Protective effects of regulatory amino acids on ischemia-reperfusion injury in the isolated perfused rat liver.
OBJECTIVE
Some amino acids (AAs) display potent regulatory activities on cell metabolism, including via anti-oxidative defences. The aim of this study was to evaluate the protective effect of these AAs on warm ischaemia-reperfusion (I/R) injury in the isolated perfused rat liver.


METHODS
Livers from fasted male Sprague-Dawley rats were isolated and perfused without (control group) or with (AP group) a mixture of regulatory AAs (glutamine, histidine, leucine, methionine, proline, phenylalanine, tryptophan and alanine). After 45 min of perfusion, warm ischaemia was induced for 45 min by clamping the portal vein catheter; thereafter, reperfusion was performed for 30 min.


RESULTS
TNF-alpha production was significantly lower in the AP group during reperfusion (


METHODS
39+/-7 versus AP: 16+/-2 pg min-1 g-1, p<0.05), and lactate dehydrogenase (LDH) release decreased significantly during the last 15 min of reperfusion (


METHODS
0.13+/-0.03 versus AP: 0.04+/-0.02 IU min-1 g-1, p<0.05), despite similar levels of oxidative stress. The addition of regulatory AAs was not associated with variations in portal flow, bile flow, hepatic glucose or urea metabolism. However, significant changes in intrahepatic glutamine (


METHODS
1.4+/-0.2 versus AP: 2.6+/-0.5 micromol g-1, p < 0.05) together with higher glutamate release in the AP group (


METHODS
10.2+/-5.4 versus AP: 42.6+/-10.9 nmol min-1 g-1, p < 0.05) indicated modifications in nitrogen metabolism.


CONCLUSIONS
Taken together, the lower TNF-alpha production, suggesting decreased inflammatory response, the decrease in LDH release in the AP group, demonstrating a better preservation of liver viability, and the increase in hepatic glutamine indicate that AAs play an important role in the liver's response to I/R.
Schuster
Heidi
H
Laboratoire de Biologie de la Nutrition, EA2498, Faculté de Pharmacie, Université Paris 5, Paris, France.
Blanc
Marie-Céline
MC
Neveux
Nathalie
N
Bonnefont-Rousselot
Dominique
D
Le Tourneau
Agnès
A
De Bandt
Jean-Pascal
JP
Cynober
Luc
L
D000465:Algorithms; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010477:Perfusion; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000596:Amino Acids; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase