Oxidative stress in gastric mucosal injury: role of platelet-activating factor-activated granulocytes.
Temporal and spatial changes due to oxidative stress in the rat gastric mucosa were visualized and quantified during the process of mucosal hemorrhagic change. The fluorescence associated with dichlorofluorescein (DCF), a hydroperoxide-sensitive fluorochrome, increased 30 min after repeated electrical stimuli to the gastric artery. The increase in the fluorescence was enhanced in the area between two adjacent collecting venules. The content of platelet-activating factor (PAF), the activity of myeloperoxidase (MPO) in the gastric mucosa, the area of mucosal lesions, and the luminol-dependent chemiluminescence activity in zymosan-treated blood samples, obtained from the gastric vein, were measured and found to increase significantly 30 min after the stimuli. The intravenous injection of CV-6209, a PAF antagonist, 5 min prior to the stimuli significantly inhibited the DCF activation, the increases in PAF level and MPO activity, the mucosal hemorrhagic change, and the elevation in chemiluminescence activity. In addition, continuous infusion of superoxide dismutase also inhibited all these changes, except for chemiluminescence activity. These results suggest that oxygen radicals derived from PAF-activated granulocytes induce oxidative stress, and that oxidative changes are actually implicated in the pathogenesis of gastric mucosal injury.
Fukumura
D
D
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kurose
I
I
Miura
S
S
Tsuchiya
M
M
Ishii
H
H
D000818:Animals; D004558:Electric Stimulation / Q000009:adverse effects; D005452:Fluoresceins; D016166:Free Radical Scavengers / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008163:Luminescent Measurements; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology
D005452:Fluoresceins; D016166:Free Radical Scavengers; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; C029569:diacetyldichlorofluorescein; D009195:Peroxidase; D013482:Superoxide Dismutase