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Biomolecules 2019, 9(2), 54; https://doi.org/10.3390/biom9020054

Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni

1
Center for the Study in Animal Science, University of Porto, (CECA/ICETA), Rua de D. Manuel II, Apt 55142, 4051-401 Porto, Portugal
2
Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
3
Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
4
Department of Microbiology, Immunology & Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA
5
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
6
University of Porto, i3S, Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
7
Department of Infectious Diseases, INSA-National Institute of Health Dr. Ricardo Jorge, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
*
Author to whom correspondence should be addressed.
Current adress: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1AS, UK.
Received: 10 December 2018 / Revised: 29 January 2019 / Accepted: 31 January 2019 / Published: 5 February 2019
(This article belongs to the Special Issue Multidrug Combinations)
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Abstract

Schistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving Bioamphalaria glabrata and newly transformed schistosomula (NTS) of Schistosoma mansoni. For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease. View Full-Text
Keywords: Schistosoma mansoni; antioxidant biomolecules; anthelmintic drug; anticancer drug; drug repurposing; combination therapy; newly transformed schistosomula Schistosoma mansoni; antioxidant biomolecules; anthelmintic drug; anticancer drug; drug repurposing; combination therapy; newly transformed schistosomula
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Gouveia, M.J.; Brindley, P.J.; Rinaldi, G.; Gärtner, F.; Correia da Costa, J.M.; Vale, N. Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni. Biomolecules 2019, 9, 54.

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