الفهرس 
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Abstract
Nanoparticles (NPs) are commonly defined as ultrafine particles having diameter below 100 nm in at least one dimension. NPs often display different properties compared with their bulk material. Gold nanoparticles (GNPs) attract the interest of scientists due to their promising potential applications in biomedical engineering such as vector of antisense cancer drugs, agent for molecular imaging, and targeting reagent in cancer therapy. One of the arguments to use gold nanoparticles (GNPs) in vivo is that gold in bulk form is nontoxic.
For safe and efficient applications, much attention has been paid to the biomedical effects of GNPs. The study of long-term and short-term biological effects of GNPs will contribute to understanding the biological behaviors and predicting nanotoxicity.
It is well known that humans are more sensitive to toxic materials in prenatal stages than in mature age and scientific studies have shown that chemicals in maternal surroundings (air, food, water) can induce pregnancy complications and embryotoxicity. The potential fetal toxicity first of all depends on the passage of particles from the maternal organism which is mainly determined by the placental barrier in the case of mammals.
The present study was aimed to investigate the bio-distribution and placental transfer of GNPs of different sizes during gestation and the effect of these GNPs on the antioxidant and redox states of maternal and fetal tissues.
To achieve these aims 20 adult albino female rats were used and divided into four experimental groups:
group I: normal saline treated female group.
group II: 20nm GNPs treated female group.
group III: 50nm GNPs treated female group.
group IV: 100nm GNPs treated female group.
Each group consists of five females which were housed with two healthy males overnight and pregnancy was ascertained by the presence of a vaginal plug with that morning which designated as gestational day (GD) 1. On GD 9 (during organogenesis), pregnant females of the first group was received intraperitoneal injection of normal saline and this represent the control group, while pregnant females of group II, III, and IV were receive intraperitoneal injection a suspension of GNPs of 20nm, 50nm and 100nm respectively.
On GD 19, the pregnant females were sacrificed and the fetuses and their placentas were obtained and dissected from the uterine horns. 20 fetal liver and placentas were obtained for the determination of NP content and also for the biochemical parameters including the determination of malondialdehyde and glutathione levels and glutathione reductase, superoxide dismutase (SOD) and catalase activities.
7. Summary and Conclusion
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The results revealed that 20, 50 and 100 nm GNPs was existed in the fetal tissues (liver and placenta) and maternal tissues (uterus and liver). These results suggest that the bio-distribution and accumulation of GNPs varied according to particle size and the smaller the GNPs the greater accumulation in the maternal tissues and fetal liver while in placenta the opposite was noted.
The results of the present study demonstared an increased levels of lipid peroxidation (measured as malondialdehyde; MDA as an index of oxidative stress) in both maternal and fetal tissues. These data indicate a state of oxidative stress as a result of GNP penetration into maternal and fetal tissues.
According to the present study, the increased oxidative stress was associated with derangements in maternal and fetal antioxidant systems. Regarding glutathione (GSH) system, maternal tissues of female rats treated with GNPs, showed significantly lower levels of total and reduced GSH compared to control females, while showed significant higher level of oxidized glutathione (GSSG). The redox states of maternal tissues expressed as GSH/GSSG ratio showed significantly lower values in the rats treated with GNP in a pattern proportional with the size of the GNP; the lowest values observed in 20 nm GNP followed by 50 nm and the highest values with 100 nm treated group indicating that the smaller the particle size the more derangement in the redox status of maternal tissues. On the other hand, the fetal tissues showed similar pattern of maternal tissues except in placenta the redox status (GSH/GSSG) is inversely associated with the particle sizes.
The present study indicated a significant inhibition of glutathione reductase (GR) enzyme activity in the maternal and fetal tissues of GNP treated rats. The SOD activity in the maternal and fetal tissues showed higher SOD activity in GNPs treated group compared to control group. The activity of SOD in GNPs treated groups appear to inversely dependent on the particle size; the highest activity in smallest size treated group and vice versa. The increased activities of SOD in different maternal and fetal tissues after treatment with GNPs may act as an adaptive response to counteract the increased ROS generation.
Regarding catalase activity, the fetal tissues (liver and placenta) showed significantly lower activity in the fetus of mothers treated with GNPs compared to control group.
from the results of the present study and other studies we can concluded that:
1- The GNPs are transferred through placental barrier during gestation.
2- The bio-distribution and accumulation of GNPs varied according to particle size and the smaller the GNPs the greater accumulation in the maternal tissues and fetal liver while in placenta the opposite was noted.
3- The GNP penetration into maternal and fetal tissues results in induction of a state of oxidative stress as indicated by elevated levels of MDA.
4- The increased oxidative stress was associated with derangements in maternal and fetal antioxidant systems including depletion of glutathione and inhibition of antioxidant enzymes.
5- The effects of GNPs on the activities of antioxidant enzymes may results from direct interaction of these nanoparticles with the proteins or indirectly through cellular inflammation and shifted redox status.
6- The placental transfer of GNP is dependent on the redox status of placenta; the more reducing stat (high GSH and GSH/GSSG ratio) the less transfer of GNP and vice versa.