Increased vaginal oxidative stress, apoptosis, and inducible nitric oxide synthase in a diabetic rat model: implications for vaginal fibrosis.

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.
DESIGN: Research experimental project.
SETTING: University research laboratory. ANIMAL(S): Female Wistar rats. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): Diabetes in the rat causes oxidative stress and fibrosis in the vagina, which may be compensated partially by iNOS induction to reduce ROS.