Gastric mucosal injury caused by hemorrhagic shock and reperfusion: protective role of the antioxidant glutathione.
Oxygen free radicals have been implicated as mediators of gastric mucosal injury caused by ischemia/reperfusion. We investigated the role of exogenous and endogenous glutathione (reduced glutathione, GSH) in gastric mucosal injury associated with hemorrhagic shock and reperfusion. Mucosal GSH content was found to be consistently higher in the antrum than in the corpus. Ischemia (hemorrhage to 25 to 30 mm Hg) followed by retransfusion of shed blood, but not ischemia alone, caused a marked drop in gastric mucosal GSH and gross mucosal injury, which was confined to the corpus and spared the antrum. Chemical depletion of gastric mucosal GSH with diethylmaleate or inhibition of GSH synthesis with buthionine sulfoximine increased mucosal injury in the corpus and also rendered the antral mucosa susceptible to ischemia/reperfusion injury. Pretreatment with exogenous GSH provided marked protection against gross mucosal ischemia/reperfusion injury and prevented the ischemia/reperfusion-induced drop in mucosal GSH. These data suggest that the mucosal availability of the antioxidant GSH is an important protective factor against the development of gastric mucosal ischemia/reperfusion injury and supports a major role of oxygen radical release in the pathogenesis of gastric ischemia/reperfusion injury.
Stein
H J
HJ
Department of Surgery, University of the Witwatersrand, Johannesburg, South Africa.
Hinder
R A
RA
Oosthuizen
M M
MM
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001803:Blood Transfusion; D019328:Buthionine Sulfoximine; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000502:physiology*; D007511:Ischemia / Q000473:pathology; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011706:Pyloric Antrum / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control; D012771:Shock, Hemorrhagic / Q000473:pathology*; D013270:Stomach / Q000473:pathology
D000963:Antimetabolites; D008298:Maleates; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C014476:diethyl maleate; D005978:Glutathione