Repository logo
 
Publication

The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni

2019-06Journal article Open access
Simple item page
dc.contributor.authorGouveia, Maria João
dc.contributor.authorBrindley, Paul J.
dc.contributor.authorAzevedo, Carlos
dc.contributor.authorGärtner, Fátima
dc.contributor.authorda Costa, José M. C.
dc.contributor.authorVale, Nuno
dc.date.accessioned2020-05-06T11:54:46Z
dc.date.available2020-05-06T11:54:46Z
dc.date.issued2019-06
dc.descriptionFree PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31221193/
dc.description.abstractBackground: Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. Despite its celebrated performance for treatment and control of schistosomiasis and other platyhelminth infections, praziquantel has some shortcomings and the inability of this drug to counteract disease sequelae prompts the need for novel therapeutic strategies. Methods: Using a host-parasite model involving Biomphalaria glabrata and Schistosoma mansoni we established mechanical transformation of S. mansoni cercariae into newly transformed schistosomula (NTS) and characterized optimal culture conditions. Thereafter, we investigated the antischistosomal activity and ability of the antioxidants N-acetylcysteine (NAC) and resveratrol (RESV) to augment the performance of praziquantel and/or artesunate (AS) against larval stages of the parasite. Drug effects were evaluated by using an automated microscopical system to study live and fixed parasites and by transmission electron microscopy (TEM). Results: Transformation rates of cercariae to schistosomula reached ~ 70% when the manipulation process was optimized. Several culture media were tested, with M199 supplemented with HEPES found to be suitable for S. mansoni NTS. Among the antioxidants studied, RESV alone or combined with anthelminthic drugs achieved better results rather N-acetylcysteine (NAC). TEM observations demonstrated that the combination of AS + RESV induced severe, extensive alterations to the tegument and subtegument of NTS when compared to the constituent compounds alone. Two anthelmintic-antioxidant combinations, praziquantel-resveratrol [combination index (CI) = 0.74] and artesunate-resveratrol (CI = 0.34) displayed moderate and strong synergy, respectively. Conclusions: The use of viability markers including staining with propidium iodide increased the accuracy of drug screening assays against S. mansoni NTS. The synergies observed might be the consequence of increased action by RESV on targets of AS and PZQ and/or they may act through concomitantly on discrete targets to enhance overall antischistosomal action. Combinations of active agents, preferably with discrete modes of action including activity against developmental stages and/or the potential to ameliorate infection-associated pathology, might be pursued in order to identify novel therapeutic interventions.pt_PT
dc.description.sponsorshipNV acknowledges support from the Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER (European Union) through Project Number IF/00092/2014/CP1255/CT0004. NV thanks FCT by IF position, Fundação Manuel António da Mota (FMAM, Portugal) and Pfzer Portugal for research group support. JMCC thanks FCT for UID/Multi/00211/2019 and Strategic Project UI211. PJB acknowledges support from award RO1CA164719 from the National Cancer Institute (NCI), National Institutes of Health (NIH), USA. The contents of this report are solely the responsibility of the authors and do not necessarily represent the ofcial views of the FCT, FMAM, the NCI, or the NIH.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationParasit Vectors. 2019 Jun 20;12(1):309. doi: 10.1186/s13071-019-3566-9pt_PT
dc.identifier.doi10.1186/s13071-019-3566-9pt_PT
dc.identifier.issn1756-3305
dc.identifier.urihttp://hdl.handle.net/10400.18/6602
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMCpt_PT
dc.relation.publisherversionhttps://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3566-9pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAcetylcysteinept_PT
dc.subjectAnimalspt_PT
dc.subjectAntioxidantspt_PT
dc.subjectAntiprotozoal Agentspt_PT
dc.subjectArtesunatept_PT
dc.subjectBiomphalariapt_PT
dc.subjectDrug Synergismpt_PT
dc.subjectFemalept_PT
dc.subjectLarvapt_PT
dc.subjectMalept_PT
dc.subjectPlant Extractspt_PT
dc.subjectPraziquantelpt_PT
dc.subjectResveratrolpt_PT
dc.subjectSchistosoma mansonipt_PT
dc.subjectSchistosomiasispt_PT
dc.subjectInfecções Sistémicas e Zoonosespt_PT
dc.titleThe antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansonipt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F00211%2F2013/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage309pt_PT
oaire.citation.titleParasites and Vectorspt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication4641127c-7dd5-44f4-a3d1-d3c4d744ba51
relation.isProjectOfPublication.latestForDiscovery4641127c-7dd5-44f4-a3d1-d3c4d744ba51

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
The antioxidants resveratrol.pdf
Size:
1.75 MB
Format:
Adobe Portable Document Format
Download

Collections

DDI - Artigos em revistas internacionais