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Size dependent effects of Gold Nanoparticles in ISO-induced Hyperthyroid Rats.

ABSTRACT: In this study, we applied different sizes of gold nanoparticles (Au-NPs) to isoproterenol (ISO)-induced hyperthyroid heart disease rats (HHD rats). Single dose of 5, 40, 100?nm Au-NPs were injected intravenously. Cardiac safety tests were evaluated by cardiac marker enzymes in serum and cardiac accumulation of Au-NPs were measured by ICP-MS. Our results showed that size-dependent cardiac effects of Au-NPs in ISO-induced hyperthyroid rats. 5?nm Au-NPs had some cardiac protective effect but little accumulation in heart, probably due to smaller size Au-NPs can adapt to whole body easily in vivo. Histological analysis and TUNEL staining showed that Au-NPs can induce pathological alterations including cardiac fibrosis, apoptosis in control groups, however they can protect HHD groups from these harmful effects. Furthermore, transmission electron microscopy and western blotting employed on H9C2 cells showed that autophagy presented in Au-NPs treated cells and that Au-NPs can decrease LC3 II turning to LC3 I and decrease APG7 and caspase 12 in the process in HHD groups, while opposite effects on control groups were presented, which could be an adaptive inflammation reacts. As there are few animal studies about using nanoparticles in the treatment of heart disease, our in vivo and in vitro studies would provide valuable information before they can be considered for clinical use in general.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6053462 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Size dependent effects of Gold Nanoparticles in ISO-induced Hyperthyroid Rats.

Zhang Jingwen J Xue Yanbo Y Ni Yajuan Y Ning Feifei F Shang Lijun L Ma Aiqun A

Scientific reports 20180719 1

In this study, we applied different sizes of gold nanoparticles (Au-NPs) to isoproterenol (ISO)-induced hyperthyroid heart disease rats (HHD rats). Single dose of 5, 40, 100 nm Au-NPs were injected intravenously. Cardiac safety tests were evaluated by cardiac marker enzymes in serum and cardiac accumulation of Au-NPs were measured by ICP-MS. Our results showed that size-dependent cardiac effects of Au-NPs in ISO-induced hyperthyroid rats. 5 nm Au-NPs had some cardiac protective effect but littl ...[more]

PMID: 30026536

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Project description:BackgroundThere is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels.MethodsWe intravenously injected monodisperse, negatively charged, radio-labelled 1.4 nm, 18 nm and 80 nm ¹??AuNP at a mass dose of 5, 3 and 27 ?g/rat, respectively, into pregnant rats on day 18 of gestation and in non-pregnant control rats and studied the biodistribution in a quantitative manner based on the radio-analysis of the stably labelled ¹??AuNP after 24 hours.ResultsWe observed significant biokinetic differences between pregnant and non-pregnant rats. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and weight of the pregnant uterus. All three sizes of ¹??AuNP were found in the placentas and amniotic fluids with 1.4 nm AuNP fractions being two orders of magnitude higher than those of the larger AuNP on a mass base. In the fetuses, only fractions of 0.0006 (30 ng) and 0.00004 (0.1 ng) of 1.4 nm and 18 nm AuNP, respectively, were detected, but no 80 nm AuNP (<0.000004 (<0.1 ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24 hours but indicate that AuNP translocation occurs across the placental tissues either through transtrophoblastic channels and/or via transcellular processes.ConclusionOur data suggest that the translocation of AuNP from maternal blood into the fetus is NP-size dependent which is due to mechanisms involving (1) transport through transtrophoblastic channels - also present in the human placenta - and/or (2) endocytotic and diffusive processes across the placental barrier.

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Size dependent effects of Gold Nanoparticles in ISO-induced Hyperthyroid Rats.

Publications

Size dependent effects of Gold Nanoparticles in ISO-induced Hyperthyroid Rats.

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