الفهرس 
INTRODUCTIONيوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Occupational high-grade lead (Pb2+) exposure has been reduced in recent decades as a result of increased regulation. However, environmental Pb2+ exposures remain widespread; as this metal is highly malleable, resistant to corrosion & extensively used in many purposes especially in building construction, for the past several millennia. Pb2+ is a ubiquitous and potent neurotoxicant, induces several neurophysiological and behavioral changes & alters the function of multiple organs and systems. The nervous system is the primary target for the low levels of Pb2+ exposures & the developing brain appears to be especially vulnerable to Pb2+ neurotoxicity. Relatively low, sub-clinical doses of Pb+2 that produce no overt signs of encephalopathy but can affect cognitive, emotional, & motor functions.
Chronic lead exposure has been shown to produce behavioral disturbances in both human & animal models involved in certain forms of learning and memory. These disturbances are associated with alterations in monoamine neurotransmitters in the central nervous system (CNS).
Also, Pb2+ induces oxidative stress and membrane disturbances in the brain and the oxidative damage has been proposed as a possible mechanism of lead neurotoxicity. Apoptosis is also thought to relate to lead neurotoxicity.
The present study, focused on the two brain areas (hippocampus & cerebral cortex). It was designed to investigate the two possible mechanisms involved in lead neurotoxicity and the potential protective effects of α-Lipoic acid (α-LA), as an antioxidant against lead-induced neurotoxicity.
α-Lipoic acid has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead-induced neurotoxicity. In this study, forty adults healthy male albino rats (130 ± 10 g) were used and divided into five equal groups (eight rats in each) as follows: (GPI ) Normal control group (C); rats were enrolled as a normal blank control group: (GPII) Initiation group (Lead acetate, Pb2+ ,control group) (A); rats were injected intraperitoneal (i.p.) once per day in a dose of 20 mg/kg.b.wt for two weeks: (GPIII) Treatment group (α-Lipoic acid control group) (B); rats were injected (i.p.) daily with α-LA (20 mg/kg.b.wt) for three weeks: (GPIV) Pre-initiation treatment group (prophylactic group) (D); rats were injected (i.p.) per day with α-Lipoic acid (20 mg/kg.b.wt) for one week and then for another two weeks received the above mentioned doses of lead acetate together with the same dose of α-Lipoic acid: (GpV) Post-initiation treatment group (therapeutic group) (E); male rats were injected (i.p.) once per day with lead acetate for two weeks then were injected (i.p.) daily with α-Lipoic acid for successive three weeks with the above-mentioned dose. At the propitiate experimental periods rats from each group were killed by sudden decapitation and then brain tissues were immediately collected for experiments.
The levels of lipid peroxidation as malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH), nitrite/nitrate (NO), also, the activity of acetylcholinesterase (AChE), norepinephrine (NE), dopamine (DA), serotonin (5- HT) and the change in the energy content measured as adenosine triphosphate (ATP) were estimated in the selected brain regions (hippocampus & cerebral cortex) of adult male albino rats in the different groups. In addition, the effect of lead acetate exposure on spatial learning and memory in Morris Water Maze (MWM) was determined. These altered biochemical variables were supported by histopathological examinations.
Results showed that administration of Pb2+ (Lead acetate) leading to enhancement of lipid peroxidation MDA, PCC in brain regions with a concomitant reduction in GSH levels, NO production, and AChE activity. In addition, the levels of NE, DA, 5- HT and ATP were decreased in the brain regions. However, the administration of α-LA showed a protective effect against lead acetate induced neurotoxicity. Rats treated with α-LA showed a corresponding decrease in brain lipid peroxidation MDA and PCC. Furthermore, there was an increase in brain GSH level, NO production, AChE activity and the levels of NE, DA & 5- HT and ATP.
Behavior data showed that Pb2+ exposure impaired spatial learning assessed in MWM and there was a significant day’s effect with significant differences between control and lead acetate groups and treated animals with α-Lipoic acid. Also, rats exposed to Pb2+ had higher platform location latency than the control group during probe trial (p < 0.05). Groups treated with α-Lipoic acid showed that α-LA can reverse cognitive dysfunction, (MWM) test, observed in rats treated with Lead acetate and improves performance on memory tasks.
Finally, histological studies showed that Pb2+ caused degeneration of neurons and pyknosis in the brain of rats. Rats treated with α-Lipoic acid revealed an improvement in histopathological alteration induced by Lead acetate.
The data showed that α-LA has a good effect when administered as a therapeutic drug more than as a prophylactic one.