3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity
- Autores
- Conde, Melisa Ailén; Maniscalchi, Athina del Valle; Nicasio, María Leticia; Benzi Juncos, Oriana Nicole; Funk, Melania Iara; 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 peroxida- tion, GSH depletion, GpX4 downregulation and mitochondrial alter- ations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replace- ment 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 experi- mental 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 per- formed on week 3 and 6 of treatment. One day after the last admin- istration, animals were sacrificed by cervical dislocation. Forebrain,midbrain and hindbrain were separated for molecular determina- tions. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a de- crease 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 del Valle. 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, María 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: Funk, Melania Iara. 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: 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
Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)
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
-
3RS
PESTICIDE
NEUROTOXICITY - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/227138
Ver los metadatos del registro completo
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3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicityConde, Melisa AilénManiscalchi, Athina del ValleNicasio, María LeticiaBenzi Juncos, Oriana NicoleFunk, Melania IaraAlza, Natalia PaolaSalvador, Gabriela Alejandra3RSPESTICIDENEUROTOXICITYhttps://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 peroxida- tion, GSH depletion, GpX4 downregulation and mitochondrial alter- ations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replace- ment 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 experi- mental 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 per- formed on week 3 and 6 of treatment. One day after the last admin- istration, animals were sacrificed by cervical dislocation. Forebrain,midbrain and hindbrain were separated for molecular determina- tions. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a de- crease 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 del Valle. 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, María 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: Funk, Melania Iara. 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: 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; ArgentinaReunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)Mar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de BiologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista MedicinaLuthy, Isabel AliciaPerez Martinez, Silvina LauraSimonovich, VenturaPinto, Gabriel2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2271383 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity; Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL); Mar del Plata; Argentina; 2023; 75-760025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:52Zoai:ri.conicet.gov.ar:11336/227138instacron: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:34982025-09-29 09:38:53.092CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity |
| title |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity |
| spellingShingle |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity Conde, Melisa Ailén 3RS PESTICIDE NEUROTOXICITY |
| title_short |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity |
| title_full |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity |
| title_fullStr |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity |
| title_full_unstemmed |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity |
| title_sort |
3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity |
| dc.creator.none.fl_str_mv |
Conde, Melisa Ailén Maniscalchi, Athina del Valle Nicasio, María Leticia Benzi Juncos, Oriana Nicole Funk, Melania Iara Alza, Natalia Paola Salvador, Gabriela Alejandra |
| author |
Conde, Melisa Ailén |
| author_facet |
Conde, Melisa Ailén Maniscalchi, Athina del Valle Nicasio, María Leticia Benzi Juncos, Oriana Nicole Funk, Melania Iara Alza, Natalia Paola Salvador, Gabriela Alejandra |
| author_role |
author |
| author2 |
Maniscalchi, Athina del Valle Nicasio, María Leticia Benzi Juncos, Oriana Nicole Funk, Melania Iara Alza, Natalia Paola Salvador, Gabriela Alejandra |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
Luthy, Isabel Alicia Perez Martinez, Silvina Laura Simonovich, Ventura Pinto, Gabriel |
| dc.subject.none.fl_str_mv |
3RS PESTICIDE NEUROTOXICITY |
| topic |
3RS PESTICIDE 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 peroxida- tion, GSH depletion, GpX4 downregulation and mitochondrial alter- ations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replace- ment 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 experi- mental 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 per- formed on week 3 and 6 of treatment. One day after the last admin- istration, animals were sacrificed by cervical dislocation. Forebrain,midbrain and hindbrain were separated for molecular determina- tions. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a de- crease 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 del Valle. 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, María 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: Funk, Melania Iara. 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: 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 Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL) 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 peroxida- tion, GSH depletion, GpX4 downregulation and mitochondrial alter- ations, indicating that ferroptosis is involved in the mechanism of cell death. We confirmed these results in a model of relative Replace- ment 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 experi- mental 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 per- formed on week 3 and 6 of treatment. One day after the last admin- istration, animals were sacrificed by cervical dislocation. Forebrain,midbrain and hindbrain were separated for molecular determina- tions. To apply the Reduction criteria all other animal organs were used for related investigations. MB-treated animals showed a de- crease 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. |
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2023 |
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2023 |
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http://hdl.handle.net/11336/227138 3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity; Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL); Mar del Plata; Argentina; 2023; 75-76 0025-7680 1669-9106 CONICET Digital CONICET |
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3 RS approaches for the study of signaling events triggered by pesticide induced neurotoxicity; Reunión Conjunta SAIC SAB AAFE AACYTAL 2023; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB); LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE); VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL); Mar del Plata; Argentina; 2023; 75-76 0025-7680 1669-9106 CONICET Digital CONICET |
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