Date Published: March 27, 2015
Publisher: Public Library of Science
Author(s): Maria A. Guimarães, Rosimeire N. de Oliveira, Leiz M. C. Véras, David F. Lima, Yuri D. M. Campelo, Stefano Augusto Campos, Selma A. S. Kuckelhaus, Pedro L. S. Pinto, Peter Eaton, Ana C. Mafud, Yvonne P. Mascarenhas, Silmara M. Allegretti, Josué de Moraes, Aleksandar Lolić, Tatjana Verbić, José Roberto S. A. Leite, Timothy G. Geary. http://doi.org/10.1371/journal.pntd.0003656
Abstract: Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported.
Partial Text: Schistosomiasis is a disease mainly found in tropical regions, whose infectious agents are Schistosoma spp., including Schistosoma mansoni . This disease is currently one of the most widely occurring neglected tropical diseases with high levels of incidence in Asia, Africa and Latin America. Studies have shown that more than 207 million people have been infected worldwide and about 779 million people are liable to infection .
The widespread use of PZQ for treatment and control schistosomiasis may select drug-resistant parasites . In countries like Egypt, an increasing number of patients have displayed resistance to treatment with PZQ, apparently due in some cases to resistance inherent in particular strains, and in other cases to an immune response from the infected host, which reduces chemotherapy effectiveness . Therefore, the discovery of new antiparasitic agents to treat schistosomiasis is an important avenue of research.