Gastric mucosal lesions induced by hemorrhagic shock in baboons. Role of oxygen-derived free radicals.
In this study we sought to define the role of oxygen-derived free radicals during ischemia and reperfusion in the production of acute damage to the gastric mucosa of baboons. The protective effect of the xanthine oxidase inhibitor, allopurinol, the superoxide scavenger, superoxide dismutase (SOD), and a long-acting SOD-albumin was determined. Mucosal damage was evaluated using light and scanning electron microscopy. Evidence for oxidative insult to the gastric mucosa was sought by measuring tissue concentrations of reduced (GSH) and oxidized (GSSG) glutathione. Gastric mucosal blood flow was estimated using the microsphere technique. A similar pattern of tissue damage was found at the end of ischemia in all three groups. Thirty minutes after reperfusion, severe mucosal damage (grade 3) increased only in the untreated control. In the two treated groups, grade 3 damage remained unchanged during reperfusion and a decrease in the percentage of moderate damage (grade 2) was seen. Both GSH and GSSG tissue concentrations were lower in the untreated controls as compared to the scavenger-treated groups, making it questionable whether GSH/GSSG tissue levels adequately reflect oxidative stress. We conclude that in our ischemia-reperfusion model the generation of oxygen-derived free radicals produces mucosal damage and prevents the restitution of moderate mucosal damage during reperfusion. In ischemia, factors other than free radicals seem to be responsible for mucosal damage. The protective effect of allopurinol and SOD was not mediated by changes in gastric mucosal blood flow.
von Ritter
C
C
Department of Surgery, University of the Witwatersrand, Johannesburg, South Africa.
Hinder
R A
RA
Oosthuizen
M M
MM
Svensson
L G
LG
Hunter
S J
SJ
Lambrecht
H
H
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D005609:Free Radicals; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D007511:Ischemia / Q000473:pathology*; D008855:Microscopy, Electron, Scanning; D010100:Oxygen / Q000633:toxicity*; D010215:Papio; D012771:Shock, Hemorrhagic / Q000473:pathology*; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013997:Time Factors
D005609:Free Radicals; D000493:Allopurinol; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide