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Background  Massive alcohol drinking can lead to gastric ulcer. In the present study we investigated the gastroprotective effect of  Citrus sinensis  peel aqueous extract (CSPE) and Hesperidin (H) in ethanol (EtOH) induced oxidative stress and peptic ulcer in rats.    Methods  Seventy adult male Wistar rats were divided into seven groups of 10 each: control, EtOH (4 g/kg b.w.), EtOH + various doses of CSPE (100, 200 and 400 mg/kg, b.w.), EtOH + Hesperidin (50 mg/kg, p.o.) and EtOH + Omeprazole (OM, 20 mg/kg, p.o.). Animals were perorally (p.o.) pre-treated with CSPE during 15 days and intoxicated with a single oral administration of EtOH (4 g/kg b.w.) during 2 h. Gastric ulcer was induced in rats with a single dose of ethanol (EtOH). Ulcer index, gene expression of gastric cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), malondialdhyde (MDA), hydrogen peroxide H 2 O 2  and Thiol groups (−SH) content in stomach and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and gluthation peroxidise (GPx) were measured. Furthermore, histopathological examinations were performed.    Results  The results showed that ethanol induced gastric damage, improving oxidative stress markers level such as MDA (121 ± 4.45 nmol/mg proteins) and H 2 O 2  (24.62 ± 1.04 μmol/mg proteins), increased pro-inflammatory cytokine (TNF-α level), as well as the expression of COX-2 in the ethanol group. However, a significant depletion of enzymatic and non-enzymatic antioxidants were observed, such as, GPx (72%), SOD (57.5%), CAT (41.6%) and -SH (50%). The lesions were associated with severe histopathological damage. The both  Citrus sinensis  peel aqueous extract (CSPE) and hesperidin significantly protect against all gastric damages caused by ethanol administration in rats.    Conclusions  We propose that CSPE and hesperidin exhibit protective effects in EtOH-induced peptic ulcer in rat. This protection might be related in to part its antioxidant properties as well as its opposite effects on some studied intracellular mediators.

Protective effects of orange (Citrus sinensis L.) peel aqueous extract and hesperidin on oxidative stress and peptic ulcer induced by alcohol in rat