Effect of Estrogen and Ovariectomy of the Response of the Rabbit Urinary Bladder to Two Forms of In-Vitro Oxidative Damage
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Issue Date
2013
Authors
Malone, Lisa Eileen '13
Degree
MS in Biotechnology
Advisor
Levin, Robert
Committee Members
Johnson, Arnold
El-Fawal, Hassan
El-Fawal, Hassan
Journal Title
Journal ISSN
Volume Title
Abstract
There are several lower urinary tract dysfunctions (LUTD) that are more common in women than men. These include incontinence, recurrent urinary tract infection and interstitial cystitis. There is increasing evidence that these conditions are related to changes in circulating estrogen levels. During periods of low estrogen levels, blood flow is decreased to the bladder smooth muscle and mucosa resulting in a period of ischemia / hypoxia which precipitates smooth muscle and mucosal damage. Estrogen increases blood flow to the bladder mucosa and smooth muscle and can protect against the damage caused by ischemia and hypoxia that occurs during low estrogen periods. For these studies we subjected the bladder to two forms of physiologically relevant oxidative damage. The first is related to ischemic-reperfusion injury which results in the production of damaging free radicals. The second is related to direct oxidative damage caused by hydrogen peroxide which can occur physiologically by the imbalance between two important intracellular antioxidant enzymes, superoxide dismutase (SOD) and catalase.
Our hypothesis is that the bladders from ovariectomized rabbits will be more susceptible to the in-vitro oxidative stress compared to control bladders, and that the bladders of estrogen-treated rabbits will be protected. Additionally, we believe that exposure to H2O2 will be more damaging to bladder tissue than ischemia/reperfusion.
Eighteen female NZW rabbits were divided into three groups: control, ovariectomized and ovariectomized receiving continuous estrogen. Eight bladder strips from each of three rabbits per group were taken for in-vitro ischemia/reperfusion physiological experiments, while eight strips from the three remaining rabbit bladders per group were taken for in-vitro hydrogen peroxide experiments. All tissue was analyzed for total antioxidant activity (AA) and malondialdehyde (MDA) levels. In addition, samples of the organ baths were also analyzed for AA.
Hydrogen peroxide was found to target the nerve, muscarinic receptor and membrane equally causing more damage to bladder tissue than I/R. Ovariectomy resulted in lower contractility and higher lipid peroxidation. However, estrogen supplementation following ovariectomy protected the bladder against both models of oxidative damage by maintaining contractile responses to stimulation and decreasing lipid peroxidation.
Our hypothesis is that the bladders from ovariectomized rabbits will be more susceptible to the in-vitro oxidative stress compared to control bladders, and that the bladders of estrogen-treated rabbits will be protected. Additionally, we believe that exposure to H2O2 will be more damaging to bladder tissue than ischemia/reperfusion.
Eighteen female NZW rabbits were divided into three groups: control, ovariectomized and ovariectomized receiving continuous estrogen. Eight bladder strips from each of three rabbits per group were taken for in-vitro ischemia/reperfusion physiological experiments, while eight strips from the three remaining rabbit bladders per group were taken for in-vitro hydrogen peroxide experiments. All tissue was analyzed for total antioxidant activity (AA) and malondialdehyde (MDA) levels. In addition, samples of the organ baths were also analyzed for AA.
Hydrogen peroxide was found to target the nerve, muscarinic receptor and membrane equally causing more damage to bladder tissue than I/R. Ovariectomy resulted in lower contractility and higher lipid peroxidation. However, estrogen supplementation following ovariectomy protected the bladder against both models of oxidative damage by maintaining contractile responses to stimulation and decreasing lipid peroxidation.
Citation
Malone, Lisa. "Effect of Estrogen and Ovariectomy of the Response of the Rabbit Urinary Bladder to Two Forms of In-Vitro Oxidative Damage." Albany College of Pharmacy and Health Sciences, New York, Proquest/UMI, 2013.
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