Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism

Autores
Kelly, Agustina; Torralba Agu, Valeria Nora; Zappia, Carlos Daniel; Monczor, Federico
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
We have previously described in vitro that histamine H1 receptor ligands potentiate the anti-inflammatory effects of glucocorticoids (GCs) and established its therapeutic potential in a murine asthma model. Though, it is crucial to evaluate how this crosstalk alters the onset of GC-induced adverse effects to assess cotreatment safety. Considering that the therapeutic use of GCs is often limited by bone loss, we used the MC3T3-E1 osteoblastic cells differentiated with ascorbic acid and β-glycerophosphate as an in-vitro model to study the joint effect of dexamethasone (DEX) and the antihistamine azelastine (AZE) on the expression of bone biomarkers OPG, RANKL and OC, determinants of the balance between bone formation and resorption. Treatment of the cells with 0.1 nM DEX reduced osteoprotegerin (OPG) and increased receptor activator of NF-kB ligand (RANKL) expression in a 17% and 100% respectively, while pre-treatment with 10 µM of AZE reversed both effects by increasing OPG and decreasing RANKL expression in a 92% and 66% respectively. Additionally, treatment with 1 nM DEX reduced osteocalcin (OC) gene expression in 48%, while in cells pre-treated with 10 µM AZE this reduction was 16%. These findings suggest that co-treatment might represent an advantage in terms of bone impairment. We also performed the MTS metabolic assay to assess the effect of AZE on cell proliferation. Treatment with DEX inhibited cell proliferation in a concentration-dependent manner, reaching the maximal effect at 1 µM while pretreatment of cells with 1 µM AZE potentiated DEX inhibition evidenced by a reduction of its pEC50 in one order of magnitude (8.28 ± 0.44 to 9.38 ± 0.2). In contrast with our previous results, this suggests that cotreatment might be unsafe in terms of bone impairment. Overall, these discrepancies grant further research to elucidate the composite effect and the molecular mechanisms by which antihistamines modulate the appearance of GC-induced adverse effects.
Fil: Kelly, Agustina. 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: Torralba Agu, Valeria Nora. 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: Zappia, Carlos Daniel. 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: Monczor, Federico. 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
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión anual de la Sociedad Argentina de Fisiología
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Materia
Glucocorticoid
Antihistamines
Adverse effects
Inaflammation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/192346
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolismKelly, AgustinaTorralba Agu, Valeria NoraZappia, Carlos DanielMonczor, FedericoGlucocorticoidAntihistaminesAdverse effectsInaflammationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have previously described in vitro that histamine H1 receptor ligands potentiate the anti-inflammatory effects of glucocorticoids (GCs) and established its therapeutic potential in a murine asthma model. Though, it is crucial to evaluate how this crosstalk alters the onset of GC-induced adverse effects to assess cotreatment safety. Considering that the therapeutic use of GCs is often limited by bone loss, we used the MC3T3-E1 osteoblastic cells differentiated with ascorbic acid and β-glycerophosphate as an in-vitro model to study the joint effect of dexamethasone (DEX) and the antihistamine azelastine (AZE) on the expression of bone biomarkers OPG, RANKL and OC, determinants of the balance between bone formation and resorption. Treatment of the cells with 0.1 nM DEX reduced osteoprotegerin (OPG) and increased receptor activator of NF-kB ligand (RANKL) expression in a 17% and 100% respectively, while pre-treatment with 10 µM of AZE reversed both effects by increasing OPG and decreasing RANKL expression in a 92% and 66% respectively. Additionally, treatment with 1 nM DEX reduced osteocalcin (OC) gene expression in 48%, while in cells pre-treated with 10 µM AZE this reduction was 16%. These findings suggest that co-treatment might represent an advantage in terms of bone impairment. We also performed the MTS metabolic assay to assess the effect of AZE on cell proliferation. Treatment with DEX inhibited cell proliferation in a concentration-dependent manner, reaching the maximal effect at 1 µM while pretreatment of cells with 1 µM AZE potentiated DEX inhibition evidenced by a reduction of its pEC50 in one order of magnitude (8.28 ± 0.44 to 9.38 ± 0.2). In contrast with our previous results, this suggests that cotreatment might be unsafe in terms of bone impairment. Overall, these discrepancies grant further research to elucidate the composite effect and the molecular mechanisms by which antihistamines modulate the appearance of GC-induced adverse effects.Fil: Kelly, Agustina. 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: Torralba Agu, Valeria Nora. 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: Zappia, Carlos Daniel. 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: Monczor, Federico. 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; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión anual de la Sociedad Argentina de FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/192346Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión anual de la Sociedad Argentina de Fisiología; Argentina; 2020; 64-651669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/reunion-anualNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:08Zoai:ri.conicet.gov.ar:11336/192346instacron: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:34982025-09-03 10:04:08.757CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
title Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
spellingShingle Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
Kelly, Agustina
Glucocorticoid
Antihistamines
Adverse effects
Inaflammation
title_short Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
title_full Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
title_fullStr Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
title_full_unstemmed Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
title_sort Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism
dc.creator.none.fl_str_mv Kelly, Agustina
Torralba Agu, Valeria Nora
Zappia, Carlos Daniel
Monczor, Federico
author Kelly, Agustina
author_facet Kelly, Agustina
Torralba Agu, Valeria Nora
Zappia, Carlos Daniel
Monczor, Federico
author_role author
author2 Torralba Agu, Valeria Nora
Zappia, Carlos Daniel
Monczor, Federico
author2_role author
author
author
dc.subject.none.fl_str_mv Glucocorticoid
Antihistamines
Adverse effects
Inaflammation
topic Glucocorticoid
Antihistamines
Adverse effects
Inaflammation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have previously described in vitro that histamine H1 receptor ligands potentiate the anti-inflammatory effects of glucocorticoids (GCs) and established its therapeutic potential in a murine asthma model. Though, it is crucial to evaluate how this crosstalk alters the onset of GC-induced adverse effects to assess cotreatment safety. Considering that the therapeutic use of GCs is often limited by bone loss, we used the MC3T3-E1 osteoblastic cells differentiated with ascorbic acid and β-glycerophosphate as an in-vitro model to study the joint effect of dexamethasone (DEX) and the antihistamine azelastine (AZE) on the expression of bone biomarkers OPG, RANKL and OC, determinants of the balance between bone formation and resorption. Treatment of the cells with 0.1 nM DEX reduced osteoprotegerin (OPG) and increased receptor activator of NF-kB ligand (RANKL) expression in a 17% and 100% respectively, while pre-treatment with 10 µM of AZE reversed both effects by increasing OPG and decreasing RANKL expression in a 92% and 66% respectively. Additionally, treatment with 1 nM DEX reduced osteocalcin (OC) gene expression in 48%, while in cells pre-treated with 10 µM AZE this reduction was 16%. These findings suggest that co-treatment might represent an advantage in terms of bone impairment. We also performed the MTS metabolic assay to assess the effect of AZE on cell proliferation. Treatment with DEX inhibited cell proliferation in a concentration-dependent manner, reaching the maximal effect at 1 µM while pretreatment of cells with 1 µM AZE potentiated DEX inhibition evidenced by a reduction of its pEC50 in one order of magnitude (8.28 ± 0.44 to 9.38 ± 0.2). In contrast with our previous results, this suggests that cotreatment might be unsafe in terms of bone impairment. Overall, these discrepancies grant further research to elucidate the composite effect and the molecular mechanisms by which antihistamines modulate the appearance of GC-induced adverse effects.
Fil: Kelly, Agustina. 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: Torralba Agu, Valeria Nora. 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: Zappia, Carlos Daniel. 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: Monczor, Federico. 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
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión anual de la Sociedad Argentina de Fisiología
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
description We have previously described in vitro that histamine H1 receptor ligands potentiate the anti-inflammatory effects of glucocorticoids (GCs) and established its therapeutic potential in a murine asthma model. Though, it is crucial to evaluate how this crosstalk alters the onset of GC-induced adverse effects to assess cotreatment safety. Considering that the therapeutic use of GCs is often limited by bone loss, we used the MC3T3-E1 osteoblastic cells differentiated with ascorbic acid and β-glycerophosphate as an in-vitro model to study the joint effect of dexamethasone (DEX) and the antihistamine azelastine (AZE) on the expression of bone biomarkers OPG, RANKL and OC, determinants of the balance between bone formation and resorption. Treatment of the cells with 0.1 nM DEX reduced osteoprotegerin (OPG) and increased receptor activator of NF-kB ligand (RANKL) expression in a 17% and 100% respectively, while pre-treatment with 10 µM of AZE reversed both effects by increasing OPG and decreasing RANKL expression in a 92% and 66% respectively. Additionally, treatment with 1 nM DEX reduced osteocalcin (OC) gene expression in 48%, while in cells pre-treated with 10 µM AZE this reduction was 16%. These findings suggest that co-treatment might represent an advantage in terms of bone impairment. We also performed the MTS metabolic assay to assess the effect of AZE on cell proliferation. Treatment with DEX inhibited cell proliferation in a concentration-dependent manner, reaching the maximal effect at 1 µM while pretreatment of cells with 1 µM AZE potentiated DEX inhibition evidenced by a reduction of its pEC50 in one order of magnitude (8.28 ± 0.44 to 9.38 ± 0.2). In contrast with our previous results, this suggests that cotreatment might be unsafe in terms of bone impairment. Overall, these discrepancies grant further research to elucidate the composite effect and the molecular mechanisms by which antihistamines modulate the appearance of GC-induced adverse effects.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/192346
Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión anual de la Sociedad Argentina de Fisiología; Argentina; 2020; 64-65
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/192346
identifier_str_mv Assessment of the influence of the antihistamine azelastine on the onset of glucocorticoid-induced adverse effects. consequences on bone metabolism; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión anual de la Sociedad Argentina de Fisiología; Argentina; 2020; 64-65
1669-9106
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://www.saic.org.ar/reunion-anual
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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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