Exploring the cytoprotective potential of oleuropein against indomethacin-induced gastric ulcer in rats

Indomethacin (INDO) can induce gastric ulcers via oxidative stress and apoptosis. This study aimed to investigate the protective effects of oleuropein (OLE), a natural antioxidant from olive plants, against INDO-induced gastric ulcers in rats, focusing on the modulation of growth factors and apoptotic pathways. Forty-eight male Wistar rats were divided into six groups: control, INDO, lansoprazole (LAN), and OLE doses (6, 12, and 18 mg/kg). INDO was administered to induce ulcers, followed by respective OLE treatments. Analyses included comet assays for DNA damage, assessment of oxidative/antioxidative enzyme activities, qRT-PCR for growth factor expression, Western blots for apoptotic protein levels, and histopathological examination. INDO significantly increased ulcer area, malondialdehyde (MDA) levels, and apoptosis while reducing antioxidant enzymes and growth factor expression. OLE (18 mg/kg), significantly reduced ulcer area (P<0.001), increased activities of superoxide dismutase (SOD) and glutathione (GSH), decreased MDA levels (P<0.001) and protected lymphocytes from DNA damage. OLE also attenuated the INDO-induced downregulation of EGF, EGFR, VEGF, VEGFR1, and VEGFR2 (P<0.05). OLE counteracted the increase in Bax and caspase-3/9 and the reduction in Bcl-2 expression (P<0.05). OLE showed strong protection against INDO-induced ulcers by reducing oxidative stress, regulating growth factors, and inhibiting apoptosis, supporting its potential for treating gastric ulcers.