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Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration

Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system’s dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that...

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Autores principales: D’Amico, Ramona, Gugliandolo, Enrico, Siracusa, Rosalba, Cordaro, Marika, Genovese, Tiziana, Peritore, Alessio Filippo, Crupi, Rosalia, Interdonato, Livia, Di Paola, Davide, Cuzzocrea, Salvatore, Fusco, Roberta, Impellizzeri, Daniela, Di Paola, Rosanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138892/
https://www.ncbi.nlm.nih.gov/pubmed/35625810
http://dx.doi.org/10.3390/biomedicines10051073
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author D’Amico, Ramona
Gugliandolo, Enrico
Siracusa, Rosalba
Cordaro, Marika
Genovese, Tiziana
Peritore, Alessio Filippo
Crupi, Rosalia
Interdonato, Livia
Di Paola, Davide
Cuzzocrea, Salvatore
Fusco, Roberta
Impellizzeri, Daniela
Di Paola, Rosanna
author_facet D’Amico, Ramona
Gugliandolo, Enrico
Siracusa, Rosalba
Cordaro, Marika
Genovese, Tiziana
Peritore, Alessio Filippo
Crupi, Rosalia
Interdonato, Livia
Di Paola, Davide
Cuzzocrea, Salvatore
Fusco, Roberta
Impellizzeri, Daniela
Di Paola, Rosanna
author_sort D’Amico, Ramona
collection PubMed
description Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system’s dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that regard, the aim of this research was to investigate the impact of ED exposure on the neuroinflammation and oxidative stress in an experimental model of Parkinson’s disease (PD). PD was induced by intraperitoneally injections of MPTP for a total dose of 80 mg/kg for each mouse. Mice were orally exposed to EDs, starting 24 h after the first MPTP administration and continuing through seven additional days. Our results showed that ED exposure raised the loss of TH and DAT induced by the administration of MPTP, as well as increased aggregation of α-synuclein, a key marker of PD. Additionally, oral exposure to EDs induced astrocytes and microglia activation that, in turn, exacerbates oxidative stress, perturbs the Nrf2 signaling pathway and activates the cascade of MAPKs. Finally, we performed behavioral tests to demonstrate that the alterations in the dopaminergic system also reflected behavioral and cognitive alterations. Importantly, these changes are more significant after exposure to atrazine compared to other EDs. The results from our study provide evidence that exposure to EDs may play a role in the development of PD; therefore, exposure to EDs should be limited.
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spelling pubmed-91388922022-05-28 Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration D’Amico, Ramona Gugliandolo, Enrico Siracusa, Rosalba Cordaro, Marika Genovese, Tiziana Peritore, Alessio Filippo Crupi, Rosalia Interdonato, Livia Di Paola, Davide Cuzzocrea, Salvatore Fusco, Roberta Impellizzeri, Daniela Di Paola, Rosanna Biomedicines Article Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system’s dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that regard, the aim of this research was to investigate the impact of ED exposure on the neuroinflammation and oxidative stress in an experimental model of Parkinson’s disease (PD). PD was induced by intraperitoneally injections of MPTP for a total dose of 80 mg/kg for each mouse. Mice were orally exposed to EDs, starting 24 h after the first MPTP administration and continuing through seven additional days. Our results showed that ED exposure raised the loss of TH and DAT induced by the administration of MPTP, as well as increased aggregation of α-synuclein, a key marker of PD. Additionally, oral exposure to EDs induced astrocytes and microglia activation that, in turn, exacerbates oxidative stress, perturbs the Nrf2 signaling pathway and activates the cascade of MAPKs. Finally, we performed behavioral tests to demonstrate that the alterations in the dopaminergic system also reflected behavioral and cognitive alterations. Importantly, these changes are more significant after exposure to atrazine compared to other EDs. The results from our study provide evidence that exposure to EDs may play a role in the development of PD; therefore, exposure to EDs should be limited. MDPI 2022-05-05 /pmc/articles/PMC9138892/ /pubmed/35625810 http://dx.doi.org/10.3390/biomedicines10051073 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
D’Amico, Ramona
Gugliandolo, Enrico
Siracusa, Rosalba
Cordaro, Marika
Genovese, Tiziana
Peritore, Alessio Filippo
Crupi, Rosalia
Interdonato, Livia
Di Paola, Davide
Cuzzocrea, Salvatore
Fusco, Roberta
Impellizzeri, Daniela
Di Paola, Rosanna
Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
title Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
title_full Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
title_fullStr Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
title_full_unstemmed Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
title_short Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration
title_sort toxic exposure to endocrine disruptors worsens parkinson’s disease progression through nrf2/ho-1 alteration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138892/
https://www.ncbi.nlm.nih.gov/pubmed/35625810
http://dx.doi.org/10.3390/biomedicines10051073
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