Glycine reduces hepatic warm ischaemia-reperfusion injury by suppressing inflammatory reactions in rats.
BACKGROUND
Glycine, a non-essential amino acid, is known to have an anti-inflammatory effect on haemorrhagic and endotoxic shock in animals. In the present study, we examined the effects of glycine on inflammatory reactions and hepatocellular damage after hepatic warm ischaemia-reperfusion (I-R) in rats.


METHODS
Using Sprague-Dawley rats, ischaemia was induced in 92% of the liver by clamping the hepatic inflows for 60 min, and part of the non-ischaemic lobe was resected after reperfusion. Before the induction of I-R, rats were treated by an intravenous administration of either glycine (Glycine group) or normal saline (Control group). The severity of hepatocellular injury was determined by serum levels of hepatic enzymes and histological necrosis. To evaluate the effect of glycine on inflammatory reactions, tumour necrosis factor (TNF)-alpha mRNA expression in the liver, serum levels of TNF-alpha and chemokine-induced neutrophil chemoattractant (CINC) and the number of neutrophils in the liver were compared between the groups.


RESULTS
At 60 min after reperfusion, the serum levels of hepatic enzymes in the Glycine group were significantly lower than those in the Control group (P<0.05). TNF-alpha mRNA expression was also suppressed in the livers in the Glycine group. Furthermore, the serum levels of TNF-alpha and CINC in the Glycine group were significantly lower than those in the Control group (P<0.05). Pretreatment with glycine also significantly reduced hepatic necrosis and the number of neutrophils at 24 h after reperfusion.


CONCLUSIONS
Glycine has a protective effect against inflammatory reactions, and reduces hepatocellular injury induced by hepatic warm I-R in rats.
Yamanouchi
Kosho
K
Department of Liver Transplantation and Digestive Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. ymanouch@gk9.so-net.ne.jp
Eguchi
Susumu
S
Kamohara
Yukio
Y
Yanaga
Katsuhiko
K
Okudaira
Sadayuki
S
Tajima
Yoshitsugu
Y
Kanematsu
Takashi
T
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D005998:Glycine / Q000627:therapeutic use*; D018684:Glycine Agents / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries; D008297:Male; D009336:Necrosis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D052096:Warm Ischemia
D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D018684:Glycine Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D005998:Glycine