Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/40025
Registo completo
Campo DC | Valor | Idioma |
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dc.contributor.author | Garcia, Juliana | por |
dc.contributor.author | Costa, Vera Marisa | por |
dc.contributor.author | Carvalho, Alexandra T. P. | por |
dc.contributor.author | Silvestre, Ricardo Jorge Leal | por |
dc.contributor.author | Duarte, José Alberto | por |
dc.contributor.author | Dourado, Daniel F. A. R. | por |
dc.contributor.author | Arbo, Marcelo D. | por |
dc.contributor.author | Baltazar, Teresa | por |
dc.contributor.author | Oliveira, Ricardo Jorge Dinis | por |
dc.contributor.author | Baptista, Paula | por |
dc.contributor.author | Bastos, Maria de Lourdes | por |
dc.contributor.author | Carvalho, Félix | por |
dc.date.accessioned | 2016-02-02T15:34:10Z | - |
dc.date.available | 2016-02-02T15:34:10Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Garcia, J., Costa, V. M., Carvalho, A. T. P., Silvestre, R., Duarte, J. A., Dourado, D. F. A. R., . . . Carvalho, F. (2015). A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B. Archives of Toxicology, 89(12), 2305-2323. doi: 10.1007/s00204-015-1582-x | - |
dc.identifier.issn | 0340-5761 | por |
dc.identifier.uri | https://hdl.handle.net/1822/40025 | - |
dc.description.abstract | Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans. | por |
dc.description.sponsorship | Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013. | por |
dc.language.iso | eng | por |
dc.publisher | Springer | por |
dc.rights | openAccess | por |
dc.subject | α-Amanitin | por |
dc.subject | RNA polymerase II | por |
dc.subject | Polymyxin B | por |
dc.subject | Liver | por |
dc.subject | Kidney | por |
dc.title | A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B | por |
dc.type | article | - |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | http://link.springer.com/journal/204 | por |
sdum.publicationstatus | published | por |
sdum.event.type | article | - |
oaire.citationStartPage | 2305 | por |
oaire.citationEndPage | 2323 | por |
oaire.citationIssue | 12 | por |
oaire.citationTitle | Archives of Toxicology | por |
oaire.citationVolume | 89 | por |
dc.date.updated | 2016-01-06T10:56:40Z | - |
dc.identifier.doi | 10.1007/s00204-015-1582-x | por |
dc.identifier.pmid | 26385100 | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Archives of Toxicology | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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garcia j_final.pdf | 8,44 MB | Adobe PDF | Ver/Abrir |