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.
Highlights
Alcohol consumption has been commonly linked to gastric mucosal lesions including gastritis, gastric ulcer and even gastric carcinoma [1]
Activation of neutrophils is associated with an upregulated inflammatory response with increased gastric expression of nuclear factor kappa B (NF-κB) which controls the generation of proinflammatory cytokines including tumor necrosis factor-α (TNF-α)
Oxidative stress has been implicated in the development of ethanol-induced gastric injury where an arsenal of reactive oxygen species (ROS) generated by activated leukocytes triggers mucosal damage via lipid peroxidation and via depletion of the antioxidant defenses such as reduced glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC) [5, 9]
Summary
Alcohol consumption has been commonly linked to gastric mucosal lesions including gastritis, gastric ulcer and even gastric carcinoma [1]. Activation of neutrophils is associated with an upregulated inflammatory response with increased gastric expression of nuclear factor kappa B (NF-κB) which controls the generation of proinflammatory cytokines including tumor necrosis factor-α (TNF-α). These events amplify the inflammatory cascade via triggering the release of other proinflammatory mediators and enhancing further recruitment of macrophages and neutrophils, thereby exacerbating the gastric insult [6, 8]. Oxidative stress has been implicated in the development of ethanol-induced gastric injury where an arsenal of reactive oxygen species (ROS) generated by activated leukocytes triggers mucosal damage via lipid peroxidation and via depletion of the antioxidant defenses such as reduced glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC) [5, 9]. Depletion of mucosal cytoprotective moieties, including prostaglandin E2 (PGE2) and nitric oxide (NO), has been intimately linked to ethanol consumption [9, 11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
