Role of elastase and active oxygen species in gastric mucosal injury induced by aspirin administration in Helicobacter pylori-infected Mongolian gerbils.

Abstract

BACKGROUND: H. pylori infection potentiates aspirin-induced gastric mucosal injury by mechanisms that include accumulation of activated neutrophils. AIM: To determine the role of elastase and active oxygen species (AOS) produced by activated neutrophils in the gastric mucosal injury induced by administration of acidified aspirin to H. pylori-infected Mongolian gerbils. METHODS: H. pylori ATCC43504 culture broth was administered by oral gavage to male Mongolian gerbils at 7 weeks of age. After 4 weeks, acidified aspirin (400 mg/kg) was administered orally, and 3 h later, the total area of gastric erosions, myeloperoxidase (MPO) activity (an index of neutrophil accumulation), thiobarbituric acid-reactive substances (TBARS, an index of lipid peroxidation), and KC/GRO (a chemo-attractive cytokine in rodents) were measured in gastric mucosa. To determine the role of elastase or AOS derived from neutrophils in these circumstances, ONO-5046 (an elastase inhibitor), a combination of superoxide dismutase (SOD) and catalase (scavengers of AOS), and polaprezinc (an anti-ulcer agent with anti-inflammatory effects) were administered before aspirin. RESULTS: ONO-5046 inhibited the increase in gastric erosions and mucosal TBARS induced by administration of aspirin to H. pylori-infected gerbils, but not the increases in MPO activity or KC/GRO contents. A combination of SOD and catalase or polaprezinc significantly reduced gastric erosions, TBARS concentrations, MPO activity and KC/GRO concentration. CONCLUSIONS: These results suggest that neutrophil-derived-elastase and -oxidants play an important role in the gastric mucosal injury induced by administration of aspirin to H. pylori-infected gerbils.