Cookies

We use cookies to ensure that we give you the best experience on our website. By continuing to browse this repository, you give consent for essential cookies to be used. You can read more about our Privacy and Cookie Policy.


Durham Research Online
You are in:

The pathopharmacological interplay between vanadium and iron in Parkinson’s Disease models.

Ohiomokhare, Samuel and Olaolorun, Francis and Ladagu, Amany and Olopade, Funmilayo and Howes, Melanie-Jayne R. and Okello, Edward and Olopade, James and Chazot, Paul L. (2020) 'The pathopharmacological interplay between vanadium and iron in Parkinson’s Disease models.', International journal of molecular sciences., 21 (18). p. 6719.

Abstract

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)B9Drosophila 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.

Item Type:Article
Full text:(VoR) Version of Record
Available under License - Creative Commons Attribution.
Download PDF
(1737Kb)
Full text:(VoR) Version of Record
Available under License - Creative Commons Attribution.
Download Archive (ZIP) (Supplementary information)
(367Kb)
Status:Peer-reviewed
Publisher Web site:https://doi.org/10.3390/ijms21186719
Publisher statement:© 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/).
Date accepted:08 September 2020
Date deposited:15 September 2020
Date of first online publication:14 September 2020
Date first made open access:15 September 2020

Save or Share this output

Export:
Export
Look up in GoogleScholar