Protective Effect of Glutathione Against Liver Warm Ischemia‐Reperfusion Injury in Rats is Associated with Regulation of P‐Selectin and Neutrophil Infiltration

Abstract

We examined the effects of glutathione (GSH) preconditioning through the portal vein on rat warm liver ischemia reperfusion injury (I/R injury) and investigated the mechanisms involved. In rats with warm liver I/R injury, administration of GSH by means of the portal vein before ischemia increased the 7-day survival rates of rats after liver I/R from 38% to 75%. This effect was correlated with significantly improved liver function, depressed MDA content in the liver and fewer histologic features of hepatocyte injury. Intrahepatic expression of P-selectin and infiltration of neutrophils were increased significantly after liver I/R. GSH pretreatment decreased intrahepatic MPO content and the expression of P-selectin. However, it did not significantly affect the mRNA levels for P-selectin after liver I/R. Thus, preconditioning with GSH protects the liver against I/R injury by a mechanism dependent on free radical species scavenging, down-regulation of adhesion molecule expression and inhibition of neutrophil accumulation. These findings document the potential clinical utility of GSH to improve the overall success of diverse procedures, such as liver surgery and liver transplantation. Anat Rec, 291:1016Rec, 291: -1022Rec, 291: , 2008 2008 Wiley-Liss, Inc.Key words: ischemia reperfusion injury; liver; glutathione; P-selectinHepatic warm ischemia/reperfusion (I/R) injury, which can occur in diverse settings, including liver transplantation, trauma, hemorrhagic shock, or liver surgery, is a serious clinical complication that may compromise liver function because of extensive hepatocellular loss (Liu et al., 1996;Eghtesad et al., 2003;Miras et al., 2007;Fowell and Benyon, 2008). The mechanisms responsible for liver I/R injury are not well understood. Previous Abbreviations used: I/R 5 ischemia reperfusion; GSH 5 glutathione; ALT 5 alanine aminotransferase; AST 5 aspartate aminotransferase; MPO 5 myeloperoxidase; MDA 5 malondialdehyde; ROS 5 reactive oxygen species; PMN 5 polymorphonuclear leukocytes.

Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions

“…Liver and kidney are probably the best representatives of this group. The portal vein brings blood from the intestine to the liver and, if not detoxified in the intestine, xenobiotics must be neutralized by hepatocytes [ 52 , 74 – 76 ]. In addition, the liver is an important biosynthetic organ where ROS are produced in substantial amounts as side products of energy production in the mitochondrial electron transport chain or as the result of biosyntheses involving diverse oxygenases.…”

Clinical Significance of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Liver Transplantation

“…Neutrophils are considered to be the main factor involved in the inflammatory process after reperfusion (21,22). Studies have shown that elimination of increased neutrophils or inhibition of their functions leads to a decrease in liver damage and inflammation (23)(24)(25). In the study, the neutrophil count was 5.7±2.4x10 9 /l in non-surviving patients, and 3.1± 2.05x10 9 /l in surviving patients.…”

Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats

“…GSH is the most abundant antioxidant in the cell. Ischemia-reperfusion injury depletes GSH in the tissue and supplementation with GSH has been found to reduce associated tissue damage [ 12 , 13 ]. GSH has also been found to reduce ONOO − associated injury [ 14 ].…”