Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine

Abstract

Here is presented a comprehensive investigation of the distribution of polyvinylpyrrolidone (PVP)-stabilized AgNP (20 or 110 nm) in pregnant rats after a single injection or oral gavage dose. The biological impacts of AgNP exposure were evaluated by metabolomic analysis, and measurement of biomarkers of cardiovascular injury, oxidative stress, and inflammation. The investigation provided a basic understanding of the distribution, internal dose, persistence, metabolomics, and elimination of AgNP following exposure in pregnant rats. Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose, and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg/kg) or by gavage (p.o.) (10 mg/kg), or vehicle alone, on gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver concentration in tissues was measured using inductively-coupled plasma mass spectrometry. The distribution of silver in dams was influenced by route of administration and AgNP size. The highest concentration of silver (μg Ag/g tissue) at 48 h was found in spleen for i.v. administered AgNP, and in lungs for AgAc. At 48 h following p.o. administration of AgNP, the highest concentration was measured in cecum and large intestine, and for AgAc in placenta. Silver was detected in placenta and fetuses for all groups. Markers of cardiovascular injury, oxidative stress marker, cytokines, and chemokines were not significantly elevated in exposed dams compared to vehicle-dosed control. NMR metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the carbohydrate, and amino acid metabolism. This study demonstrates that silver crosses the placenta and is transferred to the fetus regardless of the form of silver.

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles

“…Interestingly, the authors point out that AgNPs in the fetal circulation could originate from de novo formation following ionic Ag translocation [43]. From the limited number of in vivo studies of placental transport of NPs where pregnant animals were used, AgNPs were found to be able to cross the placental barrier of rats and reach the fetus [48][49][50][51][52]. The study of Fennell et al reported that 24 h after intravenous administration to pregnant rats with AgNPs, about 3-4%, measure as total Ag, of the administered dose was found in the fetus [48].…”

“…From the limited number of in vivo studies of placental transport of NPs where pregnant animals were used, AgNPs were found to be able to cross the placental barrier of rats and reach the fetus [48][49][50][51][52]. The study of Fennell et al reported that 24 h after intravenous administration to pregnant rats with AgNPs, about 3-4%, measure as total Ag, of the administered dose was found in the fetus [48]. The transported levels that we observed ranged between 1 and 8% as total Ag and between 1 and 5% as AgNPs and are thus in between the observations in rodents and the human placenta perfusion studies.…”

Translocation of silver nanoparticles in theex vivohuman placenta perfusion model characterized by single particle ICP-MS

“…So far, potential AgNP translocation across the placenta has only been investigated in pregnant rodents. The translocation levels of Ag, measured by ICP-MS in the tissues of pups as the total Ag mass concentrations and expressed as the percentages of the administered dose, ranged from 0.008-0.009%, 23 0.036%, 11 0.085-0.147%, 22 0.097% 59 to 0.2-0.5%, 24 while the percentage of Ag accumulated in placental tissue varied between 0.2% 13,23 and 0.04-1.3%. 24 In our study Ag translocation across the human placental barrier (0.015-0.062%, calculated as Ag mass fraction > and ≤25 nm) was in the same range as those observed in rodent studies, while the percentage of accumulated Ag in the placental tissue was about 10-times higher (12-16%).…”

“…The translocation levels of Ag, measured by ICP-MS in the tissues of pups as the total Ag mass concentrations and expressed as the percentages of the administered dose, ranged from 0.008-0.009%, 23 0.036%, 11 0.085-0.147%, 22 0.097% 59 to 0.2-0.5%, 24 while the percentage of Ag accumulated in placental tissue varied between 0.2% 13,23 and 0.04-1.3%. 24 In our study Ag translocation across the human placental barrier (0.015-0.062%, calculated as Ag mass fraction > and ≤25 nm) was in the same range as those observed in rodent studies, while the percentage of accumulated Ag in the placental tissue was about 10-times higher (12-16%). Although significant biological differences in placental structure and function between humans and rodents may contribute to the observed differences, a direct comparison is challenging due to additional physico-chemical differences in the NP types (size, surface modifications), applied doses and routes of administration, among others.…”

“…The only available data on potential transplacental transfer of AgNPs are from rodent studies, where increased Ag concentrations were detected in fetal organs. 11,13,[22][23][24] Recently, the visualization of AgNPs with similar sizes as those of the applied AgNPs in the placenta and fetal tissues has been interpreted as an indicator for placental transfer of these particles. 13 However, it is not yet clearly established if Ag transfer occurs in particulate or ionic forms and how different AgNP properties and functionalizations affect placental barrier crossing.…”