Autofluorescence in indomethacin-induced gastric mucosal lesions in rats

Autofluorescence observations enable scientists to sensitively identify var ious lesions. Non-steroidal anti-inflammatory drugs such as aspirin and ind omethacin are well known to induce gastric mucosal injuries. Our purpose wa s to clarify whether the observation of mucosal autofluorescence could help us to recognize indomethacin-induced gastric lesion formation. Gastric muc osal fluorescence intensity and gastric lesion scores were time-sequentiall y measured after indomethacin treatment in rats. To identify the localizati on of autofluorescent substances, stomach cryosections were observed with a n epifluorescence microscope. Fluorescent substances from damaged tissue we re also analyzed by high-performance liquid chromatography. In addition, to elucidate whether oxidative stress directly generates fluorescent substanc es from heme, we investigated the reaction between hydrogen peroxide and he moglobin in a cell-free system. Treatment with indomethacin induced gastric lesions by tissue peroxidation, with mucosal fluorescence intensity increa sing time-dependently. The fluorescence products were mesoporphyrin and pro toporphyrin, and they were localized in disrupted mucosal tissue. In the ce ll-free system, porphyrins were directly generated by hydrogen peroxide fro m hemoglobin. These findings indicate that indomethacin treatment increased the intensity of porphyrin fluorescence. Gastric mucosal lesion formation can be sensitively detected with fluorescence observations.