Pirfenidone mitigates demyelination and electrophysiological alterations in multiple sclerosis: Targeting NF-κB, sirt1, and neurotrophic genes.

Autor: Abo-Elsoud RAA; Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Menoufia, Egypt., Ali EA; Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Menoufia, Egypt., Al-Gholam MA; Anatomy and Embryology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Menoufia, Egypt., Rizk MS; Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Menoufia, Egypt.; Medical Biochemistry and Molecular Biology Department, Faculty of Dentistry, AlRyada University, Sadat City, Menoufia, Egypt., Elseadawy RSA; Neuropsychiatry Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Menoufia, Egypt., Ameen O; Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Menoufia, Egypt. omnia.ameen@med.menofia.edu.eg.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Oct 15. Date of Electronic Publication: 2024 Oct 15.
DOI: 10.1007/s00210-024-03496-8
Abstrakt: Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system associated with progressive neurodegeneration. Pirfenidone (Pir) is a well-known antifibrotic agent; however, Pir's function in MS is little explored. We evaluated the neuroprotective effects of Pir in MS and its possible underlying mechanisms. Forty male Swiss mice were divided equally into control, cuprizone (CPZ), Pir, and CPZ + Pir groups. Assessment of motor function was conducted using neurobehavioral tests, EMG, and nerve conduction velocity (NCV). Mice's brains were extracted to measure oxidative stress, neuroinflammatory markers, and the expression of neurotrophic genes. The corpus callosum and the sciatic nerve were subjected to histopathological and immunohistochemical studies. The CPZ group was associated with significant reductions in muscle power, frequency of contraction, sciatic NCV, SOD, IL-10, SIRT1, NGF, and neuregulin-1. Significant increases in MDA, TNF-α, INF-γ, IL-17, TGF-β, and NF-κB were also detected. Multiple areas of partially demyelinated nerve fibers in the corpus callosum, the loss of oligodendrocyte nuclei, and increased microglia and astrocytes were also observed. The sciatic nerve revealed partial demyelination with significantly reduced myelin basic protein (MBP) expression. Pir significantly restored motor function, demyelination, and neurodegenerative changes induced by CPZ. Besides the antifibrotic action of Pir, we concluded that it improves motor function in MS by alleviating the demyelinating process and neurodegeneration. Its potential anti-inflammatory, antioxidant, and antifibrotic properties could be contributing factors. These effects could be mediated by modulating the NF-κB, SIRT1, NGF, and neuregulin-1 pathways. Pir is a promising agent for treating MS.
(© 2024. The Author(s).)
Databáze: MEDLINE
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