Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4.
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.
Liu
Zuo-jin
ZJ
Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400010, China.
Yan
Lu-nan
LN
Li
Shen-wei
SW
You
Hai-bo
HB
Gong
Jian-ping
JP
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
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