Anyanwu G Emeka, Nwachukwu I Jacinta, Oria S Rademene, Obasi K Kosisochukwu, Ekwueme E Precious, Nto J Nto, Anyanwu N Chinyere
Department Of Anatomy, Faculty of Biomedical Sciences, Kampala International University, Uganda.
Department Of Anatomy, Faculty Basic Medical Sciences, College of Medicine, University of Nigeria Enugu Campus, Enugu, Enugu State, Nigeria.
Toxicol Rep. 2024 Nov 13;13:101812. doi: 10.1016/j.toxrep.2024.101812. eCollection 2024 Dec.
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.
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.
The findings in the AlCl 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.
These results imply that fisetin can attenuate AlCl-induced neurodegeneration possibly by mitigating oxidative stress and neuroinflammation.
天然黄酮类化合物对神经退行性疾病具有强大的抗氧化和抗炎活性。非瑟酮是一种强大的黄酮类化合物，可针对多种神经系统疾病。铝（Al）与多种神经系统疾病有关，如帕金森病、自闭症和阿尔茨海默病（AD）。本研究旨在评估非瑟酮在逆转氯化铝（AlCl3）诱导的大鼠神经疾病所引起的氧化应激和神经炎症中的调节作用。
成年雄性Wistar大鼠随机分为八组，每组四只动物。第1组为对照组，接受磷酸盐缓冲盐水；第2组接受100mg/kg体重的氯化铝；第3、4和5组分别接受25、50和75mg/kg体重的非瑟酮，持续21天。第6、7和8组分别接受25、50和75mg/kg体重的非瑟酮14天，随后分别接受100mg/kg体重的氯化铝7天。给药途径为口服。治疗后，对大鼠实施安乐死，通过测量血清谷胱甘肽S-转移酶（GST）和丙二醛（MDA）水平以观察氧化应激情况，测量白细胞介素-6（IL-6）水平以观察神经炎症情况，从而观察生化改变。此外，使用常规苏木精和伊红（H&E）以及甲酚紫（CFV）技术对丘脑进行组织病理学评估，同时通过免疫组织化学方法检测星形胶质细胞的胶质纤维酸性蛋白（GFAP）和小胶质细胞的离子钙结合衔接分子1（IBA1）的表达。
AlCl组的研究结果表明脂质过氧化增加、抗氧化活性降低、丘脑组织形态改变，以及星形胶质细胞和小胶质细胞的GFAP和IBA1标记物表达分别增加。在非瑟酮预处理组中，这些影响得到缓解。
这些结果表明，非瑟酮可能通过减轻氧化应激和神经炎症来减轻AlCl诱导的神经退行性变。
