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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.

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Authors

Samuel Ohiomokhare

Francis Olaolorun

Amany Ladagu

Funmilayo Olopade

Melanie-Jayne R. Howes

Edward Okello

James Olopade



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.

Citation

Ohiomokhare, S., Olaolorun, F., Ladagu, A., Olopade, F., Howes, M. R., Okello, E., …Chazot, P. L. (2020). The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models. International Journal of Molecular Sciences, 21(18), Article 6719. https://doi.org/10.3390/ijms21186719

Journal Article Type Article
Acceptance Date Sep 8, 2020
Online Publication Date Sep 14, 2020
Publication Date 2020-09
Deposit Date Sep 14, 2020
Publicly Available Date Sep 15, 2020
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 21
Issue 18
Article Number 6719
DOI https://doi.org/10.3390/ijms21186719

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