Back ground:Gold nanoparticles (GNPs) offer a great promise in biomedicine. Currently, there is no data available regarding the toxicity of GNPs .ROS and free radical production is one of the primary mechanisms of nanoparticle toxicity.The present in vivo study investigated the toxicological effects of size-sorted GNPs along four different time intervals at the cellular levels that include liver, spleen and blood cells through biophysical and biochemical studies, these studies were confirmed by histopathological studies Animals and Methods:Adult SpragueDewally male rats weighting (100- 120g) received intraperitoneal injection of colloidal gold nanoparticles of different sizes(10,50,100nm) that were repeated day by day .Animals were scarified after (14,21,30 and 40) blood samples ,liver and spleen were collected. The parameters studied included: measuring of whole blood viscosity , RBCs aggregation parameters, hepatic lipid peroxidation, Super oxide dismutase (SOD), glutathione (GSH), glutathione disulfide (GSSG), GSH/GSSG ratio, glutathione redox potential (ΔE_G) ,and tumor necrosis factor-alpha (TNF-α) were measured in both liver homogenate and plasma of all studied and control groups.Histopathological examination of the liver and spleen were done . Results:Significant increases were observed in all studied groups compared to controls in RBCs aggregation whole blood viscosities and liver lipidperoxidation, while significant decreases were noticed in hepatic SOD, GSH concentrations , GSH/GSSG ratio, glutathione redox potential (ΔE_G), and significant increase in hepatic and plasma TNF-α concentration of all studied groups after the four time intervals included in the present experiment. In all the studied parameters, the percentage of the increase or decrease was time dependentand was higher in 50nm group than 10nm and 100nm groups.Thehistopathological findings confirmed the biochemical alterations and revealed that,there were various degrees of hepatic tissue injury in the studied groups after the four time intervals of the experiment, characterized by mild to heavy inflammation, as well as necrosis and apoptosis The spleen sections of GNPs-administrated rats revealed no significant differences in histology after 14 and 21 day of GNPs administration Conclusion:In vivo cytotoxicity of size-sorted GNPs is the induction of oxidative stress and immune response. The toxicological effects of GNPs are time dependent. Different sizes of GNPs could be endocytosed by hepatic and splenic cells and have large toxic effect on hepatic tissue( apoptosis and necrosis) while its effect on splenic tissue is limited and could be observed after long-term repeated administration

Keyword: Gold nanoparticle, Sizes, Rats, Oxidative stress, Antioxidant enzymes, cell death

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