Neuroprotective Effects of Amifostine in Mouse Model of Alzheimer's Disease.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Preconditioning with amifostine had a neuroprotective effect, maintained cognitive function, and enhanced cholinergic activity in the scopolamine-induced mouse model of Alzheimer's disease.