3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity

Autores
Conde, Melisa Ailén; Maniscalchi, Athina; Nicasio, Leticia; Benzi Juncos, Oriana Nicole; Alza, Natalia Paola; Salvador, Gabriela Alejandra
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Maneb (MB), a dithiocarbamate pesticide, can cross the blood-brain barrier and is considered an environmental risk factor associated with Parkinsonism. Our aim was to characterize redox signaling during MB-induced neurotoxicity in different experimental models according to the 3Rs principle. Taking into account full Replacement we firstly exposed neuronal cell line cultures to MB and we detected increased expression levels of the redox sensitive transcription factor Nrf2 and its regulator Sirt1. Neuronal MB exposure also triggered the increase of lipid peroxidation, GSH depletion, GpX4 downregulation and mitochondrial alterations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replacement by using glial mixed primary cultures. We also demonstrate that Nrf2/Sirt1 signaling is a protective strategy against neurotoxicity. Based on these results and with the aim of evaluating phenotypical aspects for establishing a preclinical model, we design an experimental paradigm with C57BL/6 mice. Following Refinement criteria, treatments were performed with the supervision of a veterinarian who care the animal welfare during the entire procedure. C57BL/6 mice (18-20g) were intraperitoneally injected with MB (100 mg/kg) for 6 weeks. Behavioral tests (Open Field and Rotarod) were performed on week 3 and 6 of treatment. One day after the last administration, animals were sacrificed by cervical dislocation. Forebrain, midbrain and hindbrain were separated for molecular determinations. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a decrease in total distance travelled, supported and unsupported rears and in falling latency. These results indicate that MB neurotoxicity triggers a parkinsonian phenotype in C57BL/6. The results presented here constitute a platform for toxicological and preclinical studies according to 3Rs principles.
Fil: Conde, Melisa Ailén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Maniscalchi, Athina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Nicasio, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Benzi Juncos, Oriana Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Química; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
3 RS
MANEB
NEUROTOXiCITY
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:11336/240365
Acceder
id CONICETDig_62f759b4f77b89b14e34c6c46aafeba4
oai_identifier_str oai:ri.conicet.gov.ar:11336/240365
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced NeurotoxicityConde, Melisa AilénManiscalchi, AthinaNicasio, LeticiaBenzi Juncos, Oriana NicoleAlza, Natalia PaolaSalvador, Gabriela Alejandra3 RSMANEBNEUROTOXiCITYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Maneb (MB), a dithiocarbamate pesticide, can cross the blood-brain barrier and is considered an environmental risk factor associated with Parkinsonism. Our aim was to characterize redox signaling during MB-induced neurotoxicity in different experimental models according to the 3Rs principle. Taking into account full Replacement we firstly exposed neuronal cell line cultures to MB and we detected increased expression levels of the redox sensitive transcription factor Nrf2 and its regulator Sirt1. Neuronal MB exposure also triggered the increase of lipid peroxidation, GSH depletion, GpX4 downregulation and mitochondrial alterations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replacement by using glial mixed primary cultures. We also demonstrate that Nrf2/Sirt1 signaling is a protective strategy against neurotoxicity. Based on these results and with the aim of evaluating phenotypical aspects for establishing a preclinical model, we design an experimental paradigm with C57BL/6 mice. Following Refinement criteria, treatments were performed with the supervision of a veterinarian who care the animal welfare during the entire procedure. C57BL/6 mice (18-20g) were intraperitoneally injected with MB (100 mg/kg) for 6 weeks. Behavioral tests (Open Field and Rotarod) were performed on week 3 and 6 of treatment. One day after the last administration, animals were sacrificed by cervical dislocation. Forebrain, midbrain and hindbrain were separated for molecular determinations. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a decrease in total distance travelled, supported and unsupported rears and in falling latency. These results indicate that MB neurotoxicity triggers a parkinsonian phenotype in C57BL/6. The results presented here constitute a platform for toxicological and preclinical studies according to 3Rs principles.Fil: Conde, Melisa Ailén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Maniscalchi, Athina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Nicasio, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Benzi Juncos, Oriana Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Química; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaLXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de BiologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista Medicina2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2403653 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 75-760025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2020/volumen-83-ano-2023-s5/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:03:13Zoai:ri.conicet.gov.ar:11336/240365instacron: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 10:03:13.735CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
title 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
spellingShingle 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
Conde, Melisa Ailén
3 RS
MANEB
NEUROTOXiCITY
title_short 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
title_full 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
title_fullStr 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
title_full_unstemmed 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
title_sort 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity
dc.creator.none.fl_str_mv Conde, Melisa Ailén
Maniscalchi, Athina
Nicasio, Leticia
Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author Conde, Melisa Ailén
author_facet Conde, Melisa Ailén
Maniscalchi, Athina
Nicasio, Leticia
Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author_role author
author2 Maniscalchi, Athina
Nicasio, Leticia
Benzi Juncos, Oriana Nicole
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 3 RS
MANEB
NEUROTOXiCITY
topic 3 RS
MANEB
NEUROTOXiCITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Maneb (MB), a dithiocarbamate pesticide, can cross the blood-brain barrier and is considered an environmental risk factor associated with Parkinsonism. Our aim was to characterize redox signaling during MB-induced neurotoxicity in different experimental models according to the 3Rs principle. Taking into account full Replacement we firstly exposed neuronal cell line cultures to MB and we detected increased expression levels of the redox sensitive transcription factor Nrf2 and its regulator Sirt1. Neuronal MB exposure also triggered the increase of lipid peroxidation, GSH depletion, GpX4 downregulation and mitochondrial alterations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replacement by using glial mixed primary cultures. We also demonstrate that Nrf2/Sirt1 signaling is a protective strategy against neurotoxicity. Based on these results and with the aim of evaluating phenotypical aspects for establishing a preclinical model, we design an experimental paradigm with C57BL/6 mice. Following Refinement criteria, treatments were performed with the supervision of a veterinarian who care the animal welfare during the entire procedure. C57BL/6 mice (18-20g) were intraperitoneally injected with MB (100 mg/kg) for 6 weeks. Behavioral tests (Open Field and Rotarod) were performed on week 3 and 6 of treatment. One day after the last administration, animals were sacrificed by cervical dislocation. Forebrain, midbrain and hindbrain were separated for molecular determinations. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a decrease in total distance travelled, supported and unsupported rears and in falling latency. These results indicate that MB neurotoxicity triggers a parkinsonian phenotype in C57BL/6. The results presented here constitute a platform for toxicological and preclinical studies according to 3Rs principles.
Fil: Conde, Melisa Ailén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Maniscalchi, Athina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Nicasio, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Benzi Juncos, Oriana Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Química; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Maneb (MB), a dithiocarbamate pesticide, can cross the blood-brain barrier and is considered an environmental risk factor associated with Parkinsonism. Our aim was to characterize redox signaling during MB-induced neurotoxicity in different experimental models according to the 3Rs principle. Taking into account full Replacement we firstly exposed neuronal cell line cultures to MB and we detected increased expression levels of the redox sensitive transcription factor Nrf2 and its regulator Sirt1. Neuronal MB exposure also triggered the increase of lipid peroxidation, GSH depletion, GpX4 downregulation and mitochondrial alterations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replacement by using glial mixed primary cultures. We also demonstrate that Nrf2/Sirt1 signaling is a protective strategy against neurotoxicity. Based on these results and with the aim of evaluating phenotypical aspects for establishing a preclinical model, we design an experimental paradigm with C57BL/6 mice. Following Refinement criteria, treatments were performed with the supervision of a veterinarian who care the animal welfare during the entire procedure. C57BL/6 mice (18-20g) were intraperitoneally injected with MB (100 mg/kg) for 6 weeks. Behavioral tests (Open Field and Rotarod) were performed on week 3 and 6 of treatment. One day after the last administration, animals were sacrificed by cervical dislocation. Forebrain, midbrain and hindbrain were separated for molecular determinations. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a decrease in total distance travelled, supported and unsupported rears and in falling latency. These results indicate that MB neurotoxicity triggers a parkinsonian phenotype in C57BL/6. The results presented here constitute a platform for toxicological and preclinical studies according to 3Rs principles.
publishDate 2023
dc.date.none.fl_str_mv 2023
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/11336/240365
3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 75-76
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/240365
identifier_str_mv 3 Rs Approaches For The Study Of Sig- Naling Events Triggered By Pesticide Induced Neurotoxicity; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 75-76
0025-7680
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.medicinabuenosaires.com/indices-de-2020/volumen-83-ano-2023-s5/
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
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
_version_ 1842269789717790720
score 13.13397

Publicaciones similares