Reduction of liver ischemia-reperfusion injury via glutamine pretreatment

J Surg Res. 2011 Mar;166(1):95-103. doi: 10.1016/j.jss.2009.09.047. Epub 2009 Oct 22.

Abstract

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, 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.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Dipeptides / pharmacology*
  • Disease Models, Animal
  • Glutamine / pharmacology*
  • In Situ Nick-End Labeling
  • Ischemic Preconditioning / methods*
  • Laser-Doppler Flowmetry
  • Liver Circulation / physiology
  • Liver Diseases / drug therapy*
  • Liver Diseases / pathology
  • Liver Diseases / physiopathology
  • Male
  • Microcirculation / physiology
  • Oxidation-Reduction
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology

Substances

  • Dipeptides
  • Reactive Oxygen Species
  • Glutamine
  • Parp1 protein, rat
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • alanylglutamine