Participation of xanthine-xanthine oxidase system and neutrophils in development of acute gastric mucosal lesions in rats with a single treatment of compound 48/80, a mast cell degranulator

The participation of xanthine-xanthine oxidase and neutrophils in the devel opment of acute gastric mucosal lesions was examined in rats injected once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appe ared 0.5 hr after compound 48/80 injection and developed at 3 hr. The forma tion of gastric mucosal lesions at 0.5 hr after compound 48/80 injection wa s prevented by pretreatment with anti-neutrophil antiserum and NPC 14686, a n antiinflammatory agent, but not with allopurinol, a xanthine oxidase inhi bitor. The development of gastric mucosal lesions at 3 hr after compound 48 /80 injection was prevented by pretreatment with anti-neutrophil antiserum, NPC 14686, or allopurinol. Increases in the activities of gastric mucosal xanthine oxidase and myeloperoxidase, an index of neutrophil infiltration, and the content of lipid peroxide occurred 0.5 hr after compound 48/80 inje ction, and these increases were enhanced at 3 hr. The increases in gastric mucosal myeloperoxidase activity and lipid peroxide content at 0.5 hr after compound 48/80 injection were attenuated by pretreatment with anti-neutrop hil antiserum and NPC 14686, while only the increase in gastric mucosal xan thine oxidase activity at the same time point was arrested by allopurinol p retreatment. The increases in gastric mucosal xanthine oxidase and myeloper oxidase activities and lipid peroxide content at 3 hr after compound 48/80 treatment were attenuated by pretreatment with anti-neutrophil antiserum, N PC 14686, or allopurinol. When compound 48/80-injected rats were treated wi th allopurinol at 0.5 hr after compound 48/80 injection, the progression of gastric mucosal lesions at 3 hr after the injection was almost completely prevented with inhibition of the increases in gastric mucosal xanthine oxid ase and myeloperoxidase activities and lipid peroxide content. These result s indicate that in rats with a single compound 48/80 treatment neutrophils infiltrated into the gastric mucosa participated in the development of acut e gastric mucosal lesions and that the xanthine-xanthine oxidase system in the gastric mucosa participated in the progression rather than the formatio n of the gastric mucosal lesions.