ROLE OF NEUTROPHILS IN INDOMETHACIN-INDUCED GASTRIC-MUCOSAL LESIONS IN RATS

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically importa nt gastric damage by several mechanisms. In order to evaluate the role of neutrophil infiltration in lesion formation, tissue myeloperoxidas e activities were assessed in different gastric layers of the stomach both in rats with normal neutrophil levels and in neutropenic rats. Sp rague-Dawley rats were treated either with indomethacin (Indo; 25 mg/k g, s.c.) or the vehicle. A group of rats were made neutropenic by admi nistration of methotrexate (MTX; 2.5 mg/kg i.p.) once a day for 3 days . The stomachs were removed for the determination of lesion index, glu tathione, lipid peroxide levels, protein oxidation and tissue myeloper oxidase activities. MTX treatment appeared to reduce neutrophil infilt ration significantly while producing insignificant effects on eosinoph ils and macrophages. Indo administration caused multiple gastric lesio ns and treatment with MTX significantly reduced lesion index. In rats treated with Indo, neither glutathione nor LP levels showed any signif icant changes but the protein oxidation was significantly higher than that of other groups. The MPO level of gastric mucosa was increased in Indo-treated rats and reversed by MTX pretreatment. The results of th e present study indicate that neutrophil infiltration in the gastric m ucosa of rats may be involved in the pathogenesis of NSAID-induced gas tric mucosal injury, but no correlation was found between lesion forma tion and protein oxidation in the gastric mucosa.