Diosmin Protects against Ethanol-Induced Gastric Injury in Rats: Novel Anti-Ulcer Actions

被引:183
|
作者
Arab, Hany H. [1 ,2 ,3 ]
Salama, Samir A. [2 ,3 ,4 ]
Omar, Hany A. [5 ,6 ]
Arafa, El-Shaimaa A. [5 ]
Maghrabi, Ibrahim A. [7 ]
机构
[1] Cairo Univ, Fac Pharm, Dept Biochem, Cairo 11562, Egypt
[2] Taif Univ, Div Biochem, Fac Pharm, Dept Pharmacol & Toxicol, At Taif 21974, Saudi Arabia
[3] Taif Univ, GTMR Unit, Fac Pharm, Dept Pharmacol & Toxicol, At Taif 21974, Saudi Arabia
[4] Al Azhar Univ, Fac Pharm, Dept Biochem, Cairo 11751, Egypt
[5] Beni Suef Univ, Fac Pharm, Dept Pharmacol, Bani Suwayf 62514, Egypt
[6] Univ Sharjah, Sharjah Inst Med Res, Coll Pharm, Sharjah 27272, U Arab Emirates
[7] Taif Univ, Fac Pharm, Dept Clin Pharm, At Taif 21974, Saudi Arabia
来源
PLOS ONE | 2015年 / 10卷 / 03期
关键词
NF-KAPPA-B; NITRIC-OXIDE; OXIDATIVE STRESS; MUCOSAL INJURY; PROSTAGLANDIN E-2; ULCER; ANTIOXIDANT; MODULATION; SUCRALFATE; EXPRESSION;
D O I
10.1371/journal.pone.0122417
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-alpha (TNF-alpha) levels along with nuclear factor kappa B (NF-kappa B) 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 E-2 (PGE(2)) 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.
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页数:21
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