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

Abstract

H. pylori infection potentiates aspirin-induced gastric mucosal injury by mechanisms that include accumulation of activated neutrophils. 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. 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. 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. 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.