Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 7;18(11):89.
doi: 10.1007/s11306-022-01935-2.

Untargeted metabolomics of human keratinocytes reveals the impact of exposure to 2,6-dichloro-1,4-benzoquinone and 2,6-dichloro-3-hydroxy-1,4-benzoquinone as emerging disinfection by-products

Dimitra G Meintani  1 , Theodoros G Chatzimitakos  1 , Athanasia I Kasouni  2 , Constantine D Stalikas  3
Affiliations

Untargeted metabolomics of human keratinocytes reveals the impact of exposure to 2,6-dichloro-1,4-benzoquinone and 2,6-dichloro-3-hydroxy-1,4-benzoquinone as emerging disinfection by-products

Dimitra G Meintani et al. Metabolomics. .

Abstract

Introduction: The 2,6-dichloro-1,4-benzoquinone (DCBQ) and its derivative 2,6-dichloro-3-hydroxy-1,4-benzoquinone (DCBQ-OH) are disinfection by-products (DBPs) and emerging pollutants in the environment. They are considered to be of particular importance as they have a high potential of toxicity and they are likely to be carcinogenic.

Objectives: In this study, human epidermal keratinocyte cells (HaCaT) were exposed to the DCBQ and its derivative DCBQ-OH, at concentrations equivalent to their IC20 and IC50, and a study of the metabolic phenotype of cells was performed.

Methods: The perturbations induced in cellular metabolites and their relative content were screened and evaluated through a metabolomic study, using 1H-NMR and MS spectroscopy.

Results: Changes in the metabolic pathways of HaCaT at concentrations corresponding to IC20 and IC50 of DCBQ-OH involved the activation of cell membrane α-linolenic acid, biotin, and glutathione and deactivation of glycolysis/gluconeogenesis at IC50. The changes in metabolic pathways at IC20 and IC50 of DCBQ were associated with the activation of inositol phosphate, pertaining to the transfer of messages from the receptors of the membrane to the interior as well as with riboflavin. Deactivation of biotin metabolism was recorded, among others. The cells exposed to DCBQ exhibited a concentration-dependent decrease in saccharide concentrations. The concentration of steroids increased when cells were exposed to IC20 and decreased at IC50. Although both chemical factors stressed the cells, DCBQ led to the activation of transporting messages through phosphorylated derivatives of inositol.

Conclusion: Our findings provided insights into the impact of the two DBPs on human keratinocytes. Both chemical factors induced energy production perturbations, oxidative stress, and membrane damage.

Keywords: 2,6-dichloro-1,4-benzoquinone; 2,6-dichloro-3-hydroxy-1,4-benzoquinone; Disinfection byproducts; HaCaT; Metabolomics; NMR.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Heatmap with the metabolites of control HaCaT and treated with 0.10 mM and 0.30 mM of DCBQ-OH.
Fig. 2
Fig. 2
Heatmap with the metabolites of control HaCaT and treated with 0.05 mM and 0.075 mM of DCBQ.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Abbasnia A, Ghoochani M, Yousefi N, Nazmara S, Radfard M, Soleimani H, Yousefi M, Barmar S, Alimohammadi M. Prediction of human exposure and health risk assessment to trihalomethanes in indoor swimming pools and risk reduction strategy. Human and Ecological Risk Assessment: An International Journal. 2019;25(8):2098–2115. doi: 10.1080/10807039.2018.1488582. - DOI
    1. Aragonès G, Danesi F, Del Rio D, Mena P. The importance of studying cell metabolism when testing the bioactivity of phenolic compounds. Trends in Food Science and Technology. 2017;69:230–242. doi: 10.1016/j.tifs.2017.02.001. - DOI
    1. Berridge JM, Irvine RF. Inositol phosphates and cell signalling. Nature. 1989;341:197–205. doi: 10.1038/341197a0. - DOI - PubMed
    1. Berridge MJ. Inositol trisphosphate and calcium signalling mechanisms. Biochimica et Biophysica Acta - Molecular Cell Research. 2009;1793(6):933–940. doi: 10.1016/j.bbamcr.2008.10.005. - DOI - PubMed
    1. Chatzimitakos TG, Kasouni AI, Troganis AN, Stalikas CD. Carbonization of Human Fingernails: Toward the Sustainable Production of Multifunctional Nitrogen and Sulfur Codoped Carbon Nanodots with Highly Luminescent Probing and Cell Proliferative/Migration Properties [Research-article] ACS Applied Materials and Interfaces. 2018;10(18):16024–16032. doi: 10.1021/acsami.8b03263. - DOI - PubMed

LinkOut - more resources