Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase

J Physiol Pharmacol. 2006 Nov;57 Suppl 5:125-36.

Abstract

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Ascorbic Acid / administration & dosage*
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects*
  • Aspirin / antagonists & inhibitors
  • Cells, Cultured
  • Cyclooxygenase 2 / biosynthesis
  • Drug Interactions
  • Female
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / enzymology*
  • Gastric Mucosa / microbiology
  • Helicobacter Infections / enzymology
  • Helicobacter pylori
  • Humans
  • Male
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • RNA, Messenger
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Ascorbic Acid
  • Aspirin