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

• Published in: Metabolomics 2022-11, Vol.18 (11), p.89, Article 89
• Main Authors: Meintani, Dimitra G., Chatzimitakos, Theodoros G., Kasouni, Athanasia I., Stalikas, Constantine D.
• Format: Article
• Language: English
• Subjects: Benzoquinone; Benzoquinones - chemistry; Benzoquinones - toxicity; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotin; By products; Cell activation; Cell Biology; Cell membranes; Deactivation; Developmental Biology; Disinfection; Gluconeogenesis; Glutathione; Glycolysis; Humans; Inositol phosphate; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Life Sciences; Linolenic acid; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Molecular Medicine; NMR; Nuclear magnetic resonance; Original; Original Article; Oxidative stress; Phenotypes; Pollutants; Riboflavin; Spectroscopy; Steroid hormones; Toxicity
• ISSN: 1573-3890; 1573-3882; 1573-3890
• DOI: 10.1007/s11306-022-01935-2

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 IC 20 and IC 50 , 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 IC 20 and IC 50 of DCBQ-OH involved the activation of cell membrane α-linolenic acid, biotin, and glutathione and deactivation of glycolysis/gluconeogenesis at IC 50 . The changes in metabolic pathways at IC 20 and IC 50 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 IC 20 and decreased at IC 50 . 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.