Fisetin attenuates AlCl3-induced neurodegeneration by modulating oxidative stress and inflammatory cytokine release in adult albino wistar rats.

Aim: Natural flavonoids have powerful antioxidant and anti-inflammatory activities against neurodegenerative diseases. Fisetin is a powerful flavonoid that targets a variety of neurological disorders. Aluminum (Al) has been linked to several neurological conditions, such as Parkinsons disease, autism, and Alzheimer's disease (AD). This study was designed to assess the modulatory role of fisetin in reversing oxidative stress and neuroinflammation caused by Aluminum chloride (AlCl3) induced neurological conditions in rats.

Methods: Adult male Wistar were randomly divided into eight groups of four animals per group. Group 1; the control group received phosphate-buffered saline, group 2 received 100 mg/kg/bodyweight of aluminum chloride, and group 3,4, and 5 received 25, 50, and 75 mg/kg/bodyweight of fisetin respectively for 21 days. Groups 6, 7, and 8 received 25, 50, and 75 mg/kg/bodyweight of fisetin for 14 days followed by 100 mg/kg/bodyweight of aluminum chloride for 7 days respectively. The administration was via the oral route. Following treatment, the rats were euthanized, and biochemical alterations were observed by measuring the serum levels of Glutathione S-Transferase (GST) and Malondialdehyde (MDA) for oxidative stress and Interleukin-6 (IL-6) for neuroinflammation. Furthermore, histopathological evaluations of the thalamus were carried out using routine Hematoxylin and Eosin (H&E) and Cresyl Fast Violet (CFV) techniques while expressions of Glial Fibrillary Acidic Protein (GFAP) for astrocytes, and Ionized Calcium Binding Adapter Molecule 1 (IBA1) for microglia, were examined by immunohistochemical methods.

Results: The findings in the AlCl₃ group indicated a rise in lipid peroxidation, decreased antioxidant activity, altered thalamic histomorphology, and increased expression of GFAP and IBA1 markers for astrocytes and microglia, respectively. These effects were mitigated in the Fisetin pretreated groups.

Conclusion: These results imply that fisetin can attenuate AlCl₃-induced neurodegeneration possibly by mitigating oxidative stress and neuroinflammation.