Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans: gastroprotection by vitamin C

Autor: Thomas Brzozowski, Stanislaw J. Konturek, Wolfram Domschke, André Markmann, Andrzej Moniczewski, I. R. Van Der Voort, Jan C. Becker, Jan W. Konturek, Thorsten Pohle
Rok vydání: 2001
Předmět:
Zdroj: Alimentary Pharmacology & Therapeutics. 15:677-687
ISSN: 0269-2813
Popis: Background: The roles of active oxygen metabolites and anti-oxidative defenses in aspirin (ASA)-induced gastric damage have been little studied. Aim: 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.
Databáze: OpenAIRE
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