PMID- 38374598
OWN - NLM
STAT- MEDLINE
DCOM- 20240221
LR  - 20240222
IS  - 1872-2059 (Electronic)
IS  - 1000-8713 (Print)
IS  - 1000-8713 (Linking)
VI  - 42
IP  - 2
DP  - 2024 Feb
TI  - [Metabolomic interference induced by short-chain chlorinated paraffins in human 
      normal hepatic cells].
PG  - 176-184
LID - 10.3724/SP.J.1123.2023.10037 [doi]
AB  - Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent 
      organic pollutants (POPs) that are widely detected in environmental matrices and 
      human samples. Because of their environmental persistence, long-range transport 
      potential, bioaccumulation potential, and biotoxicity, SCCPs pose a significant 
      threat to human health. In this study, metabolomics technology was applied to 
      reveal the metabolomic interference in human normal hepatic (L02) cells after 
      exposure to low (1 mug/L), moderate (10 mug/L), and high (100 mug/L) doses of SCCPs. 
      Principal component analysis (PCA) and metabolic effect level index (MELI) values 
      showed that all three SCCP doses caused notable metabolic perturbations in L02 
      cells. A total of 72 metabolites that were annotated by MS/MS and matched with 
      the experimental spectra in the Human Metabolome Database (HMDB) or validated by 
      commercially available standards were selected as differential metabolites (DMs) 
      across all groups. The low-dose exposure group shared 33 and 36 DMs with the 
      moderate- and high-dose exposure groups, respectively. The moderate-dose exposure 
      group shared 46 DMs with the high-dose exposure group. In addition, 33 DMs were 
      shared among the three exposure groups. Among the 72 DMs, 9, 9, and 45 
      metabolites participated in the amino acid, nucleotide, and lipid metabolism 
      pathways, respectively. The results of pathway enrichment analysis showed that 
      the most relevant metabolic pathways affected by SCCPs were the lipid metabolism, 
      fatty acid beta-oxidation, and nucleotide metabolism pathways, and that compared 
      with low-dose exposure, moderate- and high-dose SCCP exposures caused more 
      notable perturbations of these metabolic pathways in L02 cells. Exposure to SCCPs 
      perturbed glycerophospholipid and sphingolipid metabolism. Significant 
      alterations in the levels of phosphatidylcholines, phosphatidylethanolamines, and 
      sphingomyelins indicated SCCP-induced biomembrane damage. SCCPs inhibited fatty 
      acid beta-oxidation by decreasing the levels of short- and medium-chain 
      acylcarnitines in L02 cells, indicating that the energy supplied by fatty acid 
      oxidation was reduced in these cells. Furthermore, compared with low- and 
      moderate-dose SCCPs, high-dose SCCPs produced a significantly stronger inhibition 
      of fatty acid beta-oxidation. In addition, SCCPs perturbed nucleotide metabolism. 
      The higher hypoxanthine levels observed in L02 cells after SCCP exposures 
      indicate that SCCPs may induce several adverse effects, including hypoxia, 
      reactive oxygen species production, and mutagenesis in L02 cells.
FAU - Luo, Yun
AU  - Luo Y
AD  - College of Medicine, Linyi University, Linyi 276005, China.
FAU - Geng, Ning-Bo
AU  - Geng NB
AD  - CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian 
      Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
FAU - Chen, Shuang-Shuang
AU  - Chen SS
AD  - CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian 
      Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
FAU - Cheng, Lin
AU  - Cheng L
AD  - CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian 
      Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
FAU - Zhang, Hai-Jun
AU  - Zhang HJ
AD  - CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian 
      Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
FAU - Chen, Ji-Ping
AU  - Chen JP
AD  - CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian 
      Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Se Pu
JT  - Se pu = Chinese journal of chromatography
JID - 9424804
RN  - 8002-74-2 (Paraffin)
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - 0 (Fatty Acids)
RN  - 0 (Nucleotides)
SB  - IM
MH  - Humans
MH  - *Paraffin/toxicity/analysis
MH  - Tandem Mass Spectrometry
MH  - *Hydrocarbons, Chlorinated/toxicity/analysis
MH  - Environmental Monitoring/methods
MH  - Fatty Acids
MH  - Nucleotides
MH  - Hepatocytes/chemistry
MH  - China
PMC - PMC10877471
OTO - NOTNLM
OT  - hepatic cells
OT  - lipid metabolism
OT  - liquid chromatography (LC)
OT  - mass spectrometry (MS)
OT  - metabolomics
OT  - nucleotide metabolism
OT  - short-chain chlorinated paraffins (SCCPs)
EDAT- 2024/02/20 11:50
MHDA- 2024/02/21 11:22
PMCR- 2024/02/08
CRDT- 2024/02/20 00:43
PHST- 2024/02/21 11:22 [medline]
PHST- 2024/02/20 11:50 [pubmed]
PHST- 2024/02/20 00:43 [entrez]
PHST- 2024/02/08 00:00 [pmc-release]
AID - 10.3724/SP.J.1123.2023.10037 [doi]
PST - ppublish
SO  - Se Pu. 2024 Feb;42(2):176-184. doi: 10.3724/SP.J.1123.2023.10037.