P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies

Autores
Rocha-Pereira, Carolina; Ghanem, Carolina Inés; Silva, Renata; Casanova, Alfredo G.; Duarte Araújo, Margarida; Gonçalves Monteiro, Salomé; Sousa, Emília; Bastos, Maria de Lourdes; Remião, Fernando
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In vitro studies showed that 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) increases P-glycoprotein (P-gp) expression and activity in Caco-2 cells, preventing xenobiotic toxicity. The present study aimed at investigating TX5 effects on P-gp expression/activity using Wistar Han rats: a) in vivo, evaluating intestinal P-gp activity; b) ex vivo, evaluating P-gp expression in ileum brush border membranes (BBM) and P-gp activity in everted intestinal sacs; c) ex vivo, evaluating P-gp activity in everted intestinal sacs of the distal and proximal ileum. TX5 (30 mg/kg, b.w.), gavage, activated P-gp in vivo, given the significant decrease in the AUC of digoxin (0.25 mg/kg, b.w.). The efflux of rhodamine 123 (300 μM), a P-gp fluorescent substrate, significantly increased in TX5-treated everted sacs from the distal portion of the rat ileum, when P-gp activity was evaluated in the presence of TX5 (20 μM), an effect abolished by the P-gp inhibitor verapamil (100 μM). No increases on P-gp expression or activity were found in TX5-treated BBM of the distal ileum and everted distal sacs, respectively, 24 h after TX5 (10 mg/kg, b.w.) administration. In vivo, no differences were found on digoxin portal concentration between control (digoxin 0.025 mg/kg, b.w., intraduodenal) and TX5-treated (digoxin+TX5 20 μM, intraduodenal) rats. The observed discrepancies in digoxin results can be related to differences in TX5 dose administered and used methodologies. Thus, the results show that TX5 activates P-gp at the distal portion of the rat ileum, and, at the higher dose tested (30 mg/kg, b.w.), seems to modulate in vivo the AUC of P-gp substrates.
Fil: Rocha-Pereira, Carolina. Universidad de Porto; Portugal
Fil: Ghanem, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Silva, Renata. Universidad de Porto; Portugal
Fil: Casanova, Alfredo G.. Universidad de Salamanca; España
Fil: Duarte Araújo, Margarida. Universidad de Porto; Portugal
Fil: Gonçalves Monteiro, Salomé. Universidad de Porto; Portugal
Fil: Sousa, Emília. Universidad de Porto; Portugal
Fil: Bastos, Maria de Lourdes. Universidad de Porto; Portugal
Fil: Remião, Fernando. Universidad de Porto; Portugal
Materia
ACTIVATORS
EX VIVO
IN VIVO
INDUCERS
P-GLYCOPROTEIN
THIOXANTHONES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/139132
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/139132
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studiesRocha-Pereira, CarolinaGhanem, Carolina InésSilva, RenataCasanova, Alfredo G.Duarte Araújo, MargaridaGonçalves Monteiro, SaloméSousa, EmíliaBastos, Maria de LourdesRemião, FernandoACTIVATORSEX VIVOIN VIVOINDUCERSP-GLYCOPROTEINTHIOXANTHONEShttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3In vitro studies showed that 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) increases P-glycoprotein (P-gp) expression and activity in Caco-2 cells, preventing xenobiotic toxicity. The present study aimed at investigating TX5 effects on P-gp expression/activity using Wistar Han rats: a) in vivo, evaluating intestinal P-gp activity; b) ex vivo, evaluating P-gp expression in ileum brush border membranes (BBM) and P-gp activity in everted intestinal sacs; c) ex vivo, evaluating P-gp activity in everted intestinal sacs of the distal and proximal ileum. TX5 (30 mg/kg, b.w.), gavage, activated P-gp in vivo, given the significant decrease in the AUC of digoxin (0.25 mg/kg, b.w.). The efflux of rhodamine 123 (300 μM), a P-gp fluorescent substrate, significantly increased in TX5-treated everted sacs from the distal portion of the rat ileum, when P-gp activity was evaluated in the presence of TX5 (20 μM), an effect abolished by the P-gp inhibitor verapamil (100 μM). No increases on P-gp expression or activity were found in TX5-treated BBM of the distal ileum and everted distal sacs, respectively, 24 h after TX5 (10 mg/kg, b.w.) administration. In vivo, no differences were found on digoxin portal concentration between control (digoxin 0.025 mg/kg, b.w., intraduodenal) and TX5-treated (digoxin+TX5 20 μM, intraduodenal) rats. The observed discrepancies in digoxin results can be related to differences in TX5 dose administered and used methodologies. Thus, the results show that TX5 activates P-gp at the distal portion of the rat ileum, and, at the higher dose tested (30 mg/kg, b.w.), seems to modulate in vivo the AUC of P-gp substrates.Fil: Rocha-Pereira, Carolina. Universidad de Porto; PortugalFil: Ghanem, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Silva, Renata. Universidad de Porto; PortugalFil: Casanova, Alfredo G.. Universidad de Salamanca; EspañaFil: Duarte Araújo, Margarida. Universidad de Porto; PortugalFil: Gonçalves Monteiro, Salomé. Universidad de Porto; PortugalFil: Sousa, Emília. Universidad de Porto; PortugalFil: Bastos, Maria de Lourdes. Universidad de Porto; PortugalFil: Remião, Fernando. Universidad de Porto; PortugalAcademic Press Inc Elsevier Science2020-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/139132Rocha-Pereira, Carolina; Ghanem, Carolina Inés; Silva, Renata; Casanova, Alfredo G.; Duarte Araújo, Margarida; et al.; P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies; Academic Press Inc Elsevier Science; Toxicology and Applied Pharmacology; 386; 1-2020; 1-350041-008XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0041008X19304405info:eu-repo/semantics/altIdentifier/doi/10.1016/j.taap.2019.114832info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-01-14T12:26:31Zoai:ri.conicet.gov.ar:11336/139132instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-01-14 12:26:31.501CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
title P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
spellingShingle P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
Rocha-Pereira, Carolina
ACTIVATORS
EX VIVO
IN VIVO
INDUCERS
P-GLYCOPROTEIN
THIOXANTHONES
title_short P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
title_full P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
title_fullStr P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
title_full_unstemmed P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
title_sort P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies
dc.creator.none.fl_str_mv Rocha-Pereira, Carolina
Ghanem, Carolina Inés
Silva, Renata
Casanova, Alfredo G.
Duarte Araújo, Margarida
Gonçalves Monteiro, Salomé
Sousa, Emília
Bastos, Maria de Lourdes
Remião, Fernando
author Rocha-Pereira, Carolina
author_facet Rocha-Pereira, Carolina
Ghanem, Carolina Inés
Silva, Renata
Casanova, Alfredo G.
Duarte Araújo, Margarida
Gonçalves Monteiro, Salomé
Sousa, Emília
Bastos, Maria de Lourdes
Remião, Fernando
author_role author
author2 Ghanem, Carolina Inés
Silva, Renata
Casanova, Alfredo G.
Duarte Araújo, Margarida
Gonçalves Monteiro, Salomé
Sousa, Emília
Bastos, Maria de Lourdes
Remião, Fernando
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTIVATORS
EX VIVO
IN VIVO
INDUCERS
P-GLYCOPROTEIN
THIOXANTHONES
topic ACTIVATORS
EX VIVO
IN VIVO
INDUCERS
P-GLYCOPROTEIN
THIOXANTHONES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In vitro studies showed that 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) increases P-glycoprotein (P-gp) expression and activity in Caco-2 cells, preventing xenobiotic toxicity. The present study aimed at investigating TX5 effects on P-gp expression/activity using Wistar Han rats: a) in vivo, evaluating intestinal P-gp activity; b) ex vivo, evaluating P-gp expression in ileum brush border membranes (BBM) and P-gp activity in everted intestinal sacs; c) ex vivo, evaluating P-gp activity in everted intestinal sacs of the distal and proximal ileum. TX5 (30 mg/kg, b.w.), gavage, activated P-gp in vivo, given the significant decrease in the AUC of digoxin (0.25 mg/kg, b.w.). The efflux of rhodamine 123 (300 μM), a P-gp fluorescent substrate, significantly increased in TX5-treated everted sacs from the distal portion of the rat ileum, when P-gp activity was evaluated in the presence of TX5 (20 μM), an effect abolished by the P-gp inhibitor verapamil (100 μM). No increases on P-gp expression or activity were found in TX5-treated BBM of the distal ileum and everted distal sacs, respectively, 24 h after TX5 (10 mg/kg, b.w.) administration. In vivo, no differences were found on digoxin portal concentration between control (digoxin 0.025 mg/kg, b.w., intraduodenal) and TX5-treated (digoxin+TX5 20 μM, intraduodenal) rats. The observed discrepancies in digoxin results can be related to differences in TX5 dose administered and used methodologies. Thus, the results show that TX5 activates P-gp at the distal portion of the rat ileum, and, at the higher dose tested (30 mg/kg, b.w.), seems to modulate in vivo the AUC of P-gp substrates.
Fil: Rocha-Pereira, Carolina. Universidad de Porto; Portugal
Fil: Ghanem, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Silva, Renata. Universidad de Porto; Portugal
Fil: Casanova, Alfredo G.. Universidad de Salamanca; España
Fil: Duarte Araújo, Margarida. Universidad de Porto; Portugal
Fil: Gonçalves Monteiro, Salomé. Universidad de Porto; Portugal
Fil: Sousa, Emília. Universidad de Porto; Portugal
Fil: Bastos, Maria de Lourdes. Universidad de Porto; Portugal
Fil: Remião, Fernando. Universidad de Porto; Portugal
description In vitro studies showed that 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) increases P-glycoprotein (P-gp) expression and activity in Caco-2 cells, preventing xenobiotic toxicity. The present study aimed at investigating TX5 effects on P-gp expression/activity using Wistar Han rats: a) in vivo, evaluating intestinal P-gp activity; b) ex vivo, evaluating P-gp expression in ileum brush border membranes (BBM) and P-gp activity in everted intestinal sacs; c) ex vivo, evaluating P-gp activity in everted intestinal sacs of the distal and proximal ileum. TX5 (30 mg/kg, b.w.), gavage, activated P-gp in vivo, given the significant decrease in the AUC of digoxin (0.25 mg/kg, b.w.). The efflux of rhodamine 123 (300 μM), a P-gp fluorescent substrate, significantly increased in TX5-treated everted sacs from the distal portion of the rat ileum, when P-gp activity was evaluated in the presence of TX5 (20 μM), an effect abolished by the P-gp inhibitor verapamil (100 μM). No increases on P-gp expression or activity were found in TX5-treated BBM of the distal ileum and everted distal sacs, respectively, 24 h after TX5 (10 mg/kg, b.w.) administration. In vivo, no differences were found on digoxin portal concentration between control (digoxin 0.025 mg/kg, b.w., intraduodenal) and TX5-treated (digoxin+TX5 20 μM, intraduodenal) rats. The observed discrepancies in digoxin results can be related to differences in TX5 dose administered and used methodologies. Thus, the results show that TX5 activates P-gp at the distal portion of the rat ileum, and, at the higher dose tested (30 mg/kg, b.w.), seems to modulate in vivo the AUC of P-gp substrates.
publishDate 2020
dc.date.none.fl_str_mv 2020-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/139132
Rocha-Pereira, Carolina; Ghanem, Carolina Inés; Silva, Renata; Casanova, Alfredo G.; Duarte Araújo, Margarida; et al.; P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies; Academic Press Inc Elsevier Science; Toxicology and Applied Pharmacology; 386; 1-2020; 1-35
0041-008X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/139132
identifier_str_mv Rocha-Pereira, Carolina; Ghanem, Carolina Inés; Silva, Renata; Casanova, Alfredo G.; Duarte Araújo, Margarida; et al.; P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies; Academic Press Inc Elsevier Science; Toxicology and Applied Pharmacology; 386; 1-2020; 1-35
0041-008X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0041008X19304405
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.taap.2019.114832
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.603104

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