Various iron-oxide nanoparticles have been in use for a long time as therapeutic and imaging agents and for supplemental delivery in cases of iron-deficiency. While all of these products have a specified size range of ∼ 40 nm and above, efforts are underway to produce smaller particles, down to ∼ 1 nm. Here, we show that after a 24-h exposure of SHSY-5Y human neuroblastoma cells to 10 μg/ml of 10 and 30 nm ferric oxide nanoparticles (Fe-NPs), cellular dopamine content was depleted by 68 and 52 %, respectively. Increases in activated tyrosine kinase c-Abl, a molecular switch induced by oxidative stress, and neuronal α-synuclein expression, a protein marker associated with neuronal injury, were also observed (55 and 38 % percent increases, respectively). Inhibition of cell-proliferation, significant reductions in the number of active mitochondria, and a dose-dependent increase in reactive oxygen species (ROS) were observed in neuronal cells. Additionally, using a rat in vitro blood-brain barrier (BBB) model, a dose-dependent increase in ROS accompanied by increased fluorescein efflux demonstrated compromised BBB integrity. To assess translational implications, in vivo Fe-NP-induced neurotoxicity was determined using in vivo MRI and post-mortem neurochemical and neuropathological correlates in adult male rats after exposure to 50 mg/kg of 10 nm Fe-NPs. Significant decrease in T 2 values was observed. Dynamic observations suggested transfer and retention of Fe-NPs from brain vasculature into brain ventricles. A significant decrease in striatal dopamine and its metabolites was also observed, and neuropathological correlates provided additional evidence of significant nerve cell body and dopaminergic terminal damage as well as damage to neuronal vasculature after exposure to 10 nm Fe-NPs. These data demonstrate a neurotoxic potential of very small size iron nanoparticles and suggest that use of these ferric oxide nanoparticles may result in neurotoxicity, thereby limiting their clinical application.
Silver nanoparticles (Ag-NPs) are widely used in FDA regulated products. The physical-chemical properties of Ag-NPs are characterized using various instruments. The dose-dependent activity and body weight alterations are evaluated after rats were exposed to Ag nanoparticles, suggesting a major human health risk, given the wide application of silver nanomaterials.
The effect of high- and low-fat diets with different levels of fatty acid unsaturation on plasma hormones involved in lipid metabolism was studied during different phases of the menstrual cycle in 31 premenopausal women. Subjects were divided into two groups and were fed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.3 or 1.0 for four menstrual cycles and then switched to a 19% fat diet with the same P:S for another four cycles. Blood samples were analyzed during both the follicular and luteal phases. A significant direct effect of level of dietary fat was observed on plasma cortisol and dehydroepiandrosterone-sulphate whereas an inverse relationship was seen for plasma insulin. Both plasma insulin and growth hormone levels were higher during the luteal compared with the follicular phase of the menstrual cycle. None of the hormones was affected by the level of unsaturation of dietary fats.
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