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Biblioteca Digital do IPG >
Escola Superior de Saúde (ESS) >
Artigos em Revista Internacional (ESS) >
Utilize este identificador para referenciar este registo:
http://hdl.handle.net/10314/3945
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| Título: | Flavonoid compounds as reversing agents of the P-glycoprotein-mediated multidrug resistance: An in vitro evaluation with focus on antiepileptic drugs |
| Autores: | Ferreira, Ana
Rodrigues, Márcio
Fortuna, Ana
Falcão, Amílcar
Alves, Gilberto |
| Palavras Chave: | Epilepsy Flavonoids In vitro studies P-glycoprotein Pharmacoresistance |
| Data: | 7-Oct-2017 |
| Editora: | Food Research International |
| Resumo: | The pharmacoresistance to antiepileptic drugs (AEDs) remains a major unsolved therapeutic need. The overexpression
of multidrug transporters, as the P-glycoprotein (P-gp), at the level of the blood-brain barrier of
epileptic patients has been suggested as a key mechanism underlying the refractory epilepsy. Thus, efforts have
been made to search for therapeutically useful P-gp inhibitors. Herein, the strategy of flavonoid/AED combined
therapy was exploited as a possible approach to overcome the P-gp-mediated pharmacoresistance. For this
purpose, several in vitro studies were performed using Madin-Darby canine kidney II (MDCK II) cells and those
transfected with the human multidrug resistance-1 (MDR1) gene, overexpressing the P-gp (MDCK-MDR1).
Overall, the results showed that baicalein, (−)-epigallocatechin gallate, kaempferol, quercetin and silymarin, at
200 μM, produced a marked increase on the intracellular accumulation of rhodamine 123 in MDCK-MDR1 cells,
potentially through inhibiting the P-gp activity. In addition, with the exception of lamotrigine, all other AEDs
tested (phenytoin, carbamazepine and oxcarbazepine) and their active metabolites (carbamazepine-10,11-epoxide
and licarbazepine) demonstrated to be P-gp substrates. Furthermore, the most promising flavonoids as Pgp
inhibitors promoted a significant increase on the intracellular accumulation of the AEDs (excluding lamotrigine)
and their active metabolites in MDCK-MDR1 cells, evidencing to be important drug candidates to reverse
the AED-resistance. Thus, the co-administration of AEDs with baicalein, (−)-epigallocatechin gallate, kaempferol,
quercetin and silymarin should continue to be explored as adjuvant therapy for refractory epilepsy. |
| URI: | http://hdl.handle.net/10314/3945 |
| ISSN: | doi.org/10.1016/j.foodres.2017.10.010 |
| Aparece nas Colecções: | Artigos em Revista Internacional (ESS)
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| marcio_352_a.pdf | | 1633Kb | Adobe PDF | Ver/Abrir | |
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