Laboratório de Imunofarmacologia Parasitária, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Catálise Orgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Front Cell Infect Microbiol. 2023 Jan 19;13:1025359. doi: 10.3389/fcimb.2023.1025359. eCollection 2023.
Current therapeutic ways adopted for the treatment of leishmaniasis are toxic and expensive including parasite resistance is a growing problem. Given this scenario, it is urgent to explore treatment alternatives for leishmaniasis. The aim of this study was to evaluate the effect of 3-phenyl-lawsone (3-PL) naphthoquinone on () infection, both and , using two local routes of administration: subcutaneous (higher dose) and tattoo (lower dose). 3-PL showed low toxicity for macrophages (CC >3200 µM/48h) and activity against intracellular amastigotes (IC = 193 ± 19 µM/48h) and promastigotes (IC = 116 ± 26 µM/72h), in which induced increased ROS generation. Additionally, 3-PL up-regulated the production of cytokines such as tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-10 in infected macrophages. However, the anti-amastigote action was independent of nitric oxide production. Treatment of hamsters infected with () from one week after infection with 3-PL by subcutaneous (25 µg/Kg) or tattooing (2.5 µg/Kg) route, during 3 weeks (3 times/week) or 2 weeks (2 times/week) significantly decreased the parasite load (p<0.001) in the lesion. The reduction of parasite load by 3-PL treatment was comparable to reference drug meglumine antimoniate administered by the same routes (subcutaneous 1mg/Kg and tattoo 0.1mg/Kg). In addition, treatment started from five weeks after infection with 3-PL per tattoo also decreased the parasite load. These results show the anti-leishmanial effect of 3-PL against () and its efficacy by subcutaneous (higher dose) and tattoo (lower dose) routes. In addition, this study shows that drug delivery by tattooing the lesion allows the use of lower doses than the conventional subcutaneous route, which may support the development of a new therapeutic strategy that can be adopted for leishmaniasis.
目前用于治疗利什曼病的治疗方法是有毒且昂贵的，包括寄生虫耐药性是一个日益严重的问题。鉴于这种情况，迫切需要探索利什曼病的治疗替代方法。本研究旨在评估 3-苯基劳森（3-PL）萘醌对（）感染的影响，包括和，使用两种局部给药途径：皮下（高剂量）和纹身（低剂量）。3-PL 对巨噬细胞的毒性较低（CC >3200µM/48h），对细胞内无鞭毛体（IC = 193 ± 19µM/48h）和前鞭毛体（IC = 116 ± 26µM/72h）具有活性，诱导增加 ROS 生成。此外，3-PL 上调了感染巨噬细胞中细胞因子的产生，如肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白 1（MCP-1）、白细胞介素-6（IL-6）和白细胞介素-10。然而，抗无鞭毛体作用与一氧化氮产生无关。在感染后一周用 3-PL 通过皮下（25µg/Kg）或纹身（2.5µg/Kg）途径治疗感染（）的仓鼠，在 3 周（每周 3 次）或 2 周（每周 2 次）期间，显著降低病变中的寄生虫负荷（p<0.001）。3-PL 治疗降低寄生虫负荷的效果可与皮下给予的参考药物葡甲胺锑酸钠（1mg/Kg）和纹身给予的 0.1mg/Kg 相当。此外，从感染后五周开始用 3-PL 通过纹身进行治疗也降低了寄生虫负荷。这些结果表明 3-PL 对（）具有抗利什曼原虫作用，并且通过皮下（高剂量）和纹身（低剂量）途径具有疗效。此外，本研究表明通过在病变处纹身给药可以使用比传统皮下途径更低的剂量，这可能支持开发一种新的治疗策略，可用于治疗利什曼病。
