PMID- 35696061
OWN - NLM
STAT- MEDLINE
DCOM- 20221026
LR  - 20221026
IS  - 1614-7499 (Electronic)
IS  - 0944-1344 (Linking)
VI  - 29
IP  - 52
DP  - 2022 Nov
TI  - Effects of chemical mixtures on liver function biomarkers in the Korean adult 
      population: thresholds and molecular mechanisms for non-alcoholic fatty liver 
      disease involved.
PG  - 78555-78587
LID - 10.1007/s11356-022-21090-4 [doi]
AB  - There is a scarcity of research on the effects of a mixture of chemicals on liver 
      function biomarkers and non-alcoholic fatty liver disease (NAFLD) indices, 
      including FSI, HIS, and FBI-4. Thus, we aimed to explore whether there is an 
      association between chemical mixtures, including 26 chemicals found in blood and 
      urine, liver function biomarkers, and non-alcoholic fatty liver disease (NAFLD) 
      indices in Korean adults. The effects of exposure to chemical mixtures on liver 
      function biomarkers and NAFLD indices were investigated using linear regression 
      models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), 
      and Bayesian kernel machine regression (BKMR) among 3669 adults. In silico 
      toxicogenomic data-mining, we evaluated molecular mechanisms associated with 
      NAFLD, including pathways, diseases, genes, miRNAs, and biological processes. The 
      linear regression models showed blood or urine Hg levels were the most important 
      factors associated with AST, ALT, GGT, FSI, and HSI levels, and significant 
      trends were observed for these chemical quartiles (p < 0.01). The WQS index was 
      significantly associated with ALT, GGT, FSI, and HSI. The qgcomp index also found 
      an association between chemicals and AST, ALT, GGT, and FSI. In the BKMR model, 
      the overall effect of the mixture was significantly related to ALT, GGT, FSI, and 
      HSI. In silico analysis, we found mixed chemicals interacted with the CYP1A2 gene 
      and were associated with NAFLD. Seventy-eight percent of interactions were 
      identified as physical interactions in the CYP1A2 gene related to NAFLD. 
      Transcription factor regulation in adipogenesis and lipid metabolic processes are 
      fundamental molecular mechanisms that could be influenced by NAFLD-related mixed 
      chemicals. Cutoff thresholds for chemical exposure levels associated with liver 
      function indicators and NAFLD indices were also reported. The strongest 
      interactions and expression of miRNAs involved in NAFLD development were also 
      identified.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Nguyen, Hai Duc
AU  - Nguyen HD
AD  - Department of Pharmacy, College of Pharmacy and Research Institute of Life and 
      Pharmaceutical Sciences, Sunchon National University, Sunchon, Jeonnam, 57922, 
      Republic of Korea.
FAU - Kim, Min-Sun
AU  - Kim MS
AUID- ORCID: 0000-0001-9952-0038
AD  - Department of Pharmacy, College of Pharmacy and Research Institute of Life and 
      Pharmaceutical Sciences, Sunchon National University, Sunchon, Jeonnam, 57922, 
      Republic of Korea. minsun@scnu.ac.kr.
LA  - eng
GR  - grant nos. NRF2013R1A1A3008851/This work supported by grants National Research 
      Foundation of Korea (NRF) grant funded by the Korean government (MEST)/
GR  - 2018R1D1A1B07049610/This work supported by grants National Research Foundation of 
      Korea (NRF) grant funded by the Korean government (MEST)/
PT  - Journal Article
DEP - 20220613
PL  - Germany
TA  - Environ Sci Pollut Res Int
JT  - Environmental science and pollution research international
JID - 9441769
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - 0 (Biomarkers)
RN  - 0 (MicroRNAs)
RN  - FXS1BY2PGL (Mercury)
RN  - 0 (Transcription Factors)
RN  - 0 (Lipids)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Non-alcoholic Fatty Liver Disease/chemically induced
MH  - Bayes Theorem
MH  - Cytochrome P-450 CYP1A2
MH  - Biomarkers
MH  - *MicroRNAs
MH  - *Mercury
MH  - Transcription Factors
MH  - Republic of Korea
MH  - Lipids
OTO - NOTNLM
OT  - Chemical mixture
OT  - Liver function biomarkers
OT  - Modeling
OT  - Non-alcoholic fatty liver disease
EDAT- 2022/06/14 06:00
MHDA- 2022/10/27 06:00
CRDT- 2022/06/13 11:23
PHST- 2022/03/01 00:00 [received]
PHST- 2022/05/21 00:00 [accepted]
PHST- 2022/06/14 06:00 [pubmed]
PHST- 2022/10/27 06:00 [medline]
PHST- 2022/06/13 11:23 [entrez]
AID - 10.1007/s11356-022-21090-4 [pii]
AID - 10.1007/s11356-022-21090-4 [doi]
PST - ppublish
SO  - Environ Sci Pollut Res Int. 2022 Nov;29(52):78555-78587. doi: 
      10.1007/s11356-022-21090-4. Epub 2022 Jun 13.