Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Photodiagnosis Photodyn Ther. 2013 May;10(2):141-9. doi: 10.1016/j.pdpdt.2012.11.004. Epub 2012 Dec 3.
In the present study, the in vitro susceptibilities of five Candida spp. to photodynamic antimicrobial chemotherapy (PACT) with four phenothiazinium derivatives, methylene blue (MB), new methylene blue N (NMBN), toluidine blue O (TBO) and the novel pentacyclic phenothiazinium photosensitiser S137, in combination with red light were investigated. The efficacy of each PS was determined, initially, based on its minimal inhibitory concentration (MIC). Additionally, we evaluated the effect of the photodynamic treatment with NMBN and S137 on Candida survival and on the mouse fibroblast cell line L929. MICs varied both among PS and species and decreased with light dose increase. For most treatments (species and fluences) NMBN and S137 showed the lowest MICs. MICs for NMBN and S137 were <2.5 μM for all the Candida species when a fluence of 25 J cm⁻² was used. PACT with NMBN (fluence of 15 J cm⁻²) resulted in reductions in survival from 0.3 log (Candida krusei) to 3 logs (C. parapsilosis). PACT with S137 was more effective than with NMBN. Fluence of 15 J cm⁻² resulted in reductions in survival from 1 log (C. krusei) to 3 logs (C. parapsilosis) and fluence of 25 J cm⁻² resulted in a reduction of approximately 2 logs (C. krusei) and between 3 and 4 logs in survival of the other 4 species of Candida. In vitro relative toxicities of the phenothiazinium PS to mammalian cells exhibited a similar trend to the antifungal data, i.e. greater toxicity and phototoxicity with NMBN and S137 compared to the established PS.
在本研究中，我们研究了五种念珠菌属对光动力抗菌化疗（PACT）的体外敏感性，所用的四种吩噻嗪衍生物为亚甲蓝（MB）、新型亚甲蓝 N（NMBN）、甲苯胺蓝 O（TBO）和新型五环吩噻嗪光敏剂 S137，与红光联合使用。我们首先根据最小抑菌浓度（MIC）确定每种 PS 的功效。此外，我们还评估了 NMBN 和 S137 的光动力治疗对念珠菌存活和小鼠成纤维细胞系 L929 的影响。PS 种类和光剂量的不同都会导致 MIC 发生变化。对于大多数治疗（物种和辐照度），NMBN 和 S137 显示出最低的 MIC。当使用 25 J cm⁻² 的辐照度时，NMBN 和 S137 的 MIC 对于所有念珠菌物种均<2.5 μM。NMBN（15 J cm⁻² 的辐照度）的 PACT 导致存活率从 0.3 对数（克柔念珠菌）降低至 3 对数（近平滑念珠菌）。与 NMBN 相比，S137 的 PACT 更有效。15 J cm⁻² 的辐照度导致存活率从 1 对数（克柔念珠菌）降低至 3 对数（近平滑念珠菌），而 25 J cm⁻² 的辐照度导致大约 2 对数（克柔念珠菌）和其他 4 种念珠菌的存活率降低 3 到 4 对数。体外相对毒性实验结果表明，吩噻嗪 PS 对哺乳动物细胞的毒性与抗真菌数据具有相似的趋势，即 NMBN 和 S137 的毒性和光毒性大于已建立的 PS。
