Abstract
The antifungal drug therapy often employed to treat paracoccidiodomycosis (PCM), an important neglected fungal systemic infection, leads to offensive adverse effects, besides being very long-lasting. In addition, PCM compromises the oral health of patients by leading to oral lesions that are very painful and disabling. In that way, photodynamic therapy (PDT) arises as a new promising adjuvant treatment for inactivating Paracoccidioides brasiliensis (Pb), the responsible fungus for PCM, and also for helping the patients to deal with such debilitating oral lesions. PDT has been linked to an improved microbial killing, also presenting the advantage of not inducing immediate microbial resistance such as drugs. For the present study, we investigated the generation of reactive oxygen species (ROS) by using the fluorescent probes hydroxyphenyl fluorescein (HPF) and aminophenyl fluorescein (APF) after toluidine blue (TBO—37.5 mg/L)-mediated PDT (660 nm, 40 mW, and 0.04 cm2 spot area) and the action of TBO-PDT upon Pb cultures grown for 7 or 15 days in semisolid Fava Netto’s culture medium; we also targeted oral PCM manifestations by reporting the first clinical cases (three patients) to receive topic PDT for such purpose. We were able to show a significant generation of hydroxyl radicals and hypochlorite after TBO-PDT with doses around 90 J/cm2; such ROS generation was particularly useful to attack and inactivate Pb colonies at 7 and 15 days. All three patients reported herein related an immediate relief when it came to pain, mouth opening, and also the ability to chew and swallow. As extracted from our clinical results, which are in fact based on in vitro outcomes, TBO-PDT is a very safe, inexpensive, and promising therapy for the oral manifestations of PCM.
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Acknowledgements
The authors wish to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant INCT of Redox Processes in Biomedicine–Redoxoma, and grant #304827/2012-6; Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), grant CBB-PPM #00119-14, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the grant AUX PE PNPD 2386/2011 and for the Master’s scholarship provided to Ms. Mendes A.C.
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As stated in the “Material and Methods” section, the present study received an approval of the Human Research Ethics Committee of our institution (Protocol # 968.594).
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As stated in the “Material and Methods” section, the clinical treatment of human subjects was only possible after obtaining the Ethics Committee approval and informed consents. In addition, all experiments were performed obeying the relevant laws and institutional guidelines according to the ethical principles of the Declaration of Helsinki.
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dos Santos, L.F.M., Melo, N.B., de Carli, M.L. et al. Photodynamic inactivation of Paracoccidioides brasiliensis helps the outcome of oral paracoccidiodomycosis. Lasers Med Sci 32, 921–930 (2017). https://doi.org/10.1007/s10103-017-2193-y
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DOI: https://doi.org/10.1007/s10103-017-2193-y