Cargando…

The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models

Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental...

Descripción completa

Detalles Bibliográficos
Autores principales: Ohiomokhare, Samuel, Olaolorun, Francis, Ladagu, Amany, Olopade, Funmilayo, Howes, Melanie-Jayne R., Okello, Edward, Olopade, James, Chazot, Paul L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554808/
https://www.ncbi.nlm.nih.gov/pubmed/32937783
http://dx.doi.org/10.3390/ijms21186719
_version_ 1783593860178378752
author Ohiomokhare, Samuel
Olaolorun, Francis
Ladagu, Amany
Olopade, Funmilayo
Howes, Melanie-Jayne R.
Okello, Edward
Olopade, James
Chazot, Paul L.
author_facet Ohiomokhare, Samuel
Olaolorun, Francis
Ladagu, Amany
Olopade, Funmilayo
Howes, Melanie-Jayne R.
Okello, Edward
Olopade, James
Chazot, Paul L.
author_sort Ohiomokhare, Samuel
collection PubMed
description Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK−1)(B9) Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK−1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD.
format Online
Article
Text
id pubmed-7554808
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75548082020-10-14 The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models Ohiomokhare, Samuel Olaolorun, Francis Ladagu, Amany Olopade, Funmilayo Howes, Melanie-Jayne R. Okello, Edward Olopade, James Chazot, Paul L. Int J Mol Sci Article Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK−1)(B9) Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK−1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD. MDPI 2020-09-14 /pmc/articles/PMC7554808/ /pubmed/32937783 http://dx.doi.org/10.3390/ijms21186719 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ohiomokhare, Samuel
Olaolorun, Francis
Ladagu, Amany
Olopade, Funmilayo
Howes, Melanie-Jayne R.
Okello, Edward
Olopade, James
Chazot, Paul L.
The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
title The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
title_full The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
title_fullStr The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
title_full_unstemmed The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
title_short The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
title_sort pathopharmacological interplay between vanadium and iron in parkinson’s disease models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554808/
https://www.ncbi.nlm.nih.gov/pubmed/32937783
http://dx.doi.org/10.3390/ijms21186719
work_keys_str_mv AT ohiomokharesamuel thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT olaolorunfrancis thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT ladaguamany thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT olopadefunmilayo thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT howesmelaniejayner thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT okelloedward thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT olopadejames thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT chazotpaull thepathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT ohiomokharesamuel pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT olaolorunfrancis pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT ladaguamany pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT olopadefunmilayo pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT howesmelaniejayner pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT okelloedward pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT olopadejames pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels
AT chazotpaull pathopharmacologicalinterplaybetweenvanadiumandironinparkinsonsdiseasemodels