Effect of piracetam, vincamine, vinpocetine, and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats

In this study, we investigated the effects of the memory-enhancing drugs piracetam, vincamine, and vinpocetine or the cholinesterase inhibitor donepezil on the development of oxidative stress, inflammation, and brain damage induced in rat brain by aluminum chloride (AlCl3). Saline (control), piracetam (100 or 300 mg/kg), vincamine (10 or 20 mg/kg), vinpocetine (10 or 20 mg/kg), piracetam 100 mg/kg plus vincamine 10 mg/kg, piracetam 100 mg/kg plus vinpocetine 10 mg/kg, or donepezil 5 mg/kg were administered once daily intraperitoneally for 45 days along with AlCl3 (10 mg/kg, intraperitoneally). Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, acetylcholinesterase (AChE), butrylcholinesterase (BChE), paraoxonase (PON1) activities, and prostaglandin E2 (PGE2) concentrations were measured in brain. Histopathology and caspase-3 immunohistochemistry (an apoptotic marker) were also performed. Results indicated that (1) compared to controls, injection of AlCl3 significantly increased brain lipid peroxidation (MDA) and nitric oxide concentrations together with decreased GSH concentrations. PON1 activity in brain was significantly decreased, while AChE and BChE activities were significantly increased compared to control animals. Cortical atrophy, neuronal shrinkage, red neurons, surrounded by vacuolations with cytoplasmic neurofibrillary tangles, intense caspase-3 expression in degenerated neurons, and amyloid deposition were observed; (2) in AlCl3-treated rats,...
Source: Comparative Clinical Pathology - Category: Pathology Source Type: research