Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury

文献类型： 外文期刊

第一作者： Ma, Xin

作者： Ma, Xin;Chang, Yicong;Zhang, Yuanyuan;Muhammad, Ishfaq;Shi, Chenxi;Li, Rui;Li, Zhi;Lin, Yuexia;Han, Qing;Liu, Fangping;Ma, Xin;Li, Changwen;Li, Rui;Liu, Fangping

作者机构：

关键词： GSTA1; HNF-1; C2-ceramide; oltipraz; acetaminophen; liver injury

期刊名称：FRONTIERS IN PHARMACOLOGY （ 影响因子：5.81； 五年影响因子：6.005 ）

ISSN： 1663-9812

年卷期： 2018 年 9 卷

页码：

收录情况： SCI

摘要： In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 mu mol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 mu mol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 mu mol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury.

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