Naslov
Translocation of pyridinium oximes through blood­ brain barrier

Autori
Zandona, Antonio ; Cavaco, Marco ; Castanho, Miguel ; Neves, Vera ; Katalinić, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
FEBS Open Bio 12 (Suppl. S1) / - : FEBS Press, 2022, 122-122

Skup
The Biochemistry Global Summit

Mjesto i datum
Lisabon, Portugal, 06.07.2022. - 14.07.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
translocation ; oximes ; blood-brain barrier ; pyridinium

Sažetak
Oximes are investigated as antidotes against toxic organophosphates (OP), which interrupt neurotrans mission by inhibiting acetylcholinesterase (AChE) in the synapses of central and peripheral nervous system. To be fu lly efficient in their action as antidotes, oximes have to cross BBB and reactivate OP­ inhibited AChE in the brain. The three antidotes, so far approved for medical poiso ning treatment, do not cross the BBB efficiently, thus prevailing the poisoning symptoms. To improve their efficacy new potential antidotes are being synthetized usin g diverse scaffolds and modifying the known struct ures of the oximes. In this study, we evaluated th e capacity of newly synthesised pyridinium oximes to cross a BBB model , based on in vitro cell monolayer of HBEC­ 5i cells. Initially, cytotoxicity screening determ ined how oximes act on HBEC­ 5i cells. According to the results, the concentrat ions of oximes for BBB translocation assay were se lected, to avoid paracellular leakage of BBB model and overestimation of oximes passing through the cell barrier. Most oximes translocated in a percentage up to 50 %, which is significant result, comparing to currently used antidotes. Furthermore, it was shown that there wa s no significant difference in oxime translocation after 4 or 24 h. In addition, membrane integrity was high throughout the experiment (above 85 %) and the results repres ent translocation through the intact BBB cell mono layer model. Furthermore, potential to cross BBB a lso opens up a new perspective for this compounds to be a base fo r development of BBB­ active drugs for treatment of many other diseases or conditions such as Alzheimer’s disease or cancer. Acknowledgement: This work was supported by the Cr oatian Science Foundation under the project UIP­ 2017­05­7260 and Portuguese Funding Agency, Fundação para a Ciência e a Tecnologia, FCT IP (grants: PD/ BD/128281/2017 and PTDC/BIA­BQM/5027/2020).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA