Metabolomic interference induced by short-chain chlorinated paraffins in human normal hepatic cells

• DOI: 10.3724/sp.j.1123.2023.10037
• Publication Date: 2024-03-28T01:31:23Z
• Authors: Yun LUO; Ningbo GENG; Shuangshuang CHEN; Lin CHENG; Haijun ZHANG; Jiping CHEN
• Keywords: Metabolic pathway; Chlorinated paraffins; Metabolome

<p id="p00005">Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent organic pollutants (POPs) that widely detected in environmental matrices and human samples. Because their persistence, long-range transport potential, bioaccumulation biotoxicity, SCCPs pose a significant threat to health. In this study, metabolomics technology was applied reveal the metabolomic interference normal hepatic (L02) cells after exposure low (1 μg/L), moderate (10 high (100 μg/L) doses SCCPs. Principal component analysis (PCA) metabolic effect level index (MELI) values showed all three SCCP caused notable perturbations L02 cells. A total 72 metabolites were annotated by MS/MS matched with experimental spectra Human Metabolome Database (HMDB) or validated commercially available standards selected as differential (DMs) across groups. The low-dose group shared 33 36 DMs moderate- high-dose groups, respectively. moderate-dose 46 group. addition, among Among DMs, 9, 45 participated amino acid, nucleotide, lipid metabolism pathways, results pathway enrichment most relevant pathways affected metabolism, fatty acid β-oxidation, nucleotide compared exposure, exposures more these Exposure perturbed glycerophospholipid sphingolipid metabolism. Significant alterations levels phosphatidylcholines, phosphatidylethanolamines, sphingomyelins indicated SCCP-induced biomembrane damage. inhibited β-oxidation decreasing short- medium-chain acylcarnitines cells, indicating energy supplied oxidation reduced Furthermore, low- SCCPs, produced significantly stronger inhibition β-oxidation. higher hypoxanthine observed indicate may induce several adverse effects, including hypoxia, reactive oxygen species production, mutagenesis