Tissue-Protective Effect of Glutamine on Hepatic Ischemia-Reperfusion Injury via Induction of Heme Oxygenase-1

Background/Aims:Glutamine showed cytoprotective activity in vitro on anoxia-reoxygenation injury via induction of heme oxygenase-1 (HO-1). We thus investigated its in vivo tissue-protective effect in a rat liver ischemia-reperfusion (I/R) model. Methods: Before the I/R procedure, animals were treated with glutamine. Liver injury was evaluated by serum liver enzymes, histological examination and apoptosis detection by transferase-mediated uridine nick end labeling staining. Meanwhile, expression and activities of HO-1 were measured by Western blot and a biochemical method. Liver blood flow was measured by using a laser Doppler flowmeter, and oxidative injury was investigated by the thio-barbituric acid-reactive substance (TBARS) assay. The inflammatory cytokine monocyte chemotactic protein (MCP)-1 was quantified by ELISA. Results: I/R caused a large increase in levels of liver enzymes, remarkably inducing the necrosis and apoptosis of liver tissue, which was markedly inhibited by glutamine, during which HO-1 was upregulated significantly, and the HO-1 inhibitor zinc protoporphyrin nullified the effect of glutamine. Liver blood flow was greatly reduced after I/R; however, it was significantly improved by glutamine. Lipid peroxidation (TBARS) in liver tissue was largely induced which was significantly lowered by glutamine. Similar results were also observed for the production of MCP-1. Conclusion: Glutamine protected tissue against oxidative injury during rat hepatic I/R, by induction of HO-1 to fulfill antioxidative and antiapoptotic effects. Copyright (c) 2012 S. Karger AG, Basel