الفهرس 
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Abstract
Aluminum (Al) is a potent environmental neurotoxin, which is involved in the progression of neurodegenerative diseases such as Alzheimer’s disease (AD). The aim of the present study was to investigate the toxic effects of AlCl3 on the cerebral cortex, hippocampus and hind brain regionsof male rats. Also, the present study aimed to appreciate the protective role of Spirulina (Sp.) and/or ascorbic acid (Vit.C) against AlCl3 neurotoxicity.
Forty-eight adult male Sprague Dawley rats were divided randomly into eight equal groups and treated orally by gavage for 8 weeks as follows: group I: Control was received distilled water; group IIwas received Sp. alone at a dose of (1500mg/kg BW/day); group III was received Vit.C alone at a dose of (40mg/100g BW/day); Groups IVwas received a combination of Vit.C+ Sp. daily with those a previous mentioned doses; group V was treated with AlCl3 only at a dose of (34mg/kg BW (1/25 LD50)/day); group VI, VII and VIII were pre-treated with Sp., Vit.C and Vit.C+ Sp. for 10 consecutive days and in-combination with AlCl3, respectively with those a previous mentioned doses. At the end of the experimental period, whole blood, plasma samples and brain regions (cerebral cortex, hippocampus and hind brain) were collected to evaluate hematological, biochemical, molecular alterations and metal concentrations, as well as histological and fluorescence examination of all studied groups.
In comparison with normal control group, AlCl3 administration caused significant decreased in body weight, brain weight, red blood corpusculars (RBCs) counts, hemoglobin (Hb) and hematocrit (Ht) concentrations, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC), lymphocyte, monocyte and eosinophil counts and increased white blood cells (WBCs), neutrophil, platelet counts and red blood cells distribution width (RDW). Additionally, plasma, cortical, hippocampal and hind brain thiobarbituric acid-reactive substances (TBARS) and acetylcholinesterase (AChE) activity were significantly increased due to AlCl3-intoxication. On the other hand, super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and monoamine oxidase (MAO) enzyme activities, as well as total protein were significantly decreased in plasma and different brain regions except a highly significant increase in CAT of hind brain. Furthermore, total thiol content, total antioxidant capacity (TAC) level and Na+-K+ and total ATPase activities were significantly reduced in brain cortex, hippocampus and hind brain except insignificant decreased in hind brain total ATPase of AlCl3-treated rats. Plasma triacylglycerol (TG), cholesterol, low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), atherogenic rate (Chol/HDL ratio) and apolipoprotein B (ApoB) concentrations were significantly increased in AlCl3-treated group. In contrast, concentration of high-density lipoprotein-cholesterol (HDL-C) in the same group was significantly decreased. Al and Ca concentrationsshowed significantly increased in AlCl3-treated group, whereas a significant inhibition in brain Fe and Mg concentrations. In addition, AlCl3 increased the intensity of tumor necrosis factor (TNF)-α in rat brain homogenates when compared to control. Cerebral cortex and hippocampus histological investigation of rats treated with AlCl3 showed severe congestion in blood vessels, neuronal degeneration with perivascular oedema associated with focal gliosis, neuronphagia and vacuolization, encephalomalacia with amyloid plaques (Aβ) of various sizes formation and neurofibrillary tangles (NFT), as well as more illuminated aggregates in the cerebral cortex and hippocampus of AlCl3-treated rats, higher fluorescence emission intensity in the presence of amyloid protein fibrils which is more intense and very large. Treatment with Spirulina and/or Vit.C was approximately near to control values. Meanwhile, the combined treatment with AlCl3+ Sp. and AlCl3+ Vit.C improved the neurological damages induced by AlCl3and restored the investigated parameters to be near the normal values, moreover co-administration with Vit.C upgrades action of Sp. and ameliorate the toxic effect of AlCl3 on hematological, brain damage and antioxidant parameters.
In conclusion, the present results indicated that the toxic effects of AlCl3 could be mediated through modifying the intracellular brain ions homeostasis, cholinergic dysfunction and oxidative damage in rat brains which may lead to impaired neuronal function. In addition, the results of this study revealed that treatment with Spirulina and vitamin C hadameliorative effects against the Al-induced neurotoxicity and AD. Furthermore, the combination treatment showed the best results and could normalize the tested parameters.