Abstract:
: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 α (GR-C/EBPα) signal enhancement. Furthermore, azithromycin disturbed hepatocyte differentiation, maturation and metabolic function via upregulating GR-C/EBPα 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/EBPα signal, inhibited the IGF1 signal pathway, and then disturbed the hepatic proliferation, apoptosis, differentiation, and glycose and lipid metabolism.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Liu K,Wang G,Li L,Chen G,Gong X,Zhang Q,Wang Hdoi
10.1016/j.bcp.2020.114130subject
Has Abstractpub_date
2020-10-01 00:00:00pages
114130eissn
0006-2952issn
1873-2968pii
S0006-2952(20)30366-Xjournal_volume
180pub_type
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