ABSTRACT
Metal nanoparticles have been extensively investigated for different types of pharmaceutical applications. However, their use has raised some concerns about their toxicity involving the increase of reactive oxygen species causing cellular apoptosis. Therefore, in this review we summarize the most relevant toxicity mechanisms of gold, silver, copper and copper oxide nanoparticles as well as production methods of metal nanoparticles. Parameters involved in their toxicity such as size, surface charge and concentration are also highlighted. Moreover, a critical revision of the literature about the strategies used to reduce the toxicity of this type of nanoparticles is carried out throughout the review. Additionally, surface modifications using different coating strategies, nanoparticles targeting and morphology modifications are deeply explained.
ABSTRACT
Ageing and obesity have been shown to increase the risk of cognitive decline and Alzheimer's disease (AD). Besides, elevated glucocorticoid (GCs) levels cause metabolic stress and have been associated with the neurodegenerative process. Direct pieces of evidence link the reduction of GCs caused by the inhibition of 11ß-HSD type 1 (11ß-HSD1) with cognitive improvement. In the present study, we investigated the beneficial effects of 11ß-HSD1 inhibitor (i) RL-118 after high-fat diet (HFD) treatment in the senescence-accelerated mouse prone 8 (SAMP8). We found an improvement in glucose intolerance induced by HFD in mice treated with RL-118, a significant reduction in 11ß-HSD1 and glucocorticoid receptor (GR) protein levels. Furthermore, specific modifications in the FGF21 activation after treatment with 11ß-HSD1i, RL-118, which induced changes in SIRT1/PGC1α/AMPKα pathway, were found. Oxidative stress (OS) and reactive oxygen species (ROS), as well as inflammatory markers and microglial activation, were significantly diminished in HFD mice treated with 11ß-HSD1i. Remarkably, treatment with 11ß-HSD1i altered PERK pathway in both diet groups, increasing autophagy only in HFD mice group. After RL-118 treatment, a decrease in glycogen synthase kinase 3 (GSK3ß) activation, Tau hyperphosphorylation, BACE1 protein levels and the product ß-CTF were found. Increases in the non-amyloidogenic secretase ADAM10 protein levels and the product sAPPα were found in both treated mice, regardless of the diet. Consequently, beneficial effects on social behaviour and cognitive performance were found in treated mice. Thus, our results support the therapeutic strategy of selective 11ß-HSD1i for the treatment of age-related cognitive decline and AD.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , Cognitive Dysfunction/enzymology , Cognitive Dysfunction/pathology , Stress, Physiological , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , Alzheimer Disease/pathology , Animals , Autophagy/drug effects , Behavior, Animal/drug effects , Biomarkers/metabolism , Cognitive Dysfunction/complications , Diet, High-Fat , Female , Fibroblast Growth Factors/metabolism , Glucocorticoids/metabolism , Glucose Intolerance/complications , Glycogen Synthase Kinase 3/metabolism , Inflammation/pathology , Mice , Microglia/drug effects , Microglia/metabolism , Microglia/pathology , Piperidones/pharmacology , Pyridines/pharmacology , Signal Transduction/drug effects , Social Behavior , Stress, Physiological/drug effects , eIF-2 Kinase/metabolismABSTRACT
No disponible
Subject(s)
Abstracting and Indexing/methods , Abstracting and Indexing/statistics & numerical data , Abstracting and Indexing/trends , PubMed/organization & administration , PubMed/standards , PubMed , Societies, Medical/history , Societies, Medical/organization & administration , Societies, Medical/standards , Impact Factor , BibliometricsSubject(s)
Abstracting and Indexing/methods , Periodicals as Topic , PubMed , Arteriosclerosis , Humans , SpainABSTRACT
Patient data report marked gender and pre-vs-postmenopausal differences in obstructive sleep apnea (OSA). However, no experimental data are available on how sexual hormones modulate OSA consequences. Here we report novel results on estrogen-modulated heart and brain inflammation in female mice subjected to intermittent hypoxia, a major injurious challenge in OSA. C57BL/6J (14-week old) intact and ovariectomized mice (n=6 each) were subjected to intermittent hypoxia (20 s at 5% and 40s at 21%, 60 cycles/h; 6 h/day). Identical intact and ovariectomized groups breathing room air were controls. After 30 days, the gene expressions of interleukins 6 and 8 (IL-6, IL-8) in the brain and heart tissues were measured. Whereas, compared with normoxia, intermittent hypoxia considerably increased IL-6 and IL-8 gene expressions in intact females, no change was found in ovariectomized mice when comparing normoxia and intermittent hypoxia. These data suggest that estrogens modulate the inflammatory effects of intermittent hypoxia and point to further studies on the role played by sex hormones in OSA.
