Abstract:Indomethacin is a non-steroidal anti-inflammatory drug, used in the treatment of many inflammatory diseases.The major side effect limiting its clinical use is the gastric damages. The aim of this work was to study the possible protective effects of vitamin c and ranitidine on the gastric lesion induced by indomethacin in adult albino rats. Forty adult albino rats were divided into five equal groups: The control group, indomethacin group, indomethacin plus vitamin c, indomethacin plus ranitidine, and indomethacin plus both vitamin c and ranitidine. In the control group, the rats received normal daily diet for 10 days. In the indomethacin group, the rats were treated with indomethacin for 10 consecutive days. In indomethacin plus vitamin c group, the rats were treated with indomethacin as the second group, in addition to vitamin c, 5 minutes prior to the indomethacin for 10 days. In the fourth group, the rats were treated with indomethacin as the second group, and then received ranitidine 5 min prior to the indomethacin, for 10 consecutive days. The last group received the indomethacin as the second group, and then received vitamin c and ranitidine, 5 min prior to the indomethacin, daily for 10 days. After 10 days from the treatment, all the rats were anaesthetized, and the specimens of the stomach were prepared for light and electron microscopies. Indomethacin produced erosions and ulcerations of the gastric mucosa. There are focal areas of degeneration and inflammatory cell infiltration in the lamina propria, the gastric gland cells showed vacuolations, degeneration and disappearance of their nuclei. It also induced dilatation and congestion of the blood capillaries in the submucosa of the stomach, also the surface mucin layer was decreased in its thickness. Electron microscopic examination showed that: Indomethacin induced degeneration and vacuolations of the gastric gland cells, with degeneration of their mitochondria and nuclei. Chief cells showed abnormalities in their zymogenic granules which appeared with dark central part and pale periphery. Administration of vitamin c and ranitidine prior to the indomethacin intake reduced the pathogenic changes of the gastric wall, with slight return to the picture of the control group.