PMID- 32615080
OWN - NLM
STAT- MEDLINE
DCOM- 20210111
LR  - 20210111
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 180
DP  - 2020 Oct
TI  - GR-C/EBPalpha-IGF1 axis mediated azithromycin-induced liver developmental toxicity in 
      fetal mice.
PG  - 114130
LID - S0006-2952(20)30366-X [pii]
LID - 10.1016/j.bcp.2020.114130 [doi]
AB  - Azithromycin is considered an effective drug to treat the perinatal mycoplasma 
      infection. However, there is a lack of studies on developmental toxicity of 
      azithromycin. In this study, we observed the developmental toxicity of fetal 
      liver induced by prenatal azithromycin exposure (PAE) in mice and explored the 
      potential mechanism. Pregnant Kunming mice were intraperitoneally injected with 
      azithromycin (37.5 and 150 mg/kg.d) from gestational day (GD) 9 to 18. After PAE, 
      the bodyweight gain rates of pregnant mice and the birthweights of the offspring 
      were decreased, and the liver morphology, development indexes and metabolic 
      function were all altered in different degree in the PAE fetuses. Meanwhile, PAE 
      decreased the fetal serum insulin-like growth factor 1 (IGF1) levels and liver 
      IGF1 signal pathway expression, accompanied by glucocorticoid receptor-CCAAT 
      enhancer-binding protein alpha (GR-C/EBPalpha) signal enhancement. Furthermore, 
      azithromycin disturbed hepatocyte differentiation, maturation and metabolic 
      function via upregulating GR-C/EBPalpha signal and reducing the expression and 
      secretion levels of IGF1 in HepG2 cells. These changes could be reversed by GR 
      siRNA or exogenous IGF1. These results indicated that PAE could cause fetal liver 
      developmental toxicity in mice, and one of the main mechanisms was that 
      azithromycin activated the GR-C/EBPalpha signal, inhibited the IGF1 signal pathway, 
      and then disturbed the hepatic proliferation, apoptosis, differentiation, and 
      glycose and lipid metabolism.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Liu, Kexin
AU  - Liu K
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Wang, Guihua
AU  - Wang G
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Li, Li
AU  - Li L
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Chen, Guanghui
AU  - Chen G
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Gong, Xiaohan
AU  - Gong X
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan 430071, China. Electronic address: 
      wanghui19@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200629
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (CCAAT-Enhancer-Binding Protein-alpha)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 83905-01-5 (Azithromycin)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*toxicity
MH  - Azithromycin/*toxicity
MH  - CCAAT-Enhancer-Binding Protein-alpha/*metabolism
MH  - Female
MH  - Fetal Development/drug effects
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Liver/*drug effects/embryology/metabolism
MH  - Mice
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/metabolism
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Signal Transduction
MH  - Up-Regulation
OTO - NOTNLM
OT  - Developmental toxicity
OT  - Glucocorticoid receptor
OT  - Glucose and lipid metabolism
OT  - Pregnancy azithromycin exposure
EDAT- 2020/07/03 06:00
MHDA- 2021/01/12 06:00
CRDT- 2020/07/03 06:00
PHST- 2020/02/29 00:00 [received]
PHST- 2020/06/25 00:00 [revised]
PHST- 2020/06/26 00:00 [accepted]
PHST- 2020/07/03 06:00 [pubmed]
PHST- 2021/01/12 06:00 [medline]
PHST- 2020/07/03 06:00 [entrez]
AID - S0006-2952(20)30366-X [pii]
AID - 10.1016/j.bcp.2020.114130 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2020 Oct;180:114130. doi: 10.1016/j.bcp.2020.114130. Epub 2020 
      Jun 29.