Clin Lab. 2024 Oct 1;70(10). doi: 10.7754/Clin.Lab.2024.240307.
Alzheimer's disease is a progressive neurodegenerative disease that causes an irreversible decline in the functional, cognitive, and behavioral activities of affected individuals. Amifostine is a cytoprotective drug with well-documented pleiotropic effects such as anti-inflammatory, antioxidant, and anti-apoptotic effects. The study was carried out to investigate the neuroprotective effect of amifostine in a mouse model of Alzheimer's disease.
Swiss Webster albino mice were divided into four groups (n = 10): (I) control, (II) scopolamine (1 mg/kg i.p. once daily for 7 days), and two treatment groups. The treatment groups received the test drugs prophylactically for 2 weeks, followed by induction with scopolamine and the test drug at the same doses for one week, followed by (III) donepezil (5 mg/kg daily, i.p. for three weeks) or (IV) amifostine (200 mg/kg daily, i.p. for three weeks). After the treatments, behavioral tests were conducted using the spontaneous Y maze test and the novel object recognition test (NORT). The brain tissue homogenates of the experimental mice were processed for biological analysis. The levels of inflammatory (TNF-α, IL-6, and IL-1β), and oxidative stress (SOD and MDA) markers, as well as acetyl cholinesterase, were determined.
Scopolamine intraperitoneal administration resulted in impairment of cognitive performance and neuro-toxicity. Amifostine significantly attenuated scopolamine-induced injury, as observed in improved spatial working memory. Moreover, amifostine significantly reduced lipid peroxidation, increased SOD level, and reduced the proinflammatory markers and acetyl cholinesterase activity in brain tissue homogenates.
Preconditioning with amifostine had a neuroprotective effect, maintained cognitive function, and enhanced cholinergic activity in the scopolamine-induced mouse model of Alzheimer's disease.
阿尔茨海默病是一种进行性神经退行性疾病，会导致受影响个体的功能、认知和行为活动不可逆转地下降。氨磷汀是一种细胞保护药物，具有抗炎、抗氧化和抗细胞凋亡等多种作用。本研究旨在探讨氨磷汀对阿尔茨海默病小鼠模型的神经保护作用。
将瑞士白色种系小鼠分为四组（n=10）：（I）对照组；（II）东莨菪碱（1mg/kg，腹腔注射，每天一次，连续 7 天）组；和两个治疗组。治疗组预防性给药 2 周，然后用东莨菪碱和相同剂量的测试药物诱导 1 周，随后（III）多奈哌齐（5mg/kg，腹腔注射，连续 3 周）或（IV）氨磷汀（200mg/kg，腹腔注射，连续 3 周）。治疗后，使用自发 Y 迷宫测试和新物体识别测试（NORT）进行行为测试。对实验小鼠的脑组织匀浆进行生物分析。测定炎症（TNF-α、IL-6 和 IL-1β）和氧化应激（SOD 和 MDA）标志物以及乙酰胆碱酯酶的水平。
腹腔内注射东莨菪碱导致认知功能障碍和神经毒性。氨磷汀显著减轻了东莨菪碱诱导的损伤，表现为空间工作记忆改善。此外，氨磷汀还显著降低了脑组织匀浆中的脂质过氧化产物、增加了 SOD 水平，并降低了促炎标志物和乙酰胆碱酯酶活性。
氨磷汀预处理具有神经保护作用，维持了认知功能，并增强了东莨菪碱诱导的阿尔茨海默病小鼠模型中的胆碱能活性。
