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- All Subjects: Organometallic compounds
- Creators: Sweazea, Karen L
- Creators: McCormick, Kelly Ann
Description
Cardiovascular disease has reached epidemic proportions resulting in its ranking as the number one cause of mortality in the Western world. A key player in the pathophysiology of vascular disease is oxidative stress due to free radical accumulation. This intervention study was conducted to evaluate any potential mediation of oxidative stress using a soil-derived organometallic compound (OMC) with suspected antioxidant properties. A 10-week study was conducted in male Sprague-Dawley rats (n = 42) fed either a high-fat diet (HFD) consisting of 60% kcal from fat or a standard Chow diet containing only 6% kcals from fat. Rats from each diet group were then subdivided into 3 subgroups (n = 6-10 each) that received 0.0 mg/mL, 0.6 mg/mL or 3.0 mg/mL OMC. Neither the diet nor OMC significantly changed protein expression of inducible nitric oxide synthase (iNOS) in isolated aortas. Plasma levels of the inflammatory marker, tumor necrosis factor alpha (TNFα) were below detection after the 10-week trial. Superoxide dismutase (SOD), a scavenger of the free radical, superoxide, was not significantly different following HFD although levels of SOD were significantly higher in Chow rats treated with 0.6 mg/mL OMC compared to HFD rats treated with the same dose (p < 0.05). Lipopolysaccharides (LPS) were significantly increased following 10 weeks of high fat intake (p < 0.05). This increase in endotoxicity was prevented by the high dose of OMC. HFD significantly increased fasting serum glucose levels at both 6 weeks (p < 0.001) and 10 weeks (p < 0.025) compared to Chow controls. The high dose of OMC significantly prevented the hyperglycemic effects of the HFD in rats at 10 weeks (p = 0.021). HFD-fed rats developed hyperinsulinemia after 10 weeks of feeding (p = 0.009), which was not prevented by OMC. The results of this study indicate that OMC may be an effective strategy to help manage diet-induced hyperglycemia and endotoxemia. However, further research is needed to determine the mechanism by which OMC helps prevent hyperglycemia as measures of inflammation (TNFα) and vascular damage (iNOS) were inconclusive.
ContributorsWatson, Deborah F (Author) / Sweazea, Karen L (Thesis advisor) / Johnston, Carol (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Arizona State University (Publisher)
Created2018
Description
Background: Nearly 95% of Americans will develop hypertension, and 67% will not seek treatment. Furthermore, hypertension is the leading risk factor for coronary heart disease. While previous studies have increased the use of blood pressure medication among patients that have received hypertension education, medications may not work for everyone. Due to the life-threatening nature of this condition, it is essential to find an effective alternative for treatment. The purpose of this study was to examine the impact of organometallic complex supplementation on hypertension and left ventricular hypertrophy in 6-week old male Sprague-Dawley rats that were fed either standard rodent chow or a high fat diet for 10 weeks at a university in Arizona.
Methods: Forty-two healthy six-week old male Sprague-Dawley rats were randomly assigned to one of three groups: plain water control, 0.6 mg/ml organometallic complex or 3.0 mg/ml organometallic complex as soon as they arrived. Each rat was then housed individually to prevent the sharing of microbiota through coprophagia. Rats in each treatment group were further divided into two dietary groups that were fed either a high fat diet containing 60% kcal fat that was changed every three days or standard rodent chow. Researchers were not blind to which rat was in each group. At the end of the 10-week study, rats were euthanized with an overdose of sodium pentobarbital (200 mg/kg, i.p.). Heart, left ventricle of the heart, liver, and spleen masses were recorded for each animal. Data were analyzed by two-way ANOVA using SigmaPlot 10.0 software.
Results: At the conclusion of this study, the left ventricle mass of the rats in the high fat diet group were significantly larger than those in the chow group. Neither dose of the organometallic complex supplement prevented these effects induced by high fat feeding.
Conclusion: The organometallic complex supplement was not effective at mitigating the effects of a high fat diet on cardiac hypertrophy in rats. Therefore, this supplement should not be used to treat cardiac hypertrophy.
Methods: Forty-two healthy six-week old male Sprague-Dawley rats were randomly assigned to one of three groups: plain water control, 0.6 mg/ml organometallic complex or 3.0 mg/ml organometallic complex as soon as they arrived. Each rat was then housed individually to prevent the sharing of microbiota through coprophagia. Rats in each treatment group were further divided into two dietary groups that were fed either a high fat diet containing 60% kcal fat that was changed every three days or standard rodent chow. Researchers were not blind to which rat was in each group. At the end of the 10-week study, rats were euthanized with an overdose of sodium pentobarbital (200 mg/kg, i.p.). Heart, left ventricle of the heart, liver, and spleen masses were recorded for each animal. Data were analyzed by two-way ANOVA using SigmaPlot 10.0 software.
Results: At the conclusion of this study, the left ventricle mass of the rats in the high fat diet group were significantly larger than those in the chow group. Neither dose of the organometallic complex supplement prevented these effects induced by high fat feeding.
Conclusion: The organometallic complex supplement was not effective at mitigating the effects of a high fat diet on cardiac hypertrophy in rats. Therefore, this supplement should not be used to treat cardiac hypertrophy.
ContributorsMcCormick, Kelly Ann (Author) / Sweazea, Karen L (Thesis advisor) / Whisner, Corrie M (Committee member) / Alexon, Christy (Committee member) / Arizona State University (Publisher)
Created2019