title: F2-isoprostanes as a biomarker of oxidative stress in the mouse bladder.
abstract: OBJECTIVE
  We theorized that progressive bladder dysfunction due to clinical diagnoses such as outlet obstruction occurs as a result of cyclical oxidative stress events. We hypothesized that measurement of F2-isoprostane, a marker of lipid peroxidation, could serve as a biomarker of oxidative stress in the murine bladder.
  
  
  METHODS
  At age 5 to 6 weeks oophorectomized female mice were subjected to 1 of 2 bladder injury models, that is partial bladder outlet obstruction or acute bladder distension. The time points studied after injury included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute bladder distension. In a separate group short-term repetitive acute bladder distension was performed every other day for 14 days. Bladder samples were analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean tissue F2-isoprostane levels were compared.
  
  
  RESULTS
  F2-isoprostane increased significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39 and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant increase in F2-isoprostane immediately after distension compared to controls (1.6 vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder distension F2-isoprostane did not change.
  
  
  CONCLUSIONS
  Measurement of tissue F2-isoprostane in the bladder reflects the progression of oxidative stress, primarily in chronic injury models such as partial bladder outlet obstruction. The usefulness of F2-isoprostane measurements in shorter term injury models requires further study.
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee. Electronic address: douglass.b.clayton@vanderbilt.edu.
authors.forename: Douglass B
authors.initials: DB
authors.lastname: Clayton
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Stephany
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
authors.forename: Christina B
authors.initials: CB
authors.lastname: Ching
authors.affiliation: University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: Shareena A
authors.initials: SA
authors.lastname: Rahman
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
authors.forename: Stacy T
authors.initials: ST
authors.lastname: Tanaka
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
authors.forename: John C
authors.initials: JC
authors.lastname: Thomas
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
authors.forename: John C
authors.initials: JC
authors.lastname: Pope
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Adams
authors.affiliation: Division of Pediatric Urology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.
authors.forename: John W
authors.initials: JW
authors.lastname: Brock
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Simon W
authors.initials: SW
authors.lastname: Hayward
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Matusik
authors.affiliation: Eicosanoid Core Laboratory and Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D004195:Disease Models, Animal; D018450:Disease Progression; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000097:blood; D001748:Urinary Bladder Neck Obstruction / Q000097:blood / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D017382:Reactive Oxygen Species
keywords: F(2)-isoprostanes; mice; oxidative stress; urinary bladder; urinary bladder neck obstruction