Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

Inkielewicz‐Stępniak, Iwona; Santos-Martínez, María José; Medina, Carlos; Radomski, Marek W.

doi:10.2147/ijn.s59172

Cited by 44 publications

(37 citation statements)

References 38 publications

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“…The increase in AST (aspartate aminotransferase) may be due to fluoxetine hepatotoxicity, as fluoxetine is extensively metabolized in the liver to norfluoxetine and this is a well-known side effect (Inkielewicz-Stepniak et al, 2014 ). Fluoxetine may also induce moderate lymphocyte infiltration within the portal tracts and ballooning degeneration of hepatocytes (Kwak et al, 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

et al. 2016

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In mice, disseminated coagulation, inflammation, and ischemia induce neurological damage that can lead to death. These symptoms result from circulating bubbles generated by a pathogenic decompression. Acute fluoxetine treatment or the presence of the TREK-1 potassium channel increases the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50 mg/kg) in wild-type (WT) and TREK-1 deficient mice (knockout homozygous KO and heterozygous HET). Then, we combined the same fluoxetine treatment with a 5-day treatment protocol with spadin, in order to specifically block TREK-1 activity (KO-like mice). KO and KO-like mice were regarded as antidepressed models. In total, 167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux) and 4% of mice treated with both spadin and fluoxetine (KO-likeflux) died from decompression sickness (DCS) symptoms. These values are much lower than those of WT control (62%) or KO-like mice (41%). After the decompression protocol, mice showed significant consumption of their circulating platelets and leukocytes. Spadin antidepressed mice were more likely to exhibit DCS. Nevertheless, mice which had both blocked TREK-1 channels and fluoxetine treatment were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but concomitant fluoxetine treatment not only decreased DCS severity but increased the survival rate.

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Section: Discussionmentioning

confidence: 99%

Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

et al. 2016

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“…The same membrane was stripped and β-actin (Sigma Aldrich) was used as an internal control. Western blotting analysis and protein bands quantification was performed as previously reported by our group [ 22 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

“…Then, DNA-free RNA from samples were reverse-transcribed using a high-capacity cDNA reverse transcription kit (Applied Biosystems, UK). RT-PCR as well as quantitative analysis was conducted as previously reported by our group [ 22 , 29 , 36 ].…”

Section: Methodsmentioning

confidence: 99%

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Molecular Mechanism of Silver Nanoparticles-Induced Human Osteoblast Cell Death: Protective Effect of Inducible Nitric Oxide Synthase Inhibitor

et al. 2016

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BackgroundSilver nanoparticles (AgNPs) show strong antibacterial properties, making them excellent candidates to be used in orthopaedic repair and regeneration. However, there are concerns regarding the cytotoxicity of AgNPs and molecular mechanisms underlying AgNPs-induced bone cells toxicity have not been elucidated. Therefore, the aim of our study was to explore mechanisms of AgNPs-induced osteoblast cell death with particular emphasis on the role of nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS).Methods and ResultSilver nanoparticles used in this study were 18.3±2.6 nm in size, uncoated, spherical, regular shape and their zeta potential was -29.1±2.4 mV as measured by transmission electron microscopy (TEM) and zetasizer. The release of silver (Ag) from AgNPs was measured in cell culture medium by atomic absorption spectroscopy (AAS). The exposure of human osteoblast cells (hFOB 1.19) to AgNPs at concentration of 30 or 60 μg/mL for 24 or 48 hours, respectively resulted in cellular uptake of AgNPs and changes in cell ultrastructure. These changes were associated with apoptosis and necrosis as shown by flow cytometry and lactate dehydrogenase (LDH) assay as well as increased levels of pro-apoptotic Bax and decreased levels of anti-apoptotic Bcl-2 mRNA and protein. Importantly, we have found that AgNPs elevated the levels of nitric oxide (NO) with concomitant upregulation of inducible nitric oxide synthase (iNOS) mRNA and protein. A significant positive correlation was observed between the concentration of AgNPs and iNOS at protein and mRNA level (r = 0.837, r = 0.721, respectively; p<0.001). Finally, preincubation of osteoblast cells with N-iminoethyl-l-lysine (L-NIL), a selective iNOS inhibitor, as well as treating cells with iNOS small interfering RNAs (siRNA) significantly attenuated AgNPs-induced apoptosis and necrosis. Moreover, we have found that AgNPs-induced cells death is not related to Ag dissolution is cell culture medium.ConclusionThese results unambiguously demonstrate that increased expression of iNOS and generation of NO as well as NO-derived reactive species is involved in AgNPs-induced osteoblast cell death. Our findings may help in development of new strategies to protect bone from AgNPs-induced cytotoxicity and increase the safety of orthopaedic tissue repair.

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“…62,63 It is possible that the salivary proteins in oral cavity may also form a corona on the SNPs, which would have an effect on both the bactericidal effects (via ionic Ag dissolution) and cellular effects. Therefore, the interaction of SNPs or silver ions with the other compounds and elements in human saliva should be better evaluated, 64 especially as the increased production of materials containing nanoparticles presents an important toxicological concern. 65,66 The results obtained in the present study showed that the materials modified with SNPs have a time-limited ion release.…”

mentioning

confidence: 99%

In vitro studies of nanosilver-doped titanium implants for oral and maxillofacial surgery

Pokrowiecki¹,

Zaręba²,

Szaraniec³

et al. 2017

IJN

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The addition of an antibacterial agent to dental implants may provide the opportunity to decrease the percentage of implant failures due to peri-implantitis. For this purpose, in this study, the potential efficacy of nanosilver-doped titanium biomaterials was determined. Titanium disks were incorporated with silver nanoparticles over different time periods by Tollens reaction, which is considered to be an eco-friendly, cheap, and easy-to-perform method. The surface roughness, wettability, and silver release profile of each disc were measured. In addition, the antibacterial activity was also evaluated by using disk diffusion tests for bacteria frequently isolated from the peri-implant biofilm: Streptococcus mutans, Streptococcus mitis, Streptococcus oralis, Streptococcus sanguis, Porphyromonas gingivalis, Staphylococcus aureus , and Escherichia coli . Cytotoxicity was evaluated in vitro in a natural human osteoblasts cell culture. The addition of nanosilver significantly increased the surface roughness and decreased the wettability in a dose-dependent manner. These surfaces were significantly toxic to all the tested bacteria following a 48-hour exposure, regardless of silver doping duration. A concentration of 0.05 ppm was sufficient to inhibit Gram-positive and Gram-negative species, with the latter being significantly more susceptible to silver ions. However, after the exposure of human osteoblasts to 0.1 ppm of silver ions, a significant decrease in cell viability was observed by using ToxiLight™ BioAssay Kit after 72 hours. Data from the present study indicated that the incorporation of nanosilver may influence the surface properties that are important in the implant healing process. The presence of nanosilver on the titanium provides an antibacterial activity related to the bacteria involved in peri-implantitis. Finally, the potential toxicological considerations of nanosilver should further be investigated, as both the antibacterial and cytotoxic properties may be observed at similar concentration ranges.

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Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

Cited by 44 publications

References 38 publications

Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

Molecular Mechanism of Silver Nanoparticles-Induced Human Osteoblast Cell Death: Protective Effect of Inducible Nitric Oxide Synthase Inhibitor

In vitro studies of nanosilver-doped titanium implants for oral and maxillofacial surgery

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