الفهرس 
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Abstract
Silver nanoparticles are the most widely used nanoparticle and may be considered one of the most important. They have become a high demand material for consumer products with a relatively high estimated global annual production. Oweing to that intensive toxicological studies must be preforemed for the risk assesment of AgNPs.
The current study was designed to assist in the better understanding of silver nanoparticles toxicity and genotoxicity in adult male Sprague Dawely rats through assessment of body weight, organs weight, oxidative stress analysis, histopathological examination, determination of AgNPs distribution in organs and genotoxicity in liver, kidney and brain cells in one hundred male Sprague Dawely rats were divided into four groups (25 rats each). G1 was without any treatment as a control, G2, G3and G4 were exposed to silver nanoparticles at 5, 25 and 50 mg/kg body weight respectively with stomach gavage 5 days a week for 3 months.
Seven rats from each group were weighted carefully then scarified by anesthesia using diethyl ether for samples collection after 1st, 2ndand 3rd months. Blood samples were collected from the descending aorta in clean plastic eppendorf tubes without anticoagulant to obtain serum for estimation of biochemical parameters. Tissue portions used for comet assay were kept in a homogenizing solution and the portions used for residual estimation were kept in plastic sachet and preserved in a deep freezer till the time of analysis. Samples used for histopathological examination were placed in a neutral buffer formalin solution while the portions used for TEM examination were fixed in 5 % glutaraldehyde solution.
The results revealed no significant change neither in the body weight nor organs body weight % of lungs, kidneys, liver and brain after exposing rats orally to 5, 25 and50 mg/kg b.w 5 days weakly for 3 months.
AgNPs significantly increased the serum level of MDA when compared to control group which may denote increased oxidative stress especially with the high doses. The results of this study showed significantly reduced serum levels of SOD, CAT and TAC after oral administration of AgNPs for 3 months in a dose dependent manner.
The results revealed the presence of AgNPs in kidney, liver and brain of rats exposed to AgNPs. The distribution of AgNPs increased in a dose and time dependent manner. AgNPs concentration in kidney and liver during the whole period of the experiment showed a significant increase in all groups comparing to the control group. The brain concentration of AgNPs was significantly increased at high doses only after 2 months post exposure while after 3 month it showed a significant increase in all doses. It was noted that the concentration was higher in kidney followed by liver and brain along the whole period of the experiment.
The result of the present study regarding the genotoxicity of the AgNPs was as follows; in kidney cells the present study showed a significant change in tail length (TL) at the 2nd and the 3rd months in all groups compared to control group. In liver and brain cells the significant change was observed at the 3rd month where it increased significantly in all groups compared to control group but the damage was higher in liver when compared to brain.
Histopathological examination revealed the possibility of the lung to be a remote organ for AgNPs effects after oral exposure to high or low doses. Using light microscope lungs, kidney, liver and brain sections showed variation in histopathological alteration among various groups (5, 25 and 50 mg/Kg). The observation in lungs included inflammatory cellular reaction, hyperemia of blood vessels, damaged bronchiolar epithelium and the presence of small dots inside the alveolar macrophage suggesting AgNPs penetration of the cell. Observations in kidneys included obliteration of Bowman’s capsule, shrinkage of glomerular tuft, hyaline cast and hemoglobin cast suggested a direct cytotoxic effect of the AgNPs. The hepatotoxic effects of AgNPs in the present study were manifested by hyperemia, dilatation of sinusoids, numerous bile duct formation and hyperplasia of bile duct epithelium.
TEM revealed the presence of particles inside the alveolar macrophage and suggested an evidence for the uptake of the particles by the lung macrophage.
Recommendations
The study recommended with:
Further studies are needed to identify whether small size AgNPs cause more genetic damage and oxidative stress compared with the larger ones and investigate the other possible remote organs which might be affected following oral exposure routes.
Supplying and addition of antioxidant agents to animal feedstuffs which includes AgNPs as a feed additive
Regarding the use of AgNPs in the multiple applications which affecting the human, animals and the environment it should be used with caution with monitor the dose and the duration of their use. In addition to using advanced methods for adsorption of AgNPs from drinking water.