Invesgation of the effect of metformin on indomethacin- and ethanol-induced gastric ulcer models in rat

Aim: To examine the effect of metformin -widely used in the treatment of type II diabetes mellitus- pre-treatment on different gastric ulcer models. Material and method: Two different ulcer models were induced in male Sprague- Dawley rats (280-450 g) by indomethacin (80 mg/kg) or absolute ethanol (5 ml/kg) given orally. Metformin (500 mg/kg) or ranitidine (50 mg/kg) was administered orally for three days prior to ulcerogenic agents. After decapitation on day-3, stomachs were evaluated macroscopically and microscopically. Oxidant and antioxidant parameters were determined and apoptosis was evaluated. Cytokine levels were measured in the serum. Gastric blood flow was measured via laser-doppler flowmeter before decapitation in other groups of rats. One-way ANOVA and Tukey-Kramer multiple comparison tests were used for statistical analysis. p<0,05 was considered significant. Results: Metformin reduced lesions macroscopically (p<0,001) and microscopically (p<0,1) in ethanol groups. While chemiluminescence increased in ethanol group compared to control showed a reduction with metformin (p<0,05 and p<0,001), gastric blood flow increased compared to untreaed group (p<0,01). Increased lipid peroxidation in ethanol group was reduced by metformin (p<0,01). Apoptotic index (p<0,001), which was higher in ethanol group compared to control, diminished by with metformin (p<0,001). In indomethacin group, metformin reduced lesions microscopically (p<0,05). While high chemiluminescence in indomethacin group decreased by metformin (p<0,01 and p<0,05), gastric blood flow improved compared to untreated group (p<0,05). Apoptotic index was lower in metformin administered indomethacin group than untreated group (p<0,001). Glutathione which decreased in indomethacin group (p<0,01) was restored by metformin (p<0,05). Conclusion: Metformin pre-treatment provided partial protection in two different gastric ulcer models. Possible mechanisms for this protection include decrease in oxidant formation and apoptosis and increase in gastric blood flow.