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...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6719 |
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| author | Samuel Ohiomokhare Francis Olaolorun Amany Ladagu Funmilayo Olopade Melanie-Jayne R. Howes Edward Okello James Olopade Paul L. Chazot |
| author_facet | Samuel Ohiomokhare Francis Olaolorun Amany Ladagu Funmilayo Olopade Melanie-Jayne R. Howes Edward Okello James Olopade Paul L. Chazot |
| author_sort | Samuel Ohiomokhare |
| collection | DOAJ |
| 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)<sup>B9</sup><i>Drosophila melanogaster</i> 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 <i>Aloysia citrodora</i> 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. |
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| format | Article |
| id | doaj.art-63988c4795b24d2ba4831e08023b81f6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:21:30Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-63988c4795b24d2ba4831e08023b81f62023-11-20T13:37:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118671910.3390/ijms21186719The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease ModelsSamuel Ohiomokhare0Francis Olaolorun1Amany Ladagu2Funmilayo Olopade3Melanie-Jayne R. Howes4Edward Okello5James Olopade6Paul L. Chazot7Department of Biosciences, Durham University, County Durham DH1 3LE, UKDepartment of Biosciences, Durham University, County Durham DH1 3LE, UKDepartment of Biosciences, Durham University, County Durham DH1 3LE, UKDepartment of Anatomy, College of Medicine, University of Ibadan, Ibadan 200284, NigeriaNatural Capital and Plant Health Department, Royal Botanic Gardens Kew, Surrey TW9 3DS, UKHuman Nutrition Research Centre, Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Tyne and Wear NE1 7RU, UKDepartment of Veterinary Anatomy, University of Ibadan, Ibadan 200284, NigeriaDepartment of Biosciences, Durham University, County Durham DH1 3LE, UKParkinson’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)<sup>B9</sup><i>Drosophila melanogaster</i> 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 <i>Aloysia citrodora</i> 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.https://www.mdpi.com/1422-0067/21/18/6719vanadiumironmitochondriaoxidative stressmotor activityParkinson’s |
| spellingShingle | Samuel Ohiomokhare Francis Olaolorun Amany Ladagu Funmilayo Olopade Melanie-Jayne R. Howes Edward Okello James Olopade Paul L. Chazot The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models International Journal of Molecular Sciences vanadium iron mitochondria oxidative stress motor activity Parkinson’s |
| 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 | vanadium iron mitochondria oxidative stress motor activity Parkinson’s |
| url | https://www.mdpi.com/1422-0067/21/18/6719 |
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