الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Nanotechnology is defined as the “intentional design, characterization and production of materials and systems whose structures and components exhibit novel and significantly improved physical, chemical and biological properties, by controlling their size and shape in the nanoscale range (1 to 100 nm).
Recent years enormous efforts worldwide have led to the production of many types of nanomaterials. There are a lot of manufacturer nanotechnology- based consumer products on the market. Nanotechnology has been regarded as a new technological revolution that touches almost every aspect of human life, making its presence felt in areas such as electronics, coatings, optical devices, energy, and medicine.
The present study highlight one engineered type nanoparticle; gold. Gold nanoparticles (AuNPs) have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability and unique optical properties. Gold in its bulk form has been considered an inert, noble metal with some therapeutic and medical value. Biomedical applications of gold nanoparticles (AuNPs) are rapidly increasing due to their attractive properties of relatively low cytotoxicity. AuNP-based delivery systems are being widely explored for use in cancer chemotherapy treatment as they offer increased drug efficacy with low toxicity to healthy tissue, high biocompatibility, along with versatile production methods. AuNPs have thus been predicted to have a promising future in mainstream clinical practice.
Undoubtedly, advent of any new technologies will have unexpected outcomes which may pose both beneficial and harmful to the human and environment. In spite of its beneficial outcomes in various fields, engineered nanoparticles has created a worldwide concerns and fears have been expressed regarding potential risks of nanoparticles to the environment, health, and safety.
Safety is the first concern to ensure the further application of any new kind of NPs in vivo. Due to the contradictory results of the previous investigations, the present study was aimed at examining the effect of different sizes (10, 20, 50 nm) spherical gold nanoparticles on the pulmonary alveoli and cardiomyocytes.
The study was carried out on 30 adult male albino rats, each of an average weight ranging from 100-120 gm, and of age about 3-4 months. The animals were categorized into 2 groups:
Group I (control group): 12 rats were further subdivided into two equal subgroups, 6 animals each:
Subgroup (Ia): (negative control) rats were injected intraperitoneally (IP) with 200 μl phosphate buffer saline for 7 consecutive days.
Subgroup (Ib): (positive control) rats were injected IP with 200 μl of 1% trisodium citrate dihydrate for 7 consecutive days.
Group II (experimental group): 18 rats were treated with AuNPs. They received an intraperitoneal injection of 200 μl of gold nanoparticle solution at a dose of 4000 μg/kg BW for 7 consecutive days, based on the previously identified toxic dose in vivo. The animals were subdivided into three equal subgroups as follows:
Subgroup (IIa): consisted of 6 rats injected IP with 200 μlAuNPs of size 10 nm.
Subgroup (IIb): consisted of 6 rats injected IP with 200 μlAuNPs of size 20 nm.
Subgroup (IIc): consisted of 6 rats injected IP with 200 μlAuNPs of size 50 nm.
The AuNPs were synthesized by the citrate reduction of Tetrachloroauric acid (HAuCl4.4H2O, 99.9%) solution. This process yielded spherical particles with the required size ranges (10nm, 20nm and 50nm). The prepared AuNPs were characterized using the TEM. The prepared AuNPs were spherical in shape within the size range of 9.1- 11.4 nm, 19.2- 20.8 nm and 50.4- 51.4 nm respectively.
After the designated time during the study, rats were sacrificed and specimens were taken from the lung and left ventricle of all studied groups and prepared for morphological changes and histological studies as follow:-
I. Anatomical changes: to see gross changes in lung and heart shape and size.
II.A. light microscopic examination of pulmonary alveoli by:
a. H&E stain.
b. Gomori’s Trichrome stain.
II.B. Electron microscopic examination: Ultrathin sections were studied using transmission electron microscope.
III. A. light microscopic examination of cardiac myocytes by:
a. H&E stain.
b. Periodic acid Schiff stain (PAS)
III.B. Electron microscopic examination: Ultrathin sections were studied using transmission electron microscope.
The present study revealed no evident change in the anatomy of the lungs and heart of the experimental subgroups in comparison to the control group as regards their color, shape and size.
Meanwhile the study revealed variable degrees of structural changes in the pulmonary alveoli of rats received (10, 20, 50 nm) AuNPs in all experimental subgroups. The microscopic findings in the present study revealed that the 50 nm particles induced more damage than 10, 20 nm.
Light microscopic examination of H&E stained sections of lungs subgroup subgroup II c (5o nm AuNPs) revealed diffuse affection of the lung. The alveoli showed marked collapse and separated by very thick interalveolar septum due to cellular infiltration, foamy macrophage, and acidophilic hyaline material. Whereas, histological paraffin sections of rat lung subgroups IIa (10 nm AuNPs) and IIb (20 nm AuNPs), revealed less collapsed pulmonary alveoli, some alveoli were collapsed and others distended. The collapsed alveoli were separated by thick interalveolar septa due to cellular infiltration, foamy macrophages and acidophilic hyaline material, associated with blood vessels contained acidophilic vacuolated material.
Light microscopic examination of Gomori’s Trichrome stained sections of the three experimental subgroups revealed increased collagen fibers deposition.
The ultrastructural examination of lung specimens of all subgroups confirmed the light microscopic results. Most of pulmonary alveoli subgroup (IIc) were markedly affected with collapsed alveoli lined by type I pneumocyte and numerous type II pneumocyte that contained empty lamellated structure and separated by thick interalveolar septae due to cellular infiltration and hyaline material associated with numerous alveolar macrophage filled with many vacuoles and numerous lysosomes. The ultrastructural examination of lung specimens of subgroups ( IIa and IIb) ), revealed moderate collapse in the alveoli, proliferation of type II pneumocyte, irregular nucleus of type I pneumocyte, thick interalveolar septa due to cellular infiltration and hyaline material, presence of extravasated RBCs associated with activated macrophage filled with many vacuoles and lysosomes.
Light microscopic examination of H&E stained sections of rat’s left ventricle revealed evident size dependent changes. The rat left ventricle subgroup IIa (10 nm AuNPs) revealed diffuse affection of the cardiac muscle as evident by destructed , discontinuity, loss of striation, widely separated by edema and congested dilated blood vessels. Some of the dilated blood vessels were filled with vacuolated materials and associated with cellular infiltration, whereas, histological sections of rats left ventricle subgroup IIb (20 nm AuNPs), revealed less affected cardiomyocytes as evident by preserved architecture and striation of cardiac muscle. Separation of myofibrils by edema associated with some cellular infiltration, focal hyalinosis and loss of striation. Finally, examination of rat left ventricle subgroup IIc (50nmAuNPs) showed very mild affection of cardiomyocytes which appeared dark acidiophilic with central oval vesicular nuclei and more or less with normal striation. Focal area showed hyalinosis with loss of striation associated with congested blood vessels containing hyaline material, extravasated RBCs and mild cellular infiltration. Light microscopic examination of Periodic acid Schiff stained sections of rat left ventricle subgroup IIa (10 nm AuNPs) showed focal area of low staining glycogen granules and subgroup IIb (20 nm AuNPs), revealed focal areas of decrease intensity of glycogen granules and other revealed increase intensity of staining, while subgroup IIc (50 nm AuNPs) revealed more or less normal distribution of glycogen granules in cardiomyocytes. The results of PAS confirmed H & E result as regard separation and destruction of muscle fibers.
The ultrastructural examination of AuNPs treated rat left ventricle specimens of all subgroups also confirmed the light microscopic results. Subgroup (IIa) was markedly affected with evident changes involving both sarcoplasm and nuclei; destruction and loss of striation of cardiomyocytes and widening of intercellular space by edema, irregular nuclei associated with widening of perinuclear space. Destruction, disorganization and abnormal shape mitochondria associated with disruption of intercalated disc. Ultra structural examination of rat left ventricle subgroup (IIb) revealed moderate changes of most of cardiomyocytes, widening of intercellular spaces by edema and loss of normal striation pattern by formation of contraction band due to severely contracted sarcomere. Examination of rats left ventricle subgroup (IIc), revealed mild affection of cardiomyocytes as evident by preserved architecture with some loss of normal striation pattern by contraction band, Irregular nuclei associated with widening of perinuclear space, blebbing of sarcolemma, dilated T-tubules, proliferation and swollen mitochondria associated with congested blood vessels.