Abstract
This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT) in the treatment of oral candidiasis in a murine model using Photodithazine® (PDZ). This model of oral candidiasis was developed to allow the monitoring of the infection and the establishment of the aPDT treatment. Six-week-old female mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDZ-mediated aPDT and nystatin treatment were carried out for 5 consecutive days with one application per day. The macroscopic evaluation of oral lesions was performed. After each treatment, the tongue was swabbed to recover C. albicans cells. Viable colonies were quantified and the number of CFU/ml determined. The animals were sacrificed 24 hours and 7 days after treatment and the tongues were surgically removed for histological analysis and analysis of inflammatory cytokines expression (IL-1, TNF-α and IL-6) by RT-qPCR. Data were analyzed by two-way ANOVA. PDZ-mediated aPDT was as effective as Nystatin (NYS group) in the inactivation of C. albicans, reducing 3 and 3.2 logs10 respectively, 24 h after treatment (p<0.05). Animals underwent PDZ-mediated aPDT showed complete remission of oral lesions, while animals treated with NYS presented partial remission of oral lesions in both periods assessed. Histological evaluation revealed mild inflammatory infiltrate in the groups treated with aPDT and NYS in both periods assessed. The aPDT induced the TNF-α expression when compared with the control (P-L-) (p<0.05), 24 h and 7 days after treatment. In summary, the murine model developed here was able to mimic the infection and PDZ-mediated aPDT was effective to treat mice with oral candidiasis.
Highlights
Candida species are part of the normal oral microbiota [1] being Candida albicans the most common species associated with clinical manifestations, which range from superficial mucocutaneous lesions, such as oropharyngeal candidiasis (OPC), to disseminated forms of the infection [2]
The murine model of oral candidiasis employed here was successfully established, which could be confirmed by the presence of white patches or pseudomembrane on the tongue of all immunosuppressed animals infected with C. albicans in the control group throughout 16 days (Fig 2)
The severity of the lesions was assessed at day 5 until the last day of the experiment and it was recovered 105 CFU/ml of C. albicans from the oral cavity of animals (Fig 3)
Summary
Candida species are part of the normal oral microbiota [1] being Candida albicans the most common species associated with clinical manifestations, which range from superficial mucocutaneous lesions, such as oropharyngeal candidiasis (OPC), to disseminated forms of the infection [2]. OPC is the result of adhesion and penetration of fungal species into the oral tissues [3] and it has a high incidence in patients that use immunosuppressive drugs, broad-spectrum antibiotics, anti-diabetic mediations, anticancer therapies, and in patients with the acquired immunodeficiency syndrome (AIDS) [4]. The use of topical or systemic antifungal agents (azole, polyenes) for the treatment of OPC has resulted in the development of resistant Candida species [5]. The organization of microorganisms in biofilms is a protective shell, enabling the survival of these pathogens even in unfavorable conditions and providing high resistance to antifungal agents [6]. Considering the increased incidence of resistant pathogens to conventional antifungal treatments and drug toxicity, studies have searched for strategies to control fungal species. The interaction of the appropriate wavelength of light with the PS in the presence of oxygen results in reactive oxygen species (ROS) capable of inducing death of microorganisms by oxidative damage [10]
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