title: Quercetin attenuates cyclooxygenase-2 expression in response to acute ureteral obstruction.
abstract: Unilateral ureteral obstruction (UUO) is associated with increased hydrostatic pressure, inflammation, and oxidative stress in the renal parenchyma. Previous studies have demonstrated marked cyclooxygenase (COX)-2 induction in renal medullary interstitial cells (RMICs) in response to UUO. The aim of the present study was to evaluate the effect of quercetin, a naturally occurring antioxidant, on COX-2 induction in vivo and in vitro. Rats subjected to 24 h of UUO were treated intraperitoneally with quercetin (50 mg·kg(-1)·day(-1)). Quercetin partly prevented COX-2 induction in the renal inner medulla in response to UUO. Moreover, RMICs exposed to conditions associated with obstruction, inflammation (produced by IL-1β), oxidative stress (produced by H2O2), and mechanical stress (produced by stretch) showed increased COX-2 expression. Interestingly, quercetin reduced COX-2 induction in RMICs subjected to stretched. Similarly, PGE2 production was markedly increased in RMICs exposed to stretch and was reversed to control levels by quercetin treatment. Furthermore, stretch-induced phosphorylation of ERK1/2 was blocked by quercetin, and inhibition of ERK1/2 attenuated stretch-induced COX-2 induction in RMICs. These results indicate that quercetin attenuated the induction of COX-2 expression and activity in RMICs exposed to mechanical stress as a consequence of acute UUO and that the MAPK ERK1/2 pathway might be involved in this quercetin-mediated reduction in COX-2.
authors: Department of Clinical Medicine, Aarhus University, Aarhus University Hospital, Aarhus, Denmark.
authors: Inge
authors: I
authors: Carlsen
authors: Department of Clinical Medicine, Aarhus University, Aarhus University Hospital, Aarhus, Denmark.
authors: Jørgen
authors: J
authors: Frøkiær
authors: Department of Clinical Medicine, Aarhus University, Aarhus University Hospital, Aarhus, Denmark rn@clin.au.dk.
authors: Rikke
authors: R
authors: Nørregaard
mesh_terms: D000208:Acute Disease; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D017208:Rats, Wistar; D013314:Stress, Mechanical; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000201:enzymology*
chemical_list: D011794:Quercetin; D006861:Hydrogen Peroxide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: cyclooxygenase-2; heat shock protein; quercetin; renal medullary interstitial cells; unilateral ureteral obstruction