Miranda Milena Menegazzo, Panis Carolina, Cataneo Allan Henrique Depieri, da Silva Suelen Santos, Kawakami Natalia Yoshie, Lopes Luiz Gonzaga de França, Morey Alexandre Tadachi, Yamauchi Lucy Megumi, Andrade Célia Guadalupe Tardelli de Jesus, Cecchini Rubens, da Silva Jean Jerley Nogueira, Sforcin José Maurício, Conchon-Costa Ivete, Pavanelli Wander Rogério
Department of Pathology Science, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.
Laboratory of Inflammatory Mediators, State University of Western Paraná, Francisco Beltrão, Paraná, Brazil.
PLoS One. 2015 May 14;10(5):e0125101. doi: 10.1371/journal.pone.0125101. eCollection 2015.
The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL). In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania) amazonensis and subsequently treated with a combination of nitric oxide (NO) donor (cis-Ru(bpy) 2imN(NO)3) (Ru-NO), given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis.
目前用于治疗利什曼原虫病的药物毒性很强且会产生获得性耐药，这一事实促使人们去寻找治疗美洲皮肤利什曼病（ATL）的新疗法。在本研究中，将亚马逊利什曼原虫（Leishmania (Leishmania) amazonensis）注射到BALB/c小鼠的后爪，随后用一氧化氮（NO）供体（顺式-Ru(bpy)₂imN(NO)₃）（Ru-NO）腹腔注射并联合口服巴西蜂胶进行治疗，持续30天。Ru-NO到达病变中心，且在不加重病变的情况下提高了受伤后爪的NO水平。慢性炎症的组织学和免疫学参数表明，这种联合治疗提高了巨噬细胞的功效，这由被寄生细胞数量的减少来确定，从而导致促炎和组织损伤标志物的表达降低。此外，这些药物联合使用促进了伤口愈合，增加了成纤维细胞数量、促愈合细胞因子，并在病变部位诱导了胶原蛋白合成。总体而言，我们的研究结果表明，NO供体Ru-NO与巴西蜂胶的联合使用可减轻实验性ATL病变，突出了一种新的治疗选择，可作为皮肤利什曼病治疗的候选方案进一步进行体内研究。
