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World J Gastroenterol. May 28, 2008; 14(20): 3242-3248
Published online May 28, 2008. doi: 10.3748/wjg.14.3242
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
Jing-Li Liu, Jun Du, Ling-Ling Fan, Xiao-Yan Liu, Luo Gu, Ying-Bin Ge
Jing-Li Liu, Jun Du, Xiao-Yan Liu, Luo Gu, Ying-Bin Ge, Department of Physiology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Ling-Ling Fan, Department of Physiology, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
Author contributions: Liu JL and Fan LL developed the chronic drinking rat model and performed the assay of lipid peroxidation, protein oxidation, nitric oxide, and nitrotyrosine (NT); Du J assayed the cell proliferation by Western blot; Liu XY did the immunohistochemistry; Gu L carried out the statistical analysis and assisted in the experiment design; Ge YB designed the experiment and wrote the paper.
Correspondence to: Ying-Bin Ge, MD, PhD, Department of Physiology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. ybge@njmu.edu.cn
Telephone: +86-25-86862016
Fax: +86-25-86862016
Received: January 26, 2008
Revised: April 1, 2008
Accepted: April 8, 2008
Published online: May 28, 2008
Abstract

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 generation (1.298 ± 0.135 &mgr;mol vs 1.772 ± 0.078 &mgr;mol 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 &mgr;mol vs 7.978 ± 0.334 &mgr;mol P < 0.01 for NOx; 8.986 ± 1.351 &mgr;mol vs 6.854 ± 0.460 &mgr;mol 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.

Keywords: Quercetin; Cell proliferation; Reactive oxygen species; Nitric oxide; Gastric mucosa; Ethanol