A Comparative Study on the Ameliorating Role of Flavonoids Rich Fraction Versus Zinc Oxide Nanoparticles in Spinal Cord of Multiple Sclerosis Rat Model Targeting PINK-1/PARKIN; A Biochemical, Histological and Immunohistochemical study

Introduction: Multiple sclerosis (MS) as an autoimmune condition causes demyelination and neuronal loss.Materials and Methods: Forty-eight male adult dark agouti rats divided into six equal groups, group I functioned as control group. EAE was induced in rats of group II, III and IV; Flavonoids rich fraction (FRF) used as treatment of rats in group III; zinc oxide nanoparticles (ZnO-NPs) used as treatment of rats in group IV; Group V received Flavonoids rich fraction; Group VI received zinc oxide nanoparticles. The lumbar spinal cord was divided into three parts. The first part was for enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques. The second part of the spinal cord was for histopathological and immunohistochemical studies (H&E – MBP). The third part was for electron microscopic study.Results: This study demonstrates, for the first time, the beneficial effects of ZnO-NPs over FRF in ameliorating oxidative stress, modulating immune responses, reducing inflammation, and promoting neurodegenerative changes in a rat model of MS. Both FRF, and ZnO-NPs significantly suppressed the inflammatory activity detected in EAE model, through increasing IL-10 and decreasing lL-17 and TNF-α compared to the EAE group. H&E of sections of Group IV (ZnO-NPs treated group) revealed nearly normal architecture of lumbar section of spinal cord with myelinated nerve fibers and normal blood vessels. TEM examination of Flavonoids treated group (group III) showed less affected axons with little irregularity of myelin sheath. Group IV (ZnO-NPs treated group) TEM examination showed nearly normal nerve fibers axons with normal compact myelin sheath and normally arranged mitochondria with normal cristae.Conclusion: These outcomes might lessen symptoms, reduce the rate at which the illness progresses, enhance the quality of life for MS patients, and the potential intervention of ZnO-NPs as a therapeutic strategy for MS.