Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1

doi:10.1016/j.tox.2017.03.008

	Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1
	Bai, Qingyun 1,3; Yan, Hongyu 3; Sheng, Yuchen 2; Jin, Yao 3; Shi, Liang 3; Ji, Lili 3; Wang, Zhengtao 3
刊名	Toxicology
	2017-05-01
卷号	382 页码:47-58
ISSN号	1879-3185
DOI	10.1016/j.tox.2017.03.008
文献子类	Article
英文摘要	Acetaminophen (APAP)-induced acute liver injury has already been well studied. However, whether long-term administration of APAP will cause liver fibrosis is still not very clear. This study aims to investigate the liver fibrosis in mice induced by long-term APAP treatment and the involvement of early growth response 1 (Egr-1). C57BL/6 mice were orally given with APAP (200, 300mg/kg) for 2, 6 or 10 weeks, respectively. Liver hydroxyproline content, collagen deposition and inflammatory cells infiltration were increased in mice treated with APAP (200, 300mg/kg) for 6 or 10 weeks. Liver mRNA expression of collagen (COL)1a1, Col3a1, transforming growth factor-β (TGF-β) and serum contents of COL1, COL3, TGF-β were all increased in APAP-treated mice. Liver expression of α-smooth muscle actin (α-SMA) and phosphorylated ERK1/2 and Smad2/3 were all increased in APAP-treated mice. Furthermore, increased liver mRNA expression of Egr-1 and its subsequent nuclear translocation were found in APAP-treated mice. Egr-1 knock-out mice were further applied. APAP-induced liver fibrosis was found to be more serious in Egr-1 knock-out mice. N-acetyl-p-benzoquinoneimine (NAPQI), the APAP hepatotoxic metabolite, increased cellular mRNA expression of α-SMA, Col1a1, Col3a1, TGF-β, induced ERK1/2 and Smad2/3 phosphorylation and Egr-1 nuclear translocation in hepatic stellate LX2 cells. In conclusion, long-term administration of APAP induced liver fibrosis in mice, and Egr-1 was critically involved in this process. This study points out a warning and reference for patients with long-term APAP ingestion in clinic.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266635]
专题	中国科学院上海药物研究所
通讯作者	Ji, Lili; Wang, Zhengtao
作者单位	1.College of Chemistry and Chemical Engineering, Yichun University, Yichun 336000, China; 2.Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China 3.Shanghai Key Laboratory of Complex Prescription, MOE Key Laboratory for Standardization of Chinese Medicines and SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
推荐引用方式 GB/T 7714	Bai, Qingyun,Yan, Hongyu,Sheng, Yuchen,et al. Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1[J]. Toxicology,2017,382:47-58.
APA	Bai, Qingyun.,Yan, Hongyu.,Sheng, Yuchen.,Jin, Yao.,Shi, Liang.,...&Wang, Zhengtao.(2017).Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1.Toxicology,382,47-58.
MLA	Bai, Qingyun,et al."Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1".Toxicology 382(2017):47-58.