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首页> 外文期刊>Journal of applied toxicology >Acetaminophen‐induced hepatocyte injury: C2‐ceramide and oltipraz intervention, hepatocyte nuclear factor 1 and glutathione S S ‐transferase A1 changes
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Acetaminophen‐induced hepatocyte injury: C2‐ceramide and oltipraz intervention, hepatocyte nuclear factor 1 and glutathione S S ‐transferase A1 changes

机译：乙酰氨基酚诱导的肝细胞损伤：C2-神经酰胺和奥替普拉兹介入，肝细胞核因子1和谷胱甘肽S-Transferase A1变化

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摘要

Abstract Acetaminophen (APAP) is an antipyretic and analgesic, which is commonly associated with druginduced hepatic injury. C2ceramide plays a key role in mediating cell life activities, and oltipraz was extensively studied as a cancer chemopreventive agent. GlutathioneS transferase A1 (GSTA1) acts as a vital liver detoxification enzyme. Hepatocyte nuclear factor 1 (HNF1) regulates various cellular signaling pathways. In this study, we investigated the effects of C2ceramide and oltipraz on APAPinduced hepatocyte injury and the changes of HNF1 and GSTA1. Results showed that C2ceramide (6牸mol/L) exacerbated APAPinduced hepatocyte injury and caused a significant decrease (P ??01) in HNF1 and GSTA1 expressions. Meanwhile, GSTA1 content in supernatant was significantly increased (P ??01). In contrast, oltipraz (8牸mol/L) reduced the injury and significantly elevated (P ??01) HNF1 and GSTA1 expressions while GSTA1 content in supernatant was significantly decreased (P ??01). In conclusion, these findings revealed that C2ceramide inhibited HNF1 and GSTA1 expression and exacerbated hepatocyte injury, while oltipraz treatment results in the reduction of hepatocyte injury, and promoted HNF1 and GSTA1 expression. Additionally, the changes in HNF1 and GSTA1 were related to APAPinduced hepatocyte injury. These results were useful to investigate the mechanism of an antipyretic and analgesic drug combination.
机译：摘要乙酰氨基酚（APAP）是一种退热和镇痛药，其通常与药诱导的肝损伤相关。 C2Ceramide在介导细胞寿命活动中起关键作用，并且奥尔蒂替普拉兹被广泛地研究了癌症化学预防剂。谷胱甘肽转移酶A1（GSTA1）作为一种重要的肝解毒酶。肝细胞核因子1（HNF1）调节各种细胞信号通路。在这项研究中，我们研究了C2Ceramide和Oltipraz对肝细胞损伤的影响和HNF1和GSTA1的变化的影响。结果表明，C2Ceramide（6‰Mol / L）加剧了肝细胞损伤，在HNF1和GSTA1表达中显着降低（p≤1;β01）。同时，上清液中的GSTA1含量显着增加（p？l;Δ01）。相比之下，oltipraz（8¼mol/ l）降低损伤并显着升高（p？l;Δ01）HNF1和GSTA1表达，而上清液中的GSTA1含量显着降低（p≤1;β01）。总之，这些发现表明，C2Ceramide抑制了HNF1和GSTA1表达和加剧了肝细胞损伤，而Oltipraz治疗导致肝细胞损伤的降低，并促进HNF1和GSTA1表达。另外，HNF1和GSTA1的变化与使肝细胞损伤的肝细胞损伤有关。这些结果可用于研究解热和镇痛药物组合的机制。

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  • 来源
    《Journal of applied toxicology》 |2019年第12期|共11页
  • 作者

    Chang Yicong; Wang Feng; Yang Yang; Zhang Yuanyuan; Muhammad Ishfaq; Li Rui; Li Changwen; Li Ying; Shi Chenxi; Ma Xin; Hao Beili; Liu Fangping;

  • 作者单位

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Harbin Veterinary Research Institute of Chinese Academy of Agricultural SciencesHarbin People's;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

    Department of Basic Veterinary Science College of Veterinary MedicineNortheast Agricultural;

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  • 正文语种 eng
  • 中图分类 毒物学（毒理学）;
  • 关键词

    acetaminophen; C2ceramide; GSTA1; hepatocyte; HNF1; oltipraz;

    机译：乙酰氨基酚;C2ceramide;GSTA1;肝细胞;HNF1;oltipraz;

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