Gastric damage following local intra-arterial administration of reactive oxygen metabolites in the rat.
1. The effects of reactive oxygen metabolites on the rat gastric mucosa following close-arterial infusion into the left gastric artery have been determined by macroscopic and histological assessment. 2. Local intra-arterial infusion of hydrogen peroxide (0.6-1.3 mumol kg-1 min-1) induced mucosal injury, characterised by areas of pronounced disruption and haemorrhage, which was prevented by concurrent intravenous administration of catalase. 3. Local infusion of the superoxide generating system xanthine-oxidase and hypoxanthine likewise induced extensive haemorrhagic damage and necrosis of the mucosa. Prolonged incubation of this mixture (10 min) before administration, significantly reduced the degree of injury, indicating the lability of the products so formed. 4. The gastric mucosal injury induced by the superoxide generating system was inhibited by concurrent local infusion of superoxide dismutase (96 u kg-1 min-1), as was the associated increase in mucosal permeability to radiolabelled albumin. 5. Administration of catalase did not inhibit the gastric mucosal damage induced by infusion of xanthine oxidase-hypoxanthine, yet augmented the protective effects of a low dose of superoxide dismutase (46 u kg-1 min-1 i.a.). 6. These findings directly confirm that reactive oxygen metabolites can induce extensive gastric mucosal injury, supporting their role in the pathogenesis of gastric damage following ischaemia and hypotensive shock.
Esplugues
J V
JV
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
Whittle
B J
BJ
D000818:Animals; D005753:Gastric Mucosa / Q000033:anatomy & histology / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000633:toxicity; D007042:Hypoxanthines / Q000378:metabolism; D007261:Infusions, Intra-Arterial; D007457:Iodine Radioisotopes; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000633:toxicity; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D007042:Hypoxanthines; D007457:Iodine Radioisotopes; D013481:Superoxides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen