title: Increased vaginal oxidative stress, apoptosis, and inducible nitric oxide synthase in a diabetic rat model: implications for vaginal fibrosis.
abstract: OBJECTIVE
  To determine whether vaginal fibrosis occurs in diabetic animals and is associated with oxidative stress and cell death and with the expression of inducible nitric oxide synthase (iNOS), as a putative antifibrotic mechanism.
  
  
  METHODS
  Research experimental project.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Female Wistar rats.
  
  
  METHODS
  Female rats were injected with streptozotocin or saline and killed at 3 months. The vaginas were excised and processed for paraffin-embedded sections (n = 6 per group) or were frozen for biochemical and molecular biology procedures.
  
  
  METHODS
  Immunohistochemistry and quantitative image analysis were applied to tissue sections to measure alpha-smooth muscle actin, transforming growth factor beta1, plasminogen activator inhibitor, NOS isoforms, Cu/Zn superoxide dismutase, apoptotic index, and nitrotyrosine. Xanthine dehydrogenase, reactive oxygen species (ROS), and hydroxyproline were measured in fresh vaginal tissue (n = 5 per group). Reactive oxygen species also were determined in blood.
  
  
  RESULTS
  Diabetes was associated with vaginal fibrosis, as evidenced by increased collagen, transforming growth factor beta1, plasminogen activator inhibitor, and apoptosis, and by decreased alpha-smooth muscle actin. The increment of ROS and the reduction of superoxide dismutase indicated oxidative stress in diabetic tissue, accompanied by iNOS induction and increased nitric oxide-ROS reaction.
  
  
  CONCLUSIONS
  Diabetes in the rat causes oxidative stress and fibrosis in the vagina, which may be compensated partially by iNOS induction to reduce ROS.
authors.affiliation: Department of Urology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA. mferrini@labiomed.org
authors.forename: Monica G
authors.initials: MG
authors.lastname: Ferrini
authors.forename: Gaby
authors.initials: G
authors.lastname: Nolazco
authors.forename: Dolores
authors.initials: D
authors.lastname: Vernet
authors.forename: Nestor F
authors.initials: NF
authors.lastname: Gonzalez-Cadavid
authors.forename: Jennifer
authors.initials: J
authors.lastname: Berman
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors; D000818:Animals; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005355:Fibrosis; D009130:Muscle, Smooth / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014621:Vagina / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000199:Actins; D017395:Plasminogen Activator Inhibitor 1; D017382:Reactive Oxygen Species; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase