الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Over the past few decades, inorganic nanoparticles, whose structures exhibit significantly novel and improved physical, chemical, and biological properties phenomena and functionality due to their nanoscale size, have elicited much interest.
Among inorganic agents, silver has been employed most extensively since ancient times to fight infections and control spoilage. Silver nanoparticles (AgNPs) are both found in cosmetics and food, but their increasing use is of concern due to their ability to be taken up by biological systems.
The interaction of silver nanoparticles with biosystems are just beginning to be under stood. The main molecular mechanism of in vivo nanotoxicity is the induction of oxidative stress by free radical formation. Free radicals cause damage to biological components through oxidation of lipids, proteins, and DNA.
The use of biopolymers in nanoparticle preparation has several advantages over conventional synthetic chemical agents. Macromolecular chains of these biopolymers possess a large number of hydroxyl groups and so they can complex well with metal ions – this further enables control of size, shape, and dispersion of nanoparticles – and they are less toxic to mammalian cells. Over the last decade, chitosan has been attracting increasing attention as a biomaterial and as a pharmaceutical excipient for drug delivery because of its favorable biological properties. Chitosan is an environmental friendly, nontoxic polymer.
The growth of AgNP from silver nitrate in chitosan solution was studied. Silver ion formed complicated chelate complex with both amion groups and hydroxyl groups of chitosan.
Silver nanoparticles can penetrate the placental barrier. It was stated that oxidative stress has been proposed as the causative agents of pregnancy-related disorders. Oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia and intra-uterine growth restriction. It appears likely that there are substances from the placenta that can cause endothelial dysfunction in the maternal blood vessels of susceptible women. it involves generalised damage to the kidneys, and liver.
The aim of the present study was to investigate the biochemical and histopathological alterations of the effect of an intraperitoneal administered chitosan coated silver nanoparticles in pregnant female mice compared with citrate coated silver nanoparticles.
To achieve our goal citrate coated nanoparticles and chitosan coated silver nanoparticles were prepared by chemical reduction method. The prepared particles characterized in terms of size using particle size analyzer, shape using TEM and absorption spectrum using UV-Visible sectrum.
After characterization of prepared particles, citrate coated silver nanoparticles were at a mean particle size of 26 nm, spherical in shape and have maximum absorption spectrum at 422nm confirming formation of citrate-coated silver nanoparticles with no agglomeration. Also, chitosan coated silver nanoparticles were at a mean particle size of 36 nm, spherical in shape and have maximum absorption spectrum at 437nm confirming formation of chitosan-coated silver nanoparticles with no agglomeration.
For comparision of the toxic effects of prepared nanoparticles, the present study was carried out on 45 healthy adult albino Swiss mice. They were of 3 months old and weighing 28 - 32 g each. For mating, each of the two females was housed overnight with a randomly selected experienced male.
The cage was checked daily for copulatory plugs; gestational day 0 was recorded when a copulatory plug was found.
The pregnant females were assigned randomly to three treatment groups, each of 15 female mice. The animals were treated during the time of pregnancy as following:
Control group I: The pregnant female mice in this group serve as a control group and injected intraperitoneally with saline.
Group II: The pregnant female mice were injected intraperitoneally with a suspension of citrate-coated silver nanoparticles at a dose level of 100 mg/kg.
Group III: The pregnant females mice were injected intraperitoneally with a suspension of chitosan-coated silver nanoparticles at a dose level of 100 mg/kg.
Mice of each group were chosen randomly at the time intervals (7th&14th day) from the beginning of the experiment. Animals were scarified at 20th day. Blood samples were obtained for further biochemical investigations and tissue from liver and spleen were obtained for histopathological investigations.
Biochemical studies: malondialdehyde (MDA), total antioxidant, progesterone and estrogen hormones were measured in separated serum.
At the end of the experiment, the data obtained from biochemical studies revealed:
A significant increase in serum MDA concentrations of studied groups compared to controls after the three times intervals included in our experiment.
A significant decrease in total antioxidant concentrations of studied groups compared to controls after the three time intervals included in our experiment.
A non significant decrease in progesterone hormone concentrations of studied groups compared to controls after the three time intervals included in our experiment.
A significant increase in estradiol concentration of studied groups compared to controls after the three time intervals included in our experiment.
Histopathological studies: The results of biochemical alterations were confirmed by histopathological examination of the liver and spleen of studied and control animals using light microscope and electron microscope. The histopathological findings of liver of the pregnant treated mice administered with 100 mg/kg BW silver nanoparticles (AgNPs) showed severe histopathological changes, comparing to that observed in the control mice.
Ultrastructurally, there were profound changes in the fine structure of the hepatocytes. The electron micrographs revealed that most hepatocytes were vacuolized and degenerated. The nuclei of most hepatocytes were mostly affected. The chromatin was not clearly preserved, and most of these nuclei were manifested by their electro-lucent nuclear matrix and marginated heterochromatin.
In chitosan-treated mice, general normal appearance of liver sections was seen, where the architecture strands of hepatocytes were more or less resembled those of the control liver, i.e., no evidence of damage was noticed.
Ultrastructurally, the electron micrographs revealed little injury in the hepatocytes nuclei. These changes appeared in the nuclear shape, irregularities of the nuclear envelope. These nuclei contained more than two large, dark and well developed nucleoli. An increase in the number of rounded-shaped mitochondria was observed in the cytoplasm of many hepatocytes. They were evenly distributed in most parts of the cytoplasm.
The spleen sections of the pregnant mice administered with silver nanoparticles revealed marked disruption of spleen organization, and revealed many signs of pathological alterations. There was marked loss in distinction between the white and red pulps.
Semithin sections revealed many degenerative changes in the splenic tissue, where there was marked loss in lymphocyte population.
Comparing to sections of spleen of mice treated with citrate-coated AgNPs, little histopathological alterations and marked improvement in the splenic tissue were noticed in mice administered with chitosan. Sections of spleen of mice showed an apparent normal structure of most white and red pulps.
Semithin sections revealed no apparent morphological abnormalities in most areas of both white and red pulps. The white pulp had normal accumulation of cellularity, but with a little degenerated area.