| Full text | |
| Author(s): Show less - |
Roquini, Daniel B.
[1]
;
Cogo, Ramon M.
[1]
;
Mengarda, Ana C.
[1]
;
Mazloum, Susana F.
[1]
;
Morais, Cristiane S.
[1]
;
Xavier, Rogerio P.
[1]
;
Salvadori, Maria C.
[2]
;
Teixeira, Fernanda S.
[2]
;
Ferreira, Luiz E.
[3]
;
Pinto, Pedro L.
[4]
;
Morais, Thiago R.
[1]
;
de Moraes, Josue
[1]
Total Authors: 12
|
| Affiliation: | [1] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, Guarulhos, SP - Brazil
[2] Univ Sao Paulo, Inst Fis, Sao Paulo, SP - Brazil
[3] Univ Guarulhos, Lab Inflamacao & Imunol, Guarulhos, SP - Brazil
[4] Adolfo Lutz Inst, Nucleo Enteroparasitas, Sao Paulo, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Antimicrobial Agents and Chemotherapy; v. 63, n. 12 DEC 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed, and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility and viability, and it induced severe tegumental damage in schistosomes. The 50% lethal concentration (LC50) of the drug was 5.84 mu M. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg of body weight for five successive days at different intervals from the time of infection for the evaluation of the stage-specific susceptibility (prepatent and patent infections). Various parasitological criteria indicated the following in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, hepatomegaly, and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (>90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent. (AU) | |
| FAPESP's process: | 16/22488-3 - Drug repositioning for neglected diseases: identification of novel anthelmintic agents |
| Grantee: | Josué de Moraes |
| Support Opportunities: | Regular Research Grants |