title: Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.
abstract: Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels along with nuclear factor kappa B (NF-κB) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; Biochemistry Division and GTMR Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif, 21974, Saudi Arabia.
authors.forename: Hany H
authors.initials: HH
authors.lastname: Arab
authors.affiliation: Biochemistry Division and GTMR Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif, 21974, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, 11751, Egypt.
authors.forename: Samir A
authors.initials: SA
authors.lastname: Salama
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt; Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab of Emirates.
authors.forename: Hany A
authors.initials: HA
authors.lastname: Omar
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
authors.forename: El-Shaimaa A
authors.initials: el-SA
authors.lastname: Arafa
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Taif University, Taif, 21974, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Maghrabi
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004145:Diosmin / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013392:Sucralfate / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D013392:Sucralfate; D004145:Diosmin; D009195:Peroxidase
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