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Hyperammonaemia induces hepatic injury with alteration of gene expression profiles
Author(s) -
Jia Bin,
Yu ZuJiang,
Duan ZhenFeng,
Lü XinQuan,
Li JingJing,
Liu XiaoRui,
Sun Ran,
Gao XiaoJuan,
Wang YanFang,
Yan JingYa,
Kan QuanCheng
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12365
Subject(s) - liver injury , microarray , biology , hepatic stellate cell , hepatocyte , thioacetamide , microarray analysis techniques , gene expression , apoptosis , medicine , gene , cyclin d1 , endocrinology , cell cycle , biochemistry , in vitro
Background Hyperammonaemia is a serious metabolic disorder commonly observed in patients with hepatic failure. However, it is unknown whether hyperammonaemia has a direct adverse effect on the hepatocytes and thereby serves as both a cause and effect of hepatic failure. Aims The purposes were to determine whether hepatic injury can be caused by hyperammonaemia, and if so, screen the key genes involved in hyperammonaemia. Methods Hyperammonaemic rats were established via intragastric administration of the ammonium chloride solution. The liver tissues were assessed via biochemistry, histology, immunohistochemistry and microarray analysis. Selected genes were confirmed by quantitative RT ‐ PCR . Results Administration of the ammonium chloride caused the hyperammonaemia, accompanied with the changes of plasma markers indicating hepatic injury. A pathological assessment demonstrated increased apoptosis and higher level of cyclin D1 and cyclin A in hyperammonaemic rat liver. Microarray was performed on the liver samples and 198 differentially expressed genes were identified in hyperammonaemic rats and validated by quantitative RT ‐ PCR . These genes were associated with many vital functional classes and belonged to different signal transduction pathways. Conclusions This study demonstrates that hyperammonaemia can directly induce hepatic injury via the hepatocyte apoptosis. Gene expression profile may provide the possible explanations and mechanisms for the hepatic injury induced by hyperammonaemia.