title: Vascular alterations after photodynamic therapy mediated by 5-aminolevulinic acid in oral leukoplakia.
abstract: Impairment of vascular functions after photodynamic therapy (PDT) is frequently associated with tumor remission and is considered one of the main antineoplastic PDT effects. Vascular alterations in oral leukoplakia (OL) treated with PDT have not yet been described. The aim of this study was to evaluate the effect of topical 5-ALA-mediated PDT on the vascular network of 4NQO-induced OL in rats. After applying 4NQO topically on the tongue during 16 weeks, there was induction of dysplastic lesions, which were treated with two PDT sessions (with an interval of 72 h between them), using topical application of 5-ALA and posterior irradiation with a laser (90 J/cm2fluency). Histological sections of the tongues were obtained and analyzed concerning plasmatic exudation and microvessel density after immunolabeling with CD31 and CD34 vessel markers. There was intense plasmatic exudation after 6 h of the first PDT session; at 6 h of the second PDT session, there was a significant reduction in the density of CD31- and CD34-positive microvessels in comparison to controls (p < 0.05). In the PDT intervals, there was an increase in the density of CD31 and CD34 microvessels, suggesting angiogenesis. Topical application of 5-ALA-mediated PDT caused an immediate deleterious effect on the vascular network, increasing vessel permeability and reducing vessel density, mainly after two sessions of the treatment. However, secondary angiogenesis emerged in these lesions during intervals of the PDT session. This fact may be considered during the adoption of a PDT protocol, to avoid OL resistance and recurrence after the treatment.
authors.affiliation: General Pathology Department, School of Dentistry, University of São Paulo, Av. Prof Lineu Prestes, 2227 - Cidade Universitária, 05508-000, São Paulo, SP, Brazil.
authors.forename: Flávia Cristina Perillo
authors.initials: FC
authors.lastname: Rosin
authors.affiliation: Health Department, School of Nursing, Federal University of Amapá, Rod. Juscelino Kubitschek, KM-02 Jardim Marco Zero Macapá, 68.903-419, Macapá, AP, Brazil.
authors.forename: Ana Rita Ribeiro
authors.initials: AR
authors.lastname: Barcessat
authors.affiliation: General Pathology Department, School of Dentistry, University of São Paulo, Av. Prof Lineu Prestes, 2227 - Cidade Universitária, 05508-000, São Paulo, SP, Brazil.
authors.forename: Giuliana Gadoni Giovanni
authors.initials: GG
authors.lastname: Borges
authors.affiliation: General Pathology Department, School of Dentistry, University of São Paulo, Av. Prof Lineu Prestes, 2227 - Cidade Universitária, 05508-000, São Paulo, SP, Brazil.
authors.forename: Luciana Gonçalves Valente
authors.initials: LG
authors.lastname: Ferreira
authors.affiliation: General Pathology Department, School of Dentistry, University of São Paulo, Av. Prof Lineu Prestes, 2227 - Cidade Universitária, 05508-000, São Paulo, SP, Brazil. lcorrea@usp.br.
authors.forename: Luciana
authors.identifier: http://orcid.org/0000-0002-5774-0750
authors.initials: L
authors.lastname: Corrêa
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000622:Aminolevulinic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D007972:Leukoplakia, Oral / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000473:pathology*; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D009929:Organ Size; D010778:Photochemotherapy / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000494:pharmacology; D015363:Quinolones; D017208:Rats, Wistar; D014059:Tongue / Q000187:drug effects / Q000473:pathology
chemical_list: C120195:4-nitroquinolone-1-oxide; D017319:Photosensitizing Agents; D015363:Quinolones; D015112:4-Nitroquinoline-1-oxide; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid; Angiogenesis; Microvessel density; Microvessel permeability; Oral premalignant lesion; Photodynamic therapy