Title | N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson's Disease |
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Type | Journal article |
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Authors | Mursaleen, Leah, Noble, Brendon, Chan, S., Somavarapu, Satyanarayana and Zariwala, M. |
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Abstract | Oxidative stress is a key mediator in the development and progression of Parkinson's disease (PD). The antioxidant n-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability ( = 0.0001), increased iron ( = 0.0033) and oxidative stress ( ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD. |
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Keywords | Parkinson’s disease |
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| antioxidant capacity |
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| deferoxamine |
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| iron |
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| n-acetylcysteine |
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| neurodegeneration |
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| oxidative stress |
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Journal | Antioxidants |
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Journal citation | 9 (7), p. 600 |
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ISSN | 2076-3921 |
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Year | 2020 |
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Publisher | MDPI |
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Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.3390/antiox9070600 |
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PubMed ID | 32660079 |
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Publication dates |
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Published online | 09 Jul 2020 |
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Project | FST Studentship |
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Funder | University of Westminster |
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