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

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.