Andrade Gabriela Carvalho, Brancini Guilherme Thomaz Pereira, Abe Flávia Renata, de Oliveira Danielle Palma, Nicolella Heloiza Diniz, Tavares Denise Crispim, Micas André Fernando Ditondo, Savazzi Eduardo Angelino, Silva-Junior Geraldo José, Wainwright Mark, Braga Gilberto Úbida Leite
University of São Paulo (USP), School of Pharmaceutical Sciences of Ribeirão Preto, 14040-903 Ribeirão Preto, SP, Brazil.
University of São Paulo (USP), School of Pharmaceutical Sciences of Ribeirão Preto, 14040-903 Ribeirão Preto, SP, Brazil; National Institute for Alternative Technologies of Detection, Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT-DATREM), São Paulo State University (UNESP), Institute of Chemistry, 14800-060 Araraquara, SP, Brazil.
J Photochem Photobiol B. 2022 Jan;226:112365. doi: 10.1016/j.jphotobiol.2021.112365. Epub 2021 Nov 16.
The widespread use of conventional chemical antifungal agents has led to worldwide concern regarding the selection of resistant isolates. In this scenario, antimicrobial photodynamic treatment (APDT) has emerged as a promising alternative to overcome this issue. The technique is based on the use of a photosensitizer (PS) and light in the presence of molecular oxygen. Under these conditions, the PS generates reactive oxygen species which damage the biomolecules of the target organism leading to cell death. The great potential of APDT against plant-pathogenic fungi has already been reported both in vitro and in planta, indicating this control measure has the potential to be widely used in crop plants. However, there is a lack of studies on environmental risk with ecotoxicological assessment of PSs used in APDT. Therefore, this study aimed to evaluate the environmental toxicity of four phenothiazinium PSs: i) methylene blue (MB), ii) new methylene blue N (NMBN), iii) toluidine blue O (TBO), and iv) dimethylmethylene blue (DMMB) and also of the commercial antifungal NATIVO®, a mixture of trifloxystrobin and tebuconazole. The experiments were performed with Daphnia similis neonates and zebrafish embryos. Our results showed that the PSs tested had different levels of toxicity, with MB being the less toxic and DMMB being the most. Nonetheless, the environmental toxicity of these PSs were lower when compared to that of NATIVO®. Furthermore, estimates of bioconcentration and of biotransformation half-life indicated that the PSs are environmentally safer than NATIVO®. Taken together, our results show that the toxicity associated with phenothiazinium PSs would not constitute an impediment to their use in APDT. Therefore, APDT is a promising approach to control plant-pathogenic fungi with reduced risk for selecting resistant isolates and lower environmental impacts when compared to commonly used antifungal agents.
传统化学抗真菌剂的广泛使用已引发全球对耐药菌株选择的关注。在这种情况下，抗菌光动力疗法（APDT）已成为克服这一问题的一种有前景的替代方法。该技术基于在分子氧存在下使用光敏剂（PS）和光。在这些条件下，PS产生活性氧物种，这些活性氧物种会破坏目标生物体的生物分子，导致细胞死亡。APDT对植物病原真菌的巨大潜力已在体外和植物体内得到报道，表明这种控制措施有可能在农作物中广泛应用。然而，目前缺乏对APDT中使用的PS进行生态毒理学评估的环境风险研究。因此，本研究旨在评估四种吩噻嗪类PS的环境毒性：i）亚甲蓝（MB），ii）新亚甲蓝N（NMBN），iii）甲苯胺蓝O（TBO），iv）二甲基亚甲蓝（DMMB），以及商业抗真菌剂NATIVO®（肟菌酯和戊唑醇的混合物）的环境毒性。实验是用拟水溞幼体和斑马鱼胚胎进行的。我们的结果表明，所测试的PS具有不同程度的毒性，其中MB毒性最小，DMMB毒性最大。尽管如此，与NATIVO®相比，这些PS的环境毒性较低。此外，生物富集和生物转化半衰期的估计表明，PS在环境中比NATIVO®更安全。综上所述，我们的结果表明，与吩噻嗪类PS相关的毒性不会阻碍它们在APDT中的使用。因此，与常用抗真菌剂相比，APDT是一种有前景的控制植物病原真菌的方法，具有选择耐药菌株风险降低和环境影响较小的优点。
