Alanine minimises hepatocyte injury after ischemia-reperfusion in an <i>ex vivo</i> rat liver model

Ischemia-reperfusion injury is a determinant in liver injury occurring during surgery, ischemic states and multiple organ failure. The pre-existing nutritional status of the liver, i.e., fasting, might contribute to the extent of tissue injury. This study investigated whether alanine, an amino acid precursor of glucose, could protect ex vivo perfused livers of fasting rats from reperfusion injury. The portal vein was cannulated, the liver removed and perfused in a closed ex vivo system. Isolated livers were perfused either with glucose 1 g/L and 10 g/L, or with equal concentrations of alanine (n = 10 in each group). The experiment consisted of perfusion for 15 min, ischemia for 60 min, and reoxygenation during 60 min. Enzymes, glucose, lactate and bilirubin were analysed in perfusate samples. The proportion of glycogen as well as activation of caspase 3 was determined in biopsies. Alanine at a concentration of 10 g/L attenuated enzymes release in the perfusate during reoxygenation when compared to glucose-treated groups. Lactate level in the perfusate was lowest in alanine groups. Ischemia-reperfusion and mainly alanine activated apoptosis, specifically in Kupffer and endothelial cells. Alanine presents a protective effect on normothermic ischemia-reperfusion injury of the fasting rat liver when compared to glucose