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Fucoxanthinol Mitigates the Cytotoxic Effect of Chlorpyrifos and MPTP on the Dopaminergic Differentiation of SH-SY5Y Human Neuroblastoma Cells

Lookup NU author(s): Dr Mouhamed AlsaqatiORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

This study investigates the neuroprotective effects of fucoxanthinol (FXL) against the toxic activities of two compounds known to induce neurotoxic effects in humans and animals. MPTP (1-methyl- 4-phenyl- 1,2,3,6-tetrahydropyridine) induces Parkinson's disease (PD)-like phenotypes by inhibiting mitochondrial complex I in dopaminergic neurons. Chlorpyrifos (CPF), another neurotoxic agent, is associated with acute and long-term neurotoxicity primarily through acetylcholinesterase (AChE) inhibition. FXL demonstrated the ability to reverse the neurotoxic effects of CPF and MPTP in SH-SY5Y dopaminergic neuronal cell models. Treatment with FXL enhances mitochondrial function in SH-SY5Y cells exposed to CPF and MPTP, as demonstrated by increased levels of Adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), mitochondrial complexes activities, and oxygen consumption rates, pyruvate dehydrogenase (PDH) activities, and mitophagy pathways. This improvement highlights FXL's ability to counteract the mitochondrial dysfunction induced by these neurotoxic agents. Additionally, FXL reduces oxidative damage and enhances cell viability. At the molecular level, the neuroprotective effects were also associated with the modulation of apoptotic cell markers, including Bcl- 2 and the oxidative damage markers. Molecular docking data further support the outcomes of our in vitro studies. Multivariable analysis highlights the neuroprotective effects of FXL. These findings indicate the potential of FXL to mitigate CPF- and MPTP-induced neurotoxicity, suggesting its promise as a therapeutic agent for managing neuronal damage observe in PD.


Publication metadata

Author(s): Elmorsy EM, Al-Ghafari AB, Al Doghaither HA, Elghareeb MM, Alsaqati M

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Neuroscience

Year: 2025

Volume: 75

Issue: 2

Print publication date: 08/04/2025

Online publication date: 08/04/2025

Acceptance date: 01/04/2025

Date deposited: 15/04/2025

ISSN (print): 0895-8696

ISSN (electronic): 1559-1166

Publisher: Springerlink

URL: https://doi.org/10.1007/s12031-025-02342-7

DOI: 10.1007/s12031-025-02342-7

Data Access Statement: Data of this study are available from the corresponding author upon reasonable request.


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Funding

Funder referenceFunder name
the Deanship of Scientific Research at Northern Border University, Arar, Saudi Arabia, under project number NBU-FFR- 2025–2510-011

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