PPG Biotec, Federal University of São Carlos, São Carlos, Brazil.
São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil.
PLoS Negl Trop Dis. 2024 Nov 12;18(11):e0012637. doi: 10.1371/journal.pntd.0012637. eCollection 2024 Nov.
Sporotrichosis is a zoonotic disease caused by the dimorphic fungus Sporothrix spp., leading to skin lesions that can, in some cases, progress and result in the death of infected individuals. Candida albicans is another fungus involved in several skin, oral, and vaginal mucosal infections. Fungal diseases are concerning due to increasing incidence and the limited variety of antifungal classes available for treatment. Furthermore, antifungal medications can cause various side effects, exacerbated by their prolonged use during infection treatment. There is a need to explore alternatives to conventional drugs that are effective, fast, and safe in combating sporotrichosis. This study aimed to achieve in vitro elimination of the fungi Sporothrix brasiliensis and Sporothrix schenckii through Photodynamic Inactivation (PDI), using curcumin as a photosensitizer and in combination with antifungal agents used in the treatment of sporotrichosis.
Yeasts of Candida albicans, Sporothrix brasiliensis, and Sporothrix schenckii were subjected to Photodynamic Inactivation (PDI) using light at a wavelength of 450 ± 10 nm, irradiance of 35 mW/cm2, delivering a fluence of 31.5 J/cm2, with curcumin as the photosensitizer at doses ranging from 0.75 to 150 μg/mL. After determining the Minimum Inhibitory Concentration (MIC) values of the antifungal drugs itraconazole, ketoconazole, and potassium iodide, sub-MIC doses of these antifungals were combined with sub-MIC doses of curcumin in a new PDI session.
Photodynamic inactivation is a promising technique in the treatment of sporotrichosis, as well as its combination with antifungals. The combination of curcumin in concentrations ranging from 0.75 g/mL a 7.5 g/mL with sub-MIC concentrations of itraconazole, ketoconazole, and potassium iodide was able to completely inactivate the fungi C. albicans, S. brasiliensis and S. schenckii, indicating that PDI may increase the effectiveness of antifungals. However, further studies are needed to establish protocols for future clinical applications.
孢子丝菌病是一种由双相真菌孢子丝菌属引起的人畜共患病,导致皮肤损伤,在某些情况下,会进展并导致感染个体死亡。白色念珠菌是另一种真菌,参与多种皮肤、口腔和阴道黏膜感染。由于发病率不断增加以及可用于治疗的抗真菌药物种类有限,真菌病令人担忧。此外,抗真菌药物会引起各种副作用,并且在感染治疗期间长期使用会加剧这些副作用。因此,需要探索替代传统药物的方法,这些方法在对抗孢子丝菌病方面既有效、快速又安全。本研究旨在通过光动力灭活(PDI)使用姜黄素作为光敏剂并结合用于治疗孢子丝菌病的抗真菌药物,实现巴西孢子丝菌和申克孢子丝菌的体外消除。
白色念珠菌、巴西孢子丝菌和申克孢子丝菌的酵母菌进行光动力灭活(PDI),使用波长为 450 ± 10nm、辐照度为 35mW/cm2、传递 31.5J/cm2 的光,姜黄素作为光敏剂的剂量范围为 0.75 至 150μg/mL。确定了抗真菌药物伊曲康唑、酮康唑和碘化钾的最小抑菌浓度(MIC)值后,在新的 PDI 会议中,将这些抗真菌药物的亚 MIC 剂量与姜黄素的亚 MIC 剂量组合。
光动力灭活是治疗孢子丝菌病的一种有前途的技术,以及与抗真菌药物的结合。姜黄素在 0.75g/mL 至 7.5g/mL 浓度范围内与伊曲康唑、酮康唑和碘化钾的亚 MIC 浓度联合使用,能够完全灭活白色念珠菌、巴西孢子丝菌和申克孢子丝菌,表明 PDI 可能增加抗真菌药物的有效性。然而,需要进一步的研究来建立未来临床应用的方案。