In vitro and in vivo leishmanicidal activity of a ruthenium nitrosyl complex against Leishmania (Viannia) braziliensis

被引:26
|
作者
Falcao do Nascimento, Nilberto Robson [1 ]
Nascimento de Aguiar, Francisco Leo [1 ]
Santos, Claudia Ferreira [2 ]
Luna Costa, Angelica Maria [2 ]
Hardoim, Daiana de Jesus [3 ]
Calabrese, Katia da Silva [3 ]
Almeida-Souza, Fernando [3 ,4 ]
Silva de Sousa, Eduardo Henrique [5 ]
de Franca Lopes, Luiz Gonzaga [5 ]
Teixeira, Maria Jania [6 ]
Pereira, Vandbergue Santos [6 ]
Nogueira Brilhante, Raimunda Samia [6 ]
Gadelha Rocha, Marcos Fabio [1 ,6 ]
机构
[1] Univ Estadual Ceara, Postgrad Program Vet Sci, Sch Vet, Fortaleza, Ceara, Brazil
[2] Univ Estadual Ceara, Super Inst Biomed Sci, Fortaleza, Ceara, Brazil
[3] Fundacao Oswaldo Cruz, Oswaldo Cruz Inst, Lab Immunomodulat & Protozool, Rio De Janeiro, RJ, Brazil
[4] Univ Estadual Maranhao, Dept Pathol, Sao Luis, Maranhao, Brazil
[5] Univ Fed Ceara, Bioinorgan Lab, Dept Organ & Inorgan Chem, Fortaleza, Ceara, Brazil
[6] Univ Fed Ceara, Postgrad Program Med Microbiol, Specialized Med Mycol Ctr, Dept Pathol & Legal Med,Sch Med, Fortaleza, Ceara, Brazil
关键词
Leishmania; Ruthenium nitrosyl complex; Metallodrugs; Leishmanicidal effect; NO DONOR; INVOLVEMENT; INHIBITION; RELEASE; DISEASE;
D O I
10.1016/j.actatropica.2019.01.021
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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)(2)(SO3)(NO)](PF6) 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 mu M) and by in vivo efficacy tests performed in the presence of two different concentrations of complex (100 mu g/kg/day or 300 mu g/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 mu M of ruthenium complex, it was observed a significant decrease of the infected cells, after 24 h exposure in vitro, with total reduction at 50 mu M of the ruthenium complex. In the in vivo cutaneous infection model, administration of daily doses of 300 mu g/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.
引用
收藏
页码:61 / 65
页数:5
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