title: Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4.
abstract: OBJECTIVE
  To determine whether glycine could downregulate interleukin 1 receptor associated kinase-4 (IRAK-4) expression to interfere with lipopolysaccharides (LPS) signal transduction and blunt transplantative liver ischemia-reperfusion injury (I/RI).
  
  
  METHODS
  SD rats were randomly divided into two groups: donor animals of the glycine group (n=40) were given glycine (1.5 mL; 300 mmol/L, iv) 1 h before harvest, and the control group were treated with 1.5 mL physiological saline (n= 40). Orthotopic liver transplantation was then performed according to the Kamada technique. Ten animals in each group were followed up for 7 d after surgery to assess survival. The remaining animals in each group were divided into 3 subgroups (n=10) at 1h, 2 h and 6 h after portal vein reperfusion. Levels of LPS, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin in portal circulation, as well as IRAK-4 and TNF-alpha expression, NF-kappaB transcriptional activity and morphological study of liver tissues were analyzed.
  
  
  RESULTS
  Reperfusion resulted in a significant elevation of LPS concentrations in each group persisting to the end of our study. However, glycine, which led to improved survival rate and liver function, significantly alleviated liver parenchyma cell damage by downregulating IRAK-4, TNF-alpha expression and NF-kappaB transcriptional activity compared with the control group.
  
  
  CONCLUSIONS
  Glycine can attenuate hepatic I/RI by downregulating IRAK-4 to interfere with LPS signal transduction.
authors.affiliation: Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400010, China.
authors.forename: Zuo-jin
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Lu-nan
authors.initials: LN
authors.lastname: Yan
authors.forename: Shen-wei
authors.initials: SW
authors.lastname: Li
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: You
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Gong
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005998:Glycine / Q000494:pharmacology*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000097:blood; D008099:Liver / Q000473:pathology* / Q000648:ultrastructure; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D005998:Glycine