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. Materials and Methods: Male Wistar rats underwent normothermic, 60min segmental liver ischemia followed by 24h 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 500mg/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 (PM₁₀) of the flow graph showed improving tendency (RA: P = 0.096; PM₁₀: 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 24h prior to I-R injury could be an effective method to reduce liver damage caused by hepatic inflow occlusion.