Glutathione synthesis in intestinal ischaemia-reperfusion injury: effects of moderate hypothermia.
OBJECTIVE
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 of 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.
Kimura
Yukiko
Y
Department of Paediatric Surgery, Institute of Child Health, University College London, London, UK.
Pierro
Agostino
A
Eaton
Simon
S
D000818:Animals; D004912:Erythrocytes / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis*; D007036:Hypothermia, Induced; D007082:Ileum / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000628:therapy*
D005978:Glutathione