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

Citation
T. Pohle et al., Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans: gastroprotection by vitamin C, ALIM PHARM, 15(5), 2001, pp. 677-687
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"da verificare
Journal title
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
ISSN journal
0269-2813 → ACNP
Volume
15
Issue
5
Year of publication
2001
Pages
677 - 687
Database
ISI
SICI code
0269-2813(200105)15:5<677:ROROMI>2.0.ZU;2-Z
Abstract
Background: The roles of active oxygen metabolites and anti-oxidative defen ses in aspirin (ASA)-induced gastric damage have been little studied. Aim: We determined the effects of aspirin (400 mg b.d.) with or without vit amin C (480 mg b.d.) for 3 days on gastric mucosa in human volunteers. Methods: Gastric injury was assessed endoscopically; gastric blood flow, re active 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, lip id peroxidation, and myeloperoxidase activity. It also resulted in a suppre ssion of gastric blood flow, intragastric vitamin C levels, superoxide dism utase and glutathione peroxidase activities. The addition of vitamin C sign ificantly attenuated gastric damage and reversed the effects of ASA on thes e parameters. Superoxide dismutase and glutathione peroxidase mRNAs were de creased in ASA-treated subjects; the addition of vitamin C restored their r egular 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 neutrop hils to be the major source of these radicals; (iii) vitamin C protects aga inst ASA-induced damage due to its anti-oxidizing activity.