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Peroxides with antiplasmodial activity inhibit proliferation of Perkinsus olseni, the causative agent of Perkinsosis in bivalves

2013-12Journal article Restricted
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dc.contributor.authorAraujo, Nuna C. P.
dc.contributor.authorAfonso, Ricardo
dc.contributor.authorBringela, A.
dc.contributor.authorCancela, Leonor
dc.contributor.authorCristiano, Maria Lurdes Santos
dc.contributor.authorLeite, Ricardo
dc.date.accessioned2014-01-30T15:20:00Z
dc.date.available2014-01-30T15:20:00Z
dc.date.issued2013-12
dc.date.updated2014-01-29T10:03:23Z
dc.description.abstractPerkinsus olseni, the causative agent of Perkinsosis, can drastically affect the survival of target marine mollusks, with dramatic economic consequences for aquaculture. P. olseni is a member of the Alveolata group, which also comprises parasites that are highly relevant for medical and veterinary sciences such as Plasmodium falciparum and Toxoplasma. P. olseni shares several unique metabolic pathways with those pathological parasites but is not toxic to humans. In this work, six antimalarially active peroxides, derived from the natural product artemisinin or synthetic trioxolanes, were synthesized and tested on P. olseni proliferation and survival. All peroxides tested revealed an inhibitory effect on P. olseni proliferation atmicromolar concentrations. The relevance of the peroxide functionality on toxicity and the effect of Fe(II)-intracellular concentration on activity were also evaluated. Results demonstrated that the peroxide functionality is the toxofore and intracellular iron concentration also proved to be a crucial co-factor on the activation of peroxides in P. olseni. These data points to a mechanismof bioactivation in P. olseni sharing similaritieswith the one proposed in P. falciparumparasites. Preliminary studies on bioaccumulation were conducted using fluorescent-labeled peroxides. Results show that synthetic trioxolanes tend to accumulate on a vacuolewhile the labeled artemisinin accumulates in the cytoplasm. Preliminary experiments on differential genes expression associated to Fe(II) transport protein (Nramp) and calcium transport protein (ATP6/SERCA) were also conducted by qPCR. Results point to a fourfold increase in expression of both genes upon exposure to trioxolanes and approximately twofold upon exposure to artemisinin derivatives. Data obtained in this investigation is relevant for better understanding of the biology of Perkinsus andmay also be important in the development of new strategies for Perkinsosis prevention and control.por
dc.identifier.citationAraujo, N.C.P.; Afonso, R.; Bringela, A.; Cancela, M.L.; Cristiano, M.L.S.; Leite, R.B.Peroxides with antiplasmodial activity inhibit proliferation of Perkinsus olseni, the causative agent of Perkinsosis in bivalves, Parasitology International, 62, 6, 575-582, 2013.por
dc.identifier.doihttp://dx.doi.org/10.1016/j.parint.2013.06.010
dc.identifier.issn1383-5769
dc.identifier.otherAUT: LCA00739; MCR00716;
dc.identifier.urihttp://hdl.handle.net/10400.1/3392
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.relation.publisherversionhttp://www.journals.elsevier.com/parasitology-internationalpor
dc.subjectAntimalarial peroxidespor
dc.subjectPerkinsus olsenipor
dc.subjectPerkinsosis in clamspor
dc.subjectPeroxide-based antiparasitic drugspor
dc.subjectFe(II)-bioactivationpor
dc.subjectSelective bioaccumulationpor
dc.subjectNramppor
dc.subjectATP6por
dc.titlePeroxides with antiplasmodial activity inhibit proliferation of Perkinsus olseni, the causative agent of Perkinsosis in bivalvespor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage582por
oaire.citation.issue6por
oaire.citation.startPage575por
oaire.citation.titleParasitology Internationalpor
oaire.citation.volume62por
person.familyNameAraujo
person.familyNameAfonso
person.familyNameCancela
person.familyNameCristiano
person.familyNameLeite
person.givenNameNuna
person.givenNameRicardo
person.givenNameM. Leonor
person.givenNameMaria de Lurdes
person.givenNameRicardo
person.identifier447622
person.identifier.ciencia-idE411-6006-5A01
person.identifier.ciencia-idF115-256E-C84D
person.identifier.orcid0000-0002-7602-0150
person.identifier.orcid0000-0002-3884-9312
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0002-9447-2855
person.identifier.orcid0000-0002-9622-3895
person.identifier.ridN-8531-2013
person.identifier.ridG-2345-2012
person.identifier.ridB-3389-2008
person.identifier.scopus-author-id9238724800
person.identifier.scopus-author-id8362650900
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication3423e71b-934d-4da7-9c81-4e56c7930252
relation.isAuthorOfPublication30644154-3327-45af-a3ed-f5e221951b4c
relation.isAuthorOfPublicationb9bbfe32-3dfe-4131-ad14-a4394008447f
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relation.isAuthorOfPublication3fb360e0-a481-486e-96ca-af9f6ecd6eb8
relation.isAuthorOfPublication.latestForDiscoveryb9bbfe32-3dfe-4131-ad14-a4394008447f

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