Nascimento Nilberto Robson Falcão do, Aguiar Francisco Léo Nascimento de, Santos Cláudia Ferreira, Costa Angélica Maria Luna, Hardoim Daiana de Jesus, Calabrese Kátia da Silva, Almeida-Souza Fernando, Sousa Eduardo Henrique Silva de, Lopes Luiz Gonzaga de França, Teixeira Maria Jania, Pereira Vandbergue Santos, Brilhante Raimunda Sâmia Nogueira, Rocha Marcos Fábio Gadelha
School of Veterinary, Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, Ceará, Brazil.
School of Veterinary, Postgraduate Program in Veterinary Sciences, State University of Ceará, Fortaleza, Ceará, Brazil.
Acta Trop. 2019 Apr;192:61-65. doi: 10.1016/j.actatropica.2019.01.021. Epub 2019 Jan 25.
Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. There are many complications presented by the current treatment, as high toxicity, high cost and parasite resistance, making the development of new therapeutic agents indispensable. The present study aims to evaluate the leishmanicidal potential of ruthenium nitrosyl complex cis-Ru(bpy)(SO)(NO) against Leishmania (Viannia) braziliensis. The effect of this metal complex on parasite-host interaction was evaluated by in vitro efficacy test in dermal fibrobast cells in the presence of different concentrations (1, 10, 50 and 100 μM) and by in vivo efficacy tests performed in the presence of two different concentrations of complex (100 μg/kg/day or 300 μg/kg/day) evaluating its effect on the size of the lesion and the number of parasites present in the draining lymph nodes in hamsters. Even at the lowest concentration of 1 μM of ruthenium complex, it was observed a significant decrease of the infected cells, after 24 h exposure in vitro, with total reduction at 50 μM of the ruthenium complex. In the in vivo cutaneous infection model, administration of daily doses of 300 μg/kg/day of complex reduced significantly lesion size by 51% (p < 0.05), with a 99.9% elimination of the parasites found in the lymph nodes (p < 0.001). The results suggest a promising leishmanicidal effect by that ruthenium nitrosyl complex against L. (V.) braziliensis.
利什曼病是一种由利什曼原虫属的原生动物引起的寄生虫病。当前治疗存在许多并发症，如高毒性、高成本和寄生虫耐药性，这使得开发新的治疗药物不可或缺。本研究旨在评估亚硝酰钌配合物顺式-Ru(bpy)(SO)(NO)对巴西利什曼原虫（维氏亚属）的杀利什曼原虫潜力。通过在不同浓度（1、10、50和100μM）存在下对皮肤成纤维细胞进行体外疗效试验，以及在两种不同浓度的配合物（100μg/kg/天或300μg/kg/天）存在下进行体内疗效试验，评估这种金属配合物对寄生虫-宿主相互作用的影响，评估其对仓鼠病变大小和引流淋巴结中存在的寄生虫数量的影响。即使在最低浓度1μM的钌配合物下，体外暴露24小时后也观察到感染细胞显著减少，在50μM的钌配合物下感染细胞完全减少。在体内皮肤感染模型中，每天给予300μg/kg/天的配合物可使病变大小显著减少51%（p<0.05），淋巴结中发现的寄生虫消除率达99.9%（p<0.001）。结果表明，该亚硝酰钌配合物对巴西利什曼原虫（维氏亚属）具有有前景的杀利什曼原虫作用。
