The effects of aspirin on antioxidant defences of cultured rat gastric mucosal cells

Background: Helicobacter pylori-associated inflammation leads to exposure o f the gastric epithelium to reactive oxygen species (ROS) generated in the gastric mucosa. In some pathological conditions, such as those induced by n onsteroidal anti-inflammatory drugs, the gastric mucosa may become more sus ceptible to ROS. Aim: To examine the effects of aspirin on antioxidant defenses as well as o n oxidant injury in cultured rat gastric mucosal cells. Methods: Primary monolayer cultures of rat gastric fundic mucosa were expos ed to an ROS-generating system, hypoxanthine/xanthine oxidase (XOD). Cytoto xicity was quantified by measuring Cr-51 release from prelabelled cells. Th e effects of aspirin on antioxidants and on cellular injury brought about b y the ROS-generating system were determined. Results: XOD, in the presence of hypoxanthine, caused a dose-dependent incr ease in specific Cr-51 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 mu M) produced a dose-dependent i ncrease in XOD-induced Cr-51 release. Aspirin did not affect cellular gluta thione content or activity of glutathione peroxidase, glutathione reductase or endogenous catalase. By contrast, aspirin caused a dose-dependent reduc tion in mucus synthesis, as assessed by incorporation of [H-3]-glucosamine hydrochloride into the cells. Conclusions: Aspirin at: therapeutically relevant concentrations rendered c ultured gastric cells more susceptible to subsequent exposure to ROS. Aspir in affected neither the glutathione redox cycle nor catalase activity. Thus , the enhancement of ROS-induced injury by aspirin may be accomplished thro ugh diminished gastric mucus synthesis, since mucus is a potent scavenger o f ROS. These findings provide insight into how gastric inflammation and inj ury (such as that induced by H. pylori infection) in human gastric mucosa i s modulated by the administration of nonsteroidal antiinflammatory drugs.