Neuroprotective Effects of Ethyl Pyruvate against Aluminum Chloride-Induced Alzheimer ’s Disease in Rats via Inhibiting Toll-Like Receptor 4

AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disease characterized by the formation of insoluble deposits of β-amyloid (Aβ) plaques within the parenchyma of the brain. The present study aimed to investigate the neuroprotective role of ethyl pyruvate against in vitro and in vivo model of al uminum chloride (AlCl3)-induced AD. Effect of ethyl pyruvate (5, 10, 20, 40  mM) against AlCl3 (1250  μM)-induced neurotoxicity in primary neuron-glial mixed cell culture was evaluated using cell viability assays (MTT assay as well as calcein-AM/propidium iodide fluorescent dyes). In vivo model, AlCl3 (50  mg/kg) were given through intraperitoneal route (i.p.) once daily for 4  weeks in rats and after 2 weeks, ethyl pyruvate (50, 100, 200 mg/kg/day) was co-administered with AlCl3 once daily via the oral route. The present study, in addition to perform histopathology of the brain, also estimated oxidant and antioxidant parameters as well as memory impairment using pole test, plus maze, and Morris water maze test. The binding mode of ethyl pyruvate in the hMD-2 was also studied. Results of in vitro studies showed that the AlCl3 administration resulted in neuronal cell death. AlCl3 administration in rats resulted in memory loss, oxidative stress (increased  lipid peroxide and nitric oxide), impairment of antioxidant mechanisms (superoxide dismutase, catalase, and reduced glutathione), and deposition of amyloid plaques in cerebral cortex region of the brain. ...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research