The effect of oleuropein on dna damage and oxidative stress in gastric ulcer model with indomethacin

The commonly use of Nonsteroid anti-inflamatuar drugs (NSAIDs) have gastrointestinal (GI) side effects such as gastric ulcer and upper GI bleeding. Oleuropein is an antioxidant compound commonly consumed as olive in Mediterranean diet. In order to evaluate the gastroprotective effect of oleuropein, an indomethacin-induced ulcer model has been applied in this study. Antioxidant levels, growth factors and DNA damage have been analyzed for the mechanism involved in oleuropein activity. Rats were allocated into a control group (n=8), an ulcer group indomethacin (25 mg/kg), an oleuropein (12 mg/kg) group, an ulcer group pretreated with lansoprazole (30 mg/kg) as a reference anti-ulcer drug, an ulcer group pretreated with different doses of oleuropein (6-12-18 mg/kg). The results showed that oleuropein (6mg/kg-12mg/kg-18mg/kg) exhibited significantly anti-ulcer effect 94.33%, 96.09%, 96.77%, respectively. While indomethacin administration increased the levels of lipid peroxidation (MDA) and myeloperoxidase (MPO), significantly decreased superoxide dismutase (SOD) and glutathione (GSH) levels. On the other hand, GSH and SOD levels of rats pretreated with oleuropein (18 mg/kg) increased, MDA and MPO levels decreased. Oleuropein (18mg/kg) administration significantly decreased % Tail DNA and Mean Tail Moment in the gastric ulcer group, compared with the other treatment groups. Oleuropein (18mg/kg) increased mRNA expression levels of EGF, EGFR, VEGF, VEGFR1 and VEGFR2. Histopathologic images of gastric tissues were compatible with biochemical and molecular findings. Our findings suggest that oleuropein might have protective effect against indomethacin-induced gastric ulcer and oxidative stress in rats. Keywords: Comet assay, gastric ulcer, oleuropein, oxidative stres.