Reduction of liver ischemia-reperfusion injury via glutamine pretreatment.
BACKGROUND
Surgical methods that reduce bleeding during major hepatic resections lead to warm ischemia-reperfusion (I-R) injury of the liver. This is well known to have a considerable impact on the postoperative outcome. Much research work has been done to develop possible protective techniques. We aimed to investigate the effectivity of L-alanyl-L-glutamine dipeptide pretreatment in an animal model of hepatic I-R injury.


METHODS
Male Wistar rats underwent normothermic, 60 min segmental liver ischemia followed by 24 h of reperfusion. The animals (n=30) were divided into three experimental groups: sham operated, I-R, and glutamine (Gln) pretreated. Twenty-four h prior to I-R injury, rats in the Gln group received 500 mg/kg Dipeptiven infusion as glutamine pretreatment. Hepatic microcirculation during the first hour of reperfusion was monitored by noninvasive laser Doppler flowmeter. After a 24-h reperfusion period, liver tissue was analyzed by histologic and immunohistochemical assessments. Serum necroenzyme and antioxidant levels were measured.


RESULTS
In the Gln group, the integral of the reperfusion curve (RA) and the plateau maximum (PM(10)) of the flow graph showed improving tendency (RA: P=0.096; PM(10): P=0.084). Severity of histologic damage was reduced. Serum necroenzymes (ALT: P=0.042, AST: P=0.044) were significantly lower. Chemiluminescent intensity of liver and plasma was significantly decreased (P=0.0003 and P=0.0496). Further spectrophotometric analysis of liver homogenate samples also showed significant improvement of the redox homeostasis.


CONCLUSIONS
Our results suggest that L-alanyl-L-glutamine dipeptide pretreatment given 24 h prior to I-R injury could be an effective method to reduce liver damage caused by hepatic inflow occlusion.
Stangl
Rita
R
1(st) Department of Surgery, Semmelweis University, Budapest, Hungary.
Szijártó
Attila
A
Ónody
Péter
P
Tamás
Judit
J
Tátrai
Miklós
M
Hegedus
Viktor
V
Blázovics
Anna
A
Lotz
Gábor
G
Kiss
András
A
Módis
Katalin
K
Gero
Domokos
D
Szabó
Csaba
C
Kupcsulik
Péter
P
Harsányi
László
L
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D005973:Glutamine / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D019194:Ischemic Preconditioning / Q000379:methods*; D017078:Laser-Doppler Flowmetry; D008102:Liver Circulation / Q000502:physiology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D010084:Oxidation-Reduction; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D004151:Dipeptides; D017382:Reactive Oxygen Species; D005973:Glutamine; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C054122:alanylglutamine