Caffeic acid attenuated acetaminophen-induced hepatotoxicity by inhibiting ERK1/2-mediated early growth response-1 transcriptional activation
Caffeic acid attenuated acetaminophen-induced hepatotoxicity by inhibiting ERK1/2-mediated early growth response-1 transcriptional activation
复制标题
咖啡酸通过抑制 ERK1/2 介导的早期生长反应 1 转录激活来减轻对乙酰氨基酚诱导的肝毒性
DOI：
10.1016/j.cbi.2016.10.009
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发表时间：
2016-12-25
影响因子：
5.1
通讯作者：
Ji, Lili
中科院分区：
文献类型：
--
作者：
Pang, Chun;Shi, Liang;Ji, Lili
Caffeic acid (CA) is a natural compound abundant in fruits, coffee and plants. This study aims to investigate the involved mechanism of the therapeutic detoxification of CA against acetaminophen (APAP)induced hepatotoxicity. CA (10, 30 mg/kg) was orally given to mice at 1 h after mice were pre administrated with APAP (300 mg/kg). The therapeutic detoxification of CA against APAP-induced hepatotoxicity was observed by detecting serum aminotransferases, liver malondialdehyde (MDA) amount and liver histological evaluation in vivo. CA reduced APAP-induced increase in the mRNA expression of early growth response 1 (Egr1) in hepatocytes, and inhibited APAP-induced Egr1 transcriptional activation in vitro and in vivo. CA reduced the increased expression of growth arrest and DNA damage-inducible protein (Gadd45)alpha induced by APAP in hepatocytes. Moreover, Egr1 siRNA reduced Gadd45 alpha expression and reversed APAP-induced cytotoxicity in hepatocytes. Further results showed that CA blocked APAP-induced activation of extracellular-regulated protein kinase (ERK1/2) signaling cascade in vivo and in vitro. In addition, the application of ERK1/2 inhibitors (PD98059 and U0126) abrogated the nuclear translocation of Egr1 induced by APAP in hepatocytes. In conclusion, this study demonstrated the therapeutic detoxification of CA against APAP-induced liver injury, and the inhibition of CA on ERK1/2-mediated Egr1 transcriptional activation was involved in this process. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
