Abstract
Aluminum is a potent neurotoxin used in animal models of neurodegenerative diseases like Alzheimer’s disease (AD), in which oxidative stress mediates tissue pathogenesis in vivo. N-acetyl cysteine (NAC) is a glutathione precursor with reported antioxidant and neuroprotective potentials. Recent therapy for combating AD is known to provide only symptomatic relief thus necessitating the discovery of new drugs and their mechanism of action. This study was aimed to demonstrate the in vivo neuroprotective effect of NAC against aluminum (Al3+)-induced neuro-degeneration in rats (a model for AD). Twenty- five (25) adult male Wistar rats used for this study were divided into 5 groups: Group A = Control, B = Aluminum chloride (200 mg/kg), C = 1000 mg/kg of NAC + Aluminum chloride (200 mg/kg), D = 1000 mg/kg of NAC, E = Aluminum chloride (200 mg/kg) was orally administered daily for 3 weeks and discontinued for one week. Frontal Cortex harvested for histological analysis using Haematoxylin and Eosin stain, Cresyl Fast Violet stain for Nissl granules and Glial fibrillary acidic protein immunohistochemistry specific for astrocytes. Aluminum significantly induced oxidative stress, coupled with marked neurons necrosis, chromatolysis and gliosis in the frontal cortex, upon NAC administration, there was neuro anti-inflammatory response as seen in the significant reduction in astrocytes expression, neuronal cell death and Nissl body aggregation which attenuates neuropathological deficits induced by Al3+. It was shown that aluminum is a neurotoxin mediating AD-like oxidative stress, NAC has a therapeutic potential associated with its potent in vivo interaction with astrocytes in response to Al3+ neuro-inflammation seen in positive expression of Nissl granules and glial cells in addition to possibility of endogenous glutathione neuroprotection after withdrawal of stress mediator in neurodegeneration.Graphical abstract
Highlights
Neurodegenerative disorders (e.g. Alzheimer’s disease [AD]) are associated with chronic inflammation, oxidative stress (Mayeux 2010; Ahmad et al 2018), progressive cognitive deficits and changes in neuro-behavioural pattern (Jellinger 2013)
Our study showed that there was no significant difference in weight change in the Aluminum treated group (B) as compared to initial weight before treatment
Group E self-repaired because the discontinued Aluminum treatment prevent continuous generation of ROS which is up-regulated by endogenous secretion of glutathione which mobs off free radicals or reactive oxygen species already secreted
Summary
Neurodegenerative disorders (e.g. Alzheimer’s disease [AD]) are associated with chronic inflammation, oxidative stress (Mayeux 2010; Ahmad et al 2018), progressive cognitive deficits and changes in neuro-behavioural pattern (Jellinger 2013). Pathological reports show that AD is characterized by deposition beta-amyloid (Aβ) plaques, reactive oxygen species (ROS), reduction in acetylcholine (ACh), hyper-phosphorylated tau proteins and glutamatergic abnormalities (Ahmad et al 2018; Ovais et al 2018). Aluminium exposed animals have displayed neuro fibrillary tangles formation, cholinergic neuronal axonal terminal loss, β- amyloid protein aggregation, oxidative stress and neuronal apoptosis in the hippocampus and frontal cortex site for cognition, memory and synaptic plasticity similar to the pathogenesis of AD (Praveenkumar et al 2019). Aluminum chloride (AlCl3) a white salt; administered at 200 mg/kg body weight in rats and mice (Yen-Koo 1992) have demonstrated such cognitive impairments (Lide 2008; Yokel 2005)
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