In vitro and ex vivo toxicity screening for predicting toxicological effects of synthetic carbon black nanoparticles in humans

In this study, the application of amphipods in vivo assays was evaluated. The main aim of this work was to check the potential use of this model in biocompatibility assessments of metal-organic frameworks (MOFs). Hence, six different MOFs were synthesized and the in vitro and ex vivo cytotoxicity was first assessed using a colorimetric assay and a macrophage cell line. Obtained results were compared to validate the in vivo toxicity tests carried out using amphipods and increasing concentrations of the different MOFs. Amphipods do not require the need of ethics approval and also are less expensive to keep than conventional in vivo models, showing its potential as a fast and reliable platform in toxicity studies. The obtained results showed that the amphipods based-assay was simple, easy to replicate and yielded toxicity data corresponding to the type of MOFs tested. In addition, it was observed that only CIM-80(Al) and CIM-84(Zr) did not show any toxicity to the animals at the different tested concentrations. Therefore, the developed in vivo model could be applied as a high-throughput toxicity screening method to evaluate the toxicity of numerous materials, chemicals and therapeutic agents among others.

Download Full-text

In vitro cytotoxicity of carbon black nanoparticles synthesized from solution plasma on human lung fibroblast cells

Japanese Journal of Applied Physics ◽

10.7567/jjap.57.0102bg ◽

2017 ◽

Vol 57 (1) ◽

pp. 0102BG ◽

Cited By ~ 2

Author(s):

Gasidit Panomsuwan ◽

Chayanaphat Chokradjaroen ◽

Ratana Rujiravanit ◽

Tomonaga Ueno ◽

Nagahiro Saito

Keyword(s):

Carbon Black ◽

Human Lung ◽

In Vitro Cytotoxicity ◽

Lung Fibroblast ◽

Fibroblast Cells ◽

Human Lung Fibroblast ◽

Carbon Black Nanoparticles

Download Full-text

Carbon Black Nanoparticles Selectively Alter Follicle-Stimulating Hormone Expression in vitro and in vivo in Female Mice

Frontiers in Neuroscience ◽

10.3389/fnins.2021.780698 ◽

2021 ◽

Vol 15 ◽

Author(s):

Charlotte Avet ◽

Emmanuel N. Paul ◽

Ghislaine Garrel ◽

Valérie Grange-Messent ◽

David L’Hôte ◽

...

Keyword(s):

Carbon Black ◽

Follicle Stimulating Hormone ◽

Primary Cultures ◽

Pituitary Cells ◽

Intratracheal Administration ◽

Female Mice ◽

Carbon Black Nanoparticles ◽

Stimulating Hormone

Toxic effects of nanoparticles on female reproductive health have been documented but the underlying mechanisms still need to be clarified. Here, we investigated the effect of carbon black nanoparticles (CB NPs) on the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are key regulators of gonadal gametogenesis and steroidogenesis. To that purpose, we subjected adult female mice to a weekly non-surgical intratracheal administration of CB NPs at an occupationally relevant dose over 4 weeks. We also analyzed the effects of CB NPs in vitro, using both primary cultures of pituitary cells and the LβT2 gonadotrope cell line. We report here that exposure to CB NPs does not disrupt estrous cyclicity but increases both circulating FSH levels and pituitary FSH β-subunit gene (Fshb) expression in female mice without altering circulating LH levels. Similarly, treatment of anterior pituitary or gonadotrope LβT2 cells with increasing concentrations of CB NPs dose-dependently up-regulates FSH but not LH gene expression or release. Moreover, CB NPs enhance the stimulatory effect of GnRH on Fshb expression in LβT2 cells without interfering with LH regulation. We provide evidence that CB NPs are internalized by LβT2 cells and rapidly activate the cAMP/PKA pathway. We further show that pharmacological inhibition of PKA significantly attenuates the stimulatory effect of CB NPs on Fshb expression. Altogether, our study demonstrates that exposure to CB NPs alters FSH but not LH expression and may thus lead to gonadotropin imbalance.

Download Full-text

Toxicological effects of functionalized Carbon Black Nanoparticles on Type II pneumocytes

Pneumologie ◽

10.1055/s-0033-1357068 ◽

2013 ◽

Vol 67 (12) ◽

Author(s):

N Schreiber ◽

R Hochscheid ◽

E Kotte ◽

P Weber ◽

B Müller

Keyword(s):

Carbon Black ◽

Type Ii ◽

Toxicological Effects ◽

Type Ii Pneumocytes ◽

Carbon Black Nanoparticles

Download Full-text

CarbonBlack: a joint research project to establish a test system for predicting human-toxicological effects of synthetic carbon black nanoparticles*

Pneumologie ◽

10.1055/s-0033-1357063 ◽

2013 ◽

Vol 67 (12) ◽

Author(s):

H Fehrenbach ◽

B Müller ◽

P König ◽

T Hansen ◽

H Bockhorn

Keyword(s):

Carbon Black ◽

Test System ◽

Research Project ◽

Joint Research ◽

Toxicological Effects ◽

Carbon Black Nanoparticles ◽

Joint Research Project

Download Full-text

Challenges and Opportunities for Integrating In Silico Models and Adverse Outcomes Pathways to Set and Relate New Biomarkers

Water ◽

10.3390/w12123549 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3549

Author(s):

Carlos E. Matos dos Santos ◽

Raul Ghiraldelli Miranda ◽

Danielle Palma de Oliveira ◽

Daniel Junqueira Dorta

Keyword(s):

In Silico ◽

Ex Vivo ◽

Adverse Outcomes ◽

Adverse Outcome Pathway ◽

Biological Organization ◽

Toxicological Effects ◽

New Biomarkers ◽

In Silico Models

The Adverse Outcome Pathway (AOP) framework has been considered the most innovative tool to collect, organize, and evaluate relevant information on the toxicological effects of chemicals, facilitating the establishment of links between molecular events and adverse outcomes at the critical level of biological organization. Considering the combination of the high volume of toxicological and ecotoxicological data produced and the application of artificial intelligence algorithms from the last few years, not only can higher mechanistic interpretability be reached with new in silico models, but also a potential increase in predictivity in hazard assessments and the identification of new potential biomarkers can be achieved. The current paper aims to discuss some potential challenges and ways of integrating in silico models and AOPs to predict toxicological effects and to set and relate new biomarkers for defined purposes. With the use of the AOP framework to organize the ecotoxicological, toxicological, and structural data generated from in chemico, in vitro, ex vivo, in vivo, and population studies, it is expected that the generated biological and chemical construct will improve its application, establishing a knowledge platform to set and relate new biomarkers by key event relationships (KERs).

Download Full-text

In Vitro Enhancement of Mouse T Helper 2 Cell Sensitization to Ovalbumin Allergen by Carbon Black Nanoparticles

Toxicological Sciences ◽

10.1093/toxsci/kfu010 ◽

2014 ◽

Vol 138 (2) ◽

pp. 322-332 ◽

Cited By ~ 19

Author(s):

David E. Lefebvre ◽

Bevan Pearce ◽

Jason H. Fine ◽

Emily Chomyshyn ◽

Nikia Ross ◽

...

Keyword(s):

Carbon Black ◽

T Helper ◽

T Helper 2 ◽

Carbon Black Nanoparticles

Download Full-text

Occupational exposure to carbon black nanoparticles increases inflammatory vascular disease risk: an implication of an ex vivo biosensor assay

Particle and Fibre Toxicology ◽

10.1186/s12989-020-00378-8 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Jinglong Tang ◽

Wenting Cheng ◽

Jinling Gao ◽

Yanting Li ◽

Ruyong Yao ◽

...

Keyword(s):

Endothelial Cell ◽

Carbon Black ◽

Cell Activation ◽

Disease Risk ◽

Ex Vivo ◽

Engineered Nanoparticles ◽

Mediation Effect ◽

Global Index ◽

Endothelial Cell Activation

Abstract Background Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments. Results The average elemental carbon level inside carbon black bagging facilities was 657.0 μg/m3, which was 164-fold higher than that seen in reference areas (4.0 μg/m3). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-α, IL-1β, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses. Conclusions Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.

Download Full-text

Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽

10.1024/0301-1526.34.1.11 ◽

2005 ◽

Vol 34 (1) ◽

pp. 11-17 ◽

Cited By ~ 12

Author(s):

Brunner-La Rocca ◽

Schindler ◽

Schlumpf ◽

Saller ◽

Suter

Keyword(s):

Endothelial Dysfunction ◽

Blood Lipids ◽

Ex Vivo ◽

Hdl Cholesterol ◽

Blood Lipid ◽

Tibetan Medicine ◽

Double Blind ◽

Intraarterial Infusion ◽

Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

Download Full-text