Effects of quercetin on hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol through the reactive oxygen species-nitric oxide pathway

Aim: To investigate the effect of quercetin (3,3′4′5, 7-pentahydroxy flavone), a major flavonoid in human diet, on hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol. Methods: Forty male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into control group (tap water ad libitum), ethanol treatment group (6 mL/L ethanol), quercetin treatment group (intragastric gavage with 100 mg/kg of quercetin per day), and ethanol plus quercetin treatment group (quercetin and 6 mL/L ethanol). Expression levels of proliferating cell nuclear antigen (PCNA) and Cyclin D1 were detected by Western blot to assay gastric mucosal cell proliferation in rats. To demonstrate the influence of quercetin on the production of extra-cellular reactive oxygen species/nitrogen species (ROS/RNS) in rats, changes in levels of thiobarbituric acid reactive substance (TBARS), protein carbonyl, nitrite and nitrate (NOx) and nitrotyrosine (NT) were determined. The activity of inducible nitric oxide synthase (NOS) including iNOS and nNOS was also detected by Western blot. Results: Compared to control animals, cell proliferation in the gastric mucosa of animals subjected to ethanol treatment for 7 days was significant increased (increased to 290% for PCNA density P < 0.05, increased to 150 for Cyclin D1 density P < 0.05 and 21.6 ± 0.8 vs 42.3 ± 0.7 for PCNA positive cells per view field), accompanied by an increase in ROS gener-ation (1.298 ± 0.135 μmol vs 1.772 ± 0.078 μmol for TBARS P < 0.05; 4.36 ± 0.39 mmol vs 7.48 ± 0.40 mmol for carbonyl contents P < 0.05) and decrease in NO generation (11.334 ± 0.467 μmol vs 7.978 ± 0.334 μmol P < 0.01 for NOx; 8.986 ± 1.351 μmol vs 6.854 ± 0.460 μmol for nitrotyrosine P < 0.01) and nNOS activity (decreased to 43% P < 0.05). This function was abolished by the co-administration of quercetin. Conclusion: The antioxidant action of quercetin relies, in part, on its ability to stimulate nNOS and enhance production of NO that would interact with endogenously produced reactive oxygen to inhibit hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol. © 2008 The WJG Press. All rights reserved.