الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Nanotechnology is emerging as a new interdisciplinary area of research cutting across the disciplines of biology, chemistry, engineering, and medicine, which is expected to lead to advances in many indispensable fields. Recent years have seen an explosion in the number of studies showing the variety of medical applications of nanotechnology.
Nanoparticles have become widely utilized because of their unique properties and diverse applications in biotechnology and life sciences. Among the various nanoparticles, gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Gold nanoparticles have potential applications in biomedicine, but one of the most important concerns is about their safety.
In contrast to unintentional exposure to nanoparticles through the use of consumer products, emerging biomedical applications of nanoparticles such as biosensors and drug delivery agents involve deliberate, direct ingestion or injection of nanoparticles. For this reason, toxicity is a critical factor when evaluating the biomedical potential of nanoparticles. Because of their high surface area to mass ratio, nanoparticles are highly reactive and may enter cells that they would otherwise have no access to.
Furthermore, the underlying interactions of nanoparticles with biological systems is a key feature for understanding their biological impact, which could perhaps be exploited to mitigate unwanted toxic effects. Manufactured nanoparticles can be toxic via interactions with proteins and enzymes. Acetylcholine esterase (AChE) is one of the most efficient enzymes of the central nervous system (CNS) which is concentrated at the cholinergic synapses and at neuromuscular synapses thus playing an essential role in cholinergic neurotransmission. Monoamine oxidase (MAO) plays also a pivotal role in CNS by catalyzing the oxidative deamination of many biogenic amines.
An emerging area of research is examining the neurobehavioral aspects of omega-3 fatty acids and their critical role in the proper functioning of the CNS. Omega-3 fatty acids are highly concentrated in the brain, and their deficiencies may alter neurochemical pathways that are involved in the pathophysiology of several psychiatric illnesses. Meanwhile, poly unsaturated fatty acids (PUFAs) have been shown to have an important role in the proper function of brain and CNS and to be an exquisitely modulator of neurotransmitter’s action.
The present work was devoted to study the effect of gold nanoparticles on AChE and MAO activities in different parts of rat brain (basal ganglia, frontal cortex, cerebellum and medulla oblongata) with and without supplementation of omega-3 fatty acid in a trial to minimize the cytotoxic effect of gold nanoparticles on nervous system enzymes. Results obtained through biochemical studies were confirmed by histopathological studies, thus provided an understanding relationship between the physical and chemical properties of gold nanoparticles and their in vivo behavior.
Gold nanoparticles were synthesized with diameter nearly 20 nm. Morphology and size of gold nanoparticles were determined by transmission electron microscope, zeta potential and particle size distribution which revealed presence of completely spherical gold nanoparticles with smooth surfaces and have size of nearly 20nm. The absorption spectra of gold nanoparticles suspension were also determined by UV-visible spectrophotometer and revealed that the plasmon absorption was clearly visible and their maximum absorption peaks were at 530 nm.
The present study was carried out on 60 male albino rats of mean body weight 150-250g. The animals were randomly divided into 3 main experimental groups as follows:-
1. Group I: consisted of 20 rats that were injected intraperitonealy with saline only and served as control group.
2. Group II: consisted of 20 rats that were injected intraperitonealy with a suspension of gold nanoparticles of about 20 nm for 6 days.
3. Group III: consisted of 20 rats that were injected as in group II accompanied with oral supplementation of omega-3 fatty acid for 6 days.
Animals were scarified by decapitation after the time course of the experiment. Brain tissue samples from different brain parts (basal ganglia, frontal cortex, medulla oblongata and cerebellum) in the different studied groups were obtained for further biochemical and histopathological investigations.
Biochemical studies investigated the activity of both AChE and MAO enzymes. Both enzymes activities were measured in the brain homogenate in basal ganglia, frontal cortex, medulla oblongata and cerebellum in the different studied groups in order to assess neurotoxicity of prepared gold nanoparticles and neuroprotective effects of omega-3 fatty acid supplementation. Histopathological examination using Light microscope was also performed on a biopsy from the different parts of rat brain in the different studied groups
At the end of the work, the data obtained from biochemical studies revealed that:
• There is significant decrease in both AChE and MAO activity in basal ganglia, frontal cortex, medulla oblongata and cerebellum in gold nanoparticle injected group as compared to control group.
• There is no significant difference in both AChE and MAO activities in basal ganglia and frontal cortex in gold nanoparticles injected group supplemented with omega-3 as compared to control group.
• There is a significant decrease in both AChE and MAO activities in medulla oblongata and cerebellum in gold nanoparticles injected group supplemented with omega-3 as compared to control group.
• There is a significant decrease in both AChE and MAO activities in basal ganglia, frontal cortex, medulla oblongata and cerebellum in gold nanoparticle injected group as compared to gold nanoparticles injected group supplemented with omega-3.
• In gold nanoparticles injected group the most noticed decrease in AChE activity was in basal ganglia, followed by medulla oblongata, frontal cortex, and then cerebellum.
• In gold nanoparticles injected group supplemented with omega-3 the most noticed decrease in AChE activity was in cerebellum, followed by medulla oblongata, basal ganglia, and then frontal cortex.
• In gold nanoparticle injected group the most noticed decrease in MAO activity was in basal ganglia, followed by medulla oblongata, cerebellum, and then frontal cortex.
• In gold nanoparticles injected group supplemented with omega-3 the most noticed decrease in MAO activity was in cerebellum, followed by medulla oblongata, frontal cortex and then basal ganglia.
• It is noteworthy to mention that the part of rat brain which is highly affected by gold nanoparticles in case of AChE (basal ganglia) was the same as the part affected in case of MAO. This indicates that basal ganglia is very sensitive part and can be easily affected by brain toxicants.
• On the basis of the above results, it is suggested that the rate of inhibition between the different studied parts, in vivo may be due to the difference in enzyme concentration in the different brain parts or due to the difference in the rate of blood supply to the brain.
The histopathological findings confirmed the biochemical alterations and revealed that:
• There were various degrees of brain tissue injury in basal ganglia, frontal cortex, medulla oblongata and cerebellum in gold nanoparticles injected group characterized by inflammation, pyknosis of the nuclei, neuronal cell degeneration, vacuolization and the presence of apoptotic cell bodies in brain tissues which are all signs of apoptosis (programmed cell death).
• Basal ganglia, frontal cortex, medulla oblongata, and cerebellum in gold nanoparticles injected group supplemented with omega-3 exhibited marked improvement indicated by the decrease in inflammation, decrease in neuronal degeneration and partial restoration of neuronal function.
• The destructive and degenerative changes in the different studied brain parts were highly prominent in gold nanoparticles injected group revealing the cytotoxic effects of gold nanoparticles in the brain.