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

Abstract

Gastric bleeding and the formation of gastrointestinal ulcers and erosions are the most adverse reactions in patients subjected to therapy with non-steroidal antiin¯ammatory drugs (NSAIDs) such as aspirin (ASA). 1 As shown in numerous studies, ASA damages the gastric mucosa due to the inhibition of protective prostaglandins and direct action on this mucosa. This results in enhancement in acid back-diffusion and microvascular injury accompanied by the activation of neutrophils that lead to excessive release of oxygen radicals. 2 Recent work in animal models revealed that administration of NSAIDs such as indometacin or ASA caused the release of reactive oxygen metabolites and enhanced the lipid peroxidation, but the importance of these intermediates in ASA-induced injury of human gastric mucosa has been little studied. 3 It is known that under physiological conditions in biological systems, approximately 95% of molecular oxygen undergoes controlled reduction through the addition of four electrons in the mitochondrial cytochrome oxidase system to form water. The remaining molecular SUMMARY 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¯ow, reactive oxygen release (quanti®ed 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 myeloper-

Water-Soluble Vitamin Deficiencies in Complicated Peptic Ulcer Patients Soon after Ulcer Onset in Japan

“…Ascorbic acid has been shown to have gastroprotective effects in different experimental models of gastric mucosal injury induced by stress, various antirheumatic drugs, or ethanol (16)(17)(18). It has also been suggested that ascorbic acid supplementation is protective against not only indomethacin-induced gastric ulcers in rats (19) but also aspirin-induced gastric mucosal damage in healthy volunteers with (8) or without H. pylori infection (20). Ascorbic acid supplementation has also been shown to attenuate the H. pylori-induced inflammatory response (21).…”

The effect of low dose aspirin intake on gastro-duodenal mucosa, and protective effects of GSH-vitamin C-E

“…Along with these statements, we hypothesized whether administration of glutathionevitamin C and E as upper gastrointestinal-protective agents to rats exposed to L-ASA on a long-term basis could be diminished or prevented gastro-duodenal mucosal injuries. As last scientific reports have implied that vitamin C and E possess an inhibitory effect on the activation of neutrophils and oxidative stress in aspirininduced gastric damage [3,4,24]. The induction of Hsp in the case of oxidative stress, oxidative damage to proteins could be the activating signal [14].…”

“…In response to NSAID, neutrophils are recruited to the site of inflammation and generate excessive reactive oxygen and nitrogen species and proteases. Reactive free radicals cause lipid peroxidation, protein oxidation and DNA injury and then cell or tissue damage when antioxidant defense mechanisms are not always adequate to neutralize the production of free radicals, resulting in a condition termed oxidative stress [3,4,5]. Hsp 70 expression is up regulated upon exposure to oxidative damage.…”

Anti-ulcer activity of Medicinal Herbs - A Review

“…Thus, Cissus quadrangularis has potential usefulness for treatment of peptic ulcer disease. [30][31][32][33][34][35][36][37][38] …”