PMID- 36668808
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 2305-6304 (Electronic)
IS  - 2305-6304 (Linking)
VI  - 11
IP  - 1
DP  - 2023 Jan 15
TI  - Prenatal Lipopolysaccharide Exposure Alters Hepatic Drug-Metabolizing Enzyme 
      Expression in Mouse Offspring via Histone Modifications.
LID - 10.3390/toxics11010082 [doi]
LID - 82
AB  - Inflammation is a major regulator of drug-metabolizing enzymes (DMEs), therefore 
      contributing to the interindividual variability of drug effects. However, whether 
      prenatal inflammation affects DMEs expression in offspring remains obscure. This 
      study investigated the effects of prenatal lipopolysaccharide (LPS) exposure on 
      hepatic expression of inflammatory-related genes, nuclear receptors, and DMEs in 
      offspring mice. Prenatal LPS exposure on gestational day (GD) 10 led to higher 
      expression of NF-kappaB, Pxr, and Cyp2b10, while lower expression of Car, Ahr, 
      Cyp3a11, and Ugt1a1 in postnatal day (PD) 30 offspring. However, multiple doses 
      of LPS exposure on GD10-14 resulted in higher levels of inflammatory-related 
      genes, Cyp1a2, and Cyp2b10, and lower levels of Pxr and Cyp3a11 in PD30 offspring 
      liver. For PD60 offspring, decreased hepatic expression of NF-kappaB and IL-6, and 
      increased expression of Pxr and Cyp3a11 were seen in single-dose LPS groups, 
      whereas opposite results were observed in the multiple-dose LPS groups. Notably, 
      enhanced H3K4me3 levels in the PXR response elements of the Cyp3a11 promoter were 
      observed in the liver of PD60 offspring mice from dams treated with multiple 
      doses of LPS during pregnancy. Overall, this study suggests that parental LPS 
      exposure could persistently alter the hepatic expression of DMEs, and histone 
      modifications may contribute to the long-term effects.
FAU - Zhu, Hanhan
AU  - Zhu H
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
AD  - Department of Pharmacology, School of Pharmacy, Zhengzhou University, Zhengzhou 
      450001, China.
AD  - Translational Medical Center, Weifang Second People's Hospital, The Second 
      Affiliated Hospital of Weifang Medical University, Weifang 261041, China.
FAU - Liu, Guangming
AU  - Liu G
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
AD  - Henan Provincial People's Hospital, Henan Eye Hospital, People's Hospital of 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Chang, Qi
AU  - Chang Q
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Yan, Mengyao
AU  - Yan M
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Yang, Kun
AU  - Yang K
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Li, Yanxin
AU  - Li Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Nie, Yali
AU  - Nie Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Li, Xiaotian
AU  - Li X
AD  - Department of Pharmacology, School of Pharmacy, Zhengzhou University, Zhengzhou 
      450001, China.
FAU - Han, Shengna
AU  - Han S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Wang, Pei
AU  - Wang P
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Zhang, Lirong
AU  - Zhang L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
LA  - eng
GR  - 82073931, U1604163, and 81803617/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230115
PL  - Switzerland
TA  - Toxics
JT  - Toxics
JID - 101639637
PMC - PMC9866336
OTO - NOTNLM
OT  - drug-metabolizing enzyme
OT  - histone modification
OT  - inflammation
OT  - lipopolysaccharides
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/21 06:00
MHDA- 2023/01/21 06:01
PMCR- 2023/01/15
CRDT- 2023/01/20 15:31
PHST- 2022/12/13 00:00 [received]
PHST- 2023/01/06 00:00 [revised]
PHST- 2023/01/13 00:00 [accepted]
PHST- 2023/01/20 15:31 [entrez]
PHST- 2023/01/21 06:00 [pubmed]
PHST- 2023/01/21 06:01 [medline]
PHST- 2023/01/15 00:00 [pmc-release]
AID - toxics11010082 [pii]
AID - toxics-11-00082 [pii]
AID - 10.3390/toxics11010082 [doi]
PST - epublish
SO  - Toxics. 2023 Jan 15;11(1):82. doi: 10.3390/toxics11010082.