Browsing by Subject "Oxidative stress"
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Item A combination high in antioxidant foods’ effects on blood antioxidant and oxidative stress levels in post-menopausal women(2011-08) Kloiber, Shelby; Hart, Melanie A.; McComb, Jacalyn J. R.; Park, YoonjungOxidative stress brought on by free radicals can lead to an increased risk of certain diseases such as heart disease and some cancers. Oxidative stress mediated damage can be reduced by scavengers, or antioxidants that can eliminate the high reactivity of free radicals by turning them into non-radical and nontoxic metabolites. Many scientists have investigated the effects of different kinds of foods (whole, liquid, or supplement) to measure the change in oxidative damage and antioxidant capacity. The purpose of this study is to examine the effects of two types of foods high in antioxidant on markers of oxidative stress and antioxidant capacity in postmenopausal women. Healthy post-menopausal women, (N=16) were divided into four groups (i.e., fruits, soymilk, fruits and soymilk and control). Oxidative stress and antioxidant capacity were measured before and after the intervention. Oxidative stress results indicated no significant differences. Antioxidant capacity results indicated a significant main effect for Test with the mean for the pre-test (M = 0.28 units/ml, SD = 0.15) being significantly lower than the mean for the post-test (M = 0.39 units/ml, SD = 0.23). The results from this study did not support the effectiveness of fruits and soymilk on the oxidative stress levels and antioxidant capacity in postmenopausal women.Item ATM activation by oxidative stress(2009-08) Guo, Zhi, 1978-; Paull, Tanya T.The Ataxia-telangiectasia mutated (ATM) protein is regarded as the major regulator of the cellular response to DNA double Strand Breaks (DSBs). In response to DSBs, ATM dimers dissociates into active monomers in a process promoted by Mre11-Rad50-Nbs1 (MRN) complex. ATM-deficient cells exhibit signs of chronic oxidative stress, suggesting that ATM plays an important role in the regulation of reactive oxygen species (ROS). I show for the first time that ATM can be activated by oxidative stress directly in the form of exposure to H₂O₂. In vitro kinase assays with purified ATM suggest that the activation by H₂O₂ is independent of DSBs and the MRN complex. In 293T cells, H₂O₂ induces ATM autophosphorylation on serine 1981. p53 and Chk2 are also phosphorylated by ATM after H₂O₂ treatment but not histone H2AX and heterochromatin protein Kap1, indicating that ATM activation by H₂O₂ in human cells is independent of DNA damage. I also show that the cysteine residue 2991 is critical for ATM activation by H₂O₂ in vitro.Item Chronic and acute effects of hydroxytyrosol on antioxidant status and inflammation at rest and during exercise(2012-05) Simpson, Ashlee Danielle; Ivy, John, 1945-; Farrar, Roger P.Evidence shows that consumption of a Mediterranean diet can lower the risk of all-cause and cause-specific mortality suggesting that this diet has an overall effect on health. Antioxidants found within olive oil, the primary source of fat in the Mediterranean diet, may be leading contributors to the decreased disease risk. More specifically, hydroxytyrosol (HT), one of the most active and powerful antioxidants found in olive oil, has the ability to increase total antioxidant status and lower levels of lipid peroxidation. In addition to a healthy diet, physical activity decreases the risk of cardiovascular morbidity and mortality; however, aerobic exercise of sufficient intensity or duration can induce oxidative stress. Therefore, the purpose of this study was to investigate the effects of 6 weeks of HT supplementation on antioxidant status and markers of inflammation in healthy, recreationally active males before and throughout acute aerobic exercise bouts. Using a randomized, double-blind, repeated-measures, placebo-controlled design, sixty-one (n=61) participants were randomly assigned to consume a placebo (PLA), low dose of HT (LHT, 50 mg/day), or high dose of HT (HHT, 150 mg/day). Throughout the course of the study, the participants performed four time trial rides (TT1-TT4) on cycle ergometers. TT1 occurred before supplementation, TT2 halfway through the supplementation period, and TT3 and TT4 occurred in the sixth week and final two days of supplementation. Blood was drawn prior to (pre) and just before termination (end) of each time trial to measure markers of antioxidant status and inflammation during exercise. We did not observe significant main effects for treatment on any of the markers for antioxidant status (TEAC) or for markers of inflammation (oxLDL, CRP, 8IP, TNFα, IL-6, IL-10, IL-1β, or IL-1ra). Significant treatment-by-time interactions occurred for CRP, 8IP, and IL-6 although significant treatment differences in these measures were not detected. We conclude that chronic and acute HT supplementation does not improve antioxidant status nor decrease markers of inflammation in this population at rest, during, or following exercise.Item Effects of aging or diet on oxidative modification and antioxidant enzymes(2011-05) Rosales, Brittany N; Grammas, Paula; Popp, R. Lisa; Syapin, Peter J.Aging is a risk factor for the development of many diseases. The mechanisms by which aging and age-related diseases progress are not entirely clear, however, evidence suggests that aberrant amounts of reactive oxygen species (ROS) play a role in both the aging process and the pathogenesis of age-related maladies. Oxidative stress and resulting oxidative modifications of lipids and proteins have been linked to cellular dysfunction and disease, and specifically implicated in the development of several age-related afflictions. A decline in cardiac and hepatic function is associated with aging, and previous studies report a relationship between oxidative stress and the occurrence of heart and liver disease. The objective of this study was to determine whether aging or dietary–induced oxidative stress caused deleterious oxidative modifications to the cellular content of the heart and liver, and if age or diet affect the expression of antioxidant enzymes. Fischer 344 male rats at 6, 12, and 18 months of age were exposed to oxidative stress-inducing diets (high fat or high homocysteine). Lipid peroxidation was determined as an indicator of oxidative modification. In addition, the expression levels of antioxidant enzymes, superoxide dismutase (MnSOD and ZnSOD), glutathione peroxidase 1 (GPX1), and catalase, were determined at the RNA and protein level by RT-PCR and western blot respectively. This study found that aging and diet are associated with increased oxidative modification, as well as with alterations to the expression of antioxidant enzymes.Item Green tea extract supplementation and cycling time-trial performance at moderate altitude(2008-08) Pugh, Michael Derek; Williams, James S.; Sawyer, Robert D.; Carter, D. RickReactive oxygen species are unstable molecules that have been shown to cause muscle damage and possibly be involved in the skeletal muscle fatiguing process. Reactive oxygen species are generated by high intensity exercise and also exposure to altitude related hypoxia, as well as various other conditions. Green tea extract is a known, powerful antioxidant, meaning it has the ability to scavenge reactive oxygen species, possibly decreasing muscle damage and fatigue. The purpose of this research was to determine the effects of green tea extract supplementation on reactive oxygen species production, oxidative stress, and endurance exercise performance at moderate altitude.
Ten subjects performed a graded exercise test to determine maximum oxygen consumption and power output. The subjects then participated in three time trials on a fixed gear cycle ergometer. These time trials corresponded with cycling at seventy five percent of their maximum power output for twenty minutes, if the subject pedaled faster; he completed the time trial in less than twenty minutes. One hour prior to performing in the second and third time trials, a blood sample was collected from each subject and a supplement was given. The supplement consisted of either a placebo (dextrose) or green tea extract. The supplementation was administered in a random, double blind fashion, to minimize bias of the results. One hour after completion of the time trial, a blood sample was again obtained.
The results of this study show an average twenty-nine second improvement in cycling time trial performance, and corresponding increase of approximately seven watts in mean power output, with green tea extract supplementation compared to placebo. There were no significant differences in heart rate, percent of maximum heart rate, oxygen saturation, or rating of perceived exertion between the two different supplements. There also were no significant differences in the plasma malondialdehyde (marker of oxidative stress) between the two supplementations.
This study found that while green tea extract improves endurance exercise performance at moderate altitude, the mechanism by which this performance improved is not readily known, as there was no change in malondialdehyde concentrations. Further research should be completed to determine a better quantitative measure for oxidative stress and reactive oxygen species in the body.
Item Impact of N-2-mercaptopropionylglycine (MPG) and simvastatin on exercise-induced cardiac adaptations(2008-08) Nelson, Matthew Jay; Starnes, Joseph W.Experiments were conducted to investigate the role of free radicals in exercise induced cardiac adaptations and to determine if statin administration would adversely affect cardiac adaptations to exercise. In the first experiment myocardial antioxidant enzymes, cardiac function and cardiac hypertrophy were assessed following a chronic exercise protocol previously used by our lab. MPG effectively reduced myocardial oxidative stress and activation of the signaling proteins Akt and S6 following an exercise bout. Skeletal muscle mitochondria content increased to similar levels in E and E+MPG. Similar increases (P<0.05) in both exercised groups were observed for heart wt and heart wt to body wt ratio. Cardiac function at the high workload improved in E vs S as indicated by higher (P<0.05) peak systolic pressure (SP), cardiac output (CO), coronary flow, COxSP and mechanical efficiency (COxSP/VO2). MPG prevented these exercise-induced functional improvements. This study provides evidence that free radicals do not play a role in the development of exercise-induced cardiac hypertrophy, however, they are involved in functional cardiac adaptations, which may be mediated through the PI3K/Akt pathway. In the second experiment a similar exercise protocol was used to determine if statins which have been shown to prevent pathological forms of cardiac hypertrophy, would be detrimental to exercise induced cardiac adaptations. In addition to the sedentary and exercise groups sedentary+statin and exercise+statin groups were assessed. Hearts were isolated and perfused and assessed for function at low and high workloads. Exercise treatment resulted in cardiac hypertrophy in absolute and relative terms to a similar extent in statin-treated and untreated exercised rats. Additionally it resulted in significant functional increases for SP, CO, COxSP, VO₂, and EFF in both exercised groups. In conclusion, these studies provide evidence that exercise in the cold is a valid model for physiological cardiac hypertrophy and that pathological and physiological cardiac hypertrophy signal through different pathways due to the fact that two well established treatments (mpg and statins) that prevent pathological cardiac hypertrophy did not affect exercise induced cardiac hypertrophy.Item Investigating cellular responses to mutations in the glutathione and thioredoxin pathways of Escherichia coli(2009-12) Chrysostomou, Constantine; Georgiou, George; Isaac, SanchezInhibition of disulfide bond formation in Escherichia coli implicates an intricate collaboration of proteins which comprise the glutathione and thioredoxin reducing pathways. Bioengineers have successfully engineered E. coli possessing mutated reducing pathways that promote, rather than inhibit, disulfide bond formation in the cytoplasm. The transcriptome of six such mutant E. coli strains have been characterized using Microarray technology. We find that all mutant strains, exhibit a unique response to oxidative stress, not observed in wild type. Statistical analyses revealed the expression of more than 200 genes that are affected by mutations within the reducing pathways. Significantly up-regulated biological processes include cysteine biosynthesis, histidine biosynthesis, NADH Dehydrogenase I biosynthesis, sugar catabolic processes, and activation of stress responses . The second part of this work describes the construction of an E. coli strain that promotes the complete conversion of glutathione into its seemingly dormant derivative, glutathionylspermidine. This engineered strain can be used in assays designed to evaluate the effectiveness of glutathionylspermidine as a substitute for glutathione and, hopefully, allude to its true metabolic function.Item OXIDATIVE STRESS AND RENAL AT1R FUNCTION DURING HYPERTENSION(2012-04-19) Javkhedkar, Apurva; Lokhandwala, Mustafa F.; Banday, Anees A.; Marwaha, Aditi; Tam, Vincent; Vaziri, Nosratola D.Angiotensin (Ang) II via renal Ang II type 1 receptors (AT1R) modulates proximal tubular Na/K-ATPase such that, low concentrations of Ang II stimulates Na/K-ATPase whereas at high concentrations the stimulatory effect is lost. Studies show that oxidative stress can impair Ang II-induced Na/K-ATPase regulation and can contribute to hypertension. In the present study we first determined whether renal oxidative stress precedes development of hypertension in SHR. We found that at 3-4 weeks of age, SHR are normotensive and do not exhibit proximal tubular oxidative stress. Also, renal AT1R protein expression and Ang II-induced Na/K-ATPase stimulation was similar in SHR and WKY rats. Next we determined if antioxidant treatment at an early age can prevent renal oxidative stress and alleviate increase in blood pressure in SHR. We found that in adult SHR, there was high blood pressure, increased renal oxidative stress and decreased proximal tubular Nrf-2 activation as well as antioxidant activity compared to WKY rats. In WKY rats Ang II exerted a biphasic effect on Na/K-ATPase whereas in SHR, there was loss of biphasic effect such that Ang II produced stimulation at both high and low concentrations. In presence of nitric oxide (NO) synthase (NOS) inhibitor, L-NAME, Ang II (high concentration) produced stimulation of Na/K-ATPase in WKY rats. Ang II via AT1R caused NO iv production in WKY rats but not in SHR. Ang II caused enhanced activation of NADPH oxidase and L-arginine dependent NOS mediated superoxide production in proximal tubules of SHR. NADPH oxidase inhibitor DPI prevented Ang II-induced L-arginine dependent superoxide production and normalized NO production in SHR. There was increased renal NF kappaB activation, Giα protein expression and AT1R-G protein-coupling in SHR compared to WKY rats. Antioxidant resveratrol decreased blood pressure, increased Nrf-2 mediated antioxidant enzymes, reduced oxidative stress, normalized NOS coupling and restored Ang II-induced NO production as well as biphasic effect on Na/K-ATPase. Resveratrol treatment in SHR decreased Giα protein expression and normalized AT1R-G protein-coupling. Together these results demonstrate mechanism by which renal oxidative stress contributes to hypertension in SHR.Item Pharmacokinetics and cytoprotective evaluation of Caffeic Acid Phenethyl Amide and fluorinated derivatives against oxidative stress(2012-12) Yang, John; Stavchansky, Salomon; Bowman, Phillip D; Kerwin, Sean M; Williams, Robert O; McGinity, James WIschemic injury occurs when the flow of blood is reduced or blocked to an area of the body and can cause significant tissue damage by generation of reactive oxygen species (ROS), activation of apoptotic pathways and through induction of the inflammatory response. Restoration of blood flow and reperfusion of the blocked site, while essential, can generate a second injury that itself needs to be controlled. Together the two injuries are termed ischemia/reperfusion (I/R) injury. This type of injury is frequently encountered in medicine and is a major medical problem. Therapeutic strategies to combat I/R injury include the introduction of compounds that can scavenge ROS or can induce metabolic pathways with the effect of inhibiting apoptosis. Caffeic Acid Phenethyl Ester (CAPE), a polyphenolic compound found in propolis, has been shown to protect a variety of cells types against ROS in vitro and has also been shown to induce a variety of genes including hemeoxygenase 1 (HMOX-1) , an enzyme that has been implicated in a cytoprotective pathway. Despite showing significant cytoprotection of cells against oxidant stress in vitro, CAPE is readily hydrolyzed in plasma and is also quickly removed from circulation. This result may explain the limited cytoprotective effects of CAPE in vivo. We have synthesized a series of CAPE amide derivatives, including Caffeic Acid Phenethyl Amide (CAPA), with the aim of improving CAPE’s stability properties while maintaining the cytoprotective effects of the parent compound. We found that CAPA, in addition to 2 other amide derivatives, were able to protect human umbilical vein endothelial cells (HUVEC) against ROS to a similar degree as CAPE. In addition, we have observed significant improvement in plasma stability of CAPA over CAPE at multiple temperatures. The elimination half-life of CAPA from the systemic circulation was also seen to be significantly improved over CAPE following intravenous administration to male Sprague-Dawley rats. The longer residence time of CAPA over CAPE in circulation may potentially result in greater cytoprotection in vivo.Item Role of Vascular Oxidative Stress in Hypertension(2012-04-19) Bhatt, Siddhartha; Lokhandwala, Mustafa F.; Banday, Anees Ahmad; Marwaha, Aditi; Majid, Dewan; Lewis, Russell E.Hypertension affects 1 in 3 adult Americans and is a primary risk factor for cardiovascular diseases. Better understanding of hypertension pathogenesis is important for development of effective therapeutic agents. An important underlying factor present during hypertension is oxidative stress (OS). However, causal role of OS in hypertension is unclear. Increased vascular resistance resulting from enhanced vasoconstriction and impaired vasodilation is a hallmark of hypertension. Enhanced vasoconstriction is associated with increased reactivity to vasoconstrictors such as angiotensin (Ang) II. Ang II-induced vasoconstriction is exaggerated during hypertension and is associated with Ang II type 1 receptors (AT1R) upregulation, the cause of which is unknown. OS modulates redox sensitive transcription factors including nuclear factor kappa B (NFκB), which has been associated with AT1R upregulation. Thus, OS via NFκB can transcriptionally upregulate AT1R. The impaired vasodilation in hypertension is attributed to endothelial dysfunction resulting from attenuated nitric oxide (NO) availability. OS can also contribute to endothelial dysfunction by reducing NO production and increasing NO scavenging. Our objective was to study the role of OS in hypertension development. The first part of the study investigates whether OS is a cause or consequence of hypertension. Studies in 3-4 week old spontaneously hypertensive rats (SHR) revealed that OS precedes hypertension development and is associated with NFκB activation and AT1R upregulation. Treatment of young SHR with pyrrolidine dithiocarbamate, an antioxidant with NFκB inhibitory action, attenuated hypertension development and normalized NFκB and AT1R expression. Experiments in human aortic smooth muscle cells also exhibited OS-induced AT1R upregulation through mechanisms involving NFκB. The second part of the study investigates the role of early oxidative stress in endothelial dysfunction with focus on elucidating role of resveratrol, an antioxidant polyphenol. Our results demonstrate, early resveratrol treatment lowers oxidative stress and reduces NO scavenging and eNOS uncoupling thereby preventing endothelial dysfunction and attenuating hypertension development. In conclusion, early vascular OS in SHR could contribute to hypertension by modulating AT1 receptor upregulation, possibly via NFκB. Additionally, vascular OS could also contribute to endothelial dysfunction by increasing NO scavenging and eNOS uncoupling. Resveratrol treatment lowered oxidative stress, prevented endothelial dysfunction and attenuated hypertension development in SHR.Item The effects of green tea extract supplementation on delayed onset muscle soreness and oxidative stress(Texas Tech University, 2007-08) Jordan, Shannon Lynn; Sawyer, Robert D.; Williams, James S.; Carter, RickThe purpose of this study was to determine whether the antioxidants in green tea reduce biomarkers of oxidative damage and mechanical muscle damage following a downhill endurance run involving repeated eccentric contractions. Subjects were young, healthy males ages 21 – 25 years old free from cardiovascular or musculoskeletal disease whose participation was voluntary. All subjects were currently not taking multivitamins or antioxidant supplements. Subjects reported running 3 – 5 days/week. Foods rich in antioxidants were banned from the subjects’ diets and subjects kept food journals to ensure compliance. Subjects were randomly assigned to the placebo, green tea pre-exercise group, or green tea post-exercise group. The placebo group consumed a placebo before a downhill run and at 5 and 10 hours post-run. The green tea pre-exercise group consumed a green tea extract pill prior to the run and a placebo at 5 and 10 hours post-run. The green tea post-exercise group consumed a placebo pre-exercise and a green tea extract at 5 and 10 hours post-exercise. Subjects performed an oxygen consumption test on the treadmill in order to establish the exercise intensity of the downhill run. Subjects performed a 45-minute downhill run (-10°) on a treadmill at 60-65% of their VO2peak. Prior to the downhill run, measurements of quadriceps muscle soreness, isometric force production, range of motion, and thigh circumference was obtained. A blood draw was taken pre-exercise and post-exercise. Subjects returned to the lab 24-hours post exercise for a final blood draw and measurements of quadriceps muscle soreness, isometric force production, range of motion, and thigh circumference. Blood samples were analyzed for creatine kinase (muscle damage) and malondialdehyde (oxidative stress). Creatine kinase levels were significantly elevated at 24 hours post-exercise (PItem The subcellular localization and function of APX3 in Arabidopsis(2005-05) Narendra, Savitha; Zhang, Hong; Holaday, A. Scott; Allen, Randy D.; San Francisco, Michael; Xin, ZhanguoThe physiological condition associated with increased levels of reactive oxygen species (ROS, e.g., .O2-, H2O2, .OH and 1O2) is called oxidative stress. Enzymatic actions of superoxide dismutase, catalase and ascorbate peroxidase (APX) remove ROS in plants. APX is a H2O2-scavenging enzyme that protects plant cells from detrimental effects of H2O2. Although H2O2 is toxic to cells, it also plays important roles in plants. For example, it is required for cell wall cross-linking and it serves as a secondary messenger during plant defense. Therefore, it is not entirely beneficial for plants to remove H2O2 as soon as it is produced, but rather to regulate its amounts within the cell. APX is one such enzyme that may help regulate the amounts of H2O2 in plant cells. It was previously found that a 14-3-3-protein-interacting ascrobate peroxidase, APX3, was likely to be peroxisomal membrane bound. To test this hypothesis GFP-APX3 overexpressing plants were created. Fluorescence microscopy analyses from various tissues of GFP-APX3 plants indicated that APX3 is likely to be peroxisomal in its localization. To investigate the in vivo function of APX3, anti-APX3 antisense and APX3-overexpressing transgenic plants were created. Furthermore APX3-knockout plants from ABRC were also obtained. Data from analyzing APX3-knocout mutants show that loss of APX3 leads to modified electron transport during heat stress. Results from physiology experiments indicate that APX3 may play a role in thermal tolerance. This research indicates that a decrease in APX3 leads to an increase in other antioxidation enzymes. Therefore, it appears that the plant antioxidation system is redundant and highly interconnected.