scholarly journals Is aggregated synthetic amorphous silica toxicologically relevant?

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Sivakumar Murugadoss ◽  
Sybille van den Brule ◽  
Frederic Brassinne ◽  
Noham Sebaihi ◽  
Jorge Mejia ◽  
...  

Abstract Background The regulatory definition(s) of nanomaterials (NMs) frequently uses the term ‘agglomerates and aggregates’ (AA) despite the paucity of evidence that AA are significantly relevant from a nanotoxicological perspective. This knowledge gap greatly affects the safety assessment and regulation of NMs, such as synthetic amorphous silica (SAS). SAS is used in a large panel of industrial applications. They are primarily produced as nano-sized particles (1–100 nm in diameter) and considered safe as they form large aggregates (> 100 nm) during the production process. So far, it is indeed believed that large aggregates represent a weaker hazard compared to their nano counterpart. Thus, we assessed the impact of SAS aggregation on in vitro cytotoxicity/biological activity to address the toxicological relevance of aggregates of different sizes. Results We used a precipitated SAS dispersed by different methods, generating 4 ad-hoc suspensions with different aggregate size distributions. Their effect on cell metabolic activity, cell viability, epithelial barrier integrity, total glutathione content and, IL-8 and IL-6 secretion were investigated after 24 h exposure in human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic cells (THP-1). We observed that the de-aggregated suspension (DE-AGGR), predominantly composed of nano-sized aggregates, induced stronger effects in all the cell lines than the aggregated suspension (AGGR). We then compared DE-AGGR with 2 suspensions fractionated from AGGR: the precipitated fraction (PREC) and the supernatant fraction (SuperN). Very large aggregates in PREC were found to be the least cytotoxic/biologically active compared to other suspensions. SuperN, which contains aggregates larger in size (> 100 nm) than in DE-AGGR but smaller than PREC, exhibited similar activity as DE-AGGR. Conclusion Overall, aggregation resulted in reduced toxicological activity of SAS. However, when comparing aggregates of different sizes, it appeared that aggregates > 100 nm were not necessarily less cytotoxic than their nano-sized counterparts. This study suggests that aggregates of SAS are toxicologically relevant for the definition of NMs.

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Giulia Tamborino ◽  
Marijke De Saint-Hubert ◽  
Lara Struelens ◽  
Dayana C. Seoane ◽  
Eline A. M. Ruigrok ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1806 ◽  
Author(s):  
Eirini Dimidi ◽  
Selina Rose Cox ◽  
Megan Rossi ◽  
Kevin Whelan

Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.


2020 ◽  
Vol 67 ◽  
pp. 104903 ◽  
Author(s):  
Claudia Hempt ◽  
Jean-Pierre Kaiser ◽  
Olivier Scholder ◽  
Tina Buerki-Thurnherr ◽  
Heinrich Hofmann ◽  
...  

2019 ◽  
Vol 17 (1) ◽  
pp. 685-693
Author(s):  
Chen Xi ◽  
Liu Yuanyuan ◽  
Zhao Dongshuang ◽  
Fan Ziwei ◽  
Cao Shuang ◽  
...  

AbstractIn this research, we investigated possible anti-inflammatory roles of Prunus tomentosa Thunb Total Flavones (PTTTF) in LPS-induced RAW264.7 cells. PTTTF (4μg/ml and 40μg/ml) was applied to RAW264.7 cells induced with 1μg/ml LPS to test the impact of these flavones on neutrophil phagocytosis in vitro. Levels of prostaglandin E2 (PGE2) and two pro-inflammatory interleukin cytokines (i.e. IL-6 and IL-1β) in the supernatant fraction were tested via Enzyme-linked immunosorbent assays (ELISA). Expression of cyclooxygenases COX-1 and COX-2 was detected via RT-PCR. Superoxide dismutase (SOD) content was determined with a spectrophotometric assay (Micromethod). The results revealed that PTTTF at doses higher than 4μg/ml reduces the content of IL-6, IL-1β and PGE2 (P < 0.05), and elevates the activity of SOD in LPS-induced RAW264.7 cells significantly (P < 0.05). PTTTF at 40μg/ml showed no significant effect on the expression of COX-1(P>0.05) but resulted in a significant inhibition of COX-2 in LPS-induced RAW264.7 cells (P<0.05). In summary, PTTTF had a substantial potential anti-inflammatory effect through the alteration of the synthesis of some cytokines and other mediators of the process of inflammation. Novelty statement - Prunus tomentosa Thunb Total Flavones (PTTTF) have known roles in the treatment of diabetes, but here we show that they are also potential anti-inflammatory agents. Our results show that PTTTF exhibited anti-inflammatory effects through altering the synthesis of some cytokines and other mediators of the inflammatory process.


2013 ◽  
Vol 94 (5) ◽  
pp. 692-695
Author(s):  
F Kh Kamilov ◽  
G A Timirkhanova ◽  
A I Samorodova ◽  
A V Samorodov ◽  
F A Khaliullin ◽  
...  

Aim. To study the biochemical effect on hemostasis of a new cyclohexilammonium salt of 2-[1-ethyl-3-methyl-7(dioxotiethanyl-3)xantinyl-8-thio]acetic acid in vitro. Methods. Thromboelastography was performed using the citrate blood samples of healthy male donors. Global hemostatic effect, fibrinogen and platelet function, fibrinolysis and clot strength, and stability were analyzed at thromboelastography. The impact of firstly synthesized xantine derivative and pentoxifylline on the functional activity of platelets in vitro was studied using a laser analyzer of platelet aggregation. Adenosine diphosphate, collagen, epinephrine and ristocetin induced clotting were registered. General clotting characteristics, maximal aggregation values, maximal aggregation speed, mean platelet aggregate size, activity of platelet-derived factor 3, level of platelet-derived factor 4 were measured. Release of platelet-derived factors 3 and 4 at platelet aggregation were assessed after adenosinediphosphate-induced aggregation and centrifugation. Results. Cyclohexylammonium salt of 2-[1-ethyl-3-methyl-7-(dioxotiethanyl-3)xantinyl-8-thio]acetic acid in vitro showed antiaggregatory activity that exceeds such of pentoxifylline. It has been revealed that the second platelet aggregation wave, that is induced by small dose of adenosinediphosphate, is absent in the presence of the new cyclohexylammonium salt, lag-period in collagen-induced platelet aggregation elongates, and availability and release of platelet-derived factors 3 and 4 decreases. Conclusion. The research findings show potentially high antiaggregatory activity of 2-[1-ethyl-3-methyl-7-(dioxotiethanyl-3)xantinyl-8-thio]acetic acid cyclohexylammonium salt as an inhibitor of platelet release reaction.


Author(s):  
Caroline Fontana ◽  
Anaïs Kirsch ◽  
Carole Seidel ◽  
Léa Marpeaux ◽  
Christian Darne ◽  
...  

2011 ◽  
Vol 193 (22) ◽  
pp. 6315-6322 ◽  
Author(s):  
Daniel J. Schu ◽  
Revathy Ramachandran ◽  
Jared S. Geissinger ◽  
Ann M. Stevens

The quorum-sensing regulator EsaR fromPantoea stewartiisubsp.stewartiiis a LuxR homologue that is inactivated by acyl-homoserine lactone (AHL). In the corn pathogenP. stewartii, production of exopolysaccharide (EPS) is repressed by EsaR at low cell densities. However, at high cell densities when high concentrations of its cognate AHL signal are present, EsaR is inactivated and derepression of EPS production occurs. Thus, EsaR responds to AHL in a manner opposite to that of most LuxR family members. Depending on the position of its binding site within target promoters, EsaR serves as either a repressor or activator in the absence rather than in the presence of its AHL ligand. The effect of AHL on LuxR homologues has been difficult to studyin vitrobecause AHL is required for purification and stability. EsaR, however, can be purified without AHL enabling anin vitroanalysis of the response of the protein to ligand. Western immunoblots and pulse-chase experiments demonstrated that EsaR is stablein vivoin the absence or presence of AHL. Limitedin vitroproteolytic digestions of a biologically active His-MBP tagged version of EsaR highlighted intradomain and interdomain conformational changes that occur in the protein in response to AHL. Gel filtration chromatography of the full-length fusion protein and cross-linking of the N-terminal domain both suggest that this conformational change does not impact the multimeric state of the protein. These findings provide greater insight into the diverse mechanisms for AHL responsiveness found within the LuxR family.


2018 ◽  
Vol 21 (1s) ◽  
pp. 225s-241s ◽  
Author(s):  
Jaber Emami ◽  
Hessam Yousefian ◽  
Hojjat Sadeghi

In the present study, a transferrin-conjugated nanostructured lipid carrier (TF-NLCs) for brain delivery of artemisinin (ART) was developed. ART-loaded NLCs (ART-NLCs) were prepared using solvent evaporation method and the impact of various formulation or process variables on the responses were assessed using a Taguchi design. Optimized ART-NLC was then coupled with transferrin as targeting ligand and its in vitro cytotoxicity was investigated against U-87MG brain cancer cell line. As a result, the following values are suggested by the software to prepare the optimized formulation: 20 mg Compritol®, 0.25% Tween 80, 5 mg oleic acid, 2.5 mL dichloromethane and 4 min sonication. Mean particle size (PS), zeta potential (ZP), polydispersity index (PDI), entrapment efficiency (EE), mean release time (MRT) of adopted formulation were confirmed to be 145 ± 12.5 nm, 24.3 ± 1.5 mV, 0.513 ± 0.021, 82.3 ± 7.3 % and 24.0 ± 1.1 h, respectively. Following conjugation of optimized ART-NLCs with TF, PS and MRT were increased, while ZP, and EE were decreased significantly. TF-ART-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the TF-ART-NLCs could potentially be exploited as a delivery system for anticancer and antimalarial drug ART in brain tumors and malaria.


Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3073 ◽  
Author(s):  
Anna Drabczyk ◽  
Sonia Kudłacik-Kramarczyk ◽  
Magdalena Głąb ◽  
Magdalena Kędzierska ◽  
Anna Jaromin ◽  
...  

In this work, synthesis and investigations on chitosan-based hydrogels modified with Aloe vera juice are presented. These materials were synthesized by UV radiation. Investigations involved analysis of chemical structure by FTIR spectroscopy, sorption properties in physiological liquids, strength properties by texture analyzer, surface topography by Atomic Force Microscopy (AFM technique), and in vitro cytotoxicity by MTT test using L929 murine fibroblasts. Particular attention was focused both on determining the impact of the amount and the molecular weight of the crosslinker used for the synthesis as well as on the introduced additive on the properties of hydrogels. It was proven that modified hydrogels exhibited higher swelling ability. Introduced additive affected the tensile strength of hydrogels—modified materials showed 23% higher elongation. The greater amount of the crosslinker used in the synthesis, the more compact the structure, leading to the lower elasticity and lower sorption of hydrogels was reported. Above 95%, murine fibroblasts remained viable after 24 h incubation with hydrogels. It indicates that tested materials did not exhibit cytotoxicity toward these lines. Additionally, materials with Aloe vera juice were characterized by lower surface roughness. Conducted investigations allowed us to state that such modified hydrogels may be considered as useful for biomedical purposes.


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