1. In vitro studies of the potential antioxidant activity of the selective cyclo-oxygenase-2 inhibitor celecoxib and the non-steroid anti-inflammatory drug amtolmetin guacyl (AMG) were carried out. The study included experiments on the ability of these drugs to affect some indices of the oxidative stress [lipid peroxidation (LP), activity of antioxidant enzymes, glutathione (GSH) level] in rat stomach and colon mucosa and in liver. 2. Celecoxib and AMG did not change the activity of the enzymes GSH-peroxidase, oxidased glutathione (GSSG)-reductase and glucose-6-phosphate-dehydrogenase, as well as the GSH level in all tissue preparations. An increased superoxide dismutase (SOD) activity and a tendency to a decreased Fe/ascorbic acid-induced LP in stomach and colon mucosa were found, but only in the presence of AMG. 3. In the liver, both celecoxib and AMG decreased spontaneous and Fe/ascorbic acid-induced LP. SOD activity was enhanced only in the presence of AMG. 4. Experiments aimed at studying celecoxib and AMG in free oxygen radical-generating systems were also carried out. AMG and tolmetin (the main metabolite of AMG) inhibited OH*-provoked deoxyribose degradation in a Fenton system. Celecoxib had no effect on free radicals when tested in the same system. 5. In conclusion, the results of the present in vitro studies suggest that AMG and celecoxib possess antioxidant and metal-chelating abilities, which might contribute to their beneficial effects.

1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl, a pro-drug of the NSAID tolmetin, on lipid peroxidation, glutathione levels and activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) in rat gastric mucosa, colon mucosa and liver, were compared with the effects of non-selective (indomethacin, diclofenac) and COX-2 selective (celecoxib) NSAIDs. 2. Indomethacin treatment led to an increase in lipid peroxidation, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities and to a decrease in catalase activity and glutathione levels in gastric mucosa. In contrast, amtolmetin guacyl treatment was without effects in gastric and colon mucosa, or liver from control animals. Like amtolmetin guacyl, celecoxib had no effect on the lipid peroxidation, or on enzyme and non-enzyme antioxidant defence systems in gastric mucosa. 3. It is suggested that the lack of pro-oxidant effects in vivo associated with amtolmetin guacyl treatment contribute improved gastric tolerability.