Short-term alanyl-glutamine dipeptide pretreatment in liver ischemia-reperfusion model:: Effects on mirocirculation and antioxidant status in rats

Background & aims: Ischemia-reperfusion (I-R) injury is responsible for the morbidity A associated with liver surgery. Production of toxic free radicals influences the micro circulation. The aim of our study was to examine the effect of glutamine (Gin) 4 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 mate 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 Gin pretreatment. Hepatic microcirculation was monitored by laser Doppler flowmetry. At the 6h 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 Gin group had significantly (p < 0.05) higher flow rates than the I-R group and, at the end of the 6 h of reperfusion, significantly (p < 0.05) lower serum ALATand 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. Conclusion: Glutamine pretreatment is beneficial in supporting hepatic microcirculation and can prevent hepatocellular necrosis in Liver reperfusion injury. (c) 2007 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.