Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans: gastroprotection by vitamin C.
BACKGROUND
The roles of active oxygen metabolites and anti-oxidative defenses in aspirin (ASA)-induced gastric damage have been little studied.


OBJECTIVE
We determined the effects of aspirin (400 mg b.d.) with or without vitamin C (480 mg b.d.) for 3 days on gastric mucosa in human volunteers.


METHODS
Gastric injury was assessed endoscopically; gastric blood flow, reactive oxygen release (quantified by chemiluminescence), lipid peroxidation, myeloperoxidase, superoxide dismutase and glutathione peroxidase activity and intragastric vitamin C content were measured. Expression of superoxide dismutase and glutathione peroxidase mRNAs was assayed semi-quantitatively.


RESULTS
ASA produced erosions, a marked increase in chemiluminescence, lipid peroxidation, and myeloperoxidase activity. It also resulted in a suppression of gastric blood flow, intragastric vitamin C levels, superoxide dismutase and glutathione peroxidase activities. The addition of vitamin C significantly attenuated gastric damage and reversed the effects of ASA on these parameters. Superoxide dismutase and glutathione peroxidase mRNAs were decreased in ASA-treated subjects; the addition of vitamin C restored their regular levels.


CONCLUSIONS
(i) free radical-induced lipid peroxidation and suppression of antioxidizing enzymes play an important role in gastric damage induced by aspirin; (ii) increased myeloperoxidase activity suggests activated neutrophils to be the major source of these radicals; (iii) vitamin C protects against ASA-induced damage due to its anti-oxidizing activity.
Pohle
T
T
Department of Medicine B, University of Münster, Münster, Germany. pohley@uni-muenster.de
Brzozowski
T
T
Becker
J C
JC
Van der Voort
I R
IR
Markmann
A
A
Konturek
S J
SJ
Moniczewski
A
A
Domschke
W
W
Konturek
J W
JW
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D001205:Ascorbic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage* / Q000737:chemistry; D015415:Biomarkers; D005260:Female; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D013482:Superoxide Dismutase / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D005609:Free Radicals; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; D001241:Aspirin