Induction of 8-hydroxydeoxyguanosine and ultrastructure alterations by silver nanoparticles attributing to placental transfer in pregnant rats and fetuses

Abstract

<jats:p> A quantitative assessment of the genotoxicity of silver nanoparticles (AgNPs) ascribed to its transplacental transfer and tissue distribution in pregnant rats was carried out in this study. A single intravenous (i.v.) injection of AgNPs with a size range from 4.0 to 17.0 nm was administered to pregnant rats at a dose of 2 mg/kg b.w. on the 19th day of gestation. Five groups beside control, each of the five rats were euthanized after 10 min, 1, 6, 12, or 24 h, respectively. The accumulation of nanoparticles (NPs) in mother and fetal tissues was quantified by inductively coupled plasma optical emission spectroscopy, where the highest accumulation level was recorded in maternal blood (0.523 µg/ml) after 24 h of administration. AgNPs induced accumulation in spleen tissue higher than placenta and fetal tissue homogenates. The data showed significantly detected levels of 8-hydroxydeoxyguanosine in all collected samples from administered animals compared with untreated individuals. Level of 8-OHdG in amniotic fluid exhibited the greatest values followed by maternal spleen, kidneys, and liver, respectively. Investigation by transmission electron microscope showed that the transfer of AgNPs through placental wall caused indentation of nuclei, clumped chromatin, pyknotic nuclei, and focal necrotic areas, while AgNPs appeared mainly accumulated in the macrophages of the spleen. Therefore, the data assume that the genotoxicity studies of AgNPs must be recommended during a comprehensive assessment of the safety of novel types of NPs and nanomaterials. Additionally, exposure to AgNPs must be prevented or minimized during pregnancy or prenatal periods. </jats:p>

Genotoxicity of Silver Nanoparticles

“…The protein function is specific to one conformation and an alteration can cause important cell injuries [114]. Both AgNPs and Ag + ions have been shown to interact with proteins, thereby leading to altered conformation, deactivation and even degradation [112,[115][116][117]. When AgNPs bind to proteins, they form corona structures and can express genes involved in DNA damage [112].…”

“…When AgNPs bind to proteins, they form corona structures and can express genes involved in DNA damage [112]. Ag+ ions released from the AgNPs are bioactive; they have a specific capacity to form complexes with proteins by thiol groups [32,116]. Ag + ions in complexes with proteins can interfere with Na+/Cltransport and contribute to ROS production, disrupt the physiological activity of proteins and even lead to cell death [32,110,116].…”

“…Ag+ ions released from the AgNPs are bioactive; they have a specific capacity to form complexes with proteins by thiol groups [32,116]. Ag + ions in complexes with proteins can interfere with Na+/Cltransport and contribute to ROS production, disrupt the physiological activity of proteins and even lead to cell death [32,110,116]. Whether the effects observed in AgNPs testing are produced by the NPs themselves or by the ions that are released is not clear and requires further study [32,116].…”

Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies

“…Additional studies on surface composition were included [ 49 , 61 , 90 ]; one showed a reduction in maternal-fetal transfer after chitosan-coating of Ag NPs [ 49 ]. Other studies reported a time-dependent accumulation of Ag NPs, CeO 2 NPs, and fullerenes as they found that the fetal NP concentration increased over time, reached a peak, and then declined [ 54 , 67 , 87 ]. Moreover, critical exposure windows during gestation were evaluated by defining changes in particle transfer after varying the day of NP exposure [ 60 , 61 , 70 , 71 , 87 ].…”

“… [ 53 ] Wistar rats 7 Ag NPs/ PVP and [ 110m Ag] 34.9 ± 14.8 b oral/ 1.69 or 2.21 mg/kg/ GD20 g Gamma spectroscopy / Ag NPs identified in fetuses of pregnant rats in amounts significantly exceeding the detection limit. [ 54 ] Wistar rats 30 Ag NPs 4.32 to 16.9 b i.v./ 0 or 2 mg/kg/ GD19 d ICP-OES TEM Time-dependent increase in fetal Ag NP levels, reaching a peak 6 h after injection and showing a decline afterward. [ 55 ] CD-1 mice 16 Au NPs 19.6 or 49.3 a i.v./ 0 or 100 mg/kg/ GD16–17 g ICP-MS AMG Higher amount of Au NPs in maternal livers and placentae from mice injected with 20 nm compared to 50 nm NPs without detectable levels in fetal organs for both sizes.…”