title: Role of quercetin and its in vivo metabolites in protecting H9c2 cells against oxidative stress.
abstract: The aim of this study was to investigate the potential of quercetin and two of its "in vivo" metabolites, 3'-O-methyl quercetin and 4'-O-methyl quercetin, to protect H9c2 cardiomyoblasts against H(2)O(2)-induced oxidative stress. As limited data are available regarding the potential uptake and cellular effects of quercetin and its metabolites in cardiac cells, we have evaluated the cellular association/uptake of the three compounds and their involvement in the modulation of two pro-survival signalling pathways: ERK1/2 signalling cascade and PI3K/Akt pathway. The three flavonols associated with cells to differing extents. Quercetin and its two O-methylated metabolites were able to reduce intracellular ROS production but only quercetin was able to counteract H(2)O(2) cell damage, as measured by MTT reduction assay, caspase-3 activity and DNA fragmentation assays. Furthermore, only quercetin was observed to modulate pro-survival signalling through ERK1/2 and PI3K/Akt pathway. In conclusion we have demonstrated that quercetin, but not its O-methylated metabolites, exerts protective effects against H(2)O(2) cardiotoxicity and that the mechanism of its action involves the modulation of PI3K/Akt and ERK1/2 signalling pathways.
authors.affiliation: Department of Biochemistry G. Moruzzi, Nutrition Research Centre, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Angeloni
authors.forename: J P E
authors.initials: JP
authors.lastname: Spencer
authors.forename: E
authors.initials: E
authors.lastname: Leoncini
authors.forename: P L
authors.initials: PL
authors.lastname: Biagi
authors.forename: S
authors.initials: S
authors.lastname: Hrelia
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D011794:Quercetin / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D011794:Quercetin; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3