Pulmonary and hemostatic toxicity of multi-walled carbon nanotubes and zinc oxide nanoparticles after pulmonary exposure in Bmal1 knockout mice

Luyts, Katrien; Smulders, Stijn; Napierska, Dorota; kerckhoven, Soetkin Van; Poels, Katrien; Scheers, Hans; Hemmeryckx, Bianca; Nemery, Benoît; Hoylaerts, Marc; Hoet, Peter

doi:10.1186/preaccept-1625872944135495

Cited by 10 publications

(15 citation statements)

References 41 publications

(43 reference statements)

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“…However, we did not detect subtle changes in redox status when we measured mRNA or protein expression of the redox-sensitive proteins GCLC, GCLM, and HMOX1 [36]. Furthermore, CNT-induced changes in the ratio of oxidized to reduced glutathione were previously observed to co-occur with significant decreases in total GSH levels [33], which our study would have detected.…”

Section: Discussioncontrasting

confidence: 57%

“…Decreases of 40–50% in lung total GSH were also observed in juvenile BALB/c mice exposed via inhalation (estimated deposition 5 µg/g/day, 7 days) [51]. Similarly, aspiration of 32 µg MWCNT in C57BL/6 mice was associated with a comparable decrease in total GSH, and a significant increase in the ratio of oxidized (GSSG) to reduced GSH [33].…”

Section: Introductionmentioning

confidence: 71%

“…In support of this, Muhlfeld et al reported that MWCNTs contaminated with 1.76% iron generated significantly more acellular reactive oxygen species than MWCNTs with 0.34%, as measured by electron paramagnetic resonance [39]. Indeed, in vivo studies reporting significant GSH depletion used CNTs with greater iron contamination, ranging from 2.7% [33], [50] to 17.7% [55].…”

Section: Discussionmentioning

confidence: 92%

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The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

et al. 2016

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Inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25 µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate (Gclm heterozygous) and severe (Gclm null) GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.

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Section: Discussioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 92%

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The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

et al. 2016

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“…Inflammatory cells may be detected after 48 h of a single NM exposure, but cytokines are absent or diluted during this time window, which suggests that clearance occurs earlier for cytokines than inflammatory cells. We previously observed this mechanism, whereby NM exposure led to significant changes at cellular levels but not many significant changes in cytokine levels [33]. Furthermore, some studies also showed the contradictory effects of NM exposure on inflammatory endpoints under different experimental settings [4].…”

Section: Discussionmentioning

confidence: 93%

Changes in DNA Methylation in Mouse Lungs after a Single Intra-Tracheal Administration of Nanomaterials

Tabish¹,

Poels²,

Byun³

et al. 2017

PLoS ONE

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AimsThis study aimed to investigate the effects of nanomaterial (NM) exposure on DNA methylation.Methods and ResultsIntra-tracheal administration of NM: gold nanoparticles (AuNPs) of 5-, 60- and 250-nm diameter; single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) at high dose of 2.5 mg/kg and low dose of 0.25 mg/kg for 48 h to BALB/c mice. Study showed deregulations in immune pathways in NM-induced toxicity in vivo. NM administration had the following DNA methylation effects: AuNP 60 nm induced CpG hypermethylation in Atm, Cdk and Gsr genes and hypomethylation in Gpx; Gsr and Trp53 showed changes in methylation between low- and high-dose AuNP, 60 and 250 nm respectively, and AuNP had size effects on methylation for Trp53.ConclusionEpigenetics may be implicated in NM-induced disease pathways.

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“…These particles if inhaled causes the inflammation (Luyts et al . ), epithelioid granulomas (Sanchez et al . ), and fibrosis (Wang et al .…”

Section: Safety and Toxicological Issuesmentioning

confidence: 99%

Nanotechnology based anti-infectives to fight microbial intrusions

et al. 2016

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SummaryWith the rise in human population across the globe especially in developing countries, the incidence of microbial infections are increasing with greater pace. On the other hand, available medication and therapies are found to be insufficient for the complete cure of such microbial infections due to the development of resistance against various antibiotics. Therefore, to cope up the menace of microbial infections and drug resistance, there is demand for new and compelling technology, which has the ability to impede these problems. Many research groups worldwide are finding a ray of hope in nanomaterials owing to their unique properties. In the present review we have discussed the reasons behind the development of new materials based on nanotechnology. It is mainly focused on pioneering studies on application of nanomaterials like carbon nanotube, fullerene, dendrimers, nanocomposite and metal nanoparticles in combating dreadful pathogens. Moreover, the concerns about their toxicity have also been discussed.

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Pulmonary and hemostatic toxicity of multi-walled carbon nanotubes and zinc oxide nanoparticles after pulmonary exposure in Bmal1 knockout mice

Cited by 10 publications

References 41 publications

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

Changes in DNA Methylation in Mouse Lungs after a Single Intra-Tracheal Administration of Nanomaterials

Nanotechnology based anti-infectives to fight microbial intrusions

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