title: The effects of aspirin on antioxidant defences of cultured rat gastric mucosal cells.
abstract: BACKGROUND
  Helicobacter pylori-associated inflammation leads to exposure of the gastric epithelium to reactive oxygen species (ROS) generated in the gastric mucosa. In some pathological conditions, such as those induced by nonsteroidal anti-inflammatory drugs, the gastric mucosa may become more susceptible to ROS.
  
  
  OBJECTIVE
  To examine the effects of aspirin on antioxidant defenses as well as on oxidant injury in cultured rat gastric mucosal cells.
  
  
  METHODS
  Primary monolayer cultures of rat gastric fundic mucosa were exposed to an ROS-generating system, hypoxanthine/xanthine oxidase (XOD). Cytotoxicity was quantified by measuring 51Cr release from prelabelled cells. The effects of aspirin on antioxidants and on cellular injury brought about by the ROS-generating system were determined.
  
  
  RESULTS
  XOD, in the presence of hypoxanthine, caused a dose-dependent increase in specific 51Cr release, which corresponded to the ability of XOD to produce ROS (as assessed by the production of uric acid from hypoxanthine). Incubation of cells with aspirin (1-100 microM) produced a dose-dependent increase in XOD-induced 51Cr release. Aspirin did not affect cellular glutathione content or activity of glutathione peroxidase, glutathione reductase or endogenous catalase. By contrast, aspirin caused a dose-dependent reduction in mucus synthesis. as assessed by incorporation of [3H]-glucosamine hydrochloride into the cells.
  
  
  CONCLUSIONS
  Aspirin at therapeutically relevant concentrations rendered cultured gastric cells more susceptible to subsequent exposure to ROS. Aspirin affected neither the glutathione redox cycle nor catalase activity. Thus, the enhancement of ROS-induced injury by aspirin may be accomplished through diminished gastric mucus synthesis, since mucus is a potent scavenger of ROS. These findings provide insight into how gastric inflammation and injury (such as that induced by H. pylori infection) in human gastric mucosa is modulated by the administration of nonsteroidal anti-inflammatory drugs.
authors.affiliation: Department of Gastroenterology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mitobe
authors.forename: H
authors.initials: H
authors.lastname: Hiraishi
authors.forename: T
authors.initials: T
authors.lastname: Sasai
authors.forename: T
authors.initials: T
authors.lastname: Shimada
authors.forename: A
authors.initials: A
authors.lastname: Terano
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D008297:Male; D009093:Mucus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase; D005978:Glutathione; D001241:Aspirin