Copper-indomethacinate associated with zwitterionic phospholipids preventsenteropathy in rats - Effect on inducible NO synthase

Intestinal toxicity exerted by indomethacin was compared to that induced by copperindomethacinate, free or associated to zwitterionic phospholipids. A single high dose of indomethacin (15 or 20 mg/kg), copper-indomethacinate (15 or 20 mg/kg), or copperindomethacinate liposomes or nanocapsules (15 mg /kg) was orally administered. Then 24 hr later jejunoileal tissue was taken for macroscopic observation, ex vivo nitrite production, and determination of myeloperoxydase and iNOS activities. Antiinflammatory activity of the d rugs was investigated using the carrageenan-induced paw edema model. Indome thacin induced penetrating ulcerations of the intestine that were maximal a t hour 24. Copper-indomethacinate induced significantly less ulceration tha n indomethacin with no significant difference in MPO and iNOS activities. T he injurious action of indomethacin on the small intestine was further redu ced when copper-indomethacinate was administered as the phospholipid-associ ated state while similar anti-inflammatory action was observed on rat paw e dema. The antiulcerogen effect of copper-indomethacinate seems to be linked to its free radical scavenging effect without any modification of nitric o xide release.