Short-term alanyl-glutamine dipeptide pretreatment in liver ischemia-reperfusion model: effects on microcirculation and antioxidant status in rats.
OBJECTIVE
Ischemia-reperfusion (I-R) injury is responsible for the morbidity associated with liver surgery. Production of toxic free radicals influences the microcirculation. The aim of our study was to examine the effect of glutamine (Gln) supplementation--adminstered in alanyl-glutamine dipeptide form--on liver function, immuno/histopathology and the oxidative state of the liver after injury.


METHODS
Two-hundred and fifty grams male Wistar rats underwent normothermic, 60 min, segmental liver ischemia followed by 6 h of reperfusion. The animals (n = 45) were divided into three groups: sham operated, I-R and parenteral Gln pretreatment. Hepatic microcirculation was monitored by laser Doppler flowmetry. At the 6 h of reperfusion, histological alterations, TUNEL reaction, active caspase-3 reaction, serum and liver tissue antioxidant levels, serum ALAT, ASAT and TNF-alpha levels were measured.


RESULTS
Upon reperfusion, the Gln group had significantly (p<0.05) higher flow rates than the I-R group and, at the end of the 6h of reperfusion, significantly (p<0.05) lower serum ALAT and ASAT levels. The liver chemiluminescent intensity was lower, free SH-groups were elevated, while the reducing power was decreased in the Gln-pretreated group. Positive staining for caspase-3 after Gln pretreatment was significantly increased in contrast to the control tissues.


CONCLUSIONS
Glutamine pretreatment is beneficial in supporting hepatic microcirculation and can prevent hepatocellular necrosis in liver reperfusion injury.
Szijártó
Attila
A
1st Department of Surgery, Semmelweis University, Budapest, Hungary. szijartoattila@freemail.hu
Hahn
Oszkár
O
Batmunkh
Enkhjargal
E
Stangl
Rita
R
Kiss
András
A
Lotz
Gábor
G
Schaff
Zsuzsa
Z
Váli
László
L
Blázovics
Anna
A
Gero
Domokos
D
Szabó
Csaba
C
Kupcsulik
Péter
P
Harsányi
László
L
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004151:Dipeptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000000981:diagnostic imaging / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014463:Ultrasonography
D000975:Antioxidants; D004151:Dipeptides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; C054122:alanylglutamine