Neurotherapeutic efficacy of loaded sulforaphane on iron oxide nanoparticles against cuprizone-induced neurotoxicity: role of MMP-9 and S100β

Abstract

Cuprizone (CUP) induces neurotoxicity and demyelination in animal models by provoking the activation of glial cells and the generation of reactive oxygen species (ROS). Sulforaphane (SF) is a phytochemical that exhibits a neuroprotective potential. In this study, we investigated the neurotherapeutic and pro-remyelinating activities of SF and SF-loaded within iron oxide nanoparticles (IONP-SF) in CUP-exposed rats. Magnetite iron oxide nanoparticles (IONPs) were prepared using the hydrothermal method that was further loaded with SF (IONP-SF). The loading of SF within the magnetite nanoparticles was assessed using FTIR, TEM, DLS, Zetasizer, and XPS. For the in vivo investigations, adult male Wistar rats (n = 40) were administrated either on a regular diet or a diet with CUP (0.2%) for 5 weeks. The rats were divided into four groups: negative control, CUP-induced, CUP + SF, and CUP + IONP-SF. CUP-exposed brains exhibited a marked elevation in lipid peroxidation, along with a significant decrease in the activities of glutathione peroxidase (GPx), and catalase (CAT). In addition, CUP intoxication downregulated the expression of myelin basic protein (MBP) and myelin proteolipid protein (PLP), upregulated the expression of Matrix metallopeptidase-9 (MMP-9) and S100β, and increased caspase-3 immunoexpression, these results were supported histopathologically in the cerebral cortexes. Treatment of CUP-rats with either SF or IONP-SF demonstrated remyelinating and neurotherapeutic activities. We could conclude that IONP-SF was more effective than free SF in mitigating the CUP-induced downregulation of MBP, upregulation of S100β, and caspase-3 immunoexpression.

Keywords:

• Cuprizone (CUP)
• sulforaphane (SF)
• myelin basic protein (MBP)
• S100β calcium binding protein
• matrix metallopeptidase 9 (MMP-9)
• iron oxide nanoparticles (IONPs)

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of National Research Center (NRC), Egypt (Approval no. 19-313).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This work was financially supported by the National Research Centre (NRC), Egypt (Project no.: 12060106, 2019–2022; P.I.: Dr. Ghadha Ibrahim Fouad).