Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

Frontiñán-Rubio, Javier; Gómez, M. Victoria; González, Viviana Jehová; Durán-Prado, Mario; Vázquez, Éster

doi:10.1038/s41598-020-75448-0

Cited by 17 publications

(24 citation statements)

References 76 publications

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“…Exposure of HaCaT cells to a small few‐layer graphene (sFLG) resulted in changes in intracellular glucose and lactate levels, as well as changes in glycolytic mechanisms, due to a shift from oxidative phosphorylation to glycolysis and increased use of glutamine as an alternative energy source 52 …”

Section: Resultsmentioning

confidence: 99%

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A systematic review: metabolomics‐based identification of altered metabolites and pathways in the skin caused by internal and external factors

Masutin

Kersch

Schmitz‐Spanke

2022

Experimental Dermatology

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The skin's ability to function optimally is affected by many diverse factors. Metabolomics has a great potential to improve our understanding of the underlying metabolic changes and the affected pathways. Therefore, the objective of this study was to review the current state of the literature and to perform further metabolic pathway analysis on the obtained data. The aim was to gain an overview of the metabolic changes under altered conditions and to identify common and different patterns as a function of the investigated factors. A cross‐study comparison of the extracted studies from different databases identified 364 metabolites, whose concentrations were considerably altered by the following factor groups: irradiation, xenobiotics, ageing and skin diseases (mainly psoriasis). Using metabolic databases and pathway analysis tools, the individual metabolites were assigned to the corresponding metabolic pathways and the most strongly affected signalling pathways were identified. All factors induced oxidative stress. Thus, antioxidant defence systems, especially coenzyme Q10 (ageing) and the glutathione system (irradiation, ageing, xenobiotics), were impacted. Lipid metabolism was also impacted by all factors studied. The carnitine shuttle as part of β‐oxidation was activated by all factor groups except ageing. Glycolysis, Krebs (TCA) cycle and purine metabolism were mainly affected by irradiation and xenobiotics. The pentose phosphate pathway was activated, and Krebs cycle was downregulated in response to oxidative stress. In summary, it can be ascertained that mainly energy metabolism, lipid metabolism, antioxidative defence and DNA repair systems were impacted by the factors studied.

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Section: Resultsmentioning

confidence: 99%

“…An increase in oxygen consumption factor (OCF) was observed in HaCat cells exposed to sFLG by increasing basal and maximal respiration, accompanied by a parallel increase in proton leakage, without affecting ATP production 52 49 arsenic 50 and graphene oxide particles 51 .…”

Section: Resultsmentioning

confidence: 99%

A systematic review: metabolomics‐based identification of altered metabolites and pathways in the skin caused by internal and external factors

Masutin

Kersch

Schmitz‐Spanke

2022

Experimental Dermatology

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“…Viability and necrosis were performed as reported in earlier studies 28 , 86 , 87 . Briefly, NHBE or A549 were seeded in 96-well cell culture plates and incubated for up to 6 h (10.000 cells/well), 24 h (10.000 cells/well), and 7 days (2.500 cells/well) with GO, FLG, or sFLG at increasing concentrations (0.05, 0.5, 5, 50, and 100 µg/mL).…”

Section: Methodsmentioning

confidence: 99%

Rapid and efficient testing of the toxicity of graphene-related materials in primary human lung cells

Frontiñán-Rubio

González

Vázquez

et al. 2022

Sci Rep

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Graphene and its derivative materials are manufactured by numerous companies and research laboratories, during which processes they can come into contact with their handlers' physiological barriers—for instance, their respiratory system. Despite their potential toxicity, these materials have even been used in face masks to prevent COVID-19 transmission. The increasingly widespread use of these materials requires the design and implementation of appropriate, versatile, and accurate toxicological screening methods to guarantee their safety. Murine models are adequate, though limited when exploring different doses and lengths of exposure—as this increases the number of animals required, contrary to the Three R's principle in animal experimentation. This article proposes an in vitro model using primary, non-transformed normal human bronchial epithelial (NHBE) cells as an alternative to the most widely used model to date, the human lung tumor cell line A549. The model has been tested with three graphene derivatives—graphene oxide (GO), few-layer graphene (FLG), and small FLG (sFLG). We observed a cytotoxic effect (necrosis and apoptosis) at early (6- and 24-h) exposures, which intensified after seven days of contact between cells and the graphene-related materials (GRMs)—with cell death reaching 90% after a 5 µg/mL dose. A549 cells are more resistant to necrosis and apoptosis, yielding values less than half of NHBE cells at low concentrations of GRMs (between 0.05 and 5 µg/mL). Indeed, GRM-induced cell death in NHBE cells is comparable to that induced by toxic compounds such as diesel exhaust particles on the same cell line. We propose NHBE as a suitable model to test GRM-induced toxicity, allowing refinement of the dose concentrations and exposure timings for better-designed in vivo mouse assays.

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“…The ABTS working solution was made by mixing the first three reagents at a 76:5:4 ratio. Trolox is a water-soluble vitamin E analog and serves as an antioxidant standard [ 33 ]. Trolox (10 mM) was diluted to concentrations of 0.1, 0.2, 0.4, 0.8 and 1.0 mM with distilled water.…”

Section: Methodsmentioning

confidence: 99%

Network pharmacology combined with molecular docking to explore the potential mechanisms for the antioxidant activity of Rheum tanguticum seeds

Wang

Xiong

Zhao

et al. 2022

BMC Complement Med Ther

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Background Rheum tanguticum (R. tanguticum) is an edible and medicinal plant that exhibits high antioxidant activity. The purpose of the present study was to investigate the bioactive components of its seeds and the potential mechanisms of antioxidant activity to provide a foundation for further developmental work on R. tanguticum seeds as a functional food. Methods In this study, the antioxidant activities of R. tanguticum seeds were measured using DPPH, ABTS and FRAP assays. LC-Q-TOF/MS was used to identify the active compounds in the seeds, and Swiss Target Prediction was used to identify their potential targets. The DisGENET, DrugBank, OMIM and GeneCard databases were used to search for antioxidant-related targets. Results The component–target–pathway network was constructed and included 5 compounds and 9 target genes. The hub genes included ESR1, APP, MAPK8, HSP90AA1, AKT1, MMP2, PTGS2, TGFB1 and JUN. The antioxidant activity signaling pathways of the compounds for the treatment of diseases were the cancer signaling pathway, estrogen signaling pathway, colorectal cancer signaling pathway, MAPK signaling pathway, etc. Molecular docking revealed that the compounds in R. tanguticum seeds could inhibit potential targets (AKT1, ESR1 and PTGS2). Conclusion Molecular docking studies revealed that the binding energy score between liriodenine and PTGS2 was the highest (8.16), followed by that of chrysophanol (7.10). This result supports the potential for PTGS2-targeted drug screening and design.

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Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

Cited by 17 publications

References 76 publications

A systematic review: metabolomics‐based identification of altered metabolites and pathways in the skin caused by internal and external factors

A systematic review: metabolomics‐based identification of altered metabolites and pathways in the skin caused by internal and external factors

Rapid and efficient testing of the toxicity of graphene-related materials in primary human lung cells

Network pharmacology combined with molecular docking to explore the potential mechanisms for the antioxidant activity of Rheum tanguticum seeds

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