title: Quercetin protects gastric epithelial cell from oxidative damage in vitro and in vivo.
abstract: Epithelial injury caused by reactive oxygen species (ROS) including H2O2 plays a critical role in the pathogenesis of gastric disorders. Therefore, pharmacological intervention targeting reactive oxygen species elimination has highly clinical values in therapy of gastric diseases. Although quercetin has been found to possess gastroprotective activity, whether it has a protective activity againress related injury to gastric epithelial cells remains unknown. The aim of the study is herein to investigate a possible protective effect of quercetin against oxidative stress in vitro and vivo. Human gastric epithelial GES-1 cells were pretreated with quercetin and then challenged with H2O2. In vivo reactive oxygen species production in acute gastric mocosa injury was assessed using a chemiluminescent probe L-012 (8-amino-5-chloro-7-phenylpyrido [3,4-d]pyridazine-1,4-(2H,3H)dione) after quercetin was administered to mice. In GES-1 cells, pretreatment of quercetin can significantly diminish H2O2-induced cell viability loss; decrease intracellular reactive oxygen species and Ca(2+) influx; restore H2O2-induced ΔΨm dissipation. It also upregulates peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) expression under the state of oxidative stress, and the downstream cell apoptosis significantly decreased. In vivo, chemiluminescence imaging shows that quercetin attenuates reactive oxygen species production and gastric damages in acute gastric mucosal injury. We first reported the evidence that quercetin can protect gastric epithelial GES-1 cells from oxidative damage and ameliorate reactive oxygen species production during acute gastric mucosal injury in mice. This might be ascribed to its inhibition of oxidative stress, regulation of mitochondrial dysfunction, initiation of antioxidant defense and inhibition of apoptosis.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
authors.forename: Xin-Ting
authors.initials: XT
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ding
authors.affiliation: School of Foreign Languages and Literature, Chongqing Normal University, Chongqing 401331, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China. Electronic address: xuchn@nju.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020011:Protective Agents / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D011794:Quercetin; D006861:Hydrogen Peroxide; D002118:Calcium
keywords: DMSO (dimethyl sulphoxide) (PubChem CID: 679); Ethanol (PubChem CID: 702); Gastric epithelial cell; H(2)O(2) (PubChem CID: 784); H2DCF-DA (2′,7′-dichlorodihydrofluorescein diacetate) (PubChem CID: 77718); Hoechst 33258 (PubChem CID: 5326397); In vivo chemiluminescence imaging; L-012 (8-amino-5-chloro-7-phenylpyrido [3,4-d]pyridazine-1,4-(2H,3H)dione) (PubChem CID: 126741); MTT (Methyl-thiazol Tetrazolium) (PubChem CID: 64965); Mitochondrial dysfunction; Oxidative stress; Quercetin (PubChem CID: 5280343)