Protection by metal complexes with SOD-mimetic activity against oxidative gastric injury induced by indometacin and ethanol in rats

We have investigated the protective effect or oral administration of copper and manganese complexes with superoxide dismutase (SOD)-mimetic activity a gainst oxidative gastric mucosal injury induced by the non-steroidal antiin flammatory drug indometacin with ethanol in the rat. The total area of the gastric lesions and lipid peroxidation were significantly increased 1 h aft er oral administration of indometacin (15 mg/kg) and ethanol, indicating in acute oxidative injury. The activities of SOD, catalase (CAT), glutathione -S-transferase (GST) and glutathione content were significantly decreased i n the gastric mucosa by indometacin plus ethanol. Manganese or copper compl exes showed SOD-mimetic activity. Pretreatment with these complexes protect ed against gastric mucosal lesions and decreased lipid peroxides, as well a s attenuating the decrease in the activities or SOD, CAT and GST in gastric mucosa. These findings suggest that active oxygen species and lipid peroxi dation play an important role in the pathogenesis of gastric mucosal injury induced by indometacin. In addition, we have shown that Mn and Cu complexe s have gastroprotective properties against ulceration induced by indometaci n plus ethanol. The present results suggest that appropriate copper or mang anese complex supplementation may potentially provide prophylaxis or therap y for some pathologies associated with excessive free radical production an d inhibited SOD activity.