Glutathione synthesis in intestinal ischaemia-reperfusion injury: effects of moderate hypothermia

Purpose: Intestinal glutathione (GSH) levels are dramatically decreased after intestinal ischaemia and reperfusion (I/R) injury. Hypothermia has protective effects during I/R injury. The aim of this study was to determine the effects or intestinal I/R and hypothermia on GSH synthesis in erythrocytes and ileum. Methods: Adult male rats (n = 8 per group) underwent superior mesenteric artery occlusion for 60 minutes followed by 90-minute reperfusion or sham operation (control) for 150 minutes.. Animals were maintained at either normothermia or moderate hypothermia. All rats received intravenous d(2)-glycine as a GSH synthesis precursor until the end of the experiment. Ileum and erythrocyte samples were analysed for enrichment of d(2)-glycine and GSH. The ratio of d(2)-enrichment in GSH to that in the glycine precursor represents GSH synthesis. Results: In erythrocytes, GSH synthesis was increased by normothermic I/R but decreased to control levels by hypothermic I/R. Ileal GSH synthesis was unaffected by hypothermia in sham animals but was significantly decreased by I/R at normothermia (P < .001). Hypothermic I/R, however, caused significant preservation of GSH synthesis so that GSH/Gly ratio was similar to controls and significantly higher than I/R at normothermia (P < .05). Conclusions: Intestinal I/R leads to decreased ileal GSH synthesis, which could contribute to GSH depletion. Hypothermia preserves GSH synthesis during intestinal I/R injury, and this could protect from Further tissue damage. We speculate that reactive species released during I/R injury impair the enzymes of GSH synthesis, whereas these enzymes are protected by moderate hypothermia. (C) 2009 Elsevier Inc. All rights reserved.