4.7 Article

Trimethylamine N-oxide exacerbates acetaminophen-induced liver injury by interfering with macrophage-mediated liver regeneration

期刊

JOURNAL OF CELLULAR PHYSIOLOGY
卷 237, 期 1, 页码 897-910

出版社

WILEY
DOI: 10.1002/jcp.30568

关键词

acetaminophen; hepatotoxicity; liver repair; macrophage; trimethylamine-N-oxide

资金

  1. Fundamental Research Funds for the Central Universities [3332020048]
  2. National Natural Science Foundation of China [31671945]

向作者/读者索取更多资源

TMAO exacerbates APAP-induced liver toxicity by hindering macrophage-mediated liver repair, possibly stemming from the inhibition of Mmp12. Liver damage in patients with high circulating TMAO levels may be more severe in AILI, caution should be exercised in treatment.
Acetaminophen (APAP)-induced acute liver injury (AILI) is the most frequent cause of acute liver failure in developed countries. Trimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota and is relatively high in the circulation of the elderly, individuals with diabetes, and heart disease. Herein, we showed that TMAO exacerbates APAP hepatotoxicity. It is possible that delayed liver repair and regeneration that resulted from reduced macrophage accumulation was responsible for this combined hepatotoxicity. Moreover, matrix metalloproteinase 12 (Mmp12), expressed predominantly by macrophages, were reduced by TMAO in vitro and in vivo. This led to the inhibition of macrophage migration and a subsequent decrease in the recruitment of proresolving macrophages to the necrosis area. Furthermore, the administration of recombinant Mmp12 mitigated the enhanced hepatotoxicity in mice cotreated with TMAO and APAP. Overall, this study indicates that TMAO exacerbates APAP-induced hepatotoxicity by hindering macrophage-mediated liver repair, which might stem from the inhibition of Mmp12. These findings imply that liver damage in patients with high levels of circulating TMAO may be more severe in AILI and should exercise caution when treating with NAC.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据