technology (Mirasol PRT) on functional aspects of platelet concentrates // Transfusion. Vol. 45, Issue 6. P. 911-919.
Abonnenc M., Crettaz D., Sonego G. [et al]. Towards the understanding of the UV light, riboflavin and additive solution contributions to the in vitro lesions observed in Mirasol®-treated platelets // Transfus. Clin. Biol. 2019. Vol. 26. Issue 4. P. 209-216.
Yuan Y, Zhao Y, Chen L, [et al.] Selective tumor cell death induced by irradiated riboflavin through recognizing DNA G-T mismatch // Nucleic Acids Res. 2017. Vol. 45. N. 15. P. 8676–8683.
Garg AD, Nowis D, Golab J, [et al.] Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation // Biochim. Biophys. Acta. 2010. Vol. 1805. P. 53–71.
Akasov RA, Sholina NV, Khochenkov DA, [et al]. Photodynamic therapy of melanoma by blue-light photoactivation of flavin mononucleotide // Sci Rep. 2019. Vol. 9. Issue 1. P. 9679.
Lim L, Lim EWL. A Review of Corneal Collagen Cross-linking - Current Trends in Practice Applications // Open Ophthalmol J. 2018. Vol. 12. P. 181–213.
Mohammadpour M, Masoumi A, Mirghorbani M, [et al.] Updates on corneal collagen cross-linking: Indications, techniques and clinical outcomes // J. Curr. Ophthalmol. 2017. Vol. 29(4). P. 235–247.
Zhu Y., Reinach PS., Zhu H., [et al.] High-intensity corneal collagen crosslinking with riboflavin and UVA in rat cornea // PLoS One. 2017. Vol. 12(6):e0179580.
Skaat A, Zadok D, Goldich Y, [et al.] Riboflavin/UVA photochemical therapy for severe infectious keratitis // Eur. J. Ophthalmol. 2014. Vol. 24. Issue 1. P. 21-28.
Song X, Stachon T, Wang J, [et al.]. Viability, apoptosis, proliferation, activation, and cytokine secretion of human keratoconus keratocytes after cross-linking // Biomed. Res. Int. 2015. Vol. 2015. P. 254237.
Downloads
How to Cite
Issue
Section
License
Copyright (c) 2020 Annals of Mechnikov's Institute
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.
