title: Hyperammonaemia induces hepatic injury with alteration of gene expression profiles.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jia
authors.forename: Zu-Jiang
authors.initials: ZJ
authors.lastname: Yu
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Duan
authors.forename: Xin-Quan
authors.initials: XQ
authors.lastname: Lü
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Liu
authors.forename: Ran
authors.initials: R
authors.lastname: Sun
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Gao
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Wang
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Yan
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Kan
mesh_terms: D000643:Ammonium Chloride; D000818:Animals; D017209:Apoptosis; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D022124:Hyperammonemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017207:Rats, Sprague-Dawley
chemical_list: D019925:Cyclin A; D000643:Ammonium Chloride; D019938:Cyclin D1
keywords: hepatic injury; hyperammonaemia; microarray