Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase.
Aspirin (ASA) represents an important risk factor for gastric mucosal injury. Recently, vitamin C releasing aspirin (ASA-VitC) has been shown to reduce gastric toxicity of ASA in animal model of gastric injury. The aim of the present study was to compare the effect of ASA and ASA-VitC on the gastric mucosal damage before and after Helicobacter pylori (Hp) eradication in 10 young healthy Hp-positive volunteers. All subjects underwent endoscopy at day 0 (before ASA or ASA-VitC treatment) and at day 3 following treatment (1.6 g ASA/day or 1.6 g ASA + 0.96 g Vit C/day). In addition, in vitro experiments were performed in which gastric mucosal cell line (MKN-45 cells) was incubated with ASA or ASA-VitC alone or in combination with H.pylori. Expression of constitutive and inducible NO synthase (cNOS, iNOS) was analyzed by Western blot. Moreover, COX-2 expression was analyzed in gastric biopsies at mRNA and protein level by RT-PCR and Western blot, respectively. In humans, treatment with ASA-VitC induced significantly less gastric mucosal lesions than plain ASA. Furthermore, in comparison to plain ASA, ASA-VitC caused stronger inhibition of cNOS and increase in iNOS expression in the gastric mucosa. In vitro studies demonstrated a significant increase in iNOS expression in MKN-45 cells incubated with Hp. This effect was aggravated by the addition of ASA, but not ASA-VitC, to MKN-45 cells incubated with H.pylori. Both ASA and ASA-VitC stimulated the COX-2 expression in the gastric mucosa. We conclude that ASA-VitC in comparison with ASA induces less gastric mucosal damage and this protective effect may be due to its inhibitory effect on iNOS expression.
Konturek
P C
PC
First Department of Medicine, University Erlangen-Nuremberg, Germany. pkonturek@aol.com
Kania
J
J
Hahn
E G
EG
Konturek
J W
JW
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004347:Drug Interactions; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000201:enzymology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D001205:Ascorbic Acid; D001241:Aspirin